Survivin在T细胞非霍奇金淋巴瘤组织中的表达及临床意义

【目的】了解生存蛋白Survivin在T细胞非霍奇金淋巴瘤（T—NHL）中的表达，以及Survivin表达与预后的关系。【方法】用免疫组化S-P法检测83例T细胞NHL组织Survivin表达情况，分析Survivin表达与预后的关系。【结果】Survivin表达阴性10例（12％），表达阳性73例（88％），Survivin表达与病理类型、性别、年龄、B症状、结外病变数、PS、分期、LDH水平、IPI等临床特征均无相关性（P〉0．05）。78例接受了化疗，大多数采用CHOP方案化疗，全组CR率45％，有效率86％，Survivin阴性者CR率60％，阳性者43％（P〉0．05）。中位随访22月（1—76月），全组5年生存率31％，Survivin表达阳性的T—NHL患者5年生存率明显低于Survivin表达阴性患者（21％比70％，P〈0．001）。多因素分析显示Survivin表达是T细胞NHL的独立预后指标。【结论】Survivin在T细胞NHL表达上调，Survivin阳性T—NHL患者5年生存率低于Survivin阴性者，Survivin表达可能为T细胞NHL预后的独立指标。     

survivin的siRNA靶向干扰膀胱癌的实验研究

目的实验研究靶向转染survivin的小分子干扰RNA（small interfering RNA，siRNA）对膀胱癌生物学行为的影响。方法设计1对survivin编码基因序列特异的siRNA，用脂质体转染T24膀胱癌细胞株。采用流式细胞术检测转染效率和细胞凋亡；荧光实时定量PCR检测干扰前后survivin的mRNA表达；用survivin的siRNA片段插入空载体后建立重组载体pRNAT-U6、1／Neo-survivin。结果脂质体转染T24细胞后的转染效率为92．3％；survivin编码基因序列特异的siRNA能有效下调survivin基因的表达，呈时间和剂量依赖性，最大效应浓度为100nmol／L，此时survivin表达水平下调了75．91％，并显著地抑制了细胞生长，抑制率达55．29％，差异有统计学意义（P〈0．01）；细胞凋亡率亦增至45．70％，与对照相比差异有统计学意义（P〈0．01）。用限制性内切酶将空载体线性化，T4DNA连接酶将siRNA片段插入空载体中，对该重组表达载体进行鉴定，获得RNA干扰质粒载体pRNAT-U6．1／Neo-survivin。结论siRNA．survivin能显著下调膀胱癌细胞survivin基因表达水平，促进细胞凋亡，抑制肿瘤细胞增殖，可能成为膀胱癌基因治疗的新工具。成功构建的靶向survivin基因表达的RNA干扰质粒载体为进一步应用RNA干扰技术进行survivin基因功能研究奠定了基础。     

Nuclear translocation of survivin in hepatocellular carcinoma: a key to cancer cell growth?

Survivin is a recently described anti-apoptosis protein and regulator of cell division. Its expression and localization in hepatocellular carcinoma (HCC) and in normal liver tissue has not been fully elucidated. We examined the expression of survivin, Fas, proliferating cell nuclear antigen (PCNA), and apoptosis in 47 specimens of hepatocellular carcinoma (HCC) and surrounding nonmalignant hepatic tissues. To further determine the relationship between survivin expression and cell proliferation and apoptosis, we performed double immunostaining for survivin and PCNA TUNEL staining in the same HCC specimens. Positive immunostaining for survivin was present in 35 of 47 (74%) HCCs. Twenty-two of 35 survivin-positive HCCs (63%) showed punctate nuclear staining in HCC cells, and the remaining 13 showed predominant cytoplasmic staining. In contrast, nonmalignant hepatocytes showed only cytoplasmic staining. HCC cells had significantly higher PCNA-labeling and apoptotic indices compared with the case of nonmalignant hepatic tissue (P<0.001). Furthermore, nucleus-positive HCC specimens for survivin showed the highest PCNA labeling index. The nuclear localization of survivin in HCC cells correlated with tumor cell de-differentiation with the exception of the HepG2 cell line. Survivin expression was inversely associated with apoptosis and was strongly associated with Fas expression (P=0.01). All 4 HCC cell lines examined showed survivin expression and punctate nuclear localization. Our results indicate that survivin is localized to the cytoplasm in quiescent nonmalignant liver cells to suppress apoptosis and translocates into the nucleus in HCC cells. In conclusion, translocation of survivin from the cytoplasm to the nucleus may constitute an important regulatory mechanism for cell proliferation and differentiation in HCC.     

