| Project/Area Number |
17591336
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KIM Ryungsa Hiroshima University, Research Institute for Radiation Biology and Madicine, Associate Professor, 原爆放射線医科学研究所, 助教授 (80274132)
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| Co-Investigator(Kenkyū-buntansha) |
ARIHIRO Koji Hiroshima University, Hospital, Associate Professor, 病院・助教授 (70232064)
TANABE Kazuaki Hiroshima University, Research Institute for Radiation Biology and Medicine, Research Associate, 原爆放射線医科学研究所, 助手 (40379847)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cancer chemotherapy / Cell death / Apoptosis / Non-apoptosis / Autophagy / Tumor immunity / 抗癌剤 / 胃癌 / 乳癌 |
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| Research Abstract |
In this study, we found the following results :
1) Various anticancer drugs induced non-apoptotic cell death such as autophagic cell death in solid malignancies such as gastric and breast cancer ;
2) In early phase in response to cell damage, although autophagy was involved in cell survival that produces energy in tumor microenvironment, the autophagy was committed to cell death in late phase when the damage exceeded the threshold ;
3) Autophagic cell death was induced by anticancer drugs in apoptosis-resistant cancer cells ;
4) Anticancer drugs-induced cell death including apoptosis and autophagic cell death contributed to provoking tumor immunity as a consequence of enforced cell death.
The development of molecular targeting drugs such as monoclonal antibody and small molecules is due to the modulation of anticancer drug-induced cell death and provocation of tumor immunity following the cell death. In particular, in the case of monoclonal antibody such as trastuzumab, treatment with trastuzumab provokes tumor immunity which is mediated by not only ADCC but also activation of dendritic cells through Fc γ R. The significance of autophagic cell death in tumor response needs to be demonstrated in clinical practice as a proof of principle, and the assessment will be very important for bridging between preclinical and clinical situation in cancer chemotherapy.
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