| Project/Area Number |
05671914
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
FUNATO Tadao Tohoku University, School of Medicine hospital, Lecturer, 医学部附属病院, 講師 (70165455)
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| Co-Investigator(Kenkyū-buntansha) |
HOSINO Atsusi Tohoku University, School of Medicine, Lecturer, 医学部, 講師 (60241600)
KAWAMURA Takeshi Tohoku University, School of Medicine, Associate proftess., 医学部, 助教授 (80111277)
蝦名 弘子 東北大学, 医学部・附属病院, 文部教官講師 (70223667)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Anti-Cancer-drug / Drug-resistance / Antisense / Ribozyme / Colon cancer / Leukemia / Cisplatin / Cytosine arabinoside / サイトシン・アラビノシド / 結腸癌 |
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| Research Abstract |
Our previous work has focused on implicating fos in the cellular resistance to cancer chemotherapy agents. Our hypothesis, simply standed, is that fos is resposible for directing the cellular respose to DNA damage by activating transcription of genes encoding enzymes involved in DNA synthesis and repair. Inthis study, we have investigated the cisplatin resistance in vitro and in vivo. A hammerhead ribozyme for fos was disigned to cleave selectively only expresed fos RNA the efficacy of an anti-fos ribozyme in reversing this resistant cell lines. The c-fos ribozyme was suppressed fos mRNA in cultured resistant cell line. We demonstrated that expresion of the fos ribozyme sensitivity of A2780DDP cells to antineoplastic agents. On the other hand, the reversal of this resistance is associated with down-regulation of dTMP synthase, DNA polymerase, topoisomerase I and hMT,genes linked to DNA synthesis and repair. Moreover, this fos ribozyme supresed expresion of c-fos gene on implanted tumors in an athymic mice and reversed sensitivity for cisplatin, but not inhibition.
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