To explore the immunological roles of dietary fiber, male 4-wk-old Sprague-Dawley rats were fed for 2 wk cellulose (water-insoluble), konjak mannan (water-soluble), pectin (water-soluble) or chitosan (acid-soluble) at 5 g/100 g diet. Serum IgE concentrations in rats fed konjak mannan, pectin and chitosan were significantly lower than in those fed cellulose (mean +/- SEM: 5.0 +/- 1.1, 3.6 +/- 1.3, 3.0 +/- 1.2 and 9.6 +/- 1.9 microg/L, respectively). Rats fed pectin had significantly higher serum IgA and IgG concentrations (358 +/- 38 and 424 +/- 36 mg/L for IgA and IgG, respectively) than those fed cellulose (240 +/- 31 and 337 +/- 25 mg/L) or chitosan (176 +/- 22 and 379 +/- 23 mg/L), while the IgM concentration did not differ among the groups. Concentrations of IgA, IgG and IgM in mesenteric lymph node (MLN) lymphocytes generally were greater, while IgE concentration was lower, in rats fed pectin and chitosan than in those fed cellulose. The proportion of CD4+ T-cells in MLN lymphocytes was also dietary fiber-dependent, and the CD4+/CD8+ ratio was significantly higher in the pectin fed group than in all other groups. Under certain experimental conditions, MLN lymphocytes from rats fed pectin had markedly greater interferon-gamma concentration than cells from other groups, while the effect on tumor necrosis factor-alpha concentration was less marked. Thus, dietary fiber may have an immunoregulatory effect on the intestinal immune system of rats.
Resistance of ovarian mucinous adenocarcinoma to standard chemotherapy with paclitaxel and carboplatin is associated with poor prognosis, and an effective treatment is needed. The present study aimed to identify an effective chemotherapy for ovarian mucinous adenocarcinoma. Five human ovarian mucinous adenocarcinoma cell lines (MN-1, OMC-1, RMUG-L, RMUG-S, TU-OM-1) were used in this study. Sensitivity of the cells to the anticancer agents was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and we assessed drug sensitivity by calculating the assay area under the curve for each agent. Protein expression was confirmed by Western blot analysis. We also examined the efficacy of combination chemotherapy on survival in a xenograft model of nude mice. The IC(50) to anticancer agents ranged widely. The assay area under the curve indicated that two of five cell lines (MN-1, TU-OM-1) were sensitive to oxaliplatin, 5-fluorouracil and etoposide, and only one (TU-OM-1) was sensitive to 7-ethyl-10-hydroxycamptothecin, which is an active metabolite of camptothecin. All cell lines were resistant to cisplatin and paclitaxel. The combination of oxaliplatin and 5-fluorouracil resulted in additive or synergistic effects on all cell lines. The combination of oxaliplatin and 5-fluorouracil significantly prolonged survival in a ovarian mucinous adenocarcinoma xenograft model of nude mice. Protein expression levels of the excision repair cross-complementation group 1 were lower in oxaliplatin sensitive cell lines. Exposure to 5-fluorouracil down-regulated cross-complementation group 1 expression in ovarian mucinous adenocarcinoma cells. We conclude that combination chemotherapy consisting of oxaliplatin and 5-fluorouracil was an effective treatment for ovarian mucinous adenocarcinoma and may be a pivotal candidate for a novel treatment strategy.
The imm"noregulatory effects of dietary a-tocopherol (Toc) and tocotrienols (T-3) on humoral and cell-mediated immunity and cytokine productions were examined in Brewn Norwtty rats. We found that the IgA and IgG productivity of spleen and mesenteric lymph node anN) lymphocytes was significantly enhanced in the rats fed on Toc or T-3, irrespectiye of collcanavalin A (Cen A) stim"lation of the lymphocytes. On the contrary, the IgE preductiyity ef lymphecytes from the rats fed oll Tec or T-3 was less without Con A stimulation, but was greater in the presence of Con A, especially in the T-3 group. Toc or T-3 feeding signMcantly decreased the proportion of CD4' T cells and the ratio of CD4'!CD8' in both spleen and MLN lymphocytes of the rats fed on Toc or T-3. The interferon-7 productiyity ef MI.N lymphocytes was higher in the rats fed oll Toc or T-3 than in those fed on a control diet in the presence of Con A, while that of spleell lymphocytes was lower in the rats fed on Toc or T-3. I] addition, T-3 feeding decreased the productivity of tumor necrosis factor-a of spleen lymphocytes, while it enhanced the productiyity of MLN lymphocytes. These results sugges"hat oral administration of Tec and T-3 affects the proliferation and function of spleen and MLN lymphocytes.
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