谷胱苷肽-S-转移酶-π表达对非小细胞肺癌化疗效应的影响及临床意义

目的探讨在非小细胞肺癌（NSCLC）患者中谷胱苷肽-s-转移酶-π（GST-π）表达与临床病理类型、分化程度、临床分期及其与化疗疗效的关系。方法用免疫组化方法检测50例肺癌组织中GST-π的表达,回顾性分析其与临床病理类型、分化程度、临床分期及化疗疗效的关系。结果GST-π的表达在肺癌组织中和良性肺组织具有显著差异（P〈0．05）,GST-π表达与肺癌组织病理类型、分化程度和化疗疗效有相关性,具有统计学意义（P〈0．05）GST-π在肺腺癌中阳性率的表达较鳞癌高（P〈0．05）,分化程度越高,表达越低（P〈0．05）,GST-π阴性表达组化疗有效率显著高于阳性组（P〈0．05）,而与TNM分期无相关性（P〉0．05）。结论GST-π阳性表达对指导临床NSCLC化疗有一定指导意义。     

复方五味子素B对人结肠癌细胞多药耐药性逆转作用及其机制研究

目的：研究复方五味子素B（γSC）对耐奥沙利铂人结肠癌细胞（THC-8307/OXA）多药耐药性的逆转作用及作用机制.方法：采用噻唑蓝（MTT）比色法检测奥沙利铂（OXA）和γSC的细胞毒性;碱性磷酸酶免疫组织化学法和Western blot检测γSC对THC-8307/OXA细胞GST-п蛋白水平的影响.结果：γSC（6.0,12.5,25 μg·ml-1）对人结肠癌细胞（THC-8307）和THC-8307/OXA无显著毒性作用（P＞0.05）,OXA对THC-8307的IC50为0.06 μg·ml-1,而对THC-8307/OXA的IC50为2.32 μg·ml-1,THC-8307/OXA较THC-8307耐药性提高39倍,γSC（6.0,12.5,25 μg·ml-1）能使OXA对THC-8307/OXA细胞的IC50从2.32 μg·ml-1依次下降至0.370,0.128,0.057 μg·ml-1,逆转倍数分别为6.2,18.1,40.7倍.碱性磷酸酶免疫组织化学法和Western blot检测γSC（12.5 μg·ml-1）处理48 h后,THC-8307/OXA细胞GST-n蛋白表达明显降低（P＜0.01）.结论：γSC具有逆转耐奥沙利铂人结肠癌细胞的MDR作用,其作用机制与下调GST-п表达有关.     

胆管癌中MRP-1和GST-π的表达及临床意义

目的多药耐药性（MDR）是导致胆管癌化疗疗效不佳的主要原因,本研究通过检测胆管癌组织中MRP—1和GST-π的表达情况,探讨其耐药的临床意义。方法收集2001年1至2007年12月收治并行手术切除的21例胆管癌标本,RT-PCR方法检测标本中MRP-1及GST-π mRNA的表达。结果MRP—1和GST-πmRNA在胆管癌组织中的表达阳性率分别76．2％和66．7％,显著高于对照组（P〈0．05）,上述指标与性别、年龄、病理分期、分化程度、淋巴结转移均无关（P〉0．05）。结论MRP-1、GST-π基因在未经过化疗的胆管癌组织中均有不同程度的高表达;胆管癌的原发性多药耐药可能与MRP-1、GST-π有关。     

