Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone.
Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) or with [6-D-tryptophan]luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) delayed delivery systems. Microcapsules of somatostatin analog RC-160, designed to release a dose of 5 micrograms/day, were injected twice a month and microcapsules of [D-Trp6]LH-RH, calculated to liberate 25 micrograms per day, once a month. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with [D-Trp6]LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with [D-Trp6]LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend our findings, obtained in male animals with transplanted tumors, that [D-Trp6]LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers.
D000230:Adenocarcinoma / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D006224:Cricetinae; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008647:Mesocricetus; D008854:Microscopy, Electron; D009026:Mortality; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017329:Triptorelin Pamoate
D009602:Nitrosamines; D017329:Triptorelin Pamoate; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin