1997 Fiscal Year Final Research Report Summary
p53 and genetic instability in gastric cancer
| Project/Area Number |
07671402
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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 |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
OHNO Shinji Faculty of Medicine, Kyushu University, Instructor, 医学部, 助手 (50203881)
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| Co-Investigator(Kenkyū-buntansha) |
MAEHARA Yoshihiko Faculty of Mediceine, Kyushu University, Associate Professor, 医学部, 助教授 (80165662)
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| Project Period (FY) |
1995 – 1997
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| Keywords | gastric cancer / p53 / genetic instability / DNA ploidy / proliferative activity |
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| Research Abstract |
We investiugated the signification of p53 gene and genetic instability in gastric cancer in order to clarify the mechanism of occurrence and growth of gastric cancer. The abnormality of p53 was eevaluated immunohistochemically using PAb 1801, and genetic instability was studied as DNA aneuploidy using FACScan in the resected specimen of gastric canser. Among 96 patients with gastric cancer, p53 overexpression was recognized in 52 (54%). There was a significant correlation between p53 and DNA aneuploidy. The incidence of DNA aneuploidy was 35 of 52 (69%) in those with abnormal p53 and 20 of 44 (45%) in those with normal p53 (P<0.05). The cases with abnormal p53 had significantlly higher DNA index and proliferative activity, as compared to those with normal p53.
The relationship between growth pattern and p53 was investigated in cases with early gastric cancer. The growth patterns were grouped as superficially spreading growth type (Super type), and penetrating growth type (Pen type). The incidence of p53 overexpression was 25 of 59 Super type (18%), which was significantly lower than 25 of 59 Pen type (42%). p53 was also correlated with growth pattern of advanced gastric cancer. Among 196 patients with advanced gastric cancer, p53 abnormality was observed in94 (48%). Higher incedence of abnormal p53 was observed in penetrating growrh type as compared to superficially spreading growth type. Multivariate analysis revealed that p53 overexpression was one of the independent prognostic factors of gastric cancer.
In vitro study showed that higher incidence of apoptosis and lower effect of anticancer drugs was observed in cell lines with p53 wild type as compared to those with mutant p53.
Therefore, these data indicated that p53 and genetic instability play an important role in the occurence, proliferation and growth of gastric cancer as well as the response to the anticancer therapy.
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