转移消失蛋白在肿瘤发生发展中的作用

肿瘤转移消失蛋白(missing in metastasis, MIM)是一种新近发现的肌动蛋白结合蛋白,主要参与细胞骨架的重塑、信号转导及转录活化,与肿瘤的生长和侵袭密切相关.近年来,该蛋白在不同肿瘤中作用机制的研究受到广泛关注,有着广阔的研究前景.本文通过综述MIM蛋白与肿瘤发生发展的相关性,从而为MIM蛋白在肿瘤诊断和治疗中的应用提供理论基础及新的策略.     

Rho蛋白在肿瘤发生发展中的作用

Rho蛋白是参与细胞内信号转导的重要蛋白,Rho家族成员及其各自的已知下游效应分子参与调节细胞的增殖、基因表达,同时是改变细胞骨架组装、调控细胞迁移进而参与肿瘤发生发展的关键因子,具有潜在而罩要的临床应用价值。     

Rho蛋白在肿瘤发生发展中的作用

Rho蛋白是参与细胞内信号转导的重要蛋白,Rho家族成员及其各自的已知下游效应分子参与调节细胞的增殖、基因表达,同时是改变细胞骨架组装、调控细胞迁移进而参与肿瘤发生发展的关键因子,具有潜在而重要的临床应用价值。     

人硒结合蛋白1在肿瘤发生发展中的作用

0 引言 肿瘤是当今世界发病率及死亡率最高的疾病[1].肿瘤发生发展是一个极为复杂的过程,流行病学资料显示,食物及其营养素从多方面影响着肿瘤的发生与发展[2-3].硒(selenium,75Se)是一种具有抗癌效应的元素[4-7],它以无机亚硒酸盐或有机硒酸盐的形式存在于植物和其他有机食物中.人类硒基蛋白质组包含35种含硒蛋白质,它们具有广泛的生理功能.现将硒结合蛋白1(selenium binding protein-1,SBPl)在肿瘤中的作用综述如下.     

平足蛋白在肿瘤发生发展中的研究现状

摘 要：平足蛋白（podoplanin,PDPN）作为淋巴内皮细胞的标志,在炎症的发生发展、淋巴管的分化形成及血小板的聚集等方面都起着一定作用。近来研究发现在肿瘤组织或肿瘤微环境中也有不同水平的PDPN表达,可作为评估肿瘤患者预后的生物学指标。进一步研究还发现PDPN及其相关信号通路可影响癌细胞的侵袭转移,进而促进肿瘤的发生发展。全文对PDPN研究现状进行综述。     

凹陷蛋白在肿瘤发生发展中的作用

凹陷蛋白（caveolin）是分子量为21～24 k的膜蛋白,为细胞凹陷（caveolae）的主要结构成分,参与许多细胞生命活动,包括细胞内吞、胆固醇运输、细胞膜组装、信号的跨膜传导和一些病毒的感染过程等,caveolin-1在恶性肿瘤发生、发展的多方面、多环节上还发挥着关键的调控作用.对于大多数类型的肿瘤细胞增殖、凋亡和侵袭转移均起负向调控作用;但在前列腺癌等的研究中,出现了相反的结果.其在恶性肿瘤中的研究值得进一步深入.     

Bcl-w在肿瘤发生发展中的作用

Bcl-2家族在肿瘤的发生发展中具有重要作用并在很大程度上决定了肿瘤对放化疗的敏感性。研究表明Bcl-w在膀胱癌的发生发展过程中起到重要作用。文章从下游效应和上游调控两个方面对Bcl-w在肿瘤中的研究进展作一综述。     

铜蓝蛋白在肿瘤发生发展中的功能和作用研究进展

铜蓝蛋白(ceruloplasmin, Cp)是一种含铜的α-2球蛋白,是多铜氧化酶家族的一员,主要分布在人体血浆中。铜蓝蛋白的功能主要包括铜的转运、铁稳态的调节、氧化酶活性、抗氧化活性、急性期反应蛋白等,这些功能在许多疾病的发生发展中都发挥着重要作用。随着科学研究不断进展,铜蓝蛋白在各类肿瘤中的作用也不断被揭示,但对于整体认识尚不充分,本文将综述铜蓝蛋白在肿瘤发生发展中的作用,为后续临床及基础科研提供一定参考。     

