Tokushima University / Educator and Researcher Directory --- Uto, Yoshihiro

Personal Web Page

http://www.bio.tokushima-u.ac.jp/a2group/a2index.html

https://researchmap.jp/utoyoshihiro (researchmap)

Field of Study

○	Bioorganic Chemistry

Subject of Study

○	低酸素細胞放射線増感剤の開発, フェノール性脂質過酸化阻害剤の開発 (Threading intercalator, Hypoxic cell, Inhibitor of lipid peroxidation)

Book / Paper

Book:

1.	Yoshihiro Uto, Chiaki Abe, Mana Futawaka, Hisatsugu Yamada, Masahide Tominaga and Yoshio Endo : In vivo drug screening method of radiosensitizers using tumor-bearing chick embryo, Elsevier, Oct. 2019. (Summary) In radiotherapy, tumor hypoxia is the main factor responsible for treatment resistance, and the development of radiosensitizers that can overcome this is imperative. However, many drugs that are effective in vitro and in vivo fail in clinical trials, and thus it is necessary to develop an animal model that can be used for the correct evaluation of pharmacokinetics and activity. Developing chicken eggs are commonly used in various research fields such as anticancer drug sensitivity tests and cardiotoxicity tests. We examined whether the radiosensitizing activity of etanidazole, as a hypoxic cell radiosensitizer, could be evaluated using tumor-bearing chick embryo. Following the transplantation of mouse mammary carcinoma EMT6 cells on day 11, a solid tumor was formed on day 15 and an evaluation of the time-course of the tumor revealed that the tumor weight was the highest on day 18. The maximum dose of etanidazole that did not affect tumor growth and fetal survival was 1.0mg and the maximum X-ray dose was 8Gy. Etanidazole was intravenously administered 10min prior to single dose X-ray irradiation. A significant tumor growth inhibitory effect was confirmed with 1.0mg of etanidazole in combination with 8Gy X-ray. In the case of mouse colon cancer colon26 cells, the combination of 3.0mg of etanidazole and 2Gy X-ray showed 2.79 times higher radiosensitizing activity than that observed for the control group. These results demonstrate that it is possible to evaluate the activity of radiosensitizers using tumor-bearing chick embryo. (Keyword) Etanidazole / Hypoxic cell radiosensitizer / Mouse colon cancer colon26 cell / Mouse mammary carcinoma EMT6 cell / Tumor-bearing chick embryo (Link to Publication Site) ● Publication site (DOI): 10.1016/bs.enz.2019.08.008 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31727273 ● Search Scopus @ Elsevier (PMID): 31727273 ● Search Scopus @ Elsevier (DOI): 10.1016/bs.enz.2019.08.008 (DOI: 10.1016/bs.enz.2019.08.008, PubMed: 31727273)
2.	Hitoshi Hori, Yoshihiro Uto, Hideko Nagasawa and Eiji Nakata : 酸素をターゲットとしたがんの治療, 朝倉書店, Tokyo, Sep. 2009.
3.	Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : ハイポキシアを標的とした抗癌剤, YODOSHA CO., LTD., Tokyo, Feb. 2009.
4.	Hitoshi Hori, Eiji Nakata, Yoshihiro Uto and Hideko Nagasawa : 酸化ストレスを標的とした薬剤・治療法, 株式会社診断と治療社, Tokyo, Jun. 2008.

Academic Paper (Judged Full Paper):

