Watanabe H, Hirose F, Takizawa S, Terada Y, Fujii I, Ohkita T
Pathol Res Pract. 1979 Jan;164(3):216-23. doi: 10.1016/S0344-0338(79)80044-8.
A 31-month-old female mongrel dog was orally administered with 50 mg or 100 mg of N-nitrosobutylurea (NBU) in gelatin-capsule 3 times per week for 19 months with interposing periods of complete suspension. Thirty-four foci of signet ring cell carcinoma were found in the antral region of the stomach. The majority of the foci (31 foci) were early cancer, and the remaining foci were invasive cancer. In addition to these lesions, there was "a single gland cancer" in which a row of cancer cells was confined to a single gland. The whole gland was composed of two cell layers; the inner layer facing the lumen was normal gastric cells and the outer layer was atypical or neoplastic cells underlaid by the basement membrane. Mitosis was frequently observed on the bottom of the gland. Atypical or neoplastic cells seemed to mature gradually through a process of upward migration with increase in cytoplasmic Alcian blue-PAS and HID-AB positive mucin. Some of the cells rich in mucin moved into the lamina propria. The other cells remained in the flow of the regular cell renewal system of the normal gastric cells and reached the top of the gland. This observation revealed a mode of incipient gastric cancer growth, which starts and spreads within a single gland, before it invades the surrounding lamina propria.
一只31个月大的雌性杂种犬，每周口服3次含50毫克或100毫克N-亚硝基丁脲（NBU）的明胶胶囊，持续19个月，期间有完全停药期。在胃窦部发现34个印戒细胞癌病灶。大多数病灶（31个病灶）为早期癌，其余病灶为浸润性癌。除这些病变外，还有“单腺腺癌”，其中一排癌细胞局限于单个腺体内。整个腺体由两层细胞组成；面向管腔的内层是正常胃细胞，外层是位于基底膜下方的非典型或肿瘤细胞。在腺体底部经常观察到有丝分裂。非典型或肿瘤细胞似乎通过向上迁移的过程逐渐成熟，同时细胞质中阿尔辛蓝-过碘酸雪夫（Alcian blue-PAS）和高铁二胺-阿尔辛蓝（HID-AB）阳性黏液增加。一些富含黏液的细胞迁移到固有层。其他细胞则留在正常胃细胞的正常细胞更新系统中，到达腺体顶部。这一观察结果揭示了早期胃癌的生长模式，即在侵入周围固有层之前，先在单个腺体内开始并扩散。
