Effects of sandostatin, alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters.
In a previous short-term study (4 months) we found that Sandostatin, when administered prophylactically, inhibited growth of putative pre-neoplastic ductular lesions induced in hamster pancreas by N-nitrosobis(2-oxopropyl)amine (BOP), but not of acinar lesions induced in rat pancreas by azaserine. The present long-term (12 months) study was carried out to investigate the effects of Sandostatin (3 microgram/day), alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine-treated rats and BOP-treated hamsters. In order to mimic therapy in humans, treatment of the animals started 4 months after the last injection with carcinogen, when (pre)neoplastic lesions had already developed. After treatment with Sandostatin for 8 months, rats developed fewer pancreatic atypical acinar cell nodules and tumours than those not treated with Sandostatin. Moreover, multiplicity of (pre)neoplastic acinar lesions was also lower in orchiectomized rats than in intact rats. However, Sandostatin treatment did not enhance the inhibitory effect of surgical castration on pancreatic carcinogenesis in rats. In hamsters that were both orchiectomized and treated with Sandostatin, the development of borderline lesions was significantly inhibited, whereas such an effect was not present in hamsters that were either surgically castrated or treated with Sandostatin alone. In Sandostatin-treated hamsters a significantly lower number of microcarcinomas was found than in hamsters not treated with Sandostatin. The present findings suggest that Sandostatin, particularly in combination with surgical castration, might be of therapeutic value for treatment of ductular pancreatic tumours.
Visser
C J
CJ
Department of Pathology, Toxicology Division, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
van Garderen-Hoetmer
A
A
Klijn
J G
JG
Foekens
J A
JA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001377:Azaserine; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D003131:Combined Modality Therapy; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D008853:Microscopy; D009602:Nitrosamines; D015282:Octreotide / Q000627:therapeutic use*; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000033:anatomy & histology / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000517:prevention & control / Q000628:therapy*; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D001377:Azaserine; D015282:Octreotide