令和4年度

巻頭言

2022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
岡田　斉（生化学教室教授）

　近畿大学ライフサイエンス研究所は1974年に大阪狭山キャンパスに設立され、以来、生命現象の科学的解明と人類の健康及び福祉の増進に寄与してきました。先進的な分析機器の活用により、特にがん関連遺伝子の網羅的解析を基盤とした個別化医療とプレシジョン医療の推進に貢献しています。また、2022年には難治性神経疾患の治療法開発を担う新たな研究室を設置しました。医学研究の現状は、日本の研究力の低下、大学医学部の研究者や若い医師の不足、次代を担う若手研究者の研究時間の不足など、多くの課題に直面しています。医師の働き方改革が進む中、研究活動の質と量を維持・向上させるためには、新しい組織の構築やライフサイエンス研究所を含む各部門の更なる有機的な連携が求められています。そうした挑戦的な環境の中、今年度は多くの質の高い研究成果が発表されました。これは、基礎研究および臨床研究を行う研究者と技術職員の献身的な努力の賜物であり、彼らの奮闘に深い敬意を表します。今後も、近畿大学ライフサイエンス研究所では、研究の発展のために、所員一同が一層の努力を続けていく所存です。

令和4年度ライフサイエンス研究所紀要 研究業績

永井 義隆 （ライフサイエンス研究所 副所長 兼任 近畿大学 医学部 内科学教室［脳神経内科部門］主任教授）

1. Taminato T., *Takeuchi T., Ueyama M., Mo
   ri K., Ikeda M., Mochizuki H., Nagai Y .
   Therapeutic reduction of GGGGCC repeat RNA levels by hnRNPA3 suppresses
   neurodegeneration in Drosophila models of C9orf72 linked ALS/FTD. Hum. Mol. Genet.
   32(10): 1673 1682 (2023) doi: 10.1093/hmg/ddac298
   
2. Nitta Y., Kawai H., Maki R., Osaka J., Hakeda
   S uzuki S., Nagai Y ., Doubková K., Uehara T.,
   Watanabe K., Kosaki K., Suzuki T., Tavosanis G., Sugie A. Direct evaluation of neuroaxonal
   degeneration with the causative genes of neurodegenerative diseases in Drosophila using the
   automated axon quantification system, MeDUsA. Hum. Mol. Genet. 32(9): 1524 1538
   (2023) doi: 10.1093/hmg/ddac307
   
3. Minamino M., Miyamoto K., Kuwahara M., Yoshikawa K., Koh J., Kusunoki S.,
   Nagai Y .,
   Ito H. Characteristics of Guillain Barré syndrome in super elderly individuals. J. Neur ol.
   270(4): 2191 2196 (2023) doi: 10.1007/s00415 023 11567 8
   
4. Wang E.T., Freudenreich C.H., Gromak N., Jain A., Todd P.K.,
   Nagai Y . What repeat
   expansion disorders can teach us about the Central Dogma. Mol. Cell 83 (3): 324 329 (2023)
   doi: 10.1016 /j.molce l.2022.12.017
   
5. Fujino Y., Mori K.,
   Nagai Y . Repeat associated non AUG translation in neuromuscular
   diseases: Mechanisms and therapeutic insights. J. Biochem. 173(4): 273 281 (2023) doi:
   10.1093/jb/mvad012
   
6. *Takeuchi T., Maeta K., Xin D., Oe Y., Takeda A.
   A., Inoue M., Nagano S., Fujihara T.,
   Matsuda S., Ishigaki S., Sahashi K., Minakawa E.N., Mochizuki H., Neya M., Sobue G., Nagai
   Y . Sustained therapeutic benefits by transient reduction of TDP 43 using ENA modified
   antisense oligonucleotides in ALS/FTD mice. Mol. Ther. Nucleic Acids 31: 353 366 (2023)
   doi: 10.1016/j.omtn.2023.01.006
   
