Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice.
The results of single-agent chemotherapy, with 11 anticancer agents, of 15 human gastro-intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor-bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H-thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M-83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3-4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.
Fujita
F
F
Department of Surgery, Osaka University, Suita, Japan.
Fujita
M
M
Taguchi
T
T
Shimozuma
K
K
Sakamoto
Y
Y
Kimoto
Y
Y
Hirai
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012044:Regression Analysis; D013997:Time Factors; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents