徳島大学 / 教育研究者総覧 --- 山田久嗣

個人のホームページ

https://researchmap.jp/7000008732 (researchmap)

https://orcid.org/0000-0003-1611-438X (ORCID)

専門分野

○	生物有機化学 (Bioorganic Chemistry), ケミカルバイオロジー (Chemical Biology)

研究テーマ

○	In vivo ケミカルプローブの創製と生体分子イメージングの新手法の開拓

著書・論文

著書:

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. (要約) 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. (キーワード) Etanidazole / Hypoxic cell radiosensitizer / Mouse colon cancer colon26 cell / Mouse mammary carcinoma EMT6 cell / Tumor-bearing chick embryo (出版サイトへのリンク) ● Publication site (DOI): 10.1016/bs.enz.2019.08.008 (文献検索サイトへのリンク) ● 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.	Teruyuki Kondo, Yu Kimura, Hisatsugu Yamada and Akio Toshimitsu : Magnetic Nanoparticles for Multimodal Bio-imaging, Nova Science Publishers, New York, 2014.
3.	Teruyuki Kondo, Kimura Yu, Hisatsugu Yamada and Akio Toshimitsu : Ruthenium-based catalysts for aerobic oxidation of alcohols, RSC Publishing, Cambridge, UK, 2014.

学術論文(審査論文):