7. Choong C.J., Aguirre C., Kakuda K., Kimura Y., Beck G., Nabekura K., Hideshima M., Doi
   J., Yamaguchi K., Nakajima K., Wadayama T., Hayakawa H., Baba K., Ogawa K., Takeuchi
   T., M urayama S., Nagano S., Goto Y., Miyanoiri Y., Nakanishi H., Nagai Y ., Mochizuki H.,
   Ikenaka K. Phosphatidylinositol 3,4,5 trisphosphate interacts with alpha synuclein and
   initiates its aggregation and formation of Parkinson's disease related fibril polymor phism.
   Acta Neuropathol. 145(5):573 595 (2023) doi: 10.1007/s00401 023 02555 3

宮澤 正顯（ライフサイエンス研究所 教授 兼任 近畿大学 医学部 免疫学教室 主任教授）

1. Kenta Teruya., Ayumi Oguma,Satoko Takahashi., Miki Watanabe-Matsui., Sachiyo Tsuji-
   Kawahara., Masaaki Miyazawa ., 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 Volume 107, June 2022, 108672
   doi：10.1016/j.intimp.2022.108672
   
2. Masaaki Miyazawa,.and Mario Clerici. Editorial: Host Immune Responses
   to Retroviral Infections, EDITORIAL article(2022) doi: 10.3389/fviro.2022.945530
   
3. Yoshiyuki Hakata., Kazuma Yamashita., Sonoko Hashimoto., Takashi Ohtsuki.,Masaaki
   Miyazawa.,and Mizuki Kitamatsu. Adjusting Heterodimeric Coiled-Coils (K/E Zipper) to
   ConnectAutophagy-Inducing Peptide with Cell-Penetrating Peptide Pharmaceutics 2023,
   doi: 10.3390/pharmaceutics150
   
4. Tomomasa Izumiyama., and Masaaki Miyazawa. Importance of tenosynovitis in preventing
   the progression through rheumatoid arthritis continuum Modern Rheumatology, 33, 2023,
   868–874 doi: 10.1093/mr/roac109
   
5. Shota Tsukimoto., Yoshiyuki Hakata., Sachiyo Tsuji-Kawahara., Takuji Enya.,Tetsuo
   Tsukamoto.,Seiya Mizuno., Satoru Takahashi., Shinichi Nakao and Masaaki Miyazawa.
   Distinctive High Expression of Antiretroviral APOBEC3 Protein
   in Mouse Germinal Center B Cells.Viruses 2022, 14, 832 doi:10.3390/v14040832

重吉 康史（ライフサイエンス研究所 教授 兼任 近畿大学 医学部 解剖学教室 主任教授）

1. Atsuko Fujioka.,Mamoru Nagano.,Keisuke Ikegami.,Koh-hei Masumoto.,
   Tomoko Yoshikawa.,Satoshi Koinuma.,Ken-ichi Nakahama.,Yasufumi Shigeyoshi. Circadian
   expression and specific localization of synaptotagmin17 in the suprachiasmatic nucleus, the
   master circadian oscillator in mammals Available online 1 November 2022
   0006-8993 doi:10.1016/j.brainres.2022.148129
   
2. Yuji Kanazawa.,Yuri Ikeda-Matsuo.,Hiaki Sato.,Mamoru Nagano.,Satoshi Koinuma.,
   Tatsuo Takahashi.,Hirokazu Suzuki.,Ryo Miyachi and Yasufumi Shigeyoshi. Effects of
   Obesity in Old Age on the Basement Membrane of Skeletal Muscle in Mice. Int. J. Mol. Sci.
   2023, 24, 9209. doi:10.3390/ijms24119209
   
3. Yuji Kanazawa.,Tatsuo Takahashi.,Takashi Higuchi.,Ryo Miyachi.,Mamoru Nagano.,
   Satoshi Koinuma.,Yasufumi Shigeyoshi. Effects of stretching on the basement membrane
   structure in the soleus muscle of Wistar rats. Medical Molecular Morphology (2023) 56:11–
   19 doi: 10.1007/s00795-022-00335-8
   

