Tokushima University / Educator and Researcher Directory --- Heishima, Kazuki

Personal Web Page

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

https://orcid.org/0000-0002-4629-8661 (ORCID)

Field of Study

○	Life sciences [Medical biochemistry]
○	Life sciences [Cell biology]
○	Life sciences [Experimental pathology]
○	Life sciences [Molecular biology]
○	Life sciences [Tumor biology]
○	Life sciences [Veterinary medicine]

Subject of Study

Book / Paper

(See https://researchmap.jp/kheishima (researchmap) for Published Book / Papers / Presentations.)

Academic Paper (Judged Full Paper):

1.	Komori Teiko Nomura, Kazuki Heishima, Hidefumi Mukai, Kosuke Arai, Elsayed Abdelazim Elhelaly, Hirobumi Fuchigami, Shota Warashina, Tsuyoshi Tahara, Fuminori Hyodo, Masayuki Matsuo, Masahiro Yasunaga, Kazunori Aoki and Ryo Honda : Protein-based pan-RAS inhibitor induces tumor regression in female mice via IFNγ and CD8+ T cell-dependent tumor necrosis, Nature Communications, 17, 1, 2026.
2.	Tamami Suzuki, Kazuki Heishima, Jumpei Yamazaki, Masaya Yamazaki, Ryohei Kinoshita, Sangho Kim, Kenji Hosoya, Yuko Okamatsu-Ogura, Michihito Sasaki, Peng Xu, Qin Yan, Takashi Kimura and Keisuke Aoshima : Lysine lactylation regulates ATF4-mediated stress responses under glucose starvation in canine hemangiosarcoma, Frontiers in Veterinary Science, 13, 2026.
3.	Tamami Suzuki, Kazuki Heishima, Jumpei Yamazaki, Masaya Yamazaki, Ryohei Kinoshita, Sangho Kim, Kenji Hosoya, Yuko Okamatsu-Ogura, Michihito Sasaki, Peng Xu, Qin Yan, Takashi Kimura and Keisuke Aoshima : Lysine lactylation regulates ATF4-mediated stress responses under glucose starvation in canine hemangiosarcoma, 2025.
4.	S. Minatoguchi, N. Sugito, Kazuki Heishima, Y. Ito, R. Nakashima, H. Okura, Y. Akao and S. Minatoguchi : Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models, Scientific Reports, 15, 1, 2025.
5.	S. Minatoguchi, N. Sugito, Kazuki Heishima, Y. Ito, R. Nakashima, H. Okura, Y. Akao and S. Minatoguchi : Restoration effect of chemically modified microRNA-143-3p on acute myocardial infarction in animal models, Research Square, 2024.
6.	H. Murase, S. Minatoguchi, Kazuki Heishima, S. Yasuda, A. Satake, R. Yoshizumi, H. Komaki, S. Baba, S. Ojio, T. Tanaka, Y. Akao, S. Minatoguchi and H. Okura : Plasma microRNA-143 and microRNA-145 levels are elevated in patients with left ventricular dysfunction, Heart and Vessels, 39, 10, 867-876, 2024.
7.	Kazuki Heishima : Anti-tumor effects of chemically-modified microRNA143 Lipoplexes on colorectal cancer pelvic recurrence mouse model, Cancer Science, 2024.
8.	Kazuki Heishima, Naohiko Aketa, Mizuki Heishima and Asuka Kawachi : Hemangiosarcoma in dogs as a potential non-rodent animal model for drug discovery research of angiosarcoma in humans, Frontiers in Oncology, 13, 1250766, 2023. (Summary) Since the domestication of dogs 10,000 years ago, they have shared their living environment with humans and have co-evolved. The breeding process that dogs have undergone in only a few centuries has led to a significant accumulation of specific genetic alterations that could induce particular diseases in certain breeds. These canine diseases are similar to what is found in humans with several differences; therefore, comparing such diseases occurring in humans and dogs can help discover novel disease mechanisms, pathways, and causal genetic factors. Human angiosarcoma (AS) and canine hemangiosarcoma (HSA), which are sarcomas originating from endothelium, are examples of diseases shared between humans and dogs. They exhibit similar characteristics and clinical behaviors, although with some critical differences resulting from evolution. In this review, we will describe the similarities and differences in terms of clinical and molecular characteristics between human AS and canine HSA, and discuss how these similarities and differences can be applied to advance the treatment of these diseases. (Link to Publication Site) ● Publication site (DOI): 10.3389/fonc.2023.1250766 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38130992 ● Summary page in Scopus @ Elsevier: 2-s2.0-85180477815 (DOI: 10.3389/fonc.2023.1250766, PubMed: 38130992, Elsevier: Scopus)
