Association of ERCC1 and ERCC2 polymorphisms with colorectal cancer risk in a Chinese population.

The ERCC1 and ERCC2 genes are important in repairing DNA damage and genomic instability, and are involved in the nucleotide excision repair pathway. We hypothesized that single nucleotide polymorphisms (SNPs) in ERCC1 and ERCC2 are associated with the risk of colorectal cancer in a Chinese population. To test this hypothesis, we genotyped four functional SNPs (ERCC1 Asn118Asn, C8092A, ERCC2 Asp312Asn, and Lys751Gln) in a case-control study with 213 colorectal cancer cases and 240 cancer-free controls. We found that the ERCC1 C8092A polymorphism AA and CA/AA variant genotypes were associated with a significantly increased risk of colorectal cancer, compared with the CC genotype (OR = 2.50, 95% CI = 1.10-5.70 for AA versus CC, and OR = 1.58, 95% CI = 1.08-2.30 for CA/AA versus CC). Furthermore, the effect appeared to be more prominent among men, smokers, drinkers, and patients with rectal cancer. However, no other SNPs were observed for any significant association with colorectal cancer risk. These results suggest that the ERCC1 C8092A polymorphism may contribute to colorectal cancer susceptibility in the Chinese population. Further large and functional studies are needed to confirm our findings.

Effects of uncoupling protein 2 -866G/A polymorphism on platelet reactivity and prognosis in Chinese patients with type 2 diabetes and ischemic stroke.

The purpose of this study was to assess the effects of -866G>A polymorphism of mitochondrial uncoupling protein 2 (UCP-2) on platelet reactivity and prognosis in patients with type 2 diabetes and ischemic stroke (IS). A total of 405 Chinese patients with type 2 diabetes and stroke were assessed in a 4-year follow-up case-control study. Patient response to antiplatelet therapy was measured with the Platelet Function Analyzer-100 by means of collagen/adenosine diphosphate (CADP) and collagen/epinephrine (CEPI) cartridges. The primary end point was a composite of stroke and TIA (transient ischemic attack), the secondary end point was death. The -866G>A polymorphism in UCP-2 was genotyped by TaqMan MGB probe method. The -866G>A SNP in UCP-2 was not significantly associated with recurrence of diabetic ischemical stroke (p = 0.57). A significant trend toward nonfull response to antiplatelet therapy was seen in patients carrying A allel in comparison with those carrying GG genotype, as shown by the CADP and CEPI tests (p < 0.0001). Our 4-year follow-up study shows no association between -866G>A variant of UCP-2 in type 2 diabetes and the risk of developing stroke. But in conclusion, the A allel is associated with clopidogrel resistance.

Selection and characterization of human anti-MAGE-A1 scFv and immunotoxin.

Melanoma-associated antigen (MAGE) is expressed on the surface of multiple tumor cell types and is a promising target of biotherapeutic drug delivery via the anti-MAGE-A1 antibody. In this study, a human single-chain variable fragment (scFv) antibody phage library was generated and applied to recombinant MAGE-A1-coated immunotubes by phage display technology. The soluble anti- MAGE-A1 scFv was expressed and purified by immobilized metal-chelated affinity chromatography (IMAC). The anti-MAGE-A1 scFv could bind native MAGE-A1 confirmed by enzyme-linked immunosorbent assay (ELISA), dot blot, and immunoprecipitation (IP) analysis. The immunotoxin was expressed and purified by IMAC successfully. The results indicated that the human anti-MAGE-A1 immunotoxin could provide a valuable drug for clinic cancer therapy.

Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer.

