胰腺癌细胞株化疗敏感性与胸苷酸合成酶蛋白表达的关系

目的 探讨胸苷酸合成酶(TS)在胰腺癌细胞中的表达及其蛋白表达水平与胰腺癌细胞化疗敏感性的关系.方法 利用CCK-8试剂盒检测7株胰腺癌细胞(AsPC-1、BxPC-3、Capan-1、SU86.86、T3M4、PANC-1与COLO357)对5-氟脲嘧啶(5-Fu)的化疗敏感性,应用Western blot检测其TS蛋白表达.结果 细胞株AsPC-1、BxPC-3、Capan-1、SU86.86、T3M4中TS蛋白表达水平低(低TS表达组),而PANC-1与COLO357中TS蛋白表达水平较高(高TS表达组),低TS表达组的细胞在低中高3个不同药物浓度下对5-Fu抑制率分别为0.683±0.131、0.769±0.114与0.836±0.094.同浓度下高TS表达组的细胞对5-Fu抑制率分别为0.370±0.157、0.548±0.018与0.638±0.020.TS蛋白表达低的细胞对5-Fu化疗敏感性明显高于TS表达高的细胞,差异有统计学意义(P＜0.05).结论 在胰腺癌细胞株中,TS蛋白表达水平与其对5-Fu的化疗敏感性密切相关.     

乳腺癌患者胸苷酸合成酶基因多态性及其与临床病理的关系

目的 研究胸苷酸合成酶(thymidylate synthase,TS)基因多态性在汉族女性乳腺癌患者中的分布特点及其与临床病理之间的关系.方法收集经病理学确诊的83例初诊乳腺癌患者外周静脉血,术前均未给予任何针对乳腺癌的治疗,应用聚合酶链反应限制性片段长度多态性技术(PCR-RFLP)检测墓因型.基因多态性与临床病理的关系采用卡方分析进行检验.结果 83例乳腺癌患者的基因分布情况为:(1)3R/3R、2R/3R及2R/2R 3种基因型的频率分别为68.7%、27.7%、3.6%;(2)按G→C单核苷酸多态性细分,2R/2R,2R/3C,2R/3G,3G/3G,3C/3C及3G/3C 6种基因型的频率分别为3.6%、19.3%、8.4%、19.3%、37.3%及12.1%;(3)+/+6 bp、+/-6 bp及-/-6 bp3种基因型的频率分别为8.4%、50.6%及41.0%;(4)3种基因多态性均与乳腺癌的组织学分级相关(P＜0.05);另外TS 5′-UTR多态性与淋巴结转移(P=0.019)、Ki67(P=0.022)相关,TS 3′-UTR多态性与发病年龄相关(P=0.002),G→C单核苷酸多态性与淋巴结转移相关(P=0.021).结论 汉族女性乳腺癌患者中3R/3R、-/-6 bp基因型频率较高;TS基因多态性与乳腺癌临床病理因素密切相关.     

原发性胃肠恶性肿瘤胸苷酸合成酶增强子的多态性

目的　检测原发性胃癌、结直肠癌胸苷酸合成酶 (TS)启动基因增强子区段 (TSER)的多态性。方法　采用多聚酶链式反应 (PCR)技术检测 16 0例原发性胃肠恶性肿瘤患者 (胃癌、结直肠癌各 80例 )肿瘤原发灶TSER的表达 ,并测定其DNA序列。结果　 12例表现为双串联重复系列纯合子 ( 2R/ 2R) ,10 9例为三串联重复系列纯合子 ( 3R/ 3R) ,39例为双串联和三串联杂合子( 2R/ 3R) ,而且胃癌与结直肠癌TSER表达差异无显著性 (P >0 .0 5 )。结论　胃肠恶性肿瘤TSER存在多态性 ,表现为纯合子 2R/ 2R、3R/ 3R及两者的杂合子 2R/ 3R ,其中以纯合子 3R/ 3R为主。     

