Soluble interleukin­2 receptor as a factor associated with angiogenesis in gastric cancer.

Angiogenesis serves a role in the growth, metastasis and prognosis of tumors. The aim of the present study was to evaluate the angiogenic ability and clinical significance of the immune biomarker soluble interleukin­2 receptor (sIL­2R) in gastric cancer (GC) patients. Serum levels of sIL­2R were measured in 35 GC patients with different stages of disease and 32 healthy individuals, and it was investigated whether the levels were associated with angiogenesis factors, including vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)­ß1. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without recombinant human (rh)sIL­2R, VEGF and TGF­ß1 for 24 h, and then the HUVECSs were harvested to determine the degree of angiogenesis. The supernatants were also collected for VEGF and TGF­ß1 testing. Serum levels of sIL­2R were higher in GC patients than in healthy individuals, as were the levels of VEGF and TGF­ß1. In addition, serum levels of sIL­2R were positively associated with the levels of VEGF and TGF­ß1. Angiogenesis of HUVECs was also increased by rhsIL­2R pretreatment. VEGF and TGF­ß1 secretion were also incre-ased in supernatants that were pretreated with rhsIL­2R. The results of the present study suggested that serum levels of sIL­2R contributes to the pathophysiology of GC progression and may be used as a prognostic biomarker for GC.

Corticosteroid therapy in ulcerative colitis: Clinical response and predictors.

AIM: To evaluate clinical response to initial corticosteroid (CS) treatment in Chinese ulcerative colitis patients (UC) and identify predictors of clinical response. METHODS: Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China, and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors. Short-term outcomes within one month were classified as primary response and primary non-response. Long-term outcomes within one year were classified as prolonged CS response, CS dependence and secondary non-response. CS refractoriness included primary and secondary non-response. Multivariate analyses were performed to identify predictors associated with clinical response. RESULTS: Within one month, 95.0% and 5.0% of the cases were classified into primary response and non-response, respectively. Within one year, 41.6% of cases were assessed as prolonged CS response, while 49.5% as CS dependence and 4.0% as secondary non-response. The rate of CS refractoriness was 8.9%, while the cumulative rate of surgery was 6.9% within one year. After multivariate analysis of all the variables, tenesmus was found to be a negative predictor of CS dependence (OR = 0.336; 95%CI: 0.147-0.768; P = 0.013) and weight loss as a predictor of CS refractoriness (OR = 5.662; 95%CI: 1.111-28.857; P = 0.040). After one-month treatment, sustained high Sutherland score (≥ 6) also predicted CS dependence (OR = 2.347; 95%CI: 0.935-5.890; P = 0.014). CONCLUSION: Tenesmus was a negative predictor of CS dependence, while weight loss and sustained high Sutherland score were strongly associated with poor CS response.

P53 mutations occur more commonly than KRAS mutations in colorectal adenoma.

TP53 and KRAS mutations are commonly found in colorectal tumors. The rates of mutation of these two genes in colorectal carcinoma were compared to better understand their contribution to the disease. Here, colorectal tissue samples were obtained from 49 patients with colorectal adenoma, 90 patients with single primary colorectal carcinoma, 32 patients with multiple primary colorectal carcinoma, and 50 healthy individuals. Real-time PCR was used to amplify exons 5-8 of TP53 and codons 12-13 (exon 1) of KRAS from each sample. Clinical and pathological features of tumor samples were recorded, and these features were compared against mutation status using multivariate logistic regression. The proportions of samples with mutations of KRAS and/or TP53 were significantly different between control individuals and those with colorectal lesions (P < 0.05). Indeed, more than 80% of carcinoma samples were positive for either a KRAS or TP53 mutation. Further, mutations in KRAS and/or TP53 were significantly more common among the two groups with confirmed carcinoma than in individuals with colorectal adenoma (P < 0.05). Interestingly, TP53 mutations were significantly more frequent than KRAS mutations in the colorectal adenoma group (P < 0.01). However, no associations were observed for the frequency of KRAS or TP53 mutations between well-differentiated and poorly-differentiated tumors, different tumor stages, or other clinical and pathological features like age, sex, family history, tumor location, and stage and grade of differentiation. In conclusion, KRAS and TP53 mutations are important contributors to colorectal cancer, and TP53 mutation appears to occur earlier than KRAS mutation.

Hypoxia-inducible factor-1α (HIF-1α) C1772T polymorphism significantly contributes to the risk of malignancy from a meta-analysis.

Although the association between hypoxia-inducible factor-1α (HIF-1α) C1772T polymorphism and risk of malignancy has been widely studied, results from published studies remained controversial. Therefore, the relationship between them was further assessed in this meta-analysis. The databases of PubMed, Embase, and Wanfang were searched, and odds ratio with 95% confidence interval (OR and 95% CI) were used to assess the strength of the association. A total of 38 case-control studies with 23,876 participants were included. Overall, the T allele of HIF-1α C1772T was significantly associated with increased risk of malignancy development (OR and 95% CI 1.18 (1.00-1.38), P = 0.048 for T carriers vs. CC; 1.22 (1.05-1.41), P = 0.010 for T carriers vs. C carriers). When subgroup analyses were conducted, T allele was further found to be associated with increased risk of malignancy development for Asians rather than Caucasians (OR and 95% CI 1.36 (1.10-1.67), P = 0.004 for Asians) and for population-based studies (OR and 95% CI 1.19 (1.01-1.41), P = 0.040). Between-study heterogeneity existed in genetic comparison models, and meta-regression indicated that the participants' ethnicities and types of malignancy might be the sources of heterogeneity. No publication bias was found. In conclusion, this study indicated that HIF-1α C1772T polymorphism was significantly associated with increased risk of malignancy development for Asians. More studies were further required to focus on the relationship between HIF-1α C1772T polymorphism and risk of a specific type of tumor.

Cyclooxygenase-2 polymorphisms were associated with the risk of gastric cancer: evidence from a meta-analysis based on case-control studies.

The associations between cyclooxygenase-2 (COX-2) polymorphisms (-765G>C, -1195G>A, and -587G>A) and risk of gastric cancer have been investigated, but the results were inconsistent. The aim of this study was to explore the associations between COX-2 polymorphisms and risk of gastric cancer using a meta-analytic method. We searched the databases of PubMed, Embase, and Wanfang (Chinese database) to identify the eligible studies. Odds ratio and 95 % confidence interval (OR and 95% CI) were used as effect size, and combined analyses were conducted using fixed- or random-effects model. Overall, ten studies for COX-2-765G>C, six studies for -1195G>A, and three studies for -587G>A were included in this study. The results for combined analysis for COX-2-765G>C indicated that C allele was significantly associated with increased risk of gastric cancer compared with G allele, especially for Asians (OR and 95 % CI: 1.58 (1.06-2.35), P(z-test) = 0.03, and P heterogeneity <0.01 for CC+GC vs. GG). In addition, the A allele of COX-2-1195G>A was also significantly associated with risk of gastric cancer compared with G allele (OR and 95 % CI: 1.20 (1.09-1.32), P(z-test) <0.001, and P(heterogeneity) = 0.82 for A carriers vs. G carriers). In contrast, the COX-2-587G>A polymorphism was not associated with risks of gastric cancer. In summary, this meta-analysis indicated that the COX-2-765G>C and -1195G>A polymorphisms were significantly associated with risk of gastric cancer development.