The tumor-associated calcium signal transducer 2 (TACSTD2) gene has been reported to be highly expressed in many types of human epithelial cancers, and is associated with tumor metastasis and poor prognosis. The aims of the present investigation were to analyze the TACSTD2 and Cyclin D1 expression at the mRNA and protein levels and to assess its prognostic significance in invasive ductal breast cancer (IDC). The expressions of TACSTD2 and Cyclin D1 in IDC tissues were consistently higher than those in the tumor-adjacent non-malignant tissues by a one-step real-time polymerase chain reaction and immunohistochemistry (P<0.001 and P=0.023, respectively). The statistical analysis of clinicopathologic characteristics and immunohistochemistry by the χ(2) test showed that the high expression of TACSTD2 in IDC was correlated to histological grade (P=0.023), P53 status (P=0.042), Cyclin D1 status (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.004) and TNM staging (P<0.001). Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. These analyses also showed that a high TACSTD2 expression (P=0.003), a high Cyclin D1 expression (P=0.041), and lymph node metastasis (P=0.006) were independent prognosis factors. Collectively, our studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC.

Evaluation of agricultural nonpoint source pollution potential risk over China with a Transformed-Agricultural Nonpoint Pollution Potential Index method.

Agricultural nonpoint source (NPS) pollution has been the most important threat to water environment quality. Understanding the spatial distribution of NPS pollution potential risk is important for taking effective measures to control and reduce NPS pollution. A Transformed-Agricultural Nonpoint Pollution Potential Index (T-APPI) model was constructed for evaluating the national NPS pollution potential risk in this study; it was also combined with remote sensing and geographic information system techniques for evaluation on the large scale and at 1 km2 spatial resolution. This model considers many factors contributing to the NPS pollution as the original APPI model, summarized as four indicators of the runoff, sediment production, chemical use and the people and animal load. These four indicators were analysed in detail at 1 km2 spatial resolution throughout China. The T-APPI model distinguished the four indicators into pollution source factors and transport process factors; it also took their relationship into consideration. The studied results showed that T-APPI is a credible and convenient method for NPS pollution potential risk evaluation. The results also indicated that the highest NPS pollution potential risk is distributed in the middle-southern Jiangsu province. Several other regions, including the North China Plain, Chengdu Basin Plain, Jianghan Plain, cultivated lands in Guangdong and Guangxi provinces, also showed serious NPS pollution potential. This study can provide a scientific reference for predicting the future NPS pollution risk throughout China and may be helpful for taking reasonable and effective measures for preventing and controlling NPS pollution.

The uncoupling protein 2 -866G > a polymorphism is associated with the risk of ischemic stroke in Chinese type 2 diabetic patients.

AIMS: To determine genetic predispsitions for diabetic cerebral ischemia, we investigated the relationship between the -866G>A polymorphism of uncoupling protein (UCP) 2 and the risk of ischemic stroke in two cohorts of type 2 diabetic patients. METHODS: A total of 844 type 2 diabetic patients with 4-year prospective study were examined using a case-control methodology. And 404 cases with ischemical stroke, 440 cases without ischemical stroke. The -866G>A polymorphism in UCP2 was genotyped by TaqMan MGB probe method. RESULTS: The -866G>A SNP in UCP2 was significantly associated with diabetic ischemical stroke (odds ratio [OR]= 1.94; 95% confidence interval [CI]= 0.68 to1.31; P < 0.037). Similar results were observed for baseline cases of IS. Stratification by sex confirmed an allelic association with IS in women, whereas no association was observed in men. CONCLUSIONS: The A allele of the -866G>A variant of UCP2 was associated with increased risk of IS in Chinese diabetic women with type 2 diabetes in a 4-year prospective study. This association was independent of other common IS risk factors.

[Expression and clinical significance of Trop-2 in human pancreatic cancer].

OBJECTIVE: To investigate the expression and its clinical significance of Trop-2 in human pancreatic cancer. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence assay were used to characterize the expression of Trop-2 in human pancreatic cancer. The expression of Trop-2 protein in 31 tumor tissue samples, including peritumoral tissue from patients with pancreatic cancer, was detected with immunohistochemistry by tissue microarray. The clinicopathological characteristics and the tissue expression of Trop-2 protein were analyzed statistically. RESULTS: RT-PCR, immunofluorescence assay and immunohistochemistry by tissue microarray showed a high expression of Trop-2 in pancreatic cancer. The expression rate of Trop-2 was much higher in pancreatic cancer than that in peritumoral tissues (87.1% vs 9.7%). And a high expression of Trop-2 in pancreatic cancer was correlated with the low-differentiated changes. It had statistical significance (P < 0.05). In contrast, no statistically significant correlation was found between the expression of Trop-2 and gender or age. CONCLUSION: The expression of Trop-2 is correlated with the development and malignancy of pancreatic cancer. As a clinical prognostic marker, Trop-2 may be a potential therapeutic target for pancreatic cancer.

