skp2、p27kip1在正常胃黏膜和胃癌组织中的表达

[目的]探讨细胞S相激酶相关蛋白2（skp2）和细胞周期素依赖性激酶抑制蛋白27（p27^kip1）表达与胃癌发生的关系。[方法]用免疫组化SP法检测69例胃癌组织中skp2、p27^kip1蛋白的表达，并与28例正常胃黏膜作对比；用RT-PCR方法随机检测其中3例胃癌组织中skp2的mRNA表达，并与其正常胃黏膜作对比。[结果]p27^kip1蛋白阳性表达率在胃癌中为46.38％，而正常胃组织中为96．43％（P〈0．00。p27^kip1蛋白在胃癌中的阳性表达率随肿瘤分化程度的降低、浸润深度的加深、淋巴结转移、病理分期进展而降低（10〈0．05）。skp2 mRNA在胃癌组织中的表达明显上凋（P〈0．01）。skp2蛋白阳性表达率在胃癌中为33.33％，而正常胃组织中为10．71％（P〈0．05）。skp2蛋白阳性表达率随肿瘤的分化程度降低而升高fP〈0．05）。skp2、p27^kip1蛋白在胃癌中的表达呈负相关（P〈0．01）。[结论]p27^kip1、skp2蛋白检测有助于胃癌的临床诊断及判断预后。     

survivin、bcl-2在胃癌中的表达及其临床意义

[目的]探讨凋亡抑制基因survivin在胃癌组织中的表达及其与bcl-2表达的相关性。[方法]应用免疫组织化学链霉菌抗生物素蛋白-过氧化酶连接法（SP法）检测survivin、bcl-2在20例正常胃黏膜组织、50例胃腺癌组织中的表达。[结果]survivin在正常胃黏膜组织中不表达,50例胃癌组织中35例表达阳性,表达率为70％;survivin蛋白表达与组织分型、淋巴结转移及TNM分期呈正相关（P〈0．05）,与年龄、性别及浸润程度无相关性（P〉0．05）。survivin蛋白表达阳性率与胃癌组织中bcl-2蛋白表达密切相关。[结论]survivin异常表达而引起的细胞凋亡抑制,在胃癌的发生中起重要作用,其过度表达提示胃癌预后不良。survivin蛋白表达与胃癌组织中bcl-2蛋白的异常表达密切相关。     

73例直肠癌患者MIC-1表达及与预后关系

[目的]研究巨噬细胞抑制细胞因子-1（MIC-1）在直肠癌组织中的表达情况，并明确其表达水平与临床病理学参数及预后的关系。[方法]应用免疫组织化学方法检测73例直肠癌石蜡包埋组织中MIC-1的表达。[结果]73例直肠癌组织中MIC-1的阳性率为58．90％（43／73）。在淋巴结转移组和无转移组以及不同临床分期、不同浸润深度患者MIC-1的表达有显著性差异（P〈0．05）；MIC-1阴性表达的患者总生存期较长，与阳性表达患者相比有显著性差异（P〈0．01）。[结论]MIC-1蛋白与直肠癌的肿瘤进展密切相关,在直肠癌患者中MIC-1的检测有临床意义。     

肿瘤相关巨噬细胞与胃癌血管生成及转移关系

[目的]探讨肿瘤相关巨噬细胞（TAMs）浸润与胃癌血管生成及转移的关系。[方法]采用免疫组织化学法检测51例胃癌组织微血管密度（MVD）、TAMs和血管内皮生长因子（VEGF）的表达。[结果]TAMs的表达在高分化癌组织中明显低于中-低分化组（P〈0．05）；淋巴结转移组高于无淋巴结转移组（P〈0．05）；TAMs与VEGF及MVD均呈正相关（r=0．74，P〈0．01：r=0．58，P〈0．05）。[结论]胃癌组织中TAMs在血管生成及肿瘤转移中可能起重要作用。     

