Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Serum Gamma-glutamyl Transferase Levels Predict Functional Outcomes after Aneurysmal Subarachnoid Hemorrhage

Objective We aim to explore the potential association between serum gamma-glutamyl transferase levels and functional outcome after aneurysmal subarachnoid hemorrhage in a Chinese population. Methods A total of 386 aneurysmal subarachnoid hemorrhage patients were included in the study from September 2007 to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month follow-up functional outcomes were determined. A poor outcome was defined as a modified ranking scale score of ≥ 3. The multivariable logistic model was used to analyze the relationship between serum gamma-glutamyl transferase and clinical outcomes after aneurysmal subarachnoid hemorrhage. Results The adjusted poor outcome rates of patients with gamma-glutamyl transferase levels of 〈 30 U/L, 30-50 U/L and ≥ 50 U/L were 16.7%, 19.6%, and 34.4%, respectively （P 〈 0.01）. The age-sex and multivariable adjusted odds ratios （95% confidence intervals） of poor prognosis comparing the top group （≥ 50 U/L） with the lowest group （〈 30 U/L） were 5.76 （2.74-12.13）, 6.64 （2.05-21.52）, and 6.36 （1.92-21.02）. A significant linear trend existed between gamma-glutamyl transferase level and aneurysmal subarachnoid hemorrhage prognosis. This association was also observed among nondrinkers. Conclusion Patients with higher gamma-glutamyl transferase levels were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can be considered to be an independent predictor of functional outcomes after aneurysmal subarachnoid hemorrhage.

Association of serum gamma-glutamyl transferase with treatment outcome in chronic hepatitis B patients

AIM:To investigate the association of serum gammaglutamyl transferase(GGT) levels with chronic hepatitis B infection and hepatitis B e antigen(HBe Ag) seroconversion.METHODS:A retrospective study was performed on clinical data collected from patients who had been positive for hepatitis B surface antigen for > 6 mo and who were antiviral-treatment na?ve(n = 215) attending the Hepatitis Clinic at Nanjing Drum Tower Hospital between August 2010 and December 2013. Healthy individuals without liver disease(n = 83) were included as controls. Patients were categorized into four groups based on disease status as recommended by the European Association for the Study of the Liver:immune tolerance(IT; n = 47),HBe Ag-positive hepatitis(EPH; n = 93),HBe Ag-negative hepatitis(ENH;n = 20),and inactive carrier(IC; n = 55). Prediction of complete response(CR) based on serum GGT was also examined in EPH patients(n = 33) treated for 48 wk with nucleos(t)ide analogue(NA) therapy,including lamivudine plus adefovir combination therapy(n = 20) or entecavir monotherapy(n = 13). CR was defined as a serum hepatitis B virus DNA level < 500 copies/m L and HBe Ag seroconversion by 48 wk of treatment. RESULTS:Serum GGT levels were significantly increased in EPH and ENH patients relative to the IT,IC,and healthy control groups(P < 0.01 for all). However,no significant difference in serum GGT levels was found between the EPH and ENH groups. Baseline serum GGT levels were significantly higher in patients who achieved CR(7/33; 21.2%) compared to patients in the non-CR group(26/33; 78.8%; P = 0.011). In addition,the decline in serum GGT was greater in CR patients compared to non-CR patients after 24 wk and 48 wk of treatment(P = 0.012 and P = 0.008,respectively). The receiver operating characteristic curve yielded a sensitivity of 85.71% and a specificity of 61.54% at a threshold value of 0.89 times the upper limit of normal for baseline serum GGT in the prediction of CR following NA therapy. CONCLUSION:Serum GGT is significantly elevated in EPH and ENH patients and is a potential biomarker for the prediction of HBe Ag seroconversion following NA therapy.

Mitochondrial carnitine palmitoyl transferase-Ⅱ inactivity aggravates lipid accumulation in rat hepatocarcinogenesis

AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.

Effect of <i>Lactobacillus brevis</i>SBC8803 on Gamma-Glutamyl Transferase in Japanese Habitual Drinkers: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled clinical trial in Japanese habitual drinkers was conducted to evaluate the efficacy of Lactobacillus brevis SBC8803 to alleviate adverse effect of alcohol. Subjects who drank habitually and had moderately higher levels of gamma-glutamyl transferase (GGT) (50 - 100 IU/L) were enrolled. The levels of transaminases in these subjects were almost within normal levels (aspartate transaminase (AST) <30 IU/L and alanine transaminase (ALT) <40 IU/L). Either the capsules containing placebo (n = 23) or 130 mg (4.0 × 1010 colony-forming units) of live L. brevis SBC8803 (n = 22) per day were administered for the continuous eight weeks (56 days). During the period, the subjects both in test group and placebo groups have kept each drinking behavior as usual. Regarding lipid metabolism, triacylglycerol (TG) levels in the male test group significantly decreased at week 4 as compared with week 0. Biomarkers of hepatocytes-damage;AST and ALT levels showed no significant differences between the pla- cebo and test groups at both weeks 4 and 8. Oxidative stress marker;GGT at weeks 4 was significantly lower in the test group than that in the placebo group (p = 0.017), but not at weeks 8. However, taking a reduced rate of GGT at weeks 8 comparing with that at week 0, that in the test group showed larger value comparing with that in the placebo group. These data about TG and GGT suggest that, although efficacy of L. brevis SBC8803 is limited in this study, intake of the probiotic may alleviate alcoholic influence in lipid metabolism and oxidative stress.

The Micro-determination of Serum Gamma-Glutamyl Transferase

The method of serum gamma-glutamyl transferase colorimeter assay was modified by changing the wave length from 420 nm to 400 nm, the incubated temperature from 37℃ to 50℃, the sample amount from 30 μl to 6μl. The modified method was proved to be more sensitive, with CV of intra-group being 2. 06% and accuracy 97. 4%. The method is suitable for clinical application with small-amount blood samples collected frorri earlobe or finger tip.

Oxidative stress-elevated high gamma glutamyl transferase levels, and aging, intake of tropical food plants, migration and visual disability in Central Africans

·AIM:To investigate the independent pathogenic role of high serum gamma-glutamyl transferase (GGT) levels, sociodemographic data, dietary and environmental risk factors for visual disability (VD). ·METHODS:This was a case-control study, run in 200 black Congolese patients managed in Saint Joseph Hospital Ophthalmology Division from Kinshasa town. Logistic regression model was used to identify determinants of VD (n = 58) among sex, age, cigarette smoking, alcohol abuse, rural-urban migration, education levels, aging ≥60 years, intake of red Beans, Safou fruit and Taro leaves, lipid profile, residence, socioeconomic status, and GGT. ·RESULTS:After adjusting for confounding factors, we identified migration (OR=3.7 95% CI:1.2-11.3; P =0.023), low education level (OR=3.1 95% CI 1.1-8.5; P =0.026), no intake of Safou fruit (OR=34.2 95% CI 11.5-102; P < 0.0001), age ≥60 years (OR=2.5 95% CI 1.01-6.5; P = 0.049), and serum GGT ≥10U/L (OR=3.6 95% CI 1.3-9.6; P = 0.012) as the significant and independent determinants of VD. ·CONCLUSION:VD appears as a major public health problem in Central Africa to be prevented or delayed by control of migration, lifestyle changes, antioxidant supplements, appropriate diet, nutrition education, and blocking of oxidative stress.

P-gp,ToPoⅡ和GST-π在胃癌组织中的表达及与预后的关系

目的:探讨胃癌患者中耐药基因P-糖蛋白(P-gp)、DNA拓扑异构酶Ⅱ(TopoⅡ)和谷胱苷肽-S转移酶(GST-π)的表达特点及对预后的影响.方法:用免疫组化方法检测130例胃癌组织中的P-gp,TopoⅡ及GST-π,分析其与临床病理特征的关系,并随访部分患者以研究其表达与预后的相关性.结果:在130例胃癌患者中,P-gp,TopoⅡ和GST-π表达的阳性率分别为24.62%,81.54%和75.38%.这3种耐药基因中,P-gp和GST-π与病变大小相关,病变直径>5cm患者中,其阳性率显著高于直径<5cm患者(χ2=4.56,P=0.033;χ2=5.545,P=0.020),有淋巴结转移患者P-gp的阳性表达率高于无淋巴结转移组(χ2=5.84,P=0.016),有血管侵犯患者P-gp和GST-π阳性表达率高于无血管侵犯患者(χ2=17.69,P<0.001;χ2=5.40,P=0.020),P-gp和GST-π表达为++^+++患者2a生存率明显低于-^+患者(χ2=3.964,P=0.047;χ2=4.2576,P=0.039);TopoⅡ的表达与病理类型及分化程度有关,在印戒细胞癌中表达率低于其他类型(χ2=7.29,P=0.007),且在低分化组中强阳性表达率明显低于中高分化组(χ2=7.79,P=0.005).结论:P-gp和GST-π的表达不仅与胃癌的生物学行为有关,同时也可作为判断胃癌患者预后的指标之一.耐药基因在胃癌中的表达程度及特点不同,因而有必要对其进行联合检测以判断耐药及预后情况.

