Neuropilin-2与肿瘤转移的相关研究

肿瘤转移是导致肿瘤患者死亡的重要原因，对于肿瘤转移的机制以及如何预防和抑制肿瘤的转移一直是肿瘤研究的重点和热点。目前研究认为，肿瘤相关淋巴管的形成能够促进肿瘤的转移扩散，所以现在有很多研究聚焦于如何抑制肿瘤环境淋巴管的形成。     

肿瘤原发灶的治疗与其转移灶之间关系的研究进展

由肿瘤原发灶产生的一些因子，可通过循环血液到达肿瘤转移灶，对转移灶产生促进或抑制作用，肿瘤原发病灶的治疗有可能加速其转移灶的生长，本文就肿瘤原发灶的治疗与肿瘤转移灶的关系做了介绍。     

原发性肝癌（PHC）中nm23—H1蛋白的表达及与预后的关系

肿瘤的转移往往是肿瘤病人死亡的直接原因，转移受其自身的转移基因及转移抑制基因的调控，ｎｍ２３作为转移抑制基因定位于人体１７号染色体长臂（１７ｑ２２），编码产物为二磷酸核苷激酶（ＮＤＰＫ），具有肿瘤转移抑制潜能。ｎｍ２３－Ｈ１蛋白与乳腺癌等肿瘤转移的关...     

IL-18与肿瘤转移

IL-18是近年来新发现的细胞因子，许多研究提示其与肿瘤转移有关。部分研究认为其能抑制肿瘤的转移，也有研究提示其能促进肿瘤的转移。因此，IL-18与肿瘤转移的关系仍然存在争议。     

肿瘤原发灶的治疗与其转移灶之间关系的研究进展

由肿瘤原发灶产生的一些因子，可通过循环血液到达肿瘤转移灶，对转移灶产生促进或抑制作用。肿瘤原发病灶的治疗有可能加速其转移灶的生长。本文就肿瘤原发灶的治疗与肿瘤转移灶的关系做了介绍。     

肿瘤转移抑制基因研究进展

转移是肿瘤患者死亡的主要原因之一，其基因及分子调控机制仍不清楚。肿瘤转移抑制基因在体内能直接抑制肿瘤转移潜能而对原发肿瘤生长没有影响，其发现与分离对于转移机制调节的研究具有重要意义，并具有广阔的应用前景。现综述肿瘤转移抑制基因的研究现状、临床意义及应用。     

mtal基因和癌肿转移

肿瘤转移是肿瘤致死的主要原因之一．因此研究肿瘤转移所涉及的基因和基因产物是目前国内外一项重要的课题。肿瘤转移是涉及许多基因变化的一系列复杂过程，包括肿瘤细胞从原发瘤脱离．进入血管和淋巴管，通过黏附内皮细胞在适宜部位驻留，诱导血管生成，逃避宿主抗肿瘤反应．最终在远隔部位形成转移灶。肿瘤转移整个过程受许多特殊基因的调控。近年来发现了许多与肿瘤转移相关基因。     

蛋白激酶C抑制剂CJ9111对小鼠B16黑色素瘤细胞肺转移的影响

肿瘤转移是个多步骤的连续过程。瘤细胞从原发部位扩散，浸润细胞外基质，穿透血管壁，在血管内聚积，附着于血管内皮等一系列过程形成转移灶。所有这些过程都与肿瘤细胞的粘附特性有关。自从发现佛波酯有促进肿瘤转移的作用后，表明了蛋白激酶C(PKC)在调控肿瘤转移的过程中发挥重要作用．PKC的活性与肿瘤转移呈正相关，且某些PKC抑制剂能抑制肿瘤的转移。     

KiSS-1基因在肿瘤中的研究进展

侵袭和（或）远处转移是影响恶性肿瘤患者预后的关键因素。肿瘤转移涉及肿瘤细胞的侵袭力、黏附力、与间质的相互作用等异常，是多步骤、多因素参与的过程。对肿瘤转移抑制基因的研究已成为肿瘤转移机制研究的热点。Kiss-1是近年克隆的1个新的肿瘤转移抑制基因，研究表明，其表达缺失与人类多种恶性肿瘤转移有关，本文就其在肿瘤中的研究进展作一综述。     

