共查询到17条相似文献,搜索用时 513 毫秒
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stathmin的表达和活性受多种转录因子、激酶和磷酸化酶的调控,其表达和活性异常与细胞增殖、肿瘤等病理生理过程密切相关.多种恶性肿瘤中stathmin都有高水平表达,抑制stathmin蛋白的表达已成为肿瘤基因治疗的新靶点,且已证实stathmin蛋白能够影响某些作用于微管的化疗药物的疗效,对于指导临床用药有一定意义. 相似文献
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微管不稳定蛋白Stathmin在细胞周期的不同阶段对微运动力平衡的调节发挥重要作用。多种恶性肿瘤中Stathmin都有高水平表达,抑制其表达可以干扰恶性细胞的细胞分裂、Stathmin的过表达可干扰紫杉醇与微管的结合,但增加长春碱类药物与微管的结合能力,临床用药时应予考虑。另外.Stathmin为肿瘤基因治疗提供了一个分子新靶点,腺病毒介导抗stathmin核酶治疗联合察素药物治疗可能获得更强有力的抗增殖和抗肿瘤效应。 相似文献
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背景与目的: 化疗是晚期非小细胞肺癌(NSCLC)的主要治疗手段,但是NSCLC常对化疗耐药,导致治疗失败.因此,针对不同分子生物学特点的NSCLC进行化疗疗效预测,成为提高疗效的重要方法.本研究通过研究晚期NSCLC患者肿瘤组织中Stathmin基因的表达与患者对长春碱类药物的化疗敏感性的关系,为患者选择适当的药物治疗提供依据.方法:2005年5月-2007年12月,共78例晚期NSCLC患者入组,随机分ANP方案[长春瑞滨(NVB)联合顺铂(DDP)或卡铂(CBP)]化疗组或GP方案[吉西他滨(GEM)联合DDP或CBP]化疗组,观察两组对化疗的反应;同时以RT-PCR法检测患者病理组织中Stathmin mRNA的表达,以Western印迹法检测Stathmin的蛋白含量.结果: NP组41N,GP组37例,两组患者的性别、年龄、病理类型及肿瘤分期等临床特点无显著性差异(P>0.05),对化疗总的有效率分别为46.3%(19/41)和48.6%(18/37),两者之间亦未见显著差异(P>0.05);在NP组内,有效19例,无效22例,有效患者的肿瘤组织中stathmin mRNA测量值为1.9±1.1,而无效患者为7.5±2.8,两者之间差异有显著性(P=0.003).有效患者的Stathmin蛋白测量值为1.5±0.7.无效组为4.3±1.6,两者之间差异有显著性(P=0.002).GP组18例有效,19例无效,有效与无效患者肿瘤组织中stathmin mRNA及Stathmin蛋白无明显差异(P>0.05). 结论: NSCLC患者肿瘤组织中stathmin基因的表达与患者对长春碱药物的敏感性有关,stathmin基因高表达,对长春碱药物的敏感性低,宜换用其他药物治疗. 相似文献
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肺癌紫杉醇耐药与微管蛋白 总被引:1,自引:0,他引:1
紫杉醇(taxol,paclitaxel)是红豆杉树皮的提取物,自1987年作为一种新型的化疗药物进入临床,已显示出良好的发展前景。大量研究证明,其对肺癌及其他肿瘤具有切实有效的治疗作用。紫杉醇的化学结构是紫杉烷类中一种四环二萜类化合物,是一种微管蛋白结合药物。而微管(microtubule)在肿瘤细胞染色体的分裂、位移及肿瘤细胞的运动上起重要作用。紫杉醇通过结合在微管特定位点上,能促进并稳定微管蛋白的聚合,防止解聚,导致 相似文献
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驱动蛋白KIF14是一种马达蛋白,依靠ATP水解酶的活性,向微管正极末端运动。在细胞内,KIF14参与物质运输、纤毛发生和细胞有丝分裂等过程。近年来的研究表明,在细胞质分裂的不同阶段KIF14通过与多种蛋白质相互作用来调控有丝分裂的进程。KIF14的表达异常会导致细胞有丝分裂失常,造成细胞基因组不稳定,而基因组的不稳定是导致肿瘤发生的重要原因。KIF14与多种肿瘤的发生发展密切相关,并且与肿瘤细胞的迁移、侵袭和对药物的敏感性有关,其已成为肿瘤早期诊断、治疗和预后评估的潜在靶点,因此,开发靶向KIF14的抑制剂,将为肿瘤的临床治疗提供新药物。 相似文献
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Stathmin基因在人成骨肉瘤细胞中的表达及意义 总被引:2,自引:0,他引:2
stathmin作为细胞信号转导分子在细胞分化及恶性肿瘤发生、发展上发挥重要作用。本研究旨在探讨Stathmin基因在人成骨肉瘤细胞中的表达,并探讨阻断其表达对该肿瘤细胞的生物学行为的影响。方法:RT-PCR及原位杂交法检测2个人成骨肉瘤细胞系及45例人成骨肉瘤组织中Stathmin基因表达情况;以高表达Stathmin基因的人成骨肉瘤细胞系SOSP-9607为靶细胞、反义Stathmin(ASODN)为阻断剂,通过MTT实验观察ASODN对该细胞系的生长抑制作用,并用流式细胞仪分析其对细胞增殖周期的影响。 相似文献
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《Asian Pacific journal of cancer prevention》2014,15(8):3613-3618
Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteinsthat play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one ofresponsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations withclinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNAlevels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissuesand adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706,ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot andin situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed byCox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in ECtissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positivelycorrelated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, wedemonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those,EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysisshowed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression,compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportionalhazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability.In conclusion, our data provide a basis for the concept that stathmin might be associated with EC developmentand progression.. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker forpatients with EC. 相似文献