凋亡抑制因子生存素的研究进展

生存素(survivin)是新近发现的一个IAP家族的独特成员，表达于胚胎组织和多种癌组织，但不见于正常组织。能抑制各种因子诱导的细胞凋亡，并参与血管生成，作为一种普遍表达的肿瘤特异性凋亡抑制因子，生存素可能是肿瘤靶基因蛋白治疗的理想靶点。     

Survivin在胃癌中的表达及其与COX-2相关性的研究

目的 :探究凋亡抑制基因survivin在胃癌组织中的表达与COX 2表达的相关性。方法 :运用S P免疫组化技术 ,检测survivin和COX 2蛋白在 93例胃癌组织、2 0例正常胃黏膜组织以及胃癌细胞株MGC 80 3中的阳性率。结果 :survivin蛋白在 2 0例正常胃黏膜组织中阴性 ,而 93例胃癌组织中有 66例阳性 ,占 71% ,差异有显著性 (P <0 .0 1) ,COX 2蛋白在胃癌组织中的阳性率为 76.3 % ,MGC 80 3细胞中survivin和COX 2蛋白均阳性。Survivin蛋白阳性率与胃癌组织的分化程度、淋巴结转移、TNM分期相关 ,而与浸润程度不相关 ,并与COX 2蛋白阳性呈正相关 (Pearson列联系数 0 .2 2 7P <0 .0 5)。结论 :肿瘤组织中survivin蛋白的特异性阳性在胃癌的发生发展中起重要作用 ;survivin蛋白与胃癌组织中COX 2蛋白的阳性密切相关 ,两者可能存在共同的激活机制 ,构成抑制胃癌细胞凋亡的多种途径     

结直肠癌组织中Survivin表达与细胞增殖的关系

目的 :探讨结直肠癌组织中Survivin表达的临床病理学意义及其与癌细胞增殖的关系。方法 :免疫组织化学染色方法 (SP法 )检测 10 6例结直肠癌组织中Survivin、Ki 6 7、P5 3的表达 ,分析Survivin表达与Ki 6 7增殖指数、P5 3表达及各临床病理因素的关系。结果 :Survivin阳性表达结直肠癌的Ki 6 7增殖指数 (4 1.31%± 19.83% )明显高于Survivin阴性者 (2 6 .2 1%± 2 0 .36 % ) ,Survivin表达与肿瘤细胞增殖呈正相关 (P <0 .0 5 )。Survivin表达与P5 3表达无显著相关。Survivin在结直肠癌组织中的表达率为 6 4 .2 % (6 8/10 6例 ) ,癌旁形态学正常的结直肠粘膜未见Survivin表达 ;Survivin在中高分化结直肠癌表达阳性率 72 .4 % (6 3/87例 ) ,明显高于低分化结直肠癌 (2 6 .3% ,5 /19例 ) ,P <0 .0 5。此外 ,Survivin表达与患者性别、肿瘤位置、浸润深度、淋巴结转移、远处转移以及Dukes’分期无显著相关 (P >0 .0 5 )。结论 :凋亡抑制蛋白Survivin在结直肠癌组织中阳性表达率为 6 4 .2 % ,与细胞分化程度有关 ,可促进结直肠癌细胞的增殖     

Survivin and aven: two distinct antiapoptotic signals in acute leukemias.