靶向GST-π、po1β基因的siRNA重组慢病毒对人食管鳞癌顺铂耐药逆转的体内实验研究

目的探讨靶向GST-π、polβ的siRNA重组慢病毒在裸鼠体内对人食管鳞癌顺铂耐药株耐药的逆转作用。方法采用皮下注射细胞法建立裸鼠人食管癌细胞细胞EC9706及其耐药细胞EC9706/cDDP移植瘤模型,观察其成瘤性和体内耐药性。利用靶向GST-π、polβ的siRNA重组慢病毒感染具有 MDR表型的裸鼠移植瘤,以期达到封闭GST-π、polβ的转录和表达,检测移植瘤细胞对药物的敏感性变化。结果 cDDP 联合靶向GST-π的siRNA慢病毒GSTsi2处理组中观察到移植瘤体积与cDDP组及PBS对照组比较,体积显著减小,表明经cDDP联合GSTsi2处理后,可明显恢复移植瘤细胞对 cDDP的敏感性。而在cDDP联合靶向polβ的siRNA慢病毒polsi1处理组中移植瘤体积与cDDP及PBS对照组比较无显著差异,移植瘤细胞对cDDP的敏感性无明显改变。结论靶向GST-π的重组慢病毒可有效逆转食管癌细胞的耐药性,靶向polβ的重组慢病毒逆转肿瘤细胞耐药的效果不明显。     

柴黄胃溃宁对胃溃疡肝郁脾虚证大鼠GST-α表达的影响

目的探讨柴黄胃溃宁对胃溃疡肝郁脾虚证大鼠胃组织GST-α基因表达的影响。方法 SD大鼠随机分为正常组,模型组,黄芪组,柴黄中、低、高剂量组,每组10只。除正常组外,其余各组以多因素复合模拟中医病因并结合乙酸法建立胃溃疡肝郁脾虚证大鼠模型。造模成功后,各组予以相应干预。用Real-Time PCR技术检测柴黄胃溃宁干预模型大鼠GST-α基因的表达。结果模型组大鼠差异性基因GST-α低表达。中药干预后,柴黄胃溃宁各剂量组GST-α基因出现不同程度的高表达,以中剂量组作用最明显(P0.05)。结论柴黄胃溃宁对病证结合模型大鼠胃组织中GST-α基因表达有明显调节作用,可能为其起效途径之一。     

TopoⅡ及GST-π在胃癌和结直肠癌中的表达及其临床意义

目的：探讨拓扑异构酶（ TopoⅡ）和谷胱甘肽转移酶π（ GST-π）在胃癌和结直肠癌组织中表达的临床意义。方法：采用免疫组化二步法检测TopoⅡ和GST-π在40例胃癌组织和60例结直肠癌组织中的表达情况,探讨其与临床病理参数间的关系。结果：在40例胃癌组织中TopoⅡ和GST-π阳性率分别为42.5％和82.5％,TopoⅡ在高中分化腺癌中的阳性率低于低分化腺癌（ P＜0.01）,而GST-π在高分化腺癌中阳性率高于低分化癌（ P＜0.05）,但与浸润深度及淋巴结转移无关。TopoⅡ和GST-π在结直癌中阳性率分别为43.3％和93.3％,与肿瘤的分化程度、浸润深度以及有无淋巴结转移均无关。结论：中晚期胃癌和结直肠癌广泛存在耐药性,TopoⅡ和GST-π的表达水平可作为判断胃癌恶性程度的指标,还可以指导临床对胃癌和结直肠癌化疗药物的选择。     

Fluoxetine-induced toxicity results in human placental glutathione S-transferase-π (GST-π) dysfunction

Context: The antidepressant drug fluoxetine (FLU) is considered in the group of selective serotonine re-uptake inhibitors. Its distribution in brain and binding to human brain glutathione S-transferase-π (GST-π) have been shown. FLU can cross blood brain barrier and placenta, accumulate in fetus and may cause congenital malformations. Objective: To elucidate the interaction of placental GST-π with FLU. Materials and methods: First, concentration-dependent inhibition of human placental GST-π was evaluated by using different FLU concentrations and then 0.3125, 0.625, 1.25, 2.5 and 5?mM FLU concentrations were chosen and tested while keeping GSH concentration constant and 1-chloro-2,4-dinitrobenzene (CDNB) concentration varied and vice versa. The data were evaluated with different kinetic models and Statistica 9.00 for Windows. Results: The V_m, at variable [CDNB] (142?±?16?U/mg protein) was 3 times higher than the V_m obtained at variable [GSH] (49?±?4?U/mg protein). On the other hand, the K_m for CDNB was ～10 times higher than the K_m for GSH (1.99?±?0.36?mM versus 0.21?±?0.06?mM). The IC₅₀ value for FLU was 8.6?mM. Both at constant [CDNB] and variable [GSH] and at constant [GSH] and variable [CDNB] the inhibition types were competitive with the K_i values of 5.62?±?4.37 and 8.09?±?1.27?mM, respectively. Conclusion: Although the K_i values obtained for FLU in vitro are high, due to their uneven distribution, long elimination time and inhibitory behavior on detoxification systems, it may cause defects in adults but these effects may be much more severe in fetus and result in congenital malformations.     

