肾细胞癌中内皮素-1及其受体表达与肿瘤细胞凋亡

[目的] 探讨肾癌组织中内皮素-1（endothelin-1，ET-1）、内皮素受体（endothclin receptor，ETR）的表达及其对肾癌影响的机制。[方法]采用免疫组化SABC法对46例肾癌组织及10例正常肾组织的石蜡标小切片进行染色，检测ET-1及内皮素受体A（endothelin receptor A，ETAR）的表达，原位DNA片段末端标记检测肾癌细胞凋亡状态，分析ET-1及其受体与肾癌细胞凋亡的关系。[结果] ET-1及ETAR在肾癌组织中表达主要位于胞质，阳性表达率分别为45.65％、80．43％，显著高于正常肾组织（30％），ETAR的表达与肿瘤的分级及预后密切相关（P＜0．05），与分期无关，与肿瘤细胞的凋亡呈负相关。[结论] ET-1及ETAR可能通过自分泌或旁分泌途径抑制肾癌细胞的凋亡而促进肿瘤细胞的生长，后者对肾癌患者预后有一定的判断作用。     

鼻咽癌中p73蛋白表达与细胞凋亡关系

p73基因是抑癌基因p53基因家族的一个新成员, 一般认为它能以p53同样的方式激活p53的靶基因, 抑制细胞生长, 诱导凋亡^[1]。     

凋亡素体外诱导表达Survivin膀胱癌细胞凋亡效果观察

目的:观察凋亡素对表达Survivin膀胱癌细胞株的作用效果,并结合相应机制探讨其临床意义.方法:利用免疫组织化学法检测膀胱癌细胞株BIU-87中Survivin的表达水平,并计算平均每高倍镜视野中阳性细胞比率.将肿瘤细胞分为单纯细胞组、转染空质粒pCDNA3组及转染pCDNA3/Apoptin组,利用脂质体转染法将真核表达栽体pCDNA3/Apoptin及pCDNA3空质粒转染入膀胱癌细胞中,并于转染后24h通过RT-PCR法检测细胞中Apoptin的表达情况.分别于转染后24、48、72h利用MTT法检测各组细胞存活率,并利用流式细胞仪TUNEL法检测各组细胞的凋亡率.结果:利用免疫组织化学法检测发现膀胱癌细胞株BIU-87中Survivin呈高表达状态,平均每个高倍镜视野中阳性细胞比例约70%,并有较多细胞呈现高表达状态.转染后24h通过RT-PCR法可见Apoptin在膀胱癌细胞中表达.分别于转染后24、48、72h利用MTT法检测各组细胞存活率,发现转染pCDNA3/Apoptin组肿瘤细胞存活率均明显低于对照组,差别有统计学意义(P<0.05);利用流式细胞仪TUNEL法检测各组细胞的凋亡率,发现转染pCDNA3/Apoptin组肿瘤细胞凋亡率均明显高于对照组,差别有统计学意义(P<0.05).结论:凋亡素可在体外诱导高表达Survivin的膀胱癌细胞株BIU-87高效凋亡,结合相关机制表明凋亡素可在一定程度上克服Survivin的抗凋亡作用,因此有可能成为Survivin拮抗的抗肿瘤药物的协同用药选择.     

凋亡相关因子在肿瘤细胞凋亡中的表达

目前认为,肿瘤的发生发展不仅是细胞增殖失控、分化异常的结果,而且与细胞凋亡失衡有关.引发肿瘤细胞凋亡已成为目前临床应用的肿瘤治疗手段之一.     

凋亡细胞指数与肿瘤预后

本文主要缩述凋亡细胞的辨认、凋亡细胞九的计算及凋亡细胞与肿瘤预后的关系。     

细胞凋亡和相关基因Fas在睾丸肿瘤中表达的研究

目的　探讨细胞凋亡和相关基因Fas蛋白在睾丸肿瘤发生发展中的作用。方法　应用DNA末端标记、流式细胞术和细胞免疫荧光技术检测 5 6例睾丸肿瘤细胞凋亡状态及凋亡相关基因Fas蛋白的表达。结果　凋亡指数与肿瘤病理类型和淋巴结转移密切相关 (P <0 .0 5 )。Fas蛋白的表达与肿瘤病理类型有关 ,但无显著性差异 (P >0 .0 5 )。凋亡指数与Fas蛋白表达呈正相关 (P <0 .0 5 )。结论　细胞凋亡及相关基因Fas蛋白异常表达在睾丸肿瘤发生中有重要作用     

前列腺肿瘤与细胞凋亡

前列腺肿瘤与细胞凋亡中国人民解放军海军总医院（１０００３７）张曼综述赵晓航，鹿尔训审校细胞凋亡（ａｐｏｐｔｏｓｉｓ）是细胞自主死亡的一种形式，它受到一系列特殊基因的控制。细胞凋亡与细胞分化、增殖共同对组织多少与形态的维持起着调节作用。在文献中一般将细...     

