近畿大学ライフサイエンス研究所Kindai University Life Science Research Institute

令和3年度

巻頭言

2021年度
ライフサイエンス研究所紀要発刊によせて
研究所長
稲瀬 正彦(生理学教室教授)

 ライフサイエンス研究所は、生命現象の科学的解明のための基礎研究や調査研究を実施し、人類の健康・福祉の増進に寄与することを目的として、1974年、医学部が創設された年に大阪狭山キャンパスに設置されました。それ以来、主に医学部の共同研究施設と連携して研究を進めておりますが、近畿大学の他学部との共同研究も実施して、幅広い角度から生命現象の解明に取り組んでいます。
 最近では、次世代シーケンサーをはじめ各種の先進的分析機器を揃え、特に癌関連遺伝子の網羅的解析を基盤に、個々の患者様のゲノム情報に基づく個別化医療、今後のプレシジョン医療や再生医学・医療などにも取り組んでいます。
 私立大学の医学部では、研究費も人も潤沢とはいえない現状です。その中で、ご報告するように、多くの質の高い研究成果が発表されたことは、誠に喜ばしいことであります。基礎系および臨床系の研究者の多大な御尽力と、それを支えている研究所の技術員の奮闘に敬意を表します。今後も、医学部を中心に、近畿大学での研究の発展のため、所員一同なお一層の努力をいたしてまいります。皆様のご支援、ご協力もお願い申し上げます。

令和3年度ライフサイエンス研究所紀要

生理学教室 (稲瀬 正彦 教授)

  1. Atsushi Chiba, Kazunori Morita, Ken‑ichi Oshio & Masahiko Inase
    Neuronal activity in the monkey prefrontal cortex during a duration
    discrimination task with visual and auditory cues.
    Sci Rep. 2021 Sep 1;11(1):17520. doi: 10.1038/s41598-021-97094-w.

臨床研究センター (福岡 和也 教授)

  1. Tanizaki J, Yonemori K, Akiyoshi H, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H.
    Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 2022 Feb;33(2):216-226.
  2. 高濱隆幸、米阪仁雄、白石直樹、小田いつき、池川敦子、西郷和真、福岡和也、中川和彦.
    近畿大学病院ゲノム医療センターの活動とがんゲノム医療の展望. 近畿大医誌 (Med J Kindai Univ) 2022; 47 (1・2): 19-25.
  3. 福岡和也、中川和彦.
    「7大学連携個別化がん医療実践者養成プラン」の成果. 癌と化学療法 2022; 49(6): 632-637.

ゲノム生物学教室 (西尾 和人 教授)

  1. Yonesaka K, Tanizaki J, Maenishi O, Haratani K, Kawakami H, Tanaka K, Hayashi H, Sakai K, Chiba Y, Tsuya A, Goto H, Otsuka E, Okida H, Kobayashi M, Yoshimoto R, Funabashi M, Hashimoto Y, Hirotani K, Kagari T, Nishio K, Nakagawa K.
    HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non-Small Cell Lung Cancer. Clin Cancer Res 2022; 28: 390-403.
  2. Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, Kidera Y, Fukuoka K, Ito A, Chiba Y, Sakai K, Nishio K, Nakagawa K, Hayashi H.
    Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol 2022; 33: 216-226.
  3. Takahashi T, Sakai K, Kenmotsu H, Yoh K, Daga H, Ohira T, Ueno T, Aoki T, Hayashi H, Yamazaki K, Hosomi Y, Chen-Yoshikawa TF, Okumura N, Takiguchi Y, Sekine A, Haruki T, Yamamoto H, Sato Y, Akamatsu H, Seto T, Saeki S, Sugio K, Nishio M, Inokawa H, Yamamoto N, Nishio K, Tsuboi M.
    Predictive value of EGFR mutation in non-small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy. Cancer Sci 2022; 113: 287-296.
  4. Suzuki S, Haratani K, Hayashi H, Chiba Y, Tanizaki J, Kato R, Mitani S, Kawanaka Y, Kurosaki T, Hasegawa Y, Okabe T, Tanaka K, Akashi Y, Ozaki T, Nishio K, Ito A, Nakagawa K.
    Association of tumour burden with the efficacy of programmed cell death-1/programmed cell death ligand-1 inhibitors for treatment-naïve advanced non-small-cell lung cancer. Eur J Cancer 2022; 161: 44-54.
  5. Nozaki K, Watanabe S, Nishio K, Sakai K, Kikuchi T.
    Effectiveness of afatinib in an NSCLC patient with EGFR mutation and early progression to osimertinib: a case report. Transl Cancer Res 2022; 11: 295-298.
  6. Nishio M, Nishio K, Reck M, Garon EB, Imamura F, Kawaguchi T, Yamaguchi H, Ikeda S, Hirano K, Visseren-Grul C, Ceccarelli M, Wijayawardana SR, Zimmermann A, Matsui T, Enatsu S, Nakagawa K.
    RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC. JTO Clin Res Rep 2022; 3: 100303.
  7. Maekawa M, Taniguchi T, Nishio K, Sakai K, Matsushita K, Nakatani K, Ishige T, Ikejiri M, Nishihara H, Sunami K, Yatabe Y, Hatanaka KC, Hatanaka Y, Yamamoto Y, Fukuyama K, Oda S, Saito K, Yokomura M, Kubo Y, Sato H, Tanaka Y, Fuchioka M, Yamasaki T, Matsuda K, Kurachi K, Funai K,Baba S, Iwaizumi M.
    Precision cancer genome testing needs proficiency testing involving all stakeholders. Sci Rep 2022; 12: 1494.
  8. Khandakar GI, Satoh R, Takasaki T, Fujitani K, Tanabe G, Sakai K, Nishio K, Sugiura R.
    ACAGT-007a, an ERK MAPK Signaling Modulator, in Combination with AKT Signaling Inhibition Induces Apoptosis in KRAS Mutant Pancreatic Cancer T3M4 and MIA-Pa-Ca-2 Cells. Cells 2022; 11.
  9. Kaibori M, Sakai K, Matsushima H, Kosaka H, Matsui K, De Velasco MA, Sekimoto M, Nishio K.
    Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period. Hepatol Int 2022.
  10. Yatabe Y, Yoshiki Y, Matsumura K, Togo K, Kikkawa H, Iadeluca L, Li B, Nishio K.
    Real-World Evidence of Diagnostic Testing for Driver Oncogene Mutations in Lung Cancer in Japan. JTO Clin Res Rep 2021; 2: 100136.
  11. Suzuki S, Yonesaka K, Teramura T, Takehara T, Kato R, Sakai H, Haratani K, Tanizaki J, Kawakami H, Hayashi H, Sakai K, Nishio K, Nakagawa K.
    KRAS inhibitor-resistance in MET-amplified KRAS (G12C) non-small cell lung cancer induced by RAS- and non-RAS-mediated cell signaling mechanisms. Clin Cancer Res 2021.
  12. Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S, Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T, Tamura K, Nishio K, Yamamoto N, Working Group of a Joint Task Force of Three Academic Societies for the Promotion of Cancer Genomic M.
    Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA. Cancer Sci 2021.
  13. Sakurai T, De Velasco MA, Sakai K, Nagai T, Nishiyama H, Hashimoto K, Uemura H, Kawakami H, Nakagawa K, Ogata H, Nishio K, Kudo M.
    Integrative analysis of gut microbiome and host transcriptomes reveals associations between treatment outcomes and immunotherapy-induced colitis. Mol Oncol 2021.
  14. Sakai K, Sakurai T, De Velasco MA, Nagai T, Chikugo T, Ueshima K, Kura Y, Takahama T, Hayashi H, Nakagawa K, Kudo M, Nishio K.
    Intestinal Microbiota and Gene Expression Reveal Similarity and Dissimilarity Between Immune-Mediated Colitis and Ulcerative Colitis. Front Oncol 2021; 11: 763468.
  15. Sakai K, De Velasco MA, Kura Y, Nishio K.
    Transcriptome Profiling and Metagenomic Analysis Help to Elucidate Interactions in an Inflammation-Associated Cancer Mouse Model. Cancers (Basel) 2021; 13.
