|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1995 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1994 : ¥200,000 (Direct Cost : ¥200,000)
Fiscal Year 1993 : ¥1,500,000 (Direct Cost : ¥1,500,000)
1) Expression of P-glycoprotein (pgp) was enalyzed by immunohistochemical staining with monoclonal antibody JSB-1 in 145 frozen specimens (67 were normal colorectal mucosa, 66 were colorectal carcinomas, 5 were colorectal polyps, 5 were metastatic lymph nodes, and 2 were metastatic liver tumors) of 67 patients with colorectal carcinoma and polyps. All specimens of normal colorectal mucosa and adenomatous polyps expressed pgp to various degrees. Positive for pgp were detected in 46.2% of well differentiated type but it was detected in only 14.3% of moderately differentiated type and none of 4 samples from cases of poorly differentiated type were positive for pgp. There was no correlation between the clinicopathological stage of colorectal carcinoma and the expression of pgp. These findings indicate that the expression of pgp is closely related to the differentiation of cells. In normal colorectal epithelium, pgp was expressed normally and in well differentiated type, pgp was still expre
ssed. However, expression of pgp was no longer detectable in carcinomas with moderate or poor differentiation. Moreover, in the metastatic tissues such as lymph node or liver tissues, no pgp expression was detected. Whether pgp expresses or not in the metastatic liver tissues after treatment of anticancer drugs is continuously studied. Expression of pgp, proliferating cell nuclear antigen (PCNA) , product of c-erbB-2, and product of p53 were analyzed by Western blot method in 23 cases of colorectal carcinomas. The level of PCNA expression was higher in tumors with Dukes' C and D than that of tumors with Dukes' A and B.But no correlation between the expression of c-erbB-2 or p53 and the progression of colorectal carcinoma was found. And also, no correlation between the expression of pgp and the expression of PCNA,c-erbB-2, or p53 was detected.
2) Many anticancer agents induce an active process that leads to cell death, known as, apoptosis, in sensitive tumor cells. The fragmentation of DNA,an indicator of apoptosis, was analyzed in two different lines of human gastric cancer cells (HSC-39 and MKN-28) that had been exposed to adriamycin and cisplatin. The fragmentation of DNA was detected in HSC-39 cells (signet ring cell gastric carcinoma) with short exposure time and low dose of drugs compared with MKN-28 cells (moderately differentiated gastric adenocarcinoma). The results suggest that signet ring cell gastric carcinoma is more sensitive to adriamycin and to cisplatin than moderately differentiated gastric adenocarcinoma. However, pgp expression was not detected in both two cell lines. Whether pgp express or not in both cell lines during the process to apoptosis is continuously studied. Less