9.	Jun Arima, Kohei Taniguchi, Nobuhiko Sugito, Kazuki Heishima, Yoshihisa Tokumaru, Yosuke Inomata, Kazumasa Komura, Tomohito Tanaka, Masa-Aki Shibata, Sang-Woong Lee and Yukihiro Akao : Antitumor effects of chemically modified miR-143 lipoplexes in a mouse model of pelvic colorectal cancer via myristoylated alanine-rich C kinase substrate downregulation, Molecular Therapy. Nucleic Acids, 34, 102079, 2023. (Summary) Replenishing tumor-suppressor miRNAs (TS-miRNAs) is a potential next-generation nucleic acid-based therapeutic approach. Establishing an effective miRNA delivery system is essential to successful TS-miRNA therapy. To overcome vulnerability to RNA nucleases, we previously developed a chemically modified miRNA143-3p (CM-miR-143). In clinical practice, colorectal cancer (CRC) pelvic recurrence is an occasional challenge following curative resection, requiring a novel therapy because reoperative surgery poses a significant burden to the patient. Hence, we considered the use of CM-miR-143 as an alternative treatment. In this study, we used a mouse model bearing pelvic CRC adjacent to the rectum and investigated the anticancer effects of CM-miR-143 lipoplexes formulated from miRNA and a cationic liposome. Compared with commercial synthetic miR-143, CM-miR-143 lipoplexes accumulated heavily in regions of the pelvic CRC tumor where the blood flow was high. As a result, systemic administration of CM-miR-143 lipoplexes improved animal survival by significantly suppressing pelvic CRC tumors and relieving a lethal bowel obstruction caused by rectal compression. Detailed protein analysis revealed that the myristoylated alanine-rich C kinase is a novel target for CM-miR-143 lipoplexes. Our results suggest that CM-miR-143 is a potential next-generation drug candidate in the treatment of CRC pelvic recurrence. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.omtn.2023.102079 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38213952 ● Summary page in Scopus @ Elsevier: 2-s2.0-85178177719 (DOI: 10.1016/j.omtn.2023.102079, PubMed: 38213952, Elsevier: Scopus)
10.	Junko Maeda, Ben Jepson, Kohei Sadahiro, Mami Murakami, Hiroki Sakai, Kazuki Heishima, Yukihiro Akao and Takamitsu A. Kato : PARP deficiency causes hypersensitivity to Taxol through oxidative stress induced DNA damage, Mutation Research, 827, 111826, 2023. (Summary) Taxol is an antitumor drug derived from the bark of the Pacific Yew tree that inhibits microtubule disassembly, resulting in cell cycle arrest in late G2 and M phases. Additionally, Taxol increases cellular oxidative stress by generating reactive oxygen species. We hypothesized that the inhibition of specific DNA repair machinery/mechanisms would increase cellular sensitivity to the oxidative stress capacity of Taxol. Initial screening using Chinese hamster ovary (CHO) cell lines demonstrated that base excision repair deficiency, especially PARP deficiency, caused cellular Taxol hypersensitivity. Taxane diterpenes-containing Taxus yunnanensis extract also showed hypertoxicity in PARP deficient cells, which was consistent with other microtubule inhibitors like colcemid, vinblastine, and vincristine. Acute exposure of 50 nM Taxol treatment induced both significant cytotoxicity and M-phase arrest in PARP deficient cells, but caused neither significant cytotoxicity nor late G2-M cell cycle arrest in wild type cells. Acute exposure of 50 nM Taxol treatment induced oxidative stress and DNA damage. The antioxidant Ascorbic acid 2 glucoside partially reduced the cytotoxicity of Taxol in PARP deficient cell lines. Finally, the PARP inhibitor Olaparib increased cytotoxicity of Taxol in wild type CHO cells and two human cancer cell lines. Our study clearly demonstrates that cytotoxicity of Taxol would be enhanced by inhibiting PARP function as an enzyme implicated in DNA repair for oxidative stress. (Keyword) Animals / Cricetinae / Humans / Paclitaxel / Poly(ADP-ribose) Polymerase Inhibitors / CHO Cells / Cricetulus / DNA Damage / oxidative stress / Antineoplastic Agents / Mitosis / Cell Line, Tumor / apoptosis (Link to Publication Site) ● Publication site (DOI): 10.1016/j.mrfmmm.2023.111826 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37300987 ● Summary page in Scopus @ Elsevier: 2-s2.0-85161329971 (DOI: 10.1016/j.mrfmmm.2023.111826, PubMed: 37300987, Elsevier: Scopus)
11.	Atsushi Satake, Shingo Minatoguchi, Kazuki Heishima, Shinji Yasuda, Hirotaka Murase, Ryo Yoshizumi, Hisaaki Komaki, Shinya Baba, Shinsuke Ojio, Toshiki Tanaka, Yukihiro Akao, Shinya Minatoguchi and Hiroyuki Okura : An Increase in Plasma MicroRNA-143 Levels in the Acute Phase Is Positively Correlated With Recovery of Cardiac Function in the Chronic Phase in Patients With Acute Myocardial Infarction, Circulation Journal, 87, 6, 824-833, 2023. (Summary) MicroRNA (miR)-143 and miR-145 are non-coding RNAs present in smooth muscle cells and the heart. However, their behavior and physiological role in patients with acute myocardial infarction (AMI) have not been clarified. Plasma miR-143 and miR-145 concentrations were measured on Day 0 (on admission) and on Day 7 in AMI patients who could be followed up for 6 months (n=25). The control group consisted of subjects without significant coronary stenosis (n=20). Blood samples were collected from the antecubital vein, and plasma miR-143 and miR-145 concentrations were measured by quantitative reverse transcription-polymerase chain reaction. In AMI patients (n=25), left ventricular ejection fraction (LVEF) was measured by echocardiography in the acute and chronic (6 months) phases. On Day 7, plasma miR-143 and miR-145 concentrations were significantly higher in AMI patients than in the control group and on Day 0 in AMI patients. Plasma miR-143 and miR-145 concentrations increased significantly from Day 0 to Day 7. The increase in plasma miR-143 concentrations (∆miR-143) in the acute phase was positively correlated with the increase in LVEF in the chronic phase. Among many factors, only ∆miR-143 was favorably correlated with left ventricle (LV) functional recovery in the chronic phase. An increase in plasma miR-143 concentrations in the acute phase may be a biomarker predicting recovery of LV function in the chronic phase in AMI patients. (Keyword) Humans / Stroke Volume / Ventricular Function, Left / Myocardial Infarction / heart / MicroRNAs (Link to Publication Site) ● Publication site (DOI): 10.1253/circj.CJ-22-0698 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36775328 ● Summary page in Scopus @ Elsevier: 2-s2.0-85160204511 (DOI: 10.1253/circj.CJ-22-0698, PubMed: 36775328, Elsevier: Scopus)
12.	Kazuki Heishima, N. Sugito, C. Abe, A. Hirata, H. Sakai and Y. Akao : Targeting microRNA-145-mediated progressive phenotypes of early bladder cancer in a molecularly defined in vivo model, Molecular Therapy. Nucleic Acids, 33, 960-982, 2023.
13.	Nobuhiko Sugito, Kazuki Heishima and Yukihiro Akao : Chemically modified MIR143-3p exhibited anti-cancer effects by impairing the KRAS network in colorectal cancer cells, Molecular Therapy. Nucleic Acids, 30, 49-61, 2022. (Summary) Kirsten rat sarcoma virus (KRAS) mutations are frequently detected in many cancers and are major driver genes. Therefore, KRAS inhibitors have been the subject of extensive research. We developed chemically modified MIR143-3p (MIR143#12), which exhibits higher anticancer activity and nuclease resistance than other commercial inhibitors. MIR143#12 potently suppressed cell growth in colorectal and pancreatic cancer cell lines via apoptosis induced by repression of the entire rat sarcoma virus (RAS) network, which was achieved by silencing KRAS, Son of sevenless homolog 1 ( SOS1 ), AKT, and extracellular signal-regulated kinase (ERK). We investigated the mechanistic advantages of MIR143#12 in various KRAS mutant colorectal cancer cell lines. Its effects were stronger than those of knockdown of KRAS alone in colon cancer cells because silencing of KRAS by small interfering RNA (siRNA) did not decrease the protein expression levels of AKT or ERKs. The KRAS mRNA recruitment system, called the "positive circuit" under effector signaling pathways, may contribute to insensitivity of KRAS mutant cancers to MIR143#12 and siRNAs. In an in vivo study, we newly demonstrated that MIR143#12 induced neoangiogenesis in the tumor microenvironment with growth suppression. Based on the present results, it is crucial to down-regulate not only KRAS but also the entire KRAS signaling network, which may be accomplished by MIR143#12. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.omtn.2022.09.001 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36189421 ● Summary page in Scopus @ Elsevier: 2-s2.0-85138586462 (DOI: 10.1016/j.omtn.2022.09.001, PubMed: 36189421, Elsevier: Scopus)
14.	Keisuke Okazaki, Mitsumi Takeda, Eiji Yamaguch, Kazuki Heishima and Akichika Itoh : Rapid total synthesis of petasin and isopetasin, Tetrahedron Letters, 107, 154092, 2022. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.tetlet.2022.154092 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85137744348 (DOI: 10.1016/j.tetlet.2022.154092, Elsevier: Scopus)
15.	Yukihiro Akao, Yuki Kuranaga, Kazuki Heishima, Nobuhiko Sugito, Kohei Morikawa, Yuko Ito, Tomoyoshi Soga and Tomohiro Ito : Plant hvu-MIR168-3p enhances expression of glucose transporter 1 (SLC2A1) in human cells by silencing genes related to mitochondrial electron transport chain complex I, The Journal of Nutritional Biochemistry, 101, 108922, 2022. (Summary) Diet is a crucial factor for preventing most diseases. Edible plant extracts are known to contain exosome-like nanoparticles, in which food-derived plant microRNAs are included and may serve as a novel functional component in human health. Here, we demonstrated that hvu-MIR168-3p included in the nanoparticles of rice aleurone cells down-regulated the expression of the genes related to mitochondrial electron transport chain complex I in human cells. Subsequently, hvu-MIR168-3p enhanced protein and RNA expression levels of glucose transporter I and caused a decrease in the blood glucose level, which findings were obtained by in vitro and in vivo experiments, respectively. These findings suggest that a cross-kingdom relationship between plants and humans with respect to hvu-MIR168-3p exists and may contribute to preventive medicine for GLUT1-related dysfunctions including glucose metabolism, aging, and tumor immunology. (Keyword) Animals / Blood Glucose / Cell Line, Tumor / Cell Proliferation / Down-Regulation / Electron Transport Complex I / Enterocytes / gene expression / Glucose Transporter Type 1 / Humans / male / Metabolome / Mice / Mice, Inbred ICR / MicroRNAs / mitochondria / nanoparticles / Oryza / oxidative phosphorylation / RNA Interference / RNA, Plant / Rats / Up-Regulation (Link to Publication Site) ● Publication site (DOI): 10.1016/j.jnutbio.2021.108922 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34856354 ● Summary page in Scopus @ Elsevier: 2-s2.0-85121601667 (DOI: 10.1016/j.jnutbio.2021.108922, PubMed: 34856354, Elsevier: Scopus)
16.	Kazuki Heishima : Understanding of cell death induced by the constituents of Taxus yunnanensis wood, Scientific Reports, 2022.
17.	Komori Teiko Nomura, Kazuki Heishima, Nobuhiko Sugito, Ryota Sugawara, Hiroshi Ueda, Akao Yukihiro and Ryo Honda : Specific inhibition of oncogenic RAS using cell-permeable RAS-binding domains, Cell Chemical Biology, 28, 11, 1581-1589.e6, 2021. (Summary) Oncogenic RAS proteins, common oncogenic drivers in many human cancers, have been refractory to conventional small-molecule and macromolecule inhibitors due to their intracellular localization and the lack of druggable pockets. Here, we present a feasible strategy for designing RAS inhibitors that involves intracellular delivery of RAS-binding domain (RBD), a nanomolar-affinity specific ligand of RAS. Screening of 51 different combinations of RBD and cell-permeable peptides has identified Pen-cRaf-v1 as a cell-permeable pan-RAS inhibitor capable of targeting both G12C and non-G12C RAS mutants. Pen-cRaf-v1 crosses the cell membrane via endocytosis, competitively inhibits RAS-effector interaction, and thereby exerts anticancer activity against several KRAS-mutant cancer cell lines. Moreover, Pen-cRaf-v1 exhibits excellent activity comparable with a leading pan-RAS inhibitor (BI-2852), as well as high