S100 A6蛋白在胃癌组织中的表达及生物学意义

目的：探讨钙结合蛋白S100A6在胃癌组织中的表达及生物学意义。方法：用组织微阵列技术构建包含51例胃癌、15例慢性萎缩性胃炎、15例正常胃黏膜组织的81点阵的石蜡组织芯片。免疫组化SP 法检测该芯片中S100A6蛋白的表达并测定其灰度值,分析其与胃癌的关系。结果：51例胃癌组织中,S100A6蛋白阳性表达率为80．4％（41／51）,平均灰度值为125．84±13．05;15例正常胃黏膜组织中未见表达;15例慢性萎缩性胃炎中阳性率为20．0％（3／15）,平均灰度值为115．86±3．00。胃癌组与正常胃黏膜组比较,P ＝0．001;胃癌组与慢性萎缩性胃炎组比较,P＝0．049;正常胃黏膜组与慢性萎缩性胃炎组比较,P＝0．14。S100A6蛋白的表达与年龄、性别及肿瘤组织分级、分期无明显关系。结论：S100A6蛋白与胃癌相关,可能与胃癌的发生及发展有密切关系。     

胃黏膜癌变过程中Survivin与Fas表达及其相关性

目的探讨凋亡基因Survivin、Fas在胃黏膜癌变过程中的表达、临床意义及其两者的相关性。方法采用免疫组化法检测12例正常组织、136例患者（包括浅表性胃炎22例、肠上皮化生25例、异型增生37例及胃癌52例）组织中的Survivin和Fas表达。结果Survivin在肠上皮化生、异型增生和胃癌中的阳性率分别为16％、37．8％和69．2％。胃癌组明显高于肠上皮化生（P〈0．01）和异型增生组（P〈0．05）。胃癌组Fas表达率为30．8％，显著低于对照组和异型增生组（均P〈0．01）。Survivin表达和淋巴结转移、远处转移密切相关（均P〈0．05）；Fas表达和淋巴结转移密切相关（P〈0．05）。相关回归分析显示胃癌组织病理分期中Survivin与Fas表达呈负相关。结论在胃黏膜癌变过程中，Sur-vivin的表达逐渐上调，而Fas的表达逐渐下调。在胃癌组织中Survivin和Fas的表达呈负相关。     

KAI1、E-cadherin、β-catenin在宫颈癌中的表达

[目的]探讨KAI1、E-cadherin、β-catenin在宫颈癌组织中的表达及其与宫颈癌恶变程度的相关性。[方法]采用逆转录-聚合酶链反应（RT—PCR）法和免疫组化（SP）法检测了100例宫颈癌组织、50例宫颈正常上皮组织、60例宫颈上皮内瘤变组织中的KAI1、E-cadherin和β-catenin的表达,并分析其与宫颈癌临床病理学参数间的关系。[结果]KAI1 mRNA、E-cadherinmRNA、β—cateninmRNA在宫颈癌组中的相对表达量,明显低于宫颈正常上皮组（P值均〈0．05）;蛋白表达率亦明显低于宫颈正常上皮组（P值均〈0．01）。E-cadherin与β-catenin蛋白表达之间正相关（r=-0．834,P〈0．05）,与KAI1蛋白表达呈正相关性（r=-0．604,P〈0．05）,而KAI1与β—catenin蛋白表达之间无相关性（P〉0．05）。[结论]宫颈癌中KAI1、E-cadherin和β—catenin的表达与宫颈癌的恶变程度有关．联合检测这些指标有助于判断宫颈癌的转移潜能。     

KAI1和E-钙黏蛋白在75例胃癌中的表达

[目的]探讨KAI1、E-钙黏蛋白在胃癌中的表达及意义。[方法]用免疫组织化学S-P法检测75例胃癌及癌旁组织中KAI1和E-钙黏蛋白的表达。[结果]胃癌组织中KAI1和E-钙黏蛋白的表达为52．00％和46．67％，癌旁组织为98．52％和92．43％，有显著性差异（P均〈0．01）；胃癌组织中KAI1和E-钙黏蛋白的表达与胃癌的临床分期、浸润深度和有无淋巴结转移密切相关（P均〈0．05）．与肿瘤分化程度无关（P均〉0．05）。KAI1与E-钙黏蛋白的表达呈正相关（r=-0．417，P〈0．05）。[结论]KAI1和E-钙黏蛋白表达与胃癌的浸润转移有关，联合检测这两项指标有助于判断胃癌的生物学行为。     

