上皮间质转化和肿瘤干细胞

最近,两个新的概念出现在肿瘤生物学中：上皮间质转化（epitheilal-mesenchymal transition,EMT）和肿瘤干细胞（cancer stem cells,CSCs）。EMT不仅赋予细胞迁移和侵袭特征,还可使肿瘤细胞获得自我更新能力而具有干细胞的特性,从而促进CSCs的产生。本文讨论EMT和CSCs之间的联系、EMT获得干细胞特征促进CSCs产生、EMT是形成CSCs的重要环节及二者在干细胞巢中的转化,并分析影响EMT和CSCs的因素。研究EMT在肿瘤发生中的作用,与CSCs理论相融合,从而可能发现新的肿瘤靶向治疗。     

肿瘤干细胞与肿瘤转移的分子影像学检测及研究进展北大核心CSCD

肿瘤干细胞(cancer stem cells,CSCs)是一类具有自我更新及多向分化潜能的癌细胞亚群。一些研究表明,CSCs参与并调节了肿瘤的转移过程,为转移发生的微环境建立提供了条件。因此,对CSCs的识别和示踪在研究肿瘤转移的分子机制方面显得尤为重要。近年来发展起来的分子影像技术,以CSCs表面特有的生物标志物为靶点,应用不同的显像手段,为揭示CSCs在肿瘤进展中的生物学行为和潜在分子机制提供了可视化依据。因此,本文就转移干细胞的定义、转移相关的CSCs表面标志物、分子影像技术在CSCs检测中的应用、CSCs相关的转移微环境以及干细胞导向的肿瘤治疗等方面作一综述。     

上皮间质转化和肿瘤干细胞

最近,两个新的概念出现在肿瘤生物学中:上皮间质转化(epitheilal-mesenchymal transition,EMT)和肿瘤干细胞(cancer stem cells,CSCs)。EMT不仅赋予细胞迁移和侵袭特征,还可使肿瘤细胞获得自我更新能力而具有干细胞的特性,从而促进CSCs的产生。本文讨论EMT和CSCs之间的联系、EMT获得干细胞特征促进CSCs产生、EMT是形成CSCs的重要环节及二者在干细胞巢中的转化,并分析影响EMT和CSCs的因素。研究EMT在肿瘤发生中的作用,与CSCs理论相融合,从而可能发现新的肿瘤靶向治疗。     

基于CiteSpace的肝癌代谢研究的文献计量学分析

目的:通过肝癌代谢研究进行文献计量学分析,探索近5年肝癌代谢领域的研究热点和趋势。方法:基于Web of Science核心数据库,通过CiteSpace对2016年至2020年发表文章的年度分布、国家、机构、作者、期刊、基金、被引情况和关键词等进行可视化分析,并对关键词的词频、中心性和聚类情况进行探讨。结果:筛选后共纳入5 087篇文献并呈逐年增长趋势,中国是发文量最多的国家,复旦大学是发文量最多的机构,资助该领域最多的基金资助机构是中国国家自然科学基金委员会。AMPK、AKT/mTOR等信号通路调节代谢重编的机制研究;调控代谢的转录因子HIF-1α、癌基因（p53、c-myc）和长链非编码RNA的研究;针对糖酵解途径的葡萄糖转运和关键酶的研究;谷氨酰胺分解、三羧酸循环、磷酸戊糖途径、线粒体代谢的研究;二甲双胍等调节肿瘤代谢的药物研究;新型标志物分子的研究;代谢性疾病与肝癌相关性的研究是肝癌代谢领域研究的热点。糖酵解-代谢综合征-脂肪酸代谢-代谢酶抑制剂是肝癌代谢领域的研究趋势。结论:有氧糖酵解、AMPK、AKT/mTOR信号通路、HIF-1α、p53和c-myc、代谢性疾病、标志物分子和二甲双胍等药物研究是肝癌代谢的研究热点,脂肪酸代谢、代谢酶抑制剂研究是肝癌代谢领域的重点研究方向。     

靶向肿瘤干细胞天然药物的研究进展

摘 要：在肿瘤的发生、转移及复发过程中,肿瘤干细胞的自我更新和增殖分化能力发挥着关键作用。了解调控肿瘤干细胞自我更新的分子机制对研发靶向肿瘤干细胞的抗癌药物具有深远意义。天然活性化合物在肿瘤治疗中备受关注,越来越多的研究证实其可作用于肿瘤干细胞。文章综述了近年靶向肿瘤干细胞的热点天然药物,并对其抑制肿瘤干细胞的机制作一简单介绍。     

