Ingestion of proteoglycan fraction from shark cartilage increases serum inhibitory activity against matrix metalloproteinase-9 and suppresses development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic duct carcinogenesis in hamster.

A water extract of shark cartilage was fractionated into acidic and basic fractions by preparative isoelectric focusing on the basis of the amphoteric nature of samples. The acidic fraction was further fractionated into ethanol-soluble and -precipitate fractions. After the carcinogenesis treatment using N-nitrosobis(2-oxopropyl)amine, hamsters received a diet containing each fraction or purified chondroichin sulfate to give 0.4% (w/w) for 50 days. Only administration of the acidic ethanol-precipitate-fraction-containing diet significantly increased serum inhibitory activity against matrix metalloproteinase (MMP)-9 and reduced the number of adenocarcinomas in the pancreatic duct. The active fraction predominantly consisted of chondroichin sulfate-containing proteoglycan. However, the purified chondroichin sulfate had no significant activity. These results suggest that the protein moiety of the proteoglycan might be involved in the increase of serum inhibitory activity against MMP-9 and suppression of pancreatic carcinogenesis in hamster.

Highly metastatic ovarian yolk sac carcinoma in a rat.

We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in the eosinophilic matrix. Both the intracytoplasmic droplets and the matrix were stained positively with PAS. The visceral cells were cylindriform, and proliferated in papillary and tubular patterns and occasionally formed Shiller-Duval body-like structures. In the dissemination sites, the neoplastic cells proliferated on the surface of the various tissues and often infiltrated into deeper parts of the tissues. Immunohistochemically, both neoplastic cells were positive for α-fetoprotein and keratin, and the eosinophilic matrix was positive for laminin. Ultrastructurally, the parietal cells had dilated rough endoplasmic reticulums, which were filled with electron-lucent laminated structures. The visceral cells had poorly to moderately developed intracytoplasmic organelles and were interconnected with desmosomes. Taken together, the present tumor was diagnosed as yolk sac carcinoma arising from the ovary and was characterized by not only high metastasis but also invasive infiltration with biphasic proliferation of the parietal and visceral cells.

Promoting Effects of Sucrose-rich Diet on N-Nitrosobis (2-oxopropyl) amine-induced Pancreatic Carcinogenesis in Hamsters.

It has been reported that there is an association between pancreatic cancer and obesity, impaired glucose metabolism and diabetes based on excess dietary fat and sugar intakes. A number of studies have suggested that a high-fat diet increases development of carcinomas in various organs and possible risk factors for pancreatic cancer. However, how an excess sugar intake promotes pancreatic carcinogenesis is still unknown. In the present study, we investigated the influence of an excess sugar intake on pancreatic carcinogenesis by administration of a sucrose-rich diet in which starch was replaced by sucrose in order to contain the same calories and other nutrients. Two similar experiments were performed. Six-week-old male Syrian golden hamsters were given N-nitrosobis (2-oxopropyl) amine (BOP) at a dose of 50 and 20 mg/kg body weight as a carcinogen in Week 0 and 1, respectively. In Week 2, the animals were divided into control and experimental groups. In experiment 1, 15 animals received a control diet or sucrose-rich diet in which 100% of the starch was replaced by sucrose, respectively. Since five animals fed on the sucrose-rich diet died by Week 12, the diet was changed to a sucrose-rich diet in which 50% of the starch was replaced by sucrose. In experiment 2, 15 animals received a control diet or sucrose-rich diet in which 50 or 20% of the starch was replaced by sucrose, respectively. All animals were sacrificed 25 weeks after the start of the experiment, and histological examination of the pancreas was performed. No significant difference was seen in the body weight at the end of the experiment. There were no significant differences in the glycosylated hemoglobin (HbA1c) and serum triglyceride, total cholesterol and HDL-cholesterol levels between the control and sucrose-rich diet groups in experiments 1 and 2. The incidence and number of carcinomas increased in hamsters fed the sucrose-rich diet compared with the control diet in experiments 1 and 2. These results suggest that an excess sucrose intake may promote the development of pancreatic cancer in hamsters.