2007 Fiscal Year Final Research Report Summary
ANALYSIS OF CISPLATIN RESISTANT TARGET FACTOR UNDER STRESS CONDITIOS IN SOLID TUMOR
| Project/Area Number |
18592180
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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 (40325098)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMO Tsuyoshi OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DENTISTRY AND PHARMACEUTICAL SCIENCES, ASSISTANT PROFESSOR (40362991)
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| Project Period (FY) |
2006 – 2007
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| Keywords | CDDP (Cisnlatin) resistance / solid cancer internal environment / hvnoxia / DNA repair mechanism / HIF-1α |
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| Research Abstract |
Cisplatin (CDDP) is done from an excellent antitumor effect in oral cancer for by important anti-cancer drug in the solid cancer chemotherapy. However, CDDP resistance is shown in a lot of solid cancers. It is thought that an environmental in solid cancer becomes a stress as one of the reasons and it takes part in CDDP resistance. Moreover, peculiar state of low oxygen to a solid cancer internal environment greatly influencing DNA repair mechanisms has become clear. In a word, a solid cancer internal environment in the solid cancer makes DNA repair mechanism to unstable and the CDDP resistance is induced.
We examined that DNA repair mechanism under an internal environment in the solid cancer, and to clarify CDDP resistant mechanisms. We used that A431 cell line (A431/P), CDDP resistant cell lines (A431/CDDP1, A431/CDDP2), and oral squamous cell carcinoma cell lines (HSC2, HSC3, HSC4). The A431/P has been markedly high sensitive for CDDP under the low oxygen environment. However, A431/CDDPI and A431/CDDP2 became low sensitive under hypoxic condition. When DNA repair mechanism factor that provided for this CDDP receptivity was analyzed with Western Blotting, a single regulated factor was not clearly made. However, HIF-Iα that was hypoxia induced factor became one of the factors that provided for the CDDP receptivity.
Therefore, the present results suggested that the cisplatin resistant mechanism was HIF-1α induced DNA repair factor under hypoxic condition in solid cancer (especially, oral cancer) internal environment.
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