抗肿瘤放疗与细胞凋亡

放射治疗是肿瘤综合治疗手段之一，但是由于肿瘤细胞可产生对射线的抗拒作用，最后导致肿瘤治疗失败。本文就射线诱发细胞凋亡现象，作用机制以及有丝分裂死亡关系和临床转归进行了综述，以期探讨射线对肿瘤的杀伤机制，进而指导临床肿瘤放疗。     

Survivin mRNA和蛋白在大肠癌组织中表达及与细胞凋亡的关系

目的研究Survivin基因 mRNA拷贝数、蛋白表达在大肠癌诊断、预后等方面的意义及与细胞凋亡间的关系。方法分别采用分子信标荧光绝对定量PCR、S-P免疫组化和TUNEL法，检测Survivin mRNA拷贝数、蛋白表达及细胞凋亡指数。结果Survivin mRNA拷贝数和蛋白表达阳性率，肿瘤组织显著高于正常组织；凋亡指数AI，肿瘤组织显著低于正常组织（P〈0.05）。肿瘤组织中Survivin mRNA拷贝数与淋巴结转移和病理类型显著相关；蛋白表达阳性率与肿瘤部位和患者生存状况显著相关，蛋白表达阴性组AI显著高于阳性组（P〈0.05）。Survivin mRNA拷贝数与蛋白表达无相关性（P〉0.05）。结论Survivin mRNA和蛋白在大肠癌中表达上调，可作为判断预后的生物学指标。     

Reactivation of death receptor 4 (DR4) expression sensitizes medulloblastoma cell lines to TRAIL

Object Apoptosis, a key cellular response to therapeutic agents is often inactivated in tumor cells. In this study, we evaluated the expression of the tumor necrosis family of death receptors, DR4 and DR5, in medulloblastoma tumor samples and cell lines to determine if epigenetic modulation of gene expression could sensitize tumor cell lines to TRAIL-mediated apoptosis. Methods Human medulloblastoma samples and cell lines were analyzed for DR4 and DR5 expression by quantitative PCR and immunofluorescence assays. Cell lines with downregulated expression of one or both genes were treated with the histone deacetylase inhibitor, MS-275, and the expression of DR4 and DR5 measured by quantitative PCR, Western blotting, flow cytometry and chromatin immunoprecipitation assays. Induction of apoptosis in the presence of MS-275 was evaluated by TUNEL assay and its ability to augment TRAIL-mediated cytotoxicity was determined by MTT assays, Western blotting and flow cytometry. Results Compared to normal cerebellum, DR4, but not DR5 expression was consistently downregulated in medulloblastoma tumor samples and in Daoy and D283 cell lines. Interestingly, MS-275 decreased cell growth and induced apoptosis in Daoy and D283 cells. In Daoy cells, this coincided with increased histone H3 and H4 acetylation at the DR4 promoter and enhanced DR4 gene and protein expression as well as elevated Caspase-8 activity. The involvement of DR4 in the cellular response to MS-275 was further confirmed by the observation that knockdown of DR4 and FADD abrogated apoptosis. Further, addition of TRAIL to MS-275 treated cells resulted in an enhancement of apoptosis, suggesting that the upregulated death receptors were functional. Conclusion Our study provides an understanding of the role of DR4 in apoptosis of medulloblastoma cell lines and suggests a potential contribution of aberrant histone deacetylation to the resistance of medulloblastoma cells to therapeutic death. This work was supported in part by Award P50CA127001 from the National Cancer Institutes and Grants from the National Brain Tumor Foundation and the American Cancer Society-IRG to VG.     

原发性大肠癌CD44v mRNA表达与DNA含量的关系

目的:探讨原发性大肠癌中CD44v mRNA表达与癌细胞DNA含量之间的关系及其临床意义.方法:应用RT-PCR法检测72例大肠癌中CD44v mRNA的表达情况,并根据CD44v mRNA的表达情况(阴性及微弱表达17例为Ⅰ组,中高度以上表达者55例为Ⅱ组)检测其癌细胞DNA干系水平.结果:72例受检标本中,CD44v mRNA中度以上表达55例(76.39%),其中有淋巴结转移者为93.62%(44/47),无淋巴结转移者为44.00%(11/25).在DNA干系水平方面,Ⅰ组病例二倍体明显高于Ⅱ组病例,异倍体则明显低于Ⅱ组病例(P<0.01).结论:CD44v mRNA的高表达与大肠癌的侵袭转移关系密切,CD44v mRNA表达与大肠癌细胞DNA干系水平的变化一致,再次证实了CD44v mRNA表达在大肠癌侵袭转移中的重要性     

