Experimental and Clinical Study on Glutathione S-transferase-pi in the Hepatocarcinogenesis
| Project/Area Number |
08670631
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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 |
Gastroenterology
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| Research Institution | Toho University |
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Principal Investigator |
SUGIMOTO Motonobu Toho University School of Medicine, Associate Professor, 医学部, 助教授 (30120281)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Kinji Toho University School of Medicine, Associate Professor, 医学部, 助教授 (40057758)
TAKEUCHI Yasuo Toho University School of Medicine, Research Fellow
OCHIAI Kaori Toho University School of Medicine, Research Fellow
KORA Tetsuo Toho University School of Medicine, Research Fellow
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Hepatocarcinogenesis / Glutathione S-transferase / P-glycoprotein |
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| Research Abstract |
(1) We studied the evolution of glutathione 5-transferase (GST)-P gene expression during hepatocarcinogenesis in rats treated with diethylnitrosamine (DEN) by the in situ hybridization method using a complementary RNA probe. The following findings were observed. Six weeks after the DEN treatment, distinct hybridization signals showing the presence of GST-P mRNA were found in the foci of vacuolized hepatocytes. Ten weeks after the DEN treatment, the signals were found in hepatocytes within hyperplastic nodules. Fourteen weeks after the DEN treatment, there were variously differentiated hepatocellular carcinomas, with well-differentiated hepatocellular carcinoma exhibiting signals as intense as hyperplastic nodules, and poorlydifferentiated hepatocellular carcinoma exhuliting even more intense signals. Thus, the expression of GST-P gene transcripts was confirmed in the foci of vacuolized hepatocytes, with variation of gene expression in accordance with carcinoma cell differentiation.
(2)
… More
In order to clarify the evolution of P-glycoprotein (P-GP) expression during hepatocarcinogenesis and the modulation by anticancer drugs, we performed immunohistochemical study in rat livers treated with DEN, with or without epirubicin (EPIR) or cisplatin (CDDP) pretreatmemnt. The presence of P-GP was confirmed correspondingly with the membrane of the bile canaliculi in control group. There were no significant differences between control and EPIR or CDDP groups. The expression of P-GP was prominent in the DEN treated rat livers, compared with the intact rat livers. The overexpression was observed in the hypeiplastic nodules rather than hepatocellular carcinomas. The expression of P-GP in the hyperplastic nodules in EPIR+DEN group was apparently stronger than those in CDDP+DEN group. In conclusion, the expression of P-GP was strongly observed in the hyperplastic nodules rather than hepatocellular carcinomas, suggesting that P-GP confers a protective effect and provides a great advantage to the initiated cells. Moreover, the overexpression was supposed to be induced by EPIR.Clinical study is required to be performed Less
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Report
(4 results)
Research Products
(8 results)
