齊郷 智恵美

所属 Affiliation

Chiemi SAIGO

岐阜大学高等研究院 One Medicine ﾄﾗﾝｽﾚｰｼｮﾅﾙﾘｻｰﾁｾﾝﾀｰ (COMIT)・

岐阜大学大学院連合創薬医療情報研究科・准教授（医療情報学専攻・生体制御研究領域）
准教授（革新的モダリティ創出部門）
United Graduate School of Drug Discovery and Medical Information
Sciences, Gifu University (Field of Biofunctional Control, MedicalInformation Sciences Division) ; Associate Professor
Center for One Medicine Innovative Translational Research(COMIT); Associate Professor (Division of Innovative ModalityDevelopment)

専門
Research Area

研究課題
代表的な研究Main ResearchProjects

病理学Pathology
がん代謝阻害剤とオートファジー阻害薬の併用による悪性腫瘍制御の試み
100 年以上前から、がん細胞は、正常細胞にはない解糖系エネルギー代謝経路を利用することが提唱されてきた(1924 年 Otto Heinrich Warburg)。現在では、がん細胞は好気状況下でもミトコンドリアの酸化的リン酸化よりも，解糖系で ATP を産生しエネルギーを確保することが、広く知られており、この、がん細胞に特異的な代謝性要求を阻害する薬剤開発が、試みられている。
われわれは、淡明細胞肉腫をがん代謝経路阻害剤 CPI-613®（devimistat）に暴露させると、この肉腫細胞は、細胞質内に蓄えていた豊富なグリコーゲンをオートファジーで処理し、増殖のエネルギーを確保しようとすることを明らかにした。続けて、CPI-613 とオートファジー阻害剤であるクロロキンを併用することにより、淡明肉腫細胞は、グリコーゲンを処理できず、ネクローシスに陥ることを見出した。
この CPI-613 とクロロキンの併用に関して米国製薬企業 Rafael Pharmaceuticals, Inc. （現Cornerstone Pharmaceuticals, Inc, NJ）と共同して国際特許、米国各国申請を行い、2021 年 9 月より再発・難治性淡明肉腫を対象に Phase I/II の臨床試験が、米国 6 施設で試行中である。
病理組織学的知見に基づき、淡明肉腫に類似した生物学的態度をもつことが知られている悪性腫瘍を選び出し、がん代謝阻害剤とオートファジー阻害剤の併用による治療方法の適応拡大を試みている。
Combination of a cancer metabolism inhibitor and an autophagy inhibitor
to control malignant tumors
Nearly a century ago, it was proposed that cancer cells adopt a glycolytic
pathway that is absent in normal cells for energy metabolism (Otto HeinrichWarburg, 1924). Now, it is widely accepted that cancer cells generate ATP
through glycolysis rather than mitochondrial oxidative phosphorylation, evenunder aerobic conditions, and agents that could abrogate cancer cell prefermetabolic requirements are under development.
We found that clear cell sarcoma, when exposed to CPI-613 (devimistat, aninhibitor of the metabolic pathway in cancer) use autophagic degradation of
the abundant glycogen stock in the cytoplasm to secure energy for cell growth.
We also found that use of CPI-613 in combination with chloroquine (anautophagy inhibitor) led clear cell sarcoma cells to necrosis by inhibiting theirability to use stocked glycogen.
Together with the US pharmaceutical company Cornerstone Pharmaceuticals,Inc. (formerly Rafael Pharmaceuticals, Inc.), we have applied for international
patents on the combination of CPI-613 and chloroquine in several countries. A
phase I/II clinical study was launched in September 2021 to investigate theeffectiveness of this approach for treatment of relapsed or refractory clear cellsarcoma and is currently underway at six facilities in the US.
Based on histopathological findings, we plan to select malignant tumors having
biological behaviors similar to that of clear cell sarcoma with the aim ofexpanding the indications for treatment using this approach to those tumors.

研究業績(過去 5 年)

1.