Over-expression of Reticulon 3 (RTN3) enhances TRAIL-mediated apoptosis via up-regulation of death receptor 5 (DR5) and down-regulation of c-FLIP

Reticulons (RTNs) are a group of integral membrane proteins that have no homology to other known apoptosis-related domains. Herein, we found that RTN3 overexpressing Caki cells were sensitive to TRAIL-mediated apoptosis. RTN3-induced down-regulation of c-FLIP was recovered by pan-caspase inhibitor, z-VAD to basal levels in TRAIL-treated cells. The forced expression of c-FLIP attenuated the TRAIL-mediated apoptosis in RTN3 over-expressing cells. In addition, RTN3 over-expression provoked the enhanced protein levels in DR4 and DR5 as well as levels in DR5 surface protein but slight increase in DR4 surface protein. RTN3-mediated enhancement of TRAIL-induced apoptosis was markedly blocked by the DR5/Fc chimera or DR5 siRNA, indicating that the sensitization by RTN3 was mainly mediated through interactions of TRAIL with its receptors, DR5. Over-expression of RTN3 also enhanced TNF-α and Fas-mediated apoptosis. Taken together, over-expression of RTN3 might increase DR5 surface protein and concomitantly more activate caspase pathways, which cause the c-FLIP cleavage and enhancement of TRAIL-mediated apoptosis.     

来曲唑对子宫肌瘤细胞体外增生的作用

目的探讨芳香化酶抑制剂来曲唑对子宫肌瘤细胞芳香化酶P450（P450arom）、雌二醇（E2）表达以及对细胞增生的作用,为子宫肌瘤药物治疗提供实验依据。方法体外培养子宫肌瘤细胞,不同浓度来曲唑干预后,应用四甲基偶氮唑蓝（MTT）法检测细胞增生活性,RT—PCR和免疫细胞化学检测P450arom表达,放射免疫法测定E2含量。结果低浓度（0．06μmol／L）来曲唑对肌瘤细胞P450arom表达和E2分泌无明显影响（P〉0．05）,高浓度（0．6～6μmol／L）来曲唑显著降调P450arom表达（P〈0．05）,抑制E2生成和肌瘤细胞增生,差异有统计学意义（P〈0．05）。且随着药物浓度递增,抑制作用逐渐增强。结论芳香化酶抑制剂来曲唑以浓度依赖性方式,降调P450arom表达、减少E2生成,抑制肌瘤细胞的体外增生。     

化疗药物对人肺腺癌细胞死亡受体DR4与DR5表达影响的研究

目的:研究化疗药物依托泊苷(Vp16)、顺铂(DDP)、多西他赛(TXT)对A549细胞死亡受体( death receptor, DR) DR4DR5基因表达的影响。方法:采用逆转录聚合酶链反应(PT PCR)方法对亚毒性剂量Vp 16 、DDP和TXT作用不同时间后的人肺腺癌细胞株A549 细胞的死亡受体DR4、DR5 的mRNA表达进行半定量检测。结果:1)亚毒性剂量Vp 16 可上调A549 细胞DR4、DR5 基因表达。7 5μg/mL Vp 16 处理A549 细胞8 h后, DR4/βactin、DR5/βactin 的比值分别为1. 13±0. 13 和1 .06±0. 25。7 5μg/mL Vp 16处理A549细胞12 h后,DR4/βactin、DR5/βac tin的比值分别为1 .18±0 .20和1.02±0. 02,两者与对照组之间比较,差异均有统计学意义,P<0 .05(P值分别为0 .04、0 02、0. 00和0 .02)2)亚毒性剂量DDP和TXT对A549细胞DR4DR5基因转录水平无明显影响。5μg/mLDDP、0 005μmol/L TXT (约为4 ng/mL) 作用A549细胞4、8 h后DR4、DR5基因转录水平与对照组之间比较,差异无统计学意义,P>0 .05结论:药物干预对TRAIL凋亡通路以及耐药机制的影响存在多样性。部分化疗药物可上调肿瘤细胞死亡受体DR4、DR5基因表达,同时不排除其他作用机制的存在。     