MicroRNA在肿瘤干细胞中的调控作用研究进展

肿瘤干细胞（CSCs）是导致肿瘤复发、转移和耐药的根源之一。microRNA（miRNAs）是一类小分子非编码RNA,可与靶mRNA的3＇UTR区域结合而导致该mRNA分子的翻译受到抑制,参与多种生物功能的调节。最近的研究发现,miRNAs参与CSCs的分化、自我更新等生物学特性的调控。miRNAs可以作为CSCs研究的一个新的切入点。本文就近年来该方面的研究进展做简要综述。     

核转录因子-κB与肿瘤上皮间质转化

 核转录因子-κB（NF-κB）是肿瘤上皮间充质转化（EMT）的重要调节因子。肿瘤发生EMT能够增强肿瘤浸润及远处转移能力,是肿瘤耐药的原因之一。目前研究发现,信号转导因子Snail、Slug、Twist、Zeb等在NF-κB调控肿瘤EMT中起重要作用。药物及靶向干扰NF-κB可以逆转肿瘤EMT。NF-κB有望成为将来肿瘤治疗的有效靶点之一。     

肝癌干细胞表面标记物及靶向治疗的研究进展

肝癌是一种常常致命的恶性肿瘤,具有较高的复发率和化疗耐药性。 癌症的主要恶性表现包括复发、转移和化疗耐药性,且都与肿瘤干细胞（cancer stem cells,CSCs）的存在有关。 在过去的几十年中,CSCs已经在包括肝癌在内的许多肿瘤中被鉴定和确定。 越来越多的证据揭示了许多肝癌干细胞（liver cancer stem cells,LCSCs）的生物学行为及其调控的机制。 基于这些研究结果,LCSCs的根除是靶向治疗的目标之一。 本综述重点介绍LCSCs表面标记物最新进展及其靶向治疗策略的发展。     

肿瘤细胞上皮间质转化表观遗传调控机制的研究进展

上皮间质转化(epithelial to mesenchymal transition,EMT)指上皮细胞向间质细胞转变的现象,其在组织损伤修复等生命过程中是必需的.研究发现,EMT在肿瘤细胞侵袭和转移中发挥至关重要的作用,EMT不仅使肿瘤细胞获得迁移、侵袭、转移能力,同时还与肿瘤细胞抑制衰老和凋亡、抵抗放化疗和形成肿瘤干细胞(cancer stem cells,CSCs)密切相关,因此抑制EMT成为抑制肿瘤转移的新策略.肿瘤细胞EMT受到表观遗传的复杂调控,DNA甲基化、组蛋白修饰、非编码RNA在EMT发生中扮演十分重要的角色,因此肿瘤细胞EMT的表观遗传调控已经成为国内外的研究热点.本文就肿瘤细胞EMT表观遗传调控机制的研究进展予以综述.     

上皮间质转化与肿瘤转移的研究进展

目的:总结上皮间质转化(EMT)的调节机制并揭示其与肿瘤转移的关系。方法:应用PubMed检索及CNKI中国期刊全文数据库检索系统,以上皮间质转化和肿瘤转移为关键词检索2004-2008年的相关文献。纳入标准:1)上皮间质转化调节机制的研究;2)上皮间质转化与肿瘤转移的关系。根据纳入标准,精选60篇文献,最后纳入分析33篇文献。结果:EMT存在于人体多个生理和病理过程中。EMT的发生涉及E-钙连蛋白、TGFβ、wnt信号通路、转录因子以及microRNA等机制的调节,转化为EMT的细胞具有干细胞样属性。结论:EMT与肿瘤细胞的转移关系密切,肿瘤细胞通过EMT获得侵袭能力转移至远端组织,随后MET使间质细胞恢复成上皮细胞,使肿瘤细胞重新获得增殖能力为其转移提供保证。     

肿瘤干细胞的来源

肿瘤干细胞是肿瘤演化的单位,阐明肿瘤干细胞的来源对于肿瘤的防治有重要意义.综合近年相关文献和工作中的体会探讨肿瘤干细胞的可能来源、产生途径和机制.正常干细胞转化为肿瘤干细胞需要经历漫长的基因突变积累过程;诱导重编程形成多潜能干细胞是体细胞产生肿瘤干细胞的可能途径之一;肿瘤细胞返分化为肿瘤干细胞是肿瘤干细胞来源之一;上皮-间充质转换(EMT)是细胞可塑性的重要机制,在肿瘤细胞转移和肿瘤细胞干性形成中起重要作用,细胞融合诱导EMT可能是肿瘤干细胞形成的另一重要机制;此外,一些病毒感染可能与肿瘤干细胞形成相关.文章对肿瘤生物学性状复杂性的机制也进行了讨论.     

