Biomedical subjects
Publications and source records attributed to M Ihara.
Explore the source record for details and available documents.
The effects of a combination of cis-diamminedichloroplatinum (II) (CDDP) and hyperthermia on tumor growth were examined using nude mice bearing a transplantable human esophageal cancer (ESO-2). A combination of 4 mg/kg CDDP and 43 degrees C hyperthermia for 30 min effectively inhibited tumor growth in comparison with either treatment alone. Whereas the S-phase fraction was decreased for only 3 days with hyperthermia alone, it was decreased for at least 7 days with the combination of CDDP and hyperthermia. Though the intratumoral concentration of CDDP in the heated tumor was 1.4 times higher than that in the unheated tumor, the amount of DNA-bound CDDP in the heated tumor was 2.2 times higher. The repair efficiencies of CDDP-induced DNA damage showed no significant difference between the heated tumor and the unheated tumor. Therefore, it is suggested that the enhancement of the antitumor effects of CDDP by hyperthermia is dependent on the increase in the initial amount of CDDP-induced DNA damage.
NIH3T3 cells and NIH3T3 cell lines, which were transfected with several oncogenes accompanied by pSV2neo vector, were observed for their survival rate when treated with commonly used anticancer drugs. The survival rates in the cell line transfected with the pSV2neo vector only did not differ significantly from that of parental NIH3T3 cells against bleomycin, nimustine and adriamycin, but it was significantly more resistant to cisplatin and more sensitive to mitomycin C. Therefore, the survival rate in each transfectant was compared with that in the pSV2neo transfectant. The Val-12, v-Ha-ras, v-int-2, v-erbB or v-abl transfectants accompanied by pSV2neo vector were significantly more sensitive to cisplatin than transfection with pSV2neo vector only. The Val-12, v-Ha-ras, v-int-2 and v-abl transfectants were significantly more sensitive, and the v-erbB transfectant more resistant to bleomycin than the pSV2neo transfectant. The v-int-2, v-erbB, frg, v-raf and v-myc transfectants were more sensitive, and the v-Ha-ras transfectant more resistant to nimustine than the pSV2neo transfectant. The N-ras, v-Ha-ras, v-sis, v-int, v-abl and v-myc transfectants were significantly more sensitive to adriamycin than the pSV2neo transfectant. The v-sis and v-int-2 transfectants were more sensitive, and the c-Ki-ras, Val-12, v-erbB and the v-src transfectants more resistant to mitomycin C than the pSV2neo transfectant. Thus there was no relationship between the drug sensitivity and the location of oncogenes, but the transfection was associated with either increased or decreased sensitivity to a number of commonly used anticancer drugs. Therefore, it may be important to take into consideration or overexpression of oncogenes in cancer chemotherapy.
The influence of several oncogenes on drug resistance has recently been show by transfection studies. Therefore, we investigated the influence of transfection on adriamycin (ADR) in cell line transfected with several oncogenes accompanied with pSV2neo vector. There were differences in both the intracellular accumulation of ADR and its sensitivity among the transfectants used in this study. There was a good correlation with the intracellular accumulation of ADR and its sensitivity (r = 0.76, P = 0.002). Further, there were no differences in the ADR efflux among the ras-family transfectants. Therefore, the changes in ADR sensitivity may be due to changes in ADR influx. On the other hand, the ADR accumulation showed an increase of 1.14-1.29 fold by the treatment of 10 micrograms/ml CEP. Moreover, the ADR accumulation showed an increase of 1.29-3.11 fold by hyperthermia at 42 degrees C. There was no significant difference in the ADR accumulation at 42 degrees C among the transfectants, suggesting that the influence on the ADR accumulation may be counteracted by hypethermia at 42 degrees C.
A human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53 gene, and clones of Saos-2 cells, which were transfected with wild type p53 or mutant p53 genes (123A, 143A, 175H and 273H), were observed for their surviving fraction after treatment with the commonly used anticancer drugs, cisplatin (CDDP), nimustine (ACNU), adriamicin (ADR) and bleomicin (BLM). The transfectants of the mutant 143A, 175H and 273H were significantly more resistant to CDDP than the transfectant of pOPI3 (expression plasmid only). The transfectants of the wild type p53 and mutant 123A were significantly more sensitive to ACNU than the transfectant of pOPI3. The transfectant of mutant 123A was more sensitive to ADR than the transfectant of pOPI3. There was no significant difference in sensitivity to BLM between Saos-2 and all kinds of transfectants. Thus the sensitivity of the cells to anticancer drugs varied with the mutation point of the p53 gene.