Fossmark R, Martinsen T C, Torp S H, Kawase S, Sandvik A K, Waldum H L
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, MTFS, Olav Kyrres gt 3, N-7489 Trondheim, Norway.
Endocr Relat Cancer. 2004 Mar;11(1):149-60. doi: 10.1677/erc.0.0110149.
Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer (P<0.05), whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.
在近交系雌性棉鼠（刚毛棉鼠）中，25% - 50%的动物会自发发生胃癌；雄性棉鼠的相应比例约为1%。患有癌症的动物有高胃泌素血症和胃低酸度，肿瘤源自肠嗜铬样（ECL）细胞。低酸度背后的机制尚不清楚。在所有高胃泌素血症持续超过4个月的雌性棉鼠中都发现了癌症，这是研究胃癌发生的绝佳动物模型。在本研究中，给雌性棉鼠注射生长抑素类似物奥曲肽，以预防高胃泌素血症引起的癌症发展。12只雌性棉鼠每月注射长效奥曲肽（5毫克，肌肉注射），持续6个月。20只动物的对照组未注射。在20只对照动物中，13只出现了高胃泌素血症以及组织学上有侵袭性的癌症或发育异常。在奥曲肽组的12只动物中，5只出现了高胃泌素血症。这5只动物均未发生组织学上的癌症（P<0.05），而3只出现了发育异常。然而，奥曲肽对血浆胃泌素浓度或胃窦胃泌素mRNA丰度没有显著影响。高胃泌素血症动物的泌酸黏膜发育异常伴随着嗜铬粒蛋白A免疫反应性细胞和Sevier - Munger染色阳性细胞的显著增加。恶性组织中也含有Sevier - Munger染色的细胞群。总之，奥曲肽在不降低胃泌素浓度的情况下预防了高胃泌素血症棉鼠的ECL细胞癌。