西尾 和人（ライフサイエンス研究所 ゲノムセンター長、教授 兼任 近畿大学 医学部 ゲノム生物学教室 主任教授）

1. Tsubaki M, Takeda T, Koumoto Y et al. Activation of ERK1/2 by MOS and TPL2 leads to
   dasatinib resistance in chronic myeloid leukaemia cells. Cell Prolif 2023; e13420.
   
2. Takahashi T, Nishio M, Nishino K et al. Real-world study of next-generation sequencing
   diagnostic biomarker testing for patients with lung cancer in Japan. Cancer Sci 2023.
   
3. Matsuoka H, Tsurutani J, Chiba Y et al. Morphine Versus Oxycodone for Cancer Pain
   Using a Catechol-O-methyltransferase Genotype Biomarker: A Multicenter, Randomized,
   Open-Label, Phase III Clinical Trial (RELIEF Study). Oncologist 2023; 28: 278-e166.
   
4. Fujita T, Sakai K, Uehara N et al. Genetic variants of cancer‑associated genes analyzed
   using next‑generation sequencing in small sporadic vestibular schwannomas. Oncol Lett
   2023; 25: 121.
   
5. 5. Watanabe S, Sakai K, Matsumoto N et al. Phase II Trial of the Combination of Alectinib
   with Bevacizumab in Alectinib Refractory ALK-Positive Nonsquamous Non-Small-Cell Lung
   Cancer (NLCTG1501). Cancers (Basel) 2022; 15.
   
6. Tanaka K, Chamoto K, Saeki S et al. Combination bezafibrate and nivolumab treatment of
   patients with advanced non-small cell lung cancer. Sci Transl Med 2022; 14: eabq0021.
   
7. Okamoto W, Sakai K, Makiyama A et al. A phase II study to explore biomarkers for the use
   of mFOLFOX6/XELOX plus bevacizumab as a first-line chemotherapy in patients with
   metastatic colorectal cancer (WJOG7612GTR). ESMO Open 2022; 7: 100592.
   
8. Nagai S, Nishihara H, Suzuki T et al. Recommendations related to the analytical
   equivalence assessment of gene panel testing. Cancer Sci 2022; 113: 3282-3290.
   
9. Makutani Y, Sakai K, Yamada M et al. Performance of Idylla RAS-BRAF mutation test for
   formalin-fixed paraffin-embedded tissues of colorectal cancer. Int J Clin Oncol 2022; 27:
   1180-1187.
   
10. Kanemura H, Hayashi H, Tomida S et al. The Tumor Immune Microenvironment and
    Frameshift Neoantigen Load Determine Response to PD-L1 Blockade in Extensive-Stage
    SCLC. JTO Clin Res Rep 2022; 3: 100373.
    
11. Iwahashi N, Ikezaki M, Komohara Y et al. Cytoplasmic p53 aggregates accumulated in
    p53-mutated cancer correlate with poor prognosis. PNAS Nexus 2022; 1: pgac128.
    
12. Isomoto K, Haratani K, Tsujikawa T et al. Mechanisms of primary and acquired resistance
    to immune checkpoint inhibitors in advanced non-small cell lung cancer: A multiplex
    immunohistochemistry-based single-cell analysis. Lung Cancer 2022; 174: 71-82.
    
13. Hayashi Y, Fujita K, Sakai K et al. Targeted-sequence of normal urothelium and tumor of
    patients with non-muscle invasive bladder cancer. Sci Rep 2022; 12: 16642.
    
14. Hayashi H, Yonesaka K, Nakamura A et al. Alternating therapy with osimertinib and
    afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung
    cancer: A single-group, open-label phase 2 trial (WJOG10818L). Lung Cancer 2022; 168: 38-
    45.