1.	Makoto Takeuchi, Toshihiko Nishisho, Shun-ichi Toki, Shinji Kawaguchi, Shunsuke Tamaki, Takeshi Oya, Yoshihiro Uto, Toyomasa Katagiri and Koichi Sairyo : Blue light induces apoptosis and autophagy by promoting ROS-mediated mitochondrial dysfunction in synovial sarcoma., Cancer Medicine, Vol.12, No.8, 9668-9683, 2023. (Summary) Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS. (Keyword) Humans / Mice / Animals / Reactive Oxygen Species / Sarcoma, Synovial / Apoptosis / Autophagy / Mitochondria / Cell Line, Tumor (Link to Publication Site) ● Publication site (DOI): 10.1002/cam4.5664 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36722116 ● Search Scopus @ Elsevier (PMID): 36722116 ● Search Scopus @ Elsevier (DOI): 10.1002/cam4.5664 (DOI: 10.1002/cam4.5664, PubMed: 36722116)
2.	Yoshitaka Kurashiki, Hiroshi Kagusa, Kenji Yagi, Tomoya Kinouchi, Manabu Sumiyoshi, Takeshi Miyamoto, Kenji Shimada, Keiko T Kitazato, Yoshihiro Uto and Yasushi Takagi : Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage, Journal of Cerebral Blood Flow and Metabolism, 2022. (Summary) Cerebral ischemia triggers inflammatory changes, and early complications and unfavorable outcomes of endovascular thrombectomy for brain occlusion promote the recruitment of various cell types to the ischemic area. Although anti-inflammatory M2-type macrophages are thought to exert protective effects against cerebral ischemia, little has been clarified regarding the significance of post-ischemic phase-dependent modulation of M2-type macrophages. To test our hypothesis that post-ischemic phase-dependent modulation of macrophages represents a potential therapy against ischemic brain damage, the effects on rats of an M2-type macrophage-specific activator, Gc-protein macrophage-activating factor (GcMAF), were compared with vehicle-treated control rats in the acute (day 0-6) or subacute (day 7-13) phase after ischemia induction. Acute-phase GcMAF treatment augmented both anti-inflammatory CD163 M2-type- and pro-inflammatory CD16 M1-type macrophages, resulting in no beneficial effects. Conversely, subacute-phase GcMAF injection increased only CD163 M2-type macrophages accompanied by elevated mRNA levels of arginase-1 and interleukin-4. M2-type macrophages co-localized with CD36 phagocytic cells led to clearance of the infarct area, which were abrogated by clodronate-liposomes. Expression of survival-related molecules on day 28 at the infarct border was augmented by GcMAF. These data provide new and important insights into the significance of M2-type macrophage-specific activation as post-ischemic phase-dependent therapy. (Tokushima University Institutional Repository) ● Metadata: 118878 (Link to Publication Site) ● Publication site (DOI): 10.1177/0271678X221147090 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36545833 ● Summary page in Scopus @ Elsevier: 2-s2.0-85145451559 (Tokushima University Institutional Repository: 118878, DOI: 10.1177/0271678X221147090, PubMed: 36545833, Elsevier: Scopus)
3.	Kazuto Ohkura, Atsushi Tabata, Yoshihiro Uto and Hitoshi Hori : Molecular Interaction Between Boron Tracedrug UTX-51 Derivatives and Bovine Serum Albumin: Application to an Analytical Model of AGEs Destruction by Thermal Neutron Irradiation, Anticancer Research, Vol.42, No.8, 4017-4023, 2022. (Summary) Boron tracedrugs possess global molecular tracking abilities and localized destructive power. We investigated the molecular properties of synthesized boron tracedrugs, including UTX-51, and their interactions with the advanced glycation end-product (AGE)-related protein bovine serum albumin (BSA). A conformational analysis of the compounds used in the present study was performed using CAChe (Fujitsu Inc., Tokyo, Japan) and the degree of stereo-hydrophobicity of the conformers obtained was verified using Mopac (Fujitsu Inc.). The interactive properties of global minimum conformers of the derivatives tested with BSA were assessed using Molegro Virtual Docker (CLC bio., Aarhus, Denmark). Among the compounds investigated, UTX-51 was confirmed to interact with BSA based on the formation of hydrogen bonds between BSA and UTX-51. UTX-51 is a promising boron tracedrug and can be used as the lead structure for developing a therapeutic agent for AGE-related diseases, including cancer. (Keyword) BSA / Boron tracedrugs / molecular design / UTX-51 (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.15898 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35896254 ● Search Scopus @ Elsevier (PMID): 35896254 ● Search Scopus @ Elsevier (DOI): 10.21873/anticanres.15898 (DOI: 10.21873/anticanres.15898, PubMed: 35896254)
4.	Soichiro Enomoto, Daisuke Konishi, Yoshihiro Uto and Naoyuki Shimomura : Effects of nanosecond pulsed electric fields application on cancer cell and combination of anticancer drug, Electrical Engineering in Japan, Vol.215, No.2, 2022. (Link to Publication Site) ● Publication site (DOI): 10.1002/eej.23376 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1002/eej.23376 (DOI: 10.1002/eej.23376)
5.	Soichiro Enomoto, Daisuke Konishi, Yoshihiro Uto and Naoyuki Shimomura : Effects of Nanosecond Pulsed Electric Fields Application on Cancer Cell and Combination of Anticancer Drug, IEEJ Transactions on Fundamentals and Materials, Vol.141, No.12, 657-664, 2021. (Link to Publication Site) ● Publication site (DOI): 10.1541/ieejfms.141.657 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1541/ieejfms.141.657 (DOI: 10.1541/ieejfms.141.657)
6.	Hirari Yamahana, Minoru Terashima, Risa Takatsuka, Chikako Asada, Takeshi Suzuki, Yoshihiro Uto and Takahisa Takino : TGF-β1 facilitates MT1-MMP-mediated proMMP-9 activation and invasion in oral squamous cell carcinoma cells, Biochemistry and Biophysics Reports, Vol.27, 101072, 2021. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrep.2021.101072 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85111185472 (DOI: 10.1016/j.bbrep.2021.101072, Elsevier: Scopus)
7.	hirari yamahana, Yuki Komiya, Takahisa Takino, Yoshio Endo, Hisatsugu Yamada, Chikako Asada and Yoshihiro Uto : Structure Activity Relationships of UTX-121 Derivatives for the Development of Novel Matrix Metalloproteinase-2/9 Inhibitors, Chemical & Pharmaceutical Bulletin, Vol.69, No.10, 1017-1028, 2021. (Link to Publication Site) ● Publication site (DOI): 10.1248/cpb.c21-00549 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85116523598 (DOI: 10.1248/cpb.c21-00549, Elsevier: Scopus)
8.	Kenji Shono, Yoshifumi Mizobuchi, Izumi Yamaguchi, Kohhei Nakajima, Yuri Fujiwara, Toshitaka Fujihara, Keiko Kitazato, Kazuhito Matsuzaki, Yoshihiro Uto, Oltea Sampetrean, Hideyuki Saya and Yasushi Takagi : Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway., Scientific Reports, Vol.11, No.1, 2021. (Summary) Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM. (Keyword) ATP Binding Cassette Transporter, Subfamily B, Member 1 / Aminolevulinic Acid / Animals / Cell Line, Tumor / Down-Regulation / Glioblastoma / Glioma / Male / Mice / Mice, Inbred C57BL / NF-kappa B / Neoplastic Stem Cells / Photosensitizing Agents / Proto-Oncogene Proteins c-akt / Protoporphyrins / Signal Transduction / Ultrasonic Therapy (Tokushima University Institutional Repository) ● Metadata: 116448 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-021-93896-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34301977 ● Search Scopus @ Elsevier (PMID): 34301977 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-021-93896-0 (Tokushima University Institutional Repository: 116448, DOI: 10.1038/s41598-021-93896-0, PubMed: 34301977)
9.	Hirofumi Honda, Masahide Tominaga, Motoharu Sasaki, Masataka Oita, Kanzaki Hiromitsu, Hamamoto Yasushi, Ishii Yoshiaki, Yamamoto Ryuji, Mochizuki Teruhito, Kido Teruhito and Yoshihiro Uto : Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector, Journal of Applied Clinical Medical Physics, Vol.22, No.7, 66-76, 2021. (Summary) Volumetric-modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector "Delta Discover® (D4D)" was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance-to-agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A-side and B-side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of -0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission-type detector "D4D" is thus suitable for detecting delivery errors during irradiation. (Keyword) in vivo dosimetry / transmission detector / three-dimensional dose verification system / volume-modulated arc therapy (Tokushima University Institutional Repository) ● Metadata: 116183 (Link to Publication Site) ● Publication site (DOI): 10.1002/acm2.13260 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33955161 ● Search Scopus @ Elsevier (PMID): 33955161 ● Search Scopus @ Elsevier (DOI): 10.1002/acm2.13260 (Tokushima University Institutional Repository: 116183, DOI: 10.1002/acm2.13260, PubMed: 33955161)
10.	Akihiro Miura, Hiroshi Sootome, Naoya Fujita, Takamasa Suzuki, Hiroto Fukushima, Shinji Mizuarai, Norio Masuko, Kimihiro Ito, Akihiro Hashimoto, Yoshihiro Uto, Tetsuya Sugimoto, Hidekazu Takahashi, Morihiro Mitsuya and Hiroshi Hirai : TAS-119, a novel selective Aurora A and TRK inhibitor, exhibits antitumor efficacy in preclinical models with deregulated activation of the Myc, β-Catenin, and TRK pathways, Investigational New Drugs, 2021. (Summary) Aurora kinase A, a mitotic kinase that is overexpressed in various cancers, is a promising cancer drug target. Here, we performed preclinical characterization of TAS-119, a novel, orally active, and highly selective inhibitor of Aurora A. TAS-119 showed strong inhibitory effect against Aurora A, with an IC value of 1.04 nmol/L. The compound was highly selective for Aurora A compared with 301 other protein kinases, including Aurora kinase B. TAS-119 induced the inhibition of Aurora A and accumulation of mitotic cells in vitro and in vivo. It suppressed the growth of various cancer cell lines harboring MYC family amplification and CTNNB1 mutation in vitro. In a xenograft model of human lung cancer cells harboring MYC amplification and CTNNB1 mutation, TAS-119 showed a strong antitumor activity at well-tolerated doses. TAS-119 induced N-Myc degradation and inhibited downstream transcriptional targets in MYCN-amplified neuroblastoma cell lines. It also demonstrated inhibitory effect against tropomyosin receptor kinase (TRK)A, TRKB, and TRKC, with an IC value of 1.46, 1.53, and 1.47 nmol/L, respectively. TAS-119 inhibited TRK-fusion protein activity and exhibited robust growth inhibition of tumor cells via a deregulated TRK pathway in vitro and in vivo. Our study indicates the potential of TAS-119 as an anticancer drug, especially for patients harboring MYC amplification, CTNNB1 mutation, and NTRK fusion. (Keyword) Aurora kinase A / cell cycle / Myc / TAS-119 / TRK / β-Catenin (Link to Publication Site) ● Publication site (DOI): 10.1007/s10637-020-01019-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33409897 ● Summary page in Scopus @ Elsevier: 2-s2.0-85099184411 (DOI: 10.1007/s10637-020-01019-9, PubMed: 33409897, Elsevier: Scopus)
11.	Hirari Yamahana, Yukari Kunieda, Masahide Tominaga, Hisatsugu Yamada and Yoshihiro Uto : Development of a novel acetyl glucose-modified gefitinib derivative to enhance the radiosensitizing effect, Bioorganic & Medicinal Chemistry, Vol.29, 115889, 2021. (Summary) Various radiosensitizers are being developed to increase the radiation sensitivity of hypoxic cancer cells, which show resistance to radiation. Previously, we demonstrated that an acetyl glucose-modified nitroimidazole derivative showed a high radiosensitizing effect by inhibiting glucose uptake and glycolysis. Based on this finding, we designed and synthesized novel sugar hybrid radiosensitizers, wherein acetyl glucose was introduced into gefitinib. Among them, UTX-114 had higher autophosphorylation and radiosensitizing activity than gefitinib and inhibited glucose uptake. This result supports our hypothesis that an acetyl glucose moiety improves the radiosensitizing effect of the drug, and UTX-114 can be expected to be a leading compound with a radiosensitizing effect. (Keyword) EGFR / GLUT / Gefitinib / Radiosensitizer / Sugar-hybrids (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2020.115889 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33260051 ● Search Scopus @ Elsevier (PMID): 33260051 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2020.115889 (DOI: 10.1016/j.bmc.2020.115889, PubMed: 33260051)
12.	Yoko Nabeshima, Chiaki Abe, Takeshi Kawauchi, Tomoko Hiroi, Yoshihiro Uto and Yo-Ichi Nabeshima : Simple method for large-scale production of macrophage activating factor GcMAF, Scientific Reports, Vol.10, No.1, 2020. (Summary) Human group-specific component protein (Gc protein) is a multifunctional serum protein which has three common allelic variants, Gc1F, Gc1S and Gc2 in humans. Gc1 contains an O-linked trisaccharide [sialic acid-galactose-N-acetylgalactosamine (GalNAc)] on the threonine (Thr) residue and can be converted to a potent macrophage activating factor (GcMAF) by selective removal of sialic acid and galactose, leaving GalNAc at Thr. In contrast, Gc2 is not glycosylated. GcMAF is considered a promising candidate for immunotherapy and antiangiogenic therapy of cancers and has attracted great interest, but it remains difficult to compare findings among research groups because different procedures have been used to prepare GcMAF. Here, we present a simple, practical method to prepare high-quality GcMAF by overexpressing Gc-protein in a serum-free suspension culture of ExpiCHO-S cells, without the need for a de-glycosylation step. We believe this protocol is suitable for large-scale production of GcMAF for functional analysis and clinical testing. (Tokushima University Institutional Repository) ● Metadata: 116253 (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-020-75571-y (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33154460 ● Summary page in Scopus @ Elsevier: 2-s2.0-85095132417 (Tokushima University Institutional Repository: 116253, DOI: 10.1038/s41598-020-75571-y, PubMed: 33154460, Elsevier: Scopus)
13.	Hiroshi Sootome, Akihiro Miura, Norio Masuko, Takamasa Suzuki, Yoshihiro Uto and Hiroshi Hirai : Aurora A inhibitor TAS-119 enhances antitumor efficacy of taxanes in vitro and in vivo: preclinical studies as guidance for clinical development and trial design, Molecular Cancer Therapeutics, 2020. (Summary) TAS-119 is a novel orally active, selective inhibitor of Aurora kinase A identified as a clinical candidate for efficacy testing in combination with taxanes. In vitro, TAS-119 enhanced cell growth inhibition of paclitaxel in multiple human cancer cell lines derived from various tissues, including paclitaxel-resistant cell lines. Interestingly, TAS-119 did not enhance paclitaxel antitumor activity in normal lung diploid fibroblast cell lines WI-38 and MRC5. In vivo, TAS-119 enhanced the antitumor efficacy of paclitaxel and docetaxel in multiple models at doses inhibitory to Aurora A in tumors. Moreover, the drug combination was well tolerated, and TAS-119 did not exaggerate clinically documented side effects of taxanes, neutropenia and neurotoxicity, in rats. The same TAS-119 concentration enhanced the cell growth inhibitory activity of three clinically approved taxanes, paclitaxel, docetaxel, and cabazitaxel. The degree of enhancement calculated as fold of change of the IC50 value for each taxane was almost the same among the three taxanes. We conducted in vitro and in vivo experiments to develop an optimized combination therapy regimen for TAS-119 with paclitaxel/docetaxel. Using in vitro and in vivo models, we tested the drug administration order for TAS-119 combined with paclitaxel and the TAS-119 treatment duration. The best regimen in preclinical models was combining paclitaxel or docetaxel treatment with 4 days of TAS-119 dosing, which was initiated on the same day as the paclitaxel or docetaxel administration or one day later. This information provided guidance for the design of a clinical trial of TAS-119 and paclitaxel or docetaxel combination. (Link to Publication Site) ● Publication site (DOI): 10.1158/1535-7163.MCT-20-0036 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32788206 ● Search Scopus @ Elsevier (PMID): 32788206 ● Search Scopus @ Elsevier (DOI): 10.1158/1535-7163.MCT-20-0036 (DOI: 10.1158/1535-7163.MCT-20-0036, PubMed: 32788206)
14.	Kazuto Ohkura, Atsushi Tabata, Yoshihiro Uto and Hitoshi Hori : Effect of Isomerization of TX-2036 Derivatives on the Interaction With Tyrosine Kinase Domain of EGF Receptor, Anticancer Research, Vol.40, No.8, 4675-4680, 2020. (Summary) From the design and synthesis of enantiomers, we can expect to obtain two compounds with different pharmacokinetics and pharmacological activities at the same time, which is thought to lead to the development of efficient anticancer agents. Chiral-2-nitroimidazole TX-2036 derivatives exhibit stereo-configuration (R- and S-configuration)-dependent tyrosine kinase inhibitory activity, and the activity of the tyrosine kinase domain of EGF receptor (EGFR-tyk) is suppressed. In order to clarify the reason why the effects on EGFR-tyk activity differ depending on stereoisomers, we tried to analyze the interaction between each TX-2036 derivative and EGFR-tyk. The 2-nitroimidazole-based radiosensitizer TX-2036 series were synthesized and their molecular features were examined using protein kinase inhibition assay and molecular structural analysis. R-configured TXs (TX-2043, -2030, and -2036) exhibited more potent protein kinase inhibitory activity than S-configured TXs (TX-2044, - 2031, and -2037), and the IC value of TX-2036 was 1.8 μM. R-configured TXs interacted with Lys and Thr of EGFR-tyk. The combinations of amino acid residues targeted by the S-configured TXs were different from each other (Ile and Thr (TX-2044), Ser, Thr, and Thr (TX-2031), Gly, Cys, and Thr (TX-2037)). Preparing a series of isomers with different target sites was considered beneficial when the target was mutated. (Keyword) EGF receptor / molecular design / TX-2036 derivatives / structure (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.14466 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32727791 ● Search Scopus @ Elsevier (PMID): 32727791 ● Search Scopus @ Elsevier (DOI): 10.21873/anticanres.14466 (DOI: 10.21873/anticanres.14466, PubMed: 32727791)
15.	Tohru Tasaka, Katsuhiko Maehashi, Hisatsugu Yamada, Akihiro Shirai, Hideki Unuma, Ken Tokunaga, Akio Hayakawa, Akiteru Go, Kikyo Go and Yoshihiro Uto : Therapeutic Effect and Mechanism of Action of Low-molecular-weight Whey Protein Capable of Activating Macrophages in Bovine Mastitis, Anticancer Research, Vol.40, No.8, 4701-4706, 2020. (Summary) Bovine mastitis is caused by the invasion and propagation of pathogenic microorganisms into the udder and mammary gland tissues of cattle. In this study, the therapeutic effect of a low-molecular-weight whey protein (LMW-WP) on bovine mastitis was evaluated. LMW-WP was orally, intraperitoneally, and vaginally administered to bovine with mastitis. The number of somatic cells in milk was measured 24 h before the administration of LMW-WP. The effect of LMW-WP on cytokine production was measured with a microarray that evaluates the expression of cytokines. In the group that received 1,000 mg intraperitoneally, the somatic cell count was reduced to less than 400,000 at the shipment standard value in three of the four udders, indicating 75% efficacy. The group that received 1,000 mg by vaginal administration showed 67% efficacy. It was confirmed that LMW-WP increased the production of cytokines such as IL-5, IL-6, IL-9, IL-12, MCP-1, and VEGF in mouse macrophage cells, but it did not show any antibacterial activity. LMW-WP may be an effective therapeutic agent for bovine mastitis. (Keyword) Low-molecular-weight whey protein / bovine mastitis / cytokines / macrophages (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.14470 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32727795 ● Search Scopus @ Elsevier (PMID): 32727795 ● Search Scopus @ Elsevier (DOI): 10.21873/anticanres.14470 (DOI: 10.21873/anticanres.14470, PubMed: 32727795)
16.	Hirari Yamahana, Takahisa Takino, Yoshio Endo, Hisatsugu Yamada, Takeshi Suzuki and Yoshihiro Uto : A novel celecoxib analog UTX-121 inhibits HT1080 cell invasion by modulating membrane-type 1 matrix metalloproteinase, Biochemical and Biophysical Research Communications, Vol.521, No.1, 137-144, 2020. (Summary) We designed and synthesized a celecoxib derivative UTX-121 to enhance its anti-tumor activity. Similar to celecoxib, this compound could also inhibit matrix metalloproteinase (MMP)-9 activity. In addition, UTX-121 suppressed membrane-type 1 MMP (MT1-MMP)-mediated pro-MMP-2 activation by disturbing the cell surface expression of MT1-MMP. UTX-121 also impeded the glycosylation of cell surface proteins, resulting in the suppression of cell attachment to fibronectin. This inhibition by UTX-121 caused the reduction of fibronectin-stimulated focal adhesion kinase activation, Akt activation, and cell migration. Consequently, UTX-121 treatment significantly inhibited fibronectin-induced HT1080 cell invasion into the Matrigel. UTX-121 may be a potent lead compound that can be used to develop a novel anti-tumor drug. (Keyword) COX / Cell adhesion / Invasion / MMP / MT1-MMP (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2019.10.092 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31629465 ● Search Scopus @ Elsevier (PMID): 31629465 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2019.10.092 (DOI: 10.1016/j.bbrc.2019.10.092, PubMed: 31629465)
17.	Kazuto Ohkura, Atsushi Tabata, Yoshihiro Uto and Hitoshi Hori : Correlation Between Radiosensitizing Activity and the Stereo-structure of the TX-2036 Series of Molecules, Anticancer Research, Vol.39, No.8, 4479-4483, 2019. (Summary) The stereo-configuration (R-, S-configuration) of chiral-2-nitroimidazole derivatives alters their radiosensitizing activity. This study aimed at examining the molecular features of these enantiomers by molecular simulation techniques. A series of 2-nitroimidazole-based radiosensitizer TX-2036 molecules were synthesized, and their profiles were examined using molecular structural analysis such as conformation analysis, molecular orbital analysis, and electrostatic potential analysis. R-configured TXs (TX-2043, -2030, -2036) had a weaker radiosensitizing activity than S-configured TXs (TX-2044, -2031, -2037), and R-compounds had a small minus electrostatic potential (ESP) field in the cyclopentene-1,3-dione region. S-configured TX-2046 had weaker radiosensitizing activity than R-configured TX-2045, and TX-2046 had a small minus ESP field as well as R-configured TX-2043, -2030, - 2036. The cyclopentene-1,3-dione involved in the small minus ESP field affected the radiosensitizing activity of the TX-2036 series of molecules. (Keyword) molecular design / TX-2036 / radiosensitizing activity / structure (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.13622 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31366548 ● Summary page in Scopus @ Elsevier: 2-s2.0-85070717728 (DOI: 10.21873/anticanres.13622, PubMed: 31366548, Elsevier: Scopus)
18.	Junya Iwasaki, Toshiharu Komori, Fumio Nakagawa, Hideki Nagase, Junji Uchida, Kenichi Matsuo and Yoshihiro Uto : Schlafen11 Expression Is Associated With the Antitumor Activity of Trabectedin in Human Sarcoma Cell Lines, Anticancer Research, Vol.39, No.7, 3553-3563, 2019. (Summary) Trabectedin is a DNA-damaging agent and has been approved for the treatment of patients with advanced soft tissue sarcoma. Schlafen 11 (SLFN11) was identified as a dominant determinant of the response to DNA-damaging agents. The aim of the study was to clarify the association between SLFN11 expression and the antitumor activity of trabectedin. The antitumor activity of trabectedin was evaluated under different expression levels of SLFN11 regulated by RNA interference and CRISPR-Cas9 systems, and the combined antitumor activity of ataxia telangiectasia and Rad3-related protein kinase (ATR) inhibitor and trabectedin in sarcoma cell lines using in vitro a cell viability assay and in vivo xenograft models. SLFN11-knockdown cell lines had a lower sensitivity to trabectedin, compared to parental cells. ATR inhibitor enhanced the antitumor activity of trabectedin in SLFN11-knockdown cells and in a SLFN11-knockout xenograft model. SLFN11 expression might be a key factor in the antitumor activity of trabectedin. (Keyword) DNA repair / Schlafen11 / anticancer drug / sarcoma / trabectedin (Tokushima University Institutional Repository) ● Metadata: 113620 (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.13501 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31262879 ● Search Scopus @ Elsevier (PMID): 31262879 ● Search Scopus @ Elsevier (DOI): 10.21873/anticanres.13501 (Tokushima University Institutional Repository: 113620, DOI: 10.21873/anticanres.13501, PubMed: 31262879)
19.	Yota Jiho, Ryohsuke Kurihara, Kiyohiko Kawai, Hisatsugu Yamada, Yoshihiro Uto and Kazuhito Tanabe : Enzymatic activation of indolequinone-substituted 5-fluorodeoxyuridine prodrugs in hypoxic cells, Bioorganic & Medicinal Chemistry Letters, Vol.29, No.11, 1304-1307, 2019. (Summary) Among the various enzymes, reductases that catalyze one-electron reduction are involved in the selective activation of functional compounds or materials in hypoxia, which is one of the well-known pathophysiological characteristics of solid tumors. Enzymatic one-electron reduction has been recognized as a useful reaction that can be applied in the design of tumor hypoxia-targeting drugs. In this report, we characterized the enzymatic reaction of 5-fluorodeoxyuridine (FdUrd) prodrug bearing an indolequinone unit (IQ-FdUrd), which is a substrate of reductases. IQ-FdUrd was activated to release FdUrd under hypoxic conditions after treatment with cytochrome NADPH P450 reductase. We also confirmed that IQ-FdUrd showed selective cytotoxicity in hypoxic tumor cells. (Keyword) Enzymatic activation / Prodrug / Reductase / Tumor hypoxia (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmcl.2019.04.003 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30975626 ● Search Scopus @ Elsevier (PMID): 30975626 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmcl.2019.04.003 (DOI: 10.1016/j.bmcl.2019.04.003, PubMed: 30975626)
20.	Kazuto Ohkura, Y Kawaguchi, Y Tatematsu, Atsushi Tabata, Yoshihiro Uto and Hitoshi Hori : Structure-associated Functional Control of TX-1877 Series by Glyco-conjugation, Anticancer Research, Vol.38, No.7, 4241-4245, 2018. (Summary) Sugar molecules are often used as a tool to structurally modify chemical compounds. The features of synthesized sugar-conjugated TX-1877 derivatives were herein examined. The molecular stabilities (reactivity) and hydrophobicities of sugar (e.g., monosaccharide and tetra-O-acetylated monosaccharide)-conjugated TXs were analyzed using a molecular simulation (e.g. molecular mechanics (MM) and molecular orbital (MO) analysis). The hydrophobicities of TX-1877 derivatives were increased by tetra-O-acetylation, and TX-2244 exhibited the most potent radiosensitizing activity (enhancement ratio: ER=2.30). The conformations and hydrophobicities of chemical compounds may be controlled by adding monosaccharide- and tetra-O-acetyl-conjugated sugars to TX-1877. (Keyword) molecular design / TX-1877 / structure glyco-conjugation (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.12720 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29970557 ● Summary page in Scopus @ Elsevier: 2-s2.0-85049784420 (DOI: 10.21873/anticanres.12720, PubMed: 29970557, Elsevier: Scopus)
21.	Tohru Tasaka, Emi Kuwada, Yuka Izuchi, Ryohei Nishigawa, Hisatsugu Yamada, Hideki Unuma, Ken Tokunaga, Akio Hayakawa, Akiteru Go, Kikyo Go and Yoshihiro Uto : Concentration-dependent Activation of Inflammatory/Anti-inflammatory Functions of Macrophages by Hydrolyzed Whey Protein, Anticancer Research, Vol.38, No.7, 4299-4304, 2018. (Summary) Whey protein is a mixture of globulins isolated from whey and mainly composed of β-lactoglobulin, α-lactoalbumin, and lactoferrin. In this study, whey protein was hydrolyzed using various proteases, and the macrophage activation was evaluated. Hydrolyzed whey protein was prepared using various proteases to evaluate phagocytic activity and cytokine productivity. The results of SDS-PAGE and gel permeation chromatography (GPC) analysis indicated that the molecular weight of whey protein was reduced using various proteases. The hydrolyzed whey protein showed a concentration-dependent induction of macrophage phagocytic activity. In addition, the hydrolyzed whey protein significantly enhanced the production of the inflammatory cytokine, TNF-α. Production of the anti-inflammatory cytokine, IL-10, was not observed at concentrations up to 1 μg, but significant production was confirmed at 100 μg. Hydrolyzed whey protein can induce the phagocytic activity of macrophages and activation of the inflammatory/anti-inflammatory functions of the macrophages depends on the concentration of the hydrolyzed whey protein. (Keyword) Hydrolyzed whey protein / anti-inflammation / inflammation / macrophage activation / protease (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.12728 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29970565 ● Summary page in Scopus @ Elsevier: 2-s2.0-85049804361 (DOI: 10.21873/anticanres.12728, PubMed: 29970565, Elsevier: Scopus)
22.	Tomoko Kaneko, Masahide Tominaga, Risa Kouzaki, Ayaka Hanyu, Kazuki Ueshima, Hisatsugu Yamada, Masaki Suga, Tomohiro Yamashita, Tomoaki Okimoto and Yoshihiro Uto : Radiosensitizing Effect of 5-Aminolevulinic Acid and Protoporphyrin IX on Carbon-ion Beam Irradiation, Anticancer Research, Vol.38, No.7, 4313-4317, 2018. (Summary) Carbon-ion beam is one of the most advanced radiations used for cancer treatment. However, there are tumors that are difficult to suppress with carbon-ion beam alone, thus necessitating development of drugs that can enhance its therapeutic effect. In this regard, the radiosensitizing effect of 5-aminolevulinic acid (ALA) and protoporphyrin IX (PpIX), that is a metabolic intermediate of ALA, on carbon-ion beam was investigated. Radiosensitizing activity, mitochondrial ROS and DNA double-strand break production of ALA and PpIX were evaluated by irradiation with 1.0 or 1.5-Gy carbon-ion beam to mouse mammary EMT6 tumor cells. Combination of carbon-ion beam and ALA or PpIX showed a significant enhancement of its cytotoxic activity through a significant increase in ROS production in mitochondria. Furthermore, the combined activity of carbon-ion beam and ALA resulted in a significant increase in DNA double-strand breakage. ALA selectively accumulates in the mitochondria and PpIX synthesized from ALA reacts with carbon-ion beam to produce ROS that exert antitumor activity. (Keyword) 5-Aminolevulinic acid / carbon-ion beam / mitochondria / protoporphyrin IX / reactive oxygen species (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.12730 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29970567 ● Summary page in Scopus @ Elsevier: 2-s2.0-85049771897 (DOI: 10.21873/anticanres.12730, PubMed: 29970567, Elsevier: Scopus)
23.	BC Nguyen, SA Kim, SM Won, SK Park, Yoshihiro Uto and Hiroshi Maruta : 1,2,3-Triazolyl ester of ketorolac (15K): Boosting both heat-endurance and lifespan of C. elegans by down-regulating PAK1 at nM levels, Drug Discoveries & Therapeutics, Vol.12, No.2, 92-96, 2018. (Summary) PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C. elegans, but none of them has been effective at nM levels. Thus, we examined in vivo effect of 15K at nM levels on the survival rate of C. elegans with or without heat-shock. Like the PAK1-deficient mutant, 15K (at 50 nM)-treated worm significantly lives longer, is far more heat-resistant and less productive (fertile) than the non-treated counterpart, with an increased expression of HSP16 gene. 15K has been proven to be among the most potent anti-cancerous and longevity-promoting PAK1-blockers, and therefore has a potential to treat a variety of solid tumours without severe side effect. (Keyword) 1,2,3-triazolyl ester / C. elegans / Ketorolac / PAK1 / anti-cancer / lifespan (Link to Publication Site) ● Publication site (DOI): 10.5582/ddt.2018.01018 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29760342 ● CiNii @ National Institute of Informatics (CRID): 1390282680712437504 ● Search Scopus @ Elsevier (PMID): 29760342 ● Search Scopus @ Elsevier (DOI): 10.5582/ddt.2018.01018 (DOI: 10.5582/ddt.2018.01018, PubMed: 29760342, CiNii: 1390282680712437504)
24.	Mok-Ryeon Ahn, Ji-Yeon Bae, Da-Hye Jeong, Hideaki Takahashi, Yoshihiro Uto and Hiroshi Maruta : Both triazolyl ester of ketorolac (15K) and YM155 inhibit the embryonic angiogenesis in ovo (fertilized eggs) via their common PAK1-survivin/VEGF signaling pathway., Drug Discoveries & Therapeutics, Vol.11, No.6, 300-306, 2018. (Summary) 15 K is 1,2, 3-triazolyl ester of ketorolac, an old pain-killer, that blocks PAK1 by its R-form and inhibits COX-2 by its S-form. Mainly due to a robust increase in cell-permeability, 15K is over 500 times more potent than ketorolac in both anti-cancer and anti-PAK1 activities in cell culture with IC50 around 24 nM. However, 15K has no anti-AKT activity. Angiogenesis requires at least the kinase PAK1, and perhaps the kinase AKT as well, and is essential for a robust growth of solid tumors. Thus, in this study, we examined the potential antiangiogenic activity of 15K both in ovo and cell culture, prior to its in vivo (xenograft) anti-cancer activity test. The IC50 of 15K against the embryonic angiogenesis in ovo in CAM (chorioallantoic membrane) assay is around 1 nmol/egg. Surprizingly, however, 15K failed to inhibit the tube formation of HUVECs (human umbilical vein endothelial cells) in cell culture even at high as 150 μM. In an attempt to solve this mystery, we tested both in ovo as well as HUVECs-based anti-angiogenic activity of a potent survivin-suppressor called YM155, which blocks PAK1, in addition to AKT. YM155 is slightly more potent than 15K in CAM assay with IC50 around 0.5 nmol/egg, and apparenty inhibits the tube formation of HUVECs with IC50 around 18 nM. According to a few previous findings with the direct PAK1-inhibitor frondoside A (FRA), the tube formation of HUVECs depends solely on PAK1. Thus, the failure of 15K to affect their tube formation is most likely due to their drug (15K)-resistance. Furthermore, unlike FRA, YM155 killed HUVECs with IC50 around 18 nM, clearly indicating that AKT is essential for survival of HUVECs, instead of their tube formation. (Keyword) HUVECs / PAK1 / YM155 / angiogenesis / ketorolac ester (15K) / survivin suppressor (Link to Publication Site) ● Publication site (DOI): 10.5582/ddt.2017.01058 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29332887 ● CiNii @ National Institute of Informatics (CRID): 1390282680714713472 ● Search Scopus @ Elsevier (PMID): 29332887 ● Search Scopus @ Elsevier (DOI): 10.5582/ddt.2017.01058 (DOI: 10.5582/ddt.2017.01058, PubMed: 29332887, CiNii: 1390282680714713472)
25.	Yusei Shinohara, Yoshio Endo, Chiaki Abe, Ikkyu Shiba, Masahiro Ishizuka, Tohru Tanaka, Yutaka Yonemura, Syunichiro Ogura, Masahide Tominaga, Hisatsugu Yamada and Yoshihiro Uto : Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy., Photodiagnosis and Photodynamic Therapy, Vol.20, 182-188, 2017. (Summary) 5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various cancers. Recently, we found that treatment of cancer cells with the Schiff base derivative TX-816 along with ALA could significantly increase the efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to 3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX-816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT. Furthermore, DCSA could restore the sensitivity of cancer cells that acquired resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might be a useful compound for designing prodrug-type ALA-PDT enhancers. (Keyword) 5-Aminolevulinic acid / Photodynamic therapy / Protoporphyrin IX / Schiff base (Link to Publication Site) ● Publication site (DOI): 10.1016/j.pdpdt.2017.10.014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29056554 ● Summary page in Scopus @ Elsevier: 2-s2.0-85032287431 (DOI: 10.1016/j.pdpdt.2017.10.014, PubMed: 29056554, Elsevier: Scopus)
26.	Kazuto Ohkura, Y Tatematsu, Y Kawaguchi, Yoshihiro Uto and Hitoshi Hori : Interactive Analysis of TX-1123 with Cyclo-oxygenase: Design of COX2 Selective TX Analogs., Anticancer Research, Vol.37, No.7, 3849-3854, 2017. (Summary) To date, two cyclo-oxygenase (COX) isoforms, COX1 and COX2, have been identified. In the present study, the COX-inhibitory activities of TX-1123 derivatives with the 2-hydroxyarylidene-4-cyclopentene-1,3-dione structure were examined, and the binding profiles of TX-1123 to COXs were analyzed using docking simulations. X-Ray data on COX1 [protein data bank (PDB) ID=1PGG] and COX2 (PDB ID=3LN1) were used for molecular interactive simulations. The interactive profiles of TX-1123 derivatives with COXs were examined using a molecular simulation technique with Molegro Virtual Docker (CLC bio, Aarhus, Denmark). TX-1123 exhibited COX1-inhibitory activity [half-maximal-inhibitory concentration (IC)=1.57×10 M]. The COX2 inhibitory activity of TX-1123 was potent (IC=1.16×10 M), and the ratio of COX1/COX2 inhibition was 13.5. TX-1123 bound to the COX2 molecule, and the oxygen atom of the 4-cyclopentene-1,3-dione region of TX-1123 interacted with Cys and Gln of COX2. The TX-1123-binding pocket of COX2 differs from that of the COX2-selective celecoxib-binding pocket. TX-1123 exhibited a different COX2-interactive mechanism from that of celecoxib. (Keyword) Protein kinase / cyclo-oxygenase / kinase inhibitor (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.11764 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28668885 ● Summary page in Scopus @ Elsevier: 2-s2.0-85021744282 (DOI: 10.21873/anticanres.11764, PubMed: 28668885, Elsevier: Scopus)
27.	Ikkyu Shiba, Risa Kouzaki, Hisatsugu Yamada, Yoshio Endo, Takahisa Takino, Hiroshi Sato, Keiko Kitazato, Teruyoshi Kageji, Shinji Nagahiro and Yoshihiro Uto : Design and Synthesis of Novel Anti-metastatic Hypoxic Cytotoxin TX-2137 Targeting AKT Kinase., Anticancer Research, Vol.37, No.7, 3877-3883, 2017. (Summary) The hypoxic microenvironment plays a crucial role in the malignant progression of tumor cells. Moreover, AKT, a serine/threonine kinase, is activated by various extracellular growth factors and is important for cell growth, survival, and motility of leukocytes, fibroblasts, endothelial cells, and tumor cells. Therefore, we aimed to design an anti-metastatic hypoxic cytotoxin which has inhibitory effects on AKT.TX-2137 was designed and synthesized based on the structural similarity of a preexisting AKT1/2 kinase inhibitor and a hypoxic cytotoxin tirapazamine. TX-2137 effectively reduced the expression of phosphorylated AKT and matrix metalloproteinase 9 (MMP9) and showed strong inhibition of the proliferation of B16-F10, HT-1080, and MKN-45 cells. In addition, TX-2137 exhibited hypoxia-selective cytotoxicity towards A549 cells and inhibited liver metastasis of B16-F10 cells in a xenograft chick embryo model in the same way as doxorubicin.TX-2137 may be a potent lead compound in the development of a novel anti-metastatic AKT kinase inhibitor. (Keyword) AKT / TX-2137 / anti-metastatic agent / hypoxic cytotoxin (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.11768 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28668889 ● Search Scopus @ Elsevier (PMID): 28668889 ● Search Scopus @ Elsevier (DOI): 10.21873/anticanres.11768 (DOI: 10.21873/anticanres.11768, PubMed: 28668889)
28.	Tomohiro Osaki, Isao Sakata, Yoshihiro Uto, Kazuo Azuma, Yusuke Murahata, Takeshi Tsuka, Norihiko Itoh, Tomohiro Imagawa and Yoshiharu Okamoto : Photodynamic Therapy Mediated by a Novel Chlorin Derivative, TONS 501-Na, in EMT6 cells., Anticancer Research, Vol.37, No.4, 1723-1728, 2017. (Summary) The lipophilic photosensitizer, TONS 501, is a novel porphyrin-derived methyl ester that was developed for photodynamic antimicrobial chemotherapy. This study developed a hydrophilic and anionic porphyrin salt of this compound (TONS 501-Na) for use in photodynamic therapy (PDT). This chlorin derivative is synthesized from the protoporphyrin IX dimethyl ester. We investigated the in vitro cytotoxic effects of TONS 501-Na-mediated PDT on EMT6 mouse breast cancer cells. EMT6 cells were incubated with 0-100 μg/ml TONS 501-Na for 24 h prior to replacing the culture medium and exposing the cells to 6 mW/cm diode laser irradiation at 0-13 J/cm to induce PDT. Morphological changes and cell viability were evaluated 24 h after PDT. The percentages of apoptotic cells were evaluated 4 h and 24 h after PDT. The concentrations of TONS 501-Na that killed 50% of EMT6 cells after exposure to light doses of 0, 0.4, 3, 6, or 13 J/cm were 84.6, 33.2, 18, 8.2, and 2.2 μg/ml, respectively. Tumor cells exposed to PDT showed chromatin condensation and fragmentation. The percentages of apoptotic cells increased in a TONS 501-Na concentration-dependent manner in the PDT group, and were significantly higher than those in the control group or in cells treated with TONS 501-Na or laser irradiation alone. TONS 501-Na-mediated PDT induced mouse breast cancer cell death in a concentration-dependent manner. Future studies should evaluate the in vivo pharmacokinetics, tissue distribution, and photodynamic effects of TONS 501-Na. (Keyword) apoptosis / TONS 501-Na / photodynamic therapy (Link to Publication Site) ● Publication site (DOI): 10.21873/anticanres.11504 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28373434 ● Summary page in Scopus @ Elsevier: 2-s2.0-85017456224 (DOI: 10.21873/anticanres.11504, PubMed: 28373434, Elsevier: Scopus)
29.	Tomohiro Osaki, Yoshihiro Uto, Masahiro Ishizuka, Tohru Tanaka, Nobuyasu Yamanaka, Tsukasa Kurahashi, Kazuo Azuma, Yusuke Murahata, Takeshi Tsuka, Norihiko Ito, Tomohiro Imagawa and Yoshiharu Okamoto : Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro, Molecules, Vol.22, No.4, 533, 2017. (Summary) Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required. (Keyword) 5-aminolevulinic acid / artesunate / breast cancer / sonodynamic therapy / ultrasound (Tokushima University Institutional Repository) ● Metadata: 115607 (Link to Publication Site) ● Publication site (DOI): 10.3390/molecules22040533 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28346389 ● Summary page in Scopus @ Elsevier: 2-s2.0-85016330631 (Tokushima University Institutional Repository: 115607, DOI: 10.3390/molecules22040533, PubMed: 28346389, Elsevier: Scopus)
30.	Quan Binh Cao Nguyen, Hideaki Takahashi, Yoshihiro Uto, MD Shahinozzaman, Shinkichi Tawata and Hiroshi Maruta : 1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1-blocking cancer-killer., European Journal of Medicinal Chemistry, Vol.126, 270-276, 2017. (Summary) An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC against the growth of human cancer cells such as A549 is around 13 μM). In an attempt to boost its anti-cancer activity, hopefully by increasing its cell-permeability through abolishing the negative charge, yet keeping its water-solubility, here we synthesized a 1,2,3-triazolyl ester of Toradol through "Click Chemistry". The resultant water-soluble "azo" derivative called "15K" was found to be over 500 times more potent than Toradol with the IC around 24 nM against the PAK1-dependent growth of A549 cancer cells, inactivating PAK1 in cell culture with the apparent IC around 65 nM, and inhibiting COX-2 in vitro with the IC around 6 nM. Furthermore, the Click Chemistry boosts the anti-cancer activity of Ketorolac by 5000 times against the PAK1-independent growth of B16F10 melanoma cells. Using a multi-drug-resistant (MDR) cancer cell line (EMT6), we found that the esterization of Ketorolac boosts its cell-permeability by at least 10 folds. Thus, the Click Chemistry dramatically boosts the anti-cancer activity of Ketorolac, at least in three ways: increasing its cell-permeability, the anti-PAK1 activity of R-form and anti-COX-2 activity of S-form. The resultant "15K" is so far among the most potent PAK1-blockers, and therefore would be potentially useful for the therapy of many different PAK1-dependent diseases/disorders such as cancers. (Keyword) COX-2 / cancer / Click chemistry / Ketorolac / PAK1 / Triazole ring (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ejmech.2016.11.038 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27889630 ● Summary page in Scopus @ Elsevier: 2-s2.0-84997522793 (DOI: 10.1016/j.ejmech.2016.11.038, PubMed: 27889630, Elsevier: Scopus)
31.	Eiji Nakata, Yoshihiro Yukimachi, Yoshihiro Uto, Hitoshi Hori and Takashi Morii : Latent pH-responsive ratiometric fluorescent cluster based on self-assembled photoactivated SNARF derivatives, Science and Technology of Advanced Materials, Vol.17, No.1, 431-436, 2016. (Summary) We have developed a self-assembled fluorescent cluster comprising a seminaphthorhodafluor (SNARF) derivative protected by a photoremovable o-nitrobenzyl group. Prior to UV irradiation, a colorless and nonfluorescent cluster was spontaneously assembled in aqueous solution. After UV irradiation, the self-assembled cluster remained intact and showed a large enhancement in pH-responsive fluorescence. The unique pH responsive fluorescent cluster could be used as a dual-emissive ratiometric fluorescent pH probe not only in the test tube but also in HeLa cell cultures. (Keyword) Self-assembly / Self-organized materials / Sensors and actuators / Bio-inspired and biomedical materials / Self-assembly / fluorescent material / pH indicator / photoactivation / ratiometry (Tokushima University Institutional Repository) ● Metadata: 115721 (Link to Publication Site) ● Publication site (DOI): 10.1080/14686996.2016.1204888 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27877893 ● Search Scopus @ Elsevier (PMID): 27877893 ● Search Scopus @ Elsevier (DOI): 10.1080/14686996.2016.1204888 (Tokushima University Institutional Repository: 115721, DOI: 10.1080/14686996.2016.1204888, PubMed: 27877893)
32.	Yoshiki Shimamura, Dai Tamatani, Shota Kuniyasu, Yusuke Mizuki, Takuma Suzuki, Hanayo Katsura, Hisatsugu Yamada, Yoshio Endo, Tomohiro Osaki, Masahiro Ishizuka, Toru Tanaka, Nobuyasu Yamanaka, Tsukasa Kurahashi and Yoshihiro Uto : 5-Aminolevulinic Acid Enhances Ultrasound-mediated Antitumor Activity via Mitochondrial Oxidative Damage in Breast Cancer, Anticancer Research, Vol.36, No.7, 3607-3612, 2016. (Summary) 5-Aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), is now used for photodynamic therapy (PDT) of pre-cancers of the skin and photodynamic diagnosis (PDD) of brain tumors. Sonodynamic therapy (SDT) of cancers with ultrasound has been studied using 5-ALA as a sonosensitizer. In this article, we evaluated the sonosensitizing activity and mode of action of 5-ALA/PpIX by using mouse mammary tumor EMT6 cells.5-ALA-SDT showed significant antitumor effects toward EMT6 cells in vitro and in vivo. The fluorescence of MitoSOX Red, an indicator specific for mitochondrial superoxide, was significantly increased by 5-ALA-SDT. Moreover, the fluorescence derived from JC-1, an indicator of mitochondrial membrane potential, was also significantly increased by 5-ALA-SDT. These findings suggest that mitochondria are one of the target organelles of 5-ALA-SDT. PpIX enhanced reactive oxygen species (ROS) production from tert-butyl hydroperoxide (tBHP), suggesting that PpIX might stabilize or promote ROS generation from tBHP.5-ALA-SDT showed an antitumor effect in mouse mammary tumor EMT6 cells through oxidation of the mitochondrial membrane via ROS production. (Keyword) 5-Aminolevulinic acid / mammary tumor / mitochondria / protoporphyrin IX / reactive oxygen species / sonodynamic therapy (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27354630 ● Summary page in Scopus @ Elsevier: 2-s2.0-84992109817 (PubMed: 27354630, Elsevier: Scopus)
33.	Yukio Morimoto, Hideko Nagasawa, Yoshihiro Uto, Toshiyuki Chatake and Hitoshi Hori : Structural Insight Into Protein Binding of Boron Tracedrug UTX-97 Revealed by the Co-Crystal Structure With Lysozyme at 1.26 Å Resolution, Journal of Pharmaceutical Sciences, Vol.105, No.8, 2298-2301, 2016. (Summary) Boron neutron capture therapy (BNCT) is one of the numbers of radiotherapies for treatment of certain cancers. The ability of low-dose irradiation with neutrons or radioactive beams to provide an acceptable quality of life is an objective which has not yet been achieved; therefore it will be necessary to increase the efficiency of the neutron capture reaction by lower dose irradiation and by achieving higher drug concentrations in living cells. Drug selectivity in targeting the affected cellular compartment is most important. Molecular design and synthesis of drugs should be based on high resolution structures and analysis of specific compounds and host molecules; however, it is necessary to obtain crystals for X-ray structural analysis. Because compounds containing bulky functional groups are difficult to crystalize due to their flexibility, the method described here makes it possible to stabilize these compounds by complexing them with protein molecules. We have first solved the three-dimensional structure of a BNCT drug-protein molecule combination at 1.26 Å resolution, and discuss the nature of the interaction between a BNCT drug and the protein molecule residues. (Keyword) boron tracedrug / boron neutron capture therapy / protein structure / X-ray crystal analysis (Link to Publication Site) ● Publication site (DOI): 10.1016/j.xphs.2016.06.005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27422088 ● Summary page in Scopus @ Elsevier: 2-s2.0-84978969925 (DOI: 10.1016/j.xphs.2016.06.005, PubMed: 27422088, Elsevier: Scopus)
34.	Kazuto Ohkura, Yuki Kawaguchi, Y Tatematsu, Yoshihiro Uto and Hitoshi Hori : An Antitumor 2-Hydroxyarylidene-4-cyclopentene-1,3-Dione as a Protein Tyrosine Kinase Inhibitor: Interaction Between TX-1123 Derivatives and Src Kinase, Anticancer Research, Vol.36, No.7, 3645-3649, 2016. (Summary) Protein tyrosine kinases (PTKs) play major roles in signal transduction during cell proliferation and apoptosis. Tyrphostin AG17 was previously shown to be a potent tumor growth inhibitor, while AG17 induced apoptosis and inhibited activity of cyclin-dependent kinase 2. We herein describe the binding features of tyrphostin AG17 analogs, such as TX-1123, with Src kinase (Src-K).MATERIALS AND METHODS:Structural data for Src-K were obtained from a protein data bank (ID=2SRC), and the molecular interactions between Src-K and TX-1123 derivatives were examined.RESULTS:TX-1123 exihibited potent Src-K inhibitory activity (half maximal-inhibitory concentration=2.2 M), and fit into the pocket of the Src-K molecule as well as c-AMP did.CONCLUSION:The binding profiles of TX-1123 derivatives differed from each other, while their Src-K inhibitory activities were affected by their fit in the Src-K molecule. (Keyword) Protein kinase / TX-1123 derivative / kinase inhibitor (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27354635 ● Summary page in Scopus @ Elsevier: 2-s2.0-84992160339 (PubMed: 27354635, Elsevier: Scopus)
35.	Yu Sumiya, Takahiro Inoue, Mami Ishikawa, Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Yoshihiro Uto and Takahito Nishikata : Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors, Anticancer Research, Vol.36, No.7, 3619-3623, 2016. (Summary) BACKGROUND/AIM:Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy.MATERIALS AND METHODS:We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF.RESULTS:All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent.CONCLUSION:Macrophage activation states and mechanisms are heterogeneous. (Keyword) immunotherapy / THP-1 cell line / U937 cell line / macrophage-activating factor / phagocytic activity (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27354632 ● Summary page in Scopus @ Elsevier: 2-s2.0-84992028332 (PubMed: 27354632, Elsevier: Scopus)
36.	Toshio Inui, Haruka Amitani, Kentaro Kubo, Daisuke Kuchiike, Yoshihiro Uto, Takahito Nishikata and Martin Mette : Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields, Anticancer Research, Vol.36, No.7, 3767-3770, 2016. (Summary) BACKGROUND/AIM:Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment.CASE REPORT:We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies.RESULTS:This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects.CONCLUSION:This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment. (Keyword) immunotherapy / macrophage activating factor (MAF) / Sonodynamic Therapy / Tumor Treating Field / Non-small Cell Lung Cancer (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27354652 ● Summary page in Scopus @ Elsevier: 2-s2.0-84992110623 (PubMed: 27354652, Elsevier: Scopus)
37.	Toshio Inui, Goro Katsuura, Kentaro Kubo, Daisuke Kuchiike, Leslye Chenery, Yoshihiro Uto, Takahito Nishikata and Martin Mette : Case Report: GcMAF Treatment in a Patient with Multiple Sclerosis, Anticancer Research, Vol.36, No.7, 3771-3774, 2016. (Summary) Gc protein-derived macrophage-activating factor (GcMAF) has various functions as an immune modulator, such as macrophage activation, anti-angiogenic activity and anti-tumor activity. Clinical trials of second-generation GcMAF demonstrated remarkable clinical effects in several types of cancers. Thus, GcMAF-based immunotherapy has a wide application for use in the treatment of many diseases via macrophage activation that can be used as a supportive therapy. Multiple sclerosis (MS) is considered to be an autoimmune disorder that affects the myelinated axons in the central nervous system (CNS). This study was undertaken to examine the effects of second-generation GcMAF in a patient with MS. This case study demonstrated that treatments of GcMAF in a patient with MS have potent therapeutic actions with early beneficial responses, especially improvement of motor dysfunction. GcMAF shows therapeutic potency in the treatment of MS. (Keyword) immunotherapy / macrophage activating factor (MAF) / GcMAF / colostrum MAF / multiple sclerosis / motor dysfunction (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27354653 ● Summary page in Scopus @ Elsevier: 2-s2.0-84992156930 (PubMed: 27354653, Elsevier: Scopus)
38.	Tomoko Kaneko, Masahide Tominaga, Yoshio Endo, Kazunori Yaju, Risa Kouzaki, Hisatsugu Yamada, Ikuo Nakanishi, Kenichiro Mastumoto and Yoshihiro Uto : RADIOSENSITIZING EFFECT OF PROTOPORPHYRIN IX WITH CARBON ION BEAM AGAINST MOUSE MAMMARY BREAST TUMOR CELL., Journal of Advanced Manufacturing Technology, 47-51, 2016. (Summary) 5-Aminolevulinic acid (ALA), a precursor ofprotoporphyrin IX (PpIX), has been utilized as a potent sensitizerfor photodynamic therapy (PDT) of cancer through productionof reactive oxygen species (ROS). ALA also has been proposed asa possible radiosensitizer with low linear energy transfer (LET)radiation because antitumor activity of low-LET radiation dependson ROS mainly. In this paper, we investigated the radiosensitizingactivity of PpIX in carbon ion irradiation as a high LET radiation.PpIX was detected in an EMT6 mouse mammary breast tumor cellseven at 24 h post treatment. The cytotoxicity of PpIX against EMT6cells was IC50 = 48.0 m. The combined treatment of 1.0 m of PpIXwith 2 Gy of carbon ion irradiation (290 MeV/nucleon, 85.1 keV/m)showed a more potent antitumor activity than carbon ion irradiationalone. We demonstrated that PpIX showed a radiosensitizing effectwith carbon ion beam against mouse mammary breast tumor cells. (Keyword) Carbon Ion Beam / Protoporphyrin IX / Aminolevulinic Acid / Radiosensitization
39.	Tomohiro Osaki, Misato Ono, Yoshihiro Uto, Masahiro Ishizuka, Tohru Tanaka, Nobuyasu Yamanaka, Tsukasa Kurahashi, Kazuo Azuma, Yusuke Murahata, Takeshi Tsuka, Norihiko Ito, Tomohiro Imagawa and Yoshiharu Okamoto : Sonodynamic therapy using 5-aminolevulinic acid enhances the efficacy of bleomycin., Ultrasonics, Vol.67, 76-84, 2016. (Summary) Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound and a sonosensitizer agent. We examined whether 5-aminolevulinic acid (5-ALA)-based SDT at 1 or 3MHz could enhance the cytotoxicity of bleomycin (BLM) toward mouse mammary tumor cells both in vitro and in vivo. At 1MHz, cell viability in the 5-ALA-based SDT group at 1, 2, and 3W/cm(2) was 34.30%, 50.90%, and 60.16%, respectively. Cell viability in the 5-ALA-based SDT+BLM group at 1, 2, and 3W/cm(2) was 0.09%, 0.32%, and 0.17%, respectively. In contrast, at 3MHz, 5-ALA-based SDT+BLM did not show pronounced cytotoxicity. In the in vivo study, 5-ALA-based SDT+BLM was significantly more cytotoxic than 5-ALA-based SDT at 1MHz and 3MHz. These findings suggest that the mechanism of tumor shrinkage induced by 5-ALA-based SDT+BLM might involve not only direct cell killing, but also vascular shutdown. Thus, we show here that 5-ALA-based SDT enhances the efficacy of BLM both in vitro and in vivo. (Keyword) Aminolevulinic Acid / Animals / Bleomycin / Cell Survival / Cytotoxins / In Vitro Techniques / Mammary Neoplasms, Experimental / Mice / Ultrasonic Therapy (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ultras.2016.01.003 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26799128 ● Search Scopus @ Elsevier (PMID): 26799128 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ultras.2016.01.003 (DOI: 10.1016/j.ultras.2016.01.003, PubMed: 26799128)
40.	Tomohiro Osaki, Inoru Yokoe, Yoshihiro Uto, Masahiro Ishizuka, Tohru Tanaka, Nobuyasu Yamanaka, Tsukasa Kurahashi, Kazuo Azuma, Yusuke Murahata, Takeshi Tsuka, Norihiko Ito, Tomohiro Imagawa and Yoshiharu Okamoto : Bleomycin enhances the efficacy of sonodynamic therapy using aluminum phthalocyanine disulfonate., Ultrasonics Sonochemistry, Vol.28, 161-168, 2016. (Summary) Sonodynamic therapy (SDT), or ultrasound combined with sonosensitization, is a promising approach because it is noninvasive and penetrates deeper than light does in photodynamic therapy. We examined whether bleomycin (BLM) could improve the efficacy of SDT. We performed an in vitro study using Colon-26 cells, which are derived from mouse colon cancer. SDT with BLM was significantly more cytotoxic than SDT alone both in vitro and in vivo. We also observed an ultrasound intensity-dependent cytotoxic effect of SDT with BLM. These findings suggest that SDT with BLM might provide a novel noninvasive treatment for deep-seated tumors. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ultsonch.2015.07.013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26384895 ● Search Scopus @ Elsevier (PMID): 26384895 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ultsonch.2015.07.013 (DOI: 10.1016/j.ultsonch.2015.07.013, PubMed: 26384895)
41.	Takahiro Inoue, Mami Ishikawa, Yu Sumiya, Haruka Kohda, Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Yoshihiro Uto and Takahito Nishikata : Establishment of a Macrophage-activating Factor Assay System Using the Human Monocytic Cell Line THP-1., Anticancer Research, Vol.35, No.8, 4441-4445, 2015. (Summary) As the mechanism of macrophage activation is not well-understood, standardization of an assay system for measuring phagocytic activities of macrophages will be useful for research on macrophages. Previously, we established a novel standardized macrophage-activating factor (MAF) assay system using U937. Both U937- and THP-1-derived macrophages showed obvious phagocytic activities with unique characteristics and, therefore, could not be assigned to a single sub-type. Activation of macrophages is an intricate cellular process. Comparison of our two novel assay systems provides new insights into macrophage activation mechanisms. (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26168484 ● Summary page in Scopus @ Elsevier: 2-s2.0-84939864084 (PubMed: 26168484, Elsevier: Scopus)
42.	Yu Sumiya, Mami Ishikawa, Takahiro Inoue, Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Yoshihiro Uto and Takahito Nishikata : Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages., Anticancer Research, Vol.35, No.8, 4447-4451, 2015. (Summary) Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs. (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26168485 ● Summary page in Scopus @ Elsevier: 2-s2.0-84939833125 (PubMed: 26168485, Elsevier: Scopus)
43.	Toshio Inui, Kentaro Kubo, Daisuke Kuchiike, Yoshihiro Uto, Takahito Nishikata, Norihiro Sakamoto and Martin Mette : Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports., Anticancer Research, Vol.35, No.8, 4545-4549, 2015. (Summary) Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26168499 ● Summary page in Scopus @ Elsevier: 2-s2.0-84939800500 (PubMed: 26168499, Elsevier: Scopus)
44.	Yoshihiro Uto, Tomohito Kawai, Toshihide Sasaki, Ken Hamada, Hisatsugu Yamada, Daisuke Kuchiike, Kentaro Kubo, Toshio Inui, Martin Mette, Ken Tokunaga, Akio Hayakawa, Akiteru Go and Tomohiro Oosaki : Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production., Anticancer Research, Vol.35, No.8, 4487-4492, 2015. (Summary) Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26168491 ● Summary page in Scopus @ Elsevier: 2-s2.0-84939786895 (PubMed: 26168491, Elsevier: Scopus)
45.	R Munakata, T Inoue, T Koeduka, F Karamat, A Olry, A Sugiyama, K Takanashi, A Dugrand, Y Froelicher, R Tanaka, Yoshihiro Uto, Hitoshi Hori, J Azuma, A Hehn, F Bourgaud and K Yazaki : Molecular cloning and characterization of a geranyl diphosphate-specific aromatic prenyltransferase from lemon, Plant Physiology, Vol.166, No.1, 80-90, 2014. (Summary) Prenyl residues confer divergent biological activities such as antipathogenic and antiherbivorous activities on phenolic compounds, including flavonoids, coumarins, and xanthones. To date, about 1,000 prenylated phenolics have been isolated, with these compounds containing various prenyl residues. However, all currently described plant prenyltransferases (PTs) have been shown specific for dimethylallyl diphosphate as the prenyl donor, while most of the complementary DNAs encoding these genes have been isolated from the Leguminosae. In this study, we describe the identification of a novel PT gene from lemon (Citrus limon), ClPT1, belonging to the homogentisate PT family. This gene encodes a PT that differs from other known PTs, including flavonoid-specific PTs, in polypeptide sequence. This membrane-bound enzyme was specific for geranyl diphosphate as the prenyl donor and coumarin as the prenyl acceptor. Moreover, the gene product was targeted to plastid in plant cells. To our knowledge, this is the novel aromatic PT specific to geranyl diphosphate from citrus species. (Link to Publication Site) ● Publication site (DOI): 10.1104/pp.114.246892 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25077796 ● Search Scopus @ Elsevier (PMID): 25077796 ● Search Scopus @ Elsevier (DOI): 10.1104/pp.114.246892 (DOI: 10.1104/pp.114.246892, PubMed: 25077796)
46.	Masataka Oita, Yoshihiro Uto, Masahide Tominaga, Motoharu Sasaki, Yasuo Hara, Taro Kishi and Hitoshi Hori : Radiosensitivity Uncertainty Evaluation for the In Vitro Biophysical Modeling of EMT6 Cells, Anticancer Research, Vol.34, No.8, 4621-4626, 2014. (Summary) The aims of this study were to evaluate the cell survival uncertainty distribution of radiation and to assess the accuracy of predictions of tumor response by using three different in vitro experimental cell cultures with radiosensitizers (including etanidazole). Using EMT6 cells and X-rays, the cell survival fraction was obtained from 15, 34, and 21 different experiments under normoxic, hypoxic, and hypoxic-plus-radiosensitizer culture, respectively. The α coefficients were 0.257 ± 0.188, 0.078 ± 0.080, and 0.182 ± 0.116 Gy(-1), respectively. The β coefficients were 0.0159 ± 0.0208, 0.0076 ± 0.0113, and 0.0062 ± 0.0077 Gy(-2), respectively. The α coefficient and the dose that killed half of the clonogens population (D50) were significantly different between normoxic cell and hypoxic cell cultures (p<0.01), respectively. The use of radiosensitizers under hypoxic conditions improved radiosensitivity. Our results suggest that parameter value distributions are required for biophysical modeling of applications for radiotherapy. (Keyword) Radiotherapy / biophysical modelling / in vitro / radiosensitivity uncertainty (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25075109 ● Search Scopus @ Elsevier (PMID): 25075109 (PubMed: 25075109)
47.	Toshio Inui, Kaori Makita, Hirona Miura, Akiko Matsuda, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Takahito Nishikata, Hitoshi Hori and Norihiro Sakamoto : Case Report: A Breast Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Hormone Therapy, Anticancer Research, Vol.34, No.8, 4589-4593, 2014. (Summary) Gc protein-derived macrophage-activating factor (GcMAF) occurs naturally in the human body. It has various functions, such as macrophage activation and antitumor activities. Recently, immunotherapy has become an attractive new strategy in the treatment of cancer. GcMAF-based immunotherapy can be combined with many other therapies. Sonodynamic therapy (SDT) using low-intensity ultrasound is a novel therapeutic modality. Ultrasound has been demonstrated to activate a number of sonosensitive agents allowing for the possibility of non-invasive targeted treatment for both superficial and deep-seated tumors. The current case study demonstrates that GcMAF and SDT can be used in combination with conventional therapies in patients with metastatic cancer, especially where treatment options are limited due to factors such as toxicity. This case study also suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT, to be used in combination with GcMAF immunotherapy as a systemic treatment. (Keyword) GcMAF / immunotherapy / sonodynamic therapy / breast cancer / macrophage (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25075104 ● Summary page in Scopus @ Elsevier: 2-s2.0-84908673950 (PubMed: 25075104, Elsevier: Scopus)
48.	Yoshihiro Uto, Dai Tamatani, Yusuke Mizuki, Yoshio Endo, Ikuo Nakanishi, Kei Ohkubo, Shunichi Fukuzumi, Masahiro Ishizuka, Toru Tanaka, Daisuke Kuchiike, Kentaro Kubo, Toshio Inui and Hitoshi Hori : Evaluation of the Sonosensitizing Activities of 5-Aminolevulinic Acid and Sn(IV) Chlorin e6 in Tumor-bearing Chick Embryos, Anticancer Research, Vol.34, No.8, 4583-4587, 2014. (Summary) Recently, 5-aminolevulinic acid (5-ALA), precursors of protoporphyrin IX (PpIX), and Sn(IV) chlorin e6 (SnCe6) have been proposed as possible sonosensitizers for sonodynamic therapy of cancer. Therefore, we evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in vivo by using the EMT6/KU tumor-bearing chick embryos. The concentration of PpIX in tumor and liver tissues and serum increased in a time-dependent manner after the i.v. administration of 5-ALA; PpIX concentrations reached their peak level after 5-7 h. The concentration of SnCe6 reached its maximum value in the tumor tissue and serum immediately after i.v. administration. The combined treatment of 5-ALA or SnCe6 with ultrasound irradiation showed a significant antitumor effect towards EMT6/KU solid tumors. We evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in a chick embryo model and found that 5-ALA might be more suitable as a sonosensitizer than SnCe6. (Keyword) 5-aminolevulinic acid / pharmacokinetics / Sn(IV) chlorin e6 / sonosensitizer / tumor-bearing chick embryo (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25075103 ● Summary page in Scopus @ Elsevier: 2-s2.0-84908676250 (PubMed: 25075103, Elsevier: Scopus)
49.	Hitoshi Hori, Ryu Tada, Yoshihiro Uto, Eiji Nakata, Takashi Morii and Kai Masuda : A Neutron Dynamic Therapy with a Boron Tracedrug UTX-51 Using a Compact Neutron Generator, Anticancer Research, Vol.34, No.8, 4557-4560, 2014. (Summary) We are developing a neutron dynamic therapy (NDT) with boron tracedrugs for a new mechanical-clearance treatment of pathotoxic misfolded, aggregated, and self-propagating prion-associated disease proteins. We present a compact neutron generator-based NDT using a boron tracedrug UTX-51. Our NDT is based on the weak thermal neutron-bombarded destructive action of UTX-51 on bovine serum albumin (BSA) using the neutron beams produced from a compact inertial electrostatic confinement fusion (IECF) neutron generator. BSA as an NDT molecular target was subjected to thermal neutron irradiation for eight hours using a compact neutron generator. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern showed no protein band when 2 nmoles of BSA were irradiated with more than 100 nmoles of UTX-51, while BSA was not affected when irradiated without UTX-51. For the first time, we have succeeded in the molecular destruction of a prion-disease model protein, BSA, by NDT with a boron tracedrug, UTX-51, using a compact neutron generator. (Keyword) NDT / Neutron dynamic therapy / UTX-51 / boron tracedrug / compact neutron generator (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25075099 ● Summary page in Scopus @ Elsevier: 2-s2.0-84908701600 (PubMed: 25075099, Elsevier: Scopus)
50.	Ryu Tada, Yoshihiro Uto, Shin-ichiro Masunaga, Yuko Kinashi, Koji Ono and Hitoshi Hori : An NDT Study of a Boron Tracedrug UTX-51 for Glycated BSA as an AGE Model, Anticancer Research, Vol.34, No.8, 4503-4507, 2014. (Summary) Conventional therapies for diseases that are associated with protein aggregation typically prevent rather than clear protein aggregates. We have proposed neutron dynamic therapy (NDT) as a physical clearance therapy for protein aggregates. Advanced glycation end-products (AGEs), which are aggregated proteins, have been implicated in diabetes, Alzheimer's, and heart disease. Herein, we report the use of the boron tracedrug UTX-51, under thermal neutron irradiation, as an NDT for the targeted clearance of glycated bovine serum albumin (Gly-BSA), a model of AGEs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed to detect Gly-BSA decomposition by thermal neutron irradiation treated with UTX-51. The combination of UTX-51 with neutron irradiation showed a decrease in band intensity of Gly-BSA. We present our NDT strategy, which has been used for the targeted clearance of Gly-BSA, suggesting that NDT with boron tracedrugs can be used for the treatment of AGEs-related disease. (Keyword) AGEs / Gly-BSA / Neutron dynamic therapy / UTX-51 / boron tracedrug (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25075093 ● Summary page in Scopus @ Elsevier: 2-s2.0-84908681031 (PubMed: 25075093, Elsevier: Scopus)
51.	Mami Ishikawa, Takahiro Inoue, Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Yoshihiro Uto and Takahito Nishikata : A novel assay system for macrophage-activating factor activity using a human U937 cell line, Anticancer Research, Vol.34, No.8, 4577-4581, 2014. (Summary) Macrophages play important roles in antitumor immunity, and immunotherapy with the group-specific component protein-derived macrophage-activating factor (GcMAF) has been reported to be effective in patients with various types of cancers. However, in macrophage research, it is important to properly evaluate macrophage activity. U937 macrophages were induced by 12-O-tetradecanoyl-13-phorbolacetate (TPA). The phagocytic activity of macrophages was evaluated as the internalized beads ratio. The MAF activity was assessed at 30 min after MAF addition as the activation ratio. We established a novel assay for phagocytic activities using differentiated U937 macrophages. The novel protocol was simple and rapid and was sensitive for GcMAF. This protocol should be useful not only for basic studies, such as those on molecular mechanisms underlying macrophage activation, but also for clinical studies, such as assessment of GcMAF activity prior to clinical use. (Keyword) Dose-Response Relationship, Drug / Humans / Macrophage Activation / Macrophage-Activating Factors / Macrophages / Phagocytosis / Tetradecanoylphorbol Acetate / U937 Cells / Vitamin D-Binding Protein (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25075102 ● Search Scopus @ Elsevier (PMID): 25075102 (PubMed: 25075102)
52.	Chiaki Abe, Yoshihiro Uto, Ayaka Kawasaki, Chiho Noguchi, Ryo Tanaka, Toru Yoshitomi, Yukio Nagasaki, Yoshio Endo and Hitoshi Hori : Evaluation of the in vivo antioxidative activity of redox nanoparticles by using a developing chicken egg as an alternative animal model, Journal of Controlled Release, Vol.182, 67-72, 2014. (Summary) Antioxidants have been demonstrated to exert beneficial effects as pharmacotherapies for cardiovascular diseases. The in vitro systems generally employed to evaluate antioxidants, however, are limited by having no appreciable in vivo redox status of the antioxidants. Therefore, we used our developing chicken egg model to evaluate the in vivo antioxidative activity of a redox nanoparticle possessing 2,2,6,6-tetramethylpiperidine-1-oxyl (RNP(O)). The 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) elicited strong oxidative stress and its LD50 value for chick embryos was 3.5±0.9mg/egg. The low molecular weight nitroxide compound, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), which is known to have the highest level of antioxidant activity, showed no significant protective effect against AAPH-induced embryo lethality. On the contrary, RNP(O) had potent protective effects against AAPH-induced embryo lethality. Moreover, RNP(O) could significantly suppress the production of lipid peroxides in chick serum induced by hydrocortisone. Since RNP(O) has a longer retention time in blood than TEMPOL, RNP(O) may protect the embryo against lethal oxidative stress by suppressing lipid peroxidation. The validity of in vivo experiments using developing chicken eggs was supported by our data, where RNP(O) was determined to elicit strong antioxidative activity in vivo, irrespective of the lack of a significant difference in the in vitro activity between low-molecular weight TEMPOL and RNP(O). Our results support the use of the developing chicken egg model to evaluate the potential in vivo antioxidative activity of RNP(O). (Keyword) antioxidant / redox nanoparticle / chick embryo / pharmacokinetics (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jconrel.2014.03.015 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24637467 ● Summary page in Scopus @ Elsevier: 2-s2.0-84897382722 (DOI: 10.1016/j.jconrel.2014.03.015, PubMed: 24637467, Elsevier: Scopus)
53.	Megumi Ueno, Minako Nyui, Ikuo Nakanishi, Kazunori Anzai, Toshihiko Ozawa, Ken-ichiro Matsumoto and Yoshihiro Uto : Scavenging of reactive oxygen species induced by hyperthermia in biological fluid, Journal of Clinical Biochemistry and Nutrition, Vol.54, No.2, 75-80, 2014. (Summary) The scavenging activity of rat plasma against hyperthermia-induced reactive oxygen species was tested. The glutathione-dependent reduction of a nitroxyl radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which was restricted by adding superoxide dismutase or by deoxygenating the reaction mixture, was applied to an index of superoxide (O2 (·-)) generation. A reaction mixture containing 0.1 mM 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl and 1 mM glutathione was prepared using 100 mM phosphate buffer containing 0.05 mM diethylenetriaminepentaacetic acid. The reaction mixture was kept in a screw-top vial and incubated in a water bath at 37 or 44°C. The time course of the electron paramagnetic resonance signal of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl in the reaction mixture was measured by an X-band EPR spectrometer (JEOL, Tokyo, Japan). When the same experiment was performed using rat plasma instead of 100 mM PB, the glutathione-dependent reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, i.e., generation of O2 (·-), was not obtained. Only the first-order decay reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which indicates direct reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, was obtained in rat plasma. Adding 0.5% albumin to the phosphate buffer reaction mixture could almost completely inhibit O2 (·-) generation at 37°C. However, addition of 0.5% albumin could not inhibit O2 (·-) generation at 44°C, i.e., hyperthermic temperature. Ascorbic acid also showed inhibition of O2 (·-) generation by 0.01 mM at 37°C, but 0.02 mM or more could inhibit O2 (·-) generation at 44°C. A higher concentration of ascorbic acid showed first-order reduction, i.e., direct one-electron reduction, of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl. Hyperthermia-induced O2 (·-) generation in rat plasma can be mostly inhibited by albumin and ascorbic acid in the plasma. (Link to Publication Site) ● Publication site (DOI): 10.3164/jcbn.13-61 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24688214 ● Search Scopus @ Elsevier (PMID): 24688214 ● Search Scopus @ Elsevier (DOI): 10.3164/jcbn.13-61 (DOI: 10.3164/jcbn.13-61, PubMed: 24688214)
54.	Ikuo Nakanishi, Tomonori Kawashima, Kei Ohkubo, Tsukasa Waki, Yoshihiro Uto, Tadashi Kamada, Toshihiko Ozawa, Ken-ichiro Matsumoto and Shunichi Fukuzumi : Disproportionation of a 2,2-diphenyl-1-picrylhydrazyl radical as a model of reactive oxygen species catalysed by Lewis and/or Brønsted acids, Chemical Communications, Vol.50, No.7, 814-816, 2014. (Summary) Electron-transfer disproportionation of a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH ) occurred in the presence of Sc(3+) acting as a strong Lewis acid in deaerated acetonitrile. In contrast, in the case of weaker Lewis acids than Sc(3+), such as Mg(2+) and Li(+), external protons from acetic acid were required for the disproportionation of DPPH to occur. (Keyword) Acetic Acid / Acetonitriles / Biphenyl Compounds / Catalysis / Lewis Acids / Magnesium Compounds / Mesylates / Perchlorates / Picrates / Reactive Oxygen Species / Scandium (Link to Publication Site) ● Publication site (DOI): 10.1039/c3cc47819j (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24292255 ● Summary page in Scopus @ Elsevier: 2-s2.0-84890838335 (DOI: 10.1039/c3cc47819j, PubMed: 24292255, Elsevier: Scopus)
55.	Masataka Nagahama, Naoyuki Shimomura, Akito Nakagawa, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : In Vivo Experimental Study of Nanosecond Pulsed Electric Field Effects on Solid Tumors, IEEE Transactions on Dielectrics and Electrical Insulation, Vol.20, No.4, 1266-1272, 2013. (Link to Publication Site) ● Publication site (DOI): 10.1109/TDEI.2013.6571443 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84881500583 (DOI: 10.1109/TDEI.2013.6571443, Elsevier: Scopus)
56.	Keiji Hirota, Yoshinori Nakagawa, Ryota Takeuchi, Yoshihiro Uto, Hitoshi Hori, Shinya Onizuka and Hiroshi Terada : Antitumor Effect of Degalactosylated Gc-Globulin on Orthotopic Grafted Lung Cancer in Mice, Anticancer Research, Vol.33, No.7, 2911-2915, 2013. (Summary) Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF. (Keyword) Animals / Carcinoma, Lewis Lung / Female / Galactose / Humans / Injections, Intramuscular / Injections, Intraperitoneal / Injections, Intravenous / Injections, Subcutaneous / Macrophage-Activating Factors / Mice / Mice, Inbred C57BL / Vitamin D-Binding Protein (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23780979 ● Search Scopus @ Elsevier (PMID): 23780979 (PubMed: 23780979)
57.	Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Hitoshi Hori and Norihiro Sakamoto : Clinical Experience of Integrative Cancer Immunotherapy with GcMAF, Anticancer Research, Vol.33, No.7, 2917-2920, 2013. (Keyword) Immunotherapy / GcMAF / hyper T/NK cells / high-dose vitamin C / alpha lipoic acid (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84882721482 (Elsevier: Scopus)
58.	Daisuke Kuchiike, Yoshihiro Uto, Hirotaka Mukai, Noriko Ishiyama, Chiaki Abe, Daichi Tanaka, Tomohito Kawai, Kentaro Kubo, Martin Mette, Toshio Inui, Yoshio Endo and Hitoshi Hori : Degalactosylated/Desialylated Human Serum Containing GcMAF Induces Macrophage Phagocytic Activity and In Vivo Antitumor Activity, Anticancer Research, Vol.33, No.7, 2881-2885, 2013. (Summary) The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy. (Keyword) Degalactosylated/desialylated human serum / GcMAF / macrophage phagocytic activity / in vivo antitumor activity (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23780974 ● Search Scopus @ Elsevier (PMID): 23780974 (PubMed: 23780974)
59.	Junichi Morishige, Yoshihiro Uto, Hitoshi Hori, Kiyoshi Satouchi, Tanihiro Yoshiomoto and Akira Tokumura : Lysophosphatidic Acid Produced by Hen Egg White Lysophospholipase D Induces Vascular Development on Extraembryonic Membranes, Lipids, Vol.48, No.3, 251-262, 2013. (Summary) Lysophosphatidic acid (lysoPtdOH), a lysophospholipid mediator, exerts diverse physiological effects, including angiogenesis, through its specific G-protein-coupled receptors. Previously, we showed that unfertilized hen egg white contains polyunsaturated fatty acid-rich lysoPtdOH and lysophospholipase D (lysoPLD). Here, we examined whether lysoPtdOH was produced by lysoPLD in the presence and absence of a hen fertilized ovum and what the physiological role of lysoPtdOH in hen egg white is. Mass spectrometry showed that fertilized hen egg white contained about 8 μM lysoPtdOH before incubation with an ovum, mainly comprised of 18:1- (12.6 %), 18:2- (37.8 %) and 20:4-molecular species (41.5 %). In an early gestation period, the lysoPtdOH was increased up to 9.6 μM, concomitant with a decrease in the level of polyunsaturated lysophosphatidylcholine (lysoPtdCho). Moreover, lysoPtdOH-degrading activities were found in egg white and the vitelline membrane, showing that these enzymes control lysoPtdOH levels in egg white. In an egg yolk angiogenesis assay, two lysoPtdOH receptor antagonists, Ki16425 and N-palmitoyl serine phosphoric acid (NASP), inhibited blood vessel formation induced by exogenously added 18:1-lysoPtdOH and its precursor lysoPtdCho on the hen yolk sac. Ki16425 and NASP also inhibited blood vessel formation in the chorioallantoic membrane (CAM). Furthermore, the relatively higher levels of LPA1, LPA2, LPA4 and LPA6 mRNA were present in the yolk sac and CAM. These results suggest that lysoPtdOH produced from lysoPtdCho by the action of lysoPLD in hen egg white is involved in the formation of blood vessel networks through several lysoPtdOH receptors on various extraembryonic membranes, including the yolk sac membrane and CAM. (Keyword) Animals / Chick Embryo / Chickens / Chorioallantoic Membrane / Egg White / Extraembryonic Membranes / Fertilization / Lysophospholipids / Neovascularization, Physiologic / Ovum / Phosphoric Diester Hydrolases / RNA, Messenger / Receptors, Lysophosphatidic Acid / Yolk Sac (Link to Publication Site) ● Publication site (DOI): 10.1007/s11745-013-3765-7 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23381130 ● Summary page in Scopus @ Elsevier: 2-s2.0-84878376634 (DOI: 10.1007/s11745-013-3765-7, PubMed: 23381130, Elsevier: Scopus)
60.	Tomonori Kawashima, Sushma Manda, Yoshihiro Uto, Kei Ohkubo, Hitoshi Hori, Ken-ichiro Matsumoto, Kiyoshi Fukuhara, Nobuo Ikota, Shinya Onizuka, Shunichi Fukuzumi, Toshihiko Ozawa, Kazunori Anzai and Ikuo Nakanishi : Kinetics and Mechanism for the Scavenging Reaction of the 2,2-Diphenyl-1-picrylhydrazyl Radical by Synthetic Artepillin C Analogues, Bulletin of the Chemical Society of Japan, Vol.85, No.8, 877-883, 2012. (Link to Publication Site) ● Publication site (DOI): 10.1246/bcsj.20120005 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282679119815808 ● Search Scopus @ Elsevier (DOI): 10.1246/bcsj.20120005 (DOI: 10.1246/bcsj.20120005, CiNii: 1390282679119815808)
61.	Kotaro Miyake, Masanori Nishioka, Satoru Imura, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori and Mitsuo Shimada : The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1 targeted gene expression, Experimental Cell Research, Vol.318, No.13, 1554-1563, 2012. (Summary) Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P<0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules. (Keyword) TX-2098 / Bioreductive agent / Hypoxic cytotoxin / Pancreatic cancer / Hypoxia inducible factor-1 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.yexcr.2012.03.013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22472348 ● Search Scopus @ Elsevier (PMID): 22472348 ● Search Scopus @ Elsevier (DOI): 10.1016/j.yexcr.2012.03.013 (DOI: 10.1016/j.yexcr.2012.03.013, PubMed: 22472348)
62.	Ryosuke Munakata, Tsuyoshi Inoue, Takao Koeduka, Kanako Sasaki, Yusuke Tsurumaru, Akifumi Sugiyama, Yoshihiro Uto, Hitoshi Hori, Jun-ichi Azuma and Kazufumi Yazaki : Characterization of Coumarin-Specific Prenyltransferase Activities in Citrus limon Peel, Bioscience, Biotechnology, and Biochemistry, Vol.76, No.7, 1389-1393, 2012. (Keyword) aromatic substrate prenyltransferase / coumarin / lemon fruit / bergamottin (Link to Publication Site) ● Publication site (DOI): 10.1271/bbb.120192 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22785469 ● CiNii @ National Institute of Informatics (CRID): 1390282681455225344 ● Search Scopus @ Elsevier (PMID): 22785469 ● Search Scopus @ Elsevier (DOI): 10.1271/bbb.120192 (DOI: 10.1271/bbb.120192, PubMed: 22785469, CiNii: 1390282681455225344)
63.	Yoshihiro Uto, Syota Yamamoto, Hirotaka Mukai, Noriko Ishiyama, Ryota Takeuchi, Yoshinori Nakagawa, Keiji Hirota, Hiroshi Terada, Shinya Onizuka and Hitoshi Hori : Beta-Galactosidase treatment is a common first-stage modification of the three major subtypes of Gc protein to GcMAF, Anticancer Research, Vol.32, No.6, 2359-2364, 2012. (Summary) The 1f1f subtype of the group-specific component (Gc) protein is converted into Gc protein-derived macrophage-activating factor (GcMAF) by enzymatic processing with β-galactosidase and sialidase. We previously demonstrated that preGc(1f1f)MAF, a full Gc(1f1f) protein otherwise lacking a galactosyl moiety, can be converted to GcMAF by treatment with mouse peritoneal fluid. Here, we investigated the effects of the β-galactosidase-treated 1s1s and 22 subtypes of Gc protein (preGc(1s1s)MAF and preGc22MAF) on the phagocytic activation of mouse peritoneal macrophages. We demonstrated the presence of Gal-GalNAc disaccharide sugar structures in the Gc(1s1s) protein by western blotting using peanut agglutinin and Helix pomatia agglutinin lectin. We also found that preGc(1s1s)MAF and preGc22MAF significantly enhanced the phagocytic activity of mouse peritoneal macrophages in the presence and absence of mouse peritoneal fluid. We demonstrate that preGc(1s1s)MAF and preGc22MAF proteins can be used as effective macrophage activators. (Keyword) Animals / Blotting, Western / Humans / Macrophage Activation / Macrophage-Activating Factors / Macrophages / Mice / Phagocytosis / Vitamin D-Binding Protein / beta-Galactosidase (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22641675 ● Search Scopus @ Elsevier (PMID): 22641675 (PubMed: 22641675)
64.	Chikako Asada, Chizuru Sasaki, Yoshihiro Uto, Jun Sakafuji and Yoshitoshi Nakamura : Effect of steam explosion pretreatment with ultra-high temperature and pressure on effective utilization of softwood biomass, Biochemical Engineering Journal, Vol.60, 25-29, 2012. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bej.2011.09.013 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1016/j.bej.2011.09.013 (DOI: 10.1016/j.bej.2011.09.013)
65.	Eiji Nakata, Masato Koizumi, Yohei Yamashita, Yoshihiro Uto and Hitoshi Hori : Boron tracedrug: design, synthesis, and pharmacological activity of phenolic BODIPY-containing antioxidants as traceable next-generation drug model, Advances in Experimental Medicine and Biology, Vol.737, 301-306, 2012. (Keyword) Animals / Antioxidants / boron / Boron Compounds / Drug Discovery / lipid peroxidation / Rats / Rats, Wistar (Link to Publication Site) ● Publication site (DOI): 10.1007/978-1-4614-1566-4_44 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22259117 ● Search Scopus @ Elsevier (PMID): 22259117 ● Search Scopus @ Elsevier (DOI): 10.1007/978-1-4614-1566-4_44 (DOI: 10.1007/978-1-4614-1566-4_44, PubMed: 22259117)
66.	Ryo Tanaka, Yoshihiro Uto, Kenta Ohnaka, Yuki Ohta, Kazufumi Yazaki, Naoyuki Umemoto, Eiji Nakata and Hitoshi Hori : Prenylated acylphloroglucinol derivatives: isoprenomics-based design, syntheses and antioxidative activities, Advances in Experimental Medicine and Biology, Vol.737, 251-256, 2012. (Keyword) Hop extract / Prenylated acylphloroglucinol / Isoprenomics / antioxidant / Low-density lipoprotein (LDL) (Link to Publication Site) ● Publication site (DOI): 10.1007/978-1-4614-1566-4_37 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22259110 ● Search Scopus @ Elsevier (PMID): 22259110 ● Search Scopus @ Elsevier (DOI): 10.1007/978-1-4614-1566-4_37 (DOI: 10.1007/978-1-4614-1566-4_37, PubMed: 22259110)
67.	Yusuke Tsurumaru, Kanako Sasaki, Tatsuya Miyawaki, Yoshihiro Uto, Takayuki Momma, Naoyuki Umemoto, Masaki Momose and Kazufumi Yazaki : HlPT-1, a membrane-bound prenyltransferase responsible for the biosynthesis of bitter acids in hops, Biochemical and Biophysical Research Communications, Vol.417, No.1, 393-398, 2012. (Summary) Female flowers of hop (Humulus lupulus L.) develop a large number of glandular trichomes called lupulin glands that contain a variety of prenylated compounds such as α- and β-acid (humulone and lupulone, respectively), as well as xanthohumol, a chalcone derivative. These prenylated compounds are biosynthesized by prenyltransferases catalyzing the transfer of dimethylallyl moiety to aromatic substances. In our previous work, we found HlPT-1 a candidate gene for such a prenyltransferase in a cDNA library constructed from lupulin-enriched flower tissues. In this study, we have characterized the enzymatic properties of HlPT-1 using a recombinant protein expressed in baculovirus-infected insect cells. HlPT-1 catalyzed the first transfer of dimethylallyl moiety to phloroglucinol derivatives, phlorisovalerophenone, phlorisobutyrophenone and phlormethylbutanophenone, leading to the formation of humulone and lupulone derivatives. HlPT-1 also recognized naringenin chalcone as a flavonoid substrate to yield xanthohumol, and this broad substrate specificity is a unique character of HlPT-1 that is not seen in other reported flavonoid prenyltransferases, all of which show strict specificity for their aromatic substrates. Moreover, unlike other aromatic substrate prenyltransferases, HlPT-1 revealed an exclusive requirement for Mg(2+) as a divalent cation for its enzymatic activity and also showed exceptionally narrow optimum pH at around pH 7.0. (Keyword) Aromatic substrate prenyltransferase / Acylphloroglucinol / Hop / Humulone / Lupulone (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2011.11.125 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22166201 ● Search Scopus @ Elsevier (PMID): 22166201 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2011.11.125 (DOI: 10.1016/j.bbrc.2011.11.125, PubMed: 22166201)
68.	Koichi Nonaka, Shinya Onizuka, Hiromi Ishibashi, Yoshihiro Uto, Hitoshi Hori, Toshiyuki Nakayama, Nariaki Matsuura, Takashi Kanematsu and Hikaru Fujioka : Vitamin D Binding Protein-Macrophage Activating Factor Inhibits HCC in SCID Mice, The Journal of Surgical Research, Vol.172, No.1, 116-122, 2012. (Summary) A high incidence of recurrence after treatment is the most serious problem in hepatocellular carcinoma (HCC). Therefore, a new strategy for the treatment of the disease is needed. The aim of the present study was to investigate whether vitamin D binding protein-macrophage activating factor (DBP-maf) is able to inhibit the growth of HCC. The effects of DBP-maf on endothelial cells and macrophage were evaluated by WST-1 assay and phagocytosis assay, respectively. Human HCC cells (HepG2) were implanted into the dorsum of severe combined immunodeficiency (SCID) mice. These mice were divided into control and DBP-maf treatment groups (n = 10/group). The mice in the treatment group received 40 ng/kg/d of DBP-maf for 21 d. DBP-maf showed anti-proliferative activity against endothelial cells and also activated phagocytosis by macrophages. DBP-maf inhibited the growth of HCC cells (treatment group: 126 ± 18mm(3), untreated group: 1691.5 ± 546.9mm(3), P = 0.0077). Histologic examinations of the tumors revealed the microvessel density was reduced and more macrophage infiltration was demonstrated in the tumor of mice in the treatment group. DBP-maf has at least two novel functions, namely, an anti-angiogenic activity and tumor killing activity through the activation of macrophages. DBP-maf may therefore represent a new strategy for the treatment of HCC. (Keyword) Animals / Carcinoma, Hepatocellular / Cell Line, Tumor / Cell Proliferation / Cells, Cultured / Disease Models, Animal / Endothelium, Vascular / Humans / Liver Neoplasms / Macrophage-Activating Factors / Macrophages / Male / Mice / Mice, SCID / Neovascularization, Pathologic / Phagocytosis / Rats / Vitamin D-Binding Protein / Xenograft Model Antitumor Assays (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jss.2010.07.057 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20855083 ● Search Scopus @ Elsevier (PMID): 20855083 ● Search Scopus @ Elsevier (DOI): 10.1016/j.jss.2010.07.057 (DOI: 10.1016/j.jss.2010.07.057, PubMed: 20855083)
69.	Eiji Nakata, Masato Koizumi, Yohei Yamashita, Kenta Onaka, Yoshinori Sakurai, Natsuko Kondo, Koji Ono, Yoshihiro Uto and Hitoshi Hori : Design, Synthesis and Destructive Dynamic Effects of BODIPY-containing and Curcuminoid Boron Tracedrugs for Neutron Dynamic Therapy, Anticancer Research, Vol.31, No.7, 2477-2482, 2011. (Summary) We previously designed the boron tracedrugs UTX-42, UTX-43, and UTX-44, which possess antioxidant potency. In order to explore their destructive dynamic effects when bombarded by weak thermal neutrons, we performed thermal neutron irradiation of bovine serum albumin (BSA) treated with the boron tracedrugs. Boron tracedrugs, including the boron dipyrromethene (BODIPY)-containing compounds UTX-42, UTX-44, and UTX-47 and the curcuminoid compounds UTX-50 and UTX-51, were designed for neutron dynamic therapy based on their molecular orbital calculation. Newly designed UTX-47, UTX-50, and UTX-51 were synthesized. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to detect decomposition by thermal neutron irradiation of BSA treated with these boron tracedrugs. The combination of 1.0 μM BSA with 100 μM of each of the boron tracedrugs showed a decrease in band intensity after irradiation. All boron tracedrugs tested caused destructive dynamic damage of BSA during thermal neutron irradiation, suggesting that boron tracedrugs could be used as dynamic drugs for neutron dynamic therapy. (Keyword) Boron tracedrug, BODIPY / curcuminoid / neutron dynamic therapy / dynamic drug / thermal neutron irradiation / BNCT (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21873162 ● Search Scopus @ Elsevier (PMID): 21873162 (PubMed: 21873162)
70.	Yoshihiro Uto, Syota Yamamoto, Ryota Takeuchi, Yoshinori Nakagawa, Keiji Hirota, Hiroshi Terada, Shinya Onizuka, Eiji Nakata and Hitoshi Hori : Effect of the Gc-derived Macrophage-activating Factor Precursor (preGcMAF) on Phagocytic Activation of Mouse Peritoneal Macrophages, Anticancer Research, Vol.31, No.7, 2489-2492, 2011. (Summary) The 1f1f subtype of the Gc protein (Gc(1f1f) protein) was converted into Gc-derived macrophage-activating factor (GcMAF) by enzymatic processing in the presence of β-galactosidase of an activated B-cell and sialidase of a T-cell. We hypothesized that preGc(1f1f)MAF, the only Gc(1f1f) protein lacking galactose, can be converted to GcMAF in vivo because sialic acid is cleaved by residual sialidase. Hence, we investigated the effect of preGc(1f1f)MAF on the phagocytic activation of mouse peritoneal macrophages. We examined the sugar moiety of preGc(1f1f)MAF with a Western blot using peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) lectin. We also found that preGc(1f1f)MAF significantly enhanced phagocytic activity in mouse peritoneal macrophages but only in the presence of the mouse peritoneal fluid; the level of phagocytic activity was the same as that observed for GcMAF. PreGc(1f1f)MAF can be used as an effective macrophage activator in vivo. (Keyword) Gc-Derived macrophage-activating factor precursor (preGcMAF) / 1f1f subtype of Gc protein (Gc1f1f protein) / phagocytic activity / mouse peritoneal macrophages (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21873164 ● Search Scopus @ Elsevier (PMID): 21873164 (PubMed: 21873164)
71.	Chiaki Abe, Yoshihiro Uto, Takashi Nakae, Yuuya Shinmoto, Keiichiro Sano, Hiroko Nakata, Mizue Teraoka, Yoshio Endo, Hiroshi Maezawa, Shin-ichiro Masunaga, Eiji Nakata and Hitoshi Hori : Evaluation of the In vivo Radiosensitizing Activity of EtanidazoleUsing Tumor-bearing Chick Embryo, Journal of Radiation Research, Vol.52, No.2, 208-214, 2011. (Summary) Chick embryos have been used as alternative experimental animals in various research fields, including virology, immunology, toxicology, oncology, and embryology. Until now, there have been no in vivo models using chick embryo to evaluate radiosensitizing activity. Here, the in vivo radiosensitizing activity of etanidazole, a well-known hypoxic cell radiosensitizer, was evaluated using tumor-bearing chick embryo. On the basis of tumor growth, drug administration and X-ray irradiation were performed on day 15 chick embryo, with the endpoint being day 18 chick embryo. In day 15 chick embryo, an X-ray irradiation dose of equal or less than 10 Gy did not cause significant tumor growth suppression. Intravenous administration of equal or less than 1.0 mg of etanidazole did not cause tumor growth suppression. Neither doses of equal or less than 8 Gy of irradiation nor 1.0 mg of etanidazole caused fatality of the chick embryo. On the basis of these results, we evaluated the radiosensitizing effect of a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole. As noted above, 1.0 mg of etanidazole alone and 8 Gy of irradiation alone did not show tumor growth suppression. In contrast, a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole showed 35% of significant tumor growth suppression. Thus, we succeeded in evaluating the in vivo radiosensitizing activity of etanidazole using tumor-bearing chick embryo. These results suggest that the use of tumor-bearing chick embryo may be part of a promising system for evaluating radiosensitizing activity. (Keyword) Tumor-bearing chick embryo / In vivo / Hypoxic cell radiosensitizer / Etanidazole / Radiosensitizing activity (Link to Publication Site) ● Publication site (DOI): 10.1269/jrr.10122 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21436611 ● Search Scopus @ Elsevier (PMID): 21436611 ● Search Scopus @ Elsevier (DOI): 10.1269/jrr.10122 (DOI: 10.1269/jrr.10122, PubMed: 21436611)
72.	Atsushi Ikeda, Yoshihiko Kawai, Jun-ichi Kikuchi, Motofusa Akiyama, Eiji Nakata, Yoshihiro Uto and Hitoshi Hori : Formation and regulation of fullerene-incorporation in liposomes under the phase transition temperature, Organic & Biomolecular Chemistry, Vol.9, No.8, 2622-2627, 2011. (Summary) The fullerene-exchange reaction from a cyclodextrin cavity to liposomes represents one of the best methods to prepare lipid membrane-incorporated [70]fullerenes (C(70)). The C(70)-exchange reaction occurred completely at temperatures above the phase transition temperature (T(m)) of the liposomes; however, lowering the temperature to below the T(m) led to C(70) aggregation outside the liposomes. This observation has limited the development of more functional LMIC(70) using a variety of liposome compositions. In this paper, this reaction was found to occur efficiently by the addition of small amounts of lipids bearing a ϖ-moiety. The ϖ-moieties act as a gate when hydrophobic C(70) migrates into the hydrophilic liposome surface. Therefore, the ϖ-moieties should exist in the polar head groups of the lipids and the C(70)-exchange reaction can be controlled by pH. (Keyword) Fullerenes / Hydrogen-Ion Concentration / Hydrophobic and Hydrophilic Interactions / Liposomes / Molecular Structure / Particle Size / Surface Properties / Transition Temperature (Link to Publication Site) ● Publication site (DOI): 10.1039/c0ob01030h (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21327216 ● Search Scopus @ Elsevier (PMID): 21327216 ● Search Scopus @ Elsevier (DOI): 10.1039/c0ob01030h (DOI: 10.1039/c0ob01030h, PubMed: 21327216)
73.	Takeuchi Ryota, Yoshihiro Uto, Nakagawa Yoshinori, Hirota Keiji, Hiroshi Terada and Hitoshi Hori : A retrospective study of a calcium agent (E-Ca) using data on bone mineral density obtained by DXA method, Anticancer Research, Vol.30, No.8, 3199-3205, 2010. (Summary) We performed a retrospective analysis of a calcium hydroxide-containing calcium agent (TACHIKAWA DENKAI CALCIUM™: E-Ca) based on data of bone mineral density obtained by dual-energy X-ray absorptiometry (DXA) to clarify the relationship between bone mineral density and E-Ca intake on an empty stomach in those who regularly use E-Ca. We found the percentage of volunteers with their age-matched (AM) values of above 100% to be 89%, and also a moderate positive correlation between AM values and the intake period of E-Ca. Our findings demonstrate that AM values can be used as an effective indicator assessing osteogenesis by regularly administrated calcium agents which exert their effects after long-term use. (Keyword) Absorptiometry, Photon / Adult / Aged / Bone Density / Calcium / Female / Humans / Male / Middle Aged / Retrospective Studies (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20871041 ● Summary page in Scopus @ Elsevier: 2-s2.0-77957362110 (PubMed: 20871041, Elsevier: Scopus)
74.	Eiji Nakata, Yoshihiro Yukimachi, Yoshijiro Nazumi, Yoshihiro Uto, Toshihiro Hashimoto, Yasuko Okamoto and Hitoshi Hori : Design of a SNARF-based Ratiometric Fluorescent Probe for Esterase, Chemistry Letters, Vol.39, No.7, 734-735, 2010. (Summary) A novel ratiometric fluorescent probe for esterase has been developed based on the SNARF scaffold. The new SNARF derivative was used to monitor the activity of porcine liver esterase by ratiometric emission spectrum change. (Link to Publication Site) ● Publication site (DOI): 10.1246/cl.2010.734 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1360283694088156800 ● Search Scopus @ Elsevier (DOI): 10.1246/cl.2010.734 (DOI: 10.1246/cl.2010.734, CiNii: 1360283694088156800)
75.	Eiji Nakata, Yoshihiro Yukimachi, Yoshijiro Nazumi, Yoshihiro Uto, Hiroshi Maezawa, Toshihiro Hashimoto, Yasuko Okamoto and Hitoshi Hori : A newly designed cell-permeable SNARF derivative as an effective intracellular pH indicator., Chemical Communications, Vol.46, No.20, 3526-3528, 2010. (Summary) We have successfully developed a new cell-permeable SNARF derivative that is activated inside the cell by ester hydrolysis and is notable for having reduced background fluorescence. (Link to Publication Site) ● Publication site (DOI): 10.1039/c003167d (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20379600 ● Search Scopus @ Elsevier (PMID): 20379600 ● Search Scopus @ Elsevier (DOI): 10.1039/c003167d (DOI: 10.1039/c003167d, PubMed: 20379600)
76.	Nakashima Hitomi, Ikkyu Kazuhiro, Nakashima Kouichiro, Sano Keiichiro, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, Sugimoto Hiroshi, Yoshitsugu Shiro, Nakagawa Yoshinori and Hitoshi Hori : Design of Novel Hypoxia-Targeting IDO Hybrid Inhibitors Conjugated with an Unsubstituted L-TRP as an IDO Affinity Moiety, Advances in Experimental Medicine and Biology, Vol.662, 415-421, 2010. (Summary) We presented here design, syntheses and inhibitory activities of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety without inhibitor 1MT, such as L-Trp-TPZ hybrids 1 (TX-2274), 2 (UTX-3), 3 (UTX-4), and 4 (UTX-2). TPZ-monoxide hybrids 1 and 3 were good competitive IDO inhibitors, while TPZ hybrids 2 and 4 were uncompetitive IDO inhibitors. Among them TPZ-monoxide hybrid 1 have the strongest IDO inhibitory activity. It suggests that TPZ-monoxide hybrids 1 and 3 are able to bind the active site of IDO, TPZ hybrids 2 and 4 are able to bind the enzyme-substrate complex. We proposed the possible mechanism of action of TPZ hybrid 2 that may first affect as a hypoxic cytotoxin, and then metabolized to TPZ-monoxide hybrid 1, which may do as an IDO inhibitor more effectively than its parent TPZ hybrid 2. (Keyword) Cell Hypoxia / Drug Design / Drug Screening Assays, Antitumor / Enzyme Inhibitors / Humans / Indoleamine-Pyrrole 2,3,-Dioxygenase / Kinetics / Triazines / Tryptophan (Link to Publication Site) ● Publication site (DOI): 10.1007/978-1-4419-1241-1_60 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20204824 ● Search Scopus @ Elsevier (PMID): 20204824 ● Search Scopus @ Elsevier (DOI): 10.1007/978-1-4419-1241-1_60 (DOI: 10.1007/978-1-4419-1241-1_60, PubMed: 20204824)
77.	Douglas A. Kuntz, Shinichi Nakayama, Kayla Shea, Hitoshi Hori, Yoshihiro Uto, Hideko Nagasawa and David. R. Rose : Structural Investigation of the Binding of 5-Substituted Swainsonine Analogues to Golgi -Mannosidase II, ChemBioChem, Vol.11, No.5, 673-680, 2010. (Summary) Golgi alpha-mannosidase II (GMII) is a key enzyme in the N-glycosylation pathway and is a potential target for cancer chemotherapy. The natural product swainsonine is a potent inhibitor of GMII. In this paper we characterize the binding of 5alpha-substituted swainsonine analogues to the soluble catalytic domain of Drosophila GMII by X-ray crystallography. These inhibitors enjoy an advantage over previously reported GMII inhibitors in that they did not significantly decrease the inhibitory potential of the swainsonine head-group. The phenyl groups of these analogues occupy a portion of the binding site not previously seen to be populated with either substrate analogues or other inhibitors and they form novel hydrophobic interactions. They displace a well-organized water cluster, but the presence of a C(10) carbonyl allows the reestablishment of important hydrogen bonds. Already approximately tenfold more active against the Golgi enzyme than the lysosomal enzyme, these inhibitors offer the potential of being extended into the N-acetylglucosamine binding site of GMII for the creation of even more potent and selective GMII inhibitors. (Keyword) Animals / Antineoplastic Agents / Binding Sites / Catalytic Domain / Drosophila melanogaster / Golgi Apparatus / Mannosidases / Protein Binding / Swainsonine (Link to Publication Site) ● Publication site (DOI): 10.1002/cbic.200900750 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20209559 ● Search Scopus @ Elsevier (PMID): 20209559 ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.200900750 (DOI: 10.1002/cbic.200900750, PubMed: 20209559)
78.	Kotaro Miyake, Mitsuo Shimada, Masanori Nishioka, Koji Sugimoto, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer, Cancer Chemotherapy and Pharmacology, Vol.64, No.5, 885-892, 2009. (Summary) Purpose It is well known that hypoxic milieu is the primary cancer environment. Therefore, tumor hypoxia is considered to be a potential therapeutic target. In the present study, we investigated the antitumor and antimetastatic effect of hypoxic cell radiosensitizer, TX-1877 on xenograft model of rectal cancer. Methods Nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 were treated with TX-1877, irradiation or TX-1877 with irradiation. Tumor volume, survival, expression of matrix metalloproteinase (MMP)-2, MMP-7, MMP-9 and urokinase-type plasminogen activator (uPA) and incidence of lymph node metastasis were evaluated in treatment versus control group. Results In subcutaneous model, tumor treated with TX-1877 and irradiation showed significant reductions in volume (P < 0.05 vs. control, TX-1877 or irradiation group). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that TX-1877 significantly inhibited expression of the MMP-9 and uPA. These treatments also inhibited the para-aortic lymph node metastasis, however, did not prolong the survival in orthotopic model. Conclusions These data show that the treatment of TX-1877 with irradiation decreased growth of human rectal cancer and, furthermore, suppressed lymph node metastasis. (Keyword) TX-1877 / Radiosensitizer / Hypoxic cell / Antimetastasis / Lymph node metastasis (Link to Publication Site) ● Publication site (DOI): 10.1007/s00280-009-0937-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19214512 ● Search Scopus @ Elsevier (PMID): 19214512 ● Search Scopus @ Elsevier (DOI): 10.1007/s00280-009-0937-5 (DOI: 10.1007/s00280-009-0937-5, PubMed: 19214512)
