Study on invasion and metastasis based on biological aspects of pancreatic cancer
| Project/Area Number |
05671074
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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 |
Digestive surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
HIRAOKA Takehisa Kumamoto University School of Medicine Associate Professor, 医学部, 助教授 (70094034)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | pancreatic cancer / Metastasis / invasion / serine protease / deoxyribonuclease I / insulin / glucose / carbohydrate antigen / 肝転移 / DNase-1 / Carbohydrate antigen / CA19-9 / 肺転移 / 膵外分泌系酵素 |
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| Research Abstract |
Effects of serine protease and deoxyribonuclease on blood-borne metastases in mouse liver and in rat lung, enhancing effect of insulin on pancreatic cancer cells via activated glucose metabolism, and correlation between with expression of tumor-associated carbohydrate antigens and hepatic metastases of pancreatic cancer were studied. Spontaneous liver metastases of L 5178Y-ML cells was enhanced by systemic administration of alpha-chymotrypsin after tumor cell inoculation. In contrast, systemic administration of DNase I after tumor cell inoculation inhibited liver metastases. DNase I treatment resulted in a statistically significant prolongation of the survival period. Effect of alpha-chymotrypsin and DNase I on the early phase of blood-borne lung metastases in rats were studied. Intravenous administration of alpha-chymotrypsin and DNase I apparently enhanced and inhibited, respectively, the tumor cell arrest in lung microvasculature as reflections of reduction and promotion, respective
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ly, of the tumor cell clearance in the microvasculature. It was found that insulin enhanced invasion of a human pancreatic adenocarcinoma cell line AsPC-1 in the dermal transplantation and in an invasion assay in vitro. Insulin also promoted morphological polarization of the cells in vitro. These enhancing effects disappeared, when alpha-ketoglutaric acid was substituted for glucose. Glucose transport activity of the cells was increased by insulin. Insulin enhances the invasion of the cells inducing the cell polarization, as a result of facilitating glucose metabolism. We experimentally studied a correlation between expression of three carbohydrate antigens (CA 19-9, DUPAN-2 and Span-1) and incidence of blood-borne hepatic metastases in nude mice using six human pancreatic cancer cell lines. The positive correlation between expression of the carbohydrate antigens and metastatic potential of pancreatic cancer was confirmed. We will have further study on invasion and metastasis of pancreatic cancer and prevention of intravascular tumor cell arrest in liver by DNase I treatment for clinical application. Less
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Research Products
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