Sensitivity of Gastric Cancer Cells to Chemotherapy Drugs in Elderly Patients and Its Correlation with Cyclooxygenase-2 Expression

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients andits correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-threeelderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors(control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of ChinesePeople’s Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carriedout in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and thefactors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results:The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC)and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the controlgroup, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-π(GST-π) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than incontrol group (P<0.05), while that of DNA topoisomerase IIα (TopoIIα) expression lower than in the control group(P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlationwith GST-π and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with TopoIIα (r=−0.328,P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively(r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in theobservation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) andeADM in tumor cells (r=−0.723, P=0.000; r=−0.570, P=0.000; r=−0.919, P=0.000; r=−0.781, P=0.000), but withhydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=−0.915, P=0.000; r=−0.890, P=0.000;r=−0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may berelated to high COX-2 expression.     

耐顺铂相关基因MDR1、MRP、LRP及GST-π在非小细胞肺癌中的表达及与生存相关的Meta分析

目的:采用循证医学系统分析方法了解肿瘤耐顺铂相关基因与非小细胞肺癌的相关性,为科学制定化疗方案提供理论依据.方法:检索中国学术期刊网(CNKI)全文数据库、维普科技期刊、美国国立图书馆PUBMED;检索时间段为1979 - 2011年;获得符合纳入标准的关于非小细胞肺癌耐药相关基因MDR1、MRP、LRP及GST -π的文献研究27篇;采用Stata11.0进行统计分析.结果:非小细胞肺癌组织与正常肺组织耐药基因表达合并效应显示,非小细胞肺癌组织耐顺铂相关基因表达水平明显高于正常肺组织.4种基因合并OR值并计算95％可信区间,各基因表达结果按照OR值大小顺序,OR值及95％可信区间依次为GST -π30.86(16.03,59.40)、LRP 13.96(9.27,21.01)、MRP 12.69(8.36,19.26)、MDR1 8.03 (4.45,14.48),其中LRP及MRP基因3年死亡人数明显高于3年生存人数,OR值及95％可信区间分别为LRP 4.75(2.11,10.67)、MRP 4.61(2.28,9.32).结论:耐顺铂相关基因MRP、LRP、GST -π及MDR1在非小细胞肺癌组织中呈高表达,尤以GST -π基因为著,其余依次是LRP、MRP、MDR1基因.各基因在非小细胞肺癌组织中表达的高低直接影响化疗效果和预后,是非小细胞肺癌化疗耐药中的重要基因.     

胃癌中HER-2和GST-π的表达及意义

目的：探讨胃癌组织中人表皮生长因子受体-2（HER-2）和胎盘型谷胱甘肽-S-转移酶-π（GST-π）的表达及与临床病理特征的关系。方法：应用免疫组化Envision二步法,检测70例胃癌组织中HER-2和GST-π的表达情况,并结合其临床病理特点进行分析。结果：HER-2和GST-π在胃癌组织中的表达阳性率分别为27.1%（19/70）和58.6%（41/70）。阳性表达与肿瘤分化程度,侵袭深度,有无淋巴结转移及TNM分期有关（P〈0.01,P〈0.05）,而与患者的性别及年龄、肿瘤部位和大小无关（P〉0.05）。HER-2和GST-π两者之间在胃癌组织中的表达呈正相关（P〈0.01）。结论：HER-2和GST-π的表达参与胃癌的生长、侵袭和转移过程。其联合检测有助于胃癌患者靶向药物和化疗药物的选择,也为胃癌的预后判断提供客观的参考指标。