| Project/Area Number |
16592000
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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 |
Surgical dentistry
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MESE HIROSHI OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DENTISTRY AND PHARMACEUTICAL SCIENCES, ASSOCIATE PROFESSOR, 大学院・医歯薬学総合研究科, 助教授 (40325098)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI AKIRA OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DENTISTRY AND PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・医歯薬学総合研究科, 教授 (00170663)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | CDDP (Cisplatin) resistance / stress conditions in solid tumors / glucose-starved stress / hypoxia / nucleotide excision repair (NER) / DNA mismatch repair (MMR) |
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| Research Abstract |
This study elucidated that Cisplatin (CDDP) resistant mechanism under stress conditions in solid tumor. Furthermore, I identified to CDDP resistant induced factor and new treatment strategy.
1. CDDP sensitivity under stress conditions
We used CDDP resistant subline A431/CDDP2 from human epidermoid carcinoma cell line A431 as previously established. The stress condition was hypoxia and glucose-starvation. These conditions led to cellular sensitization to CDDP in the parent A431 cell (A431/P) only. In stress conditions, A431/P induced apoptosis, but A431/CDDP2 was not different with CDDP induced apoptosis.
2. CDDP resistant induced factor in stress condition
I suggested that nucleotide excision repair (NER) and/or DNA mismatch repair (MMR) was very important factor to CDDP sensitivity in solid tumor under stress conditions.
3. Fundamental study of new treatment strategy
Hyper sensitivity of CDDP was accepted by using Aphidicolin (DNA polymerase inhibitor) together with CDDP and induced apoptosis. In other words, Aphidicolin inhibited normal DNA synthesis by DNA polymerase in healing mechanism for DNA lesion of CDDP. As a result, it was thought that apoptosis was induced by CDDP treated with Aphidicolin.
In brief, I suggested that possibility of new cancer chemotherapy by DNA polymerase inhibitor combination in CDDP resistant solid tumor.
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