胸苷酸合成酶基因表达与结肠直肠癌复发的关系及其临床意义

目的 探讨胸苷酸合成酶（ＴＳ）基因表达与结、直肠癌复发的关系及其对临床治疗的影响。方法 对６８例结、直肠癌患者采用ＲＴ－ＰＣＲ方法检测大肠癌原发灶、癌旁肠粘膜、局部复发灶、腹腔盆腔内播散和肝转移灶中ＴＳ基因的表达;用Ｗｅｓｔｅｒｎ Ｂｌｏｔ方法检测ＴＳ蛋白达表。结果 ６８例结肠直肠癌原发灶、局部复发灶、腹腔及盆腔内播散和肝转移灶中ＴＳ基因表达阳性率分别为２２．１％（１５／６８）、８８．５％（２３／     

胸苷酸合成酶在乳腺癌中的表达及其与预后的关系

目的:研究乳腺癌组织中胸苷酸合成酶(thymidylate synthase,TS)的表达水平,评估TS作为5-氟尿嘧啶(5-FU)化疗敏感性的判断指标的可行性。方法:应用S-P免疫组化方法检测94例乳腺癌组织和40例乳腺非癌组织中TS的表达情况及其与临床各病理参数的关系。结果:①TS低表达率为55.3%(52/94),高表达率44.7%(42/94),与良性对照组比较有显著差异(P0.05)。③TS高表达组的5年生存率为26.5%,TS低表达组的5年生存率为58.7%。TS低表达组的生存期及5年生存率均高于TS高表达组,差异有统计学意义(P<0.05)。结论:乳腺癌组织中TS的表达与病人对5-FU化疗敏感性及预后密切相关,可作为判断5-FU化疗敏感性及预后的指标。     

胃癌胸苷酸合成酶表达与耐药的关系及耐药逆转的研究进展

胸苷酸合成酶(thymidylate synthase,TS)是DNA生物合成反应中的关键酶,所以其编码基因成为许多化学药物治疗癌症的靶基因,比如胃癌化疗中常用的5-氟尿嘧啶(5-fluoropyrimi-dines,5-Fu)。随着对肿瘤耐药的深入研究,逐渐发现了TS与耐药之间的关系。现综述胃癌TS表达水平与耐药之间的关系、原理、TS测定方法及耐药逆转的研究进展等。     

膀胱移行细胞癌组织中胸苷酸合成酶启动基因的测定

胸苷酸合成酶（TS）是合成胸苷酸的限速酶，在肿瘤细胞DNA合成过程中起着重要的作用。本研究检测膀胱移行细胞癌（BTCC）组织中TS启动基因及其产物TS蛋白的表达，探讨TS启动基因与BTCC浸润的关系。     

胸苷酸合成酶的表达及其与胃癌的相关性研究

目的探讨胃癌组织中胸苷酸合成酶(TS)的表达对胃癌患者预后的影响。方法采用免疫组织化学染色的方法(ABC法)检测了164例胃癌(ⅠB～Ⅳ期)石蜡标本中的TS基因的表达情况。结果164例标本中TS基因表达的阳性率为48.8%(80/164),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<0.001),且TS表达阴性患者的5年生存率(52.4%)明显高于TS表达阳性者(12.3%,P<0.001)。多因素分析显示,肿瘤的病理分化程度、浸润深度和TS表达状态3者与生存率有相关性(P<0.05),其中TS的表达状态与患者5年生存率关系最为密切(P<0.0001),相对危险系数为1.197。结论胃癌组织中TS表达水平的高低可能是胃癌患者一个重要的预后指标,对临床医生选择化疗方案具有一定的指导意义。     

Smac基因调控肿瘤化疗敏感性的研究进展

细胞凋亡异常是肿瘤细胞产生耐药性的关键因素之一。Smac是近年新发现的一种由线粒体释放的促凋亡蛋白，参与细胞凋亡的线粒体通路和死亡受体通路的下游反应，通过特异性地结合凋亡抑制蛋白lAPs，解除后者对caspase的抑制而促进凋亡。肿瘤组织中Smac存在不同程度的缺失和释放障碍，利用基因转导手段将Smac基因导入胃癌细胞，提高常用的对胃癌敏感化疗药物对胃癌细胞株的诱导调亡作用，具有广泛的应用前景和现实的临床指导意义。     

