谷胱甘肽S转移酶基因多态性与中国人群骨肉瘤化疗敏感性的meta分析

目的系统评估谷胱甘肽S转移酶GSTTl、SGTMl、GSTPl基因多态性与中国人群骨肉瘤化疗敏感性。方法计算机检索PubMed、Embase、WebofScience、CochraneLibrary、中国知网（CNKI）、维普（VIP）、万方数据库及中国生物医药文献数据库（CBD），收集有关GSTMl、GSTTl、GSTPl与中国人群骨肉瘤化疗敏感性的研究，按照纳入和排除标准筛选文献，对符合标准的文献进行质量评价并提取数据，采用RevMan5．3、Statal2．0软件进行meta分析，计算合并OR值和95％CI，进行发表偏倚评价和敏感性分析。结果共纳入4篇文献由12个独立的研究组成，累计病例681例。Meta分析结果显示中国人群GSTTl（OR=0．92，95％CI=0．68～1．25，P=0．59）、GSTMI（OR=0．93，95％CI=0．68-1．26，P=-0．63）缺失型与正常型及GSTPl各遗传模型（GGVSAA＋AG，OR=0．61，95％CI=0．34～1．11，P=-0．11）对化疗的敏感性差异均无统计学意义，但GSTPlMeta分析稳健性欠佳。结论GSTTl、GSTMl基因多态性与中国人群骨肉瘤患者化疗敏感性无关。GSTPl基因多态性与中国人群骨肉瘤患者化疗敏感性可能无关，更进一步大样本研究是必要的。

Relationship between metabolic enzyme polymorphism and colorectal cancer

AIM: To clarify the influence of genetic polymorphisms on colorectal cancer. METHODS: The results of 42 related studies from 1990 to 2001 were analyzed by meta-analysis. Mantel-Haenzel fixed-effect model or Dersimonian-Laird random-effect model and ReviewManager 4.1 statistical program were applied in processing the data. RESULTS: Meta analysis of these studies showed that GSTT1 deletion (pooled OR= 1.42), N-acetyltransferase 2 (NAT2)-rapid acetylator phenotype and genotye (pooled OR = 1.08) and NAT2-rapid acetylator phenotype (pooled OR = 1.15) had a significantly increased risk for colorectal cancer (P<0.05), other genotypes like GSTM1 deletion, GSTP1 1le105Val, NAT1*10, NAT2-rapid acetylator genotype CYP1A1 Lle462Val, CYP1A1 MspI*C, MTHFR C677T and MTR A2759G had no significant relationship with colorectal cancer (P>0.05). CONCLUSION: Risks for colorectal cancer are significantly associated with the genetic polymorphisms of GSTT1 deletion, NAT2-rapid acetylator phenotype and genotye and NAT2-rapid acetylator phenotype.

Expression of thymidylate synthase and glutathione-stransferase π in patients with esophageal squamous cell carcinoma

AIM： To investigate the expression of thymidylate synthase （TS） and glutathione-s-transferase π （GST-π） in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS： Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma （ESCC） tissue sections from 102 patients （median age, 58 years） and in 28 normal esophageal mucosa （NEM） samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS： The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples （P 〈 0.05）. The expression level of TS was not only significantly lower in well-differentiated （21.88%） than in poorly-differentiated carcinomas （51.43%, P 〈 0.05）, but was also significantly higher in samples from male patients （46.51%） than from female patients （18.75%, P 〈 0.05）. GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples （P 〈 0.05）. The expression level of GST-π was also significantly higher in welldifferentiated carcinomas （65.63%） than in poorly- differentiated carcinomas （35.00%, P 〈 0.05）. CONCLUSION： The expression of TS and of GST-π may be used as molecular markers for the characterization of ESCC. Poorly-differentiated cells showed increased expression of T5 and reduced expression of GST-π.

Effects of dietary menadione on the activity of antioxidant enzymes in abalone, Haliotis discus hannai Ino

A 240-day growth experiment in a re-circulating water system was conducted to investigate the effects of dietary menadione on the growth and antioxidant responses of abalone Haliotis discus hannai Ino. Triplicate groups of juvenile abalone (initial weight: 1.19 ± 0.01 g; shell length: 19.23 ± 0.01 mm) were fed to satiation with 3 semi-purified diets containing 0, 10, and 1 000 mg menadione sodium bisulfite (MSB)/kg, respectively. Results show that there were no significant differences in the rate of weight gain or in the daily increment in shell length of abalone among different treatments. Activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione S-transferase (GST) and glutathione reductase (GR) in viscera were significantly decreased with dietary menadione. However, activities of these enzymes except for GPX in muscle were increased. Therefore, antioxidant responses of abalone were increased in muscle and decreased in viscera by dietary menadione.

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.

Role of MGST1 in reactive intermediate-induced injury

Microsomal glutathione transferase (MGST1, EC 2.5.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 (the oxidative stress sensor) has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.

Biomarker responses in the bivalve Chlamys farreri to the water-soluble fraction of crude oil

To investigate the effect of the water soluble fraction of crude oil(WSF) on marine bivalves, the scallop C hlamys farreri was exposed to three WSF concentrations(0.18 mg/L, 0.32 mg/L, and 0.51 mg/L, respectively) in seawater. Petroleum hydrocarbon contents in scallops and a suite of enzymes [7-Ethoxyresorufin-O-deethylase(EROD), aryl hydrocarbon hydroxylase(AHH), glutathione S-transferase(GST), and glutathione peroxidase(GPx)] in gills and digestive glands were monitored over 10 days. The results revealed that WSF affected the activity of the four enzymes in the gills and digestive glands. EROD activity in the gills was significantly induced in most individuals of the three test groups, while in the digestive gland it was significantly induced in the low-concentration group within 4 days but was inhibited in the middle- and high-concentration groups on days 1, 4, and 10. AHH activity in the gills of all treatment groups was significantly induced on day 1. In the digestive gland, AHH activity was induced in most individuals from the treatment groups. In all treatment groups, GST activity was significantly inhibited from days 2 to 10 in the gills and was induced after day 4 in the digestive gland. GPx activity in the gills was significantly inhibited throughout the exposure period in all treatment groups. There was no overall significant difference in GPx activity in the digestive gland between the control and treatment groups. Our results also revealed that petroleum hydrocarbon concentrations in the tissues increased linearly with exposure time. EROD activity in the digestive gland and GST and GPx activity in the gill tissue were negatively correlated with petroleum hydrocarbon body burden. These enzymes play important roles in detoxification and can act as potential biomarkers for monitoring petroleum hydrocarbon contaminants in the marine environment.

Polymorphism analysis of Glutathione S-transferase A1 in patients with hematological diseases and its effect on GST enzyme activity

Glutathione S-transferases(GSTs)are important drug-metabolizing enzymes that catalyze the binding of glutathione(GSH)to electrophilic substances.GST has genetic polymorphism,and the enzyme activity of GST affects the metabolism of certain drugs in vivo.In the present day,we investigated the GST enzyme activity and GSTA1 gene polymorphism in 170 patients with hematological diseases and explored their relationship.The GSTA1 gene polymorphism of the patient was analyzed by PCR-restriction fragment length polymorphism(PCR-RFLP)technique,and the base sequences of the four mutation sites(-631,-567,-69,and-52)in the promoter region were determined by DNA-Sequencer.The patient’s GST enzyme activity was calculated by measuring the rate at which it catalyzed the reaction between 1-chloro-2,4-dinitrobenzene(CDNB)and GSH.The average GST enzyme activities of males and females were 5.20±0.13 and 5.17±0.12 nmol/min/mL,respectively,and the difference was not significant(P=0.91).The frequencies of genotypes GSTA1*A*A(wild genotype),GSTA1*A*B(heterozygous genotype),and GSTA1*B*B(homozygous mutant genotype)were 75.3%,22.9%,and 1.8%,respectively.Alleles GSTA1*A and*B were distributed at 86.8%and 13.2%,respectively.The genotype frequency distribution between males and females was no significant difference by Pearson’s chi-square test(P=0.743).The average GST activity of the heterozygous mutant genotype(4.83±0.76 nmol/min/mL)was lower than the wild genotype(5.34±1.26 nmol/min/mL,P=0.018),and higher than that of the homozygous mutant genotype(3.32±0.07 nmol/min/mL,P=0.022).These findings might help us improve the individualized treatment of patients with hematological diseases in the future and promote the development of precision medicine for blood diseases.