Wnt通路抑制因子FrpHE的表达作用

目的研究Wnt通路抑制因子FrpHE（frizzled related—protein）表达的调控作用。方法将携带p53基因的复制缺陷型腺病毒载体（Adp53）导入到p53缺失的人肝癌细胞株Hep3B中，并以wnt通路的关键因子}eatenin的改变为功能指标评价wnt通路的变化。以RT—PCR技术检测Wnt通路抑制因子FrpHE表达的调节作用，以流式细胞术检测Adp53的转基因情况和β-catenin的表达。结果FrpHE mRNA水平在转染p5320小时后即有明显升高，其中以32小时达最高水平，随后逐渐降低。量效关系研究表明在转染剂量为0．05、0．5、5、50pfu／cell时FrpHEmRNA表达均有显著增高，尤以5pfu／cell时表达水平最高。β-catenin表达水平随着转染时间和转染剂量的增加，阳性细胞百分比强度和平均荧光量强度表达水平逐渐下降。结论外源性p53能够诱导Wnt通路抑制因子FrpHE的表达，进而产生抑制Wnt通路的作用。     

长链非编码RNA HCG4通过Wnt/β-catenin通路对垂体腺瘤细胞增殖、迁移与侵袭的影响

目的 探讨长链非编码RNA HLA复合体4(HCG4)调控Wnt/β-连环蛋白(β-catenin)通路对垂体腺瘤细胞增殖、迁移和侵袭生物学行为的影响。方法 实时荧光定量PCR(q PCR)检测35对垂体腺瘤和正常垂体组织的HCG4水平。培养垂体腺瘤HP75细胞并分为Control组(无转染)、NC组(转染空载体pc DNA3.1)、HCG4组(转染过表达质粒pc DNA3.1-HCG4)和HCG4+Wnt激动剂组(同时转染过表达质粒pc DNA3.1-HCG4和Wnt激动剂SKL2001)。CCK-8法、划痕实验和Transwell小室实验分别检测HP75细胞的增殖、迁移和侵袭的情况。q PCR和Western blotting检测HP75细胞的β-catenin和基质金属蛋白酶(MMP)-9水平。结果 垂体腺瘤组织的HCG4水平低于正常组织(0.616±0.044 vs. 1.000±0.071,P<0.05); 21例Ⅰ～Ⅱ期垂体腺瘤患者(0.712±0.053)和14例Ⅲ～Ⅳ期垂体腺瘤患者(0.473±0.060)垂体腺瘤组织的HCG4水平均低于正常组织(P<0.0...     

垂体腺瘤蛋白质组学的研究进展

目的:总结国内外蛋白质组学技术在垂体腺瘤研究中的进展并对未来研究方向做了瞻望.方法:应用Medline和CNKI期刊全文数据库检索系统,以"pituitary adenoma,proteomics"为关键词,检索1995-01-2009-10的相关文献,共检索到34篇英文和12篇中文文献.纳入标准:1)正常垂体或垂体腺瘤的表达谱特征;2)垂体腺瘤的差异蛋白质组学;3)磷酸化蛋白质组学研究;4)垂体腺瘤转录组学和蛋白质组学的整合研究.根据纳入标准符合分析的文献20篇.结果:前期蛋白质组学主要集中在正常垂体和垂体腺瘤的蛋白表达谱,磷酸化蛋白质组学以及差异蛋白质组学研究结果表明,高效多维液相色谱-电喷雾-串联质谱技术在蛋白质组学研究上,较传统二维凝胶技术有着明显的技术优势.因此,非胶蛋白质组学技术是研究垂体腺瘤发病机制的重要工具.结论:通过激光捕获切割技术获取纯净肿瘤细胞标本,运用定量蛋白质组学方法发现关键差异蛋白,可以在蛋白水平更深入的探讨垂体腺瘤的发病以及侵袭机制.     