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目的 探讨Stathmin蛋白在食管鳞癌组织中的表达及意义.方法 收集新乡医学院2006年4月至9月期间食管鳞癌切除标本及其相应癌旁组织31例,以免疫组织化学法检测Stathmin蛋白在所取标本中的表达情况.结果 在31例食管鳞癌标本中,Stathmin蛋白表达阳性的标本为23例,阳性率为74.2%,阳性颗粒可见于细胞质;分别按年龄、性别、组织类型、分化程度、淋巴结转移、肿瘤浸润深度及TNM分期将31例食管癌标本分组,Stathmin蛋白表达差异有统计学意义的因素有分化程度、淋巴结转移、肿瘤浸润深度及TNM分期(P<0.05).结论 食管鳞癌组织中Stathmin蛋白高表达,其表达与食管鳞癌的分化程度、淋巴结转移、肿瘤浸润深度及TNM分期显著相关,Stathmin蛋白可能为人食管癌的生物治疗提供一个新靶点. 相似文献
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I. Bi��che S. Lachkar V. Becette C. Cifuentes-Diaz A. Sobel R. Lidereau P. A. Curmi 《British journal of cancer》1998,78(6):701-709
Stathmin is a highly conserved cytosolic phosphoprotein that destabilizes microtubules. Stathmin, which has been proposed as a relay protein integrating diverse cell signalling pathways, acts in vitro as a tubulin-sequestering protein, and its activity is dramatically reduced by phosphorylation. Interestingly, stathmin expression and phosphorylation are regulated during the control of cell growth and differentiation, and there is much evidence suggesting that in vivo stathmin plays a role in the control of microtubule dynamics during mitosis. Stathmin may thus be considered as one of the key regulators of cell division. We examined 50 human primary breast tumours for stathmin mRNA and protein expression and screened for abnormalities in the chromosome region harbouring the stathmin gene. Overexpression of stathmin was found in 15 tumours (30%). At the present stage, no clear correlation emerged between stathmin expression and several prognosis markers. Interestingly, perfect matching was observed between stathmin mRNA overexpression, protein overexpression and strong staining for stathmin on paraffin-embedded tumour sections when specimens were available. Furthermore, a tentative link between loss of heterozygosity (LOH) in the 1p32-1pter region and stathmin overexpression was observed. Our results suggest that stathmin might play a role in breast carcinogenesis and that stathmin-overexpressing tumours may represent a new subtype of breast cancer. 相似文献
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Stathmin在Ⅳ期非小细胞肺癌中表达及紫杉类化疗耐药相关性研究 总被引:1,自引:0,他引:1
目的:探讨Ⅳ期非小细胞肺癌(NSCLC )Stathmin 蛋白表达与紫杉类化疗耐药性关系。方法:回顾性分析2003年10月~2007年10月75例接受以紫杉类化疗的Ⅳ期NSCLC 临床病理资料。免疫组织化学法检测肿瘤标本Stathmin 蛋白表达,并对化疗疗效及生存时间进行分析。结果:Stathmin 阳性表达(≥50% 阳性染色细胞)率为80.00% 60/75),男性高表达率为81.63% ,女性为76.92% ,P=0.627;鳞癌71.79% ,腺癌88.89% ,P=0.064;≥58岁78.95% ,<58岁81.08% ,P=0.817;化疗有效率(CR+PR)为34.67% ,Stathmin 高表达患者紫杉类化疗有效率低28.33%(17/60),进展率高21.67%(13/60),而Stathmin 低表达患者化疗有效率高60.00%(9/15),进展率低0(0/15),P=0.021和P=0.047。Stathmin 高表达者有较短的中位OS(12.0 个月)和PFS(8.0 个月),而Stathmin 低表达患者有较长的中位OS(17.0 个月)和PFS(13.0 个月),P=0.008 和P=0.008。患者性别、年龄和组织类型与中位OS及PFS 无相关性,P 值均>0.05。结论:Stathmin 高表达NSCLC 患者对紫杉类药物耐药且预后不良。 相似文献
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Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule-destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement-related processes. Scratch wound-healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down-regulation of cellular stathmin levels and in the absence and presence of sublethal nitrosourea ([1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]; CCNU) concentrations. We show that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 micromol/L, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain, and that nitrosoureas may have therapeutic benefits in addition to their antiproliferative effects. 相似文献