target specificity in transcriptome analysis and alanine mutation analysis. These findings demonstrate that specific inhibition of oncogenic RAS, and possibly treatment of RAS-mutant cancer, is feasible by intracellular delivery of RBD. (Keyword) Animals / Antineoplastic Agents / Binding Sites / Cell Proliferation / Cell Survival / Drug Screening Assays, Antitumor / female / Humans / male / Mice / Mice, Inbred BALB C / Neoplasms, Experimental / signal transduction / Tumor Cells, Cultured / ras Proteins (Link to Publication Site) ● Publication site (DOI): 10.1016/j.chembiol.2021.04.013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33964212 ● Summary page in Scopus @ Elsevier: 2-s2.0-85116241949 (DOI: 10.1016/j.chembiol.2021.04.013, PubMed: 33964212, Elsevier: Scopus)
18.	Kazuki Heishima : Petasin potently inhibits mitochondrial complex I-based metabolism that supports tumor growth and metastasis, The Journal of Clinical Investigation, 2021.
19.	Nobuhiko Sugito, Kazuki Heishima, Yuko Ito and Yukihiro Akao : Synthetic MIR143-3p Suppresses Cell Growth in Rhabdomyosarcoma Cells by Interrupting RAS Pathways Including PAX3–FOXO1, Cancers, 12, 11, 3312, 2020.
20.	A. Sarah Weiss, Christopher Zito, Thuy Tran, Kazuki Heishima, Veronique Neumeister, John McGuire, Adebowale Adeniran, Harriet Kluger and B. Lucia Jilaveanu : Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases, Journal of Neuro-Oncology, 152, 1, 2020.
21.	Masahiro Fukada, Nobuhisa Matsuhashi, Takao Takahashi, Nobuhiko Sugito, Kazuki Heishima, Yukihiro Akao and Kazuhiro Yoshida : Tumor Tissue MIR92a and Plasma MIRs21 and 29a as Predictive Biomarkers Associated with Clinicopathological Features and Surgical Resection in a Prospective Study on Colorectal Cancer Patients, Journal of Clinical Medicine, 9, 8, 2509, 2020.
22.	Ryutaro Yoshikawa, Kazuki Heishima, Yoshihito Ueno, Miwa Kawade, Yusuke Maeda, Kyoko Yoshida, Mami Murakami, Hiroki Sakai, Yukihiro Akao and Takashi Mori : Development of synthetic microRNA 214 showing enhanced cytotoxicity and RNase resistance for treatment of canine hemangiosarcoma, Veterinary and Comparative Oncology, 18, 4, 570-579, 2020. (Summary) MicroRNA-214 (miR-214), a pivotal tumour-suppressive miRNA, is downregulated in canine hemangiosarcoma (HSA) cells. Although these tumour-suppressive miRNAs are potential therapeutic agents, their clinical efficacy may be limited because of their vulnerability to RNase-rich microenvironments and low in vivo transfection rates. We developed synthetic miR-214s with enhanced cytotoxicity, RNase resistance and quantity of miR-214 in/on cells. These synthetic miR-214s were synthesized by various chemical modifications (such as 4'-aminoethyl-2'-fluoro, 2'-fluoro, 2'-O-methyl, phosphorothioate and oligospermine modifications) of the wild-type mature miR-214 sequences. Transfection of HSA cells with synthetic miR-214 (miR-214 5AE) demonstrated significant growth suppressive effect and induced the strongest apoptotic response. Synthetic miR-214s (miR-214 5AE, miR-214 10AE and miR-214 OS) were much more stable than mature miR-214s in foetal bovine serum. Similar to mature miR-214, 5AE and OS suppressed the expression level of COP1 in HSA cells. The quantity of synthetic miR-214s in/on cells was higher than that of mature miR-214. In conclusion, we developed a clinically applicable, synthetic miR-214 5AE that regulates the COP1 protein expression similar to that mediated by mature miR-214. Additionally, miR-214 5AE confers better cytotoxicity, nuclease resistance and transfection rate than mature miR-214. Thus, miR-214 5AE could potentially be a novel miRNA-based chemotherapeutic agent that could improve the prognosis of HSA. Its in vivo effects on canine HSA need to be examined in future. (Keyword) Animals / Antineoplastic Agents / Cell Line, Tumor / Dog Diseases / Dogs / Down-Regulation / Hemangiosarcoma / MicroRNAs / Ribonucleases / Ubiquitin-Protein Ligases (Link to Publication Site) ● Publication site (DOI): 10.1111/vco.12580 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32072720 ● Summary page in Scopus @ Elsevier: 2-s2.0-85082587819 (DOI: 10.1111/vco.12580, PubMed: 32072720, Elsevier: Scopus)
23.	O. Nami Yamada, Kazuki Heishima, Yukihiro Akao and Takao Senda : Extracellular Vesicles Containing MicroRNA-92a-3p Facilitate Partial Endothelial-Mesenchymal Transition and Angiogenesis in Endothelial Cells, International Journal of Molecular Sciences, 20, 18, 4406, 2019.
24.	Kohei Nakata, Kazuki Heishima, Hiroki Sakai, Osamu Yamato, Yu Furusawa, Hidetaka Nishida, Sadatoshi Maeda and Hiroaki Kamishina : Plasma microRNA miR-26b as a potential diagnostic biomarker of degenerative myelopathy in Pembroke welsh corgis, BMC Veterinary Research, 15, 1, 2019.
25.	Yuki Yoshikawa, Kohei Taniguchi, Takuya Tsujino, Kazuki Heishima, Teruo Inamoto, Tomoaki Takai, Koichiro Minami, Haruhito Azuma, Kanjiro Miyata, Kotaro Hayashi, Kazunori Kataoka and Yukihiro Akao : Anti-cancer Effects of a Chemically Modified miR-143 on Bladder Cancer by Either Systemic or Intravesical Treatment, Molecular Therapy. Methods & Clinical Development, 13, 2019.
26.	Tomoaki Takai, Takuya Tsujino, Yuki Yoshikawa, Teruo Inamoto, Nobuhiko Sugito, Yuki Kuranaga, Kazuki Heishima, Tomoyoshi Soga, Kotaro Hayashi, Kanjiro Miyata, Kazunori Kataoka, Haruhito Azuma and Yukihiro Akao : Synthetic miR-143 Exhibited an Anti-Cancer Effect via the Downregulation of K-RAS Networks of Renal Cell Cancer Cells In Vitro and In Vivo, Molecular Therapy, 27, 5, 2019.
27.	Takuya Tsujino, Nobuhiko Sugito, Kohei Taniguchi, Ryo Honda, Kazumasa Komura, Yuki Yoshikawa, Tomoaki Takai, Koichiro Minami, Yuki Kuranaga, Haruka Shinohara, Yoshihisa Tokumaru, Kazuki Heishima, Teruo Inamoto, Haruhito Azuma and Yukihiro Akao : MicroRNA‐143/Musashi‐2/KRAS cascade contributes positively to carcinogenesis in human bladder cancer, Cancer Science, 110, 7, 2019.
28.	Kazuki Heishima, Travis Meuten, Kyoko Yoshida, Takashi Mori and H. Douglas Thamm : Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy, BMC Veterinary Research, 15, 1, 2019.
29.	Haruka Shinohara, Nobuhiko Sugito, Yuki Kuranaga, Kazuki Heishima, Yosuke Minami, Tomoki Naoe and Yukihiro Akao : Potent antiproliferative effect of fatty‐acid derivative AIC‐47 on leukemic mice harboring BCR‐ABL mutation, Cancer Science, 110, 2, 2019.
30.	Kazuki Heishima, Ryota Iwasaki, Mifumi Kawabe, Mami Murakami, Hiroki Sakai, Kohji Maruo and Takashi Mori : Short-Term Administration of Single-Agent Toceranib in Six Cases of Inoperable Massive Canine Hepatocellular Carcinoma, Journal of the American Animal Hospital Association, 55, 1, 2019.
31.	Cathy Su, P. Jeffrey Gius, Julia Steenberg Van, H. Alexis Haskins, Kazuki Heishima, Chisato Omata, Masahiro Iwayama, Mami Murakami, Takashi Mori, Kohji Maruo and A. Takamitsu Kato : Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity, Scientific Reports, 7, 1, 2017.
32.	Sho Goto, Mami Murakami, Mifumi Kawabe, Ryota Iwasaki, Kazuki Heishima, Hiroki Sakai and Takashi Mori : Hypofractionated radiation therapy in the treatment of canine thymoma: Retrospective study of eight cases, Veterinary Radiology & Ultrasound, 58, 5, 613-620, 2017. (Summary) Thymomas are one of the most common tumors of the cranial mediastinum in dogs; however there is limited information available on the use of radiation therapy for treating this neoplasm. Objectives of the current retrospective observational study were to describe outcomes and side effects of a hypofractionated radiation therapy protocol in a group of dogs with confirmed thymoma. A total of eight dogs were included. To generate individualized treatment plans, we designed the planning target volume according to the limits on mean lung dose and the percentage of the total lung volume exceeding 20 Gy (V20). The total administered dose was 48-49 Gy, with one fraction per week for a total of six to seven fractions. After therapy, two dogs achieved complete responses, two achieved partial responses, and the disease remained stable in two. Two dogs died during the radiation therapy protocol and were not classified. The median mean lung dose and V20 were 6.0 Gy (range: 3.1-15.0 Gy) and 12.4% (range: 2.3-27.5%), respectively. The overall response rate was 50.0%, and the median time to response following treatment