胃癌高危人群胃黏膜组织中Runx3蛋白表达与Hp感染研究的关系

目的：对胃癌高危人群胃黏膜组织中的Runx3蛋白及Hp进行检测，探讨Runx3蛋白与Hp感染在陕北胃癌高发的关系。方法：免疫组化法（S—P）检测178例胃癌高危人群胃黏膜活检标本（其中1例为胃癌）和63例胃癌（GC）组织标本中Runx3蛋白的表达情况，HE染色和特殊染色检测Hp感染情况。结果：178例胃黏膜组织中，Runx3蛋白在102例慢性浅表性胃炎（CSG）中的阳性表达率为81．37％，在76例慢性萎缩性胃炎（CAG）中的阳性表达率为72．37％，在伴有肠上皮化生（IM）的60例中阳性率为61．67％，在伴有异型增生（DYS）的9例中阳性表达率为55．55％，63例GC中的阳性表达率为41．26％。GC与CSG中的阳性表达率相比有显著性差异（P〈0．005），Gc与CAG中的阳性表达率相比有显著性差异（P〈0．005），Gc与伴IM中的阳性表达率相比有统计学意义（P〈0．05），Gc与伴DYS中的阳性表达率相比无统计学意义（P〉0．05）。Hp在CSG中的感染率为40．19％，在CAG中的感染率为65．78％，在伴IM中的感染率为66．67％，在伴DYS中的感染率为77．78％，随着病变的进展Hp的感染率有逐渐升高的趋势，（P〈0．005）。91例Hp阳性组中Runx3蛋白的阳性表达率为54．94％，87例Hp阴性组中Runx3蛋白的阳性表达率为78．16％，二者有显著性差异（P〈0．005）。结论：Runx3基因和Hp感染是胃癌高发的重要因素，可能有协同致癌作用。     

MG7和PGC在胃癌及癌前疾病中的表达及意义

[目的]探讨胃癌相关抗原（MG7）和胃蛋白酶原C（PGC）在不同胃疾病中的动态表达,并对其在胃癌前疾病及胃癌诊断中的价值评价。[方法]采用免疫组织化学染色检测125例胃黏膜标本中MG7和PGC的表达情况。[结果]①MG7-Ag在12例正常胃黏膜中无表达,在31例胃癌中表达率为93．55％,由浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,MG7-Ag表达率依次逐渐上升（P〈0．05）。PGC—Ag在12例正常胃黏膜中全部阳性表达（100％）,在31例胃癌中表达率显著下降（6．45％）,从浅表性胃炎或胃糜烂溃疡→萎缩性胃炎或异型增生→胃癌,PGC—Ag表达率依次逐渐下降（P〈0．05）。②单独应用MG7和PGC诊断试验的灵敏度高;将MG7和PGC联合进行串联试验,提高了诊断胃癌的特异度和准确度。[结论]①MG7抗原和PGC抗原两个指标与胃疾病的发生发展有良好的相关性。②MG7抗原和PGC抗原联合检测可以提高特异度,可以用于胃癌的诊断和癌前疾病的筛查。     

