硫化氢对肝硬化大鼠肝脏survivin表达的影响

目的:探讨抗凋亡因子存活素(survivin)在硫化氢(hydrogen sulfide,H2S)干扰的肝硬化大鼠肝脏中的表达量,了解H2S在肝硬化过程中可能的作用机制.方法:♀SD大鼠经复合因素法复制肝硬化模型,造模结束后随机分为S组、P组、C组,分别腹腔注射硫氢化钠(sodium hydrogen sulfide,NaSH)56mg/(kgd)、炔丙基甘氨酸(Propargylglycine,PPG)30mg/(kgd)及等量生理盐水,用敏感硫电极法检测肝硬化大鼠门静脉中H2S的量,用免疫组织化学及realtime-PCR检测大鼠肝脏survivin蛋白及mRNA表达.结果:S组、P组与C组相比,门静脉血浆内H2S浓度显著改变(51.19mol/L±8.75mol/L,68.97mol/L±2.69mol/Lvs134.49mol/L±12.25mol/L,P<0.05),肝硬化H2S增加组大鼠survivin蛋白及mRNA表达显著增加(P<0.05),肝硬化大鼠体内H2S与survivin表达有相关性.结论:在大鼠肝硬化模型中,随着体内H2S浓度的变化,survivin蛋白及mRNA表达发生变化,这可能是H2S调节肝硬化作用过程中的机制之一.     

CA9基因对促进肾透明细胞癌786-O凋亡的作用机制

目的探讨抑制人CA9基因后促进肾透明细胞癌(ccRCC)786-O凋亡的作用机制。方法将5⁶万个培养的786-O细胞去血清培养8 h使细胞同步化,将慢病毒液体以1∶10 000细胞数的比例加入到培养皿中,8 h更换含血清的培养基,培养72 h后荧光显微镜下观察转染效率,采用四甲基偶氮唑盐(MTT)法观察786-O细胞活性的变化,流式细胞仪检测细胞的凋亡情况,Western印迹法检测786-O细胞Survivin蛋白的表达变化。结果慢病毒转染抑制CA9表达水平后,ccRCC786-O细胞系细胞活性降低(63±4)%,细胞凋亡增加(23.4±2)%,Western印迹法检测Survivin蛋白的表达降低(43.1±3)%。结论通过慢病毒转染抑制CA9的表达可以影响ccRCC 786-O细胞活性,促进细胞凋亡,CA9可能是通过调控Survivin基因的变化影响细胞的增殖和凋亡。     

Treat cancers by targeting survivin: Just a dream or future reality?

Since the discovery of survivin (BIRC5) as a cancer-related molecule by Grazia Ambrosini and Dario C. Altieri at 1997, our knowledge related to the function of this molecule has been extended from simple apoptosis inhibition to complicated, interlinked processes that involve interference of mitosis, apoptosis, autophagy, and even DNA repair recently. However, despite the growing amount of knowledge related to survivin in the last ten years, the development of survivin inhibitors or survivin-related molecular therapies is surprisingly and relatively slow as compared to other therapeutic inhibitors for cancer treatment. Here, the molecular functions of survivin and the progress of development of survivin-targeting therapies are discussed in detail. Functional differences between different survivin-specific inhibitors are discussed from both structural and biochemical point of views. This review also reveals different challenges that scientists are currently facing in the development of survivin inhibitors for clinical application. Finally, future directions for the development of survivin-targeted therapies are discussed in this review.     

COX-2和survivin蛋白表达与老年胃癌转移和预后的关系

 探讨环氧合酶-2 (COX-2)和生存素(survivin)蛋白表达与老年胃癌临床病理特征和患者预后的关系.方法 应用免疫组化技术检测60例老年胃癌、30例异型增生和20例癌旁正常胃黏膜组织中COX-2和survivin蛋白表达，并结合肿瘤的病理学行为和临床随访资料进行分析。结果 在老年胃癌组织中COX-2和survivin表达阳性率分别为63.3%(38/60)和70.0%(42/60)，均显著高于异型增生和正常胃黏膜组织(P<0.05）。COX-2和survivin表达与胃癌浆膜浸润、淋巴结转移和患者预后密切相关(P<0.05)。结论 COX-2和survivin表达与老年胃癌发生、转移和患者生存期密切相关，检测COX-2和survivin蛋白表达可作为判断老年胃癌预后的参考指标。     

Survivin、p53基因在脑胶质瘤组织的表达

应用免疫组织化学方法，检测Survivin和p53基因在120例胶质瘤组织（WHOⅠ级40例，WHOⅡ级40例，WHOⅢ～Ⅳ级40例）和17例正常脑组织组织的表达。结果120例胶质瘤Survivin、突变型p53基因的阳性表达率为52．5％、45．8％，17例正常脑组织中Survivin、突变型p53基因不表达，差别有统计学意义（P〈0.05）;随肿瘤分化程度降低，突变型p53和Survivin基因表达率逐渐升高（P〈0．05），Survivin与突变型p53基因的表达呈正相关（P〈0．01）.     