坂井 和子（ライフサイエンス研究所 ゲノムセンター 講師 兼任 近畿大学 医学部 ゲノム生物学教室 講師）

1. Fujita T, Sakai K, Uehara N, Hoshi Y, Mori A, Koyama H, Sato M, Saito K, Osaki Y, Nishio
   K, Doi K. Genetic variants of cancer‑associated genes analyzed using next‑generation
   sequencing in small sporadic vestibular schwannomas. Oncol Lett. 2023 Feb 8;25(3):121.
   
2. Iwahashi N, Ikezaki M, Komohara Y, Fujiwara Y, Noguchi T, Nishioka K, Sakai K, Nishio
   K, Ueda M, Ihara Y, Uchimura K, Ino K, Nishitsuji K. Cytoplasmic p53 aggregates
   accumulated in p53-mutated cancer correlate with poor prognosis. PNAS Nexus. 2022 Jul
   25;1(3):pgac128.
   
3. Watanabe S, Sakai K, Matsumoto N, Koshio J, Ishida A, Abe T, Ishikawa D, Tanaka T, Aoki
   A, Kajiwara T, Koyama K, Miura S, Goto Y, Sekiya T, Suzuki R, Kushiro K, Fujisaki T,
   Yanagimura N, Ohtsubo A, Shoji S, Nozaki K, Saida Y, Yoshizawa H, Nishio K, Kikuchi T.
   Phase II Trial of the Combination of Alectinib with Bevacizumab in Alectinib Refractory
   ALK-Positive Nonsquamous Non-Small-Cell Lung Cancer (NLCTG1501). Cancers (Basel).
   2022 Dec 29;15(1):204.
   
4. Tanaka K, Chamoto K, Saeki S, Hatae R, Ikematsu Y, Sakai K, Ando N, Sonomura K, Kojima
   S, Taketsuna M, Kim YH, Yoshida H, Ozasa H, Sakamori Y, Hirano T, Matsuda F, Hirai T,
   Nishio K, Sakagami T, Fukushima M, Nakanishi Y, Honjo T, Okamoto I. Combination
   bezafibrate and nivolumab treatment of patients with advanced non-small cell lung cancer.
   Sci Transl Med. 2022 Dec 14;14(675):eabq0021.
   
5. Okamoto W, Sakai K, Makiyama A, Yamamoto Y, Shitara K, Denda T, Izawa N, Nakano Y,
   Nishina T, Esaki T, Hara H, Miura Y, Boku N, Yamazaki K, Hironaka S, Misumi T, Hyodo I,
   Muro K, Nishio K. A phase II study to explore biomarkers for the use of mFOLFOX6/XELOX
   plus bevacizumab as a first-line chemotherapy in patients with metastatic colorectal cancer
   (WJOG7612GTR). ESMO Open. 2022 Dec;7(6):100592.
   
6. Hayashi Y, Fujita K, Sakai K, Adomi S, Banno E, Nojima S, Tomiyama E, Matsushita M,
   Kato T, Hatano K, Kawashima A, Minami T, Morii E, Uemura H, Nishio K, Nonomura N.
   Targeted-sequence of normal urothelium and tumor of patients with non-muscle invasive
   bladder cancer. Sci Rep. 2022 Oct 5;12(1):16642.
   
7. Kanemura H, Hayashi H, Tomida S, Tanizaki J, Suzuki S, Kawanaka Y, Tsuya A, Fukuda Y,
   Kaneda H, Kudo K, Takahama T, Imai R, Haratani K, Chiba Y, Otani T, Ito A, Sakai K, Nishio
   K, Nakagawa K. The Tumor Immune Microenvironment and Frameshift Neoantigen Load
   Determine Response to PD-L1 Blockade in Extensive- Stage SCLC. JTO Clin Res Rep. 2022
   Jul 1;3(8):100373.
   