Thrombospondin-1 (TSP-1) and Survivin (S) expression in non-Hogkin's lymphomas

Survivin (S) is a member of inhibitor of apoptosis family (IAP) and is expressed in the majority of malignant tumors but undetectable in normal differentiated adult tissues. S is an encouraging target for cancer therapy. TSP-1 is a multifunctional protein regulating cell growth, motility and apoptosis in both physiological and pathological conditions. The role of TSP-1 in cancer progression remains controversial. We aimed to determine the pathogenetic and prognostic role of TSP-1 and S in non-Hodgkin's lymphomas (NHL). S and TSP-1 expressions were looked for in 177 cases with NHL. S was found to be positive in 94 of the cases (53%). TSP-1 was found to be positive in 31 of the cases (17.5%). There was a strong association between S and TSP-1 and also aggressive histology with S and TSP-1. The overall survival (OS) times were longer in cases without S expression than cases with S expression (p=0.0514). Although the OS was shorter in TSP-1 expressing cases as compared with TSP-1 (-) cases, difference was not significant (p=0.2428). In conclusion, S and TSP-1 expressions were detected in 53 and 17.5% of the cases with NHL, and are associated with aggressive histology and shorter OS.     

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma

Genes coding for the glutatione S-transferase M1 (GSTM1) andTheta 1 (GSTT1) proteins are polymorphic in humans and thesegenes are absent, or homozygous null, in 10–60% of differentethnic populations. These enzymes catalyze the conjugation ofglutathione to numerous carcinogenic chemicals and previousepidemiologic studies have associated the null genotypes ofthese GST genes with higher risk of cancer. In this study thefrequency of GSTM1 and GSTT1 null genotypes was determined inJapanese patients with gastric adenocarcinoma and colorectaladenocarcinoma and compared to frequencies determined in a community-basedcontrol group. The frequency of the null GSTM1 genotype in patientswith gastric adenocarcinoma (56.8%) showed a statistically significantincrease compared to the control group frequency (43.6%) (oddsratio (OR) = 1.70; 95% CI, 1.05–2.76). The frequency ofGSTM1 null individuals was also higher among all colorectaladenocarcinoma cases, but this increase did not reach statisticalsignificance. After grouping by tumor site, the GSTM1 null genotypewas a risk factor among the subgroup with distal colorectaltumors (61.1%) (OR = 2.03; 95% CI, 1.06–3.90). No consistentdifference was observed between smoking patients and correspondingcontrols for the frequency of the GSTM1 null genotype for eithercancer, although a large risk (OR = 5.76; 95% CI 1.18–28.3)was associated with the GSTM1 null genotype in the low smokinggroup of gastric adenocarcinoma patients. On the other hand,no statistically significant differences were observed in thefrequency of null GSTT1 genotypes in gastric (47.5%) or colorectal(48.5%) adenocarcinoma patients when compared with the controlpopulation (44.4%). These results suggest that the GSTM1 nullgenotype may be associated with susceptibility to gastric adenocarcinomaand distal colorectal adenocarcinoma in Japanese; however, theassociations observed were relatively weak and additional studieswill be needed to confirm these findings.     

Polymorphisms of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) in ovarian cancer risk

Glutathione S-transferases (GSTs) are ubiquitous, multifunctional phase II metabolic enzymes responsible for the detoxification of estrogen involved in the development of ovarian cancer. Data from epidemiological studies show conflicting results that remain to be further clarified. We estimated in this study the genetic effects of GSTM1 and GSTT1 polymorphisms on ovarian cancer risk. Eligible studies of the two polymorphisms and ovarian cancer risk were identified from China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Web of Science. We summarized all data and performed a meta-analysis. Odds ratio (OR) and 95 % CI was calculated by using the fixed effects model to estimate the associations. Eight eligible studies were finally identified providing 2,397 cases and 2,910 controls for GSTM1 polymorphism and 2,049 cases and 2,668 controls for GSTT1 polymorphism. The overall data showed that carries of the GSTM1 null genotype did not have significantly increased ovarian cancer risk compared with those who carried the GSTM1 present genotype (null vs. present—OR, 1.01; 95 % CI, 0.91–1.11; heterogeneity, P?=?0.672). Similarly, for GSTT1 polymorphism, we observed no association under the investigated model in the overall analysis (null vs. present—OR, 1.02; 95 % CI, 0.89–1.17; heterogeneity, P?=?0.372), and in the subgroup of Caucasian subjects (null vs. present—OR, 0.99; 95 % CI, 0.86–1.14; heterogeneity, P?=?0.959). The meta-analysis does not provide a strong evidence for causal associations between GSTM1 and GSTT1 polymorphisms and risk of ovarian cancer in Caucasians.     

