Visser C J, van Garderen-Hoetmer A, Klijn J G, Foekens J A
Department of Pathology, Toxicology Division, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Int J Cancer. 1996 Mar 15;65(6):827-32. doi: 10.1002/(SICI)1097-0215(19960315)65:6<827::AID-IJC20>3.0.CO;2-#.
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.
在之前的一项短期研究（4个月）中，我们发现，预防性给予善得定可抑制N-亚硝基双（2-氧代丙基）胺（BOP）诱导的仓鼠胰腺中假定的癌前导管病变的生长，但对氮杂丝氨酸诱导的大鼠胰腺腺泡病变无效。本项长期（12个月）研究旨在调查善得定（3微克/天）单独使用以及与去势联合使用时，对氮杂丝氨酸处理的大鼠和BOP处理的仓鼠胰腺癌发生的影响。为了模拟人类的治疗情况，在最后一次注射致癌物4个月后开始对动物进行治疗，此时（癌前）病变已经形成。在用善得定治疗8个月后，与未用善得定治疗的大鼠相比，接受治疗的大鼠胰腺非典型腺泡细胞结节和肿瘤更少。此外，去势大鼠（癌前）腺泡病变的数量也低于完整大鼠。然而，善得定治疗并未增强手术去势对大鼠胰腺癌发生的抑制作用。在既接受去势又接受善得定治疗的仓鼠中，临界病变的发展受到显著抑制，而在仅接受手术去势或仅接受善得定治疗的仓鼠中则未出现这种效果。与未用善得定治疗的仓鼠相比，在用善得定治疗的仓鼠中发现的微癌数量显著减少。目前的研究结果表明，善得定，特别是与手术去势联合使用时，可能对导管性胰腺肿瘤的治疗具有治疗价值。