initiation was 22 days (range: 14-115 days). Acute and late side effects were common in the skin and/or lung and were self-limiting or asymptomatic. The median survival time was not reached (range: 8-1128 days) and the 1 year survival rate was 75.0%. Hypofractionated radiation therapy was well tolerated in this sample of dogs with thymoma and may be considered when owners decline surgical treatment or the tumor is deemed unresectable. (Keyword) Animals / Dog Diseases / Dogs / Dose Fractionation, Radiation / female / male / Retrospective Studies / Thymoma / Thymus Neoplasms (Link to Publication Site) ● Publication site (DOI): 10.1111/vru.12525 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28665494 ● Summary page in Scopus @ Elsevier: 2-s2.0-85021676740 (DOI: 10.1111/vru.12525, PubMed: 28665494, Elsevier: Scopus)
33.	R Iwasaki, M Murakami, M Kawabe, Kazuki Heishima, H Sakai and T Mori : Metastatic diagnosis of canine sternal lymph nodes using computed tomography characteristics: A retrospective cross-sectional study., Veterinary and Comparative Oncology, 16, 1, 140-147, 2017. (Summary) The accurate evaluation of sternal lymph nodes (StLNs) is critical for the staging of canine thoraco-abdominal tumours. Computed tomography (CT) provides a non-invasive means of assessing StLNs, but its diagnostic accuracy for identifying metastases is unclear. In this retrospective cross-sectional study, we assessed the diagnostic power of various CT measurements. Fifty-seven dogs that underwent concurrent CT and cytological examination of the StLNs were enrolled retrospectively. The size, shape, X-ray attenuation and uniformity of the StLNs were assessed. The dogs were divided into metastasis-negative (n = 21) and metastasis-positive (n = 36) groups. Logistic regression analysis showed that the size (StLN-to-second sternebra ratio [ratio-size]) and precontrast attenuation were significantly different between groups. Combining these parameters achieved a specificity and positive predictive value of 100% (cut-off values: 1.0, 37.5 Hounsfield units, respectively). This suggests that the combination of ratio-size and precontrast attenuation is effective for differentiating metastasis to the StLNs on CT. (Keyword) Animals / Cross-Sectional Studies / Dog Diseases / Dogs / female / Lymph Nodes / Lymphatic Metastasis / male / Retrospective Studies / Sternum / Tomography, X-Ray Computed (Link to Publication Site) ● Publication site (DOI): 10.1111/vco.12323 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28524617 ● Summary page in Scopus @ Elsevier: 2-s2.0-85042354332 (DOI: 10.1111/vco.12323, PubMed: 28524617, Elsevier: Scopus)
34.	Kazuki Heishima, Yukie Ichikawa, Kyoko Yoshida, Ryota Iwasaki, Hiroki Sakai, Takayuki Nakagawa, Yuiko Tanaka, Yuki Hoshino, Yasuhiko Okamura, Mami Murakami, Kohji Maruo, Yukihiro Akao and Takashi Mori : Circulating microRNA-214 and -126 as potential biomarkers for canine neoplastic disease, Scientific Reports, 7, 1, 2017.
35.	Yasuhiko Okamura, Kazuki Heishima, Tomoki Motegi, Jun Sasaki, Masanobu Goryo, Hideji Nishida, Hiroyuki Tsuchiya, Masaaki Katayama and Yuji Uzuka : Mandibular Reconstruction by Using a Liquid Nitrogen-Treated Autograft in a Dog with an Oral Tumor, Journal of the American Animal Hospital Association, 53, 3, 2017.
36.	Kazuki Heishima, Takashi Mori, Yukie Ichikawa, Hiroki Sakai, Yuki Kuranaga, Takayuki Nakagawa, Yuiko Tanaka, Yasuhiko Okamura, Mikio Masuzawa, Nobuhiko Sugito, Mami Murakami, Nami Yamada, Yukihiro Akao and Kohji Maruo : MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases, International Journal of Molecular Sciences, 16, 10, 2015.
37.	Kazuki Heishima, Takashi Mori, Hiroki Sakai, Nobuhiko Sugito, Mami Murakami, Nami Yamada, Yukihiro Akao and Kohji Maruo : MicroRNA-214 Promotes Apoptosis in Canine Hemangiosarcoma by Targeting the COP1-p53 Axis, PLoS ONE, 10, 9, e0137361, 2015.
38.	Yui Sasaki, Ryosuke Iwama, Tsubasa Sato, Kazuki Heishima, Shunsuke Shimamura, Tosihiro Ichijo, Hiroshi Satoh and Kazuhisa Furuhama : Estimation of glomerular filtration rate in conscious mice using a simplified equation, Physiological Reports, 2, 8, e12135, 2014.

