Purpose: Colorectal carcinogenesis is thought to be related to abdominal obesity and insulin resistance. To investigate whether visceral fat accumulation contributes to colorectal carcinogenesis, we examined its accumulation and the levels of the adipose tissue^derived hormone adiponectin in Japanese patients with colorectal adenoma. Experimental Design: Fifty-one consecutive Japanese patients ages z40 years and with colorectal adenoma were subjected to measurement of visceral fat area by computed tomography scanning and plasma adiponectin concentration. The patients also underwent the 75-g oral glucose tolerance test. Insulin resistance was calculated by the homeostasis metabolic assessment (HOMA-IR) method. The controls were 52 Japanese subjects ages z40 years and without colorectal polyp. Cigarette smokers and subjects who consumed alcohol (z30 g ethanol/d) were excluded. Results: The patients with colorectal adenoma showed significantly more visceral fat area and significantly less plasma adiponectin concentration in comparison with the controls [odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.47-3.28; P < 0.001 and OR, 0.24; 95% CI, 0.14-0.41; P < 0.001, respectively] by logistic regression analysis. HOMA-IR index was also associated with colorectal adenoma (OR 2.60; 95% CI, 1.20-5.64; P = 0.040). Visceral fat area and adiponectin were associated with adenoma number (1, 2, z 3), the size of the largest adenoma (<10 and z10 mm), and adenoma histology (tubular and tubulovillous/villous). Conclusions: These results suggest an association of visceral fat accumulation and decreased plasma adiponectin concentration with colorectal adenoma in Japanese patients. This study may offer a new insight to understanding the relationship of colorectal carcinogenesis with abdominal obesity and insulin resistance.

Results showed the up-regulation of these three histone-modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma.

We examined the effects of complement activation on the biological responses of cellulose acetate (CA) beads. Peripheral blood containing the complement activation inhibitor nafamostat mesilate (NM) or heparin was incubated with CA beads in vitro. Thereafter, the fraction of adsorbed granulocytes as well as the generation of complement activation fragments (C3a and C5a) and interleukin 1 receptor antagonist (IL-1ra) were measured. Granulocyte adsorption, complement activation, and IL-1ra release were significantly inhibited in the presence of NM. Adsorption was significantly increased onto CA beads pretreated with plasma containing heparin even in the presence of NM and adding C3a or C5a enhanced IL-1ra release. These results suggested that bound complement fragment (e.g., C3b) on CA beads plays a central role in granulocyte adsorption to CA beads and that C3a and C5a augment the release of anti-inflammatory substances. We therefore conclude that complement activation is involved in these biological responses of leukocyte apheresis.

Musashi-1 (Msi-1), an RNA-binding protein, had been proposed to be a specific marker for neural stem/precursor cells. Msi-1 expressing cells in the intestinal epithelium are also strongly considered as potential stem/precursor cells. To clarify the behavior of those cells in the injury or regeneration phase, we investigated Msi-1 expressing cells of intestinal mucosa in the murine model of dextran sodium sulfate (DSS)-induced colitis. Immunohistochemically, Msi-1-positive cells were found in the area just along the layer of Paneth's cells in the small intestine and in the bottom layer of crypts in the large intestine. During DSS administration, the number of PCNA-positive cells in the large intestine increased markedly. In contrast, the number of Msi-1-positive cells decreased slightly with DSS but returned to normal after DSS administration was stopped. The level of mRNA for Msi-1 was consistent with the result of immunohistochemical examinations. Conclusively, we could describe the behavior of intestinal stem/precursor cells during inflammation using Msi-1.

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