1998 Fiscal Year Final Research Report Summary
Molecular mechanisms in radiation-induced cell death of gynecologic cancer
| Project/Area Number |
09671708
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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 |
Obstetrics and gynecology
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| Research Institution | Osaka City University |
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Principal Investigator |
TANAKA Tetsuji Osaka City Univ.Medical School, Assistant Professor, 医学部, 講師 (80275255)
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| Co-Investigator(Kenkyū-buntansha) |
OGITA Sachio Osaka City Univ.Medical School, Professor, 医学部, 教授 (00047086)
UMESAKI Naohiko Osaka City Univ.Medical School, Associate Professor, 医学部, 助教授 (20106339)
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| Project Period (FY) |
1997 – 1998
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| Keywords | radiotherapy / radiosensitivity / cervical cancer / anticancer drug resistance / cytokine / apoptosis |
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| Research Abstract |
(I) Effects of cytokines and anticancer drugs on radiosensitivities of radiosensitive human cervical SCC cells. INFs and anti-Fas IgM enhanced radiation-induced cell death in the cervical SCC cells, while IL-1beta and TGF-beta1 inhibited the cell death dose-dependently. The inhibitory mechanisms by TGF-beta1, not by IL-1beta, were shown to be tissue-specific and cell cycle-dependent manners.
(2) Establishment and characterization of radioresistant subclones derived from the human cervical SCC cells Radioresistant subolones were established and examined for anticancer drug-sensitivity tests. The result that the radioresistant cells had higher sensitivities to CDDP, SN38, or THP indicates that these drugs should be chosen for the patients with postirradiation recurrent cervical SCC.Expression cloning experiments of the radioresistant genes were tried in vain.
(3) Establishment and characterization of anti cancer drug-resistant subclones derived from the human cervical SCC cells. Several drug-resistant subclones exhibited cross-resistances to several anticancer drugs and gamma-irradiation. Three CPA-resistant subclones were resistant to radiation-induced cell death. This suggests a possibility that CPA-induced apoptosis share common signaling pathways to radiation-induced apoptosis in the SCC cells. Our results indicate that acquired drug-resistance in cancer cells might be associated with acquisition of radioresistance ; and conversely this indicates that acquisition of radio-resistance in cancer cells might be associated with acquired drug-resistance. Results of the semi-quantitative RT-PCR analyses suggest a possibility that bcl-2 family gene products, c- myc, and beta-actin share some common apoptotic signals to human cervical SCC cells. Accordingly it is thus inferred that these mutations can be used for genetic markers to evaluate drug-resistance and/or radio-resistance in cervical cancer cells.
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