After stratification, positive associations persisted in subjects without metabolic syndrome, which indicates that high hs-CRP is an independent risk factor for cancer. Our findings regarding histology- and site-specific selleck chemical Dasatinib associations suggest that hs-CRP is more strongly associated with adenocarcinoma. This is compatible with previous findings, which indicate that pan-adenocarcinoma is associated with obesity9�C11 and that hs-CRP is higher in obese adults and those with metabolic syndrome. The present study has several strengths. The large sample size permitted us to evaluate associations of hs-CRP with all cancers and cancers of specific sites and pathologic types. In addition, we adjusted for several important potential confounders, including age, sex, BMI, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, exercise, aspirin use, education level, and income.

To our knowledge, this is the first study to examine the associations between hs-CRP and cancer in Koreans. There were some limitations, however. First, the study subjects may not have been representative of the general population. The participants in this study were recruited from among adults who visited our hospital for regular health check-ups; thus, they were relatively health conscious. Selection bias may have led to an underestimation of the true excess risk. Second, our study was cross-sectional. Therefore, causality cannot be inferred in the association of hs-CRP with cancer risk. Third, detailed information on lifestyle was not available in the data used in this study.

We cannot exclude the possibility that the self-reported questionnaires provided only a rough assessment of alcohol consumption and exercise status. We also recognize that a single measurement of hs-CRP may not represent an individual��s inflammatory status during the development of cancer and that measured levels may be influenced by diurnal or stress-induced variation. However, misclassification bias is unlikely because stress-induced activation of hs-CRP should not have differed by case/non-case status. Finally, the cancer site-specific analyses were based on a small numbers of cancer cases, which highlights the need for further large prospective studies. In conclusion, we have shown a positive association between serum hs-CRP level and cancer risk.

This finding supports the hypothesis that chronic Cilengitide low-grade systemic inflammation increases the risk for cancer. Large prospective studies are necessary to determine the role of hs-CRP in the etiology of cancer. ACKNOWLEDGMENTS This study was supported by the Korea Research Foundation of the Ministry of Education, Science and Technology (20100029113) and BK 21. Conflicts of interest: None declared.
During the last decade, drug-induced liver injury (DILI) has been the most frequent cause of safety-related drug marketing withdrawals in the United States (Food and Drug Administration, 2009).

Previous studies have shown macrophage expression of 11��-HSD1 in further information the context of distinct disease models of acute inflammation notably murine studies where macrophage 11��-HSD1 activity rapidly increases during the development of acute peritonitis [31]. Our human study in NASH has shown for the first time that macrophage 11��-HSD1 expression is specifically intense in a chronic inflammatory process. These results clearly lead to a number of exciting possibilities with respect to the role of 11��-HSD1 in steatohepatitis. With relevance to the inflammatory response it would be important to discern the phenotype of the response of these macrophages. Previous studies have shown that macrophage 11��-HSD1 expression is stimulated by IL-4 and IL-3 cytokines, both examples of Th2 cytokines that promote anti inflammatory responses.

In the peritonitis model referred to above, macrophage 11��-HSD1 expression was important in the induction of phagocytosis of apoptotic neutrophils [31]. However, treatment of a murine macrophage cell line with 11��-HSD1 inhibitors was able to reduce the proinflammatory cytokine response following lipopolysaccharide treatment [32]. Macrophage 11��-HSD1 mediated glucocorticoid production may therefore be a central mechanism to fine tune the phenotype of the inflammatory response. This may be to limit injury in chronic inflammation, and promote pro resolution mechanisms particularly in acute inflammation. The role of the differential activation of Type 1 (pro-inflammatory), and Type 2 (anti-inflammatory) macrophages in determining the outcome of liver inflammation has only recently been appreciated [33].

Increased hepatocyte 11��-HSD1 expression, particularly in periseptal areas would further directly expose inflamed septa to glucocorticoids. However overall increased hepatic glucocorticoid would also promote hepatic lipogenesis and hence be expected to worsen hepatic steatosis. Studies on other tissues, including synovium from patients with rheumatoid arthritis [34], human and rodent colitis Cilengitide [35], aortic smooth muscle cells [36], and granulosa cells in the inflammatory response to ovulation [37], all show a consistent picture of induction of cell specific 11��-HSD1 gene expression in response to pro inflammatory cytokines, TNF�� and IL-1�� being the most commonly implicated [38]. The molecular mechanism by which 11��-HSD1 is induced in response to cytokines is not entirely clear, but key transcription factors of the C/EBP family play a crucial role [39], [40]. Simple hepatic steatosis is a relatively benign entity in the NAFLD disease spectrum with only a 2% risk of developing progressive disease in a twenty year period.