Review, Commentary:

1.	Kazuki Heishima, Kendon Kuo, Masashi Kimura and Takashi Mori : Animal Lymphocyte Metaphase Chromosome Preparation, 2019.

Proceeding of International Conference:

1.	Kazuki Heishima : Plasma Microrna-145 and-143 Levels Increase Dependent on the Severity of Left Ventricular Dysfunction and Dilation in Patients With Heart Diseases, Circulation, 2019.

Proceeding of Domestic Conference:

1.	Kazuki Heishima : Histone lactylation drives metabolic reprogramming in response to glucose deprivation in canine hemangiosarcoma, Cancer Science, 2026.
2.	Kazuki Heishima : Investigation of the roles of histone lactylation and metabolic features in canine hemangiosarcoma, Cancer Science, 2025.
3.	Kazuki Heishima : Investigation of the roles of histone lactylation and glutamine metabolism in canine hemangiosarcoma, Cancer Science, 2024.
4.	Kazuki Heishima : MicroRNA drug and biomarker development exploiting human-canine homology in angiosarcoma and osteosarcoma, Cancer Science, 2023.
5.	Kazuki Heishima : Entire repression of KRAS network and induction of neoangiogenesis by chemically-modified MIR143#12, Cancer Science, 2023.
6.	Kazuki Heishima : Effectiveness of chemically-modified miRNA-143 against pelvic recurrence of colorectal cancer model, Cancer Science, 2023.
7.	Kazuki Heishima : Understanding of significance of RAS signaling in breast cancers through RNA-interference study, Cancer Science, 2022.
8.	Kazuki Heishima : Petasin potently inhibits mitochondrial-complex-I-based metabolism supporting tumor growth and metastasis, Cancer Science, 2022.
9.	Kazuki Heishima : Postoperative changes in plasma miR21-5p as a novel biomarker for colorectal cancer recurrence: A prospective study, Cancer Science, 2021.
10.	Kazuki Heishima : Efficacy of liponanoparticle-embedded synthetic MIR143 in a systemic KRAS-mutant multiple myeloma model, Cancer Science, 2021.
11.	Kazuki Heishima : The KRAS/PAX3-FOXO1 networks control the cell proliferation in rhabdomyosarcoma cells, Cancer Science, 2018.
12.	Kazuki Heishima : Enhanced anti-cancer activity of microRNA by chemical modification for clinical use, Cancer Science, 2018.
13.	Kazuki Heishima : Anti-neoplastic activity of Petasites japonicus extract, Cancer Science, 2018.
14.	Kazuki Heishima : A role of PTBP1 in cancer specific energy metabolism and the chemoresistance, Cancer Science, 2018.

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

ヒト-動物共通のアスパラギン"酸"標的型リンパ腫治療戦略の開拓 (Project/Area Number: 26K23105 )
新規阻害剤から開拓するミトコンドリアによる種間共通の非ATP性がん転移機構の解明 (Project/Area Number: 25K02174 )
Redefining Hemangiosarcoma through Lymphangiogenic Factors (Project/Area Number: 25K02164 )
空間メタボロミクスによる新規転移阻害剤の代謝を介した薬効解明 (Project/Area Number: 24KK0274 )
Development of cell-isolated and highly concentrated topical anticancer therapy for cutaneous lymphoma (Project/Area Number: 23K27074 )
Development of chemical derivatives of petasin (Project/Area Number: 22K14990 )
Development new materials for pneumonia (Project/Area Number: 20KK0125 )
Development of miR-143-lipid nanoparticle-based therapy against KRAS-mutant multiple myeloma (Project/Area Number: 20K16216 )
Search by Researcher Number (50826633)

Associate Professor : Heishima, Kazuki

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