大肠癌组织中P-gp和GST-π及TopoⅡ的表达及其临床意义的研究

目的:探讨多药耐药P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽转移酶(glutathione-S-trannsferaseπ,GST-π)和拓扑异构酶(DNA topoisomeraseⅡ,TopoⅡ)在大肠癌组织中的表达及临床意义。方法:应用免疫组化SP法联合检测P-gp、GST-π和TopoⅡ在84例大肠癌组织和20例正常大肠黏膜组织中的表达,并结合临床病理参数进行分析。结果:P-gp、GST-π在大肠癌组织中的表达率分别为71.4%(60/84)和75.0%(63/84),高于正常大肠黏膜组织(8/20和11/20),χ2值分别为6.91和3.14,P均<0.05;P-gp表达强度与临床分期相关,高分期P-gp表达(86.7%、39/45)较低分期(65.5%、19/29)高,χ2=5.28,P<0.05;TopoⅡ在大肠癌组织中的阳性率为45.3%(38/84),低于正常大肠黏膜组织65%(13/20),χ2=0.382,P>0.05;高、中和低分化腺癌P-gp(87.5%、80.7%和54.5%)和GST-π(87.5%、82.5%和54.5%)的表达率由高到低;TopoⅡ的表达率由低到高(37.5%、45.6%和63.6%)。淋巴结转移组P-gp和GST-π的表达显著高于无淋巴结转移组,P<0.05。结论:P-gp、GST-π和TopoⅡ均在大肠癌原发性多药耐药中起重要作用。联合检测P-gp、GST-π和TopoⅡ对于大肠癌化疗方案选择具有一定的指导意义。

P-gp、GST-π和Topo Ⅱ在巨块型宫颈癌中的表达及其与新辅助化疗的关系

目的探讨P-糖蛋白(P-gp)、谷胱甘肽-S-转移酶-π(GST-π)和拓扑异构酶Ⅱ(TopoⅡ)在巨块型宫颈癌中的表达及其与新辅助化疗疗效的关系。方法收集178例巨块型宫颈癌术后标本,根据术前是否行新辅助化疗(NACT)分为NACT组和单纯手术组,NACT组91例术前行1疗程紫杉醇加顺铂的联合化疗,单纯手术组87例直接手术治疗,应用免疫组化法检测2组标本中P-gp、GST-π和TopoⅡ的表达情况,并分析其表达与各临床病理因素间的关系。结果 (1)与单纯手术组比较,NACT组P-gp阳性表达率升高(P<0.05);GST-π阳性表达率升高,但差异无统计学意义(P>0.05);TopoⅡ阳性表达率降低(P<0.05)。(2)NACT组中P-gp、GST-π阳性表达者化疗有效率明显低于阴性表达者(P<0.05),TopoⅡ阳性表达者化疗有效率高于阴性表达者,但差异无统计学意义(P>0.05)。(3)P-gp、GST-π和TopoⅡ在宫颈癌组织中表达与患者年龄、临床分期、组织学类型、组织学分级、淋巴结转移、脉管癌栓、深肌层浸润、宫旁浸润均无相关性(P均>0.05)。结论新辅助化疗会诱导宫颈癌中P-gp、GST-π和TopoⅡ表达变化,三者联合检测,对新辅助化疗药物选择及疗效预测具有一定参考价值。

胃癌中EGFR的表达与临床、病理、预后及多药耐药蛋白P170、TopoⅡ、GST-π表达的关系

目的探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)在胃癌中的表达及其与临床病理参数、预后及多药耐药蛋白P-糖蛋白(P-glycoprotein,P170)、DNA拓扑异构酶Ⅱ(topoisomeraseⅡ,TopoⅡ)和谷胱苷肽-S转移酶(glutathione S-transferase-π,GST-π)表达的关系及意义。方法采用免疫组化ABC法检测160例胃癌组织中EGFR、P170、TopoⅡ及GST-π的表达以及EGFR在20例癌旁正常组织中的表达。研究EGFR在胃癌及癌旁正常黏膜中的表达差异,同时分析各因子表达与患者临床病理资料、预后的关系。结果 EGFR在160例胃癌标本中89例阳性,在20例癌旁正常黏膜中2例弱阳性,其在胃癌中的表达明显高于癌旁正常对照组(P<0.05)。EGFR与TopoⅡ的表达呈正相关(P<0.05)。EGFR表达与肿瘤的远处转移相关(P<0.05)。P170表达与肿瘤直径、淋巴结转移、远处转移及TNM分期相关(P<0.05)。GST-π表达与肿瘤远处转移及TNM分期相关(P<0.05)。TopoⅡ表达与病理分级、侵袭深度、远处转移及TNM分期相关(P<0.05)。单因素分析发现患者年龄、肿瘤直径、肿瘤部位、病理分级、侵袭深度、淋巴转移、远处转移、TNM分期、EGFR、TopoⅡ、GST-π均与预后有关(P<0.05)。Cox风险模型多因素分析发现病理分级、TNM分期、EGFR是影响胃癌预后的独立因素(P<0.05)。结论 EGFR在胃癌中高表达,与多药耐药蛋白TopoⅡ表达相关,是预测肿瘤预后的独立因素,可能参与化疗耐药。针对EGFR的分子靶向治疗可能使化疗或辅助化疗耐药,EGFR阳性胃癌患者获得较好的疗效。

原发性肝癌中多药耐药蛋白谷胱甘肽转移酶及拓扑异构酶Ⅱ的表达与临床病理指标的相关性

目的探讨原发性肝癌中谷胱甘肽转移酶(GST-π)及拓扑异构酶Ⅱ(Topo-Ⅱ)的表达与临床病理指标的相关性及其临床意义。方法采用免疫组织化学法检测GST-π及Topo-Ⅱ在原发性肝癌患者病理组织中的表达情况,分析GST-π及Topo-Ⅱ阳性表达与临床病理指标之间的关系,评价其临床意义。结果原发性肝癌患者肝癌组织中GST-π的阳性表达与术前甲胎蛋白水平、肿瘤直径、有无癌栓及肿瘤包膜是否完整相关(P<0.05),与患者年龄、肿瘤淋巴结转移(TNM)分期及病灶个数无关(P>0.05);Topo-Ⅱ的阳性表达与患者术前甲胎蛋白水平、肿瘤直径、TNM分期、有无癌栓及肿瘤包膜是否完整相关(P<0.05),与患者年龄及病灶个数无关(P>0.05)。结论 GST-π及Topo-Ⅱ阳性表达与肝癌患者临床病理指标密切相关,可作为判断肝癌患者预后的客观评价指标。

P-gp、GST-π、Topo-Ⅱ在宫颈癌组织中的表达及意义

目的探讨P-糖蛋白(P-gp)、谷胱甘肽S-转移酶-π(GST-π)和DNA拓扑异构酶Ⅱ(TopoⅡ)在宫颈癌组织中的表达及其临床意义。方法采用免疫组化方法检测20例正常宫颈、30例宫颈上皮内瘤变(CIN)、60例初治宫颈癌及10例复发宫颈癌组织中P-gp、GST-π、TopoⅡ的表达,分析P-gp、GST-π、TopoⅡ的表达与宫颈癌患者临床病理特征及3年生存率之间的关系。结果①P-gp、GST-π、TopoⅡ在正常宫颈、CIN、初治宫颈癌及复发宫颈癌组织中均有表达,表达强弱顺序依次为:复发宫颈癌>初治宫颈癌>CIN>正常宫颈。②宫颈癌组织中存在3种耐药蛋白的共表达,P-gp与GST-π、TopoⅡ的表达呈正相关(P<0.05);GST-π与TopoⅡ的表达无显著性相关(P>0.05)。③P-gp、GST-π与初治宫颈癌临床分期,组织学类型和病理分级无关(P>0.05);TopoⅡ在宫颈腺癌中的表达水平明显低于鳞癌(P<0.05)。④P-gp、GST-π低表达者3年生存率优于高表达者,差别有统计学意义(P<0.05);TopoⅡ低表达者与高表达者3年生存率差别无统计学意义(P>0.05)。结论P-gp、GST-π、TopoⅡ可能与宫颈癌的发生发展相关。P-gp、GST-π表达强度的增加不仅可为宫颈癌化疗用药提供参考,而且可作为宫颈癌判断预后的指标。

