Development and Characterization of a Cancer Cachexia Rat Model Transplanted with Cells of the Rat Lung Adenocarcinoma Cell Line Sato Lung Cancer (SLC).

Cancer cachexia is a complex malnutrition syndrome that causes progressive dysfunction. This syndrome is accompanied by protein and energy losses caused by reduced nutrient intake and the development of metabolic disorders. As many as 80% of patients with advanced cancer develop cancer cachexia; however, an effective targeted treatment remains to be developed. In this study, we developed a novel rat model that mimics the human pathology during cancer cachexia to elucidate the mechanism underlying the onset and progression of this syndrome. We subcutaneously transplanted rats with SLC cells, a rat lung adenocarcinoma cell line, and evaluated the rats' pathophysiological characteristics. To ensure that our observations were not attributable to simple starvation, we evaluated the characteristics under tube feeding. We observed that SLC-transplanted rats exhibited severe anorexia, weight loss, muscle atrophy, and weakness. Furthermore, they showed obvious signs of cachexia, such as anemia, inflammation, and low serum albumin. The rats also exhibited weight and muscle losses despite sufficient nutrition delivered by tube feeding. Our novel cancer cachexia rat model is a promising tool to elucidate the pathogenesis of cancer cachexia and to conduct further research on the development of treatments and supportive care for patients with this disease.

A novel highly concentrated enteral nutrition formula, EN-P05, shows nutritional effectiveness comparable to the approved OSN-001 in gastrostomized rats.

Enteral nutrition is beneficial support administered as oral supplements or via tube feeding for patients with long-term inability to meet nutritional requirements orally. However, because of the high volumes administered, vomiting and gastroesophageal reflux are often encountered in patients receiving enteral nutrition. EN-P05 is a novel, highly concentrated enteral nutrition formula that was developed to reduce dosing volume and that satisfies the Japanese recommended daily allowance for most vitamins and trace elements, even in patients who require low-calorie control, such as home-care patients. However, whether EN-P05 can provide nutritional management equivalent to that provided by approved formulas has remained unknown. To investigate the nutritional effectiveness of EN-P05, we evaluated body weight gain, serum chemistry parameters, nitrogen balance, and fat absorption in 7-week-old gastrostomized rats that received either EN-P05 or OSN-001 for 2 weeks. No difference in organ or carcass weight was found between the groups. No significant between-group differences were observed in serum albumin, total protein, triglycerides, or total cholesterol, nor in nitrogen retention or fat absorption rate. No adverse effects associated with administration of EN-P05 were found. These results suggest that EN-P05 can provide the same nutritional management as approved formulas, even when administered in smaller volume.

A ketogenic diet improves the prognosis in a mouse model of peritoneal dissemination without tumor regression.

Peritoneal dissemination describes a state where tumor cells spread to the surface of the peritoneum and become engrafted. Peritoneal dissemination reduces the quality of life and prognosis of cancer patients. Currently, there are few effective therapies or preventative treatments for peritoneal dissemination. The aim of this study was to evaluate a ketogenic diet, characterized by high fat, moderate protein and low carbohydrate content, as a novel therapy in a mouse model of peritoneal dissemination. BALB/c mice were intraperitoneally inoculated with colon 26, a murine colon adenocarcinoma cell line, to induce experimental peritoneal dissemination. After tumor inoculation, mice were fed a regular or ketogenic diet. A longer survival time and better health status score, related to improved behavior, was observed in the ketogenic diet group compared with the regular diet group. In addition, the weight of ascites was significantly smaller and the anemia symptoms, number of red blood cell, hemoglobin and hematocrit, were improved in the ketogenic diet group compared with the regular diet group. However, the tumor weight was not significantly smaller in the ketogenic diet group compared with the regular diet group. These data suggest that a ketogenic diet might be a potential preventive therapy for peritoneal dissemination.

Effects of caloric intake on intestinal mucosal morphology and immune cells in rats treated with 5-Fluorouracil.

Anticancer drugs have been reported to damage the intestinal mucosa. We evaluated the effects of caloric intake on the mucosal morphology and immune cells in rats treated with 5-fluorouracil (5-FU). Rats were received a liquid diet plus 5-FU treatment for 8 days as follows: Low calorie group (25 kcal/day with 5-FU), Normal calorie group (50 kcal/day with 5-FU), and Control group (50 kcal/day with saline). The mucosal morphology, cell numbers and phenotypes of spleen and intraepithelial lymphocytes (IEL) were assessed. As compared with the control group, the villus heights were significantly lower in the Low calorie group, but not significantly lower in the Normal calorie group. The total cell yield from the spleen, CD4+ and CD8+ T cells decreased in the Low and Normal calorie group, but these changes were less pronounced in Normal calorie group. The total cell yield from the IEL also decreased in the Low calorie group, but not in the Normal calorie group. Our study demonstrated that sufficient caloric intake attenuated the damages in intestinal morphology and in the immune cell numbers. Clinically, nutritional support would be expected to be one approach to reducing the risk of bacterial translocation or infection induced by chemotherapy.

Antifungal mechanism of hinokitiol against Candida albicans.

The growth of Candida albicans was dose-dependently inhibited by addition of hinokitiol. The sensitivity of C. albicans to hinokitiol under aerobic conditions was higher than that under anaerobic conditions. Amount of ATP in C. albicans was not inhibited by hinokitiol under both conditions. The expression of mRNAs related to the growth signal, CYR1 and RAS1, was inhibited by hinokitiol. These findings suggested that the growth inhibition of C. albicans by hinokitiol was due to the interruption of RAS-signal transmission, such as the cAMP pathway.

Changes in lymphocyte phenotypes and cytokine production by surgical stress in a rat small intestinal resection model.

Small intestinal resection rats are used widely as a malabsorption model, but the immunological changes are unclear. We examined the changes in systemic and mucosal immune status after a small intestinal resection in rats with a controlled nutritional status. Rats had 60% of their small intestine removed. At 5 days after the surgery, spleen cells and intraepithelial lymphocytes (IEL) were isolated. The phenotypes of spleen cells and IEL, the production patterns of Th1 and Th2 cytokines, and the proinflammatory cytokine levels in the plasma were measured. CD4+ T cells in the blood and spleen were significantly decreased in the Resection group (p<0.05). In contrast, IEL subpopulations were not different between the two groups. Interferon-gamma production from the spleen cells was significantly decreased in the Resection group (p<0.05). Interleukin (IL)-4 production was not different between the two groups. Plasma IL-6 concentrations were significantly elevated in the Resection group 6 h after surgery (p<0.05). In conclusions, small intestinal resection in rats suppressed systemic immunity, and this model is useful as a surgical stress model.