Type 2 Diabetes Associated with Abnormal p53 Immunohistochemical Patterns in Colorectal Cancer.

Abnormal p53 immunohistochemical pattern (p53-AP) including overexpression, complete absence and heterogeneity is surrogate of TP53 mutation. Using 742 cases of colorectal cancer (CRC), we show p53-AP is more common among type 2 diabetes (T2DM) patients than non-T2DM. Univariately, T2DM was significantly associated with p53-AP in overall patients, patients with microsatellite instability (MSI) stable/MSI-low phenotype or distal colorectal location. Furthermore, p53-AP was positively associated with lymph node metastasis and high TNM stage. Metformin treatment was negatively associated with p53-AP in T2DM patients. The results suggested T2DM might influence carcinogenesis, progression and prognosis via inducing TP53 mutation and abnormal p53 expression in CRC.

Overexpression of forkhead box M1 and urokinase-type plasminogen activator in gastric cancer is associated with cancer progression and poor prognosis.

Forkhead box M1 (FOXM1) and urokinase-type plasminogen activator (uPA) are overexpressed and associated with the pathogenesis of multiple types of human malignancy. The aims of the present study were to investigate FOXM1 and uPA expression levels in human gastric cancer using tissue microarray techniques; determining their association with clinicopathological characteristics as well as their prognostic value. Tissue microarray blocks, comprising 436 gastric cancer cases and 92 non-cancerous adjacent normal gastric tissues, were analyzed for FOXM1 and uPA protein expression levels using immunohistochemistry. The results were analyzed statistically in association with various clinicopathological characteristics and overall survival rates. FOXM1 and uPA were detected in 78.67 (343/436) and 83.26% (363/436) of cancer samples, respectively. FOXM1 and uPA were not expressed in the 92 normal gastric tissue samples. In gastric cancer, FOXM1 and uPA levels were associated with tumor size, depth of invasion, tumor-node-metastasis (TNM) stage, lymph node metastasis, vessel invasion and distant metastases. The overall survival rate was significantly decreased in patients expressing FOXM1 and uPA compared with FOXM1- and uPA-negative patients. Coxs multivariate analysis revealed that age, depth of invasion and expression levels of FOXM1 and uPA are independent predictors of survival in patients with gastric cancer. These results indicated that increased FOXM1 and uPA expression levels are associated with the invasive and metastatic processes in human gastric cancer, and inversely associated with patient prognosis. Therefore, FOXM1 and uPA may serve as novel prognostic markers independent of, but supplementing, the TNM staging system.

[Dynamic observation on MDA, iNOS and antisuperoxide anion in the liver of rats induced by acute nickel carbonyl poisoning].

OBJECTIVE: To investigate the level of malondiadehyde (MDA), antisuperoxide anion and inducible nitric oxide synthase (iNOS) in liver of rats poisoned by nickel carbonyl in order to discuss the mechanism of acute nickel carbonyl poisoning. METHODS: Healthy SD rats were intoxicated acutely by different concentrations of nickel carbonyl (20, 135 and 250mg/m3 for low, middle and high dose groups, respectively). SD rats inhaled by chlorine (250mg/m3 for chlorine group) were used as positive control group and other healthy SD rats as normal control group. Liver of animals was taken at different time points after exposure. The levels of MDA, iNOS and antisuperoxide anion were detected by biochemical assay. RESULTS: The contents of MDA and antisuperoxide anion in the liver of high dose group were significantly higher than that of other exposed groups and control group (P < 0.01). The contents of iNOS in middle and high dose group were higher than that in low dose group and control group (P < 0.05). CONCLUSION: The oxidative damage in the liver of SD rats could be induced by carbonyl nickel in air with increasing concentrations and in an obvious dose-response relationships.