Identification of Cancer Biomarker and Novel Therapeutic Molecutargets by Elucidation of Metabolism in IPMN of Pancreas
| Project/Area Number |
20K09039
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
猪股 雅史 大分大学, 医学部, 教授 (60315330)
岩下 幸雄 大分大学, 医学部, 客員研究員 (60534203)
平下 有香 大分大学, 医学部, 病院特任助教 (70771955)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵管内乳頭粘液性腫瘍 / 糖代謝 / FDG-PET / mTORC1 / PET/CT / 膵IPMN / 癌化 / 代謝 |
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| Outline of Research at the Start |
IPMNは適切な時期での手術が必要であり、悪性化を診断するためのバイオマーカーの同定と有効な治療法の確立が必要である。
本研究では、まずIPMNの悪性化のバイオマーカーの同定として、腺腫と腺癌症例におけるmTORC1活性上昇に関わる遺伝子異常や、mTORC1活性変化による代謝経路の変化を明らかにし、さらに粘液内に含まれる代謝産物との関係を検討し、最終的には粘液内に含まれる代謝産物で検出可能な癌に特異的なバイオマーカーの同定を行う。さらにmTORC1活性に伴う浸潤メカニズムの解明と治療標的の同定としてmTORC1活性の上昇により引き起こされるIPMNの浸潤のメカニズムを明らかにすることで、新たな治療標的の同定を目指す。
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| Outline of Final Research Achievements |
We plan to identify biomarkers for malignant transformation and new therapeutic target by investigating the role of S6 phosphorylation and the significance of glucose metabolic changes in IPMN.
GLUT1 expression increased with carcinogenesis from adenoma to adenocarcinoma, and glucose metabolism changed at the same time. Clinically, there was an association between IPMN carcinogenesis and FDG-PET, and it was useful to diagnose as adenoma or adenocarcinoma with a sensitivity of 85% and a specificity of 96%. During IPMN carcinogenesis, mTORC1 was activated in adenocarcinoma, and mTORC1 was associated with glucose metabolism.
Although IPMN organoids can be created, the success rate was low. They were not useful to identify therapeutic targets. Suppression of mTORC1 activity leads to suppression of proliferation in pancreatic cancer cells, and pS6 and GLUT1 are not correlated with prognosis in the clinical cases. mTORC1 activity was considered to have a strong effect on carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
IPMNは手術時期決定のためには腺腫と腺癌の鑑別が重要であり、今回その鑑別のためのバイオマーカーの同定を行った。発癌に伴うGLUT1発現の亢進が明らかとなり、FDG-PETはIPMNの癌化を診断する有用な検査法であることがわかった。また、「有効な治療法の確立」のため、mTORC1活性に伴う浸潤メカニズムの解明と治療標的の同定を行い、mTORC1活性抑制ががんの増殖抑制につながることがわかり、今後実際のIPMNにおける治療のターゲットの一因子となりうる。
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Report
(4 results)
Research Products
(3 results)
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[Presentation] mTORC1 activation is associated with glucose uptake and malignancy of intraductal papillary mucinous neoplasm of the pancreas2021
Author(s)
Teijiro Hirashita, Shota Amano, Masahiro Kawamura, Atsuro Fujinaga, Hiroaki Nakanuma, Takahide Kawasaki, Yoko Kawano, Takashi Masuda, Yuichi Endo, Masayuki Ohta, Masafumi Inomata
Organizer
第32回日本消化器癌発生学会総会
Related Report
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