丹参酮ⅡA对自发性高血压大鼠左心室谷胱甘肽-s-转移酶μ2表达的影响

目的:观察丹参酮ⅡA对自发性高血压大鼠(SHR)左心室谷胱甘肽-s-转移酶μ2(glutathione-s-transferase μ2,GSTμ2)表达的影响,探讨丹参酮ⅡA防治左心室肥厚的机制。方法:实验分3组:(1)正常对照组;(2)SHR组;(3)丹参酮ⅡA组。处理后检测血流动力学指标、左室重量指数及大鼠左心室GSTμ2的活性,采用共聚焦显微镜检测左心室O2.-的产生情况,Western blotting检测GSTμ2的表达情况。结果:SHR组血压与左室重量指数均显著高于正常对照组,左心功能明显下降;丹参酮ⅡA显著逆转了SHR的左心室肥厚,但未明显改善高血压。SHR组左心室O2.-的产生较正常对照组显著增多,而丹参酮ⅡA治疗后,O2.-产生较SHR组显著减少。GSTμ2的表达及活性在SHR组显著降低,而丹参酮ⅡA显著增加了GSTM2的表达及活性。结论:丹参酮ⅡA能逆转SHR的左心室肥厚,这可能与其增加GSTμ2表达,减少活性氧产生,消除氧化应激有关。

GST-π、TopoⅡα在口腔鳞状细胞癌不同区域中的表达差异和临床意义

目的研究口腔鳞状细胞癌的手术切除标本不同区域耐药基因产物GST-π、TopoⅡα的表达差异及其临床意义。方法运用免疫组化方法检测20例未经化疗和19例经诱导化疗的口腔鳞状细胞癌石蜡标本,分表层区和深层浸润区观察GST-π、TopoⅡα的表达。结果GST-π,TopoⅡα阳性表达在20例未经化疗的标本表层区分别为18例(90%),15例(75%),深层浸润区分别为15例(75%),1例(5%);在19例经诱导化疗的标本表层区分别为16例(84.21%),18例(94.74%);深层浸润区分别为12例(63.16%),8例(42.11%)。两组中GST-π、TopoⅡα的阳性表达在表面区和深层区之间均有显著性差异(P<0.05)。而在有否经化疗两组间,GST-π只在深层浸润区的阳性表达有显著性差异(P<0.05),TopoⅡα在表层区及深层区的阳性表达则均有显著性差异(均为P<0.05)。GST-π,TopoⅡα的表达与患者性别、年龄、病理分级、临床分期、肿瘤生长部位、三年无瘤生存期和化疗效果无明显相关。结论口腔鳞状细胞癌在耐药基因和相关蛋白方面存在着异质性;诱导化疗可产生肿瘤的耐药性变化,这对诱导化疗和辅助化疗的选择有一定的指导意义;GST-π,TopoⅡα的表达指标不能预测口腔鳞状细胞癌的化疗效果和预后。

HS-AFP GGT-Ⅱ及AFP预测肝硬化癌变的临床价值

目的:探讨肝癌特异性甲胎蛋白(HS-AFP)、甲胎蛋白(AFP)和γ-谷氨酰转肽酶同工酶Ⅱ(GGT一Ⅱ)对肝硬化患者肝癌发生风险的预警价值。方法:HS-AFP采用聚丙烯酰胺凝胶电泳技术(PAGE)结合Western blot分离检测。AFP采用放射免疫分析测定法。GGT-Ⅱ采用PAGE分离检测。对341例肝硬化患者进行跟踪随访18个月,了解肝癌发生情况,分析比较HS-AFP、GGT-Ⅱ和AFP预测肝硬化患者发生肝癌风险的价值。结果:6、12、18个月随访期内HS-AFP、GGT-Ⅱ两项指标阳性组癌变率高于阴性对照组;随访12个月以上AFP阳性组癌变率高于阴性对照组;Hs-AFP、GGT-Ⅱ阳性组癌变率高于AFP阳性组,但前两者差异不明显;HS-AFP与GGT-Ⅱ及AFP之间存在互补性,其中HS-AFP和GGT-Ⅱ联合检测预测肝硬化癌变的敏感性、特异性和准确度分别达71.6%、91.4%、91.6%。结论:HS-AFP、GGT-Ⅱ和AFP对肝硬化癌变均有预测价值;HS-AFP和GGT-Ⅱ预测肝癌的特异性、准确度优于AFP;HS-AFP与GGT-Ⅱ预测肝癌的特异性、准确度相似;多项指标联合检测可提高预测肝硬化癌变的敏感性、特异性和准确度,以HS-AFP和GGT-Ⅱ联合检测效果最优。