1.	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. (出版サイトへのリンク) ● Publication site (DOI): 10.1248/cpb.c21-00549 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85116523598 (DOI: 10.1248/cpb.c21-00549, Elsevier: Scopus)
2.	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. (要約) 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. (キーワード) EGFR / GLUT / Gefitinib / Radiosensitizer / Sugar-hybrids (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bmc.2020.115889 (文献検索サイトへのリンク) ● 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)
3.	Hisatsugu Yamada, Natsuki Matsumoto, Takanori Komaki, Hiroaki Konishi, Yu Kimura, Aoi Son, Hirohiko Imai, Tetsuya Matsuda, Yasuhiro Aoyama and Teruyuki Kondo : Photoacoustic in vivo 3D imaging of tumor using a highly tumor-targeting probe under high-threshold conditions., Scientific Reports, Vol.10, 19363, 2020. (要約) tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries. (徳島大学機関リポジトリ) ● Metadata: 115490 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-020-76281-1 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33168875 ● Search Scopus @ Elsevier (PMID): 33168875 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-020-76281-1 (徳島大学機関リポジトリ: 115490, DOI: 10.1038/s41598-020-76281-1, PubMed: 33168875)
4.	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. (要約) 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. (キーワード) Low-molecular-weight whey protein / bovine mastitis / cytokines / macrophages (出版サイトへのリンク) ● Publication site (DOI): 10.21873/anticanres.14470 (文献検索サイトへのリンク) ● 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)
5.	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. (要約) 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. (キーワード) COX / Cell adhesion / Invasion / MMP / MT1-MMP (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbrc.2019.10.092 (文献検索サイトへのリンク) ● 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)
6.	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. (要約) 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. (キーワード) Enzymatic activation / Prodrug / Reductase / Tumor hypoxia (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bmcl.2019.04.003 (文献検索サイトへのリンク) ● 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)
7.	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. (要約) 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. (キーワード) Hydrolyzed whey protein / anti-inflammation / 炎症 (inflammation) / macrophage activation / プロテアーゼ (protease) (出版サイトへのリンク) ● Publication site (DOI): 10.21873/anticanres.12728 (文献検索サイトへのリンク) ● 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)
8.	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. (要約) 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. (キーワード) 5-Aminolevulinic acid / carbon-ion beam / ミトコンドリア (mitochondria) / protoporphyrin IX / 活性酸素種 (reactive oxygen species) (出版サイトへのリンク) ● Publication site (DOI): 10.21873/anticanres.12730 (文献検索サイトへのリンク) ● 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)
9.	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. (要約) 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. (キーワード) 5-Aminolevulinic acid / Photodynamic therapy / Protoporphyrin IX / Schiff base (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.pdpdt.2017.10.014 (文献検索サイトへのリンク) ● 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)
10.	Teruyuki Kondo, Yu Kimura, Hisatsugu Yamada and Yasuhiro Aoyama : Polymeric (1) H MRI Probes for Visualizing Tumor In Vivo., Chemical Record, Vol.17, No.6, 555-568, 2017. (要約) Magnetic resonance imaging (MRI) has become a prominent non- or low-invasive imaging technique, providing high-resolution, three-dimensional images as well as physiological information about tissues. Low-molecular-weight Gd-MRI contrast agents (CAs), such as Gd-DTPA (DTPA: diethylenetriaminepentaacetic acid), are commonly used in the clinical diagnosis, while macromolecular Gd-MRI CAs have several advantages over low-molecular-weight Gd-MRI CAs, which help minimize the dose of CAs and the risk of side effects. Accordingly, we developed chiral dendrimer Gd-MRI CAs, which showed high r1 values. The association constant values (Ka ) of S-isomeric dendrimer CAs to bovine serum albumin (BSA) were higher than those of R-isomeric dendrimer CAs. Besides, based on a totally new concept, we developed (13) C/(15) N-enriched multiple-resonance NMR/MRI probes, which realized highly selective observation of the probes and analysis of metabolic reactions of interest. This account summarizes our recent study on developing both chiral dendrimer Gd-MRI CAs, and self-traceable (13) C/(15) N-enriched phosphorylcholine polymer probes for early detection of tumors. (出版サイトへのリンク) ● Publication site (DOI): 10.1002/tcr.201600144 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28387472 ● Search Scopus @ Elsevier (PMID): 28387472 ● Search Scopus @ Elsevier (DOI): 10.1002/tcr.201600144 (DOI: 10.1002/tcr.201600144, PubMed: 28387472)
11.	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. (要約) 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. (キーワード) AKT / TX-2137 / anti-metastatic agent / hypoxic cytotoxin (出版サイトへのリンク) ● Publication site (DOI): 10.21873/anticanres.11768 (文献検索サイトへのリンク) ● 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)
12.	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. (要約) 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. (キーワード) 5-Aminolevulinic acid / mammary tumor / ミトコンドリア (mitochondria) / protoporphyrin IX / 活性酸素 (reactive oxygen species) / sonodynamic therapy (文献検索サイトへのリンク) ● 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)
13.	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. (要約) 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. (キーワード) Carbon Ion Beam / Protoporphyrin IX / Aminolevulinic Acid / Radiosensitization
14.	Hisatsugu Yamada, Tetsuro Kameda, Yu Kimura, Hirohiko Imai, Tetsuya Matsuda, Shinsuke Sando, Akio Toshimitsu, Yasuhiro Aoyama and Teruyuki Kondo : ¹³C/¹⁵N-Enriched L-Dopa as a Triple-Resonance NMR Probe to Monitor Neurotransmitter Dopamine in the Brain and Liver Extracts of Mice, ChemistryOpen, Vol.5, No.2, 125-128, 2016. (徳島大学機関リポジトリ) ● Metadata: 114900 (出版サイトへのリンク) ● Publication site (DOI): 10.1002/open.201500196 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-84952838220 (徳島大学機関リポジトリ: 114900, DOI: 10.1002/open.201500196, Elsevier: Scopus)
15.	Yuka Miyake, Ishikawa Syngo, Yu Kimura, Aoi Son, Hirohiko Imai, Tetsuya Matsuda, Hisatsugu Yamada, Akio Toshimitsu and Teruyuki Kondo : Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM, Sensors, Vol.15, No.12, 31973-31986, 2015. (徳島大学機関リポジトリ) ● Metadata: 115725 (出版サイトへのリンク) ● Publication site (DOI): 10.3390/s151229900 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-84950140583 (徳島大学機関リポジトリ: 115725, DOI: 10.3390/s151229900, Elsevier: Scopus)
16.	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. (要約) Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. (文献検索サイトへのリンク) ● 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)
17.	Hisatsugu Yamada, Yoshinori Hasegawa, Yuki Suzuki, Hirohiko Imai, Tetsuya Matsuda, Yu Kimura, Akio Toshimitsu, Yasuhiro Aoyama and Teruyuki Kondo : Magnetic Resonance Imaging of Tumor with a Self-Traceable Polymer Conjugated with an Antibody Fragment, Bioorganic & Medicinal Chemistry Letters, Vol.25, No.13, 2675-2678, 2015. (要約) A (13)C-enriched phosphorylcholine polymer ((13)C-PMPC) as a self-traceable MR (magnetic resonance) tag was conjugated with a fragment (scFv) of Herceptin, a clinical antibody against antigen Her2. When injected in model mice bearing Her2(+) (gastric) and Her2(-) (pancreatic) tumors, the antibody-tag conjugate (13)C-PMPC-scFv selectively accumulated in the Her2(+) tumor with a rapid build-up/decay (accumulation/clearance) profile and, with the use of the (1)H-(13)C double-resonance (heteronuclear correlation) technique, the Her2(+) gastric tumor was clearly MR imaged. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bmcl.2015.04.072 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25958246 ● Summary page in Scopus @ Elsevier: 2-s2.0-84930503934 (DOI: 10.1016/j.bmcl.2015.04.072, PubMed: 25958246, Elsevier: Scopus)
18.	Hisatsugu Yamada, Yoshinori Hasegawa, Hirohiko Imai, Yuki Takayama, Fuminori Sugihara, Tetsuya Matsuda, Hidehito Tochio, Masahiro Shirakawa, Shinsuke Sando, Yu Kimura, Akio Toshimitsu, Yasuhiro Aoyama and Teruyuki Kondo : Magnetic resonance imaging of tumor with a self-traceable phosphorylcholine polymer., Journal of the American Chemical Society, Vol.137, No.2, 799-806, 2015. (要約) Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63 000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers. (出版サイトへのリンク) ● Publication site (DOI): 10.1021/ja510479v (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25560796 ● Summary page in Scopus @ Elsevier: 2-s2.0-84921451995 (DOI: 10.1021/ja510479v, PubMed: 25560796, Elsevier: Scopus)
19.	Tsutomu Yoshimura, Yuanjun Di, Yu Kimura, Hisatsugu Yamada, Akio Toshimitsu and Teruyuki Kondo : Simple, Selective, and Practical Synthesis of 2-Substituted 4(3H)-Quinazolinones by Yb(OTf3)-Catalyzed Condensation of 2-Aminobenzamide with Carboxyamides, Heterocycles, Vol.90, No.2, 857-865, 2015. (出版サイトへのリンク) ● Publication site (DOI): 10.3987/COM-14-S(K)79 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1520291854782706560 ● Search Scopus @ Elsevier (DOI): 10.3987/COM-14-S(K)79 (DOI: 10.3987/COM-14-S(K)79, CiNii: 1520291854782706560)
20.	Yu Kimura, Takuya Kurimoto, Hiro-aki Sugii, Akio Toshimitsu, Tetsuya Matsuda, Hirohiko Imai, Hisatsugu Yamada and Teruyuki Kondo : Novel Biocompatible Cobalt Oxide Nanoparticles for Use in Dual Photoacoustic and Magnetic Resonance Imaging, JSM Biotechnology & Biomedical Engineering, Vol.2, No.2, 1043, 2014.
21.	Hirokazu Komatsu, Kazuki Yoshihara, Hisatsugu Yamada, Yu Kimura, Aoi Son, Sei-ichi Nishimoto and Kazuhito Tanabe : Ruthenium complexes with hydrophobic ligands that are key factors for the optical imaging of physiological hypoxia., Chemistry - A European Journal, Vol.19, No.6, 1971-1977, 2012. (要約) The phosphorescence emission of ruthenium complexes was applied to the optical imaging of physiological hypoxia. We prepared three complexes with hydrophobic substituents on the phenanthroline ligand and characterized their emission, which was quenched by molecular oxygen. Among the complexes synthesized in this study, a pyrene chromophore-linked ruthenium complex, Ru-Py, exhibited optimal properties for the imaging of hypoxia; the prolonged lifetime of the triplet excited state of the ruthenium chromophore, which was induced by efficient energy distribution and transfer from the pyrene unit, provided the highest sensitivity towards molecular oxygen. The introduction of hydrophobic pyrene increased the lipophilicity of the complex, leading to enhanced cellular uptake. Consequently, the bright phosphorescence of Ru-Py was seen in the cytoplasm of viable hypoxic cells, whereas the signal from aerobic cells was markedly weaker. Thus, we could clearly discriminate between hypoxic and aerobic cells by monitoring the phosphorescence emission. Furthermore, Ru-Py was applied to optical imaging in live mice. An intramuscular injection of Ru-Py successfully visualized ischemia-based hypoxia, which was constructed by leg banding. (キーワード) Animals / Anoxia / Coordination Complexes / Hydrophobic and Hydrophilic Interactions / Ligands / Luminescent Measurements / Mice / Molecular Structure / Optical Imaging / Phenanthrolines / Photochemistry / Pyrenes / Pyridines / Ruthenium (出版サイトへのリンク) ● Publication site (DOI): 10.1002/chem.201202809 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23281056 ● Search Scopus @ Elsevier (PMID): 23281056 ● Search Scopus @ Elsevier (DOI): 10.1002/chem.201202809 (DOI: 10.1002/chem.201202809, PubMed: 23281056)
22.	Takeo Ito, Yuta Hamaguchi, Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : Transporting excess electrons along potential energy gradients provided by 2'-deoxyuridine derivatives in DNA., Angewandte Chemie International Edition, Vol.51, No.30, 7558-7561, 2012. (キーワード) Base Sequence / DNA / Deoxyuridine / Electron Transport / Electrons / Photochemical Processes (出版サイトへのリンク) ● Publication site (DOI): 10.1002/anie.201202141 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22696439 ● Search Scopus @ Elsevier (PMID): 22696439 ● Search Scopus @ Elsevier (DOI): 10.1002/anie.201202141 (DOI: 10.1002/anie.201202141, PubMed: 22696439)
23.	Hisatsugu Yamada, Masayuki Kurata, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Synthesis and photooxidation of oligodeoxynucleotides containing 5-dimethylaminocytosine as an efficient hole-trapping site in the positive-charge transfer through DNA duplexes., Organic & Biomolecular Chemistry, Vol.10, No.10, 2035-2043, 2012. (要約) We have designed and synthesized DNA duplexes containing 5-dimethylaminocytosine ((DMA)C) to investigate the effects of C(5)-substituted cytosine bases on the transfer and trapping of positive charge (holes) in DNA duplexes. Fluorescence quenching experiments revealed that a (DMA)C base is more readily one-electron oxidized into a radical cation intermediate as compared with other natural nucleobases. Upon photoirradiation of the duplexes containing (DMA)C, the photosensitizer-injected hole migrated through the DNA bases and was trapped efficiently at the (DMA)C sites, where an enhanced oxidative strand cleavage occurred by hot piperidine treatment. The (DMA)C radical cation formed by hole transfer may undergo specific hydration and subsequent addition of molecular oxygen, thereby leading to its decomposition followed by a predominant strand cleavage at the (DMA)C site. This remarkable property suggests that the modified cytosine (DMA)C can function as an efficient hole-trapping site in the positive-charge transfer in DNA duplexes. (キーワード) Base Sequence / Cytosine / DNA / Electrons / Nucleic Acid Conformation / Oligodeoxyribonucleotides / Oxidation-Reduction / Photochemical Processes (出版サイトへのリンク) ● Publication site (DOI): 10.1039/c2ob06642d (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22273807 ● Search Scopus @ Elsevier (PMID): 22273807 ● Search Scopus @ Elsevier (DOI): 10.1039/c2ob06642d (DOI: 10.1039/c2ob06642d, PubMed: 22273807)