红细胞免疫功能与肿瘤转移

肿瘤转移是恶性肿瘤的一个重要标志，也是肿瘤患者死亡的主要原因。资料[１]表明，恶性肿瘤有６０％～６２．５％发生转移。因此研究肿瘤转移是肿瘤防治的一项重要课题。本文从红细胞免疫角度对肿瘤转移与红细胞免疫的关系进行了研究。１肿瘤转移的发生与红细胞免疫功能低下现象肿瘤转移是指肿瘤细胞从原发部位扩散到远隔器官的病理过程。肿瘤转移是一个复杂的、多步骤的过程，是肿瘤细胞和宿主细胞双方作用的结果。一方面肿瘤细胞自身的特性决定它是否有能力完成转移的各个步骤，即细胞膜表面的粘附能力、转移能力、细胞所释放的某些酶及抗…     

Survivin与肿瘤转移

Survivin是一种新型凋亡抑制因子,近年来不断发现其在肿瘤组织中表达,并与肿瘤转移和预后密切相关,成为新的研究热点,同时也为肿瘤转移靶向治疗提供了全新的方向。     

Oncolytic adenovirus mediated Survivin RNA interference and 5-fluorouracil synergistically suppress the lymphatic metastasis of colorectal cancer

Colorectal cancer is one of the leading malignancies in the world. The mortality is mainly caused by tumor metastasis. It is urgent to find new therapeutics against metastatic colorectal cancer. We constructed an adenovirus carrying a Survivin targeted shRNA, tested its effects alone or with 5-fluorouracil (5-FU) both in vitro and in a nude mouse xenograft model. Results showed that the recombinant adenovirus reduced the expression of Survivin effectively, and administration of virus together with 5-FU inhibited cancer cell metastasis both in vitro and in vivo at concentrations at which each agent alone was ineffective. We conclude Survivin targeted virotherapy together with 5-FU chemotherapy may be a promising treatment for metastatic colorectal cancer.     

XIAP mRNA和Survivin mRNA在非小细胞肺癌的表达及其临床意义

 目的　检测非小细胞肺癌（NSCLC）中X连锁凋亡抑制蛋白（XIAP）mRNA和Survivin mRNA的表达,探讨其与患者临床病理因素的相关性。方法　收集59例NSCLC患者肿瘤和正常组织标本。采用RT-PCR检测XIAP mRNA和Survivin mRNA在肿瘤和正常组织中的表达。结果　XIAP mRNA在肿瘤组织的表达率高于正常组织,分别为61.0 %（36／59）和30.5 %（18／59）（P＜0.05）,其表达与临床病理因素无相关性;Survivin mRNA在肿瘤的表达率高于正常组织,分别为81.4 %（48／59）和23.7 %（14／59）（P＜0.05）,其表达与临床病理因素无相关性。结论　XIAP和Survivin可能在NSCLC发生、发展过程中有一定作用,有可能成为NSCLC诊断的标志物和治疗靶点。     