P-gp170、GST-π、TOPOⅡ在外周T细胞淋巴瘤中的表达及意义

目的:探讨多药耐药(MDR)相关的P糖蛋白(P-gp170)、谷胱甘肽-S-转移酶(GST-π)、拓扑异构酶(TOPOⅡ)在不同亚型外周T细胞淋巴瘤(PTCL)的表达情况以及和化疗反应性、预后的关系。方法:应用免疫组化方法检测64例经病理确诊的PTCL患者病理组织P-gp170、GST-π、TOPOⅡ的表达情况,并分析它们之间的相关性以及与病理亚型、化疗效果、预后的关系。结果:64例患者中PTCLP-gp170、GST-π、TO-POⅡ表达阳性率分别为57.8%(37/64)、51.6%(33/64)和53.1%(34/64)。三者的表达无显著的相关性(P>0.05)。P-gp170在PTCL-U和ALK+ALCL两组中的表达具有显著性差异(P=0.0182)。P-gp170表达强阳性和首程化疗后完全缓解(CR)、部分缓解(RR),均呈显著负相关(P=0.000)。本文综合定义的MDR高危组(≥2分)和RR具有显著负相关(P=0.002)。P-gp170表达强阳性和MDR高危组和预后相关(P=0.000;P=0.0145)。PTCL的病理亚型、对化疗的反应性(包括CR和RR)为外周T细胞淋巴瘤的独立预后因素。P-gp170糖蛋白、GST-π、TOPOⅡ尚不能作为独立预后因素。结论:P-gp170糖蛋白、GST-π、TOPOⅡ的表达在PTCL的不同亚型中有一定的差异,在一定程度上和PTCL的耐药性以及不良预后有关。

GST-π、TopoⅡ、ER、PR在乳腺癌组织中的表达及其临床意义

目的检测谷胱甘肽-S-转移酶-π(GST-π)、DNA拓扑异构酶Ⅱ(TopoⅡ)及雌、孕激素受体(ER、PR)在乳腺癌组织中的表达,分析其在乳腺癌临床病理特征间的关系。方法采用免疫组化方法检测202例未经抗肿瘤治疗的原发性乳腺癌组织中GST-π、TopoⅡ、ER、PR的表达情况。结果乳腺癌组织中TopoⅡ阳性表达率明显高于GST-π、ER、PR的阳性表达率(P<0.05)。GST-π、TopoⅡ的表达与肿瘤的浸润性、临床分期相关;GST-π的表达与腋淋巴结转移有关,与ER、PR呈正相关(P<0.05);GST-π和TopoⅡ之间的表达无相关性(P>0.05)。结论联合检测乳腺癌组织中GST-π、TopoⅡ、ER、PR的表达对乳腺癌治疗方案的制定和预后的判断有重要的参考价值。

肺癌中MDR基因产物LRP、P-gp、GST-π、TopoⅡ的表达及临床意义

目的:探讨多药耐药(MDR)基因产物LRP、P-gp、GST-π、TopoⅡ在肺癌中的表达及临床相关性。方法:应用单克隆抗体、免疫组化技术S-P法,对70例肺癌标本进行上述4种MDR指标检测。结果:在肺癌组织中LRP、P-gp、GST-π、TopoⅡ表达的阳性率分别为75.7%、70.0%、82.9%、84.3%,其与性别、年龄、部位、临床分期无关(P>0.05);在未分化、小细胞型肺癌中LRP、P-gp、GST-π表达的阳性率明显降低(P<0.05),而TopoⅡ表达的阳性率则升高(P<0.05,低分化型肺癌除外)。结论:LRP、P-gp、GST-π、TopoⅡ在未化疗过的肺癌组织中均有不同程度的高表达,且与肺癌的某些生物学行为有关,联合检测有助于化疗药物的选择及预后的判断。