BACKGROUND: Antiapoptotic signals are important in the development, progression and prognosis of malignant tumors. The aim of this study was to determine the two distinct antiapoptotic signals-survivin and aven-in acute leukemias and compare them with clinical and hematological findings and response to therapy. Real-time quantitative PCR was used and survivin and aven were detected at the messenger (m)RNA level. PATIENTS AND METHODS: Sixty-five patients with acute leukemia [37 with acute myeloblastic leukemia (AML) and 28 with acute lymphoblastic leukemia (ALL)] were used as the study group and 10 healthy subjects were used as the control group. RESULTS: Survivin was between 0.0 and 0.829 copy number/cell (median 0.0721, mean 0.5424301909 +/- 0.139799488589) and aven was between 0.0 and 0.853 copy number/cell (median 0.0124, mean 0.070335542 +/- 0.1524685709). We found an important association between survivin and aven (P = 0.000). Both survivin and aven were higher in the study group than in the controls (P = 0.001 and 0.035, respectively). When we compared survivin and aven with other clinical and hematological parameters, there was an important association between survivin and extramedullary involvement (P = 0.033), survivin and alkaline phosphatase (P = 0.06), white blood cell (WBC) count and lactate dehydrogenase (LDH) (P = 0.000), WBC count and uric acid (P = 0.074), hemoglobin level and LDH (P = 0.072), LDH and uric acid (P = 0.057), CD7 expression and survivin (P = 0.097), and CD34 expression and aven (P = 0.058). Response to therapy was evaluated according to the survivin and aven levels. Survivin level was lower in refractory patients as compared with complete responders (P = 0.085). Aven level was higher in patients with relapse as compared with non-relapse patients (P = 0.04). There was no important association between survivin or aven and performance status, lymphadenopathy or organomegaly. CONCLUSIONS: Both survivin and aven are important antiapoptotic signals in acute leukemias, and the association between extramedullary involvement, CD7 expression and CD34 expression, which are important poor prognostic indicators in acute leukemias, suggests that survivin and/or aven may be novel prognostic indicators in acute leukemias. Further studies with a higher number of patients will be more informative.     

Survivin in Brain Tumors: An Attractive Target for Immunotherapy

Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors.     

survivin和p53在食管鳞癌中的表达及意义

目的探讨凋亡抑制因子survivin和p53在食管鳞癌(ESC)组织中的表达及其与临床病理因素之间的关系.方法应用免疫组织化学S-P法和PowerVisionTM-9000(PV-9000)法检测60例ESC、15例食管良性肿瘤和10例癌旁正常食管黏膜组织中survivin和p53的表达.结果 60例ESC中survivin和p53的阳性表达率分别为71.7%和65.0%,与食管良性肿瘤(13.3%,0)和癌旁食管正常黏膜组织(0,0)比较,差异均有显著性(P<0.001).survivin和p53的表达强度与ESC的分化程度、临床分期和淋巴结转移均相关(P<0.05),而与肿瘤长度及部位均无相关(P>0.05).survivin与p53的表达呈显著相关(P<0.01).结论 survivin和p53均与ESC的发生发展有关,二者在ESC的发展过程中可能起协同作用.联合检测survivin和p53在ESC中的表达水平,对判定其恶性程度及预后可能具有重要参考价值.     

COX-2、Survivin蛋白在卵巢上皮性癌中的表达及与临床病理因素的关系

目的探讨卵巢上皮性癌组织中环氧合酶2（COX-2）与Survivin的表达以及与临床病理因素的关系。方法采用免疫组化Elivision染色法检测COX-2、Survivin蛋白在60例卵巢上皮性癌组织、20例正常卵巢、20例良性卵巢上皮性肿瘤及20例交界性卵巢上皮性肿瘤中的表达。结果COX-2、Survivin蛋白在正常卵巢、良性卵巢上皮性肿瘤、交界性卵巢上皮性肿瘤组织及卵巢上皮性癌组织中的表达差异有高度显著性（P〈O．05）。COX-2表达与卵巢上皮性癌患者盆腹腔淋巴结有无转移呈显著相关性（P〈O．05）。Survivin基因表达与卵巢上皮性癌的病理类型有相关性（P〈O．05）、Survivin基因表达与淋巴结转移有显著相关性（P〈O．05）。结论COX-2、Survivin蛋白在卵巢上皮性癌中高表达，并在卵巢上皮性癌的发生、发展中起着重要作用，说明卵巢上皮性癌的发生非单一基因作用，而是多基因协同作用。