上皮间质转化与肿瘤干细胞

上皮-间质转化(EMT)是生物胚胎发育的基础过程,与肿瘤细胞的原位侵袭和远处转移也密切相关.EMT与肿瘤干细胞(CSC)关系密切.CSC有较强的自我更新和致瘤能力以及细胞分化潜能.通过对CSC标志物的鉴定,深入研究其耐药性,可为肿瘤治疗提供新径.     

Pancreatic cancer stem cells: Emerging target for designing novel therapy

In the past few years, there have been significant advances in the research on cancer stem cells (CSCs). The emerging evidences have demonstrated that CSCs and epithelial–mesenchymal transition (EMT)-type cells, which share molecular characteristics with CSCs, play critical roles in drug resistance, invasion, and metastasis. Pancreatic cancer (PC) has a high mortality due to both intrinsic (de novo) and extrinsic (acquired) drug resistance, leading to increased invasive and metastatic potential of PC cells. Therefore, targeting pancreatic CSCs and EMT-type cells could be a novel therapeutic strategy for the treatment of PC. In this article, we will review the current state of our knowledge on the role of pancreatic CSCs and EMT-type cells, and summarize the novel therapeutic strategies that could target pancreatic CSCs and EMT-type cells, leading to the reversal of EMT phenotype, the induction of drug sensitivity, and the inhibition of invasion and metastasis of PC, which is expected to yield better treatment outcome.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

The clinical and therapeutic implications of cancer stem cell biology

Cancer stem cells (CSCs) have provided new insights into the tumorigenesis and metastatic potential of cancer. The discovery of CSCs has provided many new insights into the complexities of cancer therapy: tumor initiation, treatment resistance, metastasis, recurrence, assessment of prognosis and prediction of clinical course. Recent rapid advances in molecular analysis have contributed to the better understanding of the molecular attributes and pathways that give CSCs their unique attributes. Use of these molecular techniques has facilitated elucidation of specific surface markers and pathways that favor propagation of CSCs – allowing for targeted therapy. Furthermore, it has been discovered that a specific microenvironment, or niche, is essential for the genesis of tumors from CSCs. Therapeutic strategies that alter these microenvironments compromise CSC proliferation and constitute another method of targeted cancer therapy. We review the clinical and therapeutic implications of CSCs, with a focus on treatment resistance and metastasis, and the emerging approaches to target CSCs and their microenvironments in order to attain improved outcomes in cancer. It is noteworthy that CSCs are the only cells capable of sustaining tumorigenesis; however, the cell of origin of cancer, in which tumorigenesis is initiated, may be distinct from CSCs that propagate the tumor.     

The clinical and therapeutic implications of cancer stem cell biology

Cancer stem cells (CSCs) have provided new insights into the tumorigenesis and metastatic potential of cancer. The discovery of CSCs has provided many new insights into the complexities of cancer therapy: tumor initiation, treatment resistance, metastasis, recurrence, assessment of prognosis and prediction of clinical course. Recent rapid advances in molecular analysis have contributed to the better understanding of the molecular attributes and pathways that give CSCs their unique attributes. Use of these molecular techniques has facilitated elucidation of specific surface markers and pathways that favor propagation of CSCs - allowing for targeted therapy. Furthermore, it has been discovered that a specific microenvironment, or niche, is essential for the genesis of tumors from CSCs. Therapeutic strategies that alter these microenvironments compromise CSC proliferation and constitute another method of targeted cancer therapy. We review the clinical and therapeutic implications of CSCs, with a focus on treatment resistance and metastasis, and the emerging approaches to target CSCs and their microenvironments in order to attain improved outcomes in cancer. It is noteworthy that CSCs are the only cells capable of sustaining tumorigenesis; however, the cell of origin of cancer, in which tumorigenesis is initiated, may be distinct from CSCs that propagate the tumor.     

Krüpple样转录因子4与结肠癌发生发展关系的研究进展

Krüpple样转录因子4(KLF4)作为锌指转录因子家族的成员之一,对结肠癌的发生发展、转移、耐药等方面均有调节作用。KLF4通过上皮间充质转化(EMT)、肿瘤干细胞(CSCs)以及多个信号通路等机制在结肠癌中发挥抑癌或者促癌作用。本文就KLF4与结肠癌发生机制的最新研究进行综述,对于结肠癌治疗靶点的鉴定和分子机制的阐明具有重要意义。