  16. Rai S, Inoue H, Sakai K, Hanamoto H, Matsuda M, Maeda Y, Haeno T, Watatani Y, Kumode T, Serizawa K, Taniguchi Y, Hirase C, Espinoza JL, Morita Y, Tanaka H, Ashida T, Tatsumi Y, Nishio K, Matsumura I.
    Decreased expression of T-cell-associated immune markers predicts poor prognosis in patients with follicular lymphoma. Cancer Sci 2021.
  17. Osoegawa A, Yamaguchi M, Nakamura T, Morinaga R, Tanaka K, Kashiwabara K, Miura T, Suetsugu T, Harada T, Asoh T, Taguchi K, Nabeshima K, Kishimoto J, Sakai K, Nishio K, Sugio K.
    High Incidence of C797S Mutation in Patients With Long Treatment History of EGFR Tyrosine Kinase Inhibitors Including Osimertinib. JTO Clin Res Rep 2021; 2: 100191.
  18. Nishio K, Seto T, Nishio M, Reck M, Garon EB, Sakai K, Goto K, Kato T, Nakanishi Y, Takahashi T, Yamamoto N, Kiura K, Ohe Y, Tamura T, Visseren-Grul C, Frimodt-Moller B, Hozak RR, Wijayawardana SR, Zimmermann A, Homma G, Enatsu S, Nakagawa K.
    Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated Metastatic EGFR-Mutated NSCLC: RELAY Japanese Subset. JTO Clin Res Rep 2021; 2: 100171.
  19. Murakami K, Kanto A, Sakai K, Miyagawa C, Takaya H, Nakai H, Kotani Y, Nishio K, Matsumura N.
    Frequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma. Mod Pathol 2021.
  20. Morita M, Nishida N, Sakai K, Aoki T, Chishina H, Takita M, Ida H, Hagiwara S, Minami Y, Ueshima K, Nishio K, Kobayashi Y, Kakimi K, Kudo M.
    Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody. Liver Cancer 2021; 10: 380-393.
  21. Minami H, Kiyota N, Kimbara S, Ando Y, Shimokata T, Ohtsu A, Fuse N, Kuboki Y, Shimizu T, Yamamoto N, Nishio K, Kawakami Y, Nihira SI, Sase K, Nonaka T, Takahashi H, Komori Y, Kiyohara K.
    Guidelines for clinical evaluation of anti-cancer drugs. Cancer Sci 2021.
  22. Khadka S, Omura S, Sato F, Nishio K, Kakeya H, Tsunoda I.
    Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces. Front Cell Infect Microbiol 2021; 11: 772962.
  23. Kato R, Hayashi H, Sakai K, Suzuki S, Haratani K, Takahama T, Tanizaki J, Nonagase Y, Tanaka K, Yoshida T, Takeda M, Yonesaka K, Kaneda H, Nishio K, Nakagawa K.
    CAPP-seq analysis of circulating tumor DNA from patients with EGFR T790M-positive lung cancer after osimertinib. Int J Clin Oncol 2021; 26: 1628-1639.
  24. Imamura Y, Tanaka K, Kiyota N, Hayashi H, Ota I, Arai A, Iwae S, Minami S, Yane K, Yamazaki T, Nagatani Y, Toyoda M, Takahama T, Sakai K, Nishio K, Otsuki N, Nibu KI, Minami H.
    Docetaxel plus cisplatin in recurrent and/or metastatic non-squamous-cell head and neck cancer: a multicenter phase II trial. Med Oncol 2021; 38: 128.
  25. Hirokawa E, Watanabe S, Sakai K, Takeda M, Sato C, Takahama T, Nishio K, Nakagawa K.
    Durable response to EGFR tyrosine kinase inhibitors in a patient with non-small cell lung cancer harboring an EGFR kinase domain duplication. Thorac Cancer 2021; 12: 2283-2287.
  26. Hayashi H, Sugawara S, Fukuda Y, Fujimoto D, Miura S, Ota K, Ozawa Y, Hara S, Tanizaki J, Azuma K, Omori S, Tachihara M, Nishino K, Bessho A, Chiba Y, Haratani K, Sakai K, Nishio K, Yamamoto N, Nakagawa K.
    A Randomized Phase II Study Comparing Nivolumab with Carboplatin-Pemetrexed for EGFR-Mutated NSCLC with Resistance to EGFR Tyrosine Kinase Inhibitors (WJOG8515L). Clin Cancer Res 2021.
  27. Hatanaka Y, Kuwata T, Morii E, Kanai Y, Ichikawa H, Kubo T, Hatanaka KC, Sakai K, Nishio K, Fujii S, Okamoto W, Yoshino T, Ochiai A, Oda Y.
    The Japanese Society of Pathology Practical Guidelines on the handling of pathological tissue samples for cancer genomic medicine. Pathol Int 2021; 71: 725-740.
  28. Fukui T, Sakai K, Sasaki J, Kakegawa MI, Igawa S, Mitsufuji H, Takeda M, Takahama T, Nakagawa K, Nishio K, Naoki K.
    Implementation of clinical sequencing for molecular profiling in patients with advanced cancer. Cancer Biomark 2021.
  29. Fujino T, Suda K, Sakai K, Murakami I, Shimizu S, Ohara S, Koga T, Hamada A, Soh J, Nishio K, Mitsudomi T.
    Intra-tumor and Inter-tumor Heterogeneity in MET Exon 14 Skipping Mutations and Co-mutations in Pulmonary Pleomorphic Carcinomas. Clin Lung Cancer 2021.
  30. De Velasco MA, Kura Y, Ando N, Sako N, Banno E, Fujita K, Nozawa M, Yoshimura K, Sakai K, Yoshikawa K, Nishio K, Uemura H.
    Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer. Cancers (Basel) 2021; 13.

