Sensitization of C6 glioma to carboplatin cytotoxicity by hyperthermia and thymidine.
Thymidine (a nucleoside metabolite) and 41.8 degrees C hyperthermia were used to sensitize C6 glioma cells to carboplatin cytotoxicity in vitro. Clinically achievable thymidine concentrations (0, 200, 400, or 1000 micrograms/ml X 24 hours) significantly enhanced carboplatin killing. Clinically achievable hyperthermia exposures (40.5 or 41.8 degrees C X 1 hour) also enhanced carboplatin killing; 41.8 degrees C was more effective than was 40.5 degrees C. Thymidine and 41.8 degrees C hyperthermia together enhanced carboplatin killing significantly more than did the thymidine-carboplatin or hyperthermia-carboplatin combinations. These results illustrate the concept of 'combination chemosensitization' for simultaneously addressing the divergent drug resistance mechanisms of malignant gliomas.
Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison 53792.
J D
JD
Cohen
H I
HI
Robins
M J
MJ
Javid
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D006979:Hyperthermia, Induced; D013936:Thymidine / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016190:Carboplatin; D013936:Thymidine