DNA修复基因多态性与膀胱肿瘤的关系

DNA修复基因多态性对维持基因组的稳定性有重要作用,基因突变与膀胱肿瘤的发生、发展关系密切。近年来,DNA修复基因多态性在肿瘤发生中的作用成为研究热点。     

Expression of thymidylate synthase determines the response of gastric cancer patients undergoing gastrectomy to 5-fluorouracil-based adjuvant chemotherapy

Purpose  

We investigated whether the intensity of thymidylate synthase (TS) staining in tissue samples obtained from gastric cancer (GC) patients undergoing gastrectomy could predict response to 5-FU-based adjuvant chemotherapy after gastrectomy.     

Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA in intrahepatic cholangiocarcinoma

Purpose  

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil and possible predictive markers. We conducted this study to clarify if TS and DPD gene expressions are a prognostic indicator for intrahepatic cholangiocarcinoma (IHCC).     

胸甘酸合酶mRNA在膀胱癌中的表达及其临床意义

目的　探讨膀胱癌组织中胸苷酸合酶 (TS)基因的表达水平及临床意义。方法　从连续获得的 5 2例确诊为膀胱癌的组织样本中提取总RNA ,采用逆转录 聚合酶链反应 (RT PCR)检测所有肿瘤样本中胸苷酸合酶mRNA水平。结果　浸润性膀胱癌的TSmRNA水平较表浅性膀胱癌显著增高 (P <0 .0 5 )。发生血管浸润的膀胱癌中TSmRNA水平明显高于没有发生血管浸润的肿瘤 (P <0 .0 5 ) ,伴有转移的膀胱癌中TSmRNA表达明显高于非转移者 ,差异有非常显著性(P <0 .0 0 1)。结论　TSmRNA的表达水平与膀胱癌分期有关 ,可能是提示膀胱癌有无转移和血管浸润的指标之一。     

High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase

OBJECTIVE: To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue. MATERIALS AND METHODS: Tissue from 79 patients with localized prostate cancer was used. Thymidylate synthase and dihydropyrimidine dehydrogenase expression were determined semiquantitatively by immunohistochemistry. RESULTS: Thymidylate synthase and dihydropyrimidine dehydrogenase immunostaining grades of benign tissue were significantly higher than those of cancer tissue (both P < 0.01). Cancer tissue with a primary Gleason grade of > or = 4 expressed a higher thymidylate synthase staining grade than those with a primary Gleason grade of <4 (P < 0.01). Cancer tissue spots from patients treated with neoadjuvant therapy revealed significantly higher thymidylate synthase and dihydropyrimidine dehydrogenase grades than those with no neoadjuvant therapy (P < 0.01). CONCLUSION: High thymidylate synthase expression in localized prostate cancer might reflect an aggressive status. High expression in high-grade prostate cancers and prostate cancers after hormonal therapy suggest that thymidylate synthase could be a new therapeutic target for advanced prostate cancer.     

Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in gallbladder carcinoma

Purpose

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil, which have been examined as possible predictive markers. We conducted this study to clarify the role of TS and DPD expressions in gallbladder carcinoma (GBC).

Methods

The subjects were 28 patients who underwent surgical resection of GBC. We examined intratumoral TS and DPD mRNA expressions, using the Danenberg tumor profile method. The expression levels were classified into two groups, based on median values. Clinicopathological variables, including prognosis, were then compared between the high and low expression groups.

Results

There was a significant difference in the incidence of lymph node metastasis between the high and low TS expression groups. The incidence of advanced clinical stage was higher in the low TS expression group than in the high TS expression group. However, no clear correlation was observed between the DPD mRNA expression and any clinicopathological variable. There was no significant difference in the postoperative survival rates between the groups, in accordance with the expression of TS or DPD genes.

Conclusion

Low TS mRNA was correlated with a high incidence of lymph node metastasis and advanced clinical stage. Therefore, TS gene expression may help identify patients at increased risk of the progression of GBC.