24.	Hisatsugu Yamada, Keigo Mizusawa, Ryuji Igarashi, Hidehito Tochio, Masahiro Shirakawa, Yasuhiko Tabata, Yu Kimura, Teruyuki Kondo, Yasuhiro Aoyama and Shinsuke Sando : Substrate/Product-targeted NMR monitoring of pyrimidine catabolism and its inhibition by a clinical drug., ACS Chemical Biology, Vol.7, No.3, 535-542, 2012. (要約) We report the application of one-dimensional triple-resonance NMR to metabolic analysis and thereon-based evaluation of drug activity. Doubly (13)C/(15)N-labeled uracil ([(15)N1,(13)C6]-uracil) was prepared. Its catabolic (degradative) conversion to [(13)C3,(15)N4]--alanine and inhibition thereof by gimeracil, a clinical co-drug used with the antitumor agent 5-fluorouracil, in mouse liver lysates were monitored specifically using one-dimensional triple-resonance ((1)H-{(13)C-(15)N}) NMR, but not double-resonance ((1)H-{(13)C}) NMR, in a ratiometric manner. The administration of labeled uracil to a mouse resulted in its non-selective distribution in various organs, with efficient catabolism to labeled -alanine exclusively in the liver. The co-administration of gimeracil inhibited the catabolic conversion of uracil in the liver. In marked contrast to in vitro results, however, gimeracil had practically no effect on the level of uracil in the liver. The potentiality of triple-resonance NMR in the analysis of in vivo pharmaceutical activity of drugs targeting particular metabolic reactions is discussed. (キーワード) Animals / Dose-Response Relationship, Drug / Female / Liver / Magnetic Resonance Spectroscopy / Mice / Mice, Inbred BALB C / Molecular Structure / Pyridines / Uracil (出版サイトへのリンク) ● Publication site (DOI): 10.1021/cb2003972 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22260358 ● Search Scopus @ Elsevier (PMID): 22260358 ● Search Scopus @ Elsevier (DOI): 10.1021/cb2003972 (DOI: 10.1021/cb2003972, PubMed: 22260358)
25.	田邉一仁, 山田久嗣, 西本清一 : 光機能性修飾核酸の合成とDNA中メチル化シトシンに選択的な光-電子酸化反応, 有機合成化学協会誌, Vol.69, No.7, 814-822, 2011年. (出版サイトへのリンク) ● Publication site (DOI): 10.5059/yukigoseikyokaishi.69.814 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.69.814 (DOI: 10.5059/yukigoseikyokaishi.69.814)
26.	Koya Yamaguchi, Ryosuke Ueki, Hisatsugu Yamada, Yasuhiro Aoyama, Hiroshi Nonaka and Shinsuke Sando : In Situ Analysis of [8-13C-7-15N]-Double-Labelled Theophylline by a Triple Resonance NMR Technique, Analytical Methods, Vol.3, No.7, 1664-1666, 2011. (出版サイトへのリンク) ● Publication site (DOI): 10.1039/c1ay05100h (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.1039/c1ay05100h (DOI: 10.1039/c1ay05100h)
27.	Hisatsugu Yamada, Yuya Kitauchi, Kazuhito Tanabe, Takeo Ito and Sei-Ichi Nishimoto : Anthraquinone-sensitized photooxidation of 5-methylcytosine in DNA leading to piperidine-induced efficient strand cleavage., Chemistry - A European Journal, Vol.17, No.7, 2225-2235, 2011. (要約) One-electron photooxidations of 5-methyl-2'-deoxycytidine (d(m)C) and 5-trideuteriomethyl-2'-deoxycytidine ([D(3)]d(m)C) by sensitization with anthraquinone (AQ) derivatives were investigated. Photoirradiation of an aerated aqueous solution containing d(m)C and anthraquinone 2-sulfonate (AQS) afforded 5-formyl-2'-deoxycytidine (d(f)C) and 5-hydroxymethyl-2'-deoxycytidine (d(hm)C) in good yield through an initial one-electron oxidation process. The deuterium isotope effect on the AQS-sensitized photooxidation of d(m)C suggests that the rate-determining step in the photosensitized oxidation of d(m)C involves internal transfer of the C5-hydrogen atom of a d(m)C-tetroxide intermediate to produce d(f)C and d(hm)C. In the case of a 5-methylcytosine ((m)C)-containing duplex DNA with an AQ chromophore that is incorporated into the backbone of the DNA strand so as to be immobilized at a specific position, (m)C underwent efficient direct one-electron oxidation by the photoexcited AQ, which resulted in an exclusive DNA strand cleavage at the target (m)C site upon hot piperidine treatment. In accordance with the suppression of the strand cleavage at 5-trideuterio-methylcytosine observed in a similar AQ photosensitization, it is suggested that deprotonation at the C5-methyl group of an intermediate (m)C radical cation may occur as a key elementary reaction in the photooxidative strand cleavage at the (m)C site. Incorporation of an AQ sensitizer into the interior of a strand of the duplex enhanced the one-electron photooxidation of (m)C, presumably because of an increased intersystem crossing efficiency that may lead to efficient piperidine-induced strand cleavage at an (m)C site in a DNA duplex. (キーワード) Anthraquinones / DNA / DNA Cleavage / DNA Methylation / Deoxycytidine / Electrons / Molecular Structure / Oxidation-Reduction / Photochemistry / Piperidines / Solutions / Water (出版サイトへのリンク) ● Publication site (DOI): 10.1002/chem.201001884 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21294186 ● Search Scopus @ Elsevier (PMID): 21294186 ● Search Scopus @ Elsevier (DOI): 10.1002/chem.201001884 (DOI: 10.1002/chem.201001884, PubMed: 21294186)
28.	Takeo Ito, Tsukasa Uchida, Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : Photoinduced Electron Injection into DNA by N-Cyclopropyl-1-aminonaphthalene, Journal of Photochemistry and Photobiology A: Chemistry, Vol.219, No.1, 115-121, 2011. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.jphotochem.2011.01.025 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.1016/j.jphotochem.2011.01.025 (DOI: 10.1016/j.jphotochem.2011.01.025)
29.	Kazuhito Tanabe, Hiroshi Harada, Michiko Narazaki, Kazuo Tanaka, Kenichi Inafuku, Hirokazu Komatsu, Takeo Ito, Hisatsugu Yamada, Yoshiki Chujo, Tetsuya Matsuda, Masahiro Hiraoka and Sei-ichi Nishimoto : Monitoring of biological one-electron reduction by (19)F NMR using hypoxia selective activation of an (19)F-labeled indolequinone derivative., Journal of the American Chemical Society, Vol.131, No.44, 15982-15983, 2009. (要約) Biological reduction of fluorine-labeled indolequinone derivative (IQ-F) was characterized by (19)F NMR for quantitative molecular understanding. The chemical shift change in (19)F NMR allowed monitoring of the enzymatic reduction of IQ-F. Upon hypoxic treatment of IQ-F with NADPH:cytochrome P450 reductase, IQ-F was activated via catalytic one-electron reduction to release nonafluoro-tert-butyl alcohol (F-OH), while the formation of F-OH was significantly suppressed under aerobic conditions. Similar hypoxia-selective reduction of IQ-F occurred within A549 cells, which expresses NADPH:cytochrome P450 reductase. The kinetic analysis was also performed to propose a reaction mechanism. The molecular oxygen slightly prevents the binding of IQ-F to reductase, while the rate of net reaction was decreased due to oxidation of a semiquinone anion radical intermediate generated by one-electron reduction of IQ-F. The disappearance of IQ-F and appearance of F-OH were imaged by (19)F fast spin echo, thus visualizing the hypoxia-selective reduction of IQ-F by means of MR imaging. (キーワード) Anoxia / Cell Line / Fluorine Radioisotopes / Humans / Indolequinones / Magnetic Resonance Spectroscopy / Oxidation-Reduction (出版サイトへのリンク) ● Publication site (DOI): 10.1021/ja904953b (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19842623 ● Search Scopus @ Elsevier (PMID): 19842623 ● Search Scopus @ Elsevier (DOI): 10.1021/ja904953b (DOI: 10.1021/ja904953b, PubMed: 19842623)
30.	Takeo Ito, Akiko Kondo, Tomoyuki Kamashita, Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : Pathways of excess electron transfer in phenothiazine-tethered DNA containing single-base mismatches., Organic & Biomolecular Chemistry, Vol.7, No.10, 2077-2081, 2009. (要約) The effects of local structural disorder on excess electron transfer (EET) in DNA were investigated by evaluating photoinduced electron transfer in phenothiazine (PTZ)-modified oligodeoxynucleotides bearing single-base mismatches. Unexpectedly, more efficient electron transfer was observed for the mismatched duplexes than for the complementary DNA, suggesting that distraction of hydrogen bond interaction at the mismatch site enables electron injection or hopping beyond the mismatch sites. It was also anticipated that water accessibility of the mismatched nucleobases could affect EET because protonation of the electron-captured pyrimidine intermediates became competitive to EET, especially at the mismatch sites. (キーワード) Base Pair Mismatch / Circular Dichroism / DNA / Electrochemistry / Electron Transport / Electrons / Kinetics / Nucleic Acid Conformation / Oligodeoxyribonucleotides / Phenothiazines / Pyrimidines / Water (出版サイトへのリンク) ● Publication site (DOI): 10.1039/b820311c (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19421445 ● Search Scopus @ Elsevier (PMID): 19421445 ● Search Scopus @ Elsevier (DOI): 10.1039/b820311c (DOI: 10.1039/b820311c, PubMed: 19421445)
31.	Takeo Ito, Aiko Hayashi, Akiko Kondo, Tsukasa Uchida, Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : DNA hairpins containing a diaminostilbene derivative as a photoinduced electron donor for probing the effects of single-base mismatches on excess electron transfer in DNA., Organic Letters, Vol.11, No.4, 927-930, 2009. (要約) To investigate the effects of local structural disorder induced by a single-base mismatch on excess electron transfer (EET) in DNA, a novel hairpin DNA containing diaminostilbene (DAS) as a photoinducible electron donor has been developed. It was clearly demonstrated that EET efficiency depends on the electron injection modes from the electron donors and redox properties of the mismatched bases. (キーワード) Base Pair Mismatch / Base Sequence / DNA / DNA Damage / Molecular Structure / Nucleic Acid Conformation / Oligodeoxyribonucleotides / Organophosphorus Compounds / Oxidation-Reduction / Photochemistry / Polymorphism, Single Nucleotide / Spectrometry, Fluorescence / Stilbenes (出版サイトへのリンク) ● Publication site (DOI): 10.1021/ol802896y (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19170616 ● Search Scopus @ Elsevier (PMID): 19170616 ● Search Scopus @ Elsevier (DOI): 10.1021/ol802896y (DOI: 10.1021/ol802896y, PubMed: 19170616)
32.	Takeo Ito, Aiko Hayashi, Tsukasa Uchida, Kazuhito Tanabe, Hisatsugu Yamada and Sei-Ichi Nishimoto : Photoinduced electron transfer reaction in diaminostilbene-tethered DNA duplexes., Nucleic Acids Symposium Series, No.53, 201-202, 2009. (要約) DNA duplexes containing diaminostilbene (DAS) as a photoinduced electron donor were synthesized to investigate mechanisms of electron injection into DNA and the succeeding electron transfer in the duplexes. DAS-Capped hairpin DNA showed a high structural stability thereby attains large interaction between DAS and the terminal base pair. DAS-Tethered DNA by a single linker at the end of the duplex was also synthesized and the yields of photoinduced electron transfer through mismatched base pairs were quantified. Both duplexes showed similar electron transfer efficiencies depending on the base pairs, which suggests DAS stacks well on the "pi-way" of the duplex DNA. (キーワード) DNA / Electron Transport / Photochemical Processes / Stilbenes (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrp101 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19749330 ● Search Scopus @ Elsevier (PMID): 19749330 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/nrp101 (DOI: 10.1093/nass/nrp101, PubMed: 19749330)
33.	Kazuhito Tanabe, Hisatsugu Yamada, Takeo Ito and Sei-ichi Nishimoto : Photoelectrochemical identification of 5-methylcytosine modification in DNA: combination of photosensitization and enzymatic cleavage., Nucleic Acids Symposium Series, No.53, 205-206, 2009. (要約) We present a novel photoelectrochemical approach for discriminating between cytosine and 5-methylcytosine in DNA when used in combination with enzymatic digestion. A photosensitizer-linked DNA duplex bearing 5-methylcytosine or cytosine at a given restriction site of the strand was immobilized on a gold electrode and digested with enzyme, and the photocurrent response was measured. We observed high photocurrent density that was selective for the methylated duplex. (キーワード) 5-Methylcytosine / Cytosine / DNA / DNA Methylation / DNA Restriction Enzymes / Oligodeoxyribonucleotides / Photochemical Processes / Photochemistry (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrp103 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19749332 ● Search Scopus @ Elsevier (PMID): 19749332 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/nrp103 (DOI: 10.1093/nass/nrp103, PubMed: 19749332)
34.	Hisatsugu Yamada, Yuya Kitauchi, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Efficient photooxidative strand cleavage at 5-methylcytosine in DNA by sensitization with 9,10-anthraquinone-tethered oligonucleotides., Nucleic Acids Symposium Series, No.53, 209-210, 2009. (要約) Photoirradiation and subsequent hot piperidine treatment of the duplex consisting of 5-methylcytosine ((m)C)-containing DNA and 9,10-anthraquinone (AQ)-tethered complementary oligodeoxynucleotide led to selective oxidative strand cleavage at the target (m)C site, whereas no strand cleavage was observed for the duplex containing normal cytosine instead of (m)C. Incorporation of an AQ sensitizer into the interior of a strand induced an enhanced one-electron photooxidation, presumably because of a much larger intersystem crossing efficiency, leading to an efficient strand cleavage at the target (m)C site in DNA. Optimization of the photosensitizer could afford more strand cleavage at (m)C in DNA, thereby allowing for the more sensitive detection of the target (m)C on a sequencing gel. (キーワード) Anthraquinones / DNA / DNA Cleavage / Oligonucleotides / Oxidation-Reduction / Photochemical Processes / Photosensitizing Agents (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrp105 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19749334 ● Search Scopus @ Elsevier (PMID): 19749334 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/nrp105 (DOI: 10.1093/nass/nrp105, PubMed: 19749334)
35.	Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : pH effect on the one-electron photooxidation of 5-methylcytosine with naphthoquinone sensitizer., Nucleic Acids Symposium Series, No.52, 447-448, 2008. (要約) The pH effect on the one-electron photooxidation of 5-methyl-2'-deoxycytidine (d(m)C) by sensitization with 1,4-naphthoquinone (NQ) was investigated. Upon photoirradiation of d(m)C in the presence of NQ under slightly acidic conditions such as pH 5.0, 5-formyl-2'- deoxycytidine (d(f)C) was formed efficiently, whereas similar NQ-photosensitized oxidation of d(m)C proceeded to lesser extent under neutral or basic conditions. Under slightly acidic conditions, dmC radical cation favors to undergo irreversible deprotonation at the C(5)-methyl group to form a methyl-centered radical, leading to a higher yield of the alkali-labile oxidation products including d(f)C. In contrast, the d(m)C radical cation competitively undergoes deprotonation at the exocyclic N(4)-amino group under neutral or basic conditions, resulting in a decreased yield of NQ-photosensitized oxidation products. (キーワード) Deoxycytidine / Electrons / Hydrogen-Ion Concentration / Naphthoquinones / Oxidation-Reduction / Photosensitizing Agents (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrn227 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18776446 ● Search Scopus @ Elsevier (PMID): 18776446 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/nrn227 (DOI: 10.1093/nass/nrn227, PubMed: 18776446)
36.	Kazuhito Tanabe, Emi Kuraseko, Eiji Matsumoto, Hisatsugu Yamada, Takeo Ito and Sei-ichi Nishimoto : Radiolytic ligation of oligodeoxynucleotides possessing disulfide bond., Nucleic Acids Symposium Series, No.52, 459-460, 2008. (要約) Hypoxic X-radiolysis of diluted aqueous solutions was performed to generate hydrated electrons that induced one-electron reduction of oligodeoxynucleotides (ODNs) possessing a disulfide bond. Upon hypoxic irradiation, reductive ligation reaction between two types of ODNs occurred in the presence of a template ODN strand, resulting in the formation of a prescribed ODN in substantial amounts. (キーワード) Disulfides / Electrons / Oligodeoxyribonucleotides / Oxidation-Reduction / X-Rays (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrn233 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18776452 ● Summary page in Scopus @ Elsevier: 2-s2.0-78649425944 (DOI: 10.1093/nass/nrn233, PubMed: 18776452, Elsevier: Scopus)