Higashi T, Saigo C, Chikaishi W, Hayashi H, Hanamatsu Y, Futamura M,Matsuhashi N, Takeuchi T. Implication of IZUMO2 in the cell-in-cell
phenomenon: A potential therapeutic target for triple-negative breast
cancer.Thorac Cancer. 2024 Mar;15(7):513-518. doi: 10.1111/17597714.15189. Epub 2024 Jan 23. (IF:2.9 CS:5.2) 査読あり
2. Ichiki N, Saigo C, Hanamatsu Y, Iwata H, Takeuchi T. Inducing Melanoma Cell
Apoptosis by ERp57/PDIA3 Antibody in the Presence of CPI-613 andHydroxychloroquine.J Cancer. 2024 Feb 4;15(7):1779-1785. doi:10.7150/jca.92252. eCollection 2024. (IF:3.9 CS:8.1) 査読あり
3. Ono Y, Higashida K, Yamanouchi K, Nomura S, Hanamatsu Y, Saigo C, Tetsuka
N, Shimohata T. Balamuthia mandrillaris amoebic encephalitis mimicking
tuberculous meningitis. Neuropathology. 2024 Feb;44(1):68-75. doi:10.1111/neup.12932. Epub 2023 Jun 28. (IF:2.3 CS:4.1) 査読あり
4. Chikaishi W, Higashi T, Hayashi H, Hanamatsu Y, Futamura M, Matsuhashi N,Saigo C, Takeuchi T. Adiponectin-expressing Treg-containing T cell fraction
inhibits tumor growth in orthotopically implanted triple-negative breast
cancer.Thorac Cancer. 2023 Oct;14(30):3058-3062. doi: 10.1111/17597714.15102. Epub 2023 Sep 6. (IF:2.9 CS:5.2) 査読あり
5. Chikaishi W, Higashi T, Hayashi H, Hanamatsu Y, Kito Y, Futamura M,Matsuhashi N, Saigo C, Takeuchi T. Potential activity of adiponectin-expressing
regulatory T cells against triple-negative breast cancer cells through the cellin-cell phenomenon.Thorac Cancer. 2023 Jul;14(20):1941-1945. doi:
10.1111/1759-7714.14940. Epub 2023 May 23. (IF:2.9 CS:5.2) 査読あり
6. Hayashi H, Yasufuku I, Higashi T, Chikaishi W, Yokoi R, Fukada M, Sato Y, AsaiR, Tajima JY, Saigo C, Makiyama A, Tanaka Y, Okumura N, Murase K,Takahashi T, Futamura M, Takeuchi T, Matsuhashi N. Late recurrent gastriccarcinoma 12 years after surgery with attenuation of CD44 variant 9
expression.Surg Case Rep. 2023 May 22;9(1):87. doi: 10.1186/s40792-02301660-5. (IF:0.8 CS:0.7) 査読あり
7. Niwa R, Hanamatsu Y, Kito Y, Saigo C, Takeuchi T. Experimental model ofmicronodular thymic neoplasm with lymphoid stroma.Thorac Cancer. 2023
Feb;14(4):357-362. doi: 10.1111/1759-7714.14716. Epub 2022 Dec
16.PMID: 36524622. (IF:3.223, CS:4.8) 査読あり
8. Hanamatsu Y, Saigo C, Takeuchi T.Adiponectin-expressing Treg cells inexperimental thymic tumor model.Thorac Cancer. 2023 Feb;14(4):432-433.
doi: 10.1111/1759-7714.14792. Epub 2023 Jan 5.PMID: 36604986.
(IF:3.223, CS:4.8) 査読あり
9. Tomioka M, Saigo C, Kawashima K, Suzui N, Miyazaki T, Takeuchi S, Kawase
M, Kawase K, Kato D, Takai M, Iinuma K, Nakane K, Takeuchi T, Koie T. ClinicalPredictors of Grade Group Upgrading for Radical Prostatectomy Specimens
Compared to Those of Preoperative Needle Biopsy Specimens.
Diagnostics(Basel).
2022
Nov
11;12(11):2760.
doi:
10.3390/diagnostics12112760.PMID: 36428820. (IF:3.992, CS:3.6)査読あり
10. Hayashi H, Makiyama A, Okumura N, Yasufuku I, Saigo C, Takeuchi T,Miyazaki T, Tanaka Y, Matsuhashi N, Murase K, Takahashi T, Futamura M,Yoshida K. Gastric carcinosarcoma with FGFR2 amplification under long-termcontrol with pazopanib: a case report and literature review. BMC
Gastroenterol. 2022 Jul 28;22(1):360. doi: 10.1186/s12876-022-024325.PMID: 35902814. (IF:2.848, CS:3.9) 査読あり
11. Hasegawa M, Hanamatsu Y, Saigo C, Kito Y, Takeuchi T. Tumor suppressor
effect of an antibody on xenotransplanted sarcomatoid mesothelioma cells.
Thoracic cancer. 2022 Sep;13(18):2566-2573. doi: 10.1111/17597714.14591. Epub 2022 Aug 2. (IF:3.223, CS:3.1) 査読あり
12. Matsuo M, Saigo C, Takeuchi T, Onogi A, Watanabe N, Aikyo S, Toyoki H,Yanai H, Tanaka T. Ovarian Clear Cell Carcinoma and Mature Cystic Teratoma
Transformed to PNET and Carcinosarcoma: A Case Report with an
Immunohistochemical Investigation.Biomedicines. 2022 Feb 24;10(3):547.
doi: 10.3390/biomedicines10030547. (IF:6.081, CS:3.0) 査読あり
13. Kito Y, Kawashima K, Saigo C, Hasegawa M, Nomura S, Mikamo T, Hanamatsu
Y, Matsuo Y, Takeuchi T. Thorahcic SMARCA4-deficient undifferentiatedtumors with ganglioneuroma and enchondroma: implications for SLC7A11 andARID1A expression: a case report. Diagn Pathol. 2022 Feb 12;17(1):29. doi:
10.1186/s13000-022-01205-8. (IF:2.644, CS:4.0) 査読あり
14. Kawase M, Nakane K, Namiki S, Takeuchi Y, Ueda S, Kawase K, Nakai C,
Takeuchi S, Kato D, Takai M, Iinuma K, Fuwa M, Saigo C, Miyazaki T, Morita
H, Koie T. A Case of Localized Prostate Cancer Associated with Polymyalgia
Rheumatica with Marked Symptomatic Improvement after Robot-Assisted
Radical Prostatectomy. Case Rep Urol. 2021 Oct 15;2021:8026883. doi:
10.1155/2021/8026883. eCollection 2021. (IF:0.5, CS:0.9) 査読あり