免疫学教室 (宮澤 正顯 教授)

  1. Shunichi Shiozawa, Ken Tsumiyama, Yumi Miyazaki, Kenichi Uto, Keiichi Sakurai, Toshie Nakashima, Hiroko Matsuyama, Ai Doi, Miho Tarui, Manabu Izumikawa, Mai Kimura, Yuko Fujita, Chisako Satonaka, Takahiko Horiuchi, Tsukasa Matsubara, Motohiro Oribe, Takashi Yamane, Hidetoshi Kagawa, Quan-Zhen Li, Keiko Mizuno, Yohei Mukai, Kazuhiro Murakami, Takuji Enya, Shota Tsukimoto, Yoshiyuki Hakata, Masaaki Miyazawa and Kazuko Shiozawa. DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus. iScience 25:103537, 2022.
  2. Kenta Teruya, Ayumi Oguma, Satoko Takahashi, Miki Watanabe-Matsui, Sachiyo Tsuji-Kawahara, Masaaki Miyazawa and Katsumi Doh-ura. Anti-prion activity of cellulose ether is impaired in mice lacking pre T-cell antigen receptor α, T-cell receptor δ, or lytic granule function. International Immunopharmacology 107:108672, 2022; Available online 10 March 2022.
  3. 宮澤正顯, 時田章史. 感染免疫から考えるCOVID-19検査の使い方: 基礎編. 外来小児科 25: 16-23, 2022.
  4. 時田章史, 鈴木光幸, 宮澤正顯. 感染免疫から考えるCOVID-19検査の使い方: 臨床編. 外来小児科 25: 24-32, 2022.
  5. 宮澤正顯. 呼吸器ウイルス感染症に対する宿主免疫応答と感染防御. 技術情報協会(編) 創薬研究者・アカデミア研究者が知っておくべき最新の免疫学とその応用技術. 技術情報協会 (ISBN 978-4-86104-856-2), 2021年8月31日. pp 147-157.(※当該業績の詳細については、本紀要への記載をいたしません)

ライフサイエンス研究所 (森 樹史 助手)

  1. Mori T, Onodera Y, Itokazu M, Takehara T,Shigi K, Iwawaki N, Akagi M,
    Teramura T.
    Depletion of NIMA-related kinase Nek2 induces aberrant self-renewal
    and apoptosis in stem/progenitor cells of aged muscular tissues.
    Mech Ageing Dev. 2022 Jan;201:111619. doi: 10.1016/j.mad.2022.111619.
    Epub 2022 Jan 4.

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