胸苷酸合成酶在膀胱癌组织中的表达及意义

目的探讨膀胱癌（BC）中胸苷酸合成酶（TS）的表达对膀胱癌患者预后的影响。方法采用免疫组化S-P法检测50例膀胱癌石蜡标本中的TS蛋白表达情况。结果TS蛋白在膀胱癌与正常膀胱黏膜中的表达有显著性差异（P＜0．01），与肿瘤低分化、临床病理分期晚期、淋巴结转移密切相关（P＜0．05）。结论TS在膀胱癌中的表达增强可能是膀胱癌患者一个重要的预后指标。     

胸苷酸合成酶在膀胱癌组织中的表达及意义

目的探讨膀胱癌(BC)中胸苷酸合成酶(TS)的表达对膀胱癌患者预后的影响。方法采用免疫组化S_P法检测50例膀胱癌石蜡标本中的TS蛋白表达情况。结果TS蛋白在膀胱癌与正常膀胱黏膜中的表达有显著性差异(P<0.01),与肿瘤低分化、临床病理分期晚期、淋巴结转移密切相关(P<0.05)。结论TS在膀胱癌中的表达增强可能是膀胱癌患者一个重要的预后指标。     

TS和PCNA与子宫内膜癌的相关性研究

  目的  检测子宫内膜癌中胸苷酸合成酶(TS)和细胞增殖核抗原(PCNA)的表达情况, 探讨其与子宫内膜癌预后的关系及临床意义。  方法  用免疫组化S-P法检测15例正常子宫内膜、10例子宫不典型增生、48例子宫内膜癌石蜡标本中的TS和PCNA蛋白表达情况。  结果  采用免疫染色强度与阳性细胞率法判断免疫组化结果, TS蛋白在子宫内膜癌与正常内膜中的表达有显著性差异(P=0.008), TS表达与肿瘤低分化(P=0.021)、深层浸润(P=0.010)、手术病理分期晚期(P=0.047)、淋巴结转移(P=0.022)密切相关; 子宫内膜癌中PCNA表达显著高于正常内膜(P < 0.01)。PCNA在子宫内膜癌组织中表达高于非典型增生子宫内膜, 差异有统计学意义(P=0.002)。PCNA表达程度与分化程度(P=0.010)、肌层浸润(P=0.001)有关。TS和PCNA的表达呈正相关(r=0.71, P < 0.01)。  结论  TS和PCNA在子宫内膜癌组织中的表达增加, 其表达水平与子宫内膜癌病变程度呈正相关, 可能与子宫内膜癌预后有关      

胃癌组织中胸苷酸合成酶、胸苷磷酸化酶mRNA表达及其临床意义

背景与目的:化学治疗在胃癌治疗中扮演了重要的作用。通过肿瘤组织中某些基因表达的水平来选择化疗药物已成为今后化疗的方向。胸苷酸合成酶(TS)、胸苷磷酸化酶(TP)是氟尿嘧啶(5-FU)体内的关键代谢酶,其表达水平影响恶性肿瘤患者接受5-FU化疗后的预后。本研究探讨胃癌组织中TS、TP mRNA表达水平与预后的关系。方法:采用实时定量RT-PCR技术检测51例胃腺癌组织TS、TP mRNA表达水平。结果:胃癌组织TS、TP mRNA表达水平的中位数分别为0.94和21.20,TS高表达组和低表达组之间无瘤生存期和总生存期差异有显著性(P<0.05),TP高表达组和低表达组之间总生存期差异有显著性(P<0.05),但无瘤生存期之间差异无显著性(P>0.05)。TS、TP mRNA表达与年龄、性别、淋巴结转移、组织学分级及临床分期均无相关性(P>0.05)。结论:检测TS、TP mRNA表达水平对接受5-FU为基础治疗方案的胃癌患者的预后有很好的预测价值。     

结直肠癌组织胸苷酸合成酶的表达及临床意义

目的:探讨了胸苷酸合成酶(TS)在结直肠癌组织中的表达及其与临床病理特征和预后的关系。方法:用免疫组化SP法检测72例结直肠癌组织中TS的表达,按TS表达水平将患者分为2组:高表达组和低表达组,用Kaplan-Meier法分析TS的表达与临床病理特征和预后的相关性。用多因素COX模型分析影响患者预后的相关因素。结果:在72例结直肠癌组织中TS表达从15%~95%不等,平均(49.79±25.05)%。TS的表达随Dukes分期的增加而增加,但无统计学意义(P=0.145)。早期(Dukes A~B)结直肠癌的预后明显优于晚期结直肠癌(Dukes C、D),P<0.0001。TS低表达者预后优于高表达患者。治疗前血清CEA、CA19-9水平正常者预后较好,CEA、CA19-9升高者预后较差。多因素分析显示Dukes分期、TS表达状况、CEA是影响预后的因素。结论:结直肠癌治疗前Dukes分期是影响预后的主要因素。TS的表达状况、CEA也是影响预后的参考指标。     

胸苷酸合成酶的表达及其与胃癌的相关性

目的 探讨胃癌组织中胸苷酸合成酶(TS)的表达及其与临床病理因素的关系.方法 采用免疫组织化学染色的方法(S-P法)检测了48例胃癌组织中TS基因表达情况,并用SPSS10.0统计软件分析其与临床病理因素的关系.结果 48例胃癌组织中TS基因表达的阳性率为52.1%(25/48); TS的表达与肿瘤分化程度、浸润深度、淋巴结转移与否及临床病理分期密切相关(P<0.05).结论 胃癌组织中TS表达水平可能是胃癌患者1个重要的预后指标.     

胸苷酸合成酶基因多态性与氟尿嘧啶治疗晚期胃癌疗效相关性的研究

目的：研究胸营酸合成酶（TS）基因的5’-UTR28bp核苷酸片段重复多态和3’-UTR1494修饰处存在的6bp核苷酸片段缺失或插入多态与应用以氟尿嘧啶（5-FU）为主的联合化疗方案治疗胃癌疗效的相关性。方法：收集经病理学确诊的晚期胃癌74例,所有患者使用以5-Fu为主的化疗方案治疗,化疗前抽静脉血,提取白细胞DNA用PCR—DHPLC技术检测TS5’-UTR1R28bp及3’-UTR6bp基因型：结果：（1）74例胃癌患者的TS5’-UTR28bp31t／3R、2R／2R＋21t／3R基因型分别为21．6％（16／74）和78．4％（58／74）,而相应的化疗客观有效率分别为6．3％（1／16）和36．2％（21／58）,3R／3R组的化疗疗效比2R／2R＋2R／31／绀低（X^2=4．05,P〈0．05）;（2）74例胃癌患者的TS3’-UTR＋／＋6bp、＋／-6bp、-／-6bp基因型分别为5．4％（4／74）、52．7％（39／74）和41．9％（31／74）,相应各组的化疗有效率分别为0（0／4）、25．6％（10／39）和41．9％（13／31）,不同基因型与化疗疗效之间无相天性（P=0．076）。结论：TS5’-UTR28bp多态性与5-FU疗效之间存在相关性,其检测有助于指导晚期胃癌选择5-FU化疗,而TS3’-UTR多态性与5-FU疗效之间没有显示相关性,     

胸苷酸合成酶预测胃癌化疗敏感性的研究

目的 探讨胃癌组织中TS的表达及其对胃癌DDP+5-Fu化疗敏感性的预测价值.方法 60例胃癌均接受2个周期DDP+5-Fu化疗.化疗方案:DDP 15～20 ms/(m2·d),静脉滴注,d1～5;5-Fu 375～500 mg/(m2·d),静脉滴注8h,d1～5.间隔4周后,进行第2个周期化疗.采用免疫组织化学S-P法检测胃癌组织中TS的表达.结果 60例胃癌中TS高表达者29例,化疗有效率34.5%(10/29),TS低表达者的化疗有效率为64.5%(20/31),两者比较差异具有统计学意义(P<0.05).结论 胃癌组织中TS表达水平对胃癌DDP+5-Fu化疗的敏感性具有一定预测价值.     

