GST-7T and P-170 co-expression in multiple myeloma

Summary. Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione-S-transferase n (GST-TT), P-glycoprotein and the protein product of ras oncogenes family, p-21, on plasma cells, by immuno-cytochemical detection. 72% of evaluated samples were positive for P-170 and 82% for GST-7T without any correlation with clinical or prognostic parameters. A significant relationship between GST-7T expression and P-l 70 positivity was found and co-expression was observed in 91% of evaluated samples.
Expression of P-170 and GST-TT was found both in treated and untreated patients. However, patients evaluated before and after therapy showed an increase in the percentage of plasma cells positive for GST-7T or P-170 or both. Expression of p-21 was not associated with these mechanisms of drug resistance.
These data suggest that different resistance mechanisms are present in multiple myeloma.     

原发性肺癌^99Tc^m—MIBI显像与谷胱甘肽S转移酶π及DNA拓朴异构酶Ⅱa表达的关系

目的探讨原发性肺癌^99Tc^m-甲氧异丁基异氰（^99Tc^m-MIBI）显像与肺癌组织中谷胱甘肽s转移酶π（GST-π）、DNA拓扑异构酶IIa（TopoⅡa）表达的关系。方法对34例原发性肺癌患者术前行早期与延迟^99Tc^m-MIBI显像,应用免疫组织化学方法检测术后标本中多药耐药蛋白GST-π、TopoⅡa的表达水平。比较早期摄取比值（EUR）、晚期摄取比值（DUR）及放射性清除指数（WR）与GST-π、TopoⅡa表达的关系。结果^99Tc^m-MIBI早期、延迟显像阳性率分别为89．5％、82．4％,GST-π、TopoⅡa表达阳性率分别为78．5％、61．7％,GST-π、TopoⅡa表达阳性组和阴性组间EUR、DUR、WR差异均无统计学意义（P〉0．05）。结论^99Tc^m-MIBI显像与肺癌组织中GST-π、TopoⅡa表达无相关性,不具有检测肺癌患者肿瘤组织中GST-π、TopoⅡa表达的价值。     

Analysis of long-ranged mixed-valence states at linear polynuclear metal-complexes under electrochemical equilibrium by means of resonance of π-conjugation

When a quantum chemical technique for analyzing the resonance at π-conjugated organics was applied to mixed-valence states of linear N-nuclear metal-complexes with π-conjugated linkers, the theoretical current-potential curves under the steady state showed N waves at negative values of the overlap integral S, as well as at negative values of the interaction energy between the oxidized metal center and the reduced one. The analysis was made as follows: from a linear combination of wavefunctions of electrons relevant to a single electron transfer reaction, equations for a redox state of a given isomer were derived as a function of S, N and pair interaction energies. Analytical solutions of the current-potential curves were obtained only for N = 2 and 3. The curves for N ≥ 4 were computed numerically, exhibiting N waves. Those for a large number of N seemed to show one wave. These results were compared with the appearance of three waves at odd numbers of N and four at even numbers of N by the additive pair model previously presented.     

3-甲基芬太尼衍生物QSAR研究

Hansch途径研究了一系列3-甲基芬太尼衍生物理化性质与镇痛活性间的关系。初步结果表明,镇痛活性与化合物的油/水分配系数之间无规律性变化;与R₂取代基的立体效应(如L,B₁～B₄及MR_R2)和疏水常数(π_R2)间有一定的匹配关系,与R₃取代基的Hammen常数(σ)呈抛物线型。引入1-β羟基亦颇为有利。从作用机理推测,该类衍生物的R₂和可能是与受体相结合的基团,R₁可能仅起药物转运的载体作用,1-β羟基也可能通过氢键参与与受体的互补部位缔合。     

贫血对胃癌患者术后化疗耐药的影响

目的本研究通过检测P-糖蛋白(P-glycoprotein,P-gp)、拓扑异构酶-Ⅱ(topoisomerase-Ⅱ,TOPO-Ⅱ)、谷胱甘肽转移酶-π(glutathione-S-transferase-π,GST-π)及缺氧诱导因子-1α(hypoxia-induciblefactor-1α,HIF-1α)在胃癌组织中的表达情况,探讨贫血在胃癌术后化疗肿瘤的多药耐药[1](multidrugresistance,MDR)中的影响及其可能的内在机制。方法采用免疫组化SupervisionTM二步法检测56例胃癌组织及20例癌旁正常组织中P-gp、TOPO-Ⅱ、GST-π的表达,采用SABC法对检测上述组织中HIF-1α蛋白的表达。结果①胃癌组织P-gp、GST-π、HIF-1α表达水平高于癌旁正常组织,TOPO-Ⅱ表达水平低于癌旁正常组织。②P-gp、GST-π在不同组织学类型之间有显著性差异,HIF-1α在不同癌肿浸润深度及有、无淋巴结转移之间有显著性差异。P-gp、TOPO-Ⅱ、GST-π、HIF-1α表达水平与年龄、性别之间无关。③在胃癌组织中,P-gp、GST-π及HIF-1α表达水平与Hb成正相关,TOPO-Ⅱ表达水平与Hb成负相关,且HIF-1α与P-gp表达水平之间成正相关。结论胃癌患者术后化疗MDR与贫血成正相关,HIF-1α可能是贫血导致胃癌患者术后化疗MDR的介导因子之一。     

多药耐药基因、谷胱甘肽S-转移酶特异性siRNA逆转K562／A02细胞多药耐药.