37.	Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-Ichi Nishimoto : The pH effect on the naphthoquinone-photosensitized oxidation of 5-methylcytosine., Chemistry - A European Journal, Vol.14, No.33, 10453-10461, 2008. (要約) The pH effect on the one-electron photooxidation of 5-methyl-2'-deoxycytidine (d(m)C) by sensitization with 2-methyl-1,4-naphthoquinone (NQ) was investigated. Photoirradiation of an aqueous solution containing d(m)C and NQ under slightly acidic conditions of pH 5.0 efficiently produced 5-formyl-2'-deoxycytidine, whereas similar NQ-photosensitized oxidation of d(m)C proceeded to a lesser extent under more acidic or basic conditions. Fluorescence-quenching experiments revealed that the less-efficient photooxidation at pH values below 4.5 is attributed to the decreased rate of one-electron oxidation of d(m)C owing to protonation at the N(3)-position. The NQ-photosensitized oxidation of an N(4)-dimethyl-substituted d(m)C derivative under various pH conditions also suggests that the pH change in the range of 5.0 to 8.0 may be responsible for a reversible deprotonation-protonation equilibrium at the N(4)-exocyclic amino group of the d(m)C radical cation. In accord with the photochemical reactivity of monomeric d(m)C, the 5-methylcytosine residue in oligodeoxynucleotides was oxidized efficiently by photoexcited NQ-tethered oligodeoxynucleotides under slightly acidic conditions to form an alkali-labile 5-formylcytosine residue. (キーワード) 5-Methylcytosine / Chromatography, High Pressure Liquid / Hydrogen-Ion Concentration / Molecular Structure / Naphthoquinones / Oxidation-Reduction / Photosensitizing Agents (出版サイトへのリンク) ● Publication site (DOI): 10.1002/chem.200800840 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18830980 ● Search Scopus @ Elsevier (PMID): 18830980 ● Search Scopus @ Elsevier (DOI): 10.1002/chem.200800840 (DOI: 10.1002/chem.200800840, PubMed: 18830980)
38.	Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : Photoelectrochemical Approach to Detection of Methylation Status of Cytosine Base in DNA, Photomed. Photobiol., Vol.30, No.1, 21-22, 2008.
39.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Photocurrent response after enzymatic treatment of DNA duplexes immobilized on gold electrodes: electrochemical discrimination of 5-methylcytosine modification in DNA., Organic & Biomolecular Chemistry, Vol.6, No.2, 272-277, 2007. (要約) We demonstrate a photoelectrochemical approach to the detection of the methylation status of cytosine bases in DNA. We prepared anthraquinone (AQ) photosensitizer-tethered oligodeoxynucleotide (ODN) duplexes bearing 5-methylcytosine (mC) or the corresponding cytosine (C) at a restriction site of the ODN strand immobilized on gold electrodes, and measured their photocurrent responses arising from hole transport after enzymatic digestion. Treatment with HapII or HhaI of the duplexes bearing normal C led to strand cleavage, and the photosensitizer unit was eliminated from the ODN strand immobilized on the gold electrode, exclusively reducing the photocurrent density. With a similar treatment, the duplexes bearing mC showed higher photocurrent responses arising from hole transport through the duplex. This significant difference in the photocurrent response between mC and normal C residues in DNA on the gold electrodes is potentially applicable to the detection of mC modification in DNA. (キーワード) 5-Methylcytosine / Anthraquinones / Cytosine / DNA / DNA Methylation / Deoxyribonuclease HpaII / Deoxyribonucleases, Type II Site-Specific / Electrochemistry / Electrodes / Electroretinography / Gold / Molecular Conformation / Oligodeoxyribonucleotides / Photochemistry / Photosensitizing Agents / Time Factors (出版サイトへのリンク) ● Publication site (DOI): 10.1039/b715260d (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18174996 ● Search Scopus @ Elsevier (PMID): 18174996 ● Search Scopus @ Elsevier (DOI): 10.1039/b715260d (DOI: 10.1039/b715260d, PubMed: 18174996)
40.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Fluorometric identification of 5-methylcytosine modification in DNA: combination of photosensitized oxidation and invasive cleavage., Bioconjugate Chemistry, Vol.19, No.1, 20-23, 2007. (要約) An efficient fluorometric detection system of DNA methylation has been developed by a combination of a photooxidative DNA cleavage reaction with 2-methyl-1,4-naphthoquinone (NQ) chromophore and an invasive cleavage reaction with human Flap endonuclease-1. Enzymatic treatment of a mixture of photochemically fragmented target oligodeoxynucleotides (ODNs) at 5-methylcytosine mC) and hairpin-like probe oligomer possessing a fluorophore (F) and a quencher (D) resulted in a dramatic enhancement of fluorescence. In contrast, fluorescence emission for the ODN containing cytosine but not mC at the target sequence was extremely weak. In addition, by monitoring the fluorescence change, this system allows for the detection of mC in DNA at subfemtomole amounts. This system would provide a highly sensitive protocol for determining the methylation status in DNA by fluorescence emission. (キーワード) 5-Methylcytosine / Base Sequence / DNA Cleavage / DNA Methylation / Flap Endonucleases / Fluorometry / Humans / Oligonucleotides / Oxidation-Reduction / Photochemistry / Temperature / Vitamin K 3 (出版サイトへのリンク) ● Publication site (DOI): 10.1021/bc7003318 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18038964 ● Search Scopus @ Elsevier (PMID): 18038964 ● Search Scopus @ Elsevier (DOI): 10.1021/bc7003318 (DOI: 10.1021/bc7003318, PubMed: 18038964)
41.	Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : One-electron photooxidation and site-selective strand cleavage at 5-methylcytosine in DNA by sensitization with 2-methyl-1,4-naphthoquinone-tethered oligonucleotides., Journal of the American Chemical Society, Vol.129, No.25, 8034-8040, 2007. (要約) Photosensitized one-electron oxidation was applied to discriminate a specific base site of 5-methylcytosine (mC) generated in DNA possessing a partial sequence of naturally occurring p53 gene, using a sensitizing 2-methyl-1,4-naphthoquinone (NQ) chromophore tethered to an interior of oligodeoxynucleotide (ODN) strands. Photoirradiation and subsequent hot piperidine treatment of the duplex consisting of mC-containing DNA and NQ-tethered complementary ODN led to oxidative strand cleavage selectively at the mC site, when the NQ chromophore was arranged so as to be in close contact with the target mC. The target mC is most likely to be one-electron oxidized into the radical cation intermediate by the sensitization of NQ. The resulting mC radical cation may undergo rapid deprotonation and subsequent addition of molecular oxygen, thereby leading to its degradation followed by strand cleavage at the target mC site. In contrast to mC-containing ODN, ODN analogs with replacement of normal cytosine, thymine, adenine, or guanine at the mC site underwent less amount of such an oxidative strand cleavage at the target base site, presumably due to occurrence of charge transfer and charge recombination processes between the base radical cation and the NQ radical anion. Furthermore, well designed incorporation of the NQ chromophore into an interior of ODN could suppress a competitive strand cleavage at consecutive guanines, which occurred as a result of positive charge transfer. Thus, photosensitization by an NQ-tethered ODN led to one-electron oxidative strand cleavage exclusively at the target mC site, providing a convenient method of discriminating mC in naturally occurring DNA such as human p53 gene as a positive band on a sequencing gel. (キーワード) DNA / Electrons / Nucleic Acid Conformation / Oligonucleotides / Oxidation-Reduction / Photochemistry / Vitamin K 3 (出版サイトへのリンク) ● Publication site (DOI): 10.1021/ja071369s (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17547405 ● Search Scopus @ Elsevier (PMID): 17547405 ● Search Scopus @ Elsevier (DOI): 10.1021/ja071369s (DOI: 10.1021/ja071369s, PubMed: 17547405)
42.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-Ichi Nishimoto : Site-selective strand cleavage at methylated cytosine: regional effect of naphthoquinone chromophore on the one-electron photooxidation of 5-methylcytosine and positive charge transfer in DNA., Nucleic Acids Symposium Series, No.51, 219-220, 2007. (要約) Photoirradiation and subsequent hot piperidine treatment of the duplex consisting of 5-methylcytosine ((m)C)-containing DNA and 2-methyl-1,4-naphthoquinone (NQ)-tethered complementary ODN led to oxidative strand cleavage selectively at the (m)C site, when the NQ was arranged so as to be in close contact with the target (m)C. Well designed incorporation of NQ into an interior of ODN could suppress a competitive strand cleavage at consecutive guanines, which occurred as a result of positive charge transfer. In contrast to the ODNs bearing NQ in an interior of the strand, photoirradiation of the duplex with an NQ tethered to a flexible methylene linker at the strand end resulted in not only strong strand cleavage at (m)C but also small amount of strand cleavage at the G doublet. Thus, optimization of the regional position of photosensitizing NQ could provide exclusive strand cleavage at (m)C without unfavorable cleavage at G. (キーワード) 5-Methylcytosine / DNA / DNA Methylation / Electrons / Genes, p53 / Humans / Oligodeoxyribonucleotides / Oxidation-Reduction / Photosensitizing Agents / Sequence Analysis, DNA / Vitamin K 3 (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrm110 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18029665 ● Search Scopus @ Elsevier (PMID): 18029665 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/nrm110 (DOI: 10.1093/nass/nrm110, PubMed: 18029665)
43.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Sensitive discrimination between cytosine and 5-methylcytosine in DNA by a modified invader method., Nucleic Acids Symposium Series, No.50, 163-164, 2006. (要約) We designed a detection system of 5-methylcytosine ((m)C) in DNA by a combination of photooxidative DNA cleavage reaction of 2-methyl-1,4-naphthoquinone chromophore with invader technology. Enzymatic treatment of a mixture of photochemically fragmented target oligodeoxynucleotides (ODNs) at (m)C and probe oligomer possessing a fluorophore and a quencher resulted in a dramatic enhancement of fluorescence. In contrast, fluorescence emission for the ODN containing C but not (m)C at the target sequence was extremely weak. We could detect (m)C in sub-femtomol DNA by monitoring the fluorescence change. (キーワード) 5-Methylcytosine / Cytosine / DNA / Flap Endonucleases / Fluorescent Dyes / Nucleic Acid Hybridization / Oligodeoxyribonucleotides / Oligonucleotide Probes / Photochemistry / Spectrometry, Fluorescence (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/nrl081 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17150868 ● Search Scopus @ Elsevier (PMID): 17150868 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/nrl081 (DOI: 10.1093/nass/nrl081, PubMed: 17150868)
44.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-Ichi Nishimoto : Cleavage at 5-methylcytosine in DNA by photosensitized oxidation with 2-methyl-1,4-naphthoquinone tethered oligodeoxynucleotides., Bioorganic & Medicinal Chemistry Letters, Vol.15, No.3, 665-668, 2005. (要約) Photosensitized one-electron oxidation of 5-methylcytosine in DNA by 2-methyl-1,4-naphthoquinone, attached to 5'-end of an oligodeoxynucleotide strand, produced 5-formylcytosine and led to selective DNA strand cleavage at the original 5-methylcytosine configuration. This specified photoreaction is useful for positive display of 5-methylcytosine in DNA on a sequencing gel. (キーワード) 5-Methylcytosine / Autoradiography / DNA Damage / Humans / Hydrolysis / Naphthoquinones / Oligodeoxyribonucleotides / Oxidation-Reduction / Phosphorus Radioisotopes / Photochemistry / Structure-Activity Relationship / Vitamin K 3 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bmcl.2004.11.038 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15664833 ● Search Scopus @ Elsevier (PMID): 15664833 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmcl.2004.11.038 (DOI: 10.1016/j.bmcl.2004.11.038, PubMed: 15664833)
45.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Detection of 5-methylcytosine in DNA by photo-functionalized oligodeoxynucleotides possessing 2-methyl-1,4-naphthoquinone chromophore., Nucleic Acids Symposium Series, No.49, 149-150, 2005. (要約) We developed a method for detection of 5-methylcytosine in DNA by photosensitized oxidation, using photo-functionalized oligodeoxynucleotides possessing 2-methyl-1,4-naphthoquinone chromophores (NQ) at the interior of the strand. The photooxidation and subsequent hot piperidine treatment of duplex consisting of the NQ-tethered oligodeoxynucleotide and its complementary strand bearing 5-methylcytosine residue led to selective DNA strand cleavage at the 5-methylcytosine residue, whereas no strand cleavage was detected for the control duplex with normal cytosine residue but not 5-methylcytosine. (キーワード) 5-Methylcytosine / Light / Oligodeoxyribonucleotides / Oxidation-Reduction / Sequence Analysis, DNA / Temperature / Vitamin K 3 (出版サイトへのリンク) ● Publication site (DOI): 10.1093/nass/49.1.149 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17150677 ● Search Scopus @ Elsevier (PMID): 17150677 ● Search Scopus @ Elsevier (DOI): 10.1093/nass/49.1.149 (DOI: 10.1093/nass/49.1.149, PubMed: 17150677)
46.	Yoshihiro Matano, Teppei Hisanaga, Hisatsugu Yamada, Shingo Kusakabe, Hazumi Nomura and Hiroshi Imahori : Remarkable substituent effects on the oxidizing ability of triarylbismuth dichlorides in alcohol oxidation., The Journal of Organic Chemistry, Vol.69, No.25, 8676-8680, 2004. (要約) Substituent effects on the oxidizing ability of triarylbismuth dichlorides were examined by intermolecular and intramolecular competition experiments on geraniol oxidation in the presence of DBU. It was found that the oxidizing ability of the dichlorides increases with increasing electron-withdrawing ability of the para substituents, and by introduction of a methyl group at the ortho position of the aryl ligands attached to the bismuth. The intermolecular and intramolecular H/D kinetic isotope effects observed for the competitive oxidation of p-bromobenzyl alcohols indicate that the rate-determining step involves C-H bond cleavage. Several primary and secondary alcohols were oxidized efficiently under mild conditions by the combined use of newly developed organobismuth(V) oxidants and DBU. (出版サイトへのリンク) ● Publication site (DOI): 10.1021/jo0485740 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15575743 ● Search Scopus @ Elsevier (PMID): 15575743 ● Search Scopus @ Elsevier (DOI): 10.1021/jo0485740 (DOI: 10.1021/jo0485740, PubMed: 15575743)