79.	Eiji Nakata, Yukimachi Yoshihiro, Kariyazono Hirokazu, Im Seongwang, Abe Chiaki, Yoshihiro Uto, Hiroshi Maezawa, Hashimoto Toshihiro, Okamoto Yasuko and Hitoshi Hori : Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging, Bioorganic & Medicinal Chemistry, Vol.17, No.19, 6952-6958, 2009. (Summary) We have designed and evaluated UTX-12 as a novel fluorescent pH probe for tumor hypoxia imaging. UTX-12 consists of a p-nitro benzyl moiety, which is a latent hypoxia-selective leaving group activated by nitro reduction, directly linked to SNARF. Although UTX-12 itself is colorless and non-fluorescent in aqueous solution, nitro reduction triggers the release of SNARF which has well-characterized long wavelength absorption and fluorescence that is sensitive to pH. The resultant SNARF, released intracellularly by enzymatic reduction of UTX-12, allows measurement of pH by pH-dependent dual emission shifts. UTX-12 showed clear differences in fluorescence behavior between hypoxic and aerobic conditions in liver microsomes and inside V79 cells. These data are confirmation that UTX-12 is biologically reduced inside tumor cells and the released SNARF should monitor intracellular pH of tumor cells selectively with reduced background signal. (Keyword) Fluorescent pH probe / Tumor hypoxia / Fluorescent imaging / Bioreductive activation / Nitro reduction (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2009.08.037 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19736018 ● Search Scopus @ Elsevier (PMID): 19736018 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2009.08.037 (DOI: 10.1016/j.bmc.2009.08.037, PubMed: 19736018)
80.	Mok-Ryeon Ahn, Kazuhiro Kunimasa, Shigenori Kumazawa, Tsutomu Nakayama, Kazuhiko Kaji, Yoshihiro Uto, Hitoshi Hori, Hideko Nagasawa and Toshiro Ohta : Correlation between antiangiogenic activity and antioxidant activity of various components from propolis, Molecular Nutrition & Food Research, Vol.53, No.5, 643-651, 2009. (Summary) Propolis possesses various physiological activities. In this study, we examined the antiangiogenic and antioxidant activities of various components from propolis: acacetin, apigenin, artepillin C, caffeic acid phenethyl ester, chrysin, p-coumaric acid, galangin, kaempferol, pinocembrin, and quercetin. The effects of these components were tested on in vitro models of angiogenesis, tube formation and growth of human umbilical vein endothelial cells (HUVECs). Furthermore, these components were evaluated for their antioxidant activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging and ferric reducing/antioxidant power (FRAP) assays. Two propolis components, caffeic acid phenethyl ester, and quercetin, possessed strong inhibitory effects on tube formation and on endothelial cell proliferation and, coincidentally, showed strong antioxidant activity. Artepillin C, galangin, and kaempferol also possessed strong antiangiogenic and antioxidant activities to a slightly less degree. In contrast, acacetin, apigenin, and pinocembrin possessed a considerable degree of antiangiogenic activities, although they showed very low antioxidant activities. From these results, we propose that components from propolis such as artepillin C, caffeic acid phenethyl ester, galangin, kaempferol, and quercetin might represent a new class of dietary-derived antioxidative compounds with antiangiogenic activities. These propolis components may have the potential to be developed into pharmaceutical drugs for the treatment of angiogenesis-dependent human diseases such as tumors. (Keyword) Angiogenesis / Antioxidant / Human umbilical vein endothelial cells / Propolis / Tube formation (Link to Publication Site) ● Publication site (DOI): 10.1002/mnfr.200800021 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19065585 ● Search Scopus @ Elsevier (PMID): 19065585 ● Search Scopus @ Elsevier (DOI): 10.1002/mnfr.200800021 (DOI: 10.1002/mnfr.200800021, PubMed: 19065585)
81.	Shanta M. Messerli, Mok-Ryeon Ahn, Kazuhiro Kunimasa, Miyako Yanagihara, Tomoki Tatefuji, Ken Hashimoto, Victor Mautner, Yoshihiro Uto, Hitoshi Hori, Shigenori Kumazawa, Kazuhiko Kaji, Toshiro Ohta and Hiroshi Maruta : Artepillin C (ARC) in Brazilian green propolis selectively blocks oncogenic PAK1 signaling and suppresses the growth of NF tumors in mice, Phytotherapy Research, Vol.23, No.3, 423-427, 2009. (Summary) There are mainly three types of propolis whose major anticancer ingredients are entirely different: (1) CAPE (caffeic acid phenethyl ester)-based propolis in Europe, Far East and New Zealand, (2) artepillin C (ARC)-based Brazilian green propolis and (3) Brazilian red propolis. It was shown previously that NF (neurofibromatosis)-associated tumors require the kinase PAK1 for their growth, and CAPE-based propolis extracts such as Bio 30 suppress completely the growth of NF tumors in vivo by blocking PAK1 signaling. Also it was demonstrated that ARC suppresses angiogenesis, suggesting the possibility that ARC also blocks oncogenic PAK1 signaling. Here it is shown for the first time that both ARC and green propolis extract (GPE) indeed block the PAK1 signaling selectively, without affecting another kinase known as AKT. Furthermore, it was confirmed that ARC as well as GPE suppress almost completely the growth of human NF tumor xenografts in mice, as does Bio 30. These results suggest that both CAPE-based and ARC-based propolis extracts are natural anti-PAK1 remedies and could be among the first effective NF therapeutics available on the market. Since more than 70% of human cancers such as breast and prostate cancers require the kinase PAK1 for their growth, it is quite possible that GPE could be potentially useful for the treatment of these cancers, as is Bio 30. (Keyword) artepillin C / Brazilian green propolis / PAK1 / neurofibromatosis (Link to Publication Site) ● Publication site (DOI): 10.1002/ptr.2658 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19003952 ● Search Scopus @ Elsevier (PMID): 19003952 ● Search Scopus @ Elsevier (DOI): 10.1002/ptr.2658 (DOI: 10.1002/ptr.2658, PubMed: 19003952)
82.	Yoshihiro Uto, Daisuke Koyama, Mamoru Otsuki, Naoki Otomo, Tadashi Shirai, Chiaki Abe, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : A chemical biosynthesis design for an antiatherosclerosis drug by acyclic tocopherol intermediate analogue based on "isoprenomics", Advances in Experimental Medicine and Biology, Vol.645, 109-114, 2009. (Summary) Phytyl quinols, namely acyclic tocopherols, are key intermediates of tocopherol biosynthesis, but their biological activities remain unclear. We therefore investigated the structure-activity relationship of phytyl quinols to apply a chemical biosynthesis design for an antiatherosclerosis drug based on isoprenomics. We have achieved the biosynthesis-oriented design and synthesis of alpha- (TX-2254) and beta-(TX-2247) phytyl quinol as an unnatural intermediate, other gamma- (TX-2242) and delta-(TX-2231) phytyl quinol as a natural one. Geometry optimization and Molecular orbital (MO) calculation of TX-2254 showed a unique right-angle structure; however, MO energy of TX-2254 and d-alpha-tocopherol were very similar. Radical reactivity of TX-2231 was equal to dl-alpha-tocopherol, whereas TX-2254, TX-2247, and TX-2231 showed lower reactivity than dl-alpha-tocopherol. All four phytyl quinols showed almost the same moderate inhibitory activity against low-density lipoprotein (LDL) oxidation instead of their different degree of C-methylation with character different from tocopherols. In vivo toxicities of phytyl quinols against chick embryo chorioallantoic membrane (CAM) vasculature were hardly observed. We proposed phytyl quinols were possible antioxidants in plants and animals, like vitamin E. (Keyword) Animals / Antioxidants / atherosclerosis / Chemistry Techniques, Analytical / Chick Embryo / Drug Design / Humans / Isomerism / Models, Molecular / molecular structure / Tocopherols (Link to Publication Site) ● Publication site (DOI): 10.1007/978-0-387-85998-9_17 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19227458 ● Search Scopus @ Elsevier (PMID): 19227458 ● Search Scopus @ Elsevier (DOI): 10.1007/978-0-387-85998-9_17 (DOI: 10.1007/978-0-387-85998-9_17, PubMed: 19227458)
83.	Kotaro Miyake, Mitsuo Shimada, Masanori Nishioka, Koji Sugimoto, Erdenebulgan Batmunkh, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : The novel hypoxic cell radiosensitizer, TX-1877 has antitumor activity through suppression of angiogenesis and inhibits liver metastasis on xenograft model of pancreatic cancer., Cancer Letters, Vol.272, No.2, 325-335, 2008. (Summary) Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of hypoxic cell radiosensitizer, TX-1877 in inhibiting angiogenesis and liver metastasis on pancreatic cancer xenograft model. The antitumor effects of TX-1877 were tested against various human tumor cell lines using cell proliferation assay. Nude mice bearing s.c. or orthotopically implanted human SUIT-2 were treated with TX-1877 alone, irradiation alone or TX-1877 and irradiation. Tumor volume, survival, expression of angiogenic molecules and liver metastasis were evaluated in treatment versus control groups. In vitro, TX-1877 inhibited the proliferation and potentiated the radiosensitivity of various pancreatic cancer cell lines. In an orthotopic model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-1877 and irradiation showed significant reductions in volume (p<0.05 versus control, TX-1877 alone or irradiation alone). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that treatment with TX-1877 alone or with TX-1877 and irradiation inhibited expression of the angiogenic molecules, vascular endothelial growth factor; basic fibroblast growth factor, interleukin-8 and matrix metalloproteinase 9 more than control or did treatment with irradiation alone. These treatments also induced apoptosis in cancer cells. These data show that treatment of TX-1877 and irradiation decreased growth of human pancreatic cancer, suppressed angiogenesis and inhibited liver metastasis, leading to prolonged survival. (Keyword) Antineoplastic Agents / Cell Hypoxia / Cell Line, Tumor / Humans / Immunohistochemistry / In Situ Nick-End Labeling / Liver Neoplasms / Neovascularization, Pathologic / Nitroimidazoles / Pancreatic Neoplasms / Radiation-Sensitizing Agents / Reverse Transcriptase Polymerase Chain Reaction / Transplantation, Heterologous (Link to Publication Site) ● Publication site (DOI): 10.1016/j.canlet.2008.07.020 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18762366 ● Search Scopus @ Elsevier (PMID): 18762366 ● Search Scopus @ Elsevier (DOI): 10.1016/j.canlet.2008.07.020 (DOI: 10.1016/j.canlet.2008.07.020, PubMed: 18762366)
84.	Hitomi Nakashima, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, Kazuhiro Ikkyu, Noriko Hiraoka, Kouichiro Nakashima, Yuki Sasaki, Hiroshi Sugimoto, Yoshitsugu Shiro, Toshihiro Hashimoto, Yasuko Okamoto, Yoshinori Asakawa and Hitoshi Hori : Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors, Bioorganic & Medicinal Chemistry, Vol.16, No.18, 8661-8669, 2008. (Summary) We have designed and synthesized new hypoxic-neoplastic cells-targeted indoleamine 2,3-dioxygenase (IDO) inhibitors. 1-Methyl-tryptophan (1MT)-tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide) hybrid inhibitors including 1 (TX-2236), 2 (TX-2235), 3 (TX-2228), and 4 (TX-2234) were prepared. All of these compounds were uncompetitive IDO inhibitors. TPZ-monoxide hybrids 1 and 3 showed higher IDO inhibitory activities than TPZ hybrids 2 and 4. Among these hybrids, hybrid 1 was the most potent IDO inhibitor. TPZ hybrids 2 and 4 showed stronger hypoxia-selective cytotoxicity than TPZ to EMT6/KU cells. These data suggest that TPZ hybrids 2 and 4 may act through their dual biological functions: first, they function as hypoxic cytotoxins in hypoxic cells, and then are metabolized to their TPZ-monoxide (3-amino-1,2,4-benzotriazine 1-oxide) hybrids, which function as IDO inhibitors. (Keyword) Indoleamine 2,3-dioxygenase / 1-Methyl-tryptophan (1MT) / 1MT-TPZ hybrids / Hypoxic-neoplastic cells (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2008.07.087 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18715787 ● Search Scopus @ Elsevier (PMID): 18715787 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2008.07.087 (DOI: 10.1016/j.bmc.2008.07.087, PubMed: 18715787)
85.	Shinichi Nakayama, Yoshihiro Uto, Kanako Tanimoto, Yasuhiro Okuno, Yuki Sasaki, Hideko Nagasawa, Eiji Nakata, Ken Arai, Kaori Momose, Tetsuro Fujita, Toshihiro Hashimoto, Yasuko Okamoto, Yoshinori Asakawa, Satoru GOTO and Hitoshi Hori : TX-2152: A conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity, Bioorganic & Medicinal Chemistry, Vol.16, No.16, 7705-7714, 2008. (Summary) We designed FTY720 analogues with conformationally rigid and electron-rich acetylenic chains as antiangiogenic agents (the monoyne 1: TX-2148, the diyne 2: TX-2152, the triyne 3: TX-2256). Molecular orbital (MO) calculations of our designed acetylenic analogues and FTY720 showed that the localization of the lowest unoccupied MO and the highest occupied MO increased from phenyl ring to acetylenic chain compared with that of FTY720. These acetylenic analogues were synthesized from p-hydroxyphenylethanol as a starting material. The construction of the acetylenic chain was carried out by an iterative strategy using a Sonogashira cross-coupling reaction and desilylative bromination in two steps. The corresponding overall yields of the monoyne 1, the diyne 2, and the triyne 3 were 27% (11 steps), 13% (13 steps), and 10% (15 steps). The in vivo antiangiogenic activities of these acetylenic analogues and FTY720 were evaluated by the chick embryo chorioallantoic membrane (CAM) assay and compared to the activities of the known antiangiogenic agent TNP-470. The diyne 2 showed more potent antiangiogenic activity (90% inhibition) than FTY720 (77% inhibition) and other acetylenic analogues (the monoyne 1: 42% inhibition, the triyne 3: 60% inhibition), and TNP-470 (82% inhibition) at a dose of 10 μg/CAM, without showing toxicity. The diyne 2 also had potent inhibitory activity at a dose of 5 and 2.5 μg/CAM. These results indicate that the flexibility of C8 alkyl chain of FTY720 is not required for its antiangiogenic activity. We suggest that the diyne 2 (TX-2152) may be a promising candidate as an antiangiogenic agent for antineoplastic drug discovery. (Keyword) TX-2152 / FTY720 / Acetylenic analogue / Antiangiogenic agent / Chick embryo CAM assay (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2008.07.003 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18678496 ● Search Scopus @ Elsevier (PMID): 18678496 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2008.07.003 (DOI: 10.1016/j.bmc.2008.07.003, PubMed: 18678496)
86.	Yoshihiro Uto, Hideko Nagasawa, Cheng-Zhe Jin, Shinichi Nakayama, Ayako Tanaka, Saori Kiyoi, Hitomi Nakashima, Mariko Shimamura, Seiichi Inayama, Tomoya Fujiwara, Yoshio Takeuchi, Yoshimasa Uehara, Kenneth L. Kirk, Eiji Nakata and Hitoshi Hori : Design of antiangiogenic hypoxic cell radiosensitizers: 2-Nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety, Bioorganic & Medicinal Chemistry, Vol.16, No.11, 6042-6053, 2008. (Summary) We designed chiral 2-nitroimidazole derivatives containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety as antiangiogenic hypoxic cell radiosensitizers. Based on results of molecular orbital calculations, the 2-aminomethylene-4-cyclopentene-1,3-dione moiety is expected to show high electrophilicity comparable to that of the 2-methylene-4-cyclopentene-1,3-dione moiety included in TX-1123 and tyrphostin AG17. We evaluated the antiangiogenic and radiosensitizing effects of the new compounds, along with other biological properties including their activities as hypoxic cytotoxicities and protein tyrosine kinase (PTK) inhibitory activities. Among the compounds tested, 5 (TX-2036) proved to be the strongest antiangiogenic hypoxic cell radiosensitizer. All the other chiral 2-nitroimidazole derivatives having 2-aminomethylene-4-cyclopentene-1,3-dione moiety tested were also antiangiogenic hypoxic cell radiosensitizers. The PTK inhibitory activity of 5 (TX-2036) showed this to be a promising and potent EGFR kinase inhibitor, having an IC50 value of lower than 2 μM. This compound also was an Flt-1 kinase inhibitor having an IC50 value of lower than 20 μM. Our results show that these chiral 2-nitroimidazole derivatives that contain the 2-aminomethylene-4-cyclopentene-1,3-dione moiety as a potent antiangiogenic pharmacophoric descriptor are promising lead candidates for the development of antiangiogenic hypoxic cell radiosensitizers. (Keyword) Hypoxic cell radiosensitizers / Antiangiogenic agents / 2-Aminomethylene-4-cyclopentene-1,3-dione / Protein tyrosine kinase (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2008.04.041 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18474428 ● Search Scopus @ Elsevier (PMID): 18474428 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2008.04.041 (DOI: 10.1016/j.bmc.2008.04.041, PubMed: 18474428)
87.	Niraldo Paulino, Lemos Sheila Rago Abreu, Yoshihiro Uto, Daisuke Koyama, Hideko Nagasawa, Hitoshi Hori, Verena M. Dirsch, Angelika M. Vollmar, Amarilis Scremin and Walter A. Bretz : Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis, European Journal of Pharmacology, Vol.587, No.1-3, 296-301, 2008. (Summary) Artepillin C is the major compound in the Brazilian green propolis from Baccharis dracunculifolia. Our aim in this study was to investigate the anti-inflammatory effects, absorption, and bioavailability of Artepillin C in mice. The animals used were male Swiss mice subjected to: paw oedema by carrageenan (300 μg/paw), carrageenan-induced peritonitis, and prostaglandin E2 determination. We also measured in vitro nitric oxide production by RAW 264.7 cells and NF-κB activity in HEK 293 cells. Finally, we measured the absorption and bioavailability of Artepillin C in plasma from mice by means of GC-MS after a single oral dose (10 mg/kg). In vivo, Artepillin C produced a maximal inhibition of 38% after 360 min on paw oedema. Artepillin C also decreased the number of neutrophils during peritonitis (IC50: 0.9 (0.5 1.4) mg/kg). Treatment with Artepillin C decreased prostaglandin E2 by 29 ± 3% and 58 ± 5% at 1 and 10 mg/kg, respectively, with a mean ID50 of 8.5 (8.0 8.7)mg/kg). Similarly, in in vitro models, Artepillin C (3, 10, or 100 μM) decreased nitric oxide production by RAW 264.7 cells with a mean IC50 of 8.5 (7.8 9.2) μM. In HEK 293 cells, Artepillin C reduced NF-κB activity with a mean IC50 of 26 (22 30) μg/ml), suggesting anti-inflammatory activity, particularly during acute inflammation. Lastly, Artepillin C was absorbed after an oral dose (10 mg/kg) with maximal peaks found at 1 h (22 μg/ml). Collectively, Artepillin C showed anti-inflammatory effects mediated, at least in part, by prostaglandin E2 and nitric oxide inhibition through NF-κB modulation, and exhibited bioavailability by oral administration. (Keyword) Artepillin C / Propolis / Inflammation / NF-κB / Prostaglandin E2 / Nitric oxide (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ejphar.2008.02.067 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18474366 ● Search Scopus @ Elsevier (PMID): 18474366 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejphar.2008.02.067 (DOI: 10.1016/j.ejphar.2008.02.067, PubMed: 18474366)
88.	Takashi Nakae, Yoshihiro Uto, Motoko Tanaka, Haruna Shibata, Eiji Nakata, Masahide Tominaga, Hiroshi Maezawa, Toshihiro Hashimoto, Kenneth L. Kirk, Hideko Nagasawa and Hitoshi Hori : Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers, Bioorganic & Medicinal Chemistry, Vol.16, No.2, 675-682, 2008. (Summary) We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including β-glucose (β-Glc), β-galactose (β-Gal), α-mannose (α-Man) and N-acetyl-β-galactosamine (β-GalNAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER 1.43) and lower n-octanol/water partition coefficient (Poct) values (Poct < 1.00 × 10-2) than does 1 (TX-1877, ER = 1.75, Poct: 5.60 × 10-2). All acetylated hybrids have similar Poct values (3.55 × 10-2 1.05 × 10-1) to 1 (TX-1877) and have improved ER values (ER 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of Poct (logPoct) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and 1 (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity. (Keyword) Hypoxic cell radiosensitizers / Sugar-hybrids / Electronic states / Hydrophobicity (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2007.10.035 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18029186 ● Search Scopus @ Elsevier (PMID): 18029186 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2007.10.035 (DOI: 10.1016/j.bmc.2007.10.035, PubMed: 18029186)
89.	Kazuto Ohkura, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : Effect of molecular chirality and side chain bulkiness on angiogenesis of haloacetylcarbamoyl-2-nitroimidazole compounds, Anticancer Research, Vol.27, No.6A, 3693-3700, 2007. (Summary) BACKGROUND: Angiogenesis is required for tumor growth and metastasis, and is an exciting target for cancer treatment. We designed and synthesized antiangiogenetic TX agent (TX-1898, -1900), and analyzed their structural features. TXs have a chiral center and S- and R-enantiomers. Conformation analysis and molecular dynamics simulation were undertaken. Materials and METHODS: Molecular models of TXs were constructed using InsightlI-Discover. Conformation analysis was performed with CONFLEX, and z-matrix data were extracted to calculate molecular orbital (MO) parameters (i.e. solvation free energy (dGW)). Their molecular dynamics were simulated with the Discover3 module, and the total energy and dihedral angles were estimated. RESULTS: The methyl-including TXs (Group 1: TX-1863, -1878, -1866, -1879) had 130-229 conformers (-1.26-14.6 kcal/mol). The t-butyl-including group (Group 2: TX-1880, -1881, -1882, -1883) had 244 - 294 conformers (3.69 - 16. 76 kcal/mol), and the p-t-butylphenyl-containing TXs (Group 3: TX-1897, -1899, -1898, -1900) had 584 - 711 conformers (-7.48 -5.18 kcal/mol). The dGWprofile of nine samples, which were extracted from these conformers, were examined and one minimum dGW point was observed in the haloacetylcarbamoyl-2-nitroimidazole TXs (Group 1 -3). CONCLUSION: TX-1898 exhibited significant antiangiogenic activity. The order of antiangiogenic activity was as follows: TX-1898 (93% at 5 microg/pellet) > TX-1900 (82% at 5 microg/pellet) > TX-1897 (64% at 10 microg/pellet) > TX-1899 (58% at 10 microg/pellet). The chiral center has an important role for orienting the molecular characteristics. (Keyword) Angiogenesis Inhibitors / Animals / Cell Proliferation / Chick Embryo / Computer Simulation / Cyclohexanes / Endothelium, Vascular / Nitroimidazoles / Protein Conformation / Rats / Sesquiterpenes / Stereoisomerism / Structure-Activity Relationship (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17970030 ● Search Scopus @ Elsevier (PMID): 17970030 (PubMed: 17970030)
90.	Haruhiko Sakuraba, Kazunari Yoneda, Kumiko Yoshihara, Kyoko Satoh, Ryushi Kawakami, Yoshihiro Uto, Hideaki Tsuge, Katsuyuki Takahashi, Hitoshi Hori and Toshihisa Ohshima : Sequential aldol condensation catalyzed by hyperthermophilic 2-deoxy-D-ribose-5-phosphate aldolase., Applied and Environmental Microbiology, Vol.73, No.22, 7427-7434, 2007. (Summary) Genes encoding 2-deoxy-d-ribose-5-phosphate aldolase (DERA) homologues from two hyperthermophiles, the archaeon Pyrobaculum aerophilum and the bacterium Thermotoga maritima, were expressed individually in Escherichia coli, after which the structures and activities of the enzymes produced were characterized and compared with those of E. coli DERA. To our surprise, the two hyperthermophilic DERAs showed much greater catalysis of sequential aldol condensation using three acetaldehydes as substrates than the E. coli enzyme, even at a low temperature (25 degrees C), although both enzymes showed much less 2-deoxy-d-ribose-5-phosphate synthetic activity. Both the enzymes were highly resistant to high concentrations of acetaldehyde and retained about 50% of their initial activities after a 20-h exposure to 300 mM acetaldehyde at 25 degrees C, whereas the E. coli DERA was almost completely inactivated after a 2-h exposure under the same conditions. The structure of the P. aerophilum DERA was determined by X-ray crystallography to a resolution of 2.0 A. The main chain coordinate of the P. aerophilum enzyme monomer was quite similar to those of the T. maritima and E. coli enzymes, whose crystal structures have already been solved. However, the quaternary structure of the hyperthermophilic enzymes was totally different from that of the E. coli DERA. The areas of the subunit-subunit interface in the dimer of the hyperthermophilic enzymes are much larger than that of the E. coli enzyme. This promotes the formation of the unique dimeric structure and strengthens the hydrophobic intersubunit interactions. These structural features are considered responsible for the extremely high stability of the hyperthermophilic DERAs. (Keyword) Acetaldehyde / Aldehyde-Lyases / Archaeal Proteins / Binding Sites / Catalysis / Enzyme Stability / Hot Temperature / Hydrogen-Ion Concentration / Magnetic Resonance Spectroscopy / Models, Molecular / molecular structure / Protein Structure, Secondary / Protein Structure, Tertiary / Pyrobaculum / Ribosemonophosphates / structureactivity relationship / Substrate Specificity / Thermotoga maritima (Link to Publication Site) ● Publication site (DOI): 10.1128/AEM.01101-07 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17905878 ● Search Scopus @ Elsevier (PMID): 17905878 ● Search Scopus @ Elsevier (DOI): 10.1128/AEM.01101-07 (DOI: 10.1128/AEM.01101-07, PubMed: 17905878)
91.	Shin-ichiro Masunaga, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, G Kashino, Yuko Kinashi and Koji Ono : The usefulness of mild temperature hyperthermia combined with continuous tirapazamine administration under reduced dose-rate irradiation with gamma-rays, International Journal of Hyperthermia, Vol.23, No.1, 29-35, 2007. (Summary) We clarified the usefulness of mild temperature hyperthermia (MTH) in combination with the continuous administration of tirapazamine (TPZ) under reduced dose-rate irradiation (RDRI) using gamma-rays. SCC VII tumour-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. Then, they received a 24 h continuous subcutaneous infusion of TPZ either with or without MTH under high dose-rate irradiation (HDRI) or RDRI using gamma-rays. After the irradiation, the tumour cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in non-proliferating tumour cells without BrdU labeling (= quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total tumour cell populations was determined using tumours that were not pretreated with BrdU. The sensitivity of both the total and Q cell populations, especially the latter, was significantly reduced with RDRI compared with HDRI. TPZ increased the sensitivity of both populations, with a slightly more remarkable increase in Q cells. Further, MTH combined with TPZ raised the sensitivity of both the total and Q cell populations, especially the latter, under RDRI more markedly than under HDRI. From the viewpoint of solid tumour control as a whole, including intratumour Q-cell control, the use of TPZ, especially in combination with MTH, is useful for suppressing the reduction in the sensitivity of tumour cells caused by the decrease in irradiation dose rate in vivo. (Keyword) Animals / Antineoplastic Agents / Carcinoma, Squamous Cell / Cell Line, Tumor / Cell Survival / Combined Modality Therapy / Fever / Gamma Rays / Humans / Mice / Radiation-Sensitizing Agents / Triazines (Link to Publication Site) ● Publication site (DOI): 10.1080/02656730601135366 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17575721 ● Search Scopus @ Elsevier (PMID): 17575721 ● Search Scopus @ Elsevier (DOI): 10.1080/02656730601135366 (DOI: 10.1080/02656730601135366, PubMed: 17575721)
92.	Shin-ichiro Masunaga, Hideko Nagasawa, Kenji Nagata, Minoru Suzuki, Yoshihiro Uto, Hitoshi Hori, Yuko Kinashi and Koji Ono : Dependency of the effect of a vascular disrupting agent on sensitivity to tirapazamine and gamma-ray irradiation upon the timing of its administration and tumor size, with reference to the effect on intratumor quiescent cells, Journal of Cancer Research and Clinical Oncology, Vol.133, No.1, 47-55, 2007. (Summary) The effect of vascular disrupting agent ZD6126 with time on the sensitivity to the hypoxic cytotoxin tirapazamine (TPZ) and gamma-rays was examined in large and small solid tumors. Mice bearing SCC VII tumors 1 or 1.5 cm in diameter received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells, followed by injection with or without ZD6126. In the absence of ZD6126, or 1 or 24 h following ZD6126 injection, the response to TPZ or gamma-ray irradiation in quiescent (Q) cells was assessed in terms of induced micronucleus (MN) frequency using immunofluorescence staining for BrdU. The MN frequency in the total cell population was determined from the tumors not pretreated with BrdU. Another group of tumor-bearing mice received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors. One hour after ZD6126 injection, both small and large tumors showed lower and higher sensitivity, and 24 h after, higher and lower sensitivity, to gamma-rays and TPZ, respectively, than the tumors not treated with ZD6126. Further, they showed larger and smaller HFs 1 and 24 h after ZD6126 injection, respectively. Without ZD6126 and 1 h after injection, small tumors were more sensitive to gamma-rays and less sensitive to TPZ than large tumors, probably due to the smaller HFs than large tumors. In contrast, 24 h after the injection, these differences in sensitivity and the HF between small and large tumors were reversed. The changes in sensitivity and the size of the HF were more marked in the total cell population than in Q cells. Following ZD6126 treatment, in terms of tumor control, especially large tumors and total tumor cell population, administering TPZ 1 h later and gamma-ray irradiation 24 h later were effective. Intratumor physiologic factors such as the size of the HF, depending on the time after ZD6126 injection, have to be taken into account when combining another treatment with ZD6126. (Keyword) Angiogenesis Inhibitors / Animals / Antineoplastic Agents / Carcinoma, Squamous Cell / Cell Line, Tumor / Gamma Rays / Mice / Organophosphorus Compounds / Radiation-Sensitizing Agents / Radiotherapy Dosage / Time Factors / Triazines (Link to Publication Site) ● Publication site (DOI): 10.1007/s00432-006-0145-1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16924543 ● Search Scopus @ Elsevier (PMID): 16924543 ● Search Scopus @ Elsevier (DOI): 10.1007/s00432-006-0145-1 (DOI: 10.1007/s00432-006-0145-1, PubMed: 16924543)
93.	Shin-ichiro Masunaga, Yoshinori Sakurai, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and Koji Ono : The usefulness of a continuous administration of tirapazamine combined with reduced dose-rate irradiation using gamma-rays or reactor thermal neutrons, The British Journal of Radiology, Vol.79, No.948, 991-998, 2006. (Summary) We clarified the usefulness of the continuous administration of tirapazamine (TPZ) in combination with reduced dose-rate irradiation (RDRI) using gamma-rays or reactor thermal neutrons. Squamous cell carcinoma (SCC) VII tumour-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. Then, they received a single intraperitoneal injection or 24 h continuous subcutaneous infusion of TPZ in combination with conventional dose-rate irradiation (CDRI) or RDRI using gamma-rays or thermal neutrons. After irradiation, the tumour cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labelling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total tumour cells was determined using tumours that were not pre-treated with BrdU. The sensitivity of both total and Q cells, especially of Q cells, was significantly reduced with RDRI compared with CDRI. Combination of TPZ increased the sensitivity of both populations, with a slightly more remarkable increase in Q cells. Furthermore, the continuous administration of TPZ raised the sensitivity of both total and Q cell populations, especially the former, more markedly than the single administration, whether combined with CDRI or RDRI using gamma-rays or thermal neutrons. From the viewpoint of solid tumour control as a whole, including intratumour Q-cell control, the use of TPZ, especially when administered continuously, combined with RDRI, is useful for suppressing the reduction in the sensitivity of tumour cells caused by the decrease in irradiation dose rate in vivo. (Keyword) Animals / Bromodeoxyuridine / Carcinoma, Squamous Cell / Cell Survival / Fluorescent Antibody Technique / Gamma Rays / Hyperthermia, Induced / Infusions, Parenteral / Mice / Mice, Inbred C3H / Micronucleus Tests / Neoplasm Transplantation / Neutrons / Radiation-Sensitizing Agents / Radiotherapy Dosage / Skin Neoplasms / Treatment Outcome / Triazines (Link to Publication Site) ● Publication site (DOI): 10.1259/bjr/10893584 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16916808 ● Search Scopus @ Elsevier (PMID): 16916808 ● Search Scopus @ Elsevier (DOI): 10.1259/bjr/10893584 (DOI: 10.1259/bjr/10893584, PubMed: 16916808)
94.	Kazuto Ohkura, Hideko Nagasawa, Yoshihiro Uto, Natsuko Okamura, Aya Murakami and Hitoshi Hori : The Role of Gc Protein Oligosaccharide Structure as a Risk Factor for COPD, Anticancer Research, Vol.26, No.6A, 4073-4078, 2006. (Summary) The risk of chronic obstructive pulmonary disease (COPD) is related to Gc protein allele type, such as Gc1F, GcIS, Gc2. It has been reported that Gc1F increased COPD risk, while Gc*2 suppressed the risk. Thus, the allele type of Gc protein is an important factor in COPD. These Gc proteins differ in sugar composition at Thr418 or Thr420. In this study, features of the sugar structure of modeled Gc proteins were investigated. Gc protein (GclF, Gc1S, Gc2) models were constructed based on X-ray data of vitamin D binding protein (ID=1J7E) using InsightII-Discover with the Homology module, and the molecular orbital (MO) parameters [e.g., dipole moment, solvation free energy (dGW)] of the oligosaccharide were analyzed. The MO parameter of the sugar moiety was different for each Gc protein model. In beta-1,4 bond models, the dipole moment of Gc2 protein was larger (56.6 debye) than Gcl type (GclF: 21.9, Gc1S: 29.8 debye) protein, and it was directed towards the intermolecular space. The Gc2 oligosaccharide region was the most hydrophobic (dGW=-999.4 KI) among the Gc proteins analyzed in this study. The electrostatic potential (ESP) field of beta-1,4 type Gc2 protein was similarly distributed to beta-1,4 linked Gcl-type proteins (GclF, GclS). In the beta-1,3 type Gc protein models, the results of these parameters (i.e., dipole moment, dGW and ESP) were similar to those of beta-1,4 type models. Conclusion: The relationship between COPD risk and the features of the sugar structure in Gc proteins was examined, and it appeared that the active factors (i.e., dipole moment, dGW) might be risk factors for COPD, but passive factors (i.e., ESP) did not affect COPD risk. The bond type (beta-1,4 or beta-1,3) between galactose and N-acetylgalactosamine did not affect the molecular features. (Keyword) Gc protein / Gc protein-derived macrophage activating factor (GcMAF) / N-acetylgalactosamine (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17195460 ● Search Scopus @ Elsevier (PMID): 17195460 (PubMed: 17195460)
95.	Atsushi Miyoshi, Yoshihiko Kitajima, Takao Ide, Kazuma Ohtaka, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and Kohji Miyazaki : Hypoxia accelerates cancer invasion of hepatoma cells by upregulating MMP expression in an HIF-1alpha-independent manner, International Journal of Oncology, Vol.29, No.6, 1533-1539, 2006. (Summary) Tumor hypoxia has been reported to induce tumor progression in several carcinomas. Current studies have shown that hypoxia inducible factor-1alpha (HIF-1alpha) is stabilized under hypoxic conditions and transactivates various genes related to cancer aggressiveness. In the present study, we examined whether hypoxia affects cancer invasion in hepatocellular carcinoma. We aimed to solve the molecular mechanism of tumor invasion under the hypoxic condition. We showed that tumor hypoxia accelerated cancer invasion in two hepatoma cell lines. Using Western blot and RT-PCR analyses we demonstrated striking evidence that the expression of HIF-1alpha, ETS-1, MMP-7 and MT1-MMP was strongly upregulated by hypoxic stimulation. To examine whether these invasion-related genes are regulated by HIF-1alpha, we treated hepatoma cells with TX-402, which was reported to repress HIF-1alpha expression. HIF-1alpha expression was strongly repressed by the TX-402 treatment. In contrast, the expression of ETS-1, MMP-7 and MT1-MMP mRNA was not affected by TX-402 treatment. We further established stable transfectants in which HIF-1alpha dominant negative vector was introduced into Hep3B cells (pHIF-1alphaDN). In the pHIF-1alphaDN cells, the expression of ETS-1, MMP-7 and MT1-MMP was not repressed. Moreover, the invasion activity of pHIF-1alphaDN was not altered, compared with that of the mock. In hepatoma cells, we provided evidence that hypoxic stress accelerates cancer invasion by upregulating ETS-1 and the MMP family by an HIF-1alpha-independent pathway. (Keyword) hypoxia / HIF-1alpha / invasion / MMP / hepatocellular carcinoma (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17088993 ● Summary page in Scopus @ Elsevier: 2-s2.0-33947302545 (PubMed: 17088993, Elsevier: Scopus)
96.	Yoshihiro Uto, Shutaro Ae, Daisuke Koyama, Mitsutoshi Sakakibara, Naoki Otomo, Mamoru Otsuki, Hideko Nagasawa, Kenneth L. Kirk and Hitoshi Hori : Artepillin C isoprenomics: design and synthesis of artepillin C isoprene analogues as lipid peroxidation inhibitor having low mitochondrial toxicity, Bioorganic & Medicinal Chemistry, Vol.14, No.16, 5721-5728, 2006. (Summary) We designed and synthesized isoprene analogues of artepillin C, a major component of Brazilian propolis, and investigated the inhibitory activity on lipid peroxidation of rat liver mitochondria (RLM) and RLM toxicity based on isoprenomics. We succeeded in the synthesis of artepillin C isoprene analogues using regioselective prenylation within the range from 22% to 53% total yield. Reactivity of artepillin C and its isoprene analogues with ABTS (2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)) radical cations showed only a slight difference among the molecules. The isoprene side-chain elongation analogues of artepillin C showed almost the same inhibitory activity against RLM lipid peroxidation as artepillin C. Artepillin C and its isoprene analogues had very weak RLM uncoupling activity. Moreover, artepillin C and its isoprene analogues exhibited a lower inhibitory activity against adenosine 5'-triphosphate (ATP) synthesis by about two orders of magnitude than the effective inhibitory activity against RLM lipid peroxidation. From these results we conclude that artepillin C isoprene analogues could be potent lipid peroxidation inhibitors having low mitochondrial toxicity. We also conclude that elongation of the isoprene side chain of artepillin C to increase lipophilicity had little influence on the inhibitory activity toward RLM lipid peroxidation. (Keyword) Adenosine Triphosphate / Animals / Butadienes / Drug Design / Fatty Acids / Hemiterpenes / Lipid Peroxidation / Male / Mitochondria, Liver / Models, Chemical / Pentanes / Phenylpropionates / Rats / Rats, Wistar (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2006.04.015 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16697207 ● Search Scopus @ Elsevier (PMID): 16697207 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2006.04.015 (DOI: 10.1016/j.bmc.2006.04.015, PubMed: 16697207)
97.	Yoshihiro Uto, Shutaro Ae, Azusa Hotta, Junji Terao, Hideko Nagasawa and Hitoshi Hori : Artepillin C isoprenomics: design and synthesis of artepillin C analogues as antiatherogenic antioxidants, Advances in Experimental Medicine and Biology, Vol.578, 113-118, 2006. (Keyword) Antioxidants / Atherosclerosis / Cholesterol, LDL / Drug Design / Humans / Hypolipidemic Agents / Lipid Metabolism / Phenylpropionates / Structure-Activity Relationship (Link to Publication Site) ● Publication site (DOI): 10.1007/0-387-29540-2_18 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16927679 ● Search Scopus @ Elsevier (PMID): 16927679 ● Search Scopus @ Elsevier (DOI): 10.1007/0-387-29540-2_18 (DOI: 10.1007/0-387-29540-2_18, PubMed: 16927679)
98.	Shin-ichiro Masunaga, Hideko Nagasawa, Yoshinori Sakurai, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi and Koji Ono : The usefulness of mild temperature hyperthermia combined with a newly developed hypoxia-oriented 10B conjugate compound, TX-2100, for boron neutron capture therapy, International Journal of Hyperthermia, Vol.22, No.4, 287-299, 2006. (Summary) To evaluate the usefulness of a new 10B-compound (TX-2100) as a 10B-carrier in boron neutron capture therapy (BNCT), compared with the simultaneous use of its component drugs, sodium borocapate-10B (BSH) and 3-amino-2-quinoxalinecarbonitrile 1,4-dioxide (TX-402). Further, the usefulness of mild temperature hyperthermia (MTH, 40 degrees Celsius, 30 min) combined with TX-2100 was also examined compared with MTH combined with the concurrent administration with its component drugs. TX-2100 is a hybrid compound that has both a hypoxic cytotoxin unit (TX-402) and a thermal neutron-sensitizing unit (BSH). TX-2100 or both TX-402 plus BSH in combination with MTH or not was administered to SCC VII tumour-bearing mice intra-peritoneally. Then, the 10B concentrations in the tumours and normal tissues were measured by gamma-ray spectrometry. Meanwhile, SCC VII tumour-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumours, then treated with TX-2100, TX-402 plus BSH or BSH only, in the same manner as in the biodistribution experiments, either with or without MTH. Right after thermal neutron irradiation during which intra-tumour 10B concentrations remained at similar levels, the tumours were excised, minced and trypsinized. The tumour cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker) and the micronucleus (MN) frequency in cells without BrdU labelling (=quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in the total (P + Q) tumour cell population was determined from the tumours that were not pre-treated with BrdU. The clonogenic cell survival was also determined in mice given no BrdU. 10B biodistribution analyses in tumours, brain, skin, muscles, blood and liver indicated that the administration of TX-2100 plus MTH is most favourable for concentrating a sufficient amount of 10B in tumours and maintaining a high enough 10B concentration during irradiation. In addition, MTH had a stronger sensitizing effect when combined with TX-2100 than with the concurrent administration of its components TX-402 and BSH on both the total and Q cell populations in solid tumours. MTH was very effective in combination with the newly-developed TX-2100. The sensitizing effect in combination with MTH should be examined when new 10B-carriers are designed. (Keyword) Animals / Anoxia / Borohydrides / Boron Compounds / Boron Neutron Capture Therapy / Carcinoma, Squamous Cell / Cell Proliferation / Cell Survival / Combined Modality Therapy / Cyclic N-Oxides / Female / Fluorescent Antibody Technique / Hyperthermia, Induced / Mice / Mice, Inbred C3H / Micronucleus Tests / Quinoxalines / Quinuclidines / Sulfhydryl Compounds / Time Factors / Tissue Distribution / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1080/02656730600708171 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16754350 ● Search Scopus @ Elsevier (PMID): 16754350 ● Search Scopus @ Elsevier (DOI): 10.1080/02656730600708171 (DOI: 10.1080/02656730600708171, PubMed: 16754350)
99.	Shin-ichiro Masunaga, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Yuko Kinashi and Koji Ono : Evaluation of Hypoxic Cell Radio-sensitizers in Terms of Radio-sensitizing and Repair-inhibiting Potential Dependency on p53 Status of Tumor Cells and the Effects on Intratumor Quiescent Cells, Anticancer Research, Vol.26, No.2A, 1261-1270, 2006. (Summary) Intratumor quiescent (Q) cells and p53-mutated tumor cells are more difficult to control than intratumor proliferating (P) cells and p53 wild-type tumor cells, respectively. The usefulness of 3 hypoxic cell radio-sensitizers was compared in terms of a radio-sensitizing effect under aerobic and hypoxic conditions and a repair-inhibiting effect following irradiation on both Q and total (P + Q) cell populations in solid tumors. The dependency of these effects on the p53 status of tumor cells was also examined using tumor cell lines with identical genetic backgrounds except for their p53 status. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The nude mice bearing the tumors and C3H/He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all the P cells in the tumors. Tumor-bearing mice received gamma-ray irradiation while alive or following tumor clamping after being administered no drug, nimorazole, SR-2514 or misonidazole, or received no drug, nimorazole, SR-2514 or misonidazole straight after gamma-ray irradiation. For the group irradiated after receiving the drug, the tumors were excised immediately following irradiation, while for the group irradiated before receiving the drug, the tumors were excised 24 h after irradiation. The excised tumors were minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in the cells without BrdU labelling (= quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in the total tumor cell population was determined from the tumors that had not been pretreated with BrdU. The clonogenic cell survival was also determined in the mice given no BrdU. Both the radio-sensitizing effects under aerobic and hypoxic conditions and the repair-inhibiting effects following gamma-ray irradiation increased in the following order: nimorazole < SR-2514 < misonidazole in both total and Q cells in these 3 tumors. Both effects were more marked in the Q cells and p53-mutated tumors than in the total cells and p53-wild tumors, respectively. In terms of controlling radio-resistant Q tumor cells and p53-mutated tumor cells, the combination of radio-sensitizers and conventional radiotherapy is promising both for radio-sensitization and for repair-inhibition, but further study of the toxicity to normal tissues is needed. (Keyword) Animals / Antineoplastic Agents / Carcinoma, Squamous Cell / Cell Hypoxia / Combined Modality Therapy / DNA Repair / Dose-Response Relationship, Radiation / Female / Gamma Rays / Genes, p53 / Head and Neck Neoplasms / Humans / Mice / Mice, Inbred BALB C / Mice, Inbred C3H / Misonidazole / Nimorazole / Radiation-Sensitizing Agents / Xenograft Model Antitumor Assays (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16619533 ● Search Scopus @ Elsevier (PMID): 16619533 (PubMed: 16619533)
100.	Shin-ichiro Masunaga, Hideko Nagasawa, Keiko Gotoh, Yoshinori Sakurai, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi and Koji Ono : Evaluation of Hypoxia-Specific Cytotoxic Bioreductive Agent-Sodium Borocaptate-¹⁰B Conjugates, as ¹⁰B-Carriers in Boron Neutron,Capture Therary, Radiation Medicine, Vol.24, No.2, 98-107, 2006. (Summary) To evaluate the usefulness of 5 new 10B-compounds (TX-2091, TX-2095, TX-2097, TX-2100, and TX-2110) as 10B-carriers in boron neutron capture therpy (BNCT). They were conjugates that had been synthesized from a hypoxia-specific cytotoxic bioreductive agent, quinoxaline oxide TX-402, and a clinically used 10B-carrier, sodium borocaptate-10B (BSH). The 5 new compounds were hybrid compounds that have both a hypoxic cytotoxin unit and a thermal neutron-sensitizing unit, BSH. These new compounds and BSH were administered intraperitoneally to SCC VII tumor-bearing mice. Then, the 10B concentrations in the tumors and normal tissues were measured by gamma-ray spectrometry. Subsequently, SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with TX-2100, which was chosen based on the results of the above-mentioned biodistribution analyses, or BSH in the same manner as in the biodistribution studies. Right after irradiation, during which intratumor 10B concentrations were kept at levels similar to each other, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling [= quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in the total (P+Q) tumor cell population was determined from the tumors that were not pretreated with BrdU. Clonogenic cell survival was also determined in mice given no BrdU. 10B biodistribution analyses in tumors, brain, skin, muscles, blood, and liver indicated that TX-2100 has the most favorable characteristics for concentrating a sufficient amount of 10B in tumors and maintaining a high enough 10B concentration during irradiation. In addition, TX-2100 had a significantly stronger radio-sensitizing effect with reactor thermal neutron beams than BSH on both total and Q cells in solid tumors. Further, TX-2100 clearly exhibited a radio-sensitizing effect with gamma-rays not only on total cells but also on Q and hypoxic tumor cells, which was not achieved by BSH. A 10B-carrier that acts as a hypoxic cytotoxin on tumor cells as well as having the potential to keep 10B in tumors and sensitize tumor cells more markedly than conventional 10B-carriers, such as TX-2100, is a promising candidate for use in BNCT. (Keyword) Animals / Borohydrides / Boron / Boron Neutron Capture Therapy / Carcinoma, Squamous Cell / Fluorescent Antibody Technique, Indirect / Isotopes / Mice / Molecular Structure / Nitriles / Nitroimidazoles / Quinoxalines / Sulfhydryl Compounds / Tissue Distribution (Link to Publication Site) ● Publication site (DOI): 10.1007/BF02493275 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16715670 ● Summary page in Scopus @ Elsevier: 2-s2.0-33645778985 (DOI: 10.1007/BF02493275, PubMed: 16715670, Elsevier: Scopus)
101.	Hideko Nagasawa, Yoshihiro Uto, Hideyuki Sasaki, Natsuko Okamura, Aya Murakami, Shin-ichi Kubo, Kenneth L.Kirk and Hitoshi Hori : Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity, Anticancer Research, Vol.25, No.6A, 3689-3695, 2005. (Summary) Gcタンパク質(ビタミンD結合タンパク質)がpolymorphismによってそのGcMAF前駆体活性に影響を及ぼすことをgenotyping, phenotyping, 酵素学的研究によって明らかにした． (Keyword) Amino Acid Sequence / Animals / Drug Design / Genotype / Humans / Macrophage-Activating Factors / Molecular Sequence Data / Protein Structure, Tertiary / Structure-Activity Relationship / Vitamin D-Binding Protein (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16302727 ● Search Scopus @ Elsevier (PMID): 16302727 (PubMed: 16302727)
102.	Yoshihiro Uto, Shutaro Ae, Hideko Nagasawa and Hitoshi Hori : Artepillin C Isoprenomics: Facile Total Synthesis and Discovery of Amphiphilic Antioxidant, ACS symposium series, No.909, 176-187, 2005. (Link to Publication Site) ● Publication site (DOI): 10.1021/bk-2005-0909.ch015 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1021/bk-2005-0909.ch015 (DOI: 10.1021/bk-2005-0909.ch015)
103.	Shin-ichiro Masunaga, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori, K. Ohnishi, A. Takahashi, T. Ohnishi, M. Suzuki, K. Nagata, Y. Kinashi and K. Ono : Combination of the antivascular agent ZD6126 with hypoxic cytotoxin treatment, with reference to the effect on quiescent tumor cells and the dependency on p53 status of tumor cells, Oncology Reports, Vol.14, No.2, 394-400, 2005. (Summary) Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. Mice bearing the tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. The mice then received a hypoxic cytotoxin, tirapazamine (TPZ) or TX-402, with or without a vascular targeting agent (VTA), ZD6126. Another group of mice given ZD6126 received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors. After each treatment, the tumor cells were isolated and incubated with a cytokinesis blocker (cytochalasin-B), and the micronucleus (MN) frequency in cells without BrdU labeling [quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumor cells was determined from the tumors that were not pretreated with BrdU. Both hypoxic cytotoxins showed significantly greater toxicity toward SAS/mp53 and Q than SAS/neo and total tumor cells, respectively. The sensitivity to TX-402 was significantly higher than that to TPZ in both total and Q tumor cells of both tumors. The significant enhancive effect by ZD6126 combined with each hypoxic cytotoxin was similar irrespective of p53 status, and slightly greater for total than Q cells probably because of a more marked increase in the size of the HFs in total than Q cells on the use of ZD6126 in both tumors, resulting in a reduction of the difference in the sensitivity to the hypoxic cytotoxin between total and Q cells. In the treatment of conventional cancer therapy-resistant Q tumor cells or p53-mutated tumor cells, the use of hypoxic cytotoxin was very promising either alone or when VTA was co-administered. TX-402 might be more promising than TPZ, although further study of the toxicity to normal tissue is needed. (Keyword) Animals / Antineoplastic Combined Chemotherapy Protocols / Carcinoma, Squamous Cell / Cell Hypoxia / Cell Line, Tumor / Cell Proliferation / Cell Survival / Combined Modality Therapy / Cyclic N-Oxides / Gamma Rays / Head and Neck Neoplasms / Humans / Mice / Mice, Inbred BALB C / Mice, Nude / Micronucleus Tests / Mutation / Organophosphorus Compounds / Quinoxalines / Radiotherapy / Triazines / Tumor Suppressor Protein p53 / Xenograft Model Antitumor Assays (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16012721 ● Search Scopus @ Elsevier (PMID): 16012721 (PubMed: 16012721)
104.	Suzuki Kenji, Hideko Nagasawa, Yoshihiro Uto, Sugimoto Yoshikazu, Noguchi Kazuharu, Wakida Motojii, Wierzba Konstanty, Terada Tadafumi, Asao Tetsuji, Yamada Yuji, Kitazato Kenji and Hitoshi Hori : Napthalimidobenzamide DB-51630: A Novel DNA binding agent inducing p300 gene expression and exerting a potent anti-cancer activity, Bioorganic & Medicinal Chemistry, Vol.13, No.12, 4014-4021, 2005. (Summary) Desined napthalimidobenzamide DB-51630 was a novel DNA binding agent inducing p300 gene expression and exerting a potent anti-cancer activity. (Keyword) DNA binding agent / naphtalimidobenzamide / p300 gene / anti-cancer activity (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2005.03.053 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15911314 ● Search Scopus @ Elsevier (PMID): 15911314 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2005.03.053 (DOI: 10.1016/j.bmc.2005.03.053, PubMed: 15911314)
105.	Tetsuya Oshikawa, Masato Okamoto, Sharif U. Ahmed, Sachiko Furuichi, Tomoyuki Tano, Akiko Sasai, Shin Kan, Soko Kasai, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori and Mitsunobu Sato : TX-1877, a bifunctional hypoxic cell radiosensitizer, enhances anticancer host response: immune cell migration and nitric oxide production., International Journal of Cancer, Vol.116, No.4, 571-578, 2005. (Summary) TX-1877はマクロファージや樹状細胞などの免疫担当細胞を癌組織に集積させNO産生により制癌作用を示すことを明らかにし，免疫賦活作用をもつ低酸素細胞放射線増感剤であることを報告した． (Keyword) Animals / CD4-Positive T-Lymphocytes / CD8-Positive T-Lymphocytes / Carcinoma, Squamous Cell / Cell Hypoxia / Cell Movement / Dendritic Cells / Disease Models, Animal / Humans / Mice / Nitric Oxide / Nitroimidazoles / Radiation Tolerance / T-Lymphocytes, Cytotoxic (Link to Publication Site) ● Publication site (DOI): 10.1002/ijc.21101 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15825172 ● Search Scopus @ Elsevier (PMID): 15825172 ● Search Scopus @ Elsevier (DOI): 10.1002/ijc.21101 (DOI: 10.1002/ijc.21101, PubMed: 15825172)
106.	Shin-ichiro Masunaga, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori, Minoru Suzuki, Kenji Nagata, Yuko Kinashi and Koji Ono : The usefulness of continuous administration of hypoxic cytotoxin combined with mild temperature hyperthermia, with reference to effects on quiescent tumor cell populations., International Journal of Hyperthermia, Vol.21, No.4, 305-318, 2005. (Summary) To evaluate the usefulness of continuous administration of hypoxic cytotoxins in terms of targeting acute hypoxia in solid tumours and the significance of combination with mild temperature hyperthermia (MTH) (40 degrees C, 60 min), the cytotoxic effects of singly or continuously administered tirapazamine (TPZ) and TX-402 were examined in combination with or without MTH in vivo. Further, the effects were also analysed on total (=proliferating (P)+quiescent (Q)) and Q cell populations in solid tumours with the method for selectively detecting the Q cell response. C3H/He mice bearing SCC VII tumours received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days to label all P cells. The tumour-bearing mice then received a single intra-peritoneal injection or 24 h continuous subcutaneous infusion of hypoxic cytotoxin, TPZ or TX-402, with or without MTH. On the other hand, to detect the changes in the hypoxic fraction (HF) in the tumours by MTH, another group of mice with or without MTH received a series of test doses of gamma-rays while alive or after tumour clamping. After each treatment, the tumour cells were isolated and incubated with a cytokinesis blocker (=cytochalasin-B) and the micronucleus (MN) frequency in cells without BrdU labelling (=Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total tumour cells was determined from the tumours that were not pre-treated with BrdU. The sensitivity to TX-402 was slightly higher than that to TPZ in both total and Q tumour cells. Continuous administration elevated the sensitivity of both total and Q cells, especially total cells. MTH raised the sensitivity of Q cells more remarkably than that of total cells in both single and continuous administrations. It was thought to be probably because of the higher dose distribution of hypoxic cytotoxin in intermediately hypoxic areas derived mainly from chronic hypoxia through MTH. From the viewpoint of tumour control as a whole including both total and Q tumour cells, the continuous administration of hypoxic cytotoxin combined with MTH may be useful for sensitizing tumour cells in vivo. (Keyword) Animals / Antineoplastic Agents / Bromodeoxyuridine / Carcinoma, Squamous Cell / Combined Modality Therapy / Cyclic N-Oxides / Female / Fluorescent Antibody Technique / Hyperthermia, Induced / Mice / Mice, Inbred C3H / Micronucleus Tests / Neoplasm Transplantation / Neoplasms / Quinoxalines / Triazines (Link to Publication Site) ● Publication site (DOI): 10.1080/02656730500060574 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16019857 ● Search Scopus @ Elsevier (PMID): 16019857 ● Search Scopus @ Elsevier (DOI): 10.1080/02656730500060574 (DOI: 10.1080/02656730500060574, PubMed: 16019857)
107.	Hideko Nagasawa, Hideyuki Sasaki, Yoshihiro Uto, Shin-ichi Kubo and Hitoshi Hori : Association of the Macrophage Activating Factor (MAF) Precursor Activity with Polymorphism in Vitamin D-binding Protein, Anticancer Research, Vol.24, No.5c, 3361-3366, 2004. (Summary) Gcタンパク質(ビタミンD結合タンパク質)がpolymorphismによってそのGcMAF前駆体活性に影響を及ぼすことをgenotyping, phenotyping, 酵素学的研究によって明らかにした． (Keyword) vitamin D-binding protein / Gc protein / macrophage activating factor (MAF) / Gc typing / carbohydrate processing / GalNAc / GROUP-SPECIFIC COMPONENT / FACTOR DBP-MAF / BETA-GALACTOSIDASE / STRUCTURAL BASIS / GC / SYSTEM / ACTIN / ANGIOGENESIS / PURIFICATION / VARIANTS (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15515432 ● Search Scopus @ Elsevier (PMID): 15515432 (PubMed: 15515432)
108.	Cheng-Zhe Jin, Hideko Nagasawa, Mariko Shimamura, Yoshihiro Uto, Seiichi Inayama, Yoshio Takeuchi, L. Kenneth Kirk and Hitoshi Hori : Angiogenesis inhibitorTX-1898: synthesis of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers, Bioorganic & Medicinal Chemistry, Vol.12, No.18, 4917-4927, 2004. (Summary) 立体多様性のある工学活性ハロアセチルカルバモイル-2-ニトロイミダゾ-ル系低酸素細胞放射線増感剤の分子設計し，新規血管新生阻害活性のある (R)-p-tert-butylphenyl-bromoacetylcarbamoyl-w-nitroimidazoleであるTX―1898を創製した． (Keyword) Angiogenesis inhibitor / Hypoxic cell radiosensitizer / Haloacetylcarbamoyl-2-nitroimidazole / Enantiomers (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2004.06.039 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15336271 ● Search Scopus @ Elsevier (PMID): 15336271 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2004.06.039 (DOI: 10.1016/j.bmc.2004.06.039, PubMed: 15336271)
109.	Shin-ichiro Masunaga, Hideko Nagasawa, Masamitsu Hiraoka, Yoshinori Sakurai, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi and Koji Ono : The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as10B-carriers in boron neutron capture therapy, Applied Radiation and Isotopes, Vol.61, No.5, 953-958, 2004. (Summary) BNCTの10Bキャリアーとして2-Nitroimidazole-BSH-10B Conjugate, TX-2041がγ線に対して放射線増感効果，BNCTの10BキャリアーとしてBSHそのものより優れていることを明らかにした． (Keyword) Animals / Boron Compounds / Boron Neutron Capture Therapy / Carcinoma, Squamous Cell / Cell Hypoxia / Cell Survival / Drug Carriers / Female / Isotopes / Mice / Mice, Inbred C3H (Link to Publication Site) ● Publication site (DOI): 10.1016/j.apradiso.2004.05.018 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15308174 ● Search Scopus @ Elsevier (PMID): 15308174 ● Search Scopus @ Elsevier (DOI): 10.1016/j.apradiso.2004.05.018 (DOI: 10.1016/j.apradiso.2004.05.018, PubMed: 15308174)
110.	Shin-ichiro Masunaga, Hideko Nagasawa, Masamitsu Hiraoka, Yoshinori Sakurai, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi and Koji Ono : Applicability of the 2-Nitroimidazole-sodium borocaptate-10B Conjugate, TX-2060, as a 10B-carrier in Boron Neutron Capture Therapy, Anticancer Research, Vol.24, No.5, 2975-2983, 2004. (Summary) BNCTの10Bキャリアーとして2-Nitroimidazole-BSH-10B Conjugate, TX-2060がBSHそのものより，薬物動態学的にも，Q細胞および全がん細胞に対する毒性においても優れていることを明らかにした． (Keyword) Animals / Borohydrides / Boron / Boron Neutron Capture Therapy / Carcinoma, Squamous Cell / Female / Isotopes / Mice / Mice, Inbred C3H / Micronucleus Tests / Nitroimidazoles / Sulfhydryl Compounds / Tissue Distribution (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15517904 ● Search Scopus @ Elsevier (PMID): 15517904 (PubMed: 15517904)
111.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Kazuto Ohkura, Kenneth L. Kirk, Yoshimasa Uehara and Mariko Shimamura : Design of Hypoxia-Trageting Protein Tyrosine Kinase Inhibitor using an innovative pharmacophore 2-methylene-4-cyclopentene-1,3-dione, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol.1697, No.1-2, 29-38, 2004. (Summary) 本総説は，低酸素を標的とするPTK阻害剤の開発戦略を紹介し，特にその分子設計におけるファルマコホアとして，2-methylene-4-cyclopentene-1,3-dione構造の重要性に関して，我々の研究成果をもとに論述したものである． (Keyword) Animals / Antineoplastic Agents / Benzylidene Compounds / Cell Hypoxia / Cyclopentanes / Drug Design / Enzyme Inhibitors / Humans / Mitochondria / Models, Molecular / Protein-Tyrosine Kinases / Structure-Activity Relationship / Tyrphostins (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbapap.2003.11.011 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15023348 ● Search Scopus @ Elsevier (PMID): 15023348 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbapap.2003.11.011 (DOI: 10.1016/j.bbapap.2003.11.011, PubMed: 15023348)
112.	Tomoya Fujita, Hideko Nagasawa, Yoshihiro Uto, Toshihiro Hashimoto, Yoshinori Asakawa and Hitoshi Hori : Synthesis of the new mannosidase inhibitor, diversity-oriented 5-substiruted swainsonine analogues, via stereoselective Mannich reaction, Organic Letters, Vol.6, No.5, 827-830, 2004. (Summary) 本論文では，免役修飾剤をめざしたswainsonineアナログの分子設計とαーマンノシダーゼ阻害剤活性に関する構造活性相関，及び多様性を指向した医薬品分子設計において有用な立体選択的Mannish反応の開発について報告した． (Keyword) Enzyme Inhibitors / Mannosidases / Models, Molecular / Molecular Structure / Stereoisomerism / Swainsonine (Link to Publication Site) ● Publication site (DOI): 10.1021/ol049947m (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14986985 ● Search Scopus @ Elsevier (PMID): 14986985 ● Search Scopus @ Elsevier (DOI): 10.1021/ol049947m (DOI: 10.1021/ol049947m, PubMed: 14986985)
113.	Saharuddin Bin Mohamad, Hideko Nagasawa, Hideyuki Sasaki, Yoshihiro Uto, Yoshinori Nakagawa, Ken Kawashima and Hitoshi Hori : Gc Protein-derived Macrophage Activating Factor (GcMAF): Isoelectric Focusing Pattern and Tumoricidal Activity, Anticancer Research, Vol.23, No.6, 4451-4458, 2003. (Summary) 本論文において，等電点電気泳動法によってGcタンパク質の多型を分類し，種々の多型の糖鎖構造の違いによって，これより生成するGcMAFのマクロファージ活性化作用，及びそれを介した殺細胞活性が異なることを明らかにした． (Keyword) Adult / Aged / Aged, 80 and over / Animals / Cell Line, Tumor / Coculture Techniques / Female / Humans / Immunotherapy, Adoptive / Isoelectric Focusing / Macrophage-Activating Factors / Macrophages / Mice / Mice, Inbred ICR / Middle Aged / Neoplasms, Experimental / Nitric Oxide / Tumor Necrosis Factor-alpha / Vitamin D-Binding Protein (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14666733 ● Search Scopus @ Elsevier (PMID): 14666733 (PubMed: 14666733)
114.	Hideko Nagasawa, Naoko Mikamo, Yoshimi Nakajima, Hideki Matsumoto, Yoshihiro Uto and Hitoshi Hori : Antiangiogenic hypoxic cytotoxin TX-402 inhibits hypoxia-inducible factor 1 signaling pathway, Anticancer Research, Vol.23, No.6a, 4427-4434, 2003. (Summary) 本論文で，血管新生阻害作用を有する新規hypoxic cytotoxin TX-402は，低酸素誘導因子(HIF-1)シグナル経路を阻害することによって，血管新生阻害作用などの低酸素応答反応を抑制することを明らかにした． (Keyword) Angiogenesis Inhibitors / Animals / Carcinoma, Non-Small-Cell Lung / Cell Hypoxia / Cell Line, Tumor / Chick Embryo / DNA-Binding Proteins / Dose-Response Relationship, Drug / Gene Expression Regulation, Neoplastic / Genes, p53 / Humans / Hypoxia-Inducible Factor 1 / Hypoxia-Inducible Factor 1, alpha Subunit / Lung Neoplasms / Nuclear Proteins / Signal Transduction / Transcription Factors / Transfection / Triazines (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14666730 ● Search Scopus @ Elsevier (PMID): 14666730 (PubMed: 14666730)
115.	紅林淳一, 山本裕, 大久保澄子, 園尾博司, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and 森谷卓也 : 乳癌の内分療法抵抗性克服を目指した研究:Hypoxic cytotoxinsを用いた実験, 乳癌基礎研究, Vol.12, 35-38, 2003. (Summary) 本論文において，乳がんホルモン療法におけるホルモン依存性の消失をめざして，hypoxic cytotoxinの併用について検討した．その結果，hhypoxic cytotoxinはホルモン療法抵抗性の獲得を遅延させ，効果を増強する可能性があることを示した．
116.	Ikuo Nakanishi, Yoshihiro Uto, Kei Ohkubo, Kentaro Miyazaki, Haruko Yakumaru, Shiro Urano, Haruhiro Okuda, Jun-Ichi Ueda, Toshihiko Ozawa, Kiyoshi Fukuhara, Shunichi Fukuzumi, Hideko Nagasawa, Hitoshi Hori and Nobuo Ikota : Efficient radical scavenging ability of artepillin C, a major component of Brazilian propolis, and the mechanism, Organic & Biomolecular Chemistry, Vol.1, No.9, 1452-1454, 2003. (Summary) 本論文では，ブラジル産プロポリスの主要な活性成分であるartepillin Cのラジカル消去作用とその機構について解析した． (Keyword) Catechin / Free Radical Scavengers / Free Radicals / Hydrogen / Kinetics / Nucleic Acid Synthesis Inhibitors / Peroxides / Phenylpropionates / Propolis (Link to Publication Site) ● Publication site (DOI): 10.1039/b302098c (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12926271 ● Search Scopus @ Elsevier (PMID): 12926271 ● Search Scopus @ Elsevier (DOI): 10.1039/b302098c (DOI: 10.1039/b302098c, PubMed: 12926271)
117.	Saharuddin B. Mohamad, Hitoshi Hori, Hideko Nagasawa, Kenji Usui and Yoshihiro Uto : Characterization of human Gc protein-derived macrophage activation factor (GcMAF) and its functional role in macrophage tumoricidal activity, Advances in Experimental Medicine and Biology, Vol.510, 77-82, 2003. (Summary) 本論文では，GcMAFの抗腫瘍作用の作用機構として，マクロファージ貪食能と活性酸素生成を活性化することを明らかにした． (Keyword) Animals / Cell Survival / Humans / Macrophage Activation / Macrophage-Activating Factors / Macrophages, Peritoneal / Mice / Neoplasms / Phagocytosis / Superoxides / Vitamin D-Binding Protein (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12580408 ● Search Scopus @ Elsevier (PMID): 12580408 (PubMed: 12580408)
118.	Mariko Shimamura, Hideko Nagasawa, H Ashino, Y Yamamoto, T Hazato, Yoshihiro Uto, Hitoshi Hori and Seiichi Inayama : A novel hypoxia-dependent 2-nitroimidazole KIN-841 inhibits tumour-specific angiogenesis by blocking production of angiogenic factors, British Journal of Cancer, Vol.88, No.2, 307-313, 2003. (Summary) 本論文において，我々が分子設計した新規低酸素細胞放射線増感剤KIN-841が強い放射線増感効果のほかに，血管新生因子の生成を阻害することによって強い血管新生阻害作用を示すことを明らかにした． (Keyword) Angiogenesis Inhibitors / Animals / Anoxia / Carcinoma, Lewis Lung / Cattle / Cell Division / Chick Embryo / Chorion / Endothelial Growth Factors / Endothelium, Vascular / Enzyme-Linked Immunosorbent Assay / Imidazoles / Injections, Intraperitoneal / Intercellular Signaling Peptides and Proteins / Lung Neoplasms / Lymphokines / Mice / Neovascularization, Pathologic / Nitro Compounds / Pulmonary Artery / Tumor Cells, Cultured / Vascular Endothelial Growth Factor A / Vascular Endothelial Growth Factors (Link to Publication Site) ● Publication site (DOI): 10.1038/sj.bjc.6600667 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12610518 ● Search Scopus @ Elsevier (PMID): 12610518 ● Search Scopus @ Elsevier (DOI): 10.1038/sj.bjc.6600667 (DOI: 10.1038/sj.bjc.6600667, PubMed: 12610518)
119.	Shin-ichiro Masunaga, Koji Ono, Mitsunori Kirihata, Masao Takagaki, Yoshinori Sakurai, Yuko Kinashi, Tooru Kobayashi, Minoru Suzuki, Kenji Nagata, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Potential of α-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, regarding its enantiomers, Journal of Cancer Research and Clinical Oncology, Vol.129, No.1, 21-28, 2003. (Summary) We evaluated the potential of a newly developed (10)B-containing alpha-amino alcohol of p-boronophenylalanine-(10)B (BPA), p-boronophenylalaninol (BPAol), as a boron carrier in boron neutron capture therapy. C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously via implanted mini-osmotic pumps to label all proliferating (P) cells. After oral administration of L-BPA or D-BPA, or intraperitoneal injection of L-BPAol or D-BPAol, the tumors were irradiated with reactor thermal neutron beams. Some of the tumors were heated at 40 degrees C for 30 min (mild temperature hyperthermia (MTH)) right before neutron exposure, and/or tirapazamine (TPZ) was intraperitoneally injected 30 min before irradiation. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling [ =quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, tumor cell suspensions obtained in the same manner were used for determining the apoptosis frequency in Q cells. The apoptosis and MN frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Without TPZ or MTH, L- and D-BPAol increased both frequencies markedly, especially for total cells. Although not significantly larger, L-BPA and D-BPAol increased both frequencies slightly more than D-BPA and L-BPAol, respectively. Combination with both MTH and TPZ markedly reduced the sensitivity difference between total and Q cells. Both L- and D-BPAol have potential as a (10)B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ. (Keyword) Amino Alcohols / Animals / Apoptosis / Boranes / Boron Neutron Capture Therapy / Dose-Response Relationship, Drug / Dose-Response Relationship, Radiation / Drug Carriers / Female / Fluorescent Antibody Technique / Hyperthermia, Induced / Mice / Mice, Inbred C57BL / Phenylalanine / Radiation-Sensitizing Agents / Radiotherapy Dosage / Triazines (Link to Publication Site) ● Publication site (DOI): 10.1007/s00432-002-0397-3 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12618897 ● Search Scopus @ Elsevier (PMID): 12618897 ● Search Scopus @ Elsevier (DOI): 10.1007/s00432-002-0397-3 (DOI: 10.1007/s00432-002-0397-3, PubMed: 12618897)
120.	Shin-ichiro Masunaga, Koji Ono, Akihisa Takahashi, Ken Onishi, Takeo Onishi, Minoru Suzuki, Kenji Nagata, Yuko Kinashi, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Usefulness of combined treatment with mild temperature hyperthermia and/or tirapazamine in the treatment of solid tumors: its independence of p53 states, Cancer Science, Vol.94, No.1, 125-133, 2003. (Summary) 本論文では，p53正常または変異がん細胞を移植した担癌マウスモデルにおける放射線または化学療法による治療において，マイルドハイパーサーミア単独あるいはTPZとの併用処理が，p53ステータスにかかわらず特にQ細胞に対して有効であることを示した． (Keyword) Animals / Antineoplastic Agents / Antineoplastic Combined Chemotherapy Protocols / Apoptosis / Bromodeoxyuridine / Carcinoma, Squamous Cell / Cell Hypoxia / Cisplatin / Combined Modality Therapy / DNA Damage / Gamma Rays / Genes, p53 / Head and Neck Neoplasms / Humans / Hyperthermia, Induced / Mice / Mice, Inbred BALB C / Mice, Nude / Micronucleus Tests / Neoplasm Proteins / Paclitaxel / Radiation-Sensitizing Agents / Triazines / Tumor Cells, Cultured / Tumor Suppressor Protein p53 / Xenograft Model Antitumor Assays (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1349-7006.2003.tb01363.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12708486 ● Search Scopus @ Elsevier (PMID): 12708486 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1349-7006.2003.tb01363.x (DOI: 10.1111/j.1349-7006.2003.tb01363.x, PubMed: 12708486)
121.	Saharuddin B. Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Preparation of Gc Protein-derived macrophage Activation Factor (GcMAF) and its Structural Characterization and Biological Activities., Anticancer Research, Vol.22, No.6C, 4297-4300, 2002. (Summary) 本論文において，Gcタンパク質からマクロファージ活性化因子(GcMAF)へのプロセシング反応を解明するため，糖鎖修飾と生物活性の相関を検討した．その結果GcMAFのマクロファージ活性化作用においてN-acetylgalactosamine糖鎖が重要であることを明らかにした． (Keyword) Animals / Blotting, Western / Chromatography, Affinity / Humans / Macrophage Activation / Macrophage-Activating Factors / Macrophages, Peritoneal / Mice / Neuraminidase / Superoxides / Vitamin D-Binding Protein / beta-Galactosidase (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12553073 ● Search Scopus @ Elsevier (PMID): 12553073 (PubMed: 12553073)
122.	Hitoshi Hori, Hideko Nagasawa, Masaki Ishibashi, Yoshihiro Uto, Akihiko Hirata, Kouichi Saijo, Kazuto Ohkura, Kenneth L. Kirk and Yoshimasa Uehara : TX-1123: an antitumor 2-hydroxyarylidene-4-cyclopentene-1,3-dione as a protein tyrosine kinase inhibitor having low mitochondrial toxicity, Bioorganic & Medicinal Chemistry, Vol.10, No.10, 3257-3265, 2002. (Summary) A series of 2-hydroxyarylidene-4-cyclopentene-1,3-diones were designed, synthesized, and evaluated with respect to protein tyrosine kinase (PTK) inhibition, mitochondrial toxicity, and antitumor activity. Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyrphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17, a potent antitumor tyrphostin. The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties, including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to protein tyrosine kinase inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates that PTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AG17. (Keyword) Antineoplastic Agents / Benzylidene Compounds / Calcium-Calmodulin-Dependent Protein Kinases / Cell Division / Cyclopentanes / Elongation Factor 2 Kinase / Enzyme Inhibitors / Hepatocytes / Humans / Mitochondria / Protein-Tyrosine Kinases / Structure-Activity Relationship / Tumor Cells, Cultured / src-Family Kinases (Link to Publication Site) ● Publication site (DOI): 10.1016/S0968-0896(02)00160-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12150871 ● Search Scopus @ Elsevier (PMID): 12150871 ● Search Scopus @ Elsevier (DOI): 10.1016/S0968-0896(02)00160-8 (DOI: 10.1016/S0968-0896(02)00160-8, PubMed: 12150871)
123.	Kimiko Tamemoto, Yoshihisa Takaishi, Kazuyoshi Kawazoe, Gisho Honda, Michiho Ito, Fumiyuki Kiuchi, Yoshio Takeda, Olimjon K. Kodzhimatov, Ozodbek Ashurmetov, Katsuhide Shimizu, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : An Unusual Sesquiterpene Derivative from Ferula Kuhistanica, Journal of Natural Products, Vol.65, No.9, 1323-1324, 2002. (Summary) Ferula Kuhistanicaより単離したセスキテルペン誘導体の構造決定と活性を明らかにした． (Keyword) Anti-Bacterial Agents / Antineoplastic Agents, Phytogenic / Colonic Neoplasms / Drug Screening Assays, Antitumor / Ferula / Fruit / Humans / Inhibitory Concentration 50 / Methicillin / Molecular Conformation / Molecular Structure / Nuclear Magnetic Resonance, Biomolecular / Plants, Medicinal / Sesquiterpenes / Staphylococcus aureus / Tumor Cells, Cultured / Uzbekistan (Link to Publication Site) ● Publication site (DOI): 10.1021/np020020+ (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12350156 ● Search Scopus @ Elsevier (PMID): 12350156 ● Search Scopus @ Elsevier (DOI): 10.1021/np020020+ (DOI: 10.1021/np020020+, PubMed: 12350156)
124.	Yoshihiro Uto, Akihiko Hirata, Tomoya Fujita, Syunsuke Takubo, Hideko Nagasawa and Hitoshi Hori : First Total Synthesis of Artepillin C Established by o,o'-Diprenylation of p-Halophenols in Water, The Journal of Organic Chemistry, Vol.67, No.7, 2355-2357, 2002. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した． (Keyword) Brazil / Catalysis / Cinnamates / Mass Spectrometry / Molecular Structure / Nuclear Magnetic Resonance, Biomolecular / Phenols / Phenylpropionates / Propolis / Water (Link to Publication Site) ● Publication site (DOI): 10.1021/jo0056904 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11925254 ● CiNii @ National Institute of Informatics (CRID): 1363670318679107584 ● Search Scopus @ Elsevier (PMID): 11925254 ● Search Scopus @ Elsevier (DOI): 10.1021/jo0056904 (DOI: 10.1021/jo0056904, PubMed: 11925254, CiNii: 1363670318679107584)
125.	Saharuddin B. Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation, Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology, Vol.132, No.1, 1-8, 2002. (Summary) 本論文では，GcMAFのマクロファージ活性化機構を明らかにするため，腫瘍細胞株におけるalpha-N-acetylgalactosaminidase(alpha-NaGalase)がエキソ型であり，正常細胞に比べて活性化されていることを示した．また，alpha-NaGalaseによってGcMAFのマクロファージ活性化能が阻害されることを明らかにした． (Keyword) Animals / Cell Division / Hexosaminidases / Humans / Hydrogen-Ion Concentration / Lipopolysaccharides / Macrophage Activation / Macrophage-Activating Factors / Mice / Signal Transduction / Substrate Specificity / Tumor Cells, Cultured / Vitamin D-Binding Protein / alpha-N-Acetylgalactosaminidase (Link to Publication Site) ● Publication site (DOI): 10.1016/S1095-6433(01)00522-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12062184 ● Search Scopus @ Elsevier (PMID): 12062184 ● Search Scopus @ Elsevier (DOI): 10.1016/S1095-6433(01)00522-0 (DOI: 10.1016/S1095-6433(01)00522-0, PubMed: 12062184)
126.	Yoshihiro Uto, Akihiko Hirata, Masaki Ishibashi, Hideko Nagasawa and Hitoshi Hori : Design and synthesis of 2,6-diprenyl-4-iodophenol TX-1952 with a novel and potent anti-peroxidative activity, Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology, Vol.132, No.1, 41-45, 2002. (Summary) 本論文において，抗酸化剤をめざして2,4,6-三置換フェノール誘導体の分子設計·合成を行い，これらの生物活性を調べたところ，TX-1952は非常に強い抗酸化活性を有することを明らかにした． (Keyword) Animals / Antioxidants / Biphenyl Compounds / Dose-Response Relationship, Drug / Free Radical Scavengers / Inhibitory Concentration 50 / Iodobenzenes / Lipid Peroxidation / Mitochondria, Liver / Phenols / Picrates / Rats (Link to Publication Site) ● Publication site (DOI): 10.1016/S1095-6433(01)00527-X (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12062189 ● Search Scopus @ Elsevier (PMID): 12062189 ● Search Scopus @ Elsevier (DOI): 10.1016/S1095-6433(01)00527-X (DOI: 10.1016/S1095-6433(01)00527-X, PubMed: 12062189)
127.	Hideko Nagasawa, Mao Yamashita, Naoko Mikamo, Mariko Shimamura, Shigenori Oka, Yoshihiro Uto and Hitoshi Hori : Design, synthesis and biological activities of antiangiogenic hypoxic cytotoxin, triazine-N-oxide derivatives, Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology, Vol.132, No.1, 33-40, 2002. (Summary) 本論文において，hypoxic cytotoxinであるTPZをリードとして，トリアジンまたはキノキサリンーNーオキシド類の分子設計を行い，生物活性を調べた．その結果，Hypoxic cyto-toxinはp53非依存的アポトーシス誘導作用を有し，さらに強い血管新生阻害作用を示すことを明らかにした． (Link to Publication Site) ● Publication site (DOI): 10.1016/S1095-6433(01)00526-8 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-0036010210 (DOI: 10.1016/S1095-6433(01)00526-8, Elsevier: Scopus)
128.	Soko Kasai, Hideko Nagasawa, Mariko Shimamura, Yoshihiro Uto and Hitoshi Hori : Design and Synthesis of Antiangiogenic/Heparin-Binding Arginine Dendrimer Mimicking the Surface of Endostatin, Bioorganic & Medicinal Chemistry Letters, Vol.12, No.6, 951-954, 2002. (Summary) 本論文では，血管新生阻害タンパク質のエンドスタチン構造ミミックとしてアルギニンデンドリマーの分子設計，合成，生物活性の検討を行った．その結果，我々の開発したTX-1944は，強い血管新生阻害作用を示し，ヘパリン結合能を有することを明らかにした． (Keyword) ANGIOGENESIS INHIBITOR ENDOSTATIN / TUMOR-GROWTH (Link to Publication Site) ● Publication site (DOI): 10.1016/S0960-894X(02)00066-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11959001 ● CiNii @ National Institute of Informatics (CRID): 1573105976568216832 ● Search Scopus @ Elsevier (PMID): 11959001 ● Search Scopus @ Elsevier (DOI): 10.1016/S0960-894X(02)00066-5 (DOI: 10.1016/S0960-894X(02)00066-5, PubMed: 11959001, CiNii: 1573105976568216832)
129.	Farid A. Abou-Bedair, Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Medhat Abu-Zeid and Seiichi Inayama : Comparision of Hypoxic Cell Radiosensitizers, KIN-804, KIN-844, KIN-806 and TX-1877, on Brain and Liver Metabolizing Capacities in Mice Bearing Ehrlich Ascites Carcinoma, Biological & Pharmaceutical Bulletin, Vol.25, No.5, 591-596, 2002. (Summary) 本論文において，エーリッヒ癌細胞移殖マウスを用いて，低酸素細胞放射線増感剤KIN-804，844，806及びTX-1877の脳及び肝臓の代謝能におよぼす影響を検討した．まず，神経毒性の指標としてアセチルコリンエステラーゼ(AChE)阻害作用について検討し，上記の増感剤はいずれもMISOと異なり毒性を示さないことを見出した．また，KIN-806とTX-1877は，抗酸化システムであるGSH及びSOD活性を上昇させた．以上より，KIN-806及びTX-1877は放射線照射によって減少する抗酸化システムを回復させるユニークで毒性の低い低酸素細胞放射線増感剤として有望な化合物であることを明らかにした． (Keyword) Acetylcholinesterase / Animals / Brain Chemistry / Carcinoma, Ehrlich Tumor / Catalase / Cell Hypoxia / Female / Free Radical Scavengers / Glucosephosphate Dehydrogenase / Glutathione / Hydroxamic Acids / Liver / Mice / Nitroimidazoles / Radiation-Sensitizing Agents / Superoxide Dismutase / Whole-Body Irradiation (Link to Publication Site) ● Publication site (DOI): 10.1248/bpb.25.591 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12033498 ● Search Scopus @ Elsevier (PMID): 12033498 ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.25.591 (DOI: 10.1248/bpb.25.591, PubMed: 12033498)
130.	佃孝彦, Yoshihiro Uto, 中川美典 and Hitoshi Hori : 4,4'-[3-[2-(1-Ethyl-4(1H)-quinolinylidene)ethylidene]propenylene]bis(1-ethylquinolinium iodide)(NK-4)の物理化学的性質及び安定性, Pharmaceutical Regulatory Science, Vol.32, No.11, 709-716, 2001.
131.	Shin-ichiro Masunaga, Koji Ono, Mitsunori Kirihata, Masao Takagaki, Yoshinori Sakurai, Yuko Kinashi, Tooru Kobayashi, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : EVALUATION OF THE POTENTIAL OF PARA-BORONOPHENYLALANINOL AS A BORON CARRIER IN BORON NEUTRON CAPTURE THERAPY, REFERRING TO THE EFFECT ON INTRATUMOR QUIESCENT CELLS, Japanese Journal of Cancer Research, Vol.92, No.9, 996-1007, 2001. (Summary) C57BL mice bearing EL4 tumors and C3H / He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Three hours after oral administration of l-p-boronophenylalanine-(10)B (BPA), or 30 min after intraperitoneal injection of sodium borocaptate-(10)B (BSH) or l-p-boronophenylalaninol (BPA-ol), a newly developed (10)B-containing alpha-amino alcohol, the tumors were irradiated with thermal neutron beams. For the combination with mild temperature hyperthermia (MTH) and / or tirapazamine (TPZ), the tumors were heated at 40 degrees C for 30 min immediately before neutron exposure, and TPZ was intraperitoneally injected 30 min before irradiation. The tumors were then excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, tumor cell suspensions obtained in the same manner were used for determining the apoptosis frequency in Q cells. The MN and apoptosis frequency in total (P + Q) tumor cells were determined from tumors that were not pretreated with BrdU. Without TPZ or MTH, BPA-ol increased both frequencies most markedly, especially for total cells. However, as with BPA, the sensitivity difference between total and Q cells was much larger than with BSH. On combined treatment with both MTH and TPZ, this sensitivity difference was markedly reduced, similarly to when BPA was used. MTH increased the (10)B uptake of all (10)B-compounds into both tumor cells. BPA-ol has good potential as a (10)B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ. (Keyword) Administration, Oral / Animals / Antineoplastic Agents / Apoptosis / Boranes / Boron Neutron Capture Therapy / Bromodeoxyuridine / Carcinoma, Squamous Cell / Combined Modality Therapy / Cytochalasin B / Drug Screening Assays, Antitumor / Fluorescent Antibody Technique, Indirect / Hindlimb / Hyperthermia, Induced / Injections, Intraperitoneal / Interphase / Lymphoma / Mice / Mice, Inbred C3H / Mice, Inbred C57BL / Micronucleus Tests / Molecular Structure / Neutrons / Phenylalanine / Radiation-Sensitizing Agents / Radiometry / Triazines (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11572769 ● Search Scopus @ Elsevier (PMID): 11572769 (PubMed: 11572769)
132.	Shin-ichiro Masunaga, Koji Ono, Minoru Suzuki, Yasumasa Nishimura, Yuko Kinashi, Masao Takagaki, Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Izumi Tsuchiya, Sotaro Sadahiro and Chieko Murayama : Radiosensitization effect by combination with paclitaxel in vivo, including the effect on intratumor quiscent cells, International Journal of Radiation OncologyBiologyPhysics, Vol.50, No.4, 1063-1072, 2001. (Summary) To evaluate the radiosensitization effect on solid tumors upon combination treatment with paclitaxel (TXL), including the effect on intratumor quiescent (Q) cells. Mice bearing SCC VII or EL4 solid tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days to label all proliferating (P) cells. The mice then received gamma-irradiation with or without tirapazamine (TPZ) at various time points after TXL administration. Another group of mice received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors at various time points after TXL administration. Immediately after irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, the tumor cells were isolated from the solid tumors in another group of mice, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P + Q) tumor cells were determined from the tumors that were not pretreated with BrdU. For the measurement of the HFs, the MN or apoptosis frequency of Q cells was then used to calculate the surviving fraction of Q cells from the regression line for the relationship between the MN or apoptosis frequency and the surviving fraction of total tumor cells. In both SCC VII and EL4 tumors, maximum values of mitotic index (MI) and apoptosis frequency were observed 9 and 24 h after TXL administration, respectively. However, on the whole, the apoptosis frequency for SCC VII was very low. gamma-Irradiation 9 h after TXL administration induced significant radiosensitization effects on the total cells of both tumors. Irradiation at 60 h had a more significant effect on total cells of EL4 tumor, but no significant effect on total cells of SCC VII tumor. Combined treatment with TXL induced no radiosensitization effect on Q cells in either tumor. The effect on Q cells was observed only after TPZ was administered. The HF of total cells in EL4 tumors decreased significantly 60 h after TXL administration. No radiosensitization effect upon combination treatment with TXL is induced in Q tumor cells. However, the effect on P cells is produced by irradiation at the time when the maximum values of MI are induced following TXL administration. In addition, for tumors that are susceptible to apoptosis after TXL administration alone, irradiation at the time of sufficient reoxygenation in tumors after TXL administration produces a greater radioenhancement effect on P cells. (Keyword) Animals / Apoptosis / Bromodeoxyuridine / Carcinoma, Squamous Cell / Cell Survival / Humans / Mice / Mice, Inbred C3H / Micronucleus Tests / Neoplasms / Paclitaxel / Radiation Tolerance / Radiation-Sensitizing Agents / Radiobiology / Radiotherapy Dosage / Time Factors / Triazines (Link to Publication Site) ● Publication site (DOI): 10.1016/S0360-3016(01)01553-X (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11429234 ● Search Scopus @ Elsevier (PMID): 11429234 ● Search Scopus @ Elsevier (DOI): 10.1016/S0360-3016(01)01553-X (DOI: 10.1016/S0360-3016(01)01553-X, PubMed: 11429234)
133.	Soko Kasai, Hideko Nagasawa, Mao Yamashita, Mie Masui, Hideki Kuwasaka, Tomoko Oshodani, Yoshihiro Uto, Taisuke Inomata, Shigenori Oka, Seiichi Inayama and Hitoshi Hori : New Antimetastatic Hypoxic Cell Radiosensitizers: Design, Synthesis, and Biological Activities of 2-Nitroimidazole-acetamide, TX-1877, and its Analogues, Bioorganic & Medicinal Chemistry, Vol.9, No.2, 453-464, 2001. (Summary) We designed, based on the molecular orbital (MO) calculation, synthesized, and evaluated the biological activities of the new antimetastatic hypoxic cell radiosensitizer, 2-nitroimidazole-acetamide, TX-1877, and its analogues. Each analogue has an electron-affinic imidazole group, an acetamide group and a certain hydrophilic group to control its biological effect, toxicity, and pharmacokinetics. In in vitro radiosensitization assay, most TX-1877 analogues, which have an electron affinity (EA) of more than 0.9 eV and partition coefficient (P) of more than 0.021, showed satisfactory enhancement ratios (ER > 1.60) at doses of I mM. On the other hand, imidazole analogues, such as TX-1908 (EA = 0.67 eV), TX-1910 (EA = -0.34 eV) and TX-1931 (EA = -0.37 eV), which have low electron affinities, had an ER of 1.31 or less. TX-1877 and KIN-806 effectively inhibited tumor regrowth when administered with irradiation in vivo at a dose of 0.4 mg/g. Tumor lung metastasis was inhibited by treatment with either TX-1877 or KIN-806 without irradiation at a dose of 0.4 mg/g. TX-1877 reduced markedly the mean number of metastatic lung nodules in comparison with KIN-806. Moreover, TX-1877 and KIN-806 enhanced macrophage and helper T lymphocyte infiltration for 3 weeks after drug treatment. TX-1877 shows a high EA value and has the C2 of HOMO localizing on N-methylamide and the C2 of LUMO localizing on 2-nitroimidazole group. The MO data might be useful for designing a bifunctional hypoxic cell radiosensitizer. TX-1877 and its analogues are potential antimetastatic hypoxic cell radiosensitizers, which would improve the efficiency of radiotherapy and quality of life in cancer treatment. (Keyword) Animals / Anoxia / Antineoplastic Agents / Breast Neoplasms / Cell Movement / Drug Design / Electrochemistry / Female / Leukocytes, Mononuclear / Lung Neoplasms / Macrophages / Mice / Mice, Inbred C3H / Models, Molecular / Neoplasm Metastasis / Neoplasm Transplantation / Nitroimidazoles / Radiation-Sensitizing Agents / Structure-Activity Relationship / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1016/S0968-0896(00)00265-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11249137 ● Summary page in Scopus @ Elsevier: 2-s2.0-0035083176 (DOI: 10.1016/S0968-0896(00)00265-0, PubMed: 11249137, Elsevier: Scopus)
134.	Shin-ichiro Masunaga, Koji Ono, Hitoshi Hori, Minoru Suzuki, Yuko Kinashi, Masao Takagaki, Soko Kasai, Hideko Nagasawa and Yoshihiro Uto : Change in oxygenation status in intratumour total and quienscent cells following γ-ray irradiation,tirapazamine administration, cisplatin injection and bleomycin treatment, The British Journal of Radiology, Vol.73, No.873, 978-986, 2000. (Summary) C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received gamma-ray irradiation, or administration of tirapazamine (TPZ), cisplatin or bleomycin. At various time points after each treatment, tumour-bearing mice were irradiated with a series of test doses of gamma-rays, while alive or after being killed, to obtain hypoxic fractions (HFs) in the tumours. Immediately after gamma-ray test irradiation, the tumours were excised, minced and trypsinized. Tumour cell suspensions obtained were incubated with cytochalasin-B, a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labelling (i.e. quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. MN frequency in the total (P + Q) tumour cells was determined from the tumours that were not pre-treated with BrdU. MN frequency of BrdU-unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total tumour cells. TPZ and cisplatin reduced the HF after treatment, especially in Q cells, and this tendency was particularly marked with TPZ. In contrast, bleomycin increased the HF after treatment. Both reoxygenation following gamma-ray irradiation or bleomycin treatment and a subsequent return to pre-treatment levels of HF following TPZ or cisplatin treatment (rehypoxiation) occurred more rapidly in total (P + Q) cells than in Q cells. Based on our previous report that total (P + Q) and Q cells within this tumour have large acutely and chronically HFs, respectively, we conclude that acute hypoxic cells play a major role in reoxygenation and rehypoxiation in SCC VII tumours. (Keyword) Animals / Antibiotics, Antineoplastic / Antineoplastic Agents / Bleomycin / Bromodeoxyuridine / Carcinoma, Squamous Cell / Cell Hypoxia / Cisplatin / Cytochalasin B / Injections / Mice / Micronucleus Tests / Triazines / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1259/bjr.73.873.11064652 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11064652 ● Summary page in Scopus @ Elsevier: 2-s2.0-0033819629 (DOI: 10.1259/bjr.73.873.11064652, PubMed: 11064652, Elsevier: Scopus)
135.	Shin-ichiro Masunaga, Koji Ono, Minoru Suzuki, Yuko Kinashi, Masao Takagaki, Soko Kasai, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Changes in the Sensitivity of Intratumor Cells during Fractionated Tirapazamine Administration, Japanese Journal of Cancer Research, Vol.91, No.7, 731-736, 2000. (Summary) Mice bearing solid tumors received 10 intraperitoneal administrations of 5-bromo-2'-deoxyuridine (BrdU) to label the proliferating (P) tumor cells. Then, as a priming treatment, tirapazamine (TPZ) was intraperitoneally administered. Further, 0 through 48 h later, the tumor-bearing mice received TPZ again at various doses. The tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequencies in cells with and without BrdU labeling, which were regarded as P and quiescent (Q) cells at the priming treatment, respectively, were determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. In addition, P cell ratios in the tumors at the second treatment were determined using immunofluorescence staining for P cell nuclear antigen. In each cell fraction, the longer the interval between the two treatments, the higher was the sensitivity to TPZ, except 1 h after the priming treatment. More than 24 h later, total and P cells, especially P cells, showed significantly higher sensitivity to TPZ than in the case of a single TPZ treatment. The longer the period between the two TPZ treatments, the lower was the P cell ratio at the second treatment. These findings were thought to indicate that the use of TPZ in the treatment of solid tumors causes a shift from the P to the Q state in vivo. (Keyword) Animals / Antineoplastic Agents / Carcinoma, Squamous Cell / Cell Cycle / Cell Division / Dose-Response Relationship, Drug / Drug Administration Schedule / Female / Injections, Intraperitoneal / Mice / Mice, Inbred C3H / Micronuclei, Chromosome-Defective / Neoplasm Transplantation / Triazines / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1349-7006.2000.tb01006.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10920281 ● Summary page in Scopus @ Elsevier: 2-s2.0-0033860907 (DOI: 10.1111/j.1349-7006.2000.tb01006.x, PubMed: 10920281, Elsevier: Scopus)
136.	Shigeori Takenana, Kenichi Yamashita, Makoto Takagi, Yoshihiro Uto and Hiroki Kondo : DNA Sensing on a DNA Probe-Modified Electrode Using Ferrocenylnaphthalene Diimide as the Electrochemically Active Ligand, Analytical Chemistry, Vol.72, No.6, 1334-1341, 2000. (Summary) Naphthalene diimide derivative 1 carrying ferrocenyl moieties at the termini of imide substituents binds intact calf thymus DNA 4 times more strongly than the denatured DNA, and its complex with the intact DNA dissociates 80 times more slowly than that with the denatured DNA. On the basis of these observations, ligand 1 was applied to a probe of electrochemical DNA sensing. A thiol-linked single-stranded DNA probe was immobilized through the S-Au bonding to 20-30 pmol/mm2 on a gold electrode. Following hybridization with the complementary DNA, the electrode was soaked in a solution containing 1 (intercalation step) and then washed with buffer for 5 s. The cyclic voltammogram and differential pulse voltammogram for this electrode gave an electrochemical signal due to the redox reaction of 1 that was bound to the double-stranded DNA on the electrode. Thus, dA20 and the yeast choline transport gene were quantitated at the subpicomole level. The sensitivity of DNA detection was improved to 10 zmol by reducing the amount of immobilized DNA probe and protecting the uncovered surface of the electrode with 2-mercaptoethanol. (Keyword) Base Sequence / DNA / DNA Probes / Electrochemistry / Electrodes / Ferrous Compounds / Imides / Kinetics / Ligands / Magnetic Resonance Spectroscopy (Link to Publication Site) ● Publication site (DOI): 10.1021/ac991031j (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10740879 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034654434 (DOI: 10.1021/ac991031j, PubMed: 10740879, Elsevier: Scopus)
137.	Shin-ichiro Masunaga, Koji Ono, Minoru Suzuki, Yuko Kinashi, Masao Takagaki, Hitoshi Hori, Soko Kasai, Hideko Nagasawa and Yoshihiro Uto : Usefulness of Tirapazamine as a Combined Agent in Chemoradiation and Thermo-chemoradiation Therapy at Mild Temperatures: Reference to the Effect on Intratumor Quiescent Cells, Japanese Journal of Cancer Research, Vol.91, No.5, 566-572, 2000. (Summary) C3H / He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received one of six different DNA-damaging agents with or without mild temperature hyperthermia (40 degrees C, 30 min, MTH). These agents were adriamycin (ADM), mitomycin C (MMC), cyclophosphamide (CPA), bleomycin (BLM), cisplatin (CDDP), and tirapazamine (TPZ). After the drug treatment, the tumor-bearing mice were irradiated with a series of doses of gamma-rays. Immediately after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that had not been pretreated with BrdU. MTH significantly increased the MN frequency of total cells in tumors irradiated with gamma-rays combined with CPA, BLM, CDDP or TPZ, and that of Q cells in tumors irradiated with gamma-rays combined with BLM or TPZ. The sensitivity difference in the MN frequency between total and Q tumor cells was significantly decreased by the combination with TPZ. TPZ combined with radiotherapy and TPZ combined with thermo-radiotherapy at mild temperatures appear to be promising modalities for sensitizing tumor cells in vivo, including Q tumor cells. (Keyword) Animals / Antineoplastic Combined Chemotherapy Protocols / Bleomycin / Bromodeoxyuridine / Carcinoma, Squamous Cell / Cisplatin / Combined Modality Therapy / Cyclophosphamide / Dose-Response Relationship, Radiation / Doxorubicin / Hyperthermia, Induced / Mice / Mice, Inbred C3H / Micronucleus Tests / Mitomycin / Radiation-Sensitizing Agents / Triazines (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10835503 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034081410 (PubMed: 10835503, Elsevier: Scopus)
138.	Medhat Abu-Zeid, Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto and Seiichi Inayama : Studies of Methyl 2-Nitroimidazole-1-acetohydroxamate (KIN-804)1: Effect on Free Radical Scavenging System in Mice Bearing Ehrlich Ascites Carcinoma, Biological & Pharmaceutical Bulletin, Vol.23, No.2, 190-194, 2000. (Summary) Methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) is a 2-nitroimidazole derivative containing a hydroxamate side chain designed to enhance the radiosensitization response of hypoxic cells. The possible sensitization of tumor tissue by KIN-804 can be evaluated through investigation of the levels of the free radical scavengers; namely, glutathione (GSH) and its complex enzyme system including glutathione reductase (GR) and glutathione peroxidase (GSH-Px), as well as glucose-6-phosphate dehydrogenase (G-6-PD). Female albino mice were inoculated with Ehrlich carcinoma in the thigh. Administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. The data revealed that KIN-804 administration, followed or not by gamma irradiation, resulted in a significant decrease in GSH content in tumor tissues associated with inhibition in GR and G-6-PD activities. Blood GSH-Px was enhanced in tumor inoculated mice and the administration of KIN-804 returned it to the normal value. These changes were more noticeable in tumor bearing mice exposed to both KIN-804 and irradiation. (Keyword) Animals / Carcinoma, Ehrlich Tumor / Female / Free Radical Scavengers / Glucosephosphate Dehydrogenase / Glutathione / Glutathione Peroxidase / Glutathione Reductase / Hydroxamic Acids / Mice / Nitroimidazoles / Oxidation-Reduction / Radiation-Sensitizing Agents (Link to Publication Site) ● Publication site (DOI): 10.1248/bpb.23.190 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10706382 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034094594 (DOI: 10.1248/bpb.23.190, PubMed: 10706382, Elsevier: Scopus)
139.	Medhat Abu-Zeid, Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto and Seiichi Inayama : Studies of Methyl 2-Nitroimidazole-1-acetohydroxamate (KIN-804)2: Effect on Certain Antioxidant Enzyme Systems in Mice Bearing Ehrlich Ascites Carcinoma, Biological & Pharmaceutical Bulletin, Vol.23, No.2, 195-198, 2000. (Summary) In order to decrease toxicity and/or increase radiosensitizing activity, a new 2-nitroimidazole derivative, methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804), was synthesized to solve the problem of tumor hypoxia. Evaluation of the efficiency of KIN-804 was carried out through studying the antioxidant enzyme system: The superoxide dismutase (SOD), catalase and lipid peroxide levels provide a rough index of the balance between free radical generation and scavenging. Female albino mice were inoculated with Ehrlich ascites carcinoma (EAC) in the thigh. The administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. In general, the data revealed that KIN-804 administration, followed or not by gamma irradiation, exerted significant inhibition of SOD and catalase activities accompanied by a significant increase in lipid peroxide level in tumor-bearing mice. (Keyword) Animals / Anoxia / Antioxidants / Carcinoma, Ehrlich Tumor / Catalase / Female / Hydroxamic Acids / Lipid Peroxides / Liver / Lung / Mice / Nitroimidazoles / Radiation-Sensitizing Agents / Superoxide Dismutase (Link to Publication Site) ● Publication site (DOI): 10.1248/bpb.23.195 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10706383 ● Summary page in Scopus @ Elsevier: 2-s2.0-0034062025 (DOI: 10.1248/bpb.23.195, PubMed: 10706383, Elsevier: Scopus)
140.	Ji-Wen Zhu, Hideko Nagasawa, Fumi Nagura, Saharuddin B. Mohamad, Yoshihiro Uto, Kazuto Ohkura and Hitoshi Hori : Elucidation of Strict Structural Requirements of Brefeldin A as an Inducer of Differentiation and Apoptosis, Bioorganic & Medicinal Chemistry, Vol.8, No.2, 455-463, 2000. (Summary) Brefeldin A (BFA) can induce a wide variety of human cancer cells to differentiation and apoptosis and is in development as an anticancer agent. To elucidate structural requirements for cytotoxicity and induction of differentiation and apoptosis, BFA was structurally modified into various derivatives including 4-epi-BFA in this study. Their inducing activities of apoptosis were evaluated with their cytotoxicities, DNA fragmentation and morphological changes in human colon cancer cell HCT 116. The cytotoxicity of 4-epi-BFA (TX-1923) (IC50 = 60 microM) was 300 times lower than that of BFA (IC50 = 0.2 microM). Furthermore, 4-epi-BFA induced DNA fragmentation and apoptotic morphological changes at much higher concentrations (70 and 50 microM, respectively) than BFA (0.11 and 0.36 microM, respectively). These results indicated that the configuration of 4-hydroxyl group of brefeldin A plays a key role in the cytotoxicity and induction of apoptosis. On the other hand, 7-O-acetyl-BFA, 4-O-acetyl-BFA, and 4,7-di-O-acetyl-BFA exhibited potential activities in cytotoxicity and inducibility of apoptosis. We suggested that the structural determinants for BFA include the moiety of the Michael acceptor, the conformational rigidity of the 13-membered ring, and the configuration of 4-hydroxyl group. (Keyword) Apoptosis / Brefeldin A / Cell Differentiation / Cell Line / Magnetic Resonance Spectroscopy / Mass Spectrometry / Structure-Activity Relationship / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1016/S0968-0896(99)00297-7 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10722169 ● Summary page in Scopus @ Elsevier: 2-s2.0-0033998897 (DOI: 10.1016/S0968-0896(99)00297-7, PubMed: 10722169, Elsevier: Scopus)
141.	Shin-ichiro Masunaga, Koji Ono, Hitoshi Hori, Minoru Suzuki, Yuko Kinashi, Masao Takagaki, Soko Kasai, Hideko Nagasawa and Yoshihiro Uto : Potentially Lethal Damage Repair by Total and Quiescent Tumor Cells Following Various DNA-damaging Treatments, Radiation Medicine, Vol.17, No.4, 259-264, 1999. (Summary) 本論文では，マウス移殖腫瘍モデルにおいて，全腫瘍細胞とQ細胞に対する放射線，TPZ投与，シスプラチン投与などのDNA障害性処理による潜在的致死損傷の回復(PLDR)に関する解析を行った．Q細胞では全細胞に比べて，いずれの処理においても強い回復能を示した．ただし，TPZ処理の場合には，他の処理に比べて両者の細胞ともに回復能の低下が見られた． (Keyword) Animals / Antineoplastic Agents / Carcinoma, Squamous Cell / cell division / Cell Survival / Cisplatin / DNA Damage / DNA Repair / DNA, Neoplasm / Female / Fluorescent Antibody Technique / Gamma Rays / Lethal Dose 50 / Mice / Mice, Inbred C3H / Micronuclei, Chromosome-Defective / Neoplasm Transplantation / Neoplasms, Experimental / Radiotherapy, Adjuvant / Triazines / Tumor Cells, Cultured (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10510897 ● Search Scopus @ Elsevier (PMID): 10510897 (PubMed: 10510897)
142.	Shin-ichiro Masunaga, Koji Ono, Hitoshi Hori, Yuko Kinashi, Minoru Takagaki, Minoru Suzuki, Soko Kasai, Hideko Nagasawa and Yoshihiro Uto : Modification of tirapazamine-induced cytotoxycity in combination with mild hyperthermia and/or nicotinamide: reference to effect on quiescent tumour cells, Int. J. Hyperthermia, Vol.15, No.1, 7-16, 1999. (Summary) 本論文では，マウス移殖腫瘍モデルにおいて，TPZのQ細胞および低酸素細胞に対する細胞毒性が．マイルドハイパーサーミアまたはmicotinamideを併用することにより，増感されることを明らかにした．
143.	Hitoshi Hori, Masaki Ishibashi, Saharuddin B. Mohamad, Hideko Nagasawa, Yoshihiro Uto, Hiroyuki Sakamaki, Ning Pan, Kazuto Ohkura and Sansei Nishibe : Enhancement Effect of Methyl α-D-Glucoside for Inhibitory Effects of Antioxidants on ADP/Fe²⁺-Induced Lipid Peroxidation in Rat Liver Mitochondria, Advances in Experimental Medicine and Biology, Vol.471, 395-401, 1999. (Summary) 本論文では，ラット肝ミトコンドリアにおいて，ADP/Fe2+で誘導される膜脂質過酸化に対する，種々の抗酸化剤の効果をmethyl -D-glucosideが増強することを示した．本論文では，ラット肝ミトコンドリアにおいて，ADP/Fe2+で誘導される膜脂質過酸化に対する，種々の抗酸化剤の効果をmethyl -D-glucosideが増強することを示した．
144.	Shin-ichiro Masunaga, Koji Ono, Hitoshi Hori, Ken-ichi Akaboshi, Minoru Suzuki, Yuko Kinashi, Soko Kasai, Hideko Nagasawa and Yoshihiro Uto : Enhancement of Cisplatin Sensitivity of Quiescent Cells in Solid Tumors by Combined Treatment with Tirapazamine and Low-Temperature Hyperthermia, Radiation Medicine, Vol.16, No.6, 441-448, 1998. (Summary) 本論文では，マウス移殖腫瘍モデルにおいて，tirapazamine(TPZ)とマイルドハイパーサーミアの併用により，固形腫瘍に存在すると考えられる休止期の細胞(Q細胞)のシスプラチンに対する化学療法感受性が増感することを明らかにした． (Keyword) Animals / Antineoplastic Agents / Bromodeoxyuridine / Carcinoma, Squamous Cell / Cell Count / Cisplatin / Dose-Response Relationship, Drug / Drug Hypersensitivity / Drug Therapy, Combination / Female / Hyperthermia, Induced / Infusion Pumps, Implantable / Injections, Intralesional / Isotopes / Mice / Mice, Inbred BALB C / Mice, Inbred C3H / Platinum / Sarcoma, Experimental / Treatment Outcome / Tumor Cells, Cultured (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9929144 ● CiNii @ National Institute of Informatics (CRID): 1572543024206097024 ● Summary page in Scopus @ Elsevier: 2-s2.0-0032446512 (PubMed: 9929144, CiNii: 1572543024206097024, Elsevier: Scopus)
145.	Shigeori Takenana, Makoto Takagi, Yoshihiro Uto and Hiroki Kondo : Construction of a Polyferrocene array with ferrocenyl naphthalene diimide intercalated to the double stranded DNA, Nucleic Acids Symposium Series, No.39, 107-108, 1998.
146.	Shigeori Takenana, Kenichi Yamashita, Yoshihiro Uto, Makoto Takagi and Hiroki Kondo : Electrochemistry of Ferrocenyl Naphthalene Diimide Derivative and Its Behavior on Hairpin DNA Immobilized Electrode, DENKI KAGAKU, Vol.66, No.12, 1329-1334, 1998.
147.	Yoshihiro Uto, Hiroki Kondo, Masako Abe, Tomokazu Suzuki and Shigeori Takenana : Quantitative Analysis of the Muscular Dystrophin Gene Using a Polymerase Chain Reaction and High-Performance Liquid Chromatography with Electrochemical Detection, Analytical Sciences, Vol.13, 209-212, 1997. (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-19044375490 (Elsevier: Scopus)

