Circulating and local nuclear expression of survivin and fibulin-3 genes in discriminating benign from malignant respiratory diseases: correlation analysis

Survivin is an inhibitor of apoptosis as well as a promoter of cell proliferation. Fibulin-3 is a matrix glycoprotein that displays potential for tumor suppression or propagation. The present study aimed to validate the expression levels of survivin and fibulin-3 in benign and malignant respiratory diseases. This case–control study included 219 patients categorized into five groups. Group A included 63 patients with lung cancer, group B included 63 patients with various benign lung diseases, group D included 45 patients with malignant pleural mesothelioma (MPM), and group E included 48 patients with various benign pleural diseases. Group C included 60 healthy individuals (control group). Serum survivin and fibulin-3 levels were measured by ELISA, whereas their nuclear expressions in the lung and pleura were assessed via Western blot analysis. The results showed significantly higher survivin serum levels and significantly lower fibulin-3 levels in group A compared with in group B and controls (P<0.001). There were significantly higher serum levels of survivin and fibulin-3 in group D compared with in group E and controls (P<0.001), consistent with observed nuclear survivin and fibulin-3 expression levels. Fibulin-3 was determined to have higher value than survivin in discriminating lung cancer from MPM (P<0.05). Survivin and fibulin-3 could be useful diagnostic markers for lung and pleural cancers, and fibulin-3 expression was particularly useful in differentiating lung cancer from MPM.     

Design,synthesis and biological studies of Survivin Dimerization Modulators that prolong mitotic cycle

Survivin, a member of the inhibitor of apoptosis protein (IAP) family proteins, has essential roles in cell division and inhibition of apoptosis. Several clinical studies in cancer patients have shown that the elevated levels of survivin correlate with aggressiveness of the disease and resistance to radiation and chemotherapeutic treatments. Survivin is an integral component of chromosomal passenger complex (CPC) where it binds to borealin and INCENP through its dimerization interface. Thus, disruption of functional survivin along its dimer interface with a small molecule is hypothesized to inhibit the proliferation of cancer cells and sensitize them to therapeutic agents and radiation. Recently, a small molecule (Abbott8) was reported to bind at the dimerization interface of survivin. Further development of this compound was accomplished by computational modeling of the molecular interactions along the dimerization interface, which has led to the design of promising survivin dimerization modulators. Two of the most potent survivin modulators, LLP3 and LLP9 at concentrations between 50 and 100 nM, caused delay in mitotic progression and major mitotic defects in proliferating human umbilical vein endothelial cells (HUVEC) and prostate cancer cells (PC3).     

食管癌组织中HIF-1α、Survivin、CyclinD 1蛋白的表达及其意义

目的：探讨缺氧诱导因子-1α（HIF-1α）、生存蛋白（survivin）、细胞周期蛋白D1（cyclinD 1）在食管癌组织中的表达及其临床意义。方法：应用免疫组化技术检测50例食管癌组织和10例手术切除的远端正常食管组织中HIF-1α、Survivin、CyclinD 1蛋白的表达。结果：食管癌组织中HIF-1α、Survivin、CyclinD 1蛋白阳性表达率均与肿瘤浸润深度以及淋巴结转移相关（P〈0.05）,Survivin阳性表达率与肿瘤分级相关（P〈0.05）,HIF-1α与CyclinD 1的表达呈显著正相关（P〈0.05）。结论：检测HIF-1α、Survivin、CyclinD 1的蛋白的表达有助于判断食管癌的恶性程度以及推断其临床预后。     