総説・解説:

1.	芝一休, 山田久嗣, 富永正英, 宇都義浩 : 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, 放射線生物研究, Vol.51, No.3, 216-229, 2016年9月.
2.	山田久嗣 : 生体内代謝プロセスの多重共鳴 NMR モニタリングと多重共鳴 MRI に展開可能な高感度化分子プローブの開発, 公益社団法人日本化学会生体機能関連化学部会ニュースレター, Vol.27, No.3, 17-20, 2012年.
3.	小松広和, 原田浩, 山田久嗣, 伊藤健雄, 田邉一仁, 西本清一 : Rhodol骨格に基づく新規低酸素環境認識プローブの開発とバイオイメージングへの応用, 日本分析化学会第58年会展望とトピックス, 14, 2009年9月.
4.	Takeo Ito, Kazuhito Tanabe, Hisatsugu Yamada, Hiroshi Hatta and Sei-ichi Nishimoto : Radiation- and photo-induced activation of 5-fluorouracil prodrugs as a strategy for the selective treatment of solid tumors., Molecules, Vol.13, No.10, 2370-2384, Oct. 2008. (要約) 5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation. (キーワード) Drug Delivery Systems / Fluorouracil / Humans / Neoplasms / Prodrugs / Radiation, Ionizing / Ultraviolet Rays (出版サイトへのリンク) ● Publication site (DOI): 10.3390/molecules13102370 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18830160 ● Summary page in Scopus @ Elsevier: 2-s2.0-55249084962 (DOI: 10.3390/molecules13102370, PubMed: 18830160, Elsevier: Scopus)