NIRF蛋白和CyclinE在细胞周期调控及肿瘤发生中的作用

[目的]观察NIRF是否可与CyclinE结合，探讨NIRF在细胞周期调控和肿瘤发生中的作用。[方法]从人脑cDNA文库中PCR扩增CyclinA2及CyclinE，cDNA，先分别构建含CyclinA，和CyclinE，cDNA的重组克隆载体，再分别构建含CyclinA，和CyclinE，cDNA的重组真核表达载体，将FLAG标记的4种细胞周期素和Myc标记的NIRF分别或共同转染HEK293细胞，再进行免疫沉淀及Westernblot。[结果]4种细胞周期素的蛋白水平在单独转染和与NIRF共同转染时并无明显不同，而在加入蛋白泛素化降解抑制剂MG-132后，4种细胞周期素的蛋白水平均有增加，其中尤以CyclinE1蛋白最为明显。[结论]NIRF可能通过与CyclinE，结合参与细胞周期进程，并可能参与了CyclinE1的泛素化降解。     

The Role of MicroRNA in Chemical Carcinogenesis

MicroRNAs (miRNAs) are important regulators of gene expression. Alteration of miRNA expression caused by exposure of different carcinogens has been well reported. This review aims to present the miRNAs dysregulated by exposure of different types of carcinogens in different biological systems and to discuss their potential roles in different stages of chemical carcinogenesis, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification. Available information shows that expression of a large number of miRNAs is readily changed by exposure of carcinogens in tissue- and chemical-specific manners. Carcinogenic agents generally induce many more changes in miRNA expression than non-carcinogenic chemicals. There are many more changes in cancer-target tissues than in the non-target tissues after acute or chronic exposure to carcinogens. Many of the miRNAs deregulated by carcinogens are involved in regulation of genes that are important for every stage of chemical carcinogenesis, including xenobiotic metabolism, carcinogen-induced hypomethylation, DNA repair, apoptosis, cell proliferation, tumor suppression, cell transformation, oncogenesis, tumor angiogenesis, tumor progress, mangliant transformation, and other functions. Many miRNAs function as putative oncogenes and tumor suppressor genes. The carcinogenic functions of carcinogens may be dependent on the balance between tumor-suppressor miRNAs and oncogenic miRNAs. Thus, the miRNA profiles and miRNAs specific to carcinogen exposure have the potential to be used as biomarkers for identifying genotoxicity and carcinogenicity of chemicals and indicating exposure of carcinogens.     

错配修复蛋白hMSH2 hMLH1表达在胃癌发生中的作用及临床意义

目的：探讨错配修复蛋白hMSH2、hMLH1表达及其在细胞内表达位置对胃癌发生的影响及临床意义.方法：收集大连医科大学附属第一医院胃癌标本172例、癌旁胃粘膜标本151例，非癌患者胃粘膜标本34例．应用免疫组织化学方法检测每例胃粘膜标本hMSH2、hMLH1蛋白的表达情况（包括其在细胞内表达位置），应用χ^2检验，Speannan等级相关分析在SPSS13．0统计软件上作相关统计结果：胃癌、癌旁胃粘膜和非癌患者胃粘膜hMSH2蛋白表达率分别为69．8％（120／172）、49．7％（75／151）和32．4％（11／34），胃癌组显著高于后两组（P=0．000），而后两组间无显著性差异（P=0．067）；hMLH1蛋白表达率分别为73.3％（126／172）、57．6％（87／151）和41．2％（14／34），胃癌组显著高于后两组（P=0．000），而后两组间无显著性差异（P=-0．082）．hMSH2和hMLH1蛋白表达率与胃癌患者的性别、年龄及胃癌分化程度均无显著相关关系．胃癌、癌旁胃粘膜和非癌患者胃粘膜hMSH2蛋白细胞核表达率分别为70．0％（84／120）、58．7％（44／75）和36．4％（4／11），细胞浆表达率分别为30．0％（36／120）、41.3％（31／75）和63．6％（7／11）；胃癌、癌旁胃粘膜、非癌患者胃粘膜中，hMSH2蛋白细胞核表达率逐渐降低，而细胞浆表达率则逐渐增高（r=0．161，P=0．020）。三种不同胃粘膜间，hMLH1蛋白在细胞内表达位置无显著性差异（P=0．878）。结论：同时检测胃粘膜错配修复蛋白hMSH2和hMLH1的表达及其细胞内表达位置可能有助于胃癌的早期预警。     