子宫乳头状浆液性癌的临床病理分析

目的探讨子宫乳头状浆液性癌的临床病理特点．预后及治疗方法。方法对我院1984．1～1998．1间收治的6例子宫乳头状浆液性癌的临床资料进行回顾性分析。结果子宫乳头状浆液性癌6例,占同期子宫内膜癌的7％,患者平均年龄62岁。病检：单纯型4例、混合型2例;病理分级均为Ⅱ、Ⅲ级,3例有淋巴／血管间隙受浸,3例复发（50％）。结论UPSC的临床及病理学特点与一般子宫内膜癌不同,具有高侵袭性,易子宫扩散,预后差,应采取相应治疗措施。     

Net Survival of Elderly Patients with Gynecological Cancer Aged Over 75 Years in 2006-2008

Background: The number of elderly patients with gynecological cancer in Japan is increasing in line with the agingof society. However, little has been reported on the survival of elderly patients aged 75 or older with gynecologicalcancer in Japan. Methods: To clarify survival in women aged 75 years or older with gynecological cancer, we analyzeddata of 4,089 gynecological cancer cases (cervical cancer, 1,309 cases; endometrial cancer, 1,319 cases; and ovariancancer, 1,461 cases) in patients aged 75 or older from 21 population-based cancer registries in Japan, diagnosed in2006-2008. We calculated the net survival (NS) of younger (75-79 years old), older (80-84 years old) and the oldestage group (85-99 years old). We also calculated NS stratified by extent of disease and histological type. Results: FiveyearNS of cervical cancer patients was 54.5% in the younger age group, 40.8% in the older age group and 28.2%in the oldest age group. Five-year NS of endometrial cancer patients was 64.5%, 51.6% and 39.0% in the younger,older and oldest age groups, respectively. Five-year NS of ovarian cancer was 34.7%, 18.8% and 8.3%, respectively.Conclusion: We estimated NS in elderly patients aged 75 years or older with gynecological cancers in Japan usingdata from population-based cancer registries.     

表没食子儿茶素没食子酸酯的抗肿瘤机制

 表没食子儿茶素没食子酸酯(EGCG)是一种具有抗肿瘤活性的天然药物,可通过抑制肿瘤细胞增殖、血管生成及促进肿瘤细胞凋亡等机制发挥抗肿瘤作用。EGCG在抗消化系统、生殖系统、呼吸系统等肿瘤的机制研究中取得的新发现,缩短了EGCG应用于临床肿瘤治疗的进程。     

放疗对宫颈鳞癌细胞凋亡及FHIT基因表达的影响

目的: 探讨放疗对宫颈癌FHIT蛋白表达、细胞凋亡的影响及FHIT蛋白与细胞凋亡的关系.方法:采用免疫组织化学和TUNNEL标记法检测50例ⅡB-ⅢB期宫颈癌患者在放疗前、放疗中(Dt 10、30 Gy)和放疗结束后,宫颈癌组织中FHIT蛋白表达水平的改变与细胞凋亡情况.结果:50例患者在放疗Dt 10、30Gy和放疗结束时FHIT蛋白表达的阳性率分别为56%、68%和84%,与放疗前的36%相比,表达率明显升高,差异有统计学意义(P＜0.05);细胞凋亡阳性率分别为52%、64%和78%,与放疗前的28%相比,亦明显升高(P＜0.05);随着放疗进展,细胞凋亡阳性率与FHIT蛋白表达的阳性率呈正相关(P＜0.05).结论:放疗能增强FHIT蛋白表达,同时诱导细胞凋亡;FHIT蛋白在放射线诱导的细胞凋亡过程中可能起调控作用.     

胰岛素样生长因子l及其受体对子宫肌瘤生长的影响

目的 测定胰岛素样生长因子1(IGF 1)及其受体(IGF 1R)在子宫肌瘤患者的子宫平滑肌瘤组织、血清中的表达,旨在探讨IGF 1、IGF 1R在子宫肌瘤发病机制中的作用。方法 采用酶联免疫吸附实验(ELISA)方法,测定26例子宫肌瘤患者子宫平滑肌瘤、正常子宫平滑肌组织及血清中IGF1、IGF 1R的表达,每例患者充当组织测定的自身对照,选择30例健康妇女作为血清测定的对照组。结果 ①子宫平滑肌瘤组织中IGF 1、IGF 1R的表达较正常子宫平滑肌增强,进行统计学分析,两组差异有显著性(P<0.01)。②子宫肌瘤患者血清中IGF-1表达与对照组差异无显著性(P>0.05);IGF1R表达较对照组增强,两组差异有显著性(P<0.01)。结论 由此推测子宫平滑肌瘤组织中IGF 1、IGF 1R过度表达可能是子宫肌瘤发生的机制之一,IGF 1主要以自分泌、旁分泌作用方式促进肌瘤的生长,IGF 1可能是子宫肌瘤生长的调节因子。