Survivin mediates resistance to antiandrogen therapy in prostate cancer

Resistance to antiandrogen therapy in patients with metastatic prostate cancer poses a major challenge, which, if overcome, may lead to significant advances in the treatment of these patients. Hormone resistance of prostate cancer develops, in part, from upregulation of antiapoptotic genes after androgen deprivation. Given the accumulating evidence that Survivin, a new member of the inhibitor of apoptosis (IAP) family, is associated with both cancer progression and drug resistance, we hypothesized that Survivin plays a potentially important role in hormone therapy resistance, and that targeting of Survivin may enhance sensitivity to antiandrogen therapy in prostate cancer. Patterns of Survivin expression were assessed in three prostate cancer cell lines LNCaP, PC-3, and DU-145 using quantitative Western analysis. All three cell lines were found to strongly express Survivin. In LNCaP cells with intact androgen receptors (ARs), it was observed that androgen stimulation with 5alpha-dihydrotestosterone (DHT) increased Survivin expression. Conversely, treatment with Flutamide decreased Survivin expression in LNCaP cells. We next studied the functional effect of Survivin on sensitivity to Flutamide. LNCaP cells were infected with replication-deficient adenoviruses encoding either wild-type Survivin pAd-S(WT) or a phosphorylation-defective Survivin Thr34 --> Ala dominant-negative mutant pAd-S(T34A), and then treated with Flutamide. Cell viability and apoptosis were assessed in vitro and in vivo. It was determined that Survivin can mediate resistance to such antiandrogen therapies based on our assays. Direct androgen stimulation resulted in pan-cell cycle expression of Survivin, which was found to be mediated by AKT, as it was determined that exogenous insulin-like growth factor-1 (IGF-1), a known activator of AKT signaling, could increase Survivin expression and result in pan-cell cycle expression even in AR-negative prostate cancer cell lines PC-3 and DU-145. Given this alternative mechanism of Survivin expression and our findings that Survivin can mediate resistance to Flutamide treatment, we further investigated whether IGF-1-mediated activation of Survivin via AKT could mediate resistance to antiandrogen therapy. Both in vitro and in vivo, this was found to be the case, supporting a novel mechanism of resistance to antiandrogen therapy. Our study indicates that upregulation of Survivin via IGF-1 signaling confers resistance to Flutamide in prostate cancer cells. Targeted inhibition of Survivin appears to enhance the therapeutic effects of Flutamide in vitro and in vivo, revealing a novel strategy to enhance sensitivity to androgen ablation therapy.     

Significance of survivin and Bcl-2 homologous antagonist/killer mRNA in detection of bone metastasis in patients with breast cancer

The aim of this study was to assess the diagnostic value of survivin and Bcl-2 homologous antagonist/killer (Bak) mRNA in the detection of patients with bone metastatic breast cancer. This study included 92 patients with breast carcinoma (54 non-metastatic and 38 bone metastatic) and 31 patients with benign breast lesions. Survivin in cell lysates was measured by ELISA while tissue Bak mRNA was detected by RT-PCR. Survivin was significantly increased in bone metastatic breast cancer patients compared to non-metastatic cases or benign ones. Bak mRNA was markedly decreased in bone metastatic patients compared to non-metastatic ones, while significant expression of Bak mRNA was observed in bone metastatic cases compared to benign patients. High survivin level was associated with high grade, late stages and lymph node involvement, whereas low Bak mRNA was associated with late stages. Our data indicate that survivin and Bak mRNA were considerable markers for the identification of breast cancer patients with bone metastasis.     

Significance of survivin and Bcl-2 homologous antagonist/killer mRNA in detection of bone metastasis in patients with breast cancer

The aim of this study was to assess the diagnostic value of survivin and Bcl-2 homologous antagonist/killer (Bak) mRNA in the detection of patients with bone metastatic breast cancer. This study included 92 patients with breast carcinoma (54 non-metastatic and 38 bone metastatic) and 31 patients with benign breast lesions. Survivin in cell lysates was measured by ELISA while tissue Bak mRNA was detected by RT-PCR. Survivin was significantly increased in bone metastatic breast cancer patients compared to non-metastatic cases or benign ones. Bak mRNA was markedly decreased in bone metastatic patients compared to non-metastatic ones, while significant expression of Bak mRNA was observed in bone metastatic cases compared to benign patients. High survivin level was associated with high grade, late stages and lymph node involvement, whereas low Bak mRNA was associated with late stages. Our data indicate that survivin and Bak mRNA were considerable markers for the identification of breast cancer patients with bone metastasis.     

