1996 Fiscal Year Final Research Report Summary
CLINICAL AND EXPERIMENTAL STUDY OF APOPTOSIS IN GASTRIC AND ESOPHAGEAL CARCINOMAS
| Project/Area Number |
06671255
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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 | NIIGATA UNIVERSITY |
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Principal Investigator |
AIZAWA Kikuo NIIGATA UNIVERSITY,SCHOOL OF MEDICINE,UNIVERSITY HOSPITAL,ASSISTANT, 医学部・附属病院, 助手 (10222449)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Tsutomu NIIGATA UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESOR, 医学部, 助教授 (40183420)
NISHIMAKI Tadashi NIIGATA UNIVERSITY,SCHOOL OF MEDICINE,UNIVERSITY HOSPITAL,LECTURER, 医学部・附属病院, 講師 (70242427)
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| Project Period (FY) |
1994 – 1996
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| Keywords | apoptosis / bcl-2 / p53 / proliferative activity / gastric carcinoma / prognostic factors / ecophageal carcinoma / cisplatin-resistance |
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| Research Abstract |
Summary 1. Apoptosis and Bcl-2 expression in gastric carcinomas
Two-hundred and twenty one advanced gastric carcinomas were investigated using Gavrieli's method for detection of apoptotic cells and immunohistochemistry for Bcl-2, p53 and proliferating cell nuclear antigen (PCNA). The apoptotic index (AI) was associated with differentiated type tumors, positive lymphatic vessel invasion and a high PCNA-labeling index. Bcl-2 expression was detected in 72 of 221 cases (32.6%) and found to be inversely correlated with depth of tumor invasion, blood vessel invasion and lymph node metastasis. Moreover, it was correlated with a low AI.p53 expression was detected in 64 cases (29.0%) and neither correlated with AI nor Bcl-2 expression. Bcl-2 expression was associated with a better prognosis. These results indicate that apoptosis is associated with cell proliferation and Bcl-2 expression in gastric carcinomas. Bcl-2 may be expressed in the early phase of gastric carcinogenesis.
Summary 2. Induction of apoptosis in cisplatin-resistant human esophageal cancer cells
We have attempted to determine whether buthionine sulfoximine (BSO) and cyclosporin A (CsA) enhance cisplatin-induced apoptosis in cisplatin-resistant human esophageal cancer cells. The human esophageal cancer cell line TE2 and its 2.4-fold cisplatin-resistant derivative TE2R were used in this study. Cisplatin induced DNA fragmentation corresponding to the nucleosome ladders characteristics of apoptosis in TE2 but not in TE2R.BSO enhanced cisplatin sensitivity of both cell lines but affected neither cisplatin resistance nor induction of apoptosis, although CsA showed a resistance-modifying activity in TE2R.This effect was associated with induction of apoptosis at a relatively low concentration of cisplatin, when tested alone did not induce apoptosis. Our data indicate that CsA may overcome cisplatin resistance by enhancing the susceptibility to cisplatin-induced apoptosis in human esophageal cancer cells.
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