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms and lung cancer risk among Northwestern Mediterraneans

Several polymorphic genes including those encoding for glutathione S- transferases (GST) have been reported to be involved in modifying lung cancer risk in smokers. The gene GSTM1 is frequently deleted in humans and a possible association between the null genotype and lung cancer risk is controversial. Another polymorphic gene of the same supergene family, GSTT1, is also involved in the detoxification of some environmental carcinogens. Both genes were genotyped in (a) a group of lung cancer patients (n = 160); (b) a group of healthy smokers (n = 120); (c) a group of blood donors from the general population (n = 192). All patients and controls were Northwestern Mediterranean Caucasians. The results show that the GSTM1 null genotype (GSTM1*0/GSTM1*0) was slightly over represented in the lung cancer patients (frequency of 58%; OR: 1.40, 95% CI: 0.74-2.61, referred to healthy smokers). The histological type most clearly modified was small cell carcinoma (frequency of 62.2%, OR: 1.91, CI: 0.78-4.69). The subdivision of the patients with one or two copies of the GSTM1 gene according to a GSTM1*A, GSTM1*B or GSTM1*A/B genotype (frequencies of 28.2%, 11.2%, 2.5% respectively) revealed no significant differences between the cases and both control groups. The frequency of the deleted GSTT1 genotype among the lung cancer patients (24%) was not significantly increased (OR: 1.08, CI: 0.57-2.05, referred to healthy smokers). The results showed that 14.4% of the patients presented homozygous deletion of both GSTT1 and GSTM1 (12.5% among healthy smokers) suggesting no potentiation between null genotypes for lung cancer risk.      

电穿孔法介导醛脱氢酶基因与多药耐药基因的转移和表达

背景与目的：将不同类型的耐药基因同时导入造血细胞,以扩大耐药范围和进行体内选择是基因治疗的重要策略,这类载体基因片段较长,进行基因转移有一定的难度。本研究旨在寻找安全有效的长片段基因转移G1Na-AIM以NdeⅠ酶切线性化,电穿孔法转导PA317细胞,经长春新碱（VCR）和4－氢过氧化环磷酰胺（4－HC）选择后,应用Southern blot法确定原病毒的整合,逆转录聚合酶链反应（RT－PCR）和流式细胞术（FCM）分析转移基因的表达,筑巢式聚合酶链反应（nested PCR)检验转移系统的安全性。结果：电穿孔法有效介导了ALDH1与MDR1基因的同时转移,Southern blot法证实ALDH1与MDR1基因稳定整合至宿主细胞基因组,RT－PCR检测到转移基因的转录,FCM测定下游基因MDR1蛋白表达增高4倍,转导率达98％。nested PCR未检测到辅助病毒（env)。结论：电穿孔法安全有效地介导了ALDH1与MDR1基因的共移和高表达。     

X-RAY REPAIR CROSS-COMPLEMENTING GROUP 1 （XRCC1） Arg 399 Gin POLYMORPHISM AND AFLATOXIN B1 （AFB1）-RELATED HEPATOCELLULAR CARCINOMA （HCC） IN GUANGXI POPULATION

In Guangxi Zhuang Autonomous Region,Hepatocellular carcinoma(HCC)is one of the maincancer killers,the incidence rate of which is5～40/1,000,000per year.Clinic-epidemiological evidencesuggests AFB1exposure is the most cause[1].However,the exact mechanisms of AFB1hepatocarcinogenesishave not been fully elucidated.Recently,there is agrowing realization that genetic constitution is ofimportance in determining individual’s susceptibility toHCC.This genetic susceptibility may result frominhe…