15. Takeuchi Y, Kato D, Nakane K, Kawase K, Takai M, Iinuma K, Saigo C, Miyazaki
T, Koie T. Solitary Fibrous Tumor of the Prostate: A Case Report and Literature
Review.
Medicina(Kaunas).
2021
Oct23;57(11):1152.
doi:10.3390/medicina 57111152. (IF:2.430, CS:2.7) 査読あり
16. Takeuchi S, Nakane K, Saigo C, Miyazaki T, Koie T. A Case of Muscle-InvasiveBladder Cancer With Pelvic Lymph Node Involvement Treated WithPembrolizumab and Subsequent Radical Cystectomy and Maintained No
Evidence of Disease After Surgery. Cureus. 2021 Nov 8;13(11):e19375. doi:
10.7759/cureus.19375. eCollection 2021 Nov. (IF:-, CS:-) 査読あり
17. Hano K, Hatano K, Saigo C, Kito Y, Shibata T, Takeuchi T. Combination ofClptm1L and TMEM207 Expression as a Robust Prognostic Marker in Oral
Squamous Cell Carcinoma. Front Oral Health. 2021 Mar 29;2:638213. doi:
10.3389/froh.2021.638213. eCollection 2021. (IF:-, CS:-) 査読あり
18. Saigo C,Hanamatsu Y, Hasegawa M,Nomura S,Mikamo T,Kito Y,Yasufuku I,Tanaka H,Yoshida K,Takeuchi T.:Submucosal tumor-like esophageal cancer
mimicking a cutaneous sweat gland carcinoma: A case report. Human
Pathology : Case Reports. 26(2021) 300551. (IF:3.526, CS:0.6) 査読あり
19. Saigo C, Kito Y, Hasegawa M, Nomura S,Mikamo T, Hanamatsu Y, Mori R,Futamura M, Yoshida K, Takeuchi T.:Incidental cytokeratin-positive interstitial
reticulum cell tumor of the lymph node accompanied by breast cancer: Status
of YAP/TAZ expression in tumor cells. Human Pathology: Case
Reports.Available online 5 June 2021,200526(2021). (IF:3.526, CS:0.6) 査読あり
20. Tanaka H, Saigo C, Iwata Y, Yasufuku I, Kito Y, Yoshida K, Takeuchi T.:Humancolorectal cancer-associated carbohydrate antigen on annexin A2 protein. JMol Med (Berl). 2021 Aug;99(8):1115-1123.doi: 10.1007/s00109-02102077-z. Epub 2021 Apr 27.PMID: 33904933 (2021). (IF:4.599, CS:7.7) 査
読あり
21. Takao K, Tani A, Suwa T, Kuwabara-Ohmura Y, Nonomura K, Liu Y, Kato T,Mizuno M, Hirota T, Enya M, Iizuka K, Horikawa Y, Saigo C, Kito Y, Miyazaki
T, Ohe N, Iwama T, Yabe D.:Diagnosis and treatment of primary central
nervous system lymphoma with the primary lesion in the hypothalamus: acase report.BMC Endocr Disord. 2021 Jan 11;21(1):13. doi: 10.1186/ s12902020-00675-5.PMID: 33430828 (2021). (IF:2.763, CS:3.5) 査読あり
22. Iwata Y, Yasufuku I, Saigo C, Kito Y, Takeuchi T, Yoshida K.:Anti-fibroticproperties of an adiponectin paralog protein, C1q/TNF-related protein 6(CTRP6), in diffuse gastric adenocarcinoma.J Cancer. 2021 Jan 1;12 (4):11611168. doi: 10.7150/jca.46765.eCollection 2021.PMID: 33442414 (2021).
(IF:4.207, CS:6.4) 査読あり
23. Hanamatsu Y, Saigo C, Kito Y, Takeuchi T.:An obstructive role of NK cells on
metastatic growth of clear-cell sarcoma cells in a xenoplant murine model. MolClin Oncol. 2021 Jan;14(1):9. doi:10.3892/mco.2020.2171.Epub 2020 Nov
12.PMID: 33262889 Free PMC article. (2021). (IF:0.693, CS:1.6) 査読あり
24. Yasufuku I, Saigo C, Kito Y, Yoshida K, Takeuchi T.:Prognostic significance of
LDL receptor-related protein 1B in patients with gastric cancer.J Mol Histol.
2021 Jan 3. doi: 10.1007/s10735-020-09932-2. Online ahead of print.PMID:33389427 (2021). (IF:2.611, CS:3.8) 査読あり
25. Sakuratani T, Takeuchi T, Yasufuku I, Iwata Y, Saigo C, Kito Y, Yoshida
K.:Downregulation of ARID1A in gastric cancer cells: a putative protective
molecular mechanism against the Harakiri-mediated apoptosis pathway.
Virchows Arch. 2020 Aug 13. doi: 10.1007/s00428-020-02899-1.Online
ahead of print.PMID: 32789692(2020). (IF:4.064, CS:6.5) 査読あり
26. Mizutani T, Araki H, Saigo C, Takada J, Kubota M, Ibuka T, Suzui N, Miyazaki
T, Shimizu M.:Endoscopic and Pathological Characteristics of Helicobacter
pylori Infection-Negative Early Gastric Cancer.Dig Dis. 2020;38(6):474-483.
doi:10.1159/000506120. Epub 2020 Feb 11.PMID:32045929 (2020).
(IF:2.404, CS:4.2) 査読あり
27. Hatano K, Saigo C, Kito Y, Shibata T, Takeuchi T. Overexpression of JAG2 isrelated to poor outcomes in oral squamous cell carcinoma. Clin Exp Dent Res.
6(2):174-180 (2020). (IF:1.45, CS:2.1) 査読あり
28. Kito Y, Hanamatsu Y, Kawashima K, Saigo C, Takeuchi T.A unique transgenic
mouse model exhibiting a myeloproliferative disease-like phenotype. Biol
Open. 2019 Nov 7. pii: bio.044438. doi: 10.1242/bio.044438. (IF:2.33,
CS:4.6) 査読あり
29. Hanamatsu Y, Saigo C, Asano N, Kito Y, Nakada K, Takeda Y, Takeuchi T. A
Case of Gastric Amphicrine Signet-Ring Cell Carcinoma.Clin Pathol. 2019 Oct
10;12:2632010X19880535. doi: 10.1177/2632010X19880535. (IF:1.16,CS:1.1) 査読あり

30. Hano K, Hatano K, Saigo C, Kito Y, Shibata T, Takeuchi T.An adiponectinparalog protein, CTRP6 decreased the proliferation and invasion activity of oral
squamous cell carcinoma cells: possible interaction with laminin receptor
pathway. Mol Biol Rep. 46(5):4967-4973. (2019) doi: 10.1007/s11033-01904947-9. (IF:2.316, CS:3.3) 査読あり
31. Kawashima K, Saigo C, Kito Y, Hanamatsu Y, Egawa Y, Takeuchi T.:CD151
confers metastatic potential to clear cell sarcoma of the soft tissue in animalmodel. Oncol Lett. 17(6):4811-4818. (2019) doi: 10.3892/ol.2019. 10164.
(IF:2.967, CS:5.8) 査読あり
32. Asano Y, Saigo C, Kito Y, Iwata Y, Yoshida K, Takeuchi T. : Response to Yanget. al. J Mol Med (Berl). doi:10.1007/s00109-019-01775-z, (2019). (IF:4.599,CS:7.7) 査読あり
33. Inoue K, Hatano K, Hanamatsu Y, Saigo C, Kito Y, Bunai K, Shibata T, Takeuchi
T. : Pathobiological role of cleft palate transmembrane protein 1 family
proteins in oral squamous cell carcinoma. J Cancer Res Clin Oncol.
145(4):851-859. doi: 10.1007/s00432-019-02843-0, (2019). (IF:4.553,CS:6.9) 査読あり
34. Asano Y, Takeuchi T, Okubo H, Saigo C, Kito Y, Iwata Y, Futamura M, Yoshida
K. : Nuclear localization of LDL receptor-related protein 1B in mammary gland
carcinogenesis. J Mol Med. 97(2):257-268. (2019). (IF:4.599, CS:7.7) 査読あり

外部資金
(過去 5 年)

特許

略歴

国際特許 3 件＃1 WIPO|PCT WO2020/132395AI(国際特許審査新規性あり、産業性ありで Taiwan、米国、メキシコ各国申請)＃2 PCT/JP2022/ 13783(国際特許審査新規性あり、産業性ありで EU および米国各国申請)＃3 C20210538WO＃P01(特許庁国際出願審査中)
平成 19 年 3 月 佐賀大学医学部医学科卒業
平成 19 年 4 月 岐阜大学医学部附属病院研修医
平成 21 年 4 月 同病理部医員
平成 26 年 4 月 岐阜大学大学院医学系研究科 形態機能病理学 助教
令和２年 3 月
同准教授
令和４年 1 月
岐阜大学大学院連合創薬医療情報研究科・准教授
令和 5 年 1 月
岐阜大学高等研究院 One Medicine ﾄﾗﾝｽﾚｰｼｮﾅﾙﾘｻｰﾁｾﾝﾀｰ (COMIT)・准教授 現在に至る。