国際会議:

1.	Nobuya Fujita, Hisatsugu Yamada, Takanori Komaki, Yu Kimura, Yasuhiro Aoyama and Teruyki Kondo : In Vivo 3D Photoacoustic Imaging of Tumor Using a Near-infrared Dye-conjugated Polymer Probe under Hemoglobin-suppressing Conditions, The International Chemical Congress of Pacific Basin Societies 2020 (Pacifichem 2020), Dec. 2021.
2.	Yuta Matsui, Hisatsugu Yamada, Yasuhiro Aoyama, Yu Kimura and Teruyuki Kondo : Near-Infrared Dye-Conjugated Betain Polymer Probes for Photoacoustic Imaging of ROS in Tumor, JGP Chem&ChemEn International Workshop: Sustainability-Oriented Organic Synthesis, Sep. 2018.
3.	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.
4.	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.
5.	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.
6.	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.
7.	Yuki Suzuki, Hisatsugu Yamada, Yu Kimura, Aoi Son, Kazuhito Tanabe, Akio Toshimitsu, Yasuhiro Aoyama and Teruyuki Kondo : A New Theranostic Probe for Tumor Hypoxia Based on Triple-resonance NMR and Radio-sensitization, Pacifichem 2015, Honolulu, HI, Dec. 2015.
8.	Natsuki Matsumoto, Hisatsugu Yamada, Yu Kimura, Akio Toshimitsu, Yasuhiro Aoyama and Teruyuki Kondo : Biocompatible Phosphorylchline Polymer Probes for In Vivo Photoacoustic Imaging, Pacifichem 2015, Honolulu, HI, Dec. 2015.
9.	Hisatsugu Yamada, Yoshinori Hasegawa, Hirohiko Imai, Yuki Takayama, Fuminori Sugihara, Tetsuya Matsuda, Hidehito Tochio, Masahiro Shirakawa, Shinsuke Sando, Yu Kimura, Akio Toshimitsu, Yasuhiro Aoyama and Teruyuki Kondo : Magnetic resonance imaging of tumor with a self-traceable phosphorylcholine polymer., IKCOC-13, Kyoto, Nov. 2015.
10.	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.
11.	Hisatsugu Yamada, Keigo Mizusawa, Ryuji Igarashi, Hidehito Tochio, Masahiro Shirakawa, Yasuhiko Tabata, Yu Kimura, Teruyuki Kondo, Yasuhiro Aoyama and Shinsuke Sando : Triple resonance NMR in application to in situ monitoring of targeted metabolic reaction and its inhibition by a clinical drug, 244th ACS National Meeting, Philadelphia, PA, Aug. 2012.
12.	Hisatsugu Yamada, Keigo Mizusawa, Ryuji Igarashi, Hidehito Tochio, Masahiro Shirakawa, Yasuhiko Tabata, Yu Kimura, Teruyuki Kondo, Yasuhiro Aoyama and Shinsuke Sando : Direct In Situ Monitoring of Pyrimidine Catabolism and Its Inhibition Using Triple Resonance NMR Analysis, 38th International Symposium on Nucleic Acids Chemistry, Sapporo, Japan, Nov. 2011.
13.	Yuya Kitauchi, Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Efficient One-Electron Photooxidation and Site-Selective Strand Cleavage at 5-Methylcytosine in DNA by Oligonucleotide Bearing 9,10-Anthraquinone Sensitizer, Pacifichem 2010, Honolulu, HI, Dec. 2010.
14.	Masayuki Kuraka, Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Selective Trapping at Cytosine Derivatives of Photosensitizer-Injected and Migrated Hole in DNA, Pacifichem 2010, Honolulu, HI, Dec. 2010.
15.	Shosuke Aoai, Kazuhito Tanabe, Takeo Ito, Hisatsugu Yamada, Hiroshi Hatta and Sei-ichi Nishimoto : Radiolytic Reduction Characteristics of Thiothymidines Dimmer with A Disulfide Linkage between Both 4-Positions, Pacifichem 2010, Honolulu, HI, Dec. 2010.
16.	Hirokazu Komatsu, Hiroshi Harada, Hisatsugu Yamada, Takeo Ito, Kazuhito Tanabe, Masahiro Hiraoka and Sei-ichi Nishimoto : Design of Hypoxia-Sensitive Fluorescent Probes Activated by Enzymatic One-Electron Reduction for Hypoxic Cancer Cell Imaging, Pacifichem 2010, Honolulu, HI, Dec. 2010.
17.	Masayuki Kurata, Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Efficient Hole Trapping at C(5)-Substituted Cytosine in the Photosensitizer-Injected Positive Charge Transfer through DNA Duplex, 7th International Symposium on Nucleic Acids Chemistry, Yokohama, Japan, Nov. 2010.
18.	Yuya Kitauchi, Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : One-Electron Oxidation at 5-Methylcytosine Induced by the Photosensitizer-Injected Positive Charge Transfer through DNA, 7th International Symposium on Nucleic Acids Chemistry, Yokohama, Japan, Nov. 2010.
19.	Takeo Ito, Tsukasa Uchida, Kazuhito Tanabe, Hisatsugu Yamada and Sei-ichi Nishimoto : Photoinduced Electron Injection into DNA by N-Cyclopropyl-1-aminonaphthalene, 7th International Symposium on Nucleic Acids Chemistry, Yokohama, Japan, Nov. 2010.
20.	Shosuke Aoai, Kazuhito Tanabe, Takeo Ito, Hisatsugu Yamada and Sei-ichi Nishimoto : Photoinduced Modification of 4-Thiothymidine into Thymidine and 5-Methylcytidine Derivatives, 7th International Symposium on Nucleic Acids Chemistry, Yokohama, Japan, Nov. 2010.
21.	Hisatsugu Yamada, Yuya Kitauchi, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Efficient Photooxidative Strand Cleavage at 5-Methylcytosine in DNA by Sensitization with 9,10-Anthraquinone-Tethered Oligonucleotides, 6th International Symposium on Nucleic Acids Chemistry, Takayama, Japan, Sep. 2009.
22.	Kazuhito Tanabe, Hisatsugu Yamada, Takeo Ito and Sei-ichi Nishimoto : Photoelectrochemical Identification of 5-Methylcytosine Modification in DNA: Combination of Photosensitization and Enzymatic Cleavage, 6th International Symposium on Nucleic Acids Chemistry, Takayama, Japan, Sep. 2009.
23.	Hisatsugu Yamada, Yuya Kitauchi, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : Photochemical Approach to Discrimination of Methylated Cytosine in DNA: pH Effect on the Naphthoquinone-Sensitized One-Electron Photooxidation of 5-Methylcytosine, XXIV International Conference on Photochemistry, Toledo, Spain, Jul. 2009.
24.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Fluorometric Identification of Methylated Cytosine in DNA: Combination of Naphthoquinone-Sensitized Photooxidation and Invasive Cleavage, 2nd International Symposium on Nanomedicine Asian Core Symposium Nano and Biomedical Molecular Science, Okazaki, Japan, Feb. 2009.
25.	Hisatsugu Yamada, Kazuhito Tanabe, Takeo Ito and Sei-ichi Nishimoto : pH Effect on the One-Electron Photooxidation of 5-Methylcytosine with Naphthoquinone Sensitizer, Joint Symposium of the 18th International Roundtable on Nuclesides, Nucleotides and Nucleic Acids and the 35th International Symposium on Nucleic Acids Chemistry, Kyoto, Japan, Sep. 2008.
26.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Site-Selective Strand Cleavage at Methylated Cytosine: Regional Effect of Naphthoquinone Chromophore on the One-Electron Photooxidation of 5-Methylcytosine and Positive Charge Transfer in DNA, 5th International Symposium on Nucleic Acids Chemistry, Tokyo, Japan, Nov. 2007.
27.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Evaluation of the Regional Effect of 2-Methyl-1,4-naphthoquinone Chromophore on the One-Electron Photooxidation and Selective Strand Cleavage at 5-Methylcytosine in DNA, XXIIIst International Conference on Photochemistry, Cologne, Germany, Jul. 2007.
28.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Photooxidative DNA Cleavage at 5-Methylcytosine by Naphthoquinone-Containing Oligodeoxynucleotides, XXIst IUPAC Symposium on Photochemistry, Kyoto, Japan, Apr. 2006.
29.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Detection of 5-Methylcytosine in DNA by Photo-Functionalized Oligodeoxynucleotides Possessing 2-Methyl-1,4-naphthoquinone Chromophore, Pacifichem 2005, Honolulu, HI, Dec. 2005.
30.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Detection of 5-Methylcytosine in DNA by Photo-Functionalized Oligodeoxynucleotides Possessing 2-Methyl-1,4-naphthoquinone Chromophore, 4th International Symposium on Nucleic Acids Chemistry, Hakata, Japan, Sep. 2005.

