Medical journal of Osaka University最新文献

The incidence of spontaneously occurring colon cancer and its spontaneous regression in the highly inbred Wistar Furth (WF) rat was studied using 1346 rats from the 19th to the 21st inbreeding generation. A statistical analysis revealed a positive phenotypical correlation between parents and offspring concerning the incidence of colon cancer and its spontaneous regression. The incidences of cancer-bearing offspring born from the crosses of cancer-free dams and cancer-bearing, spontaneous regression and cancer-free sires were 21%, 14.1% and 22.7%, respectively, and these results manifested a statistically significant difference. The incidences of spontaneous regression in the male offspring born from the same crosses mentioned above were 35%, 46.8% and 23.5%, respectively; they also represented a significant difference. Based on the analysis, two independent genetic factors, one carcinogenic and the another regressive, were suggested to determine the phenotypes of offspring. The cancer-bearing offspring have the carcinogenic factor but not the regressive factor, while the spontaneous regression ones have both factors. The frequencies of the carcinogenic and the regressive factors in male rats were estimated to be 54.1% and 59.8%, respectively, on average from the 19th to the 21st generation. A genetic pool of the carcinogenic and the regressive factors was established in the WF rat.

Among 659 female recipient rats inoculated with the transplantable carcinomas of the stomach (S1 and S3), the colon (C1 and C2) and the corpus uteri (U2) in the same strain of Wistar-Furth Osaka (WF Osaka) rats, 160 adenocarcinomas of the corpus uteri were found. 79 cases of them were grossly diagnosed as carcinomas, because the uteri were tremendously enlarged and kinking in the peritoneal cavity. The rest of them were confirmed to be carcinomas histologically. They were all well differentiated tubular adenocarcinomas with some papillary growth in the uterine cavity. Only one case showed to be an invasive carcinoma. Average age of female rats at the time of inoculation was 42 days after birth, and the uterine carcinomas were found in 34 days in average thereafter. Such carcinomas of the corpus uteri in young adolescent female rats have not been seen, excluded the cases inoculated with those transplantable tumors mentioned above into the peritoneal cavity on this WF Osaka rat strain. Therefore, it was thought that each transplantable carcinoma had played an important role for the induction of the adenocarcinoma of the corpus uteri.

We have established four lines of transplantable gastric carcinoma in WF Osaka rats. They were derived from adenocarcinomas of the glandular stomach, which were developed along with the lesser curvature, measuring less than 1.0 square centimeter. Morphology of these four lines of the transplantable tumor showed essentially an identical figure in their respective generations. Histology in the early generation of transplanted tumors showed well differentiated tubular adenocarcinoma similar to the primary lesion of the stomach. Later the histological appearance of these four lines of the transplanted tumor altered from glandular structure to keratinizing squamous cell metaplasia of cancer cells. The lines of S4 and S5 transplantable tumor were recently established, but the lines of S1 and S3 transplantable tumor have been transplanted as far as more than the 60th generation, and changed their histological appearance to scirrhous carcinoma in the line of S1 and medullary carcinoma in the line of S3. The growth speed of S1 line became slow in the later generations compared to the former ones, and that of S3 line became extremely rapid and recipient rats died with cachexia within two weeks. Effectual activities of tumor enhancement for the gastric and the colon cancer, previously reported elsewhere, recently decreased, and gastric carcinoma was rarely induced by these two lines. Lately established S4 and S5 transplantable tumor lines showed vigorous flourish of inducing gastric and colon cancers.

A simple purification method using DEAE cellulose column chromatography and immunoaffinity column chromatography was developed for purifying Shiga-like toxin produced by Escherichia coli O157:H7. About 0.75 mg of purified toxin was obtained from 5 liters of culture (62% recovery). The purified toxin was demonstrated to be immunologically, biologically and structurally indistinguishable from Shiga toxin. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed for detection of Shiga-like toxin. In the ELISA assay, Shigella dysenteriae type 1, Escherichia coli O157:H7 and some strains of Escherichia coli isolated from traveller's diarrhea were positive. Shiga toxin-resistant Vero cells were isolated by treatment of the cells with nitrosoguanidine. Immunofluorescence studies showed that the mutant Vero cells had lost toxin binding capacity. Samples of S. dysenteriae type 1 and E. coli O157:H7 showed cytotoxicity to the parent cells, but not to the mutant cells. Samples of other organisms showed either no cytotoxicity or cytotoxicity to both cell lines. The results suggested that (1) the presence of a receptor for Shiga-like toxin on Vero cells is essential for expression of cytotoxicity of the toxin, (2) the mutant Vero cells could be used to identify Shiga-like toxin producing organisms.

In order to study the spontaneous regression of the colon cancers of WF Osaka strain rats, laparotomies were carried on 701 rats in sequence at the age of four months. Among them, 260 cases were found having colon cancers at the laparotomy. 107 out of them showed spontaneous regression of the colon cancer in the ascending colon. Most of the cases which spontaneously regressed were rather the early stage (stage 1 and 2) of the colon cancer, though 26 cases of advanced cancer also showed spontaneous regression. Grossly the lesions of the spontaneous regression were those of thickened, elongated ascending colon, with occasional dilation. Some cases showed the cystic formation at the portion of former lesions. There was a case which showed normal appearance of the ascending colon with regional lymph node metastasis measuring 1.5 x 1.5 centimeters. Histological appearance was varied showing reconstruction of the muscular layer and mucularis mucosae. Mucosal epithelium was almost normal looking, but glandular arrangement showed cystic dilation. The ectopic existence of glandular composition was seen in the restored lesion in the muscular layer. Macrophage infiltration was indispensably main histological reaction with central necrosis of formerly existed cancer cells, which was considered to be cellular immunity against cancer cells, or exogenous substances, such as viruses in cancer cells.