[Effects of mixed chelators on the leaching of cadmium in contaminated soils under intercropping system].

In order to elucidate the influence of chelators on Cd leaching in contaminated soil, outdoor soil column (100 cm) leaching experiments were conducted using two paddy soils irrigated with Pb-Zn mining wastewater. Soil samples which under intercropping systems were collected from Qingyuan City (acid soil with pH 4.63) and Lechang city (neutral soil with pH 6.51), Guangdong Province of China. The mixture of chelators (MC) comprised of citric acid, monosodium glutamate waste liquid, EDTA and KCl with molar ratio of 10 : 1 : 2 : 3 at the concentration of 5 mmol x kg(-1) soil. The intercropping system used in this study was a Zn- and Cd-hyperaccumulator (Sedum alfredii) and a low-accumulating crop (Zea mays). Results showed that at day 2 after the application of MC, the Cd concentrations in leachates from every layer of neutral and acid soils increased significantly in the treatment with intercropping and MC. At day 8 the concentrations of Cd in leachate from layers below 20 cm in the neutral soil and below 60 cm in the acid soil were still significantly higher than those of control. However, the mobility of Cd was decreased greatly compared with that at day 2. At day 2 and day 8 the Cd concentrations in leachates from every layer of neutral and acid soils in the Co-crop + MC treatments exceed the value of the Groundwater Quality Standards (GB/T 14848-93). Cd in all soil columns showed the trend to migrate downwards, especially in the acid soil. The total Cd in the soil layers of 20 cm and 40 cm was decreased by 40% -58% and 39%-49% respectively at the end of the experiments compared to the initial value. After leaching of 100 days,the total Cd in 0-40 cm soil layer of acid soil reached the limit of National Soil Environmental Quality Standards (GB 15618-1995). The results also implied that in Cd-contaminated soil MC addition might enhance the potential risks of Cd contamination in groundwater.

[Expression of HER-2 and leptin in gastric cancer and their clinical significance].

OBJECTIVE: To assess the expression of HER-2 and leptin in gastric cancer and evaluate their relationship with VEGF expression and clinicopathological features, and their prognostic value for gastric cancer patients. METHODS: One hundred and ten gastric cancer specimens and the corresponding metastatic lymph nodes were detected for HER-2 by immunohistochemistry (IHC). All primary cancer tissues were detected for leptin, OB-Rb and VEGF. Ninty-six specimens of normal gastric mucosa served as the control. RESULTS: The expression level of HER-2, leptin and OB-Rb in gastric cancer tissues were significantly higher than those in normal tissues (19.1% vs. 8.0%, 49.1% vs. 34.0%, and 60.9% vs. 46.0%, P < 0.05). HER-2 overexpression was moderately homogenous in primary gastric cancer and matastatic lymph nodes (P = 0.607, Kappa = 0.581). There was a correlation between the expression of HER-2 and leptin, both of which were significantly correlated with tumor invasion depth, metastatic lymph nodes ratio (NR), distal metastasis, TNM stage and VEGF expression. However, there was no significant correlation between OB-Rb expression and the clinicopathological features evaluated. Cox regression multivariate analysis showed that tumor size, histological grade, NR, stage, chemotherapy and HER-2 expression were independent prognostic factors. CONCLUSIONS: HER-2 is stably expressed in primary gastric cancer and metastatic lymph nodes. HER-2 and leptin play an important role in the progression and angiogenesis of gastric cancer. High expression of HER-2 is a prognostic factor for poor outcome.