胸苷酸合成酶基因多态性与消化道肿瘤个体化治疗

消化道肿瘤的发生率在我国位居第一,而多数患者确诊时即为中晚期,已失去手术的机会,故化疗已成为此类患者的主要治疗手段。虽然以氟尿嘧啶（5-Fu）为基础的联合化疗可以延长胃癌、结直肠癌等晚期消化道肿瘤的生存期,但是接受此类方案中至少50％患者对化疗无效,而且同一化疗方案对不同患者的疗效可从完全缓解到无效,产生差别的主要原因在于个体间对化疗药物敏感性不同所致,近年来的各项研究逐渐表明,TS基因的多态性与患者对化疗药物的敏感性密切相关。     

子宫内膜癌中诱导型一氧化氮合酶表达及与肿瘤血管形成关系

[目的]探讨诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)在子宫内膜癌组织中表达及与肿瘤血管形成的关系。[方法]采用免疫组化S-P法检测30例子宫内膜癌组织中iNOS和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的表达和微血管密度(microvesseldensity,MVD)。[结果]iNOS在30例子宫内膜癌组织中的阳性表达率为73.3%;而对照组正常子宫内膜均未见表达。子宫肌层浸润深度>1/2的iNOS表达明显高于肌层未受累或≤1/2的患者(100%vs57.9%,P<0.05)。iNOS表达阳性组和阴性组MVD均值分别为45.6±3.5和20.8±4.5,两组比较差异有显著性(P<0.01)。iNOS的表达与VEGF及MVD均呈正相关(r=0.95,P<0.01;r=0.25,P<0.01)。[结论]iNOS在子宫内膜癌组织中的高表达与肿瘤血管形成及子宫肌层浸润程度的密切相关性,提示iNOS的高表达可能参与诱导肿瘤血管的形成。     

子宫内膜癌组织中环氧化酶-2表达及其与血管生成的关系

目的　研究环氧化酶 2 (COX 2 )在子宫内膜癌组织中的表达及其与血管生成的关系。方法　用免疫组化法检测42例子宫内膜癌和15例正常子宫内膜组织中COX 2的表达,并检测微血管密度(MVD)。结果　子宫内膜癌组织中COX 2、MVD明显高于正常子宫内膜组织(P <0 0 5 ) ,COX 2高表达与子宫内膜癌组织学分级和浸润深度有关(P <0 0 5 ) ,与临床分期、淋巴结转移和组织学分型无关(P >0 0 5 ) ,COX 2表达阳性者MVD明显高于COX 2表达阴性者(P <0 0 5 )。结论　COX 2过表达可能参与子宫内膜癌发生发展过程,且与子宫内膜癌新生血管形成有关。     

A Novel Approach to Cloning and Expression of Human Thymidylate Synthase

Thymidylate synthase (TS) catalyzes the transfer of a methyl group from methylenetetrahydrofolate to dUMPto form dTMP. It is a primary target in the chemotherapy of colorectal cancers and some other neoplasms. Inorder to obtain pure protein for analysis of structure and biological function, an expression vector TS-pET28b(+) was constructed by inserting wild-type human thymidylate synthase (hTS) cDNA into pET28b (+). Then anexpression strain was selected after transformation of the recombined plasmid into Rosetta (DE3). Fusion proteinwith His-tag was efficiently expressed in the form of inclusion bodies after IPTG induction and the content wasapproximately 40.0% of total bacteria proteins after optimizing expression conditions. When inclusion bodieswere washed, dissolved and purified by Ni-NTA under denatured conditions, the purity was up to 90%. OnSDS-PAGE and West-blotting, the protein band was found to match well with the predicted relative molecularmass-36kDa. Bioactivity was 0.1 U/mg. The results indicated that high-level expression of wild-type hTS cDNAcan be achieved in prokaryotes with our novel method, facilitating research into related chemotherapy.     