垂体腺瘤相关microRNAs的研究进展

垂体腺瘤是颅内常见良性肿瘤,但部分垂体腺瘤可表现出恶性肿瘤的生物学特性。目前垂体腺瘤的具体发生机制尚不明确。近年来,微小RNAs（microRNAs,miRNAs）的出现为我们研究垂体瘤的发病机制提供了新的思路和途径,miRNAs是一类新发现的非编码RNA,它在转录后水平调节靶基因的表达水平,在机体发育,细胞增殖、分化、凋亡以及肿瘤发生等多种生理和病理过程中起着重要作用。     

侵袭性垂体腺瘤的分子生物学研究进展

垂体腺瘤为来源于垂体前叶腺细胞的单克隆腺瘤,根据其生物学行为分为非侵袭性与侵袭性。侵袭性垂体腺瘤生物学行为介于恶性与良性腺瘤之间,它可破坏鞍区骨质,侵袭海绵窦等鞍区结构,其高复发率、低治愈率以及术后并发症等给临床治疗带来很大的困难[1]。近年来,随着细胞生     

Wnt信号通路与肿瘤的研究进展

Wnt信号通路不仅与肿瘤侵袭转移的相关事件如癌细胞的迁移黏附、细胞外基质的降解及肿瘤的血管生成密切相关,而且在调节肿瘤干细胞的自我更新、增殖与分化中发挥重要作用,并且针对Wnt信号通路不同基因靶点的高特异性基因药物开发及其肿瘤靶向治疗方面也取得一定进展。     

大肠癌干细胞相关Wnt信号通路调控分子的研究进展

大肠癌是中国发病率排名第三的癌症。虽然近年来手术技术和术后化疗效果已经取得不小的进展,但大肠癌的预后仍不令人满意,主要原因是肿瘤的复发和转移。大肠癌干细胞Wnt信号通路在肿瘤复发和转移中起重要作用,并已成为抗癌药物研发的新靶点。大肠癌干细胞Wnt信号通路的失调导致细胞内β-catenin水平升高,继而激活一系列致癌相关基因。因此,如果针对Wnt信号通路的小分子靶向药物可阻止或逆转这些异常变化,将有助于治疗大肠癌。本文对以Wnt通路为靶标的小分子药物的研究现状进行了回顾,并展望其未来可能的发展方向。     

肺癌干细胞Wnt信号通路的研究进展

Wnt信号通路在维持肺癌干细胞的增殖和克隆形成方面发挥着重要作用,可通过影响其关键蛋白质抑制肺癌干细胞增殖,为肺癌的治疗提供新的路径.本文旨在通过总结2005年-2010年肺癌干细胞及Wnt通路的研究现状,探讨Wnt通路与肺癌干细胞的关系.     

经典Wnt信号通路在恶性淋巴瘤中的研究进展

Wnt信号通路是调控机体胚胎及器官发育的重要信号通路之一,在细胞增殖、分化、极化、黏附和运动等生理过程中发挥重要作用;许多肿瘤的发病涉及经典Wnt通路的异常持续性激活。近年来,在恶性淋巴瘤发病研究中有许多涉及Wnt信号通路的激活。本文就经典Wnt信号通路在淋巴细胞发育和恶性淋巴瘤发病中的研究进展进行简要综述,旨在进一步探索淋巴瘤的发病机制,揭示基于该通路的潜在靶向治疗的可能。     

Wnt信号通路影响肺癌干细胞机制的研究进展

检索2001年至2011年Medline、PubMed及CNKI 期刊全文数据库检索系统与Wnt信号通路及肺癌干细胞相关的中、英文文献发现,Wnt信号主要通过Wnt经典信号传导途径、Wnt Ca2+途径、Wnt 细胞平面极化途径在细胞中起作用。作为Wnt信号通路中最关键的通道传递分子,Wnt／β catenin信号通路在维持肺癌干细胞的增殖和克隆形成方面发挥着重要作用,通过对关键蛋白的影响抑制肺癌干细胞增殖,为肺癌的治疗提供了新路径。     

Targeting Raf/MEK/ERK pathway in pituitary adenomas

Pituitary adenomas are the common neoplasms that cause mass effect and/or endocrine dysfunction. Studies in the pathogenesis and functional regulation of pituitary adenomas are mainly focused on the following two topics: (a) the origin of pituitary adenomas and abnormal physical adjustment due to the activation of oncogenes and loss of function for tumour-suppressor genes; and (b) the mechanistic anomalies of the intracellular signal transduction. Among which, the Raf/MEK/ERK signalling has been considered to be one of the major and central pathways in disease aetiology. Raf/MEK/ERK signalling is evolutionarily conserved that controls cellular growth, differentiation and survival. Altered functionality of this signalling pathway has been found to be involved in the development of several types of cancers in humans including pituitary adenomas. This review summarises the roles of Raf/MEK/ERK signalling pathway in pituitary tumourigenesis and highlights the clinical potential of this signalling pathways to be a therapeutic target for intervention and treatment of pituitary adenomas.     