槐定碱联合顺铂对卵巢癌中FHIT，Survivin 及PTEN表达的影响

目的:探讨槐定碱联合顺铂对卵巢癌中脆性组氨酸三联(FHIT)、凋亡抑制基因survivin、抑癌基因PTEN的表达影响研究。方法:收集我院卵巢癌患者60例,随机分为实验组和对照组,每组30例,所有患者在给予纠正电解质与酸碱平衡等常规治疗后,对照组患者给予顺铂注射液进行治疗,实验组患者在对照组的基础上给予槐定碱注射液进行治疗。观察并比较治疗前后两组患者卵巢癌组织中FHIT,survivin及PTEN表达水平的变化情况以及不良反应的发生率。结果:与治疗前相比,治疗后两组患者FHIT及PTEN表达水平均升高,survivin表达水平均降低(P0.05),治疗结束后与对照组相比,实验组患者FHIT及PTEN表达水平较高(P0.05);与对照组相比,实验组患者survivin表达水平较低(P0.05);且两组患者不良反应率相当(P0.05)。结论:槐定碱联合顺铂可以有效降低卵巢癌的恶性程度,减慢肿瘤细胞的增殖发展,延缓病情,其机制可能与升高抑癌基因FHIT和PTEN的表达水平,以及降低凋亡抑制基因survivin的表达有关。     

顺铂短期诱导人腺样囊性癌细胞NACC 产生耐药性的研究

目的:探讨人腭部涎腺腺样囊性癌细胞(NACC)经顺铂(DDP)短期诱导后耐药性产生情况及耐药机制。方法:采用恒定浓度DDP反复间歇诱导法诱导NACC细胞,获得耐药细胞NACC/DDP3,MTT法检测细胞耐药指数;实时荧光定量PCR检测存活蛋白(Survivin)及核苷酸切除修复交叉互补基因1(ERCC1)的mRNA表达;裸鼠右侧腋部皮下接种NACC及NACC/DDP3细胞,成瘤后将荷瘤裸鼠随机分为生理盐水对照组和DDP 2 mg·kg~(-1)组,比较2 mg·kg~(-1) DDP对两组荷瘤裸鼠的抑瘤率,HE染色观察肿瘤组织形态。结果:诱导后的NACC/DDP3对DDP耐药性增强,耐药指数为1.44;在NACC/DDP3细胞中,Survivin及ERCC1的mRNA表达明显上调,分别为亲本细胞的2.02(P0.01)和1.59(P0.05)倍;2 mg·kg~(-1) DDP对NACC组抑瘤率为(31.64±1.15)%,对NACC/DDP3组抑瘤率为(16.66±0.76)%,两组间差异具有统计学意义(P0.01),HE染色观察两组瘤体标本均符合腺样囊性癌实体型组织学表现。结论:NACC细胞经DDP短期诱导即产生一定耐药性,NACC/DDP3细胞中Survivin及ERCC1的mRNA表达上调,提示Survivin及ERCC1可能参与了腺样囊性癌细胞对DDP的耐药。相同剂量DDP对NACC/DDP3所建立的皮下移植瘤模型抑瘤率显著低于NACC组,提示NACC/DDP3接种到裸鼠体内仍具有耐药性,这将为体内研究耐药腺样囊性癌的治疗提供良好的平台。     

Survivin基因在肺癌中的作用

Survivin是凋亡蛋白抑制因子(inihibitor of apoptosis protein,IAP)家族中的一员,发挥强大的抑制凋亡功能,同时也参与细胞周期调控,使该基因在肿瘤的发生发展过程中起重要作用。Survivin基因特异性的表达于大多数常见的恶性肿瘤(如肺癌、乳腺癌、肝癌、胃癌等),而在正常成人组织中不表达或低表达。大量的研究涉及Survivin基因与肺癌的关系,目前的研究认为,Survivin基因可能成为一个提示预后不良的肿瘤标志物,可为肺癌的诊断提供新的方法。而且很多研究已经进入临床试验阶段,使得Survivin基因在肺癌治疗方面的应用前景广泛。随着研究的不断深入,Survivin有望成为肺癌治疗的理想靶点。本文对Survivin基因在肺癌中作用的研究进展作如下简要综述。     