Correlation between Thymidylate Synthase Genotype and Susceptibility to Gastric Carcinoma

Objective  To investigate the correlation between polymorphism of the 5′-untranslated region (5′-UTR) of thymidylate synthase genes, as well as the lifestyle, and the susceptibility of gastric carcinoma. Methods  A case-control study, with 60 cases of gastric carcinoma and 170 cases of general risk population-based controls from Nantong, Jiangsu province, China, was conducted. The epidemiological data, such as living habits of the cancer patients, were collected. DNA of peripheral blood leukocytes was obtained from all of the subjects. The TS 5′-UTR tandem repeat genotype was detected using polymerase chain reaction (PCR). Results  There were three TS 5′-UTR genotypes in the group of gastric cancer cases (2R/2R, 2R/3R and 3R/3R) and six TS 5′-UTR genotypes in the group of the controls (2R/2R, 2R/3R, 3R/3R, 2R/4R, 2R/5R and 3R/4R). The genotypic frequencies were respectively 5.0%, 43.3% and 51.7% in the gastric cancer group. Compared with the parameters in the control group, i.e., 4.7%, 31.7%, 60.6%, 1.2%, 1.2% and 0.6%. There were no significant differences between the two groups. Compared with the 3R/3R-genotype individuals who where non-smokers, drank alcohol twice or less each week, drank tea and did not intake pickled food (PF), the risk of gastric cancer significantly went up in the 2R/2R or 2R/3R-genotype people who had habits of smoking, drinking alcohol more than twice each week, no tea drinking but with frequent intake of PF. The adjusted ORs were as follows, 3.79 (95% CI: 2.45∼8.64), 3.41 (95% CI: 1.21∼8.47), 5.99 (95% CI: 3.01∼14.7), and 3.61 (95% CI: 1.81∼8.78). Conclusion  There is an obvious correlation between the polymorphisms of TS 5′-UTR genotypes and the lifestyle of individuals in the development of gastric carcinoma. The work was supported by a grant from Nantong Municipal Bureau of Public Health, Jiangsu Province, China (2006 [No.29]).     

MIR-379-5p Expression in Endometrial Cancer and Its Correlation with ROR1 Expression

Objective: To asses miR-379-5p expression in endometrial cancer (EC) and its correlation with ROR1 expression and to investigate the relation between miR-379-5p and ROR1 expressions and the clinicopathological picture of EC. Methods: Fifty female of EC were joined to this study. The gene expression of miR-379-5p (by quantitative real time-PCR) and ROR1 (by quantitative real time-PCR and immunohistochemistry) were studied in EC and normal nearby endometrial tissue. Results: The gene expression of miR-379-5p was significantly downregulated while that of ROR1 was significantly upregulated in EC tissues compared to adjacent normal endometrial tissues. Furthermore, miR-379 and ROR1 expressions significantly associated with tumor stage (P< 0.045), grade (P< 0.001), myometrial invasion (P <0.001) and LN metastasis (P< 0.034). In addition, miR-3795p and ROR1 gene expression were negatively correlated (r = -0.746, P < 0.001). Conclusions: In EC, miR-379-5p can be used as a diagnostic marker, and ROR1 could be a potential target of miR-379-5p.     

松弛素在正常、不典型增生性子宫内膜和子宫内膜癌中的表达

[目的]探讨松弛素（relaxin，RLx）对子宫内膜癌的可能作用。[方法]采用免疫组织化学方法检测正常子宫内膜（12例）、不典型增生性子宫内膜（16例）和子宫内膜癌（42例）中RLx的表达情况。[结果]RLx阳性物质定位于子宫内膜腺上皮细胞的胞质中。RLx在正常子宫内膜、不典型增生性子宫内膜和子宫内膜癌中的阳性表达率分别为50．00％、93．75％、95．24％，高表达率分别为0、68．75％、50．00％。正常子宫内膜、不典型增生性子宫内膜和子宫内膜癌三者中RLx阳性表达率和高表达率的差异均有统计学意义。[结论]RLx在不典型增生性子宫内膜和子宫内膜癌中的高表达可能成为临床诊断和治疗的新靶点。