自噬在肿瘤发生发展及治疗中的作用

自噬是真核细胞生长分化、功能发挥及死亡的重要调控机制,自噬异常与肿瘤等多种人类疾病的发生发展有关。在分子水平,自噬与细胞的凋亡、增殖信号相互作用,共同影响肿瘤细胞的存活与死亡。由于自噬主要起维持细胞生存的功能,抑制自噬就成为辅助肿瘤治疗的一个新方向;然而,抑制自噬后的肿瘤细胞又具有逃避死亡的潜在危险,而限制了这一疗法的应用。自噬与肿瘤的复杂关系正日益受到关注,揭示其分子机制必将对肿瘤治疗产生深刻的影响。     

CD133 Role in Oral Carcinogenesis

Objective: to investigate CD133 immunoexpression, cancer stem cells marker, in oral epithelial dysplasias (OEDs) and oral squamous cells carcinomas (OSCCs) and understandits possible involvement in the malignant transformation process of these lesions and to better elucidate their biological behavior. Material and methods: Tissue samples of 15 cases of OSCCs and 15 OEDs were subjected to CD133 antibody immunohistochemistry reactions. The analysis used quantitative parameters (number of immunostained cells regardless of immunostaining sublocations). Results: All samples of OSCCs and OEDs showed positive immunostaining, with no significant difference between these groups (p = 0.283). We did not observe statistical difference between the degree of dysplasia and the amount of CD133+ cells (p = 0.899). CD133 immunoexpression showed no association with the OEDs and OSCCs sites. It was observed that nuclear and cytoplasmic immunostaining was more evident with the progression of the malignant process. Conclusion: It is suggested that the CD133 cellular localization together with the histopathological criteria of OEDs classification can contribute to provide more concrete indications about the oral carcinogenesis process.     

Role of p27 in Prostate Carcinogenesis

The cyclin dependent kinase inhibitor p27 binds to and inhibits preferentially S-phase kinases thereby halting cell cycle progression. Loss of p27 expression has been shown to be associated with aggressive behavior in a variety of human epithelial tumors including prostate cancer. In this review, the role of p27 in cell cycle progression as well as its regulation by the ubiquitin-proteasome pathway are discussed. The experimental evidence pointing to the role of p27 as a tumor suppressor gene is outlined. The data generated to date on the prognostic significance of loss of p27 protein expression in human prostate cancers are summarized. Finally, the implications of the changes in p27 expression which occur as a result of androgen ablation in normal and neoplastic prostate are discussed.     

Possible Role of Oxidative Damage in Metal-Induced Carcinogenesis

This review presents and evaluates evidence relevant to the mechanisms of metal carcinogenicity with special emphasis on the emerging hypothesis of the oxidative nature of metals' effect on DNA. The carcinogenic transition metals are capable of in vivo binding with the cell nucleus and causing promutagenic damage that includes DNA base modifications, inter- and intramolecular crosslinking of DNA and proteins, DNA strand breaks, rearrangements, and depurination. The chemistry of that damage and the resulting mutations observed in vitro and in metal-induced tumors are both characteristic for oxidative attack on DNA. The underlying mechanism involves various kinds of active oxygen and other radical species arising from metal-catalyzed redox reactions of O₂, H₂O₂, lipid peroxides, and others, with certain amino acids, peptides, and proteins. Other metal-mediated pathogenic effects, such as enhancement of lipid peroxidation, stimulation of inflammation, inhibition of cellular antioxidant defenses, and inhibition of DNA repair, may also contribute to that mechanism. Thus far, published data revealing the oxidative character of metal-induced promutagenic DNA alterations are particularly strong for two of the most powerful human metal carcinogens, chromium and nickel. However, without excluding contribution of other effects, the promotion of oxidative damage tends to take the leading role in explaining mechanisms of carcinogenicity and acute toxicity of certain other metals as well.