国内講演発表:

1.	樫原誉, 合田萌々花, 宇都義浩, 山田久嗣 : 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, 2022年11月.
2.	横山寛樹, 三浦理紗子, 山田久嗣, 今井宏彦, 木村祐, 青山安宏, 古矢修一, 近藤輝幸 : ホウ素中性子捕捉療法のための薬剤輸送担体の開発と構造解析, 第15回日本分子イメージング学会学術集会, 2021年5月.
3.	藤田展也, 山田久嗣, 青山安宏, 木村祐, 近藤輝幸 : 近赤外蛍光色素を導入した双極性ホスホリルコリンポリマープローブを用いた腫瘍の3次元光音響イメージング, 第15回日本分子イメージング学会学術集会, 2021年5月.
4.	村上知広, 山田久嗣, 今井宏彦, 青山安宏, 木村祐, 近藤輝幸 : 化学交換飽和移動(CEST)MRIに有効な新規ホスホリルセリンポリマープローブ, 第101回日本化学会春季年会, 2021年3月.
5.	藤田展也, 山田久嗣, 青山安宏, 木村祐, 近藤輝幸 : 近赤外蛍光色素を導入した双極性ポリマープローブを用いる腫瘍の3次元光音響イメージング, 第101回日本化学会春季年会, 2021年3月.
6.	宇都義浩, 井土侑香, 山田久嗣, 永尾司, 呉貴卿, 田坂徹, 鵜沼英樹, 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, 2020年12月.
7.	田坂徹, 井土侑香, 小林彩, 藤井理, 山田久嗣, 永尾司, 永尾公基, 永尾侑士, 宇都義浩 : 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, 2020年12月.
8.	村上知広, 山田久嗣, 今井宏彦, 青山安宏, 木村祐, 近藤輝幸 : 化学交換飽和移動(CEST)MRIに有効なホスホリルセリンポリマープローブ:側鎖ホスホリル基がCEST効果に及ぼす影響, 第100回日本化学会春季年会, 2020年3月.
9.	國枝由香莉, 篠原侑成, 田中雄也, 山花啓梨, 藤原由莉, 山田久嗣, 宇都義浩 : 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, 2020年2月.
10.	宇都義浩, 小西大輔, 折村奈美, 山田久嗣, 富永正英, 生島仁史, 大豆本圭, 上原久典 : 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, 2020年2月.
11.	田坂徹, 前橋克彦, 井土侑香, 山田久嗣, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿, 宇都義浩 : 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, 2019年12月.
12.	藤原由莉, 二若真菜, 小西大輔, 折村奈美, 山田久嗣, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 宇都義浩 : 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, 2019年11月.
13.	小西大輔, 二若真菜, 藤原由莉, 折村奈美, 山田久嗣, 富永正英, 生島仁史, 上原久典, 大豆本圭, 宇都義浩 : 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, 2019年11月.
14.	坂東康平, 小林彩, 中川千明, 山田久嗣, 久保健太郎, 乾利夫, 宇都義浩 : 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, 2019年11月.
15.	岸田理沙, 嶋田宏輝, 山田久嗣, 今井宏彦, 宇都義浩 : 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, 2019年11月.
16.	國枝由香莉, 篠原侑成, 田中雄也, 山花啓梨, 藤原由莉, 山田久嗣, 宇都義浩 : 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, 2019年11月.
17.	村上知広, 山田久嗣, 今井宏彦, 青山安宏, 木村祐, 近藤輝幸 : 化学交換飽和移動(CEST)–MRIプローブとしての新規ホスホリルセリンポリマーの合成と機能評価, 第58回 NMR討論会(2019), 2019年11月.
18.	宇都義浩, 羽生紋佳, 楠橋由貴, 二若真菜, 山田久嗣, 富永正英, 生島仁史 : 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, 2019年6月.
19.	宇都義浩, 楠橋由貴, 二若真菜, 山田久嗣, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 山中信康, 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, 2019年4月.
20.	田坂徹, 前橋克彦, 井土侑香, 山田久嗣, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿, 宇都義浩 : 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, 2019年3月.
21.	宇都義浩, 山田久嗣, 中島元夫, 石塚昌宏, 田中徹, 山中信康, 倉橋司, 久保健太郎, 乾利夫 : 医工連携による超音波増感剤および免疫賦活剤の開発, 日本化学会第99春季年会, 2019年3月.
22.	西山真央, 羽生紋佳, 山田久嗣, 宇都義浩 : 細胞核移行性をもつ新規ベンゾトリアジオキサイド誘導体の創製と低酸素がんに対する放射線増感効果, 日本化学会第99春季年会, 2019年3月.
23.	井土侑香, 田坂徹, 西川諒平, 中村雄太, 坂東康平, 山田久嗣, 前橋克彦, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿, 宇都義浩 : 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, 日本化学会第99春季年会, 2019年3月.
24.	山花啓梨, 篠原侑成, 羽生紋佳, 田中雄也, 山田久嗣, 宇都義浩 : 放射線増感効果の向上を目指した新規アセチルグルコース修飾Gefitinib誘導体の創製, 日本化学会第99春季年会, 2019年3月.
25.	二若真菜, 楠橋由貴, 藤原由莉, 小西大輔, 山田久嗣, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 山中信康, 倉橋司, 宇都義浩 : アミノレブリン酸を用いた超音波力学療法に対する低酸素細胞放射線増感剤の増強効果, 日本化学会第99春季年会, 2019年3月.
26.	宇都義浩, 前橋克彦, 井土侑香, 山田久嗣, 田坂徹, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 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, 2018年11月.
27.	宇都義浩, 勝占華世, 楠橋由貴, 山田久嗣, 土屋浩一郎, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 山中信康, 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, 2018年4月.
28.	羽生紋佳, 上﨑里砂, 上島一輝, 金子友子, 山田久嗣, 富永正英, 壽賀正城, 山下智弘, 沖本智昭, 宇都義浩 : 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, 2018年3月.
29.	楠橋由貴, 勝占華世, 二若真菜, 林佑美, 山田久嗣, 大崎智弘, 石塚昌宏, 田中徹, 山中信康, 倉橋司, 宇都義浩 : 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, 2018年3月.
30.	宮崎豊久, 楠橋由貴, 羽生紋佳, 嶋田宏輝, 山田久嗣, 近藤輝幸, 宇都義浩 : 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, 2018年3月.
31.	西川諒平, 桒田依洋, 井亀沙紀, 井土侑香, 遠藤亮, 山田久嗣, 宇都義浩, 田坂徹, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 呉貴卿 : 低分子化したホエイプロテインを用いたマクロファージ活性化剤の開発, 日本化学会第98春季年会, 2018年3月.
32.	篠原侑成, 芝一休, 山田久嗣, 遠藤良夫, 石塚昌宏, 田中徹, 宇都義浩 : 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, 2018年3月.
33.	宇都義浩, 宮本大輔, 上崎里砂, 羽生紋佳, 二若真菜, 山田久嗣 : 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, 2018年2月.
34.	宇都義浩, 井亀沙紀, 桒田依洋, 西川諒平, 山田久嗣, 大崎智弘, 久保健太郎, 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, 2017年12月.
35.	金子友子, 上﨑里砂, 羽生紋佳, 山田久嗣, 宇都義浩, 壽賀正城, 山下智弘, 沖本智昭, 富永正英 : 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, 2017年12月.
36.	宇都義浩, 桒田依洋, 井亀沙紀, 西川諒平, 井土侑香, 遠藤亮, 山田久嗣, 田坂徹, 鵜沼英樹, 徳永彦, 早川明夫, 呉明輝, 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, 2017年12月.
37.	宇都義浩, 井亀沙紀, 桒田依洋, 西川諒平, 山田久嗣, 大崎智弘, 久保健太郎, 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, 2017年7月.
38.	宇都義浩, 勝占華世, 楠橋由貴, 山田久嗣, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 中馬篤, 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, 2017年6月.
39.	宇都義浩, 鈴木拓磨, 勝占華世, 楠橋由貴, 山田久嗣, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 中馬篤, 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, 2017年4月.
40.	松本夏季, 山田久嗣, 小西宏明, 孫安生, 木村祐, 青山安宏, 近藤輝幸 : 近赤外蛍光色素を結要したホスホリルコリンポリマープローブの腫瘍集積性と体内動態, 第11回日本分子イメージング学会学術集会, 2016年5月.
41.	鈴木祐貴, 山田久嗣, 木村祐, 田邉一仁, 孫安生, 青山安宏, 近藤輝幸 : 腫瘍低酸素領域に集積するセラノスティクスを目指した13C/15N-ラベル化ホスホリルコリンプローブの合成と機能評価, 第96回日本化学会春季年会, 2016年3月.
42.	宇都義浩, 遠藤秀彰, 八重和憲, 山田久嗣, 原毅弘, 富永正英 : 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, 2016年2月.
43.	宇都義浩, 井亀沙紀, 九十九咲, 藤洸臣, 佐々木俊英, 濱田健, 桒田依洋, 山田久嗣, 西方敬人, 口池大輔, 久保健太郎, Mette Martin, 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, 2015年12月.
44.	伊木悠, 土谷享, 野中洋, 金野智浩, 山田久嗣, 近藤輝幸, 青山安宏, 山東信介 : 双性イオンポリマーを基盤とする新規DDS材料設計指針の構築, 第5回CSJ化学フェスタ, 2015年10月.
45.	松本夏季, 山田久嗣, 木村祐, 年光昭夫, 青山安宏, 近藤輝幸 : 腫瘍の光音響イメージングに向けた色素結合型ホスホリルコリンポリマープローブの開発, 第5回 CSJ化学フェスタ 2015, 2015年10月.
46.	伊木悠, 土谷亨, 野中洋, 金野智浩, 山田久嗣, 近藤輝幸, 青山安宏, 山東信介 : 双性イオンポリマーの腫瘍選択的集積能に関する研究, 第9回バイオ関連化学シンポジウム, 2015年9月.
47.	松本夏季, 山田久嗣, 木村祐, 年光昭夫, 青山安宏, 近藤輝幸 : 近赤外色素を結合したホスホリルコリンポリマープローブによる腫瘍の光音響イメージング, 第9回バイオ関連化学シンポジウム, 2015年9月.
48.	鈴木祐貴, 山田久嗣, 木村祐, 田邉一仁, 孫安生, 杤尾豪人, 白川昌宏, 年光昭夫, 青山安宏, 近藤輝幸 : がん低酸素領域に集積するセラノスティックスを目指した安定同位元素ラベル化ホスホリルコリンプローブの合成と機能評価, 第9回バイオ関連化学シンポジウム, 2015年9月.
49.	松本夏季, 山田久嗣, 木村祐, 年光昭夫, 青山安宏, 近藤輝幸 : In vivo 光音響イメージングに向けた生体適合性ホスホリルコリンポリマープローブの物性および体内動態評価, 第10回日本分子イメージング学会学術集会, 2015年5月.
50.	宇都義浩, 玉谷大, 國安翔太, 水木佑輔, 鈴木拓磨, 山田久嗣, 遠藤良夫, 大崎智弘, 中島元夫, 石塚昌宏, 田中徹, 中馬篤, 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, 2015年4月.
51.	鈴木祐貴, 山田久嗣, 木村祐, 田邉一仁, 孫安生, 杤尾豪人, 白川昌宏, 年光昭夫, 青山安宏, 近藤輝幸 : 三重共鳴 NMR を用いたがん低酸素モニタリング: 低酸素細胞を標的とする安定同位元素ラベル化ホスホリルコリンプローブの合成, 第95回日本化学会春季年会, 2015年3月.
52.	松本夏季, 山田久嗣, 木村祐, 年光昭夫, 近藤輝幸 : In Vivo 光音響イメージングのための生体適合性ホスホリルコリンポリマープローブの合成と機能評価, 第95回日本化学会春季年会, 2015年3月.
53.	山田久嗣, 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, 宇都義浩 : 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, 2015年2月.
54.	山田久嗣, 亀田哲郎, 木村祐, 杤尾豪人, 白川昌宏, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 : 脳代謝過程の多重共鳴 NMR 解析に向けた安定同位元素ラベル化 L-Dopaプローブ, 第8回バイオ関連化学シンポジウム, 2014年9月.
55.	山田久嗣, 長谷川嘉則, 鈴木祐貴, 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 : 安定同位元素を集積したポリマーナノプローブによるがんの分子標的 MR イメージング, 第9回日本分子イメージング学会学術集会, 2014年5月.
56.	山田久嗣 : 安定同位体集積化高分子プローブの開発と革新的分子標的磁気共鳴イメージングへの応用, (公社)新化学技術推進協会第3回新化学技術研究奨励賞受賞講演, 2014年5月.
57.	亀田哲郎, 山田久嗣, 木村祐, 杤尾豪人, 白川昌宏, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 : 安定同位元素ラベル化L-DOPAの合成と多重共鳴NMR法によるその代謝反応追跡, 第94回日本化学会春季年会, 2014年3月.
58.	長谷川嘉則, 山田久嗣, 木村祐, 今井宏彦, 松田哲也, 山東信介, 年光昭夫, 青山安宏, 近藤輝幸 : 生体適合性ホスホリルコリンポリマープローブを用いた生体磁気共鳴イメージング, 第94回日本化学会春季年会, 2014年3月.
59.	亀田哲郎, 山田久嗣, 木村祐, 杤尾豪人, 白川昌宏, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 : 生体内代謝プローブとしての ¹³C/¹⁵N ラベル化 L-dopa の合成，および多重共鳴 NMR 法による機能解析, 第3回CSJ Festa, 2013年10月.
60.	長谷川嘉則, 山田久嗣, 木村祐, 今井宏彦, 松田哲也, 杤尾豪人, 白川昌宏, 青山安宏, 年光昭夫, 近藤輝幸 : 多重磁気共鳴イメージングのための安定同位元素集積化高分子プローブ, 第7回バイオ関連化学シンポジウム, 2013年9月.
61.	長谷川嘉則, 山田久嗣, 木村祐, 今井宏彦, 高山裕生, 杉原文徳, 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 : 分子標的 MR イメージングのための新手法, 第8回日本分子イメージング学会学術集会, 2013年5月.
62.	長谷川嘉則, 山田久嗣, 木村祐, 杤尾豪人, 白川昌宏, 杉原文徳, 今井宏彦, 高山裕生, 松田哲也, 矢野哲哉, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 : 高感度多重共鳴 NMR 解析のための安定同位元素ラベル化生体適合性高分子プローブ, 第93回日本化学会春季年会, 2013年3月.
63.	長谷川嘉則, 山田久嗣, 木村祐, 杤尾豪人, 白川昌宏, 杉原文徳, 今井宏彦, 高山裕生, 松田哲也, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 : 安定同位元素ラベル化生体適合性高分子プローブの開発と磁気共鳴イメージングへの応用, 第93回日本化学会春季年会, 2013年3月.
64.	長谷川嘉則, 山田久嗣, 木村祐, 杤尾豪人, 白川昌宏, 杉原文徳, 今井宏彦, 高山裕生, 松田哲也, 矢野哲哉, 山東信介, 青山安宏, 年光昭夫, 近藤輝幸 : 安定同位元素を集積化した生体適合性高分子プローブの合成と多重共鳴 NMR 法による機能評価, 第2回CSJ Festa, 2012年10月.
65.	山田久嗣, 長谷川嘉則, 木村祐, 杤尾豪人, 白川昌宏, 矢野哲哉, 山東信介, 青山安宏, 近藤輝幸 : 高感度多重共鳴 NMR に向けた安定同位体ラベル化高分子タグの開発, 第6回バイオ関連化学シンポジウム, 2012年9月.
66.	長谷川嘉則, 山田久嗣, 木村祐, 杤尾豪人, 白川昌宏, 矢野哲哉, 山東信介, 青山安宏, 近藤輝幸 : 安定同位体ラベル化高分子タグの合成と多重共鳴 NMR 法による機能評価, 第7回日本分子イメージング学会学術集会, 2012年5月.
67.	山田久嗣, 水澤圭吾, 五十嵐龍二, 杤尾豪人, 白川昌宏, 田畑泰彦, 木村祐, 近藤輝幸, 青山安宏, 山東信介 : 基質/代謝物選択的NMRを応用した生体内代謝プロセスの直接追跡と薬剤活性のその場評価, 第92回日本化学会春季年会, 2012年3月.
68.	山田久嗣, 水澤圭吾, 五十嵐龍二, 杤尾豪人, 白川昌宏, 田畑泰彦, 木村祐, 近藤輝幸, 青山安宏, 山東信介 : 多重共鳴NMRを応用した生体内代謝プロセスの直接追跡と薬剤活性のその場評価, 第5回バイオ関連化学シンポジウム, 2011年9月.
69.	山田久嗣, 水澤圭吾, 五十嵐龍二, 杤尾豪人, 白川昌宏, 田畑泰彦, 木村祐, 近藤輝幸, 山東信介, 青山安宏 : 多重共鳴NMR法を用いた生体内代謝プロセスの直接追跡, 第6回日本分子イメージング学会学術集会, 2011年5月.
70.	山田久嗣, 水澤圭吾, 五十嵐龍二, 杤尾豪人, 白川昌宏, 田畑泰彦, 山東信介, 青山安宏 : 生体内代謝プロセスの多重共鳴NMR追跡: 多核多重ラベル化ウラシルの異化代謝反応, 第91回日本化学会春季年会, 2011年3月.
71.	山田久嗣 : 光化学反応を利用したDNAメチル化検出法の開発, バイオ計測・試薬研究会, 2010年3月.
72.	山田久嗣, 北内佑哉, 田邉一仁, 伊藤健雄, 西本清一 : メチル化DNAの光増感酸化反応に及ぼす重水素同位体効果, 第90回日本化学会春季年会, 2010年3月.
73.	北内佑哉, 山田久嗣, 田邉一仁, 伊藤健雄, 西本清一 : アントラキノン光増感剤を導入したオリゴDNA:5-メチルシトシン塩基部位での選択的DNA切断, 第24回生体機能関連化学シンポジウム, 2009年9月.
74.	藏田真之, 山田久嗣, 田邉一仁, 伊藤健雄, 西本清一 : C(5)位に置換基を導入した修飾シトシン含有DNAオリゴマーの合成と四重鎖形成特性, 第24回生体機能関連化学シンポジウム若手フォーラム, 2009年9月.
75.	山田久嗣, 田邉一仁, 西本清一 : 金電極固定化DNA二重鎖に対する制限酵素反応後の光電流応答:DNA内メチル化シトシン塩基の光電気化学的検出, 2008年光化学討論会, 2008年9月.
76.	山田久嗣, 田邉一仁, 伊藤健雄, 西本清一 : DNA内メチル化シトシン塩基の光一電子酸化反応に及ぼすpH効果, 第3回バイオ関連化学合同シンポジウム, 2008年9月.
77.	山田久嗣, 田邉一仁, 西本清一 : DNA内メチル化シトシン塩基の光電気化学的検出法, 第88回日本化学会春季年会, 2008年3月.
78.	山田久嗣, 田邉一仁, 西本清一 : DNA内5-メチルシトシンの光一電子酸化反応に及ぼすpH効果, 2007年光化学討論会, 2007年9月.
79.	山田久嗣, 田邉一仁, 西本清一 : DNA内メチル化シトシン塩基の光化学反応特性, 第87回日本化学会春季年会, 2007年3月.
80.	Hisatsugu Yamada, Kazuhito Tanabe and Sei-ichi Nishimoto : Sensitive Discrimination between Cytosine and 5-Methylcytosine in DNA by A Modified Invader Method, 33rd Symposium on Nucleic Acids Chemistry, Nov. 2006.
81.	山田久嗣, 田邉一仁, 西本清一 : DNAメチル化検出に向けた光化学的アプローチ:ナフトキノン誘導体によるDNA内メチル化シトシン塩基の光酸化反応, 第21回生体機能関連化学シンポジウム若手フォーラム, 2006年9月.
82.	山田久嗣, 田邉一仁, 西本清一 : DNA内5-メチルシトシン塩基検出に向けた光化学的アプローチ:ナフトキノン誘導体の光酸化反応を利用したメチルシトシン部位特異的なDNA切断, 2006年光化学討論会, 2006年9月.
83.	山田久嗣, 田邉一仁, 西本清一 : ナフトキノン部位を持つ光機能性核酸を利用したDNA内5-メチルシトシン塩基の検出, 第86回日本化学会春季年会, 2006年3月.
84.	山田久嗣, 田邉一仁, 西本清一 : ナフトキノン部位をもつ光機能性核酸の合成と物性:5-メチルシトシン変異部位における光酸化的DNA切断, 第85回日本化学会春季年会, 2005年3月.
85.	山田久嗣, 田邉一仁, 八田博司, 西本清一 : ナフトキノン誘導体を導入した機能性DNAの合成とその光化学反応特性, 第84回日本化学会春季年会, 2004年3月.
86.	山田久嗣, 俣野善博, 野村弾, 今堀博 : 新規高原子価ビスマス酸化剤を用いたアルコールの酸化, 第83回日本化学会春季年会, 2003年3月.