 目的　研究多药耐药基因（mdr1）、谷胱甘肽S-转移酶（GSTπ）特异性siRNA逆转K562／A02细胞多药耐药性。方法　以mdr1 mRNA第79～99和GSTπmRNA第308～327核苷酸为作用靶点，合成针对靶区域序列的siRNA，克隆入pSilence2.1-U6 neo，克隆产物为pSilence-mdr1和pSilence-GSTπ，脂质体介导下转染K562／A02细胞。用实时荧光定量PCR检测K562／A02细胞 mdr1和GSTπ mRNA的表达；流式细胞仪检测细胞凋亡；MTT法检测多柔比星的半数抑制浓度（IC50）。结果　经酶切、测序分析表明，成功构建siRNA真核表达载体。经pSilence-mdr1转染后的K562／A02细胞株mdr1 mRNA表达量下降了71.5 %，从（2.8±1.65）×108拷贝／μg RNA下降至（3.9±2.37）×107拷贝／μg RNA（P＜0.01）；同时pSilence-GSTπ 作用后，K562／A02细胞 GSTπmRNA表达量较显示空载体pSilence2.1-U6 转染组下降了39.8 %，从（2.3±1.14）×105拷贝／μg RNA下降至（5.4±2.45）×104拷贝／μg RNA（P＜0.01）；流式细胞仪显示空载体pSilence2.1-U6 转染组细胞凋亡率为（11.65±4.06）%，pSilence-mdr1和 pSilence-GSTπ共转染组细胞凋亡率为（44.98±11.27）%（P＜0.01）；空载体转染组耐药指数为23，pSilence-mdr1和pSilence-GSTπ共转染组耐药指数降低为7，IC50值从转染前的（1.16±0.38）mmol／ml下降为（0.33±0.04）mmol／ml（P＜0.01）。结论　siRNA 真核表达载体pSilence-mdr1、pSilence-GSTπ对K562／A02细胞株多药耐药性具有明显的下调作用。     

结直肠癌组织中耐药基因P-gp、GST、TopoⅡ的表达

目的分析耐药基因P-gp(P-糖蛋白)、GST-π(谷胱甘肽S-转移酶)及TopoⅡ(DNA拓扑异构酶Ⅱ)在结直肠癌组织中的表达,并探讨其临床病理意义。方法采用免疫组化SP法(链霉菌抗生物素蛋白-过氧化物酶连结法)检测74例结直肠癌组织中P-gp、GST-π及TopoⅡ的表达情况,并分析其与结直肠癌临床分期、组织类型、肿瘤大小、浸润程度、淋巴结转移及预后等之间的关系。结果本组74例患者中P-gp阳性62例(83.78%),TopoⅡ阳性60例(81.08%),GST-π阳性70例(94.59%)。P-gp表达与患者年龄、性别、分化程度无明显相关性(P0.05),但与淋巴结转移、浸润程度有关,发生淋巴结转移患者阳性率明显高于未转移者(P0.05);TopoⅡ表达仅与淋巴结转移情况有关,而结直肠癌组织中GST-π表达与患者年龄、性别、转移及浸润程度等临床病理特征无关(P0.05)。结论 P-gp、GST-π及TopoⅡ耐药基因的表达与结直肠癌患者多药耐药密切相关,化疗治疗前,对患者P-gp、GST-π及TopoⅡ的检测对化疗药物的选择、化疗效果及预后具有指导意义。     

P-gp、GST-π和TopoⅡ在涎腺黏液表皮样癌中的表达及意义

目的：探讨涎腺黏液表皮样癌多药耐药基因P-gp、GST-π和TopoⅡ的表达情况及意义。方法：应用免疫组织化学技术（SP法）检测37例涎腺黏液表皮样癌及12例正常涎腺组织中P-gp、GST-π和TopoⅡ的表达。结果：P-gp、GST-π和TopoⅡ在涎腺黏液表皮样癌及正常涎腺组织中均有不同程度表达。涎腺黏液表皮样癌组织中P-gp、GST-π和TopoⅡ表达阳性率分别为91.9%（34/37）、86.5%（32/37）和21.6%（8/37）。TopoⅡ的表达与肿瘤的分化程度呈负相关。结论：P-gp、GST-π和TopoII在涎腺黏液表皮样癌的多药耐药机制具有重要作用。检测P-gp、GST-π和TopoⅡ可为临床拟定化疗方案提供依据,也可作为判断涎腺黏液表皮样癌预后的参考。