胰蛋白酶抑制剂对Wnt信号通路的作用

Wnt信号通路中的蛋白质分子在多种肿瘤的发生发展过程中扮演着重要角色,它们不仅调节细胞分裂,且与细胞骨架运动紧密相关.胰蛋白酶抑制剂能通过影响肿瘤细胞间的黏附及运动对肿瘤细胞的发生、浸润和转移起到抑制作用.它还可通过提高凋亡酶活性而加速细胞凋亡;通过细胞膜上钙黏蛋白下调β连接蛋白在细胞质中的含量,抑制Wnt信号通路的异常激活.     

Classification of pituitary adenomas

Angiogenesis is of vital importance for the growth of solid tumors and constitutes a target for anti-cancer therapy. Glioblastomas (GBMs) are histologically characterized by striking microvascular proliferation. The identification of the mechanism of angiogenesis is of major importance for the further development of anti-angiogenic therapy. Tumor angiogenesis might be the result of a combination of local tissue conditions (especially hypoxia) and specific genetic alterations acquired during oncogenesis. In order to investigate the relationship between genetic aberrations and tumor angiogenesis in GBM xenograft lines, the genetic alterations were examined by Comparative Genomic Hybridization (CGH). Two vascular phenotypes of GBM xenografts could be identified: a well vascularized and a poorly vascularized type. In this model, the poorly vascularized type had a larger number of genetic alterations. However, there was no unequivocal correlation between angiogenesis, growth rate and patterns of genetic alterations as detected by CGH.     

Management of aggressive pituitary adenomas and pituitary carcinomas

Pituitary tumors are benign but not uncommonly invade locally into adjacent tissues such as the cavernous sinus and dura. Some of these invasive tumors exhibit varying degrees of resistance to standard therapy and tend to recur. Early prediction of which pituitary tumors will recur and/or exhibit an invasive phenotype remains difficult despite introduction of several tissue-based molecular markers. Management of these recurrent invasive pituitary tumors usually comprises combination medical, surgical and radiation therapy but in some instances is suboptimal. Earlier diagnosis of invasive/recurrent pituitary tumor and application of aggressive multi-modal therapy at presentation may be advantageous in some cases. Clinical trials to develop additional therapeutic options are needed for this subgroup of pituitary tumors. Although it is not yet possible to diagnose at presentation, the subset of pituitary tumors that will become invasive and/or recurrent pituitary tumors, broader use of molecular markers and standardization of histopathological criteria for “atypical” pituitary tumor features have assisted earlier diagnosis. Aggressive therapy early in disease may be warranted and exploration of recently available targeted therapies may improve disease management.     

Surgical management of pituitary adenomas

As experience with endocrine diagnosis, radiologic evaluation, and transsphenoidal microsurgery has accumulated, more effective therapy has become available for patients with pituitary adenomas. The amelioration of the various endocrinopathies and the potential for restoration of vision in patients with visual impairment make this aspect of modern neurosurgery most satisfying, both for the patient and for the surgeon.     

Molecular pathology of pituitary adenomas

Malignant gliomas are highly resistant tumors against -irradiation and contained overexpression of p21^WAF1/CIP1 (p21). Overexpression of p21 enhanced clonogenic survival and suppressed apoptosis after -irradiation in human brain tumor cell lines with or without p53 protein deficiency. The effect of antisense oligonucleotide to p21 against the -irradiation-induced apoptosis and cytotoxicity in malignant glioma cell lines was examined. Antennapedia homeodomain internalization peptide was used as an insertion vector. The high transfection efficiency of Antennapedia homeodomain internalization peptide joined with antisense oligonucleotide was observed. The pretreatment with antisense oligonucleotide enhanced the -irradiation-induced apoptosis and cytotoxicity in radioresistant glioma cells. p21 may represent an important new target for radiosensitization protocols, possibly involving antisense oligonucleotide directed against.