Survivin在大肠癌中的表达及其与Bcl-2、P53的关系

目的:研究凋亡抑制因子Survivin蛋白在大肠癌中的表达及其与患者临床病理和预后的关系。检测大肠癌组织中Survivin的表达与Bcl-2,P53的表达的关系。方法:用免疫组织化学方法检测115例大肠癌组织中Survivin,Bcl-2及P53的蛋白表达,并对病例随访5年。结果:Survivin在大肠癌中的阳性表达率为74/115(64．3%)。正常肠黏膜组织不表达Survivin。Survivin与患者的临床病理特征无显著相关性(P＞0．05)。Survivin的表达率在Bcl-2阳性的患者明显高于Bcl-2阴性的患者(P＜0．001),但是和P53的表达无显著相关性(P＞0．05)。Survivin阳性的患者5年生存率明显低于Survivin阴性的患者(P=0．001)。结论:在大肠癌组织中检测Survivin对于肿瘤患者的预后以及基于抗凋亡机制的肿瘤靶向治疗都有很重要的意义。     

Participation of Survivin in mitotic and apoptotic activities of normal and tumor-derived cells

Survivin is a member of the inhibitor of apoptosis (IAP) gene family, containing a single baculovirus IAP repeat (BIR) and no RING finger, that is expressed in many human cancers. Although it has been proposed to be involved in mitotic and cytokinetic processes, its functional subcellular distribution in the cytoplasm and nucleus, and its binding to centrosomes, spindle fibers, and centromeres in relation to these processes, is not fully resolved. We have analyzed the localization of Survivin in normal (Detroit 551, IMR-90) and tumor-derived (HeLa, Saos-2) cell lines, and found that it does colocalize with centrosomes in the cytoplasm during interphase, then moves to centromeres during mitosis, and finally localizes to the midbody spindle fibers during telophase. However, Taxol, a popular microtubule stabilizing agent that is frequently used in the study of these processes, severely disrupted the localization of Survivin. Taxol treatment of cells promoted extensive relocalization of Survivin with alpha-tubulin on microtubules during either interphase or mitosis. Survivin antisense oligonucleotide markedly sensitized HeLa cells to cell death induced by agents acting at the level of cell surface receptor (Fas pathway) or at the level of mitochondria (etoposide). HeLa cell death induced by Survivin antisense oligonucleotide could be partially complemented by Deterin, the Drosophila homolog of Survivin (Jones et al. [2000] J. Biol. Chem. 275:22157-22166). Reciprocally, a chimera of the Deterin BIR domain and Survivin C-terminus could rescue Drosophila Kc cells from death induced by transfection of a human caspase-7-expressing plasmid. These results indicate common components of Survivin and Deterin antiapoptotic action in the vertebrate and invertebrate phyla.     

苦参碱对大鼠宫颈癌组织中Survivin、Caspase-3和Caspase-7表达的影响

目的:探讨苦参碱对宫颈癌模型大鼠组织中Survivin、Caspase-3和Caspase-7的表达影响。方法:选取Wistar雌性大鼠34只,宫颈癌造模成功的19只分成阴性对照组(A组)和苦参碱组(B组);未造模的10只大鼠作为正常对照组(C组)。采用免疫印迹法检测三组大鼠宫颈癌组织中Survivin、Caspase-3和Caspase-7表达水平。结果:1A组大鼠组织中Survivin表达明显高于B、C组大鼠组织中Survivin水平,差异有统计学意义(P0.05);2A组大鼠组织中Caspase-3和Caspase-7的表达明显低于B、C组,差异有统计学意义(P0.05);3B组大鼠组织中Survivin、Caspase-3和Caspase-7的表达水平与C组比较存在差异,差异有统计学意义(P0.05)。结论:苦参碱能够明显下调宫颈癌大鼠凋亡抑制因子Survivin水平,改善凋亡因子Caspase-3和Caspase-7的表达。