Spl和Survivin在结肠癌中的表达及意义

目的观察转录因子Spl和凋亡抑制因子Survivin在结肠癌组织和癌旁正常组织中的表达,探讨其与结肠癌生物学行为和预后的关系。方法应用免疫组织化学方法检测60例结肠癌组织和25例癌旁正常组织中Spl和Survivin的表达。结果在正常组织中,Spl多呈阴性或弱阳性表达,阳性率8％（2／25）,Survivin无阳性表达。结肠癌组织中Spl和Survivin阳性率表达分别为45％（27／60）和53．3％（32／60）。Spl和Survivin阳性表达率呈显著相关（P〈0．01）。Spl表达与肿瘤大小、肿瘤生长方式、TNM分期及Dukes分期显著相关。Survivin与患者分化程度、淋巴结转移、TNM分期及Dukes分期显著相关,Cox多因素分析表明Spl、Survivin和Dukes分期是预后的独立影响因素。结论Spl和Survivin对于判断结肠癌生物学行为有重要价值并可以作为判断结肠癌预后的临床指标。     

Sp1和Survivin在结肠癌中的表达及意义

目的 观察转录因子Sp1和凋亡抑制因子Survivin在结肠癌组织和癌旁正常组织中的表达,探讨其与结肠癌生物学行为和预后的关系。方法 应用免疫组织化学方法检测60例结肠癌组织和25例癌旁正常组织中Sp1和Survivin的表达。结果 在正常组织中,Sp1多呈阴性或弱阳性表达,阳性率8%(2/25),Survivin无阳性表达。结肠癌组织中Sp1和Survivin阳性率表达分别为45%(27/60)和53.3%(32/60)。Sp1和Survivin阳性表达率呈显著相关(P＜0.01)。Sp1表达与肿瘤大小、肿瘤生长方式、TNM分期及Dukes分期显著相关。Survivin与患者分化程度、淋巴结转移、TNM分期及Dukes分期显著相关,Cox多因素分析表明Sp1、Survivin和Dukes分期是预后的独立影响因素。结论 Sp1和Survivin对于判断结肠癌生物学行为有重要价值并可以作为判断结肠癌预后的临床指标。     

Survivin基因在胃癌中的研究进展

Survivin是细胞凋亡抑制蛋白（IAP）家族的一个新成员，是分子量最小的IAP，具有抑制细胞凋亡的作用。研究表明，Survivin在胃癌以及许多恶性肿瘤中广泛特异表达，与肿瘤的早期发生、淋巴结转移及预后有很高的相关性，并可能参与肿瘤细胞耐药性的产生。同时，Survivin基因也为胃癌的早期诊断、靶向基因治疗应用提供了新的前景。     

BKM1740, an acyl-tyrosine bisphosphonate amide derivative, inhibits the bone metastatic growth of human prostate cancer cells by inducing apoptosis

PURPOSE: Survivin overexpression has been associated with an unfavorable outcome in human PCa; however, its role in metastasis remains elusive. We aim to (a) evaluate the clinical implications of survivin expression in PCa bone metastasis; (b) determine in vivo efficacy of BKM1740, a small-molecule compound, against PCa skeletal growth and survival; and (c) investigate molecular mechanism by which BKM1740 augments apoptosis in bone metastatic PCa cells. EXPERIMENTAL DESIGN: Survivin expression was analyzed in PCa specimens and experimental models. Bone metastatic C4-2 and ARCaP(M) cell lines were used to evaluate the in vitro effects of BKM1740 and molecular mechanism for the induction of apoptosis. C4-2 cells were grown intratibially in athymic nude mice to evaluate the in vivo efficacy of BKM1740. Tumor growth in mouse bone was assessed by serum prostate-specific antigen and radiography and confirmed by immunohistochemical analyses. RESULTS: Survivin expression is positively associated with clinical PCa bone metastasis. BKM1740 induced apoptosis in PCa cells by repressing survivin. Mice with established C4-2 tumors in tibia showed a marked decrease in serum prostate-specific antigen and much improved bone architecture radiographically after treatment with BKM1740. Immunohistochemical assays of mouse tumor samples confirmed that the in vivo effects were mediated by inhibition of survivin and induction of apoptosis. CONCLUSIONS: Survivin expression is associated with PCa bone metastasis. BKM1740 treatment specifically inhibited survivin and induced apoptosis in vitro and was efficacious in retarding PCa skeletal growth in a mouse model. BKM1740 is a promising small-molecule compound that could be used to treat PCa bone metastasis.