Effect of Expression of Anticancer Drug-Resistance Related Factors on Chemotherapy for Animal Tumors

• Project/Area Number: 16580251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Kagoshima University
• Principal Investigator: MIYOSHI Noriaki Kagoshima University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (80229905)
• Co-Investigator(Kenkyū-buntansha): ENDO Yasuyuki Kagoshima University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90332600)
• Project Period (FY): 2004 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: animal / neoplasm / chemotherapy / drug resistance / immunohistochemistry / 乳腺

Research Abstract

7 canine cutaneous mast cell tumors were analyzed immunohistochemically for expression of anticancer drug-resistance related factors, such as P-glycoprotein, MRP and metallothionein, and then dogs were administered prednisolone, vinblastine, CCNU and doxorubicin. However, correlations between the expression of the factors and the efficacy of the anticancer drugs or prognosis were not found. Accordingly, we continue to study to more 30 dogs with mast cell tumors by applying the same methods. 57 canine soft-tissue sarcc mas were classified according to the histological grade and immunohistochemically analyzed for expression of the drug-resistance related factors. The main resistance mechanism was via P-glycoprotein, but the correlation with the histological grade was not significant. 81 feline mammary gland cancers were analyzed immunohistochemically for expression of c-erbB-2, p53, estrogen receptor and the drug-resistance related factors. Subsequently, analysis was performed for correl ations between the expression and the histological grade or the prognosis. The cancers showed a high rate of spontaneous resistance to anticancer drugs, but there was no correlation with the prognosis. 80% cats that expressed c-erbB-2 died for a year following surgery, and this was thus an important prognostic factor. Expression of p53 showed no correlation with the one-year mortality rate. The incidence of expression of estrogen receptor was low, and it was elucidated that the proliferation of the cancer cells was not estrogen-dependent. It is clear that the expression profiles of the drug-resistance related factors by immunohistochemical analysis in various animal tumors provide important information for designing the treatment, including chemotherapy. However, we did not find any candidate prognostic factors similar to c-erbB-2, whose expression showed a close correlation with the prognosis in feline mammary gland cancer. It will be necessary to gather more data from retrospective studies and investigate more animals undergoing chemotherapy for drug-resistance related factors.