Survivin在子宫内膜样腺癌中的表达

目的研究Survivin在正常子宫内膜、子宫内膜不典型增生和子宫内膜样腺癌(EA)三种组织中表达的差异。方法选取华北石油管理局总医院2010年1月~2012年6月手术切除子宫并经病理证实的EA存档标本40例(EA组),经诊刮或宫腔镜检查病理结果示子宫内膜不典型增生20例(AHE组),同时选取同期因子宫脱垂或子宫肌瘤行子宫切除的正常子宫内膜20例作为对照(CON组)。通过免疫组织化学法检测三组中Survivin表达情况的差异。应用SPSS 16.0统计软件进行数据分析。结果 EA组的Survivin表达阳性率为90%,显著高于CON组(75%),差异有统计学意义(P<0.05)。在EA组中,组织分级为G1、G2、G3级的患者Survivin阳性率分别为85.0%、90.9%、100.0%,差异有统计学意义(P<0.05);手术-病理分期为Ⅰ期、Ⅱ期、Ⅲ期的患者Survivin阳性率分别为62.1%、85.7%、100.0%,差异有统计学意义(P<0.05);肌层浸润深度<1/2及≥1/2的患者Survivin阳性率分别为88.5%、92.9%,差异无统计学意义(P>0.05);存在淋巴结转移及无淋巴结转移的患者Survivin阳性率为100.0%、80.6%,差异无统计学意义(P>0.05);存在脉管浸润及无脉管浸润的患者Survivin阳性率分别为100.0%、84.2%,差异无统计学意义(P>0.05)。结论相较于正常子宫内膜,EA组织中Survivin表达显著增多。Survivin的阳性表达率与EA组织学分级和手术-病理分期相关,与肌层浸润、淋巴结转移及有无脉管浸润无关。     

miR-34a通过靶向抗凋亡基因Survivin抑制皮肤鳞状细胞癌增殖的研究

[摘要]　目的　研究miR-34a在皮肤鳞状细胞癌(SCC)中的表达及对肿瘤细胞增殖、抗凋亡的调控作用及机制。　方法　采用实时定量PCR检测46例SCC病人肿瘤组织及15例正常皮肤组织中miR-34a及Survivin的表达;将miR-34a mimic转染进皮肤鳞状细胞癌A431细胞系,探讨miR-34a对SCC细胞增殖、Survivin表达的影响;评估miR-34a及Survivin表达对SCC预后的生物诊断价值。 　结果　　（1）低分化SCC患者miR-34a显著低于高分化组,而Survivin则显著高于高分化组（P均<0.05）。与正常皮肤比较,SCC病人的miR-34a显著降低,而Survivin表达则显著提高,P值分别为0.0013及<0.0001,差异均有极显著性意义。（2）与未转染组相比,miR-34a mimic可以显著抑制A431细胞增殖（P<0.05）;同时显著降低Survivin蛋白表达（P<0.01）。（3）高miR-34a表达的SCC患者生存率显著高于低表达者,P=0.020567;高Survivin表达的SCC患者生存率则显著低于高表达者,P=0.008198。　结论　　miR-34a可通过对Survivin表达调控影响SCC细胞增殖,同时它也可作为一个很好的生物学诊断指标为评估SCC病人预后提供参考。     

Adenovirus expressing p27kip1 suppresses growth of established esophageal carcinoma xenograffs

AIM: To investigate the growth suppression of adenovirus expressing p27kip1 on established esophageal tumors in nude mice.METHODS: Esophageal carcinoma xenografts in nude mice were established by tumor tissue mass transplantation. The successfully constructed recombinant adenoviral vectors carrying p27kip1 gene (Adp27kip1) were directly injected into the esophageal tumors in nude mice. Compared to control group, the growth curve of tumor was drawn and the growth inhibition rate of tumor was calculated. The histology of tumors was examined by hematoxylin and eosin (H&E) staining. The expression of p27kip1 and survivin was detected in tumors by immunohistochemical technique.RESULTS: The growth of tumors in gene therapy group with Ad-p27kip1 was obviously suppressed compared to control group (0.42±0.08 g vs 1.17±0.30 g, t=6.39,P＜0.01), the inhibition rate of tumor growth reached 64.1%. Pathological detection showed that the tumors in nude mice were poorly differentiated esophageal squamous carcinoma. In addition, the expression of p27kip1 was increased, while the expression of survivin was decreased in tumors after being transfected with Ad-p27kip1.CONCLUSION: p27kip1 gene therapy mediated by adenovirus vector has a significant inhibitory effect on esophageal carcinoma in vivo. Up-regulated p27kip1expression and down-regulated survivin expression may be its important mechanisms.     

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM: To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS: Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS: The survivin positive unit (PU) was higher in cancerous tissues (38.76±5.14) than in para-cancerous (25.17±7.26) or normal tissues (0.57±0.03) (P<0.05). The apoptosis index (AI) of para-cancerous tissues was (7.51±2.63%) higher than cancerous tissues (4.65±1.76%). The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION: Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.