8. Hayashi H, Yonesaka K, Nakamura A, Fujimoto D, Azuma K, Sakata S, Tachihara M, Ikeda
   S, Yokoyama T, Hataji O, Yano Y, Hirano K, Daga H, Okada H, Chiba Y, Sakai K, Nishio K,
   Yamamoto N, Nakagawa K. Alternating therapy with osimertinib and afatinib for treatmentnaive
   patients with EGFR-mutated advanced non-small cell lung cancer: A single-group,
   open-label phase 2 trial (WJOG10818L). Lung Cancer. 2022 Jun;168:38-45.
   
9. Makutani Y, Sakai K, Yamada M, Wada T, Chikugo T, Satou T, Iwasa Y, Yamamoto H, de
   Velasco MA, Nishio K, Kawamura J. Performance of Idylla™RAS-BRAF mutation test for
   formalin-fixed paraffin-embedded tissues of colorectal cancer. Int J Clin Oncol. 2022
   Jul;27(7):1180-1187.
   ※本ページで記載している坂井 和子 先生の研究業績は、
   西尾 和人 先生の業績と重複するため、業績の詳細までは、本紀要に記載いたしません。
   業績の詳細を参照される場合、西尾 和人 先生の研究業績から内容をご確認ください。
   

武内 敏秀（ライフサイエンス研究所 特任講師）

1. Toshihide Takeuchi et al. Emerging roles of extracellular vesicles in polyglutamine diseases:
   Mutant protein transmission, therapeutic potential, and diagnostics
   Neurochemistry International 2022, 105357. doi: 10.1016/j.neuint.2022.105357
   
2. Yukari Hatanaka.,Tomohiro Umeda.,Keiko Shigemori.,Toshihide Takeuchi et al.
   C9orf72 Hexanucleotide Repeat Expansion-Related Neuropathology Is Attenuated by Nasal
   Rifampicin in Mice.Biomedicines (2022) doi: 10.3390/biomedicines10051080
   
3. TomoyaTaminato.,ToshihideTakeuchi.,MorioUeyama.,Kohji Mori.,Manabu Ikeda.,
   Hideki Mochizuki.,Yoshitaka Nagai.Therapeutic reduction of GGGGCC repeat RNA levels
   by hnRNPA3 suppresses neurodegeneration in Drosophilamodels of C9orf72-linkedALS/
   FTD.Human Molecular Genetics, 2023, Vol. 32, 10, 1673–1682.doi:10.1093/hmg/ddac298
   
4. Xiaoman Zhang.,Toshihide Takeuchi., Akiko Takeda.,Hideki Mochizuki et al.
   Comparison of serum and plasma as a source of blood extracellular vesicles: Increased
   levels of platelet-derived particles in serum extracellular vesicle fractions alter content
   profiles from plasma extracellular vesicle fractions.PLOSONE(2022).
   doi:10.1371/journal.pone.0270634
   
5. Toshihide Takeuchi.,Kazuhiro Maeta.,Xin Ding.,Yukako Oe.,Akiko Takeda.,Mana Inoue.,
   Seiichi Nagano.,Tsuyoshi Fujihara.,Seiji Matsuda.,Shinsuke Ishigaki.,Kentaro Sahashi.,Eiko
   N. Minakawa.,Hideki Mochizuki.,Masahiro Neya.,Gen Sobue and Yoshitaka Nagai.
   Sustained therapeutic benefits by transient reduction of TDP-43 using ENA-modified
   antisense oligonucleotides in ALS/FTD mice. Molecular Therapy(2023)
   doi:10.1016/j.omtn.2023.01.006.
   ※本ページで記載している武内 敏秀 先生の研究業績3 番及び5 番については、
   永井 義隆 先生の業績と重複するため、業績の詳細までは、本紀要に記載いたしません。
   業績の詳細を参照される場合、永井 義隆 先生の研究業績から内容をご確認ください。