特許:

1.	近藤輝幸, 青山安宏, 山田久嗣, 長谷川嘉則, 山東信介, 木村祐, 山内文生, 矢野哲哉, 南昌人, 高橋淳, 金﨑健吾, 小河賢史 : 重合体，前記重合体を有する光音響イメージング用造影剤, 特願2014-217451 (2014年10月), .
2.	近藤輝幸, 青山安宏, 山田久嗣, 今井宏彦, 高山裕生, 長谷川嘉則, 木村祐, 杤尾豪人, 白川昌宏, 杉原文徳, 年光昭夫, 松田哲也, 山東信介, 都築英 : 多核多重核磁気共鳴画像化方法, 特願PCT/JP2014/055848 (2014年3月), 特開WO2014136905 A1 (2014年9月), .
3.	近藤輝幸, 青山安宏, Hisatsugu Yamada, 長谷川嘉則, 杤尾豪人, 木村祐, 白川昌宏, 杉原文徳, 松田哲也, 山東信介, 南昌人, 山内文生, 矢野哲哉 and 都築英寿 : POLYMER, CONTRAST AGENT FOR NUCLEAR MAGNETIC RESONANCE ANALYSIS OR MAGNETIC RESONANCE IMAGING USING THE POLYMER, COMPOUND, AND METHOD OF NUCLEAR MAGNETIC RESONANCE ANALYSIS AND METHOD OF MAGNETIC RESONANCE IMAGING USING THE POLYMER, PCT/JP2013/064819 (May 2013), WO2013176292 A3 (Mar. 2014), .
4.	近藤輝幸, 青山安宏, 山田久嗣, 長谷川嘉則, 杤尾豪人, 木村祐, 白川昌宏, 杉原文徳, 松田哲也, 山東信介, 南昌人, 山内文生, 矢野哲哉, 都築英寿 : 重合体，前記重合体を用いた核磁気共鳴分析用または磁気共鳴イメージング用の造影剤，化合物，前記重合体を用いた核磁気共鳴分析方法および磁気共鳴イメージング方法, 特願2013-103159 (2013年5月), 特開2014-1371 (2014年1月), .
5.	近藤輝幸, 青山安宏, 山田久嗣, 今井宏彦, 高山裕生, 長谷川嘉則, 木村祐, 杤尾豪人, 白川昌宏, 杉原文徳, 年光昭夫, 松田哲也, 山東信介, 都築英 : 多核多重核磁気共鳴画像化方法, 特願2013-45724 (2013年3月), 特開WO2014136905 A1 (2014年9月), .
6.	近藤輝幸, 青山安宏, 山田久嗣, 長谷川嘉則, 杤尾豪人, 木村祐, 白川昌宏, 杉原文徳, 松田哲也, 山東信介, 南昌人, 山内文生, 矢野哲哉, 都築英寿 : 重合体，前記重合体を用いた核磁気共鳴分析用または磁気共鳴イメージング用の造影剤，化合物，前記重合体を用いた核磁気共鳴分析方法および磁気共鳴イメージング方法, 特願2012-118061 (2012年5月), 特開2014-1371 (2014年1月), .
7.	Nishimoto Sei-ichi, Tanabe Kazuhito and Hisatsugu Yamada : METHOD OF DETECTING 5-METHYLCYTOSINE IN GENE AND DETECTION KIT, PCT/JP2007/056296 (Mar. 2007), WO 2007/111324 A1 (Oct. 2007), .
8.	西本清一, 田邉一仁, 山田久嗣 : 遺伝子中の5-メチルシトシン検出方法および検出キット, 特願2006-092180 (2006年3月), 特開WO 2007/111324 A1 (2007年10月), .
9.	Nishimoto Sei-icni, Tanabe Kazuhito and Hisatsugu Yamada : PHOTOFUNCTIONAL NUCLEIC ACID, METHOD OF PRODUCING THE SAME AND METHOD OF DETERMINING METHYLATION, PCT/JP2006/302322 (Feb. 2006), WO 2006/137190 A1 (Dec. 2006), .
10.	西本清一, 田邉一仁, 山田久嗣 : 光機能性核酸及びその製造方法，並びにメチル化判定方法, 特願2005-181137 (2005年6月), 特開WO 2006/137190 A1 (2006年12月), .
11.	山田久嗣, 野村弾, 今堀博 : 新規ビスマス化合物およびそれを用いたアルコールの選択的酸化反応, 特願2003-270582 (2003年7月), 特開2005-23052 (2005年1月), .

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

植物ポリマーを利用した多機能バイオ化成品製造エコリファイナリーシステムの開発 (研究課題/領域番号: 22H00573 )
アセチルグルコース修飾ダサチニブの分子設計・合成と放射線増感作用の評価 (研究課題/領域番号: 21K07567 )
多重共鳴MRI技術の拡張による双極性ポリマープローブの粒子径イメージング法の構築 (研究課題/領域番号: 19H02852 )
光音響イメージングに必須の近赤外蛍光色素複合化ベタイン型ポリマープローブの創製 (研究課題/領域番号: 18K05353 )
アセチルグルコース修飾ゲフィチニブの放射線増感機序の解明と新規増感剤の創製 (研究課題/領域番号: 17K10480 )
生体適合性ポリマー”そのもの”を可視化するDDSイメージングの新手法開発 (研究課題/領域番号: 16K01935 )
光超音波－磁気共鳴デュアルイメージングプローブの創製 (研究課題/領域番号: 15K01819 )
多重共鳴NMR技術を基盤とする生体分子イメージングの新手法の開拓 (研究課題/領域番号: 25350977 )
多重共鳴NMR法を用いた生体内化学反応プロセスの動的挙動解析 (研究課題/領域番号: 23710268 )
DNA内メチルシトシン塩基の光酸化反応機構の解明と新規DNAメチル化検出系の探索 (研究課題/領域番号: 21710228 )
高効率な過剰電子移動反応を誘起するDNA構造の精密設計 (研究課題/領域番号: 20750009 )
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国内講演発表:

特許:

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

准教授 : 山田 久嗣

研究活動

個人のホームページ

専門分野

研究テーマ

著書・論文

著書:

学術論文(審査論文):

総説・解説:

国際会議:

国内講演発表:

特許:

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

准教授 : 山田久嗣