Treatment of N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancer in Syrian golden hamsters with D-Trp-6-LH-RH and somatostatin analogue RC-160 microcapsules.
Antitumoral effects of the agonist of luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) and the somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) on chemically induced ductal pancreatic adenocarcinomas were studied. The tumors were induced in female Syrian golden hamsters by weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine at a dose of 10 mg/kg b.w. for 6 weeks. 18 weeks after the last injection, the peptides in controlled-release microcapsule formulations were administered s.c. The animals received the following therapies: Group 1 (N = 15), vehicle only; Group 2 (N = 13), D-Trp-6-LH-RH microcapsules releasing 25 micrograms/day injected s.c. once a month; Group 3 (N = 14), RC-160 microcapsules, liberating 25 micrograms/day administered s.c. every 15 days; Group 4 (N = 14), the combination of D-Trp-6-LH-RH plus RC-160 microcapsules. The experiment was terminated on the 80th day when all hamsters in the control group were dead, but in the treated Groups 2, 3, and 4, we observed 71, 77, and 86% of survival rate, respectively. In addition to the prolongation of survival, the combination treatment resulted in a significant decrease in the tumorous pancreatic weight, increase in the body weight of the animals, reduction in ascites from 100 to 8.3% and regressive histological changes in 67% of the specimens. Our findings suggest that somatostatin analogues and D-Trp-6-LH-RH could be considered for the development of hormonal therapy for pancreatic cancer.
Zalatnai
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Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, LA 70146.
Schally
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AV
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D002214:Capsules; D006224:Cricetinae; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008647:Mesocricetus; D009362:Neoplasm Metastasis; D009602:Nitrosamines; D009929:Organ Size / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017329:Triptorelin Pamoate
D000970:Antineoplastic Agents; D002214:Capsules; D009602:Nitrosamines; D017329:Triptorelin Pamoate; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; C013622:nitrosobis(2-oxopropyl)amine