Academic Paper (Unrefereed Paper):

1.	Masamitsu Ichihashi, Yoshitaka Nakamura, Masahiko Muto, Takahito Nishikata, Tosio Inui and Yoshihiro Uto : A case of chronic actinic dermatitis that responded completely to treatment with oral colostrummacrophageactivating factor (colostrumMAF), Photodermatology, Photoimmunology & Photomedicine, Vol.35, No.4, 290-292, 2019. (Tokushima University Institutional Repository) ● Metadata: 115686 (Link to Publication Site) ● Publication site (DOI): 10.1111/phpp.12469 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30951213 ● Summary page in Scopus @ Elsevier: 2-s2.0-85065179901 (Tokushima University Institutional Repository: 115686, DOI: 10.1111/phpp.12469, PubMed: 30951213, Elsevier: Scopus)
2.	田中涼, Yoshihiro Uto, 山下洋平, 大仲健太, Eiji Nakata and Hitoshi Hori : システムバイオロジー構築のためのフィチルキノールの合成と抗酸化活性評価, ビタミンE研究の進歩XIV, Vol.14, 81-86, 2010. (Keyword) Systems biology / Phytyl quinol / Antioxidant / Vitamin E
3.	中西郁夫, Yoshihiro Uto, 大久保敬, 白井斉, Eiji Nakata, Hideko Nagasawa, Hitoshi Hori, 福原潔, 奥田晴宏, 伊古田暢夫, 福住俊一, 小澤俊彦 and 安西和紀 : ビタミンEの生合成前駆体およびその非環状類縁体のラジカル消去速度, ビタミンE研究の進歩Ⅷ, 83-87, 2009.
4.	Yoshihiro Uto, 小山大輔, 大友直紀, 安部千秋, 白井斉, Eiji Nakata and Hitoshi Hori : イソプレン側鎖を有する植物成分のex vivo 有機合成とその生理活性の評価, Bulletin of Institute of Technology and Science, The University of Tokushima, No.53, 52-56, 2008. (Summary) Phytyl quinols, namely acyclic tocopherols, are key intermediates of tocopherol biosynthesis,but their biological activities remain unclear. We therefore investigated the structure-activityrelationship of phytyl quinols to apply a chemical biosynthesis design for an antiatherosclerosisdrug based on isoprenomics. We have achieved the biosynthesis-oriented synthesis of α- andβ-phytyl quinol as an unnatural intermediate, other γ- and δ-phytyl quinol as a natural one. All fourphytyl quinols showed almost the same moderate inhibitory activity against low-density lipoproteinoxidation instead of their different degree of C-methylation with character different fromtocopherols. In vivo toxicities of phytyl quinols against chick embryo chorioallantoic membranevasculature were hardly observed. We proposed phytyl quinols were possible antioxidants in plantsand animals, like vitamin E. (Tokushima University Institutional Repository) ● Metadata: 59702 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050282812440398720 (Tokushima University Institutional Repository: 59702, CiNii: 1050282812440398720)
5.	Yoshiko Matsuda, Hitoshi Hori, Akihiko Tsuji, Hideko Nagasawa, Yoshihiro Uto, Rieko Kuroda, 葛西宗江, Miwa Bando, 吉田一郎, 上田祐司 and サハルディン B. モハマッド : 新医薬品の開発をめざした脳神経特異的発現遺伝子産物のプロテオミクス解析, Bulletin of Faculty of Engineering, The University of Tokushima, Vol.46, 49-56, 2001. (Summary) 本論文では，新薬開発における新規標的分子の同定のための脳神経特異的遺伝子産物のプロテオミクス解析に関する成果を報告した．

Academic Letter:

1.	Tomohiro Osaki, Isao Sakata, Yoshihiro Uto, Masamichi Yamashita, Yusuke Murahata, Kazuo Azuma, Takeshi Tsuka, Norihiko Ito, Tomohiro Imagawa and Yoshiharu Okamoto : Effects of TONS504-photodynamic therapy on mouse mammary tumor cells, Oncology Letters, Vol.16, No.2, 2078-2084, 2018. (Summary) In the present study, TONS504 (CHNOI; molecular weight, 1,116.9), a novel cationic hydrophilic photosensitizer, was synthesized from protoporphyrin IX dimethyl ester through a five-step process according to a patented method for use in photodynamic therapy (PDT). The subcellular localization of TONS504 and the cytotoxic effects of TONS504-mediated PDT in the mouse mammary tumor EMT6 cell line were investigated. TONS504 was localized primarily in the lysosomes and partially in the mitochondria. The cytotoxic effects of TONS504-mediated PDT in the mouse mammary tumor EMT6 cell line were investigated using a WST8 assay and an Oxidative Stress kit. The cell viability values following treatment with 10 µg/ml TONS504 at light energies of 0, 1, 5 and 10 J/cm were 92.5, 101.8, 27.7 and 1.8%, respectively. The percentages of reactive oxygen species (ROS)(+) cells following the same treatment were 8.6, 8.5, 29.2 and 70.1%, respectively, whereas the percentages of apoptotic cells were 7.1, 5.6, 24.8 and 48.7%, respectively. The percentages of ROS(+) and apoptotic cells in the group subjected to TONS504-mediated PDT increased in a manner dependent on the TONS504 concentration and light energy. Further studies are required to evaluate the pharmacokinetics, tissue distribution and photodynamic effects of TONS504. (Keyword) TONS504 / apoptosis / mammary tumor / photodynamic therapy / reactive oxygen species (Tokushima University Institutional Repository) ● Metadata: 115667 (Link to Publication Site) ● Publication site (DOI): 10.3892/ol.2018.8887 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30008903 ● Search Scopus @ Elsevier (PMID): 30008903 ● Search Scopus @ Elsevier (DOI): 10.3892/ol.2018.8887 (Tokushima University Institutional Repository: 115667, DOI: 10.3892/ol.2018.8887, PubMed: 30008903)
2.	Hideaki Takahashi, Quan Binh Cao Nguyen, Yoshihiro Uto, Md Shahinozzaman, Shinkichi Tawata and Hiroshi Maruta : 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability., Drug Discoveries & Therapeutics, Vol.11, No.2, 104-109, 2017. (Summary) Artepillin C (ARC) and caffeic acid (CA) are among the major anti-cancer ingredients of propolis, and block the oncogenic/melanogenic/ageing kinase PAK1. However, mainly due to their COOH moiety, cell-permeability of these herbal compounds is rather limited. Thus, in this study, in an attempt to increase their cell-permeability without any significant loss of their water-solubility, we have esterized both ARC and CA with the water-soluble 1,2,3-triazolyl alcohol through Click Chemistry. We found that this esterization boosts the anti-cancer activity of ARC and CA by 100 and over 400 folds, respectively, against the PAK-dependent growth of A549 lung cells, but show no effect on the PAK1-independent growth of B16F10 melanoma cells. Confirming this "selective" toxicity, these esters are still capable of blocking the kinase PAK1 strongly in cell culture (with IC around 5 µM), and the anti-PAK1 activity of 15A (ARC ester) and 15C (CA ester) appears to be 30-fold and 140-fold higher than ARC and CA, respectively. The 15A and 15C are 8-fold and 70-fold more cell-permeable (through the multi-drug resistant cell line EMT6) than ARC and CA, respectively. These data altogether suggest that both 15A and 15C would be far more useful than propolis for the treatment of a wide variety of PAK1-dependent diseases/disorders such as cancers, Alzheimer's diseases (AD), hypertension, diabetes (type 2), and hyper-pigmentation. (Keyword) PAK1 / artepillin C / caffeic acid / click chemistry / triazolyl esters (Link to Publication Site) ● Publication site (DOI): 10.5582/ddt.2017.01009 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28442677 ● Search Scopus @ Elsevier (PMID): 28442677 ● Search Scopus @ Elsevier (DOI): 10.5582/ddt.2017.01009 (DOI: 10.5582/ddt.2017.01009, PubMed: 28442677)
3.	Naoyuki Shimomura, Masataka Nagahama, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : Introduction of Embryonic Chick Assay on Experiment Applying Nanosecond Pulse Electric Fields on Solid Tumor, IEEJ Transactions on Fundamentals and Materials, Vol.133, No.4, 231-232, 2013. (Summary) Embryonic chick assay was introduced as a biological method for an experiment to apply a nanosecond pulse electric field on a tumor. Embryonic chick assay allowed many in vivo tests. Pulsed electric fields were applied on a solid tumor of the mouse breast adenocarcinoma cell, EMT6/KU, which was formed on the chorioallantoic membrane. We found that average weight of solid tumors applied pulsed electric fields was significantly smaller than that of controls. (Keyword) embryonic chick assay / in vivo / bioelectrics / nanosecond pulse electric fields / solid tumor (Link to Publication Site) ● Publication site (DOI): 10.1541/ieejfms.133.231 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390282679577350016 ● Summary page in Scopus @ Elsevier: 2-s2.0-84877149408 (DOI: 10.1541/ieejfms.133.231, CiNii: 1390282679577350016, Elsevier: Scopus)
4.	Eiji Nakata, Yoshijiro Nazumi, Yoshihiro Yukimachi, Yoshihiro Uto, Hiroshi Maezawa, Toshihiro Hashimoto, Yasuko Okamoto and Hitoshi Hori : Synthesis and photophysical properties of new SNARF derivatives as dual emission pH sensors, Bioorganic & Medicinal Chemistry Letters, Vol.21, No.6, 1663-1666, 2011. (Summary) We report the synthesis and properties of two new seminaphthorhodafluor (SNARF) derivatives, SNARF-F and SNARF-Cl. Both these derivatives exhibit typical red shifts of absorption and fluorescence, and higher cell permeability as compared to traditional SNARF, while the pH-dependent dual-emission characteristics are well retained. In particular, the lower pK(a) (7.38) of SNARF-F makes it more suitable than traditional SNARF derivatives for intracellular applications. (Keyword) Benzopyrans / Fluorescent Dyes / Hydrogen-Ion Concentration / Photochemistry / Spectrometry, Fluorescence (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmcl.2011.01.105 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21324690 ● Search Scopus @ Elsevier (PMID): 21324690 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmcl.2011.01.105 (DOI: 10.1016/j.bmcl.2011.01.105, PubMed: 21324690)
5.	Manda Sushma, Nakanishi Ikuo, Ohkubo Kei, Yoshihiro Uto, Kawashima Tomonori, Hitoshi Hori, Fukuhara Kiyoshi, Okuda Haruhiro, Ozawa Toshihiko, Ikota Nobuo, Fukuzumi Shunichi and Anzai Kazunori : Enhanced radical-scavenging activity of naturally-oriented artepillin C derivatives, Chemical Communications, No.5, 626-628, 2008. (Summary) More than two-fold augmentation in the radical-scavenging activity of artepillin C could be achieved via altering the O H bond dissociation enthalpy of artepillin C by means of structural modifications. (Keyword) Benzene Derivatives / Free Radical Scavengers / Molecular Structure / Peroxides / Phenylpropionates / Photochemistry / Stereoisomerism / Thermodynamics / Time Factors (Link to Publication Site) ● Publication site (DOI): 10.1039/b715973k (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18209811 ● Summary page in Scopus @ Elsevier: 2-s2.0-38349124227 (DOI: 10.1039/b715973k, PubMed: 18209811, Elsevier: Scopus)
6.	Mok-Ryeon Ahn, Kazuhiro Kunimasa, Toshiro Ohta, Shigenori Kumazawa, Miya Kamihira, Kazuhiko Kaji, Yoshihiro Uto, Hitoshi Hori, Hideko Nagasawa and Tsutomu Nakayama : Suppression of tumor-induced angiogenesis by Brazilian propolis: Major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation, Cancer Letters, Vol.252, No.2, 235-243, 2007. (Summary) Propolis, a resinous substance collected by honeybees from various plant sources, possesses various physiological activities such as antitumor effects. We have previously shown that propolis of Brazilian origin was composed mainly of artepillin C and that its constituents were quite different from those of propolis of European origin. In this report, we examined an antiangiogenic effects of Brazilian propolis and investigated whether artepillin C was responsible for such effects. In an in vivo angiogenesis assay using ICR mice, we found that the ethanol extract of Brazilian propolis (EEBP) significantly reduced the number of newly formed vessels. EEBP also showed antiangiogenic effects in an in vitro tube formation assay. When compared with other constituents of EEBP, only artepillin C was found to significantly inhibit the tube formation of HUVECs in a concentration-dependent manner (3.13-50microg/ml). In addition, artepillin C significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-50microg/ml). Furthermore, artepillin C significantly reduced the number of newly formed vessels in an in vivo angiogenesis assay. Judging from its antiangiogenic activity in vitro and in vivo, we concluded that artepillin C at least in part is responsible for the antiangiogenic activity of EEBP in vivo. Artepillin C may prove useful in the development of agents and foods with therapeutic or preventive activity against tumor angiogenesis. (Keyword) Animals / Brazil / Cell Proliferation / Cells, Cultured / Endothelium, Vascular / Humans / Mice / Neoplasms / Neovascularization, Pathologic / Phenylpropionates / Propolis (Link to Publication Site) ● Publication site (DOI): 10.1016/j.canlet.2006.12.039 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17343983 ● Search Scopus @ Elsevier (PMID): 17343983 ● Search Scopus @ Elsevier (DOI): 10.1016/j.canlet.2006.12.039 (DOI: 10.1016/j.canlet.2006.12.039, PubMed: 17343983)
7.	Shigeori Takenana, Yoshihiro Uto, Makoto Takagi and Hiroki Kondo : Enhanced Electron Transfer from Glucose Oxidase to DNA-Immobilized Electrode Aided by Ferrocenyl Naphthalene Diimide, a Threading Intercalator, Chemistry Letters, 989-990, 1998.
8.	Shigeori Takenana, Yoshihiro Uto, Hideki Saita, Makoto Yokoyama, Hiroki Kondo and David W. Wilson : Electrochemically active threading intercalator with high double stranded DNA selectivity, Chemical Communications, Vol.10, 1111-1112, 1998.

Review, Commentary:

1.	Hirofumi Honda, Masahide Tominaga, Motoharu Sasaki, Masataka Oita and Yoshihiro Uto : 放射線治療における透過型検出器の現状と展望, Radiation Biology Research Communications, Vol.56, No.3, 245-259, Sep. 2021. (Keyword) 透過型検出器 / 生体内線量測定 / 強度変調回転放射線治療 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520853835303095424 (CiNii: 1520853835303095424)
2.	大崎智弘 and Yoshihiro Uto : 低侵襲的がん治療法としての5-アミノレブリン酸を用いた超音波力学療法, Optical Alliance, Vol.32, No.1, 12-17, Jan. 2021. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1522262180921833472 (CiNii: 1522262180921833472)
3.	本田弘文, Masataka Oita, Masahide Tominaga and Yoshihiro Uto : 放射線治療における In Vivo Dosimetryの発展と応用, Radiation Biology Research Communications, Vol.51, No.3, 255-267, Sep. 2016.
4.	原毅弘, Masahide Tominaga, Masataka Oita, 本田弘文 and Yoshihiro Uto : Flattening Filter Free(高線量率)モードを用いた放射線治療の効果, Radiation Biology Research Communications, Vol.51, No.3, 230-240, Sep. 2016.
5.	芝一休, Hisatsugu Yamada, Masahide Tominaga and Yoshihiro Uto : 低酸素を標的とした抗転移剤による化学放射線療法の可能性, Radiation Biology Research Communications, Vol.51, No.3, 216-229, Sep. 2016.
6.	Yoshihiro Uto and Hitoshi Hori : 放射線療法と免疫反応/療法を組み合わせた統合的がん治療の基礎と臨床:マクロファージ活性化因子GcMAFの利用可能性, Radiation Biology Research Communications, Vol.48, No.2, 199-210, Jun. 2013. (Keyword) 放射線療法 / cancer immunotherapy / マクロファージ活性化因子GcMAF
7.	Hitoshi Hori, Yoshihiro Uto and Eiji Nakata : Boron tracedrugs challenge for neutron dynamic therapy, Anticancer Research, Vol.32, No.6, 2235-2239, Jun. 2012. (Summary) In this short review we describe our innovative boron tracedrugs and drugs for neutron dynamic therapy (NDT), as a newly emerging challenge beyond conventional drug treatments. (Keyword) Animals / Antineoplastic Agents / Boron Compounds / Boron Neutron Capture Therapy / Drug Design / Humans / Neoplasms (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22641657 ● Search Scopus @ Elsevier (PMID): 22641657 (PubMed: 22641657)
8.	Yoshihiro Uto, Hitoshi Hori, Kentaro Kubo, Masamitsu Ichihashi, Norihiro Sakamoto, Martin Mette and Toshio Inui : GcMAF: our next-generation immunotherapy, Nature Outlook, Vol.485, No.7400, May 2012.
9.	Eiji Nakata, 森井孝, Yoshihiro Uto and Hitoshi Hori : がんの特異的な検出を目指した蛍光イメージング法の最近の展開, Radiation Biology Research Communications, Vol.46, No.3, 234-246, Sep. 2011. (Keyword) がんの蛍光イメージング / 蛍光プローブ / 分子標的イメージング / 代謝活性イメージング / がん低酸素環境 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520853834327504256 (CiNii: 1520853834327504256)
10.	安部千秋, Yoshihiro Uto, 遠藤良夫 and Hitoshi Hori : 発育鶏卵を利用した創薬研究と将来展望, Radiation Biology Research Communications, Vol.46, No.3, 221-233, Sep. 2011. (Keyword) 発育鶏卵 / 放射線増感活性 / 抗酸化活性 / 血管新生阻害活性 / 抗腫瘍活性 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520009409051788416 (CiNii: 1520009409051788416)
11.	Hitoshi Hori, Yoshihiro Uto and Eiji Nakata : Medicinal bricolage design of hypoxia-targeting drugs and invention of boron tracedrugs as next-generation universal drugs, Shikoku Acta Medica, Vol.67, No.1,2, 7-14, Apr. 2011. (Keyword) hypoxia-targeting antitumor drug / hypoxic cell radiosensitizer / hypoxic cytotoxin / boron tracedrug / neutron dynamic therapy (Tokushima University Institutional Repository) ● Metadata: 110345 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050845762395234944 (Tokushima University Institutional Repository: 110345, CiNii: 1050845762395234944)
12.	Hitoshi Hori, Yoshihiro Uto and Eiji Nakata : Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs, Anticancer Research, Vol.30, No.9, 3233-3242, Sep. 2010. (Summary) We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas. (Keyword) Animals / Antineoplastic Agents / Boron Compounds / Cell Hypoxia / Drug Design / Electrons / Humans / Neoplasms / Radiation-Sensitizing Agents (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20944092 ● Search Scopus @ Elsevier (PMID): 20944092 (PubMed: 20944092)
13.	安部千秋, Yoshihiro Uto, 遠藤良夫, 新元優也, 中島宏一郎, 佐野圭一郎, 佐々木有紀, 皆巳和賢, Hiroshi Maezawa, 慎一郎増永, Eiji Nakata and Hitoshi Hori : 次世代動物実験系としての腫瘍移植鶏卵の構築と放射線照射による腫瘍成長阻害活性, Radiation Biology Research Communications, Vol.44, No.2, 233-241, Jun. 2009. (Keyword) 腫瘍移植鶏卵 / 放射線増感剤 / 低酸素がん細胞 / ハイスループットスクリーニング / in ovo試験 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520009408165390592 (CiNii: 1520009408165390592)
14.	Yoshihiro Uto, 中江崇, Hideko Nagasawa, Eiji Nakata and Hitoshi Hori : 解糖系代謝のエネルギー源となる単糖に対するがん細胞特異性:糖ハイブリッド低酸素細胞放射線増感剤/制癌剤の分子設計-Pharmacokinetic drug designのすすめ-, Radiation Biology Research Communications, Vol.43, No.1, 68-79, Mar. 2008. (Keyword) がんの単糖特異性 / 糖ハイブリッド分子設計 / 低酸素細胞放射線増感剤 / ワールブルグ効果
15.	Hideko Nagasawa, Yoshihiro Uto, Kenneth L. Kirk and Hitoshi Hori : Design of Hypoxia-Targeting Drugs as New Cancer Chemotherapeutics, Biological & Pharmaceutical Bulletin, Vol.29, No.12, 2335-2342, Dec. 2006. (Summary) The tumor microenvironment is now recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also helps define the potential for malignant progression and metastasis. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment. Furthermore, discovery of the hypoxia inducible factor 1alpha (HIF-1alpha) has led to a rapidly increasing understanding of the molecular mechanisms involved in tumor hypoxia. This in turn has led to the current extensive interest in the signal molecules related to tumor hypoxia as potential molecular targets for cancer therapeutics. In this paper we give an overview of recent advances in hypoxia research, including cancer treatments that target tumor hypoxia. Progress in the development of hypoxia-targeting drugs will be discussed, including antiangiogenic hypoxic cell radiosensitizers and hypoxic cytotoxins, hypoxia targeting boron carriers and p53-inhibiting bifunctional radiosensitizers. We will also review our own recent research results in these areas. For example, we have found that certain of the 2-nitroimidazole radiosensitizers and heterocycle-N-oxide hypoxic cytotoxins we developed have antiangiogenic activity and antimetastatic activity. We propose that these activities are based on the inhibition of signal transduction mediated by HIF-1alpha. The anti-tumor activities of hypoxia response are considered to be cytostatic (tumor dormancy-inducing) effects in contrast to cytotoxic DNA damaging effects. The combination of these cytostatic effects that are related to radiosensitization with the cytotoxic effects of radiation should improve the prognosis and QOL of patients receiving radiation and lead to an overall response to treatment. Based on these considerations, we developed the antiangiogenic hypoxic cell radiosensitizers, TX-1877, TX-1898 and the hypoxic cytotoxin TX-402 that inhibits the HIF-1alpha pathway We will also discuss our research involved with the development of other drugs to exploit tumor hypoxia, including a hypoxia-targeting boron carrier for boron neutron capture therapy (BNCT) and a p53 inhibiting radiosensitizer. (Keyword) Angiogenesis Inhibitors / Antineoplastic Agents / Cell Hypoxia / Drug Design / Humans / Radiation-Sensitizing Agents (Link to Publication Site) ● Publication site (DOI): 10.1248/bpb.29.2335 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17142959 ● Search Scopus @ Elsevier (PMID): 17142959 ● Search Scopus @ Elsevier (DOI): 10.1248/bpb.29.2335 (DOI: 10.1248/bpb.29.2335, PubMed: 17142959)
16.	Hitoshi Hori, Hideko Nagasawa and Yoshihiro Uto : 癌化学療法の新展開, PHARMSTAGE, Vol.6, No.3, 46-52, Jul. 2006.
17.	Yoshihiro Uto, Hideko Nagasawa, 後藤恵子, 中嶌瞳, 中江崇, 田中智子, 田中彩子, 慎一郎増永, 小野公二 and Hitoshi Hori : Hypoxia drug discovery: design of hypoxic cell radiosensitizer having p53 inhibitory activity and hypoxia-oriented boron carrier for boron neutron capture therapy (BNCT), Japanese Journal of Cancer Clinics, Vol.52, No.1, 11-14, Jul. 2006. (Keyword) Hypoxia drug / Hypoxic cell radiosensitizer / p53 Inhibitor / Hypoxia-oriented boron carrier / BNCT (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1523951028235480704 (CiNii: 1523951028235480704)
18.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, モハマッドサハルディンビン and 中川美典 : Gcタンパク質(ビタミンD結合タンパク質)の糖鎖プロセシングをベースにしたドラマタイプがん治療薬の創製, Radiation Biology Research Communications, Vol.39, No.3, 328-341, Dec. 2004. (Summary) ビタミンD結合タンパク質由来マクロファージ活性化因子(GcMAF)についての研究成果を概説し，我々の研究結果を基に新しい癌治療薬としてのドラマタイプがん治療薬の創製について提言した．
19.	Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : 低酸素性癌細胞を標的とする放射線増感剤/制癌剤の分子設計, Radiation Biology Research Communications, Vol.37, No.4, 359-375, Dec. 2002. (Summary) 本総説において，低酸素細胞を標的とする放射線増感剤あるいは制癌剤の分子設計に関して，我々のこれまでの成果を中心に紹介し，今後の制癌剤開発における標的として，近年急速に明らかにされてきた低酸素シグナル伝達系の重要性を論述した．

Proceeding of International Conference:

1.	Honda Hirofumi, Masahide Tominaga, Motoharu Sasaki, Yoshihiro Uto, Masataka Oita, Hamamoto Yasushi, Mochizuki Teruhito, Kido Teruhito, Ishii Y, Yamamoto Ryuji and Omoto K : Detectability of MLC Stop Position Error During Treatment by Gantry-Mounted Transmission Detector, AAPM 62th annual meeting (WEB), Jul. 2020.
2.	Yoshihiro Uto : Drug discovery of anticancer drugs using a developing chicken egg tumor model, The 2nf Asian Symposium on Cutting-edge Biotechnology and Chemistry, 北九州市, Dec. 2019.
3.	Soichiroh Enomoto, Yasuo Yamamoto, Daisuke Konishi, Mana Futawaka, Yuki Kusuhashi, Kenji Teranishi, Yoshihiro Uto and Naoyuki Shimomura : Effects of Nanosecond Pulsed Electric Fields Application and Combination of Anticancer Drug on Cancer Cell, The 2019 IEEE Pulsed Power and Plasma Science Conference, 4-pages, Orlando, Jun. 2019. (Link to Publication Site) ● Publication site (DOI): 10.1109/PPPS34859.2019.9009682 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85081539457 (DOI: 10.1109/PPPS34859.2019.9009682, Elsevier: Scopus)
4.	Masataka Oita, M Udaka, H Aoyama, Motoharu Sasaki, Masahide Tominaga and Yoshihiro Uto : Immunological aspects of Improved Tumor and Normal Tissue Responses Using Biophysical modelling, AAPM 60th Annual Meeting, Jul. 2018.
5.	Teruaki Ito, Yoshihiro Uto, Toshihiro Moriga, Abidin Zaimi Zainal Muhammad, Effendi Mohammad and Salleh Rizal Mohd : Concurrent Engineering-based Team Working for Japan-Malaysia Academic Collaboration, Proceedings of International Conference on Design and Concurrent Engineering Conference 2017 & Manufacturing Systems Conference 2017, Vol.17, No.205, 46-1-46-3, Osaka, Sep. 2017.
6.	Yasuo Yamamoto, Hanayo Katsura, Shun Ogura, Naoyuki Shimomura, Kenji Teranishi and Yoshihiro Uto : Consideration of Pulse-Width Effects of Nanosecond Pulsed Electric Fields Application on Cancer Cell, IEEE International Pulsed Power Conference 2017, 1-4, Brighton, Jun. 2017. (Link to Publication Site) ● Publication site (DOI): 10.1109/PPC.2017.8291240 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85054234742 (DOI: 10.1109/PPC.2017.8291240, Elsevier: Scopus)
7.	Honda Hirofumi, Kubo Kei, Yamamoto Ryuuji, Ishii Yoshiaki, Kanzaki Hiromitsu, Hmamoto Yasushi, 望月輝一, Masataka Oita, Motoharu Sasaki, Masahide Tominaga and Yoshihiro Uto : Feasibility of dose delivery error detection by a transmission detector for patient-specific QA, Radiotherapy and Oncology, Vol.123, No.1, S787-S788, May 2017. (Link to Publication Site) ● Publication site (DOI): 10.1016/S0167-8140(17)31909-6 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1016/S0167-8140(17)31909-6 (DOI: 10.1016/S0167-8140(17)31909-6)
8.	Yoshihiro Uto, takuma Suzuki, Hanayo Katsura, Hisatsugu Yamada, Tomohiro Osaki, Masahiro Ishizuka, Tohru Tanaka, Nobuyasu Yamanaka and Tsukasa Kurahashi : Development of Sonodynamic therapy for breast cancer using 5-aminolevulinic acid, 10th Anniversary International Symposium on Nanomedicine, Nov. 2016.
9.	Shun Ogura, Shuzo Matsubara, Shouta Kuniyasu, Kenji Teranishi, Yoshihiro Uto and Naoyuki Shimomura : Study of Effects of Nanosecond Pulsed Electric Fields on Cancer Cell by using in Vivo and ex vivo Assay, Proceedings of 2016 IEEE International Power Modulator and High Voltage Conference, 377-381, San Francisco, Jul. 2016. (Link to Publication Site) ● Publication site (DOI): 10.1109/IPMHVC.2016.8012798 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1109/IPMHVC.2016.8012798 (DOI: 10.1109/IPMHVC.2016.8012798)
10.	Masataka Oita, Nakata K., Motoharu Sasaki, Masahide Tominaga, Hideki Aoyama, Hirofumi Honda and Yoshihiro Uto : Does the Biophysical Modeling for Immunological Aspects in Radiotherapy Precisely Predict Tumor and Normal Tissue Responses?, AAPM 58th Annual Meeting, Jun. 2016.
11.	Yoshitaka Kurashiki, Keiko Kitazato, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Tomoya Kinouchi, Manabu Sumiyoshi, Takeshi Miyamoto, Tadashi Yamaguchi, Junichiro Satomi, Yoshihiro Uto and Shinji Nagahiro : Activation of M2 macrophages in the late phase of cerebral ischemia may contribute to phagocytosis of infarct area and neurogenesis, 25th European Stroke Conference, Apr. 2016.
12.	Masataka Oita, Hideki Aoyama, Motoharu Sasaki, Masahide Tominaga, Hirofumi Honda and Yoshihiro Uto : Application of biophysical modelling for normal tissue response with immunological aspects in radiotherapy, Radiotherapy and Oncology, Vol.118, No.S1, S79-S80, Feb. 2016. (Link to Publication Site) ● Publication site (DOI): 10.1016/s0167-8140(16)30162-1 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1016/s0167-8140(16)30162-1 (DOI: 10.1016/s0167-8140(16)30162-1)
13.	Ryu Tada, Hisatsugu Yamada, Eiji Nakata, Kai Masuda, Takashi Morii and Yoshihiro Uto : Development of a PARP-inhibiting boron tracedrug for neutron dynamic therapy, Pacifichem 2015, Honolulu, HI, Dec. 2015.
14.	Yoshihiro Uto, Hisatsugu Yamada, Daisuke Kuchiike, Kentaro Kubo, Toshio Inui, Martin Mette, Ken Tokunaga, Akio Hayakawa, Akitetsu Go and Tomohiro Oosaki : Degalactosylated/desialylated human serum and bovine colostrum induces macrophage phagocytic activity., Pacifichem 2015, Honolulu, HI, Dec. 2015.
15.	Hisatsugu Yamada, Yoshinori Hasegawa, Yu Kimura, Hirohiko Imai, Tetsuya Matsuda, Yoshihiro Uto, Yasuhiro Aoyama and Teruyuki Kondo : Probe-Targeted Magnetic Resonance Imaging of Tumor with A Self-Traceable ¹H-¹³C Polymeric Nanoprobe, Pacifichem 2015, Honolulu, HI, Dec. 2015.
16.	Junpei Hashimoto, Miyuki Oshimura, Tomohiro Hirano, Yoshihiro Uto and Koichi Ute : Stereospecific radical polymerization of methacrylamide derivatives in the presence of lithium salts, 14th Pacific Polymer Conference, Kauai, Dec. 2015.
17.	Yoshihiro Uto, Tomohito Kawai, Toshihide Sasaki, Ken Hamada, Saki Ikame, Eri Kuwada, Hisatsugu Yamada, Kentaro Kubo, Daisuke Kuchiike, Martin Mette, Toshio Inui, Ken Tokunaga, Akio Hayakawa, Akitetsu Go and Tomohiro Oosaki : Development of Macrophage Activating Glycoproteins by Using Bovine Colostrum as an Immunotherapeutic agent., 9th International Symposium on Nanomedicine (ISNM2015), Nov. 2015.
18.	Shuzo Matsubara, Akito Nakagawa, Shota Kuniyasu, Kenji Teranishi, Yoshihiro Uto and Naoyuki Shimomura : Investigation of Effect of Applied Nanosecond Pulsed Electric Fields on Tumor, Digest of Technical Papers-IEEE International Pulsed Power Conference, 374-378, Austin, Jun. 2015. (Link to Publication Site) ● Publication site (DOI): 10.1109/PPC.2015.7296945 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1109/PPC.2015.7296945 (DOI: 10.1109/PPC.2015.7296945)
19.	Ryu Tada, Hitoshi Hori, Shinichiro Masunaga, Yuko Kinashi, Koji Ono and Yoshihiro Uto : NDT-based Approach of Boron tracedrug UTX-51 to Glycated BSA as a AGE model., 15th International Congress of Radiation Research (ICRR2015), May 2015.
20.	Takehiro Hara, Masahide Tominaga, Hideaki Endo and Yoshihiro Uto : The effect of dose rate on radiation-induced in vitro antitumor activity by low-LET radiation., 15th International Congress of Radiation Research (ICRR2015), May 2015.
21.	Akito Nakagawa, Masataka Nagahama, Kenji Teranishi, Yoshihiro Uto and Naoyuki Shimomura : Effects of Applied Ultrashort Pulsed Electric Fields on Solid Tumor, Proceedings of the 2014 IEEE International Power Modulator and High Voltage Conference, 45-48, Santa Fe, Jun. 2014. (Link to Publication Site) ● Publication site (DOI): 10.1109/IPMHVC.2014.7287203 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-84947067911 (DOI: 10.1109/IPMHVC.2014.7287203, Elsevier: Scopus)
22.	Masataka Oita, Yoshihiro Uto, Hitoshi Hori, Masahide Tominaga and Motoharu Sasaki : Effects of Uncertainties of Radiation Sensitivity of Biological Modelling for Treatment Planning, AAPM 56th Annual Meeting, Jun. 2014.
23.	Yoshihiro Uto, Chiaki Abe, Toru Yoshitomi, Yukio Nagasaki, Yoshio Endo and Hitoshi Hori : Evaluation of in vivo antioxidative activity of O-TEMPO-RNP using our newly developed chicken egg assay, The 16th biennial meeting for the Society for Free Radical Research International (SFRRI), London, Sep. 2012.
24.	Masataka Nagahama, Naoyuki Shimomura, Yoshihiro Magori, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : Development of Techniques Applying Nanosecond Pulse Electric Fields on Solid Tumor, Proceedings of the 2012 IEEE International Power Modulator and High Voltage Conference, 516-519, San Diego, Jun. 2012. (Summary) Bioelectrics has become a notable field of pulsed power application at the present day. Cancer therapy using apoptosis with nanosecond pulsed electric fields (nsPEFs) has been studied in laboratories. We introduced embryonic chick assay to study in vivo. The embryonic chick assay has several advantages and is categorized as in vivo experiment. Many samples can be prepared with low cost by the assay. This study adopted EMT6/KU (mouse breast adenocarcinoma cells) as tumor cells, which formed a solid tumor on the chorioallantoic membrane (CAM) of a fertilized hen egg in the assay. Nanosecond pulsed electric fields with width of 1.5 ns were applied on the solid tumor on CAM with needle electrodes. Stainless wires of 1 mm in diameter were used as the needle electrodes. The two or four needle electrodes were used in this experiment. The solid tumor was dissected and extracted from the egg on a three days after application of nsPEF and was then weighed. The controls of tumor sample were also prepared without nsPEF application. Significance test on the weight of tumors was adopted to determine the effect of nsPEFs application. The difference of weight between the tumor with nsPEF application and control was significantly confirmed. The difference enlarged with the charging voltage of pulsed power generator. (Link to Publication Site) ● Publication site (DOI): 10.1109/IPMHVC.2012.6518794 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1109/IPMHVC.2012.6518794 (DOI: 10.1109/IPMHVC.2012.6518794)
25.	Yoshihiro Magori, Seiji Ohta, Tatsuya Kageyama, Kenji Teranishi, Naoyuki Shimomura, Yoshihiro Uto and Hitoshi Hori : In Vivo Experiment of Applying Nanosecond Pulsed Electric Fields on Solid Tumor, Proceedings of the 18th IEEE International Pulsed Power Conference, 1237-1241, Chicago, Jun. 2011. (Link to Publication Site) ● Publication site (DOI): 10.1109/PPC.2011.6191594 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1109/PPC.2011.6191594 (DOI: 10.1109/PPC.2011.6191594)
26.	Yoshihiro Uto, Chiaki Abe, Toru Yoshitomi, Yukio Nagasaki, Yoshio Endo, Eiji Nakata and Hitoshi Hori : In vivo antioxidative activity of radical-containing-nanoparticle (RNP) in fertilized chicken egg assay, International Conference on Biomaterials Science 2011, Tsukuba, Mar. 2011.
27.	Yoshihiro Uto, Chiaki Abe, Takashi Nakae, Yoshio Endo, Masahide Tominaga, Hiroshi Maezawa, Eiji Nakata and Hitoshi Hori : Systems biology-based drug design of sugar-hybrid hypoxic cell radiosensitizers using the tumor-implantable chick embryo model, PACIFICHEM 2010, Honolulu, Dec. 2010.
28.	Hitoshi Hori, Eiji Nakata, Masato Koizumi, Yohei Yamashita and Yoshihiro Uto : Boron tracedrug: Design, synthesis and pharmacological activity of phenolic BODIPY-containing antioxidants as traceable next-generation drug model, International Society on Oxygen Transport to Tissue 2010 (ISOTT 2010), Ascona, Switzerland, Jul. 2010.
29.	Yoshihiro Uto, Ryo Tanaka, Kenta Ohnaka, Yuki Ohta, Kazufumi Yazaki, Naoyuki Umemoto, Eiji Nakata and Hitoshi Hori : Prenylated acylphloroglucinol derivatives: Isoprenomics-based design, syntheses and antioxidative activities, International Society on Oxygen Transport to Tissue 2010 (ISOTT 2010), Ascona, Switzerland, Jul. 2010.
30.	Eiji Nakata, Yukimachi Yoshihiro, Nazumi Yoshijiro, Abe Chiaki, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : Design of a Bioreductively-Activated Fluorescent pH Probe for Tumor Hypoxia Imaging, SJBC2009, Tokyo, Sep. 2009.
31.	Hitomi Nakashima, Kazuhiro Ikkyu, Kouichiro Nakashima, Keiichiro Sano, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshinori Nakagawa and Hitoshi Hori : Design of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety, ISOTT2008 (2008 International Society on Oxygen Transport to Tissue Conference), Sapporo, Aug. 2008. (Summary) Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate limiting step of L-Tryptophan (L-Trp) catabolism in the kynurenine pathway. IDO expresses in many neoplasms, and play a role in immunosuppression. IDO is activated only reductive or hypoxic conditions, because the heme iron of active site is easily oxidized to its inactive form. Hypoxic neoplastic cells indicate chemo- and radioresistances and also cause neoplasm' progression, invasion and metastasis. Previously we focused to the mode of activation of IDO only in hypoxic and reductive condition to design hypoxia-targeting IDO hybrid inhibitors, which constituted an IDO inhibitor 1-methyl-tryptophan (1MT) and hypoxic cytotoxin tirapazamine (TPZ), such as TX-2236, TX-2235, TX-2228 and TX-2234. They were good hypoxia-targeting IDO inhibitors. 1MT-TPZ hybrids inhibited IDO uncompetitively. Thus, it suggests that 1MT-TPZ hybrids were able to bind the only enzyme-substrate complex, not to bind the active site. In this study, we present here the novel design and syntheses of hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety without inhibitor 1MT such as L-Trp-TPZ hybrids 1 (n = 4, monoxide), 2 (n = 4, dioxide), 3 (n = 5, monoxide), and 4 (n = 5, dioxide). These L-Trp-TPZ hybrids were synthesized from 3-chlorinated TPZ monoxide with various length alkyldiamines to give the corresponding amine derivatives, which were conjugated with Boc-L-Trp to give the L-Trp-TPZ monoxide hybrids 1 and 3. L-Trp-TPZ dioxide hybrids 2 and 4 were also synthesized from the corresponding TPZ-dioxide trifluoroacetamide intermediates. L-Trp-TPZ hybrids were good competitive inhibitors of IDO. Thus, it suggests that these L-Trp-TPZ hybrids were able to bind the active site. In conclusion, we discovered IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety. Additionally we are under evaluation of their hypoxic cytotoxicity to develop hypoxia-targeting IDO hybrid inhibitors as our final goal.
32.	Yoshihiro Uto, Chiaki Abe, Yoshio Endo, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : Development of an in vivo evaluation system of antioxidants for their vascular protective activities using the chick embryo chorioallantoic membrane, ISOTT2008 (2008 International Society on Oxygen Transport to Tissue Conference), Sapporo, Aug. 2008. (Summary) The blood vessel is one of the most important organs in the oxygen transport, and the drug discovery research of clinical-use antioxidants, which may control various vascular disorders caused by the oxidative stress, is extremely important. In fact, the in vitro evaluation system of antioxidants being mainly used now, however, has a problem of no appreciable in vivo redox status of the antioxidants. We, therefore, tried the development of an in vivo model for the evaluation of antioxidants for their vascular protective activities using the chick embryo having many advantages, such as handy, quick, cheap, and possible high-throughput screening. The topical administration (doses from 150 to 350 g) of 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), a water-soluble prooxidant, to the chorioallantoic membrane (CAM) of 6-days chick embryos, resulted in their vascular injuries of percentage from 25 to 100% dose dependently, which were correlated with their increased fatal rate of the percentage from 29 to 86%. Artepillin C, a potent natural antioxidant, showed a weak vascular injury (26% at 10 g). These results suggest that immature developing CAM vasculature might have low tolerance to oxidative injury. In the case of 12-days chick embryos, AAPH (doses from 0.3 to 7 mg) induced their vascular injuries (20 to 80%) against the CAM veins and venous capillaries without their fatal damage. Artepillin C, with its dose of up to 30 g, did not show the chick embryo's venous injury, and pre-treatment with artepillin C dose-dependently protected the CAM venous and venous capillary injuries induced by the post-administration of 3 mg of AAPH: 1 g artepillin C decreased 60% of venous injury. These results suggest that artepillin C efficiently protected the AAPH-induced vascular injury of chick embryonic CAM. In conclusion, artepillin C might be a promising clinical-use antioxidant for prevention of vascular disease.
33.	Hitoshi Hori, Yoshihiro Uto, Daisuke Koyama, Mamoru Otsuki, Naoki Otomo, Tadashi Shirai, Chiaki Abe, Eiji Nakata and Hideko Nagasawa : A chemical biosynthesis design for antiatherosclerosis drug by acyclic tocopherol intermediate analogue based on ``isoprenomics'', ISOTT2007 (2007 International Society on Oxygen Transport to Tissue Conference), Uppsala, Sweden, Aug. 2007. (Summary) Tocopherols constitute members of the vitamin E group and act as a potent lipid peroxidation inhibitor against for cell membrane such as blood vessels. Phytyl quinols, namely acyclic tocopherols, are key intermediate of tocopherol biosynthesis, but their biological activities remain unclear. We therefore investigated the structure-activity relationship of phytyl quinols to apply chemical biosynthesis design for an antiatherosclerosis drug. We have achieved the biosynthesis-oriented design and synthesis of alpha- (TX-2254) and beta- (TX-2247) phytyl quinol as an unnatural intermediate, other gamma- (TX-2242) and delta- (TX-2231) phytyl quinol as a natural one. Free radical reactivity was determined by using DPPH radical. Inhibitory activity of human low density lipoprotein (LDL) oxidation was measured by TBARS assay. Free radical reactivity of TX-2242 (EC50 = 24.6 microM) and TX-2231 (24.2 microM) were equal with DL-alpha-tocopherol (22.3 microM), whereas TX-2254 (38.0 microM) and TX-2247 (30.2 microM) showed lower reactivity than DL-alpha-tocopherol. TX-2242 (IC50 = 61 microM) and TX-2231 (69 microM) also showed almost same LDL antioxidant activity as DL-alpha-tocopherol (64 microM), while TX-2254 (149 microM) and TX-2247 (254 microM) showed lower antioxidant activity than DL-alpha-tocopherol. We suggested from these results that the cyclization of phytyl quinol to tocopherol is not indispensable for the appearance of the potent antioxidant activity. We also have found an interesting negative correlation between methylation and antioxidant activity of phytyl quinols. We will present ex vivo antioxidant activity for blood vessels in the chick embryo chorioallantoic membranes (CAM) as an alternative in vivo model.
34.	Hitoshi Hori, Yoshihiro Uto, Hideko Nagasawa, Shutaro Ae, Daisuke Koyama, Naoki Otomo, Mamoru Otsuki and Takashi Tuji : Design and synthesis of LDL oxidation inhibitor based on isoprenomics, XIII Biennial Meeting of the Society for Free Radical Research International, Davos, Aug. 2006.
35.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Masamitsu Hiraoka, Keiko Goto, Hitomi Nakashima, Satoru GOTO and Shin-ichiro Masunaga : Design, synthesis, and pharmacokinetics of hypoxic tumor-targeting boron carriers, IMEBORON12, Sendai, Sep. 2005. (Summary) Purpose: The presence of hypoxic tumor cells is also associated with resistance to boron neutron capture therapy (BNCT). To accomplish the effective boron carrier for BNCT, we have recently developed 2-nitroimidazole-sodium borocaptate-10B (BSH) conjugates, TX-2016, 2017, 2018, 2041, 2042, and 2060, that is, hybrids that have both hypoxic tumor cell g-ray-sensitizing unit, 2-nitroimidazoles, and thermal neutron-sensitizing unit, BSH [1]. Furthermore, In this communication, to improve the hypoxia-targating character, we report the design, synthesis, and pharmacokinetics of hypoxic cytotoxin-hybrid boron carriers, TX-2091, 2095, 2097, 2100, 2124 and 2125, having hypoxic cytotoxin moiety, such as 2-quinoxalinecarbonitrile-1,4-di-N-oxide (TX-402) and tirapazamine (TPZ), and BSH via some carbon chain linker as a pharmacokinetic controlling unit. Result: TX-2016, 2017, and 2018: tertamethylammonium salts of alkyl sulfides of BSH. TX-2041, 2042 and 2060: sodium salts of an alkyl sulfide or a dialkyl sulfonium derivatives of BSH. They were synthesized from their corresponding haloacetylcarbamoyl-2-nitroimidazoles[2] and BSH. To synthesize hypoxic cytotoxin conjugate, 3-clorinated hypoxic cytotoxin (TX-402 or TPZ) was condensed with ethyl-, propyl-, or hexyl-alcoholamine to obtain the corresponding hydroxyalkylamino derivatives. They were treated with bromoacetyl isocyanate followed by disodium (2-cyanoethyl)-thio-undecahydro-closo-dodecaborate(2-) to yield cyanoethyl sulfonium compounds, TX-2095, 2100, 2110, 2124, and 2125. Among the 2-nitroimidazole conjugates, TX-2041 has the most favorable pharmacokinetic characteristics with higher tumor affinity of 10B during neutron beam irradiation. In addition, TX-2041 showed a significantly higher radiosensitizating effect with reactor thermal neutron beams than that of BSH. Cyanoethyl sulufonium derivative, TX-2060 showed better tumor affinity of 10B and more cytotoxicity after irradiation with reactor thermal neutron beams than that of TX-2041. Furthermore, TX-2100 achieved significantly higher tumor affinity than 2-nitoroimidazoles, TX-2041 and 2060, and also showed cytotoxicity comparable to TX-2060. In conclusion, these hypoxic tumor trageting cytotoxin-hybrid 10B-carriers , such as TX-2100, with the potential tumor affinty of10B, are expected to have clinical applications as promising boron carriers for use in BNCT.
36.	Shinichi Nakayama, Hideko Nagasawa, Tomoya Fujita, Toshihiro Hashimoto, Yoshinori Asakawa, Yoshihiro Uto, Hitoshi Hori and Douglas A. Kuntz : Synthesis of new GMII mannosidase inhibitors, diversity-oriented 5-substituted swainsonine analogues, via stereoselective Mannich reaction, 230th American Chemical Society Meeting & Exposition, Washington, D.C., Aug. 2005. (Summary) A potent Golgi a-mannosidase (GMII) inhibitor, (-)-swainsonine, exhibits pleiotropic effects such as anticancer activities including metastasis and immunomodulatory effects. To develop more potent immunomodulatory anticancer agents and gain insight on the molecular bases of these activities, we synthesized 5-substituted swainsonine analogues stereoselectivity using our developed diversity-oriented modification reaction (ref.1). We have developed amine acetal (1) as a versatile intermediate for the preparation of 5a-(3) and 5b-acyl (4). Swainsonine analogues were synthesized by stereoselective Mannich reaction of an in situ generated (-)-swainsonine iminium ion intermediate (2) followed by their epimerization reaction. Their carbonyl groups were reduced by Pd-catalyzed hydrogenation to afford 5a-(5a) and 5b-alkyl analogues(5b). Some of these new 5a-substituted swainsonine analogues possessing aromatic group showed more potent a-mannosidase inhibitory activities than swainsonine itself. To gain insight on the molecular bases of these activities, we also analyzed the crystal structures of Dorosophila GMII in complex with some of these swainsonine analogues.
37.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Cheng-Zhe Jin, Ayako Tanaka, Mariko Shimamura, Yoshio Takeuchi, Kenneth L. Kirk and Seiichi Inayama : Design of 2-methylene-4-cyclopentene-1,3-dione-containing azomycin derivatives as antiangiogenic hypoxic cell radiosensitizers, 96th American Association for Cancer Research Annual Meeting, Anaheim, Apr. 2005.
38.	Hitoshi Hori, Yoshihiro Uto, Mitsutoshi Sakakibara and Hideko Nagasawa : Artepillin C isoprenomics; first total synthesis of artepillin C and medicinal approach for artepillin C analogues, 3rd International Symposium on Natural Drugs, Napoli, Italy, Oct. 2003. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．
39.	Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : Phenolic natural product isoprenomics; first total synthesis of artepillin C and medicinal approach for artepillin C analogues, 226th ACS National Meeting, New York, Sep. 2003. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．さたにこれをリード化合物としてアルキルフェノール誘導体を分子設計·合成し，そのミトコンドリア呼吸阻害活性及び脂質過酸化阻害活性についても検討した．
40.	Hitoshi Hori, Hideko Nagasawa and Yoshihiro Uto : Structure-based design of the antitumor 2-hydroxyarylidene-4-cyclopentene-1,3-dione TX-1123 as a protein tyrosine kinase inhibitor having low mitochondrial toxicity, 3rd International Conference on Inhibitors of Protein Kinases and Workshop on Phosphoryl-Transfer Mechanisms, Warsaw, Poland, Jun. 2003. (Summary) 本発表において，チロシンキナーゼ阻害を介した抗腫瘍剤をめざして2-hydroxyarylidene-4-cyclopentene-1,3-dione誘導体の分子設計·合成及び生物活性の検討を行った．その結果，AG17と比較してミトコンドリア毒性の低い，強いCOX-2阻害活性を有する強力な抗腫瘍性チロフォスチンであるTX-1123の開発に成功したことを示した．
41.	Hideko Nagasawa, Naoko Mikamo, Yoshimi Nakajima, Hideki Matsumoto, Yoshihiro Uto and Hitoshi Hori : TX-402: Hypoxic cytotoxin as an inhibitor pf hypoxia-inducible factor 1 pathway, The Tumor Microenvironment and Its Inpact on Cancer Therapies 8th International Workshop, Miami, Florida, May 2003. (Summary) 本発表で，血管新生阻害作用を有する新規hypoxic cytotoxin TX-402は，低酸素誘導因子(HIF-1)シグナル経路を阻害することによって，血管新生阻害作用などの低酸素応答反応を抑制することを示した．
42.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, Kazuto Ohkura, Y. Takeuchi, K.L. Kirk, H. Miyataka and T. Sato : Design of selective arachidonic acid cascade inhibitors of low-mitochondrial-toxic PTK inhibitor TX-1123 analogues based on their COX-1, 2 and 5-LO inhibitory activities, The 8th International Workshop on the Tumor Microenvironment and Its Impact on Cancer Therapies, Miami, Florida, USA, May 2003. (Summary) 本発表において，チロシンキナーゼ阻害を介した抗腫瘍剤をめざして2-hydroxyarylidene-4-cyclopentene-1,3-dione誘導体の分子設計·合成及び生物活性の検討を行った．その結果，AG17と比較してミトコンドリア毒性の低い，強いCOX-2阻害活性を有する強力な抗腫瘍性チロフォスチンであるTX-1123の開発に成功したことを示した．
43.	Atsushi Umemoto, M.A. Momen, J. Honda, J.-W. Zhu, Megumi Yukawa, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori and Yasumasa Monden : Possible potent activity of 7-Oac-UDCA, a novel compound, in the prevention of colon cancer, 18th World Congress of Digestive Surgery (International Society for Digestive Surgery), 9th Hong Kong International Cancer Congress, Hong Kong, China, Dec. 2002. (Summary) 新規大腸発がん予防薬として7-OAc-UDCAの分子設計·合成を行いその活性を明らかにした．
44.	Hitoshi Hori, Soko Kasai, Hideko Nagasawa, Yoshihiro Uto, T. Inomata, S. Oka and S. Inayama : TX-1877: Designed antimetastatic hypoxic cell radiosensitizer, The 6th China-Japan Joint Symposium on Drug Design and Development (Asian Federation for Medicinal Chemistry), Dalian, China, Oct. 2001. (Summary) 本発表において，多機能性低酸素細胞放射線増感剤TX-1877及びそのアナログの分子設計を行い，これらの低酸素放射線増感作用，血管新生阻害作用，転移抑制作用について，構造活性相関を行い，それらの有効性を示した．
45.	S.B. Mohamad, Hitoshi Hori, Hideko Nagasawa, Kenji Usui and Yoshihiro Uto : Characterization of human Gc protein-derived macrophage activation factor (GcMAF) and its functional role in macrophage tumoricidal activity, 29th ISOTT (International Society on Oxygen Transport to Tissue) annual meeting, Philadelphia, PA, USA, Aug. 2001. (Summary) 本発表では，GcMAFの抗腫瘍作用の作用機構として，マクロファージ貪食能と活性酸素生成を活性化することを明らかにした．
46.	Hitoshi Hori, Yoshihiro Uto, Akihiko Hirata, Mitsutoshi Sakakibara, Masaki Ishibashi and Hideko Nagasawa : Structure-based elucidation nof antioxidative and antiperoxidative effects with 2,4,6-trisubstituted phenols, 10th Biennial Meeting of the International Society for Free Radical Research (SFRR 2000), Kyoto, Oct. 2000. (Summary) 2,4,6三置換フェノール類の抗酸化作用美ついての構造活性相関を論述した．
47.	Hideko Nagasawa, Fumi Nagura, Saharuddin B. Mohamad, Ji-Wen Zhu, Yoshihiro Uto, T. Hashimoto, Yoshimori Asakawa and Hitoshi Hori : Apoptosis Induc-tion of Cyto-chalasins Iso-lated from The Japanese Fungus Daldinia Ver-nicaso for Human Colon Cancer Cell, Third Interna-tional Congress on Phytomedi-cine, Munich, Germany, Oct. 2000. (Summary) 本論文において，Daldinia Venicosaより単離，構造決定したサイトカラシン類の大腸がん由来HCT116細胞に対するアポトーシス誘導作用を明らかにし，これらの構造活性相関について論述した．
48.	Hitoshi Hori, Soko Kasai, Hideko Nagasawa, Mao Yamashita, Yoshihiro Uto, I Ota and N Matsuura : Design, Synthesis, and Activities of Antimetastatic Hypoxic Cell Radiosensitizer TX-1877 and its Analogues Inhibiting Endothelial Cells Migration, 11th Int'l Conference of Chemical Modifiers of Cancer Treatment, Banff, Alberta, Canada, Oct. 2000. (Summary) 腫瘍転位抑制作用を有する低酸素細胞放射線増感剤TX-1877の分子設計·合成，生物活性について発表した．
49.	Hitoshi Hori, Soko Kasai, Hideko Nagasawa, Mao Yamashita, Yoshihiro Uto, I Ota and N. Matsuura : Design, synthesis, and activities of antimetastatic hypoxic cell radiosensitizer TX-1123 and its analogues inhibiting endotherlial cells migration, Tumor Physiology and Cancer Treatment, 8th International Conference-Chemical Modifiers of Cancer Treatment Series, Banff, Alberta, Canada, Oct. 2000. (Summary) 腫瘍転位抑制作用を有する低酸素細胞放射線増感剤TX-1877の分子設計·合成，生物活性について発表した．
50.	Yoshihiro Uto, Akihiko Hirata, Masaki Ishibashi, Hideko Nagasawa and Hitoshi Hori : Design and synthesis of 2,6-diprenyl-4-iodophenol TX-1952 having a novel and potent anti-peroxidative activity, ISOTT(International Society on Oxygen Transport to Tissue) 2000 annual meeting, Nijmegen, Netherlands, Aug. 2000. (Summary) 2,6-Diprenyl-4-iodophenol 類のTX-1952及びその誘導体の，抗酸化作用における構造活性相関について発表した．
51.	Hideko Nagasawa, Mao Yamashita, Naoko Mikamo, Mariko Shimamura, S. Oka, Yoshihiro Uto and Hitoshi Hori : Design, synthesis and biological activities od antiangiogenic hypoxic cytotoxin, triazine-N-oxide derivatives, ISOTT2000 (International Society on Oxygen Transport to Tissue), Nijmegen, Netherlands, Aug. 2000. (Summary) Hypoxic cytotoxinであるトリアジン-N-オキシド類の分子設計·合成及び生物活性について発表した．
52.	S.B. Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation, ISOTT2000 (International Society on Oxygen Transport to Tissue), Nijmegen, Netherlands, Aug. 2000. (Summary) 腫瘍由来α-N-アセチルガラクトサミニダーゼ活性のGcMAFマクロファージ活性化作用に対する影響について発表した．
53.	Hitoshi Hori, J.-W. Zhu, Hideko Nagasawa, Fumi Nagura, S.B. Mohamad, Yoshihiro Uto and Kazuto Ohkura : Brefeldin A: Toward new Differentiation and Apoptosis Inducers, Fourth Australia/Japan Joint Symposium on Drug Design and Development, Werribee, Victoria, Australia, May 2000. (Summary) ブレフェルジンAの分化誘導作用と抗腫瘍活性及びアポトーシス誘導作用について発表した．
54.	Soko Kasai, Hideko Nagasawa, Mao Yamashita, Yoshihiro Uto, I Ota, N Matuura and Hitoshi Hori : Design, Synthesis and effect of hypoxic cell radiosensitizer TX-1877 and its derivatives as endothelial cells migration inhibitor, MILLENNIAL WORLD CONGRESS OF PHARMACEUTICAL SCIENCES, San Francisco, Apr. 2000. (Summary) 新規な転位抑制作用を有する低酸素細胞放射線増感剤TX-1877とその誘導体の設計·合成，及び内皮細胞の浸潤移行抑制効果をはじめとする生物活性について発表した
55.	Hitoshi Hori, Yoshihiro Uto, Masaki Ishibashi, Akihiro Hirata and Hideko Nagasawa : Artepillin C: Molecular modeling and synthetic approach, 2nd International Conference on Food Factors, Kyoto, Dec. 1999. (Summary) プロポリス成分，アルテピリンCの全合成を完成させてた．
56.	J.-W. Zhu, Hideko Nagasawa, Fumi Nagura, S.B. Mohamad, Yoshihiro Uto, Kazuto Ohkura and Hitoshi Hori : 4-epi-Brefeldin A: probing new structural requirements of brefeldin A for inducing activity of differentiation and apoptosis in human colon cancer cell HCT 116, AACR-NCI-EORTC International Conference: Molecular Tragets and Cancer Therapeutics, Discovery, Development, and Clinical Validation, Washington, DC, USA, Nov. 1999. (Summary) ブレフェルジン誘導体4-epi-Brefeldin Aの設計·合成と分化誘導作用，抗腫瘍活性及びアポトーシス誘導作用について発表した．

Proceeding of Domestic Conference:

1.	Yoshihiko Ueno, Yosuke Seki, Takefumi Hattori, Atsushi Tabata, Rie Mukai, Naohiro Oka and Yoshihiro Uto : B学部における学校推薦型選抜Ⅰ地方創生型(地域産業振興枠)の設計と実施 ―入試業務効率化に向けた新たな取り組みを踏まえて―, 令和5年度全国大学入学者選抜研究連絡協議会大会(第18回), May 2023.
2.	篠原侑成, 藤井理, 吉野颯真, 中山清美 and Yoshihiro Uto : シアル酸を含む糖混合物の老化線維芽細胞に対する抗老化活性の評価, 日本薬学会第143年会, Mar. 2023.
3.	田坂徹, 鵜沼英樹, 早川明夫, 田坂啓太, 呉明輝, 呉貴卿 and Yoshihiro Uto : MetAGin(メタジン)®(アメリカ人参複合乳酸菌発酵エキス末)の筋萎縮抑制効果, 第26回日本バイオ治療法学会, Dec. 2022.
4.	Yoshihiro Uto, 梅田亜里, 美野田晃大, 美野田啓二 and 長島孝樹 : ストレスケアカウンセリングとマックビーの自律神経失調症に対する改善効果, 第38回日本ストレス学会学術総会, Nov. 2022.
5.	KASHIHARA Takashi, GOHDA Momoka, Yoshihiro Uto and Hisatsugu Yamada : アセチルグルコース修飾Ceritinibの放射線増感剤としての創薬研究, 2022年日本化学会中四国支部大会, Nov. 2022.
6.	MUROYA Kanae, 田坂徹, 鵜沼英樹, 早川明夫, 田坂啓太, 呉明輝, 呉貴卿 and Yoshihiro Uto : 複合乳酸菌発酵処理したアメリカ人参の筋萎縮抑制効果, 2022年日本化学会中四国支部大会, Nov. 2022.
7.	SHIRAKATA Hina, TAKARA Tsuyoshi, TAKARA Rei, 安倍忍, Yoshihiro Uto and 小林彩 : GcMAF のマクロファージ活性化を介した抗腫瘍効果に関する作用機序の解明, 2022年日本化学会中四国支部大会, Nov. 2022.
8.	小宮悠生, MORIMOTO Kashin, 篠原侑成, 二宮致, 遠藤良夫, 滝野隆久 and Yoshihiro Uto : アミロライド誘導体の構造活性相関による新規Na+/H+交換輸送体5 (NHE5) 選択的阻害剤UTX-143の創製, 2022年日本化学会中四国支部大会, Nov. 2022.
9.	YAMANOUCHI Daisuke, Hirari Yamahana, 滝野隆久, 遠藤良夫, 鈴木健之 and Yoshihiro Uto : マトリックスメタロプロテアーゼ阻害を介した抗転移活性を有する新規Celecoxib誘導体の開発, 2022年日本化学会中四国支部大会, Nov. 2022.
10.	TAKARA Tsuyoshi, TAKARA Rei and Yoshihiro Uto : Elucidation of anti-tumor action mediated by macrophage-producing cytokines by macrophage activating factor GcMAF, 第81回日本癌学会学術総会, Sep. 2022.
11.	田坂徹, 鵜沼英樹, 早川明夫, 呉明輝, 呉貴卿 and Yoshihiro Uto : MetAGin™(アメリカ人参複合乳酸菌発酵エキス末) の筋萎縮抑制効果, 第65回一般社団法人比較統合医療学会学術大会, Aug. 2022.
12.	Yoshihiko Ueno, Eiji Sakuradani, Yosuke Seki, Maiko Kamioka, Chikako Asada, Tetsuya Akamatsu, Katsuyuki Miyawaki, Yoshihiro Uto and Tamotsu Tanaka : 一般選抜後期日程における入学辞退率改善の取り組みーー徳島大学B学部の事例からーー, 第17回大学教育カンファレンスin徳島, Jan. 2022.
13.	Hirofumi Honda, Masahide Tominaga, Motoharu Sasaki, Masataka Oita, 石井香明, 山本竜次, 大元謙二, 上津孝太郎, 城戸輝仁 and Yoshihiro Uto : ガントリー搭載型検出器を用いたMLC位置エラーのγ解析の検討, 第34回高精度放射線外部照射部会学術大会(WEB開催), Apr. 2021.
14.	Yoshihiro Uto, Yuka Izuchi, Hisatsugu Yamada, 永尾司, 呉貴卿, Toru Tasaka, 鵜沼英樹 and 呉明輝 : 瞬芽ブドウ種子エキスiGS4000のアトピー性皮膚炎に対する基礎的検討, 第50回日本皮膚免疫アレルギー学会総会学術大会, Dec. 2020.
15.	Toru Tasaka, Yuka Izuchi, 小林彩, Osamu Fujii, Hisatsugu Yamada, 永尾司, 永尾公基, 永尾侑士 and Yoshihiro Uto : 瞬芽ブドウ種子成分のアトピー性皮膚炎モデルマウスに対する改善効果, 第24回バイオ治療法研究会学術集会, Dec. 2020.
16.	Yoshihiro Uto : 大学研究者による大学発ベンチャーの創出, 産業医科大学令和2年度第1回知的財産セミナー, Dec. 2020.
17.	Yoshihiro Uto : 腫瘍移植鶏卵モデルを用いた癌の創薬研究とPDXモデルの開発, 患者由来がんモデル講演会2020, Oct. 2020.
18.	Yoshihiro Uto, Kei Daizumoto, Yayoi Fukuhara, Hisanori Uehara and Hiro-omi Kanayama : 発育鶏卵を用いた患者由来がんモデルの開発, 第24回日本がん分子標的治療学会学術集会, Oct. 2020.
19.	Yusei Shinohara, Itasu Ninomiya, Yoshio Endo, Takahisa Takino and Yoshihiro Uto : Development of a Novel Amiloride Derivative as a Na+/H+ exchanger 5 selective inhibitor, 第79回日本癌学会学術総会, Oct. 2020.
20.	Hirari Yamahana, Takahisa Takino, Yoshio Endo, Takeshi Suzuki and Yoshihiro Uto : Development of a Novel Celecoxib Derivative UTX-121 as an Antimetastatic Agent, 第79回日本癌学会学術総会, Oct. 2020.
21.	Yusei Shinohara, 遠藤良夫, Chiaki Abe, 小幡徹, 小倉俊一郎, 米村豊 and Yoshihiro Uto : 5-ALAを用いた光線力学療法における新規シッフ塩基併用による増強作用, 日本農芸化学会2020年度中四国支部大会, Sep. 2020.
22.	Yukari Kunieda, Yusei Shinohara, Yuya Tanaka, Hirari Yamahana, Yuri Fujiwara, Hisatsugu Yamada and Yoshihiro Uto : 放射線増感ユニットであるアセチルグルコースを修飾したEGFR阻害剤Erlotinib誘導体の創製, 第22回癌治療増感シンポジウム, Feb. 2020.
23.	Yusei Shinohara, 遠藤良夫, 安部千秋, 小幡徹, 小倉俊一郎, 米村豊 and Yoshihiro Uto : 5-アミノレブリン酸を用いたがん光線力学療法における新規シッフ塩基の併用による増強作用, 第22回癌治療増感シンポジウム, Feb. 2020.
24.	Yoshihiro Uto, Daisuke Konishi, Nami Orimura, Hisatsugu Yamada, Masahide Tominaga, Hitoshi Ikushima, Kei Daizumoto and Hisanori Uehara : リニアックの FFFビームに対する新規増感剤の創製, 第22回癌治療増感シンポジウム, Feb. 2020.
25.	Tohru Tasaka, 前橋克彦, Yuka Izuchi, Hisatsugu Yamada, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿 and Yoshihiro Uto : 低分子化ホエイプロテインを用いたウシ乳房炎に対する治療剤の開発, 第23回バイオ治療法研究会学術集会, Dec. 2019.
26.	Hirofumi Honda, Masahide Tominaga, Motoharu Sasaki, Masataka Oita, 石井香明, 高田紀子, 鶴岡慎太郎, 石川浩史, 濱本泰, 望月輝一 and Yoshihiro Uto : ガントリー搭載型検出器を用いたMLC解析の検討, 第32回日本放射線腫瘍学会学術大会, Nov. 2019.
27.	Yuri Fujiwara, Mana Futawaka, Daisuke Konishi, Nami Orimura, Hisatsugu Yamada, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹 and Yoshihiro Uto : 乳がんに対するアミノレブリン酸を用いた超音波力学療法における温熱療法の増強作用, 日本化学会中国四国支部大会徳島大会, Nov. 2019.
28.	Daisuke Konishi, Mana Futawaka, Yuri Fujiwara, Nami Orimura, Hisatsugu Yamada, Masahide Tominaga, Hitoshi Ikushima, Hisanori Uehara, Kei Daizumoto and Yoshihiro Uto : 医療用直線加速器の高線量率モードX線に対するGemcitabineの増感効果, 日本化学会中国四国支部大会徳島大会, Nov. 2019.
29.	Kohei Bando, 小林彩, Chiaki Nakagawa, Hisatsugu Yamada, 久保健太郎, Toshio Inui and Yoshihiro Uto : ヒト血清由来マクロファージ活性化因子GcMAFの免疫調節作用に関する基礎および臨床研究, 日本化学会中国四国支部大会徳島大会, Nov. 2019.
30.	Risa Kishida, Hiroki Shimada, Hisatsugu Yamada, 今井宏彦 and Yoshihiro Uto : 双極性ポリマープローブの生体内粒子径解析に向けた多重共鳴拡散 NMR の利用, 日本化学会中国四国支部大会徳島大会, Nov. 2019.
31.	Yukari Kunieda, Yusei Shinohara, Yuya Tanaka, Hirari Yamahana, Yuri Fujiwara, Hisatsugu Yamada and Yoshihiro Uto : アセチルグルコースを修飾した放射線増感作用を有する抗腫瘍剤の創薬研究, 日本化学会中国四国支部大会徳島大会, Nov. 2019.
32.	Yoshihiro Uto : 低侵襲的がん治療法としての5-アミノレブリン酸を用いた超音波力学/温熱療法, 第40回日本レーザー医学会総会, Oct. 2019.
33.	Yoshihiro Uto : 発育鶏卵を用いたがんの創薬研究, 第69回日本薬学会関西支部総会・大会, Oct. 2019.
34.	Yoshihiro Uto : 自己免疫疾患に対する免疫調節剤``初乳MAF''および水溶性藍粉末の研究開発, 第46回技術士会全国大会, Oct. 2019.
35.	Yoshihiro Uto, Ayaka Hanyu, Yuki Kusuhashi, Mana Futawaka, Hisatsugu Yamada, Masahide Tominaga and Hitoshi Ikushima : 医療用直線加速器の高線量率モードX線を増感する抗がん剤の探索, 第25回癌治療増感研究会, Jun. 2019.
36.	Yoshihiro Uto, Yuki Kusuhashi, Mana Futawaka, Hisatsugu Yamada, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 山中信康 and 倉橋司 : 5-アミノレブリン酸を用いた超音波力学療法に対する温熱又は放射線の併用効果, 第9回ポルフィリンーALA学会年会, Apr. 2019.
37.	Tohru Tasaka, 前橋克彦, Yuka Izuchi, Hisatsugu Yamada, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿 and Yoshihiro Uto : 低分子化ホエイプロテインを用いたウシ乳房炎に対する治療剤の開発, 日本農芸化学会2019, Mar. 2019.
38.	遠藤良夫, Yoshihiro Uto, Yusei Shinohara, Chiaki Abe, 小幡徹, 小倉俊一郎 and 米村豊 : アミノレブリン酸を用いるがん光線力学的療法に対する新規シッフ塩基誘導体の感受性増強作用, 日本薬学会第139年会, Mar. 2019.
39.	Yoshihiro Uto, Hisatsugu Yamada, 中島元夫, 石塚昌宏, 田中徹, 山中信康, 倉橋司, 久保健太郎 and 乾利夫 : Development of sonosensitizer and immunoactivator by medical-engineering cooperation, 日本化学会第99春季年会, Mar. 2019.
40.	Mao Nishiyama, Ayaka Hanyu, Hisatsugu Yamada and Yoshihiro Uto : Development of Novel Benzotriazine 1,4-Dioxide Sensitizer with Cell Nucleus Targeting and Its Radiosensitizing Effect for Hypoxic Tumor, 日本化学会第99春季年会, Mar. 2019.
41.	Yuka Izuchi, Tohru Tasaka, Ryohei Nishigawa, Yuta Nakamura, Kohei Bando, Hisatsugu Yamada, 前橋克彦, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿 and Yoshihiro Uto : The therapeutic effect of low molecular weight whey protein against bovine mastitis, 日本化学会第99春季年会, Mar. 2019.
42.	Hirari Yamahana, Yusei Shinohara, Ayaka Hanyu, Yuya Tanaka, Hisatsugu Yamada and Yoshihiro Uto : Development of a Novel Acetyl Glucose-modified Gefitinib Derivative for Improvement of Radiosensitizing Effect, 日本化学会第99春季年会, Mar. 2019.
43.	Mana Futawaka, Yuki Kusuhashi, Yuri Fujiwara, Daisuke Konishi, Hisatsugu Yamada, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 山中信康, 倉橋司 and Yoshihiro Uto : Enhancement effects of hypoxic cell radiosensitizer on sonodynamic therapy using 5-aminolevulinic acid, 日本化学会第99春季年会, Mar. 2019.
44.	Yoshihiro Uto : 腫瘍移植鶏卵を用いた癌の創薬研究と医工連携による免疫療法の開発, 神戸薬科大学特別研究セミナー, Jan. 2019.
45.	Atsushi Tabata, Yoshihiro Uto, Hitoshi Hori and 大倉一人 : Chiral-2-nitroimidazole骨格を有するTX-2036 誘導体の開発:放射線増感能の修飾に関わる分子特性の検証, 第22回バイオ治療法研究会学術集会, Dec. 2018.
46.	Yoshihiro Uto, 前橋克彦, Yuka Izuchi, Hisatsugu Yamada, Tohru Tasaka, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝 and 呉貴卿 : ウシ乳房炎に対する低分子化ホエイプロテインの治療効果, 比較統合医療学会第62回大会, Nov. 2018.
47.	Yusei Shinohara and Yoshihiro Uto : Development of acetylglucose-modified gefitinib derivatives as a novel radiosensitizer, 第77回日本癌学会学術総会, Sep. 2018.
48.	Yoshihiro Uto, Hanayo Katsura, Yuki Kusuhashi, Hisatsugu Yamada, Koichiro Tsuchiya, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 山中信康 and 倉橋司 : ESR法を用いたALA-SDTの抗腫瘍作用機序の解析, 第8回ポルフィリン‐ALA学会年会, Apr. 2018.
49.	遠藤良夫, Yoshihiro Uto, Ikkyu Shiba, Yusei Shinohara, 安部千秋, 小幡徹, 小倉俊一郎 and 米村豊 : アミノレブリン酸を用いるがん光線力学的療法に対するシッフ塩基誘導体の感受性増強作用, 日本薬学会第138年会, Mar. 2018.
50.	Ayaka Hanyu, Risa Kouzaki, Kazuki Ueshima, Tomoko Kaneko, Hisatsugu Yamada, Masahide Tominaga, 壽賀正城, 山下智弘, 沖本智昭 and Yoshihiro Uto : 5-アミノレブリン酸およびプロトポルフィリンⅨの炭素線増感作用, 日本化学会第98春季年会, Mar. 2018.
51.	Yuki Kusuhashi, Hanayo Katsura, Mana Futawaka, Yumi Hayashi, Hisatsugu Yamada, 大崎智弘, 石塚昌宏, 田中徹, 山中信康, 倉橋司 and Yoshihiro Uto : アミノレブリン酸を用いた超音波療法に対する温熱の増強効果, 日本化学会第98春季年会, Mar. 2018.
52.	Toyohisa Miyazaki, Yuki Kusuhashi, Ayaka Hanyu, Hiroki Shimada, Hisatsugu Yamada, 近藤輝幸 and Yoshihiro Uto : 2-ニトロイミダゾール基を導入した新規ホスホリルコリンポリマーの合成と機能評価, 日本化学会第98春季年会, Mar. 2018.
53.	Ryohei Nishigawa, Emi Kuwada, Saki Ikame, Yuka Izuchi, Makoto Endo, Hisatsugu Yamada, Yoshihiro Uto, Tohru Tasaka, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝 and 呉貴卿 : Development of macrophage activator with protease-treated whey protein, 日本化学会第98春季年会, Mar. 2018.
54.	Yusei Shinohara, Ikkyu Shiba, Hisatsugu Yamada, 遠藤良夫, 石塚昌宏, 田中徹 and Yoshihiro Uto : 5-アミノレブリン酸を用いた光線力学治療ALA-PDTに対する増感剤TX-816の創製, 日本化学会第98春季年会, Mar. 2018.
55.	Yoshihiro Uto : 血清糖タンパク質由来マクロファージ活性化剤の創製と免疫療法への応用, 日本農芸化学会2018年度大会, Mar. 2018.
56.	Yoshihiro Uto, Daisuke Miyamoto, Risa Kouzaki, Ayaka Hanyu, Mana Futawaka and Hisatsugu Yamada : 放射線増感作用の向上を目指したアセチルグルコース修飾Gefitinib誘導体の創製, 第20回癌治療増感研究シンポジウム, Feb. 2018.
57.	Yoshihiro Uto, Saki Ikame, Emi Kuwada, Ryohei Nishigawa, Hisatsugu Yamada, 大崎智弘, 久保健太郎 and 乾利夫 : 糖タンパク質由来マクロファージ活性化剤MAFの開発, 比較統合医療学会第60回大会, Dec. 2017.
58.	立松洋平, 川口遊喜, Atsushi Tabata, Yoshihiro Uto, 堀均 and 大倉一人 : 糖付加によるTX-1877系列化合物の機能制御:放射線増感能との相関解析, 第21回バイオ治療法研究会, Dec. 2017.
59.	Tomoko Kaneko, Risa Kouzaki, Ayaka Hanyu, Hisatsugu Yamada, Yoshihiro Uto, 壽賀正城, 山下智弘, 沖本智昭 and Masahide Tominaga : 5-アミノレブリン酸およびその代謝物であるプロトポルフィリンⅨの炭素線増感作用, 第21回バイオ治療法研究会, Dec. 2017.
60.	Yoshihiro Uto, Emi Kuwada, Saki Ikame, Ryohei Nishigawa, Yuka Izuchi, Makoto Endo, Hisatsugu Yamada, 田坂徹, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝 and 呉貴卿 : 低分子化ホエイプロテインのマクロファージ活性化能, 第21回バイオ治療法研究会, Dec. 2017.
61.	Yoshihiro Uto : 低酸素腫瘍細胞に対する平坦化フィルターフリービームの抗腫瘍活性における線量率効果, 第76回日本癌学会学術総会, Sep. 2017.
62.	Yoshihiro Uto : 元気で長生きするための自然免疫の活性化-血清MAFおよび初乳MAFの臨床研究, 第14回日本循環器看護学会学術集会, Sep. 2017.
63.	Yoshihiro Uto, Saki Ikame, Emi Kuwada, Ryohei Nishigawa, Hisatsugu Yamada, 大崎智弘, 久保健太郎 and 乾利夫 : 血清糖タンパク質由来マクロファージ活性化剤の創製と免疫療法への応用研究, 比較統合医療学会第59回大会, Jul. 2017.
64.	Yoshihiro Uto, Hanayo Katsura, Yuki Kusuhashi, Hisatsugu Yamada, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 中馬篤 and 山中信康 : 5-アミノレブリン酸と超音波の併用による抗腫瘍効果の評価と作用機序の解析, 第70回日本酸化ストレス学会学術集会, Jun. 2017.
65.	Yoshihiro Uto : ウシ初乳タンパク質を用いたマクロファージ作用剤の開発と自己免疫疾患に対する臨床応用, 日本農芸化学会中四国支部第48回講演会, Jun. 2017.
66.	Yoshihiro Uto, Takuma Suzuki, Hanayo Katsura, Yuki Kusuhashi, Hisatsugu Yamada, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 中馬篤 and 山中信康 : 5-アミノレブリン酸を用いた超音波と温熱の併用による抗腫瘍活性の評価, 第7回ポルフィリンALA学会年会, Apr. 2017.
67.	Teruaki Ito, Yoshihiro Uto, Mohammad Bin Effendi and Salleh Rizal Bin Mohd : TMAC Design Workshop 2016 によるアカデミックコラボレーション, 日本機械学会設計工学システム部門講演会2016・講演論文集, Vol.16, No.1402, 1-8, Oct. 2016. (Keyword) 大学間国際交流 / 教育研究交流 / 研究教育ユニット
68.	小倉瞬, 山本靖旺, Kenji Teranishi, Yoshihiro Uto and Naoyuki Shimomura : ナノ秒パルスパワーを用いたがん治療のIn vivoおよびEx vivo実験, 電気学会パルスパワー研究会資料, 43-47, Aug. 2016.
69.	Yoshihiro Uto, 遠藤秀彰, 八重和憲, Hisatsugu Yamada, 原毅弘 and Masahide Tominaga : TrueBeamを用いた低LET放射線の線量率と生物効果の相関について, 第18回癌治療増感研究シンポジウム, Feb. 2016.
70.	Yoshihiro Uto, 井亀沙紀, 九十九咲, 藤洸臣, 佐々木俊英, 濱田健, 桒田依洋, Hisatsugu Yamada, 西方敬人, 口池大輔, 久保健太郎, Mette Martin and 乾利夫 : ビオチン化GcMAFの作製とマクロファージGcMAF受容体の探索, 第19回バイオ治療法研究会, Dec. 2015.
71.	Masahide Tominaga, Hideaki Endo, Takahiro Hara and Yoshihiro Uto : 細胞を用いた低LET放射線の線量率と抗腫瘍効果の相関, 第11回中国四国放射線技術フォーラム, Nov. 2015.
72.	Yoshitaka Kurashiki, 北里慶子, Yoshiteru Tada, Kenji Yagi, Manabu Sumiyoshi, 宮本健志, Kazuyuki Kuwayama, Junichiro Satomi, Kenji Shimada, Tomoya Kinouchi, Yoshihiro Uto and Shinji Nagahiro : 脳虚血後後期におけるGcMAF投与はM2 macrophageを増加させ神経再生に寄与する, 一般社団法人日本脳神経外科学会第74回学術総会, Oct. 2015.
73.	Yoshihiro Uto, Yoshio Endo and Motowo Nakajima : Evaluation of the Sonosensitizing Activities of 5-Aminolevulinic Acid in Breast Tumor Chick Embryos and Mice Model., 第74回日本癌学会学術総会, Oct. 2015.
74.	Yoshitaka Kurashiki, 北里慶子, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Tomoya Kinouchi, Manabu Sumiyoshi, Takeshi Miyamoto, Kazuyuki Kuwayama, Junichiro Satomi, Shinji Nagahiro and Yoshihiro Uto : 脳虚血後後期におけるGroup-specific protein-derived macrophage activating factor (GcMAF)投与は，M2 macrophage, 第2回日本心血管脳卒中学会学術集会, Jun. 2015.
75.	Yoshihiro Uto, 玉谷大, 國安翔太, 水木佑輔, 鈴木拓磨, Hisatsugu Yamada, 遠藤良夫, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 中馬篤 and 山中信康 : 乳がん移植鶏卵およびマウスモデルを用いたALA+SDTの抗腫瘍作用の評価, 第5回ポルフィリンALA学会, Apr. 2015.
76.	Hisatsugu Yamada, 長谷川嘉則, 木村祐, 今井宏彦, 松田哲也, 杤尾豪人, 白川昌宏, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 and Yoshihiro Uto : 安定同位元素を集積した高分子ナノプローブによるがんの分子標的 MR イメージング, 第17回癌治療増感研究シンポジウム, Feb. 2015.
77.	松原修三, 中川晃登, 國安翔太, Kenji Teranishi, Naoyuki Shimomura and Yoshihiro Uto : ナノ秒パルス電界印加による鶏卵の死亡率の検討, 平成26年度電気関係学会四国支部連合大会講演論文集, 233, Sep. 2014.
78.	橋本惇平, Miyuki Oshimura, Tomohiro Hirano, Yoshihiro Uto and Koichi Ute : 立体規則性の規制されたポリ[N-(2-ヒドロキシプロピル)メタクリルアミド]の合成, 第60回高分子研究発表会(神戸), Jul. 2014.
79.	Yoshihiro Uto : 発育鶏卵を用いた次世代動物実験法の開発と制癌剤の創薬研究, 甲南大学FIRST/FIBER産学連携サロン=Part 8= 神戸市6月クラスター交流会・第46回甲南ニューフロンティアサロン, Jun. 2014.
80.	Saki Tsukumo, Yoshihiro Uto, 石山統子, Chiaki Matsui, 久保健太郎, Toshio Inui, Mette Martin and Hitoshi Hori : 血清中GcMAFのELISAによる測定法の検討, 日本薬学会第134年会, Mar. 2014.
81.	Dai Tamatani, Yoshihiro Uto, Yusuke Mizuki, Shota Kuniyasu, Chiho Noguchi, 遠藤良夫, 中西郁夫, 大久保敬, 石塚昌宏, 田中徹, Daisuke Kuchiike, 久保健太郎, Toshio Inui and Hitoshi Hori : 腫瘍移植鶏卵モデルを用いた5-Aminolevulinic acidおよびTin Chlorin e6の超音波増感活性の評価, 日本薬学会第134年会, Mar. 2014.
82.	Tomohito Kawai, Yoshihiro Uto, Toshihide Sasaki, Saki Tsukumo, Hiromi Fuji, 大谷美紀 and Hitoshi Hori : マクロファージ活性化因子GcMAFのサイトカイン産生に対する影響, 日本薬学会第134年会, Mar. 2014.
83.	Ikkyu Shiba, Yoshihiro Uto, 那住善治郎, Tada Ryu, 笠井亮平, Eiji Nakata, Hitoshi Hori and 慎一郎増永 : VeliparibをリードとしたPARP標的中性子捕捉療法剤UTX-89の分子設計, 日本薬学会第134年会, Mar. 2014.
84.	Chiaki Matsui, Yoshihiro Uto, 島千尋, 笠井亮平 and Hitoshi Hori : 4-nitroimidazole型類似体を用いた低酸素細胞放射線増感剤TX-2244の作用機序の解析, 日本薬学会第134年会, Mar. 2014.
85.	Masataka Oita, Yoshihiro Uto, Hitoshi Hori, Masahide Tominaga, Motoharu Sasaki and 岸太郎 : 細胞間放射線感受性の違いを考慮した治療計画技術応用に関する基礎的検討, 第16回癌治療増感研究シンポジウム, Feb. 2014.
86.	Yoshihiro Uto, Dai Tamatani, Yusuke Mizuki, 遠藤良夫, 大久保敬, 中西郁夫, 石塚昌宏, 田中徹, Daisuke Kuchiike, 久保健太郎, Toshio Inui and Hitoshi Hori : 超音波による癌治療に対する 5-aminolevulinic acidの増感作用の検討, 第16回癌治療増感研究シンポジウム, Feb. 2014.
87.	Hitoshi Hori, 多田竜, Yoshihiro Uto, Eiji Nakata, 森井孝 and 増田開 : 小型中性子発生機を用いたボロントレースドラッグUTX-51のNDT評価, 第17回バイオ治療法研究会学術集会, Dec. 2013.
88.	Tada Ryu, Yoshihiro Uto and Hitoshi Hori : AGEモデルである糖化BSA を標的とするボロントレースドラッグUTX-51のNDT評価, 第17回バイオ治療法研究会学術集会, Dec. 2013.
89.	Masataka Oita, Yoshihiro Uto, Hitoshi Hori, Masahide Tominaga, Motoharu Sasaki and 岸太郎 : 細胞間放射線感受性の違いを考慮した最適放射線治療計画法に関する検討, 第17回バイオ治療法研究会学術集会, Dec. 2013.
90.	Toshio Inui, 牧田香理, 三浦洋菜, Daisuke Kuchiike, 久保健太郎, Mette Martin, Yoshihiro Uto, Hitoshi Hori and 坂本憲広 : ソノダイナミック治療，GcMAFを併用した乳癌の1症例, 第17回バイオ治療法研究会学術集会, Dec. 2013.
91.	Yoshihiro Uto, Dai Tamatani, Yusuke Mizuki, 遠藤良夫, 大久保敬, 中西郁夫, 石塚昌宏, 田中徹, Daisuke Kuchiike, 久保健太郎, Toshio Inui and Hitoshi Hori : 発育鶏卵を用いた5-Aminolevulinic acidおよびTin Chlorin e6の薬物動態と超音波増感活性の評価, 第17回バイオ治療法研究会学術集会, Dec. 2013.
92.	Yoshihiro Uto, ryota Takeuchi, Yoshinori Nakagawa, Keiji Hirota, Hiroshi Terada, Shinya Onizuka, Kentaro Kubo, Daisuke Kuchiike, Mette Martin, Toshio Inui, Yoshio Endo and Hitoshi Hori : Development of Immunomodulatory Cancer Therapy Based on Gc protein-derived Macrophage Activating Factor (GcMAF), 7th International Symposium on Nanomedicine, Nov. 2013. (Keyword) cancer immunotherapy / GcMAF
93.	Yoshihiro Uto, Yoshio Endo, Hiroshi Sato and Hitoshi Hori : Development of antimetastatic hypoxic cytotoxin TX-2137 targeting for Akt/protein kinase B, 72th Annual Meeting of the Japanese Cancer Association, Oct. 2013. (Keyword) metastasis / Akt
94.	中川晃登, 永濱匡高, Kenji Teranishi, Yoshihiro Uto and Naoyuki Shimomura : 極短パルス電界の固形腫瘍への効果に関する研究, 平成25年度電気関係学会四国支部連合大会講演論文集, 241, Sep. 2013.
95.	原毅弘, Yoshihiro Uto, Ayaka Nakashima, Koushirou Fukushima, Chiho Noguchi, 遠藤良夫, Hiroshi Maezawa, Masahide Tominaga, 福本修一 and Hitoshi Hori : 発育鶏卵を用いたオオバギ葉抽出物の放射線防護活性の評価, 第19回癌治療増感研究会, Jun. 2013.
96.	Yoshihiro Uto, 玉谷大, 遠藤良夫, 石塚昌宏, 田中徹 and Hitoshi Hori : 発育鶏卵を用いた5-ALAの超音波増感による抗腫瘍活性の評価, 第3回ポルフィリン‐ALA学会年会, Apr. 2013.
97.	Yoshihiro Uto, 遠藤良夫, 久保健太郎, 乾利夫 and Hitoshi Hori : 発育鶏卵を工学的動物モデルとした制がん剤のメディシナルケミストリー, 日本化学会第93春季年会, Mar. 2013.
98.	Yoshihiro Uto : Design, synthesis and in ovo evaluation of prenylated antioxidants based on isoprenomics., International Free Radical Winter School 2013, Mar. 2013.
99.	Yoshihiro Uto, 皆巳和賢, 原田浩, 遠藤良夫, Hiroshi Maezawa, 慎一郎増永 and Hitoshi Hori : 解糖系からみた癌増感のターゲット:糖修飾放射線増感剤のメディシナルケミストリー, 第15回癌治療増感研究シンポジウム, Feb. 2013.
100.	Yoshihiro Uto : ヒト血清糖タンパク質の糖鎖修飾による免疫賦活剤の創製と臨床応用, 第8回香川大学工学部先端工学研究発表会, Feb. 2013.
101.	Yoshihiro Uto, 田中涼, 田中大地, 野口智帆 and Hitoshi Hori : FTY720をリードとした血管新生阻害性α-トコフェロール誘導体UTX-93の分子設計, 第24回ビタミンE研究会, Jan. 2013.
102.	Yoshihiro Uto, 遠藤良夫 and 佐藤博 : ヒトがん細胞を用いた抗転移性低酸素サイトトキシン類の開発, 平成24年度がん進展制御研究所共同利用・共同研究拠点研究成果報告会, Dec. 2012.
103.	Yoshihiro Uto, 向井大貴, 石山統子, 田中大地, 久保健太郎, 坂本憲広, 乾利夫 and Hitoshi Hori : GcMAF含有ヒト血清のマクロファージ貪食活性化能および抗腫瘍活性の評価, 第16回バイオ治療法研究会学術集会, Dec. 2012.
104.	永濱匡高, Naoyuki Shimomura, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : ナノ秒パルス電界の腫瘍への印加効果に関する研究, 平成24年度電気関係学会四国支部連合大会講演論文集, 43, Sep. 2012.
105.	Yoshihiro Uto and Hitoshi Hori : beta-Galactosidase treatment is common modification method of three major subtypes of Gc protein to GcMAF in vivo, 71th Annual Meeting of the Japanese Cancer Association, Sep. 2012.
106.	Yoshihiro Uto, 田中大地, 野口智帆, 原田浩, 遠藤良夫, Hiroshi Maezawa, 慎一郎増永 and Hitoshi Hori : HIF-1/GFP発現系を利用した腫瘍移植鶏卵における低酸素領域の解析と放射線による分布変化の観察, 第18回癌治療増感研究会, Jun. 2012.
107.	Yoshihiro Uto, 田中涼, 大仲健太 and Hitoshi Hori : イソプレノミクスを基盤としたプレニルアシルフロログルシノール類の合成と抗酸化活性の評価, 第65回日本酸化ストレス学会学術集会, Jun. 2012.
108.	Yoshihiro Uto : 血清Gc protein の糖鎖構造-マクロファージ活性相関解析と免疫賦活剤創生へのメディシナルケミストリー, 第3回グライコバイオロジクス研究会, Jun. 2012.
109.	Yoshihiro Uto : 天然物志向創薬のGREENING:イソプレノミクス創薬と発育鶏卵を用いた抗酸化活性評価系の構築, グリーンサイエンス講演会, May 2012.
110.	Yoshihiro Uto : 発育鶏卵を用いた放射線増感剤・血管新生阻害剤・抗酸化剤の創薬研究, NMR関連ミニシンポジウム∼最新研究動向∼, Apr. 2012.
111.	向井大貴, 石山統子, Yoshihiro Uto, 山本将太, 竹内亮太, 中川美典, 廣田慶司, Hiroshi Terada, 鬼塚伸也 and Hitoshi Hori : 1s1sおよび22型Gc proteinの脱ガラクトース体におけるマクロファージ活性化能の評価, 日本薬学会第132年会, Mar. 2012.
112.	田中涼, Yoshihiro Uto, 大仲健太, 矢崎一史, 梅基直行 and Hitoshi Hori : イソプレノミクスを基盤としたプレニル化アシルフロログルシノール類の合成と抗酸化活性の評価, 日本薬学会第132年会, Mar. 2012.
113.	田中大地, Yoshihiro Uto, 安部千秋, 遠藤良夫, Hiroshi Maezawa, 原田浩, 慎一郎増永 and Hitoshi Hori : 腫瘍移植鶏卵における低酸素腫瘍の同定とetanidazoleのin vivo放射線増感活性の評価, 日本薬学会第132年会, Mar. 2012.
114.	Yoshihiro Uto, 村井絵美, 寺岡瑞絵, Hiroshi Maezawa and Hitoshi Hori : アセチル化グルコースハイブリッド放射線増感剤TX-2244をリードとした6位修飾グルコース型放射線増感剤の分子設計, 第14回癌治療増感研究シンポジウム, Feb. 2012.
115.	Yoshihiro Uto, Ryo Tanaka, Kenta Onaka and Hitoshi Hori : イソプレノミクスによる7位メチルトコフェロールの合成とLDL抗酸化活性, 第23回ビタミンE研究会, Jan. 2012.
116.	Yoshihiro Uto : 発育鶏卵を用いた低酸素細胞放射線増感剤およびラジカル含有ナノ粒子のin vivo評価法の開発, バイオインダストリー協会大学発・選り抜きセミナー徳島大学研究者との集い・第3回東京編, Dec. 2011.
117.	Yoshihiro Uto, Chiaki Abe, Toru Yoshitomi, Yukio Nagasaki, Yoshio Endo and Hitoshi Hori : In Vivo Antioxidative Activity of O-TEMPO-RNP using Our Developed Chicken Egg Assay, 第21回日本MRS学術シンポジウム, Dec. 2011.
118.	Yoshihiro Uto, 山本将太, Hirotaka Mukai, Noriko Ishiyama, Ryota Takeuchi, 中川美典, 廣田慶司, Hiroshi Terada, 鬼塚伸也 and Hitoshi Hori : β-ガラクトシダーゼによる糖鎖修飾を受けた1s1sおよび22型Gcグロブリンのマクロファージ活性化能の評価, 第15回バイオ治療法研究会学術集会, Dec. 2011.
119.	Hiroshi Maezawa, 権藤賢悟, 松原隆敏, 美濃部遥, Yoshihiro Uto and Hitoshi Hori : 5フルオロウラシルの低酸素ヒト肺がん細胞X線致死増感効果, 日本放射線影響学会第54回大会, 120, Nov. 2011. (Keyword) radiation therapy / radiation / dose-survival curve / 放射線増感剤 / 低酸素
120.	Yoshihiro Uto : Development of an in vivo screening system for radiosensitizers and antioxidants using a chick embryo model, 4th Japan-Korea Joint Symposium on Bio-microsensing Technology, Oct. 2011.
121.	馬郡義弘, Naoyuki Shimomura, 影山達也, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : 超高速パルス電界の腫瘍への印加に関する研究, 第34回日本生体医工学中国四国支部大会講演抄録, 41, Oct. 2011.
122.	Yoshihiro Uto, Onizuka Shinya and Hitoshi Hori : Effect of the Macrophage Activating Factor Precursor (preGcMAF) on Phagocytic Activation of Mouse Peritoneal Macrophages, 70th Annual Meeting of the Japanese Cancer Association, Oct. 2011.
123.	Chiaki Abe, Yoshihiro Uto, Yoshio Endo, Hiroshi Maezawa, Shin-ichiro Masunaga and Hitoshi Hori : Evaluation of the In vivo Radiosensitizing Activity of Etanidazole Using Tumor-bearing Chick Embryo, 70th Annual Meeting of the Japanese Cancer Association, Oct. 2011.
124.	Yoshihiro Uto, 安部千秋, 川崎彩加, 吉冨徹, 長崎幸夫, 遠藤良夫 and Hitoshi Hori : 酸化ストレス発育鶏卵モデルを用いたラジカル含有ナノ粒子TEMPO-RNPのin vivo抗酸化活性評価, 第64回日本酸化ストレス学会学術集会, Jul. 2011.
125.	Yoshihiro Uto, 小泉允人, 山下洋平, 大仲健太, Eiji Nakata and Hitoshi Hori : ボロントレースドラッグを指向したBODIPY含有フェノールの抗酸化剤分子設計, 第17回癌治療増感研究会, Jun. 2011.
126.	関場一裕, 辻美恵子, 平山祐, 奥田健介, Yoshihiro Uto, Hitoshi Hori and Hideko Nagasawa : 多機能性糖タンパク質Gc proteinの質量分析を通した糖ペプチド構造解析法の開発, 日本薬学会第131年会, Mar. 2011.
127.	金森小百合, Yoshihiro Uto, 太田依里 and Hitoshi Hori : GalNAc-リジンクラスターのマクロファージ細胞NR8383による貪食活性評価, 日本薬学会第131年会, Mar. 2011.
128.	大仲健太, Yoshihiro Uto, 田中涼, 矢崎一史, 梅基直行 and Hitoshi Hori : ホップに含まれるプレニル化アシルフロロアシルグルシノール誘導体のLDL抗酸化活性とイソプレノミクスに基づく評価, 日本薬学会第131年会, Mar. 2011.
129.	Mizue Teraoka, Yoshihiro Uto, Eigo Uehata, Chizuru Sasaki, Yoshitoshi Nakamura and Hitoshi Hori : MTT法によるスギ水蒸気爆砕抽出物の抗腫瘍活性の評価, 日本薬学会第131年会, Mar. 2011.
130.	山本将太, Yoshihiro Uto, 竹内亮太, 中川美典, 廣田慶司, Hiroshi Terada, 鬼塚伸也 and Hitoshi Hori : 二糖鎖Gcタンパク質(GcX)の調製とマクロファージ活性化能評価, 日本薬学会第131年会, Mar. 2011.
131.	河井芳彦, 池田篤志, 秋山元英, 菊池純一, Eiji Nakata, Yoshihiro Uto and Hitoshi Hori : リポソームへのフラーレン交換反応のπ分子による制御, 日本化学会第91春季年会, Mar. 2011.
132.	Eiji Nakata, 行待芳浩, Yoshijiro Nazumi, Ayumi Tomotsuka, Yoshihiro Uto and Hitoshi Hori : SNARFを基本骨格とした蛍光プローブの設計戦略, 日本化学会第91春季年会, Mar. 2011.
133.	Yoshihiro Magoori, Seiji Ota, Kenji Teranishi, Naoyuki Shimomura, Yoshihiro Uto and Hitoshi Hori : 固形腫瘍に対するナノ秒パルスパワー印加効果に関する研究, 平成23年電気学会全国大会講演論文集, Vol.1, 237, Mar. 2011.
134.	Hitoshi Hori, Eiji Nakata, 小泉允人, Yoshihiro Uto and Kazuto Ohkura : ダイナミックドラッグ創生へのアプローチ - ボロントレースドラッグ仕様BODIPY含有抗酸化物質のメディシナルケミストリー, 第14回バイオ治療法研究会学術集会, Dec. 2010.
135.	Yoshihiro Uto, 山本将太, 竹内亮太, 中川美典, 廣田慶司, Hiroshi Terada, 鬼塚伸也, Eiji Nakata and Hitoshi Hori : 癌免疫療法の確立を目指したマクロファージ活性化因子(GcMAF)前駆物質GcXの創製, 第14回バイオ治療法研究会学術集会, Dec. 2010.
136.	小畑勝稔, Eiji Nakata, Yoshihiro Uto and Hitoshi Hori : メディシナル・エレクトロノミクス分子としてのオリゴアセチレニック芳香族化合物の疎水性, 第38回構造活性相関シンポジウム, Oct. 2010.
137.	馬郡義弘, 大田誠二, Kenji Teranishi, Naoyuki Shimomura, Yoshihiro Uto and Hitoshi Hori : ナノ秒パルス電界の固形腫瘍に対する印加効果に関する研究, 平成22年度電気関係学会四国支部連合大会講演論文集, 187, Sep. 2010.
138.	Eiji Nakata, 那住善治郎, 行待芳浩, Yoshihiro Uto and Hitoshi Hori : SNARF を基本骨格とした蛍光プローブの合理的設計戦略, 第4回バイオ関連化学シンポジウム, Sep. 2010.
139.	Eiji Nakata, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : Development of fluorescent pH probe for measuring intracellular pH of tumor hypoxic cells, 第69回日本癌学会学術総会, Sep. 2010.
140.	Hitoshi Hori, Eiji Nakata and Yoshihiro Uto : Design of boron tracedrug phenolic BODIPY-containing antioxidants as autopsy/virtopsy imaging agents, 第69回日本癌学会学術総会, Sep. 2010.
141.	Yoshihiro Uto, Chiaki Abe, Eiji Nakata and Hitoshi Hori : SAR analysis of electron-rich polyyne analogues of FTY720 based on in vivo chick embryo antiangiogenic assay, 第69回日本癌学会学術総会, Sep. 2010.
142.	那住善治郎, Eiji Nakata, 行待芳浩, Yoshihiro Uto and Hitoshi Hori : 蛍光プローブの合理的設計を目指したSNARF誘導体の自己集合化能についての検討, 第22回生体機能関連化学若手の会サマースクール, Jul. 2010.
143.	Yoshihiro Uto, 安部千秋, 吉冨徹, 長崎幸夫, 遠藤良夫, Eiji Nakata and Hitoshi Hori : 酸化ストレス発育鶏卵モデルを用いたラジカル含有ナノ粒子TEMPO-RNPのin vivo抗酸化活性評価, 第63回日本酸化ストレス学会, Jun. 2010.
144.	Yoshihiro Uto, 安部千秋, 中江崇, 村井絵美, 遠藤良夫, Masahide Tominaga, Hiroshi Maezawa, 慎一郎増永, Eiji Nakata and Hitoshi Hori : 腫瘍移植鶏卵モデルによる糖ハイブリッド放射線増感剤のin vivo放射線増感活性の評価, 第16回国際癌治療増感研究会, Jun. 2010.
145.	Eiji Nakata, Yoshihiro Yukimachi, Yoshijiro Nazumi, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : 外部刺激応答型蛍光プローブの開発と低酸素細胞の選択的可視化への応用, 第16 回国際癌治療増感研究会, Jun. 2010.
146.	Eiji Nakata, 行待芳浩, 那住善治郎, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : Newly designed cell-permeable SNARF derivative as an effective intracellular pH indicator, 日本ケミカルバイオロジー学会第5回年会, May 2010.
147.	太田依里, Yoshihiro Uto, Eiji Nakata, 柴田明奈, 辻祐亮, 山本将太 and Hitoshi Hori : Design of small molecular GcMAF: GalNAc-lysine derivatives as macrophage activate agents., 日本薬学会第130年会, Mar. 2010.
148.	小泉允人, Eiji Nakata, Yoshihiro Uto, 山下洋平, 大仲健太, 行待芳浩, 中嶌瞳 and Hitoshi Hori : Boron TraceDrug : Synthesis and biological activity of BODIPY containing SF6847(AG17) analogue, 日本薬学会第130年会, Mar. 2010.
149.	小畑勝稔, Yoshihiro Uto, Eiji Nakata, 新元優也, 中山真一, 百瀬郁理, 藤多哲朗 and Hitoshi Hori : Design and antiangiogenic activity of UTX-32 as an acetylenic analogue of FTY720, 日本薬学会第130年会, Mar. 2010.
150.	田中涼, Yoshihiro Uto, Eiji Nakata, 白井斉, 山下洋平 and Hitoshi Hori : Design, synthesis, and antioxidant activity of natural and unnatural phytyl quinols based on isoprenomics, 日本薬学会第130年会, Mar. 2010.
151.	行待芳浩, Eiji Nakata, Yoshihiro Uto, 那住善治郎, Hiroshi Maezawa and Hitoshi Hori : Newly designed SNARF derivative as the intracellular pH indicator, 日本薬学会第130年会, Mar. 2010.
152.	Eiji Nakata, 行待芳浩, 那住善治郎, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : 細胞内pH計測に適した新規SNARF誘導体の設計とその機能評価, 日本化学会第90春季年会, Mar. 2010.
153.	Yoshihiro Uto : 抗酸化剤と酸化ストレスの新しい評価法, 第7回学際物質戦略イニシアチブバイオGPワークショップ, Mar. 2010. (Keyword) Antioxidant / Oxidative stress / Developing chick embryo / Isoprenomics
154.	Yoshihiro Uto : 有機化学におけるu-Learningを利用した学習効果について, 平成21 年度全学FD 大学教育カンファレンス in 徳島, Mar. 2010. (Keyword) organic chemistry / u-Learning
155.	Yoshihiro Uto, Yohei Yamashita, Ryo Tanaka, Eiji Nakata and Hitoshi Hori : システムバイオロジー構築のためのフィチルキノールの合成と抗酸化活性評価, 第21回ビタミンE研究会, Jan. 2010. (Keyword) Systems biology / Phytyl quinol / Antioxidant / Vitamin E
156.	Eiji Nakata, 行待芳浩, 那住善治郎, Hiroshi Maezawa, Yoshihiro Uto and Hitoshi Hori : 細胞内pH計測により適合した新規SNARF誘導体の設計, 第12回生命化学研究会, Jan. 2010.
157.	Takashi Nakae, Yoshihiro Uto, Chiaki Abe, Takeyuki Kanazono, Yuuya Shinmoto, Keiichiro Sano, Eiji Nakata, Yoshio Endo, Masahide Tominaga, Hiroshi Maezawa, Toshihiro Hashimoto, 慎一郎増永 and Hitoshi Hori : 鶏胚異種移植腫瘍モデルを基盤とした糖ハイブリッド低酸素細胞放射線増感剤の創製, 創薬懇話会2009, Dec. 2009. (Keyword) 鶏胚異種移植腫瘍モデル / 糖ハイブリッド低酸素細胞放射線増感剤
158.	Ryota Takeuchi, Yoshinori Nakagawa, Yoshihiro Uto and Hitoshi Hori : 水酸化カルシウムの後ろ向き研究による骨密度改善に関するAM値の有用性, 第13回バイオ治療法研究会・学術集会, Dec. 2009. (Keyword) 水酸化カルシウム / 骨密度 / AM値 / タチカワ電解カルシウム
159.	Eiji Nakata, Yukimachi Yoshihiro, Nazumi Yoshijiro, Abe Chiaki, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : Bioreductively-Activated Fluorescent pH Probe for Tumor Hypoxia Imaging, 第7回がんとハイポキシア研究会, Dec. 2009.
160.	Hitoshi Hori, Yoshihiro Uto and Eiji Nakata : インドールアミン2,3-ジオキシゲナーゼ(IDO)阻害剤のハイポキシアドラッグ・デザインブリゴラージュ, 第28回メディシナルケミストリーシンポジウム, Nov. 2009. (Keyword) ハイポキシアドラッグ / デザインブリゴラージュ / IDO阻害剤
161.	Eiji Nakata, Yoshihiro Uto and Hitoshi Hori : 合理的にデザインされた蛍光プローブの開発, 分子化学研究会, Oct. 2009.
162.	Yoshihiro Uto, Chiaki Abe, Yoshio Endo, Hiroshi Maezawa, Eiji Nakata and Hitoshi Hori : Pharmacokinetic drug design of sugar-hybrid radiosensitizers using the tumor implant chick embryo model, 第68回日本癌学会学術総会, Oct. 2009. (Keyword) Pharmacokinetics / Radiosensitivity
163.	大田誠二, 城山和己, 中川亮佑, Kenji Teranishi, Naoyuki Shimomura, Yoshihiro Uto and Hitoshi Hori : 固形腫瘍に対するナノ秒パルス電界印加実験, 平成21年度電気関係学会四国支部連合大会講演論文集, 242, Sep. 2009.
164.	行待芳浩, Eiji Nakata, 那住善治郎, Hiroshi Maezawa, Yoshihiro Uto and Hitoshi Hori : 効果的な細胞内pHの計測を目指した改良型SNARFの設計とその評価, 第24回生体機能関連化学若手フォーラム, Sep. 2009.
165.	行待芳浩, Eiji Nakata, 那住善治郎, Yoshihiro Uto and Hitoshi Hori : 細胞内pHの計測を志向した改良型SNARFの設計とその評価, 第24回生体機能関連化学シンポジウム第12回バイオテクノロジーシンポジウム, Sep. 2009.
166.	Eiji Nakata, 行待芳浩, 安部千秋, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : がん低酸素環境を標的とした蛍光性pHプローブの開発, 第24回生体機能関連化学シンポジウム第12回バイオテクノロジーシンポジウム, Sep. 2009.
167.	Yoshihiro Uto : 若手研究の申請について∼主観的な意見として∼, 科学研究費補助金採択率上昇のための説明会, Sep. 2009. (Keyword) 科学研究費補助金 / 若手研究
168.	Eiji Nakata, 行待芳浩, 安部千秋, Yoshihiro Uto, Hiroshi Maezawa and Hitoshi Hori : 癌低酸素環境で選択的に機能する蛍光性pHプローブの開発, 生体機能関連若手の会サマースクール2009, Jul. 2009.
169.	Hitoshi Hori, Yoshihiro Uto and Eiji Nakata : メディシナル・ブリゴラージュ:ハイポキシアを標的とした制がん剤の分子設計, 第39 回放射線による制癌シンポジウム, Jul. 2009.
170.	金世洸, 前濱慶祐, 鈴木諭, Yoshihiro Uto, Eiji Nakata, Hitoshi Hori and Hiroshi Maezawa : ピリミジン系核酸誘導体のチャイニーズハムスターV79細胞に対する放射線増感効果, 第48回日本医学放射線学会生物部会学術大会, Jul. 2009.
171.	Yoshihiro Uto, 中江崇, 安部千秋, 新元優也, 佐野圭一郎, 遠藤良夫, Masahide Tominaga, Hiroshi Maezawa, Eiji Nakata and Hitoshi Hori : 腫瘍移植鶏卵モデルによる糖ハイブリッド放射線増感剤の薬物動態解析, 第15回国際癌治療増感研究会, Jun. 2009.
172.	Yoshihiro Uto, Chiaki Abe, Yohei Yamashita, Ryo Tanaka, Yoshio Endo, Eiji Nakata and Hitoshi Hori : イソプレノミクスを基盤としたプレニル化フェニルプロパノイドの分子設計と発育鶏卵を用いたin ovo抗酸化活性の評価, 第62回日本酸化ストレス学会学術集会, Jun. 2009. (Keyword) Isoprenomics / Developing chick embryo / Antioxidant
173.	Eiji Nakata, 行待芳浩, 假屋園大和, 任仙光, Yoshihiro Uto and Hitoshi Hori : 癌の低酸素環境を標的とした蛍光プローブの開発, 日本化学会第89春季年会, Mar. 2009.
174.	三原法秀, 林慧, 岡部泰之, 上田聡, 奥田健介, Yoshihiro Uto, Hitoshi Hori and Hideko Nagasawa : 交差共役ケトン骨格を有する抗腫瘍性血管新生阻害剤の構造活性相関, 日本薬学会第129年会, Mar. 2009.
175.	佐野圭一郎, Yoshihiro Uto, 中島宏一郎, Eiji Nakata, 山本五郎 and Hitoshi Hori : 温熱療法;Radio FrequencyとThermal Hyperthermia の抗がん効果, 日本薬学会第129年会, Mar. 2009.
176.	新元優也, Yoshihiro Uto, 遠藤良夫, 安部千秋, 中島宏一郎, 佐野圭一郎, 佐々木有紀, 皆巳和賢, Hiroshi Maezawa, 慎一郎増永, Eiji Nakata and Hitoshi Hori : 腫瘍移植鶏卵を用いた in ovo 放射線増感活性評価系の確立, 日本薬学会第129年会, Mar. 2009.
177.	安部千秋, Yoshihiro Uto, 遠藤良夫, Eiji Nakata and Hitoshi Hori : 鶏卵胚を用いた静脈投与による致死率を指標としたin vivo抗酸化活性評価法の構築, 日本薬学会第129年会, Mar. 2009.
178.	辻祐亮, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, 河野悠介, 藤田秀司, 千葉一裕 and Hitoshi Hori : マクロファージ活性化に関わるGalNAcの結合様式, 日本薬学会第129年会, Mar. 2009.
179.	山下洋平, Yoshihiro Uto, 大津木護, 白井斉, Eiji Nakata and Hitoshi Hori : プレニル化3,4-ジヒドロキシケイ皮酸(カフェ酸)誘導体のLDL抗酸化活性, 日本薬学会第129年会, Mar. 2009.
180.	金園剛行, Yoshihiro Uto, 中江崇, 柴田明奈, 中島宏一郎, 佐野圭一郎, Masahide Tominaga, Hiroshi Maezawa, Eiji Nakata and Hitoshi Hori : メチル化グルコース・糖ハイブリッド低酸素細胞放射線増感剤の分子設計, 日本薬学会第129年会, Mar. 2009.
181.	中江崇, Yoshihiro Uto, 安部千秋, 新元優也, 金園剛行, 中島宏一郎, 佐野圭一郎, Masahide Tominaga, Hiroshi Maezawa, 慎一郎増永, 遠藤良夫, Eiji Nakata and Hitoshi Hori : 腫瘍移植鶏卵モデルによる糖ハイブリッド低酸素細胞放射線増感剤TX-2244の腫瘍移行性, 日本薬学会第129年会, Mar. 2009.
182.	中西郁夫, Yoshihiro Uto, 大久保敬, 川島知憲, 松本謙一郎, MANDA Sushma, Hitoshi Hori, 福原潔, 奥田晴宏, 伊古田暢夫, 小澤俊彦 and 安西和紀 : ブラジル産プロポリスに含まれるフェノール性抗酸化物質およびその誘導体のラジカル消去機構, 日本薬学会第129年会, Mar. 2009.
183.	Kazuki Shiroyama, Taiki Yano, Kenji Teranishi, Naoyuki Shimomura, Yoshihiro Uto and Hitoshi Hori : 腫瘍へのナノ秒パルスパワー印加インビボ実験, 平成21年電気学会全国大会講演論文集, 219, Mar. 2009.
184.	Yoshihiro Uto, 安部千秋, 新元優也, 中江崇, 中島宏一郎, 佐野圭一郎, 遠藤良夫, 皆巳和賢, Hiroshi Maezawa, 慎一郎増永, Eiji Nakata and Hitoshi Hori : 腫瘍移植鶏卵を用いた in ovo 放射線増感活性評価系の確立, 第11回癌治療増感研究シンポジウム, Feb. 2009.
185.	Hitoshi Hori, Yoshihiro Uto, Hideko Nagasawa, 島村真里子, 稲山誠一 and 上原至雅 : 2-アミノメチレン-4-シクロペンテン-1，3-ジオン構造を有する抗血管新生低酸素細胞放射線増感剤の創製, 第67回日本癌学会学術総会, Oct. 2008.
186.	Yoshihiro Uto, 遠藤良夫, Hiroshi Maezawa, Hideko Nagasawa and Hitoshi Hori : 腫瘍移植鶏卵を用いたin vivo放射線増感活性評価モデルの開発, 第67回日本癌学会学術総会, Oct. 2008.
187.	城山和己, 矢野大輝, Kenji Teranishi, Naoyuki Shimomura, Yoshihiro Uto and Hitoshi Hori : ナノ秒パルスパワーの腫瘍へのインビボ印加実験, Journal of Shikoku-Section Joint Convention of the Institutes of Electrical and Related Engineers, 25, Sep. 2008.
188.	Naoyuki Shimomura, 矢野大輝, 山中卓, 城山和己, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : 固形腫瘍に対するナノ秒パルス電界印加実験, 平成20年電気学会基礎・材料・共通部門大会講演論文集, 227, Aug. 2008.
189.	皆巳和賢, Yoshihiro Uto, 中江崇, Eiji Nakata, Hideko Nagasawa, Hitoshi Hori and Hiroshi Maezawa : 低酸素細胞に対するニトロイミダゾールアセトアミド誘導体の放射線増感効果, 第47回日本医学放射線学会生物部会学術大会, Jun. 2008.
190.	Yoshihiro Uto, 大津木護, 白井斉, 山下洋平, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : イソプレノミクスを基盤とするプレニル化3,4-ジヒドロキシケイ皮酸誘導体の分子設計とLDL抗酸化活性, 第61回日本酸化ストレス学会学術集会, Jun. 2008.
191.	Yoshihiro Uto, 中江崇, 佐々木有紀, 安部千秋, 中島宏一郎, 新元優也, 佐野圭一郎, 遠藤良夫, 皆巳和賢, Hiroshi Maezawa, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : 次世代動物実験系としての腫瘍移植鶏卵の構築と放射線照射による腫瘍成長阻害活性, 第14回癌治療増感研究会, Jun. 2008.
192.	Eiji Nakata, Gautier Arnaud, Yoshihiro Uto, Hitoshi Hori and Johnsson Kai : 直交性を有する蛋白質標識システムを利用した細胞内蛋白質間相互作用の検出, 日本化学会第88春季年会, Mar. 2008.
193.	岩木孝晴, 稲田俊行, 榎本幸浩, 小林拓, 須藤智美, 上田聡, Yoshihiro Uto, Hitoshi Hori and Hideko Nagasawa : 血管新生阻害及び転移抑制作用をめざすhypoxic cytotoxinの分子設計, 日本薬学会第128年会, Mar. 2008.
194.	安部千秋, 佐々木有紀, Yoshihiro Uto, 遠藤良夫, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : 鶏卵胚を用いた酸化的血管障害に対するin vivo抗酸化活性評価法の構築, 日本薬学会第128年会, Mar. 2008.
195.	百瀬郁理, 中山真一, 佐々木有紀, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa, 谷本加奈子, 藤多哲朗 and Hitoshi Hori : 新規血管新生阻害剤の開発を目指したFTY720アセチレニックアナログの分子設計, 日本薬学会第128年会, Mar. 2008.
196.	一久和弘, 中嶌瞳, Yoshihiro Uto, Hideko Nagasawa, Eiji Nakata, 杉本弘, 城宜嗣 and Hitoshi Hori : 低酸素腫瘍を標的としたTirapazamineハイブリッド型新規IDO阻害剤の分子設計, 日本薬学会第128年会, Mar. 2008.
197.	中島宏一郎, 中江崇, 柴田明奈, 田中智子, Yoshihiro Uto, Masahide Tominaga, Hiroshi Maezawa, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : がんによるグルコースの高い取り込みを利用した糖ハイブリッド低酸素細胞放射線増感剤の分子設計, 日本薬学会第128年会, Mar. 2008.
198.	白井斉, Yoshihiro Uto, 大津木護, 大友直紀, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : イソプレノミクスを基盤としたトコフェロール生合成前駆体フィチル化キノールのLDL抗酸化剤分子設計, 日本薬学会第128年会, Mar. 2008.
199.	柴田明奈, 中江崇, 滝口公康, Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : マクロファージ活性化因子GcMAFの糖鎖構造部位をミミックしたGalNAc-Thrデンドリマーの分子設計, 日本薬学会第128年会, Mar. 2008.
200.	皆巳和賢, Yoshihiro Uto, 中江崇, Eiji Nakata, Hideko Nagasawa, Hitoshi Hori and Hiroshi Maezawa : ニトロイミダゾールアセトアミド誘導体による低酸素放射線増感効果, 第10回癌治療増感研究シンポジウム, Feb. 2008.
201.	木村禎亮, 河村泰男, 上田聡, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and 慎一郎増永 : インテグリンを標的とする新規ボロンキャリアの分子設計, 第10回癌治療増感研究シンポジウム, Feb. 2008.
202.	Eiji Nakata, Gautier Arnaud, Yoshihiro Uto, Hitoshi Hori and Johnsson Kai : 直交性を有する蛋白質標識システムによる蛋白質間相互作用の解析, 第10回生命化学研究会シンポジウム, Jan. 2008.
203.	滝口公康, 荒井健, 辻祐亮, Hideko Nagasawa, Yoshihiro Uto, Eiji Nakata, 鬼塚伸也, 野中孝一, 藤岡ひかる and Hitoshi Hori : マクロファージ活性化に関わるGc proteinの糖ペプチド構造解析, 第11回バイオ治療法研究会学術集会, Dec. 2007.
204.	Yoshihiro Uto : イソプレノミクスを基盤とした抗酸化剤の分子設計, 日本農芸化学会中部支部第151回例会若手シンポジウム, Nov. 2007. (Summary) 微生物，植物や動物が産生するテルペン，ステロイドやカロテンなどのイソプレノイド系化合物は，メバロン酸もしくは非メバロン酸経路により合成される炭素5個(C5)を基本単位とするイソプレン骨格を有する化合物の総称であり生理活性物質として重要なものが数多く同定されている．一方，フェニルプロパノイドやフラボノイドにおいては，シキミ酸経路による骨格合成後位置選択的にイソプレン鎖の修飾を受けた化合物の存在が報告されているが，それらの生理活性や存在理由についてはほとんど明らかになっていない．そこで私は，イソプレノミクス(isoprenomics，微生物，植物や動物が産生するイソプレン鎖修飾化合物を探索して生物活性を調べ，合成に関わるDNAやタンパクを同定してchemotypeを明らかにし，医薬品開発に応用する研究)を提唱し，この問題の解明に取り組んでいる．本シンポジウムでは，アルテピリンC及びトコフェロール(ビタミンE)に対するイソプレノミクスから得られた抗酸化剤分子設計に関する知見について報告する．
205.	三宅講太朗, Masanori Nishioka, 杉本光司, 宮谷知彦, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori and Mitsuo Shimada : 直腸癌に対する低酸素細胞放射線増感剤TX-1877の放射線増感作用と抗腫瘍効果に関する基礎的研究, 第66回日本癌学会学術総会, Oct. 2007.
206.	Yoshihiro Uto, Hitoshi Hori and Hideko Nagasawa : 解糖系基質と低酸素細胞放射線増感剤のハイブリッド分子設計, 第66回日本癌学会学術総会, Oct. 2007.
207.	Hitoshi Hori, Yoshihiro Uto and Hideko Nagasawa : 血管新生阻害活性をもつアセチレン型FTY720アナローグTX-2152の設計, 第66回日本癌学会学術総会, Oct. 2007.
208.	Hideko Nagasawa, 林慧, 岡部泰之, 上田聡, Hitoshi Hori and Yoshihiro Uto : 交差共役系マイケル受容体構造を有する新規血管新生阻害剤の構造活性相関, 第66回日本癌学会学術総会, Oct. 2007.
209.	慎一郎増永, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori, 永田憲司, 鈴木実, 菓子野元郎, 木梨友子 and 小野公二 : 低減線量率γ線照射において低温度温熱処置とTirapazamine連続的投与を併用する有用性についての検討, 第46回日本医学放射線学会生物部会学術大会, Jul. 2007.
210.	Yoshihiro Uto, 大津木護, 大友直紀, 白井斉, 安部千秋, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : イソプレノミクスを基盤とするハイドロプレニルp-クマリン酸誘導体の分子設計とLDL抗酸化活性, 第29回日本フリーラジカル学会学術集会・日本過酸化脂質・フリーラジカル学会第31回大会合同学会, Jun. 2007.
211.	Hideko Nagasawa, 須藤智美, 岡部泰之, 林慧, 稲田俊行, 上田聡, Yoshihiro Uto and Hitoshi Hori : 交差共役系マイケル受容体構造を有する新規血管新生阻害剤の分子設計, 第13回癌治療増感研究会, May 2007.
212.	Yoshihiro Uto, Masahide Tominaga, Takashi Nakae, Motoko Tanaka, Aya Murakami, Yuki Sasaki, Haruna Shibata, Kouichiro Nakashima, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori : 低酸素がん選択的ハイブリッド型放射線増感剤の創製, 第13回癌治療増感研究会, May 2007.
213.	中西郁夫, Yoshihiro Uto, 大久保敬, 川島知憲, マンダスシュマ, 金澤秀子, Hideko Nagasawa, Hitoshi Hori, 奥田晴宏, 福原潔, 小澤俊彦, 福住俊一, 伊古田暢夫 and 安西和紀 : 抗酸化作用の増強を目的としたアルテピリンC誘導体の開発, 第127年会日本薬学会, Mar. 2007.
214.	Hideko Nagasawa, 田中彩子, 稲田俊行, 佐々木有紀, 中嶌瞳, 岩木孝晴, Yoshihiro Uto and Hitoshi Hori : 低酸素シグナルを標的とする癌治療薬の分子設計と低酸素転写活性化スクリーニング, 第127年会日本薬学会, Mar. 2007.
215.	佐々木有紀, Yoshihiro Uto, 田中彩子, 谷本加奈子, Hideko Nagasawa, 藤多哲朗 and Hitoshi Hori : 新規FTY720アナログのCAM法による血管新生阻害活性, 第127年会日本薬学会, Mar. 2007.
216.	荒井健, Yoshihiro Uto, 岡村菜摘子, 滝口公康, 村上綾, Hideko Nagasawa and Hitoshi Hori : Non-secosteroidal Vitamin D mimicを用いたGc-Proteinのアフィニティーカラムの作成, 第127年会日本薬学会, Mar. 2007.
217.	大津木護, Yoshihiro Uto, 小山大輔, 大友直紀, Hideko Nagasawa and Hitoshi Hori : アルテピリンCイソプレノミクスを基盤としたハイドロプレニルクマリン酸の分子設計とLDL抗酸化活性, 第127年会日本薬学会, Mar. 2007.
218.	Hideko Nagasawa, 田中彩子, 稲田俊行, 佐々木有紀, 中嶌瞳, 岩木孝晴, Yoshihiro Uto and Hitoshi Hori : 低酸素シグナルを標的とする癌治療薬のための低酸素転写活性化スクリーニングシステム, 第9回癌治療増感研究シンポジウム, Feb. 2007.
219.	田中智子, Yoshihiro Uto, Masahide Tominaga, 中江崇, 村上綾, Hideko Nagasawa and Hitoshi Hori : 低酸素腫瘍移行性糖ハイブリッド放射線増感剤の創製, 第9回癌治療増感研究シンポジウム, Feb. 2007.
220.	Yoshihiro Uto, 小山大輔, 大津木護, 大友直紀, 白井斉, Hitoshi Hori and Hideko Nagasawa : トコフェロールの生合成前駆体フィチル化キノールのイソプレノミクス的考察, 第18回ビタミンE研究会, Jan. 2007.
221.	大倉一人, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : 血管新生の制御を目指して:抗血管新生作用を有するchiral haloacetyl-carbamoyl-1-2-nitroimidazoleの構造解析, 第10回バイオ治療法研究会学術集会, Dec. 2006.
222.	滝口公康, Yoshihiro Uto, 岡村菜摘子, 村上綾, Hideko Nagasawa, 鬼塚伸也, 野中孝一, 藤岡ひかる and Hitoshi Hori : 多機能性糖タンパク質Gc protein及びその糖ペプチドの構造解析, 第10回バイオ治療法研究会学術集会, Dec. 2006.
223.	稲田俊行, 田中彩子, 佐々木有紀, 中嶌瞳, Yoshihiro Uto, Hitoshi Hori, 岩木孝晴 and Hideko Nagasawa : HIF-1{alpha}抑制作用及び血管新生阻害作用を有する新規hypoxic cytotoxinの分子設計, 第4回がんとハイポキシア研究会, Nov. 2006.
224.	Yoshihiro Uto, 大友直紀, 小山大輔, 大津木護 and Hitoshi Hori : イソプレノミクスを基盤とするプレニル化フェルラ酸の分子設計とLDL抗酸化活性, 日本過酸化脂質・フリーラジカル学会第30回大会, Oct. 2006.
225.	Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : マクロファージ活性化能を有する糖ハイブリッド低酸素細胞放射線増感剤の創製, 第65回日本癌学会学術総会, Sep. 2006.
226.	Hitoshi Hori, Hideko Nagasawa and Yoshihiro Uto : 低分子性血管新生阻害剤2-メチレン-4-シクロペンテン-1,3-ジオン化合物の創製, 第65回日本癌学会学術総会, Sep. 2006.
227.	越川信子, Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto and 竹永啓三 : ヒト乳癌細胞株における転移抑制遺伝子nm23-H1発現の低酸素による抑制, 第65回日本癌学会学術総会, Sep. 2006.
228.	三宅講太朗, 西岡将規, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and Mitsuo Shimada : 膵臓癌に対する低酸素細胞放射線増感剤TX-1877誘導体の放射線増感作用と抗腫瘍効果に関する基礎的研究, 第65回日本癌学会学術総会, Sep. 2006.
229.	中江崇, Yoshihiro Uto, 村上綾, 田中彩子, Hitoshi Hori and Hideko Nagasawa : 細胞表面を構成するsugar scaffoldに基づくハイブリッド型低酸素細胞放射線増感剤の創製, 第4回次世代を担う有機化学シンポジウム, May 2006.
230.	Hideko Nagasawa, 稲田俊行, 田中彩子, 佐々木有紀, 中嶌瞳, Yoshihiro Uto, Hitoshi Hori and 松本英樹 : 新規hypoxic cytotoxinの分子設計及び生物活性, 第12回癌治療増感研究会, May 2006.
231.	川島知憲, 中西郁夫, Yoshihiro Uto, 大久保敬, 鈴木桂子, 川口久美子, 金澤秀子, 福原潔, 奥田晴宏, Hideko Nagasawa, Hitoshi Hori, 福住俊一, 小澤俊彦 and 伊古田暢夫 : 4-プロペニルフェノール構造を有する抗酸化物質のラジカル消去活性の評価, 第126年会日本薬学会, Mar. 2006.
232.	Yoshihiro Uto, 阿江周太郎, 小山大輔, Hideko Nagasawa and Hitoshi Hori : アルテピリンCイソプレノミクス:抗動脈硬化剤の創製を目指したアルテピリンCイソプレン誘導体の分子設計, 第126年会日本薬学会, Mar. 2006.
233.	田中彩子, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : 2-メチレン-4-シクロペンテン-1，3-ジオン構造を有する新規血管新生阻害剤の分子設計, 第126年会日本薬学会, Mar. 2006.
234.	岡村菜摘子, Hideko Nagasawa, Yoshihiro Uto, 滝口公康 and Hitoshi Hori : ヒト血清Gc proteinサブタイプの糖鎖構造解析, 第126年会日本薬学会, Mar. 2006.
235.	中嶌瞳, 後藤恵子, Hideko Nagasawa, Yoshihiro Uto, 慎一郎増永, 小野公二 and Hitoshi Hori : 新規ボロンキャリアーの分子設計:Hypoxic cytotoxinハイブリッドの合成及び体内動態, 第8回癌治療増感研究シンポジウム, Feb. 2006.
236.	Hideko Nagasawa, 稲田俊行, Yoshihiro Uto, Hitoshi Hori and Semenza G. : HIF1αノックダウンHCT116細胞株の樹立とHIF1α阻害剤解析への応用, 第8回癌治療増感研究シンポジウム, Feb. 2006.
237.	川島知憲, 中西郁夫, Yoshihiro Uto, 大久保敬, 金澤秀子, 福原潔, 奥田晴宏, Hideko Nagasawa, Hitoshi Hori, 福住俊一, 小澤俊彦 and 伊古田暢夫 : 4-プロペニルフェノール誘導体およびビタミンEモデルのラジカル消去活性, 第17回ビタミンE研究会, Jan. 2006. (Summary) 天然抗酸化物質のラジカル消去反応に対する構造活性相関を明らかにするため，種々の4-プロペニルフェノール誘導体やビタミンEモデルのラジカル消去活性について速度論的に検討した．その結果，カフェイン酸は(+)-カテキンと同程度の2次反応速度定数k2値を示し，カフェイン酸のエステル体は2倍の値を示した．また，アルテピリンCのアルコール体はアルテピリンCと比較して約20倍のラジカル消去活性を示した．さらに，ビタミンEモデルであるPMCは極めて高い消去活性を示した．
238.	村上綾, 中江崇, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : N-アセチルガラクトサミン基を有する低酸素細胞放射線増感剤TX-2068およびアナログによるマクロファージの活性化能について, 第9回バイオ治療法研究会学術集会, Dec. 2005. (Summary) ヒト固形腫瘍中に存在する低酸素がん細胞は一般的な癌治療法である放射線や抗がん剤に対する感受性が低く，血管新生や湿潤·転移などがん細胞特性に深く関わっていることが明らかになってきている．マクロファージはがん細胞，低酸素領域に顕著に集積することが知られている．このような現象に注目して，低酸素指向性マクロファージを薬剤キャリアーとして利用する目的で低酸素細胞放射線増感剤TX-1877とマクロファージ結合能をもつN-アセチルガラクトサミンを1-β型で結合させたTX-2068を分子設計した．すでにEMT6/KU細胞に対する低酸素細胞放射線増感実験の結果から，TX-2068のERはTX-1877(ER=1.75, 1 mM)より高い増感活性を有することが分かっている．(ER=1.88, 1 mM)しかし，TX-2068 のマクロファージ活性化能および認識能については不明である．そこで我々はまずTX-2068のマクロファージ活性化能について検討した．また，糖鎖部位をグルコサミンに変えたアナログ(TX-2068(Glu)と記す)についても同様の検討を行い，糖鎖とマクロファージ活性化能との相関についても検討した． TX-2068の貪食活性試験の結果，1 mMまで濃度依存的に活性が増加し，5 mMで抑制が見られた．この挙動は免疫反応で一般的に見られるベルシャープ型の活性であり，TX-2068がマクロファージを活性化することを示唆している．次にMTT Assayから，TX-2068はマクロファージに対し5 mMまで細胞毒性を示さないことがわかった．以上の結果より，TX-2068は細胞毒性を示すことなくマクロファージを活性化することが明らかになった．
239.	岡村菜摘子, Hideko Nagasawa, Yoshihiro Uto, 滝口公康 and Hitoshi Hori : ヒト血清Gc proteinサブタイプの糖鎖構造解析, 第9回バイオ治療法研究会学術集会, Dec. 2005. (Summary) Gc protein(ビタミンD結合タンパク質)はヒト染色体4q11‐q13に位置しており，分子量約52kDaのタンパク質である．3つの対立遺伝子Gc1F，Gc1S，Gc2によりGc1F‐1F，Gc1S‐1S，Gc2‐2の3つのホモタイプとGc1F‐1S，Gc2‐1F，Gc2‐1Sの3つのヘテロタイプがあることが知られており，これらは異なる糖鎖を有すると推定されている． Gc proteinは，糖鎖修飾を受けることでマクロファージ活性化作用を発揮し，その糖鎖構造はマクロファージ活性化能に関与することが報告されている．我々はβ-galactosidaseとsialidaseで処理したGc1F-1F由来GcMAFが有意にマクロファージ貪食能を亢進し，Gc1S-1S，Gc2-2にはそれが見られなかったことを既に報告した(H.Nagasawa, H.Sasaki, Y.Uto, S.Kubo and H.Hori 2004 Anticancer Res.,24:3361‐3366)．そこでこれらのGc proteinホモタイプの糖鎖構造を解析し，マクロファージ活性化作用との相関について検討した． Gc1F-1F，Gc1S-1S，Gc2-2をβ-galactosidaseとsialidaseとで混合処理し，エスカルゴ(helix pomatia)lectinによるlectin blotを行った結果，いずれもGalNAc残基を持つことが示唆された．一方，Gc1F-1F，Gc1S-1S をsialidaseによって処理し，ピーナッツ(Arachis hypogaea)lectinを用いてlectin blotを行ったところ，Gc1F-1F，Gc1S-1SにGal-GalNAc残基があることが明らかになった．これにより，Gc1S-1Sの糖鎖にシアル酸が存在することを示唆する興味深い結果が得られた．
240.	Yoshihiro Uto, 阿江周太郎, 小山大輔, Hideko Nagasawa and Hitoshi Hori : アルテピリンCイソプレノミクスを基盤としたLDL抗酸化剤の分子設計, 日本過酸化脂質·フリーラジカル学会第29回大会, Oct. 2005. (Summary) 我々は，ブラジル産プロポリスの主成分で強い抗酸化活性を有するアルテピリンCのイソプレノミクス(イソプレン骨格やイソプレニル基を有する分子の創薬研究)より得られた知見から，LDL抗酸化活性と抗酸化剤の疎水性(脂溶性)は単純な比例関係ではなく，抗酸化剤の立体的構造，特に直線的構造が重要であることを示唆している．今回，抗酸化剤とラジカルとの反応性，すなわち電子的効果に関してイソプレノミクスによる分子設計を行い，それら分子のラジカル反応性及びLDL抗酸化活性について検討した．アルテピリンCがもつ2つのプレニル基の内1つをメチル基に置換したmethyl-TX-1959(仮名)は，TX-1959と比較してもほとんど電子状態は変わらなかったが，ラジカルとの反応によって生じるフェノキシラジカル体ではメチル基の存在がその後の副反応を抑制することが示唆された．合成に関しては，4-Iodo-2-methylphenolを出発原料としてオルト位選択的モノプレニル化反応を行い，得られた生成物をアセチル化，次いで溝呂木-Heck反応によりα，β-不飽和エステルを導入後，脱保護して目的物であるmethyl-TX-1959，methyl-TX-2012，methyl-TX-2101(仮名)を得た．
241.	川島知憲, 中西郁夫, Yoshihiro Uto, 大久保敬, 川口久美子, 金澤秀子, 福原潔, 奥田晴宏, Hideko Nagasawa, Hitoshi Hori, 福住俊一, 小澤俊彦 and 伊古田暢夫 : 4-プロペニルフェノール誘導体のラジカル消去活性, 第20回生体機能関連化学シンポジウム, Sep. 2005.
242.	Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : p53の阻害を介して正常細胞のダメージを軽減する低酸素細胞放射線増感剤の開発, 第64回日本癌学会学術総会, Sep. 2005.
243.	Yoshihiro Uto, 後藤恵子, 中嶌瞳, 中江崇, 田中智子, 田中彩子, Hideko Nagasawa, 増永慎一郎, 小野公二 and Hitoshi Hori : 低酸素薬剤(hypoxia drug)の創製:p53阻害型低酸素細胞放射線増感剤および低酸素指向性ハイブリッド型ボロンキャリアーの分子設計, 第35回放射線による制癌シンポジウム, Jul. 2005.
244.	Yoshihiro Uto, 阿江周太郎, 小山大輔, Hideko Nagasawa and Hitoshi Hori : LDL抗酸化剤を指向したブラジル産プロポリス成分アルテピリンCのイソプレノミクス解析, 第5回AOB研究会, Jun. 2005.
245.	Atsushi MIyoshi, Hideko Nagasawa, Yoshihiko Kitajima, Takao Ide, Koji Miyazaki, Yoshihiro Uto and Hitoshi Hori : 低酸素環境による肝細胞癌の悪性進展機序と低酸素標的治療の確立, 第17回日本肝胆膵外科学会, Jun. 2005. (Summary) 低酸素環境による肝細胞癌の悪性進展機序とhypoxic cytotoxinによる低酸素標的治療の確立について報告した．
246.	Yoshihiro Uto, 中江崇, 田中智子, 田中彩子, Hideko Nagasawa and Hitoshi Hori : p53の阻害を介して正常細胞のダメージを軽減する低酸素細胞放射線増感剤の分子設計, 第11回癌治療増感研究会, May 2005.
247.	Yoshihiro Uto, 阿江周太郎, 小山大輔, Hideko Nagasawa and Hitoshi Hori : 抗動脈硬化剤の創製を目指したArtepillin C Isoprenomics, 第3回次世代を担う有機化学シンポジウム, May 2005.
248.	Shin-ichi Nakayama, Hideko Nagasawa, Tomoya Fujita, Toshihiro Hashimoto, Yoshinori Asakawa, Yoshihiro Uto, Hitoshi Hori and Kuntz Doauglas-A : 標的タンパク質の立体構造に基づくswainsonine アナログの分子設計，立体選択的Mannich 反応によるDiversity-oriented 合成及びGMII 阻害活性, 第125年回日本薬学会, Mar. 2005. (Summary) 標的タンパク質の立体構造に基づくswainsonine アナログの分子設計，立体選択的Mannich 反応によるDiversity-oriented 合成及びGMII 阻害活性について報告した．
249.	Yoshihiro Uto, Shutaro Ae, Hideko Nagasawa, Hitoshi Hori and Junji Terao : ブラジル産プロポリス成分アルテピリンCのLDL抗酸化剤を目指したイソプレノミクス解析, 第125年回日本薬学会, Mar. 2005. (Summary) ブラジル産プロポリス成分アルテピリンCのLDL抗酸化剤を目指したイソプレノミクス解析に関して報告した．
250.	Keiko Goto, Hideko Nagasawa, Hitomi Nakashima, Yoshihiro Uto, 慎一郎増永, Koji Ono and Hitoshi Hori : ホウ素中性子捕捉療法のための低酸素指向性molecular beacon:hypoxic cytotoxinハイブリッド型TX-2100の分子設計, 日本薬学会第125年会, Mar. 2005. (Summary) ウ素中性子捕捉療法のための低酸素指向性molecular beacon:hypoxic cytotoxinハイブリッド型TX-2100の分子設計·合成，活性に関して報告した．
251.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, CZ Jin, Ayako Tanaka, Mariko Shimamura, Yoshio Takeuchi, Kirk L Kenneth and Seiichi Inayama : 2ーメチレン-4ーシクロペンテンー1，3-ジオン含有アゾマイシン誘導体の血管新生阻害活性をもつ低酸素細胞放射線増感剤の分子設計, 日本薬学会第125年会, Mar. 2005. (Summary) 2 -4 1 3-
252.	Hitoshi Hori, Hideko Nagasawa, Yoshihiro Uto, CZ Jin, Ayako Tanaka, Mariko Shimamura, Yoshio Takeuchi, Kenneth-L Kirk and Seiichi Inayama : TX-2036: Desing of an anti-angiogenic hypoxic cell radiosensitizer, 2-methylene-4-cyclopentene-1,3-dione-containing azomycin derivative, 第2回がんとハイポキシア研究会, Mar. 2005. (Summary) 血管新生阻害作用を有する低酸素細胞放射線増感剤TX-2036の分子設計·合成及び活性に関して報告した．
253.	Hitomi Nakashima, Keiko Goto, Hideko Nagasawa, Yoshihiro Uto, 慎一郎増永, Koji Ono and Hitoshi Hori : BNCTのためのTirapazamineハイブリッド型新規低酸素毒性ボロンキャリアーの分子設計, 第7回癌治療増感研究シンポジウム, Feb. 2005. (Summary) 中性子捕捉療法(BNCT)のためのTirapazamineハイブリッド型新規低酸素毒性ボロンキャリアーの分子設計·合成，活性について報告した．
254.	Yoshihiro Uto, Hideyuki Sasaki, Yoshimi Nakajima, Natsuko Okamura, Ayako Tanaka, Takashi Nakae, Aya Murakami, Hideko Nagasawa and Hitoshi Hori : TX-2068: マクロファージの低酸素指向性を利用した低酸素細胞放射線増感剤の分子設計, 第7回癌治療増感研究シンポジウム, Feb. 2005. (Summary) TX-2068: マクロファージの低酸素指向性を利用した低酸素細胞放射線増感剤の分子設計について報告した．
255.	Yoshihiro Uto, Shutaro Ae, Yoshihito Nakatsuma, Hideko Nagasawa and Hitoshi Hori : アルテピリンCイソプレノミクスを基盤とした抗動脈硬化剤の開発, 日本過酸化脂質·フリーラジカル学会第28回大会, Oct. 2004. (Summary) アルテピリンCをリード化合物としたイソプレノミクスを基盤とした抗動脈硬化剤の開発について報告した．
256.	Hitoshi Hori, Hideko Nagasawa and Yoshihiro Uto : 演出型がん治療薬としての低酸素微小環境指向性制がん剤の創製への試み, 第63回日本癌学会, Sep. 2004. (Summary) 演出型がん治療薬としての低酸素微小環境指向性制がん剤の創製への試みについて，最近の知見をまとめて報告した．
257.	Ikuo Nakanishi, Tomonori Kawashima, Yoshihiro Uto, Kei Ohkubo, Haruko Yakumaru, Mitsuko Takusakawa, Hideko Kanazawa, Haruhiro Okuda, Kiyoshi Fukuhara, Toshihiko Ozawa, Hideko Nagasawa, Shun-ichi Fukuzumi, Hitoshi Hori and Nobuo Ikota : アルテピリンCによるラジカル消去反応の速度論的解析, 第26回日本フリーラジカル学会学術集会, Jun. 2004. (Summary) アルテピリンC及びその誘導体によるラジカル消去反応の速度論的解析について報告した．
258.	Ikuo Nakanishi, Yoshihiro Uto, Tomonori Kawashima, Haruko Yakumaru, Toshihiko Ozawa, Hideko Nagasawa, Hitoshi Hori and Nobuo Ikota : 金属イオン存在下における4ーヒドロキシケイ皮酸誘導体のラジカル消去反応, 第14回金属の関与する生体関連反応シンポジウム, Jun. 2004. (Summary) アルテピリンアルテピリンCをリードとする4ーヒドロキシケイ皮酸誘導体の金属イオン存在下におけるラジカル消去反応について報告した．
259.	Yoshihiro Uto, Jyunya Azuma, Sayuri Iseki, Risa Kaitani, Hideko Nagasawa and Hitoshi Hori : 可逆的p53阻害作用を有する低酸素細胞放射線増感剤の分子設計, 第10回癌治療増感研究会, May 2004. (Summary) 可逆的p53阻害作用を有する低酸素細胞放射線増感剤の分子設計·合成及びp53阻害作用について報告した．
260.	Hideko Nagasawa, Keiko Goto, Masamitsu Hiraoka, Hitomi Nakashima, Yoshihiro Uto, Hitoshi Hori, 慎一郎増永 and Koji Ono : 中性子捕捉療法のための低酸素細胞指向性ハイブリッド型ホロンキャリアの分子設計, 第10回癌治療増感研究会, May 2004. (Summary) 中性子捕捉療法のための低酸素細胞指向性ハイブリッド型ホロンキャリアの分子設計·合成，活性について報告した．
261.	Tomoya Fujita, Shin-ichi Nakayama, Hideko Nagasawa, Masahiro Hashimoto, Yoshinori Asakawa, Yoshihiro Uto and Hitoshi Hori : Mannich反応によるswainsonine5位置換アナログの立体選択的合成とグリコシダーゼ阻害活性及び免疫賦活作用, 第124年回日本薬学会, Mar. 2004. (Summary) 免役修飾剤をめざしたswainsonineアナログの分子設計とαーマンノシダーゼ阻害剤活性に関する構造活性相関，及び多様性を指向した医薬品分子設計において有用な立体選択的Mannish反応の開発について報告した．
262.	Jyunya Azuma, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : p53阻害作用を有する低酸素細胞放射線増感剤TX-2004の分子設計, 第124年回日本薬学会, Mar. 2004. (Summary) p53阻害作用を有するピフィスリンα誘導体の分子設計·合成し，これが低酸素細胞放射線増感及び正常細胞防護作用を兼ね備えていることを示した．
263.	Yoshimi Nakajima, Hideko Nagasawa, Sayuri Iseki, Yoshihiro Uto and Hitoshi Hori : hypoxic cytotoxin, TX-402のHIF-1抑制作用を介した血管新生阻害作用, 第124年回日本薬学会, Mar. 2004. (Summary) 血管新生阻害作用を有する新規hypoxic cytotoxin TX-402は，低酸素誘導因子(HIF-1)シグナル経路を阻害することによって，血管新生阻害作用などの低酸素応答反応を抑制することを明らかにした．
264.	Yoshihiro Uto, Takafumi Yano, Shutaro Ae, Hideko Nagasawa and Hitoshi Hori : ブラジル産プロポリス成分アルテピリンCの化学予防剤を目指したイソプレノミクス解析, 第124年回日本薬学会, Mar. 2004. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．さたにこれをリード化合物としてアルキルフェノール誘導体を分子設計·合成し，そのミトコンドリア呼吸阻害活性及び脂質過酸化阻害活性についても検討した．
265.	Hideyuki Sasaki, Hideko Nagasawa, Masayo Kiyokawa, Yoshihiro Uto and Hitoshi Hori : ヒト血清GcタイプとGcMAF precursor activityの相関に関する検討, 第7回バイオ治療法研究会学術集会, Dec. 2003. (Summary) 等電点電気泳動法によってGcタンパク質の多型を分類し，種々の多型の糖鎖構造の違いによって，これより生成するGcMAFのマクロファージ活性化作用，及びそれを介した殺細胞活性が異なることを明らかにした．
266.	Yoshihiro Uto, Shutaro Ae, Hideko Nagasawa and Hitoshi Hori : Isoprenomicsを基盤としたArtepillin Cの分子変換とラット肝ミトコンドリア膜脂質過酸化阻害活性との相関, 日本過酸化脂質·フリーラジカル学会, Oct. 2003. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．さたにこれをリード化合物としてアルキルフェノール誘導体を分子設計·合成し，そのミトコンドリア呼吸阻害活性及び脂質過酸化阻害活性についても検討した．
267.	Jyunya Azuma, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori and Hideki Matsumoto : p53の阻害を介して正常細胞へのダメージを軽減する低酸素細胞放射線増感剤の開発, 第62回日本癌学会, Sep. 2003. (Summary) p53阻害作用を有するピフィスリンα誘導体の分子設計·合成，活性に関して発表した．
268.	Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : イソプレノミクスを基盤とした抗酸化剤の分子設計·合成とミトコンドリア機能修飾, 第62回日本癌学会, Sep. 2003. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．さたにこれをリード化合物としてアルキルフェノール誘導体を分子設計·合成し，そのミトコンドリア呼吸阻害活性及び脂質過酸化阻害活性についても検討した．
269.	Hideko Nagasawa, Yoshimi Nakajima, Naoko Mikamo, Yoshihiro Uto, Hitoshi Hori and Hideki Matsumoto : 血管新生阻害作用を有するhypoxic cytotoxin TX-402のHIF-1阻害効果, 第62回日本癌学会, Sep. 2003. (Summary) 血管新生阻害作用を有する新規hypoxic cytotoxin TX-402は，低酸素誘導因子(HIF-1)シグナル経路を阻害することによって，血管新生阻害作用などの低酸素応答反応を抑制することを明らかにした．
270.	Hideko Nagasawa, Masamitsu Hiraoka, Keiko Goto, Satoru GOTO, Yoshihiro Uto, Hitoshi Hori, 慎一郎増永 and Koji Ono : 低酸素細胞を標的とするホウ素熱中性子捕捉分子の分子設計, 第1回日本中性子捕捉療法研究会, Sep. 2003. (Summary) 低酸素細胞を標的とするホウ素熱中性子捕捉分子の分子設計，合成及び活性について報告した．
271.	Hideko Nagasawa, Masamitsu Hiraoka, Keiko Goto, Satoru GOTO, Yoshihiro Uto, Hitoshi Hori, 慎一郎増永 and Koji Ono : 低酸素細胞を標的とするホウ素熱中性子捕捉分子の分子設計, 第1回日本中性子捕捉療法研究会, Aug. 2003. (Summary) 中性子捕捉療法における新規ボロンキャリアとして，低酸素細胞親和性を有する新規ニトロイミダゾール誘導体の分子設計と合成について発表した．
272.	Masamitsu Hiraoka, Hideko Nagasawa, Keiko Goto, Yoshihiro Uto, 慎一郎増永 and Hitoshi Hori : 低酸素細胞を標的とするホウ素熱中性子捕捉分子の分子設計, 第9回癌治療増感研究会, Jun. 2003. (Summary) 中性子捕捉療法における新規ボロンキャリアとして，低酸素細胞親和性を有する新規ニトロイミダゾール誘導体の分子設計と合成について発表した．
273.	Hideko Nagasawa, Yoshimi Nakajima, Naoko MIkamo, Yoshihiro Uto, Hitoshi Hori and Hideki Matsumoto : Hypoxic cytotoxin TX-402によるHIF1及びその下流遺伝子の発現抑制, 第9回癌治療増感研究会, Jun. 2003. (Summary) 血管新生阻害作用を有する新規hypoxic cytotoxin TX-402は，低酸素誘導因子(HIF-1)シグナル経路を阻害することによって，血管新生阻害作用などの低酸素応答反応を抑制することを明らかにした．
274.	中西郁夫, Yoshihiro Uto, 薬丸晴子, 宮崎健太郎, 大久保敬, 浦野四郎, 奥田晴宏, 小澤俊彦, 福原潔, 福住俊一, 伊古田暢夫, Hideko Nagasawa and Hitoshi Hori : アルテピリンCのラジカル消去反応に及ぼす金属イオンの効果, 日本薬学会第123年会, Mar. 2003.
275.	中西郁夫, Yoshihiro Uto, 薬丸晴子, 宮崎健太郎, 大久保敬, 浦野四郎, 奥田晴宏, 小澤俊彦, 福住俊一, 福原潔, 伊古田暢夫, Hideko Nagasawa and Hitoshi Hori : 4-ヒドロキシケイ皮酸誘導体のラジカル消去機構, 日本化学会第83春年会, Mar. 2003.
276.	Yoshihiro Uto, Mitsutoshi Sakakibara, Naoko MIkamo, Hideko Nagasawa and Hitoshi Hori : イソプレノミクスを基盤としたアルテピリンCアナログの分子設計とその抗酸化活性及びミトコンドリア機能修飾, 日本薬学会第123年回, Mar. 2003. (Summary) 本論文では，プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．さたにこれをリード化合物としてアルキルフェノール誘導体を分子設計·合成し，そのミトコンドリア呼吸阻害活性及び脂質過酸化阻害活性についても検討した．
277.	CZ Jin, Hideko Nagasawa, Yoshihiro Uto, Naoko Mikamo, Saori Kiyoi and Hitoshi Hori : サイクロペンテンジオン骨格を有する2-nitroimidazole系低酸素性細胞放射線増感剤の分子設計とその生物活性, 日本薬学会第123年回, Mar. 2003. (Summary) 血管新生阻害作用を有する多機能性低酸素細胞放射線増感剤の分子設計·合成について報告した．
278.	Hideko Nagasawa, Naoko Mikamo, Yoshimi Nakajima, Jyunya Azuma, Yoshihiro Uto and Hitoshi Hori : Hypoxic cytotoxinの低酸素細胞毒性及び作用機構に関する検討, 日本薬学会第123年回, Mar. 2003. (Summary) 血管新生阻害作用を有する新規hypoxic cytotoxin TX-402は，低酸素誘導因子(HIF-1)シグナル経路を阻害することによって，血管新生阻害作用などの低酸素応答反応を抑制することを明らかにした．
279.	Masamitsu Hiraoka, Hideko Nagasawa, Keiko Goto, Saori Kiyoi, Yoshihiro Uto, 慎一郎増永, Koji Ono and Hitoshi Hori : 低酸素細胞を標的とするホウ素熱中性子捕捉分子の分子設計, 日本薬学会第123年回, Mar. 2003. (Summary) 中性子捕捉療法における新規ボロンキャリアとして，低酸素細胞親和性を有する新規ニトロイミダゾール誘導体の分子設計と合成について発表した．
280.	Tomoya Fujita, Hideko Nagasawa, Akihiro Fukuta, Hideyuki Sasaki, Yoshihiro Uto and Hitoshi Hori : 抗腫瘍及び免疫賦活効果を目指したswainsonine analogの分子設計·合成, 日本薬学会第123年回, Mar. 2003. (Summary) マンノシダーゼ阻害作用を介する免疫修飾作用を目的とするSwainsonine 誘導体の分子設計·合成に関して報告した．
281.	Tomoya Fujita, Hideko Nagasawa, Akihiro Fukuta, Hideyuki Sasaki, Yoshihiro Uto and Hitoshi Hori : 抗腫瘍及び免疫賦活効果を目指したswainsonine analogの分子設計·合成, 第2回複素環化学討論会, Dec. 2002. (Summary) マンノシダーゼ阻害作用を介する免疫修飾作用を目的とするSwainsonine 誘導体の分子設計·合成に関して報告した．
282.	Yoshihiro Uto, Mitsutoshi Sakakibara, Hideko Nagasawa and Hitoshi Hori : 抗酸化剤Artepillin Cの3,5位置換基変換による置換基効果が膜脂質過酸化阻害活性に与える影響について, 日本過酸化脂質·フリーラジカル学会第26回大会, Nov. 2002. (Summary) 新たにArtepillin Cをリード化合物として分子設計·合成したアルキルフェノール誘導体の膜脂質過酸化阻害活性における構造活性相関ついて報告した．
283.	Naoko Mikamo, Hideko Nagasawa, Jyunya Azuma, Yoshihiro Uto and Hitoshi Hori : Hypoxic cytotoxinの低酸素細胞毒性及びアポトーシス誘導効果に対するp53statusの影響, 第61回日本癌学会, Oct. 2002. (Summary) 血管新生阻害作用を有する新規hypoxic cytotoxin TX-402及びその誘導体のアポトーシス誘導作用についてp53非依存的であることを明らかにした．
284.	Yoshihiro Uto, Naoko Mikamo, Hideko Nagasawa and Hitoshi Hori : 野生型p53をターゲットとした新しい低酸素放射線増感剤の分子設計, 第61回日本癌学会, Oct. 2002. (Summary) p53阻害作用を有するピフィスリンα誘導体の分子設計·合成，活性に関して発表した．
285.	Tomoya Fujita, Hideko Nagasawa, Tetsuya Okabe, Naoko Mikamo, Mohamad Saharuddin, Yoshihiro Uto and Hitoshi Hori : 抗腫瘍活性及び,免疫増強を目指したSwainsonine enamineの分子設計·合成, 日本薬学会第122年会, Mar. 2002. (Summary) マンノシダーゼ阻害作用を介する免疫修飾作用を目的とするSwainsonine 誘導体の分子設計·合成に関して報告した．
286.	Megumi Yukawa, Satomi Okuyama, Hideko Nagasawa, Yoshihiro Uto, Atsushi Umemoto and Hitoshi Hori : 大腸がん化学予防剤の創製を目的としたUDCA誘導体の分子設計及び合成, 日本薬学会第122年会, Mar. 2002. (Summary) 新規大腸発がん予防薬としてUDCAをリード化合物とする誘導体の分子設計·合成を行いその活性について報告した．
287.	Yoshihiro Uto, Mitsutoshi Sakakibara, Naoko Mikamo, Hideko Nagasawa and Hitoshi Hori : 新規脂質過酸化阻害剤3,5-ジゲラニルシンナム酸TX-2007の分子設計·合成とミトコンドリア活性, 日本薬学会第122年会, Mar. 2002. (Summary) 新たに分子設計·合成したアルキルフェノール誘導体の抗酸化作用における構造活性相関ついて報告した．
288.	Hideko Nagasawa, Masamitsu Hiraoka, Yoshihiro Uto, Naoko Mikamo and Hitoshi Hori : 低酸素細胞を標的とするボロン熱中性子捕捉分子の分子設計, 日本薬学会第122年会, Mar. 2002. (Summary) 中性子捕捉療法における新規ボロンキャリアの分子設計と合成について発表した．
289.	Saharuddin Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Preparation of Gc Protein-derived Macrophage Activating Factor (GcMAF) and, 第5回バイオ治療法研究会, Dec. 2001.
290.	Mohamad Saharuddin, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : マウスマクロファージ系細胞株J 774.1を用いたGcMAFのマクロファージ活性化能に関する検討, 第60回日本癌学会, Sep. 2001.
291.	Yoshihiro Uto, 平田彰彦, Hideko Nagasawa and Hitoshi Hori : パラハロゲン化フェノールの水系プレニール化反応を経由したプロポリス抗腫瘍物質アルテピリンCの合成, 日本化学会第80秋季年会, Sep. 2001.
292.	Naoko Mikamo, Hideko Nagasawa, Mariko Shimamura, Yoshihiro Uto and Hitoshi Hori : Hypoxic cytotoxin, 2-cyano-1,4-quinoxaline 1,4-dioxide (TX-402)の分子設計とアポトーシス誘導及び血管新生阻害, 第60回日本癌学会, Sep. 2001. (Summary) 血管新生阻害作用を有する新規hypoxic cytotoxin TX-402及びその誘導体について，低酸素細胞毒性，血管新生作用，アポトーシス誘導作用について解析し報告した．
293.	Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : プロポリス由来抗酸化物質アルテピリンC及びその誘導体の分子設計·合成とミトコンドリア活性, 第60回日本癌学会, Sep. 2001. (Summary) プロポリスの生理活性成分として注目される，artepillin Cの初の全合成を達成した．さたにこれをリード化合物としてアルキルフェノール誘導体を分子設計·合成し，そのミトコンドリア呼吸阻害活性及び脂質過酸化阻害活性についても検討した．
294.	Masato Okamoto, 古市幸子, 押川哲也, 大江剛, Hidetomo Nishikawa, 田野智之, アハマドシャリフウディン, 葛西宗江, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and Mitsunobu Sato : 低酸素細胞放射線増感剤Tx-1877誘導体のTh1ケモカイン誘導と抗腫瘍効果, 第7回癌治療増感研究会, May 2001. (Summary) 低酸素細胞放射線増感剤Tx-1877誘導体のTh1ケモカイン誘導と抗腫瘍効果について報告した．
295.	Yoshihiro Uto, Koichi Saijyo, Hideko Nagasawa and Hitoshi Hori : 転写因子を分子標的とする新規抗がん剤/放射線増感剤の分子設計, 第7回癌治療増感研究会, May 2001. (Summary) p53阻害作用を有するピフィスリンα誘導体の分子設計·合成，活性に関して発表した．
296.	Saharuddin Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : GcMAFのマクロファージの活性化に及ぼすHepG2がん細胞由来α―NaGalaseの影響, 第7回癌治療増感研究会, May 2001. (Summary) Gcタンパク質からマクロファージ活性化因子(GcMAF)へのプロセシング反応を解明するため，糖鎖修飾と生物活性の相関を検討した．その結果GcMAFのマクロファージ活性化作用においてN-acetylgalactosamine糖鎖が重要であることを明らかにした．
297.	Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : 新規bifunctional radiosensitizerの分子設計と低酸素細胞毒性, 第7回癌治療増感研究会, May 2001. (Summary) 血管新生作用を有する新規多機能性放射線増感剤の分子設計と合成．生物活性に関して発表した．
298.	平田彰彦, 榊原光敏, Yoshihiro Uto, Hideko Nagasawa and Hitoshi Hori : 抗酸化活性を有する新規2,4,6ー三置換フェノール誘導体の分子設計·合成とミトコンドリア活性, 日本薬学会第121年会, Mar. 2001. (Summary) 抗酸化活性を有する新規2,4,6ー三置換フェノール誘導体の分子設計·合成とミトコンドリア活性について報告した．
299.	Naoko Mikamo, Hideko Nagasawa, 山下真緒, 勝浦恵子, Shigenori Oka, Mariko Shimamura, Hiroshi Maezawa, Yoshihiro Uto and Hitoshi Hori : 低酸素細胞修飾剤Triazine-N-oxideの分子設計 - アポトーシス誘導活性と血管新生阻害活性 -, 日本薬学会第121年会, Mar. 2001. (Summary) 低酸素細胞修飾剤Triazine-N-oxideの分子設とそのアポトーシス誘導活性及び血管新生阻害活性について報告した．
300.	Hideko Nagasawa, Naoko Mikamo, Mohamad Saharuddin, Yoshihiro Uto, Hashimoto Toshihisa, Yoshinori Asakawa and Hitoshi Hori : Daldinia vernicosa属由来抗腫瘍性サイトカラシンのp53非依存的アポトーシス誘導作用, 日本薬学会第121年会, Mar. 2001. (Summary) Daldinia vernicosa属由来抗腫瘍性サイトカラシン類がp53非依存的アポトーシス誘導作用を有することを報告した．
301.	Tomoya Fujita, Hideko Nagasawa, 高島有美, Mohamad Saharuddin, 鎌田美帆, Yoshihiro Uto and Hitoshi Hori : 免疫調節作用を有する抗腫瘍剤の創製を目指したSwainsonine-emamineの分子設計, 日本薬学会第121年会, Mar. 2001. (Summary) 免疫調節作用を有する抗腫瘍剤の創製を目指したSwainsonine-emamineの分子設計及び合成について報告した．
302.	山下真緒, Hideko Nagasawa, 勝浦恵子, 葛西宗江, Yoshihiro Uto, 島村眞里子, 稲山誠一 and Hitoshi Hori : 新規bifunctinal低酸素細胞放射線増感剤2-nitroimidazole oxazoline及び2-nitroimidazole haloalkylamideの分子設計, 日本薬学会第121年会, Mar. 2001. (Summary) 新規bifunctinal低酸素細胞放射線増感剤2-nitroimidazole oxazoline及び2-nitroimidazole haloalkylamideの分子設計，合成，生物活性について報告した．
303.	清水克英, Hideko Nagasawa, 段宏泉, Yoshihisa Takaishi, Yoshihiro Uto and Hitoshi Hori : 雷公藤(Triptergium wilfordii Hook F.)由来テルペノイドの抗腫瘍活性, 日本薬学会第121年会, Mar. 2001. (Summary) 雷公藤(Triptergium wilfordii Hook F.)由来テルペノイドの抗腫瘍活性について報告した．
304.	Yoshihiro Uto, 西条浩一, 勝浦恵子, Hideko Nagasawa and Hitoshi Hori : DNAを標的とするスレーディングインターカレータ型抗がん·放射線増感剤の開発, 日本薬学会第121年会, Mar. 2001. (Summary) DNAを標的とするスレーディングインターカレータ型抗がん·放射線増感剤の分子設計及び合成とその抗腫瘍活性について報告した．
305.	葛西宗江, 島村眞里子, 勝浦恵子, 新本永樹, 湯川めぐみ, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : 血管新生阻害作用を有する新規ペプチド性デンドリマ-の分子設計, 日本薬学会第121年会, Mar. 2001. (Summary) 血管新生阻害作用を有する新規ペプチド性デンドリマ-の分子設計と生物活性について報告した．
306.	Saharuddin Mohamad, 福永光展, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Stimulation of macrophage activity by GcMAF and influence of tumor derived alpha-NaGalase in GcMAF-directed macrophage activation, 第3回国際癌治療増感研究シンポジウム, Feb. 2001. (Summary) GcMAFによるマクロファージ活性化及び，腫瘍由来のα-NaGalaseによる影響について報告した．
307.	Hideko Nagasawa, 山下真緒, 美甘尚子, 勝浦恵子, Yoshihiro Uto and Hitoshi Hori : p53非依存性低酸素修飾分子及びアポトーシス誘導剤の分子設計, 第3回国際癌治療増感研究シンポジウム, Feb. 2001. (Summary) 申請者の開発した低酸素修飾分TX-402 はp53非依存的にアポトーシス誘導することを報告した．
308.	Yoshihiro Uto, 西条浩一, 勝浦恵子, Hideko Nagasawa and Hitoshi Hori : DNAを標的とするスレーディングインターカレータ型放射線増感剤の分子設計, 第3回国際癌治療増感研究シンポジウム, Feb. 2001. (Summary) DNAを標的とするスレーディングインターカレータ型放射線増感剤の分子設計と合成及び抗腫瘍活性について報告した．
309.	Yoshihiro Uto, 山下真緒, Hideko Nagasawa and Hitoshi Hori : スレーディング型インターカレータを利用したDNA選択的低酸素放射線増感剤TX-1932の分子設計, 第59回日本癌学会, Oct. 2000. (Summary) スレーディング型インターカレータを利用したDNA選択的低酸素放射線増感剤TX-1932の分子設計·合成及び放射線増感活性について報告した．
310.	葛西宗江, 島村真里子, Hideko Nagasawa, 山下真緒, Yoshihiro Uto and Hitoshi Hori : 血管新生阻害作用を有するデンドリマーTX-1943及びTX-1944の分子設計, 第59回日本癌学会, Oct. 2000. (Summary) 血管新生阻害作用を有するデンドリマーTX-1943及びTX-1944の分子設計と抗腫瘍活性，血管新生阻害作用について報告した．
311.	葛西宗江, Hideko Nagasawa, 山下真緒, Yoshihiro Uto, Hitoshi Hori, 太田一郎, 松浦成昭, Hiroshi Maezawa and 稲山誠一 : 血管内皮細胞遊走阻害活性を有する低酸素細胞放射線増感剤TX-1877及びその誘導体の分子設計·合成·生物活性, 第6回癌治療増感研究会, May 2000. (Summary) 血管内皮細胞遊走阻害活性を有する低酸素細胞放射線増感剤TX-1877及びその誘導体の分子設計·合成·生物活性について発表した．
312.	山下真緒, 勝浦恵子, 葛西宗江, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori and 島村眞理子 : oxazoline及びdihydro-oxadine骨格を有する新規bi-functional低酸素細胞放射線増感剤の分子設計, 第6回癌治療増感研究会, May 2000. (Summary) oxazoline及びdihydro-oxadine骨格を有する新規bi-functional低酸素細胞放射線増感剤の分子設計·合成，生物活性について報告した．
313.	Yoshihiro Uto, 西条浩一, 山下真緒, Hideko Nagasawa and Hitoshi Hori : スレーディング型インターカレータを利用した新規低酸素放射線増感剤TX-1932の分子設計, 第6回癌治療増感研究会, May 2000. (Summary) スレーディング型インターカレータを利用した新規低酸素放射線増感剤TX-1932の分子設計と合成について発表した．
314.	藤田智也, Hideko Nagasawa, 高島有美, Yoshihiro Uto and Hitoshi Hori : ヒドロキシル基の立体配座制御を目的としたswainsonine平面性誘導体の分子設計, 日本薬学会第120年会, Mar. 2000. (Summary) ヒドロキシル基の立体配座制御を目的としたsp2カーボンを有するswainsonine平面性誘導体の分子設計と合成について発表した．
315.	Yoshihiro Uto, 田窪俊亮, 山下真緒, 増井美恵, Hideko Nagasawa and Hitoshi Hori : スレーディング型インターカレータ系抗がん剤TX-1932の低酸素放射線増感剤としての分子設計, 日本薬学会第120年会, Mar. 2000. (Summary) 低酸素放射線増感剤としてのスレーディング型インターカレータ系抗がん剤TX-1932の分子設計·合成，生物活性について発表した．
316.	山下真緒, Hideko Nagasawa, 増井美恵, 葛西宗江, Yoshihiro Uto and Hitoshi Hori : TX-1877をリードとするbifunctional低酸素細胞放射線増感剤の分子設計, 日本薬学会第120年会, Mar. 2000. (Summary) 血管新生阻害作用を有する低酸素細胞放射線増感剤TX-1877をリード化合物とする誘導体の分子設計·合成，生物活性について発表した．
317.	葛西宗江, Hideko Nagasawa, 山下真緒, Yoshihiro Uto, Hitoshi Hori, 太田一郎, 松浦成昭 and 稲山誠一 : 内皮細胞遊走阻害活性能を有する低酸素細胞放射線増感剤TX-1877及びその誘導体の分子設計·合成·生物活性, 日本薬学会第120年会, Mar. 2000. (Summary) 内皮細胞遊走阻害活性能を有する低酸素細胞放射線増感剤TX-1877の分子設計·合成，生物活性について発表した．
318.	石橋賢樹, Yoshihiro Uto, 平田彰彦, Hideko Nagasawa and Hitoshi Hori : 抗がん剤を目的として新規2,4,6-三置換フェノール誘導体の分子設計·合成, 日本薬学会第120年会, Mar. 2000. (Summary) 本論文において，抗酸化剤をめざして2,4,6-三置換フェノール誘導体の分子設計·合成を行い，これらの生物活性を調べたところ，TX-1952は非常に強い抗酸化活性を有することを明らかにした．
319.	Hiroshi Maezawa, Keiko Hamada, Soko Kasai, Saharuddin Mohamad, Hideko Nagasawa, Yoshihiro Uto, Hitoshi Hori and Seiichi Inayama : 低酸素細胞増感剤TX1877によるマウス腹腔マクロファージの活性化, 日本医学放射線学会第38回生物部会学術大会抄録集, 27, Apr. 1999. (Summary) 多機能性放射線増感剤TX1877によるマウス腹腔マクロファージの活性化について報告した．

Et cetera, Workshop:

1.	Atsushi Tabata, Yoshihiro Uto and 大倉一人 : UTX-51誘導体とモデル標的タンパク質との相互作用:中性子照射による終末糖化産物破壊に寄与するボロントレース化合物の開発, 第25回バイオ治療法研究会学術集会, Dec. 2021.
2.	Atsushi Tabata, Yoshihiro Uto, Hitoshi Hori and Kazuto Ohkura : Chiral-2-nitroimidazole骨格を足場としたTX-2036誘導体の特性:EGF受容体キナーゼドメインとの相互作用, 第23回バイオ治療法研究会学術集会, Dec. 2019.
3.	Yoshihiro Uto : 免疫療法って何?∼血液や初乳を利用した免疫活性化剤の開発∼, 第62回けいはんなサイエンスカフェ, Dec. 2015.
4.	Yoshihiro Uto, 多田竜, 山田久継, Michihiro Nakamura, Teruyoshi Kageji, 増田開, Eiji Nakata, 森井孝 and 増永慎一郎 : 中性子増感作用を有する多機能性BNCT剤の創薬研究, 第1回徳島ナノメディシン・シンポジウム, Jul. 2015.
5.	Michihiro Nakamura, Yoshihiro Tsuruo, Yoshihiro Uto, Teruyoshi Kageji and 増田開 : 有機シリカ粒子技術とBNCTセラノスティックスへの展望, 第1回徳島ナノメディシン・シンポジウム, Jul. 2015.
6.	Yoshihiro Uto : 糖タンパク質由来マクロファージ活性化剤の創製と免疫療法への応用, 第5回細胞再生医療研究会, Jul. 2015.
7.	Naoyuki Shimomura, 馬郡義弘, 永濱匡高, Kenji Teranishi, Yoshihiro Uto and Hitoshi Hori : Experiment of Applying Nanosecond Pulsed Electric Fields on Solid Tumor Using Embryonated Chick Assay, The Papers of Technical Meeting, IEE JAPAN, Vol.PPT-12, No.1, 1-4, Mar. 2012. (Keyword) pulse electric fields / solid tumor / embryonated chick assay / apoptosis (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1572543025639745152 (CiNii: 1572543025639745152)
8.	Yoshihiro Uto : 発育鶏卵によるin vivo活性を基盤とした創薬研究, 平成22年度香川大学工学部先端工学研究発表会, Jan. 2011.
9.	Yoshihiro Uto : 有機化学におけるu-Learningを利用した自己主導型学習の試み, 平成22年度全学FD 大学教育カンファレンス in 徳島, Jan. 2011.
10.	Yoshihiro Uto : 創薬化学者から見た分析化学の概念, 日本分析化学会若手交流会, May 2010.

Report:

1.	Yoshihiko Ueno, Yosuke Seki, Satoshi Kinugawa, Hisayoshi Morioka, Akira Takahashi, Kenji Mori, Naozumi Ishimaru, Kazumi Ozaki, Tetsuo Yamazaki, Atsushi Takada, Yoshihiro Uto, Takahito Saito and Maiko Kamioka : 令和4年度徳島大学高等教育研究センターアドミッション部門報告書, 令和4年度徳島大学高等教育研究センターアドミッション部門報告書, Mar. 2023.

Patent:

1.	呉明輝 and Yoshihiro Uto : サルコペニア抑制食品の製造方法，サルコペニア抑制食品及び筋肉増強食品, 2023-520364 (Jun. 2022), WO2023/084389 (May 2023), 7406199 (Dec. 2023).
2.	Yoshihiro Uto : 藍葉加工産物を含有する着色料, 2018-049332 (Mar. 2018), .
3.	高橋秀明, Yoshihiro Uto, ビンカオクァングエン, ファムチーべトゥ, 多和田真吉 and 丸田浩 : カルボキシル基により酸性になったPAK1遮断剤のエステル体の調製および癌やその他のPAK1依存性疾患治療への応用, 2016-052369 (Mar. 2016), 6082488 (Jan. 2017).
4.	Yoshihiro Uto, Hitoshi Hori and 福本修一 : 放射線障害防護剤, 2012-286278 (Dec. 2012), .
5.	Yoshihiro Uto, Hitoshi Hori and 福本修一 : フラバノン化合物，並びにそれを含有する抗酸化剤及びその製造方法, 2012-286277 (Dec. 2012), 5985386 (Aug. 2016).
6.	Yoshihiro Uto, Hitoshi Hori, 乾利夫 and 久保健太郎 : 医薬組成物およびその製造方法, 2012-551822 (Sep. 2012), 5860817 (Dec. 2015).
7.	Yoshihiro Uto, Hitoshi Hori, 乾利夫 and 久保健太郎 : Pharmaceutical composition and method of preparing same, US 13/988,376 (Sep. 2012), US8,747,919 (Jun. 2014).
8.	遠藤良夫, Yoshihiro Uto, Hitoshi Hori, 田中徹, 石塚昌宏 and 高橋究 : PDT効果増強剤, 2012-136227 (Jun. 2012), .
9.	Hitoshi Hori, Yoshihiro Uto, 竹内亮太 and 中川美典 : 新規Gcグロブリンガラクトース脱糖体の製造方法, 2010-197485 (Sep. 2010), .
10.	Eiji Nakata, Hitoshi Hori, Yoshihiro Uto and Yukimachi Yoshihiro : ナノ集合体, 2010-129211 (Feb. 2010), .
11.	Eiji Nakata, Hitoshi Hori and Yoshihiro Uto : 蛍光プローブ, 2010-27884 (Feb. 2010), .
12.	Teruyoshi Kageji, Yoshihiro Uto, Shinji Nagahiro, Hitoshi Hori, 北里慶子 and 中嶌瞳 : ベンゾトリアジン化合物及びその用途, 2009194744 (Aug. 2009), 201146628 (Mar. 2011), .
13.	Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : 血管新生阻害剤, 2004-345233 (Nov. 2004), 2006-151879 (Jun. 2006), .

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

アセチルグルコース修飾スルファサラジンの分子設計・合成と放射線増感作用の評価 (Project/Area Number: 24K10911 )
RCC Precision Medicine Project using PDX models (Project/Area Number: 23K08736 )
Design and synthesis of acetylglucose-modified dasatinib and evaluation of radiosensitizing effect (Project/Area Number: 21K07567 )
多機能性チロシンキナーゼ阻害薬の創出とがん光線力学療法への応用研究 (Project/Area Number: 21K07215 )
Experimental research on the biological action of nanosecond pulsed electric fields and its evolving to medical technology (Project/Area Number: 21H01313 )
Development of a selective inhibitor against Na+/H+ exchange transporter 5 (NHE5), which is a target candidate molecule for gastrointestinal cancer. (Project/Area Number: 20K09030 )
Development of a next-generation patient-derived cancer model using chicken eggs and establishment of a drug screening method (Project/Area Number: 19K22689 )
Elucidation of radiosensitization mechanism of acetylglucose-modified gefitinib and development of novel radiosensitizer (Project/Area Number: 17K10480 )
Development of novel colon cancer treatment by Na+/H+ exchanger inhibitor (Project/Area Number: 16K10530 )
Creation and evaluation of tetraplex DNA specific molecules aiming at anti-cancer drug with low side effect (Project/Area Number: 15K13748 )
Activation of M2-type macrophages in the late phase of cerebral ischemia promotes neurogenesis with cleaning of the infarct area. (Project/Area Number: 15K10306 )
Development of chronoradiobiology model in combination of immune cells and radiosensitizer (Project/Area Number: 15K09998 )
Development of radiosensitizers based on antitumor/molecular targeted drugs modified by acetylglucose (Project/Area Number: 26461891 )
Development of novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy (Project/Area Number: 26430160 )
Establishment of Cancer Therapy Using Pulsed High Electric Fields and the Development Based on Acceleration of In Vivo Experiments (Project/Area Number: 25289075 )
Development of production process of high value-added and environmentally friendly products from lignocellulosic biomass (Project/Area Number: 25281048 )
Development of boron trace drug with broad molecule pursuit and destructive power by neutron irradiation (Project/Area Number: 24659566 )
Design of radiosensitizers targeting for glycolysis of hypoxic tumor based on tumor implanted chick embryo (Project/Area Number: 23591842 )
Development of novel lead compounds with enhancing effect on ALA-based photodynamic therapy (Project/Area Number: 23501305 )
Development of multi-functional radiosensitizer based on in vivo radiosensitizing activity using tumor-implant chick embryo (Project/Area Number: 21791198 )
低酸素環境を標的とした膵臓癌に対する新たな治療法の開発 (Project/Area Number: 19591590 )
Design of radiosensitizer and p53-reactivator using hypoxic tumor associated macrophage (Project/Area Number: 18790892 )
Development of new chemoradiosensitizing method for colorectal cancer (Project/Area Number: 18591466 )
標的分子との空間的相互作用のコントロールを指向したナノアセンブリー薬剤の分子設計 (Project/Area Number: 16659031 )
p53の阻害を介して正常細胞へのダメージを軽減する低酸素細胞放射線増感剤の開発 (Project/Area Number: 15790671 )
Design of hypoxic cell radiosensitizer utilized for hypoxia orientation of macrophage (Project/Area Number: 14370758 )
DNAに作用するスレーディングインターカレータ型低酸素細胞放射線増感剤の開発 (Project/Area Number: 13770507 )
Search by Researcher Number (20304553)

Professor : Uto, Yoshihiro

Research

Personal Web Page

Field of Study

Subject of Study

Book / Paper

Book:

Academic Paper (Judged Full Paper):

Academic Paper (Unrefereed Paper):

Academic Letter:

Review, Commentary:

Proceeding of International Conference:

Proceeding of Domestic Conference:

Et cetera, Workshop:

Report:

Patent:

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)