乳腺癌肿瘤干细胞的研究进展

干细胞(stem cell,SC)是一类具有自我更新、多向分化潜能的特殊细胞群体.而肿瘤干细胞(cancer stem cell,CSC)不仅具备了干细胞方面的特征,同时还有其自身特殊性.乳腺癌中肿瘤干细胞的发现为乳腺癌的治疗提供了创新性策略.近年来,有关乳腺癌肿瘤干细胞的筛选标记和方法以及信号转导通路方面的研究颇多,但其中也不乏争议.就乳腺癌干细胞研究的最新进展作一端述.     

成体干细胞与肿瘤发生的关系

干细胞最重要特性之一是可自我更新,越来越多的证据显示肿瘤可认为是由干细胞生长调控机制失调引起的.该文从三个方面概述干细胞与肿瘤的关系,即：（1）肿瘤细胞中有一小部分称为肿瘤干细胞,具有无限增殖能力;（2）肿瘤干细胞与正常干细胞有相似的生长调控机制;（3）突变最先发生于干细胞.另外,对干细胞理论在肿瘤治疗中的意义也作了阐述.     

前列腺癌的靶向治疗研究现状与展望

前列腺癌难以根治,研究雄激素非依赖型前列腺癌的靶向治疗具有实际的临床意义,涉及抗体靶向治疗、靶向抗前列腺癌药物研制、细胞生长信号转导通路抑制、微小RNA应用等多方面,而靶向清除肿瘤干细胞则是根治前列腺癌的有效策略。     

胃癌干细胞研究进展

胃癌是仅次于肺癌的第二大致死率癌症,尽管近年来对胃癌研究有了很大进展,但由于缺乏良好的动物模型,对胃癌的发病机理仍然不是很清楚.近年的研究表明,肿瘤组织不是由均一细胞构成的,其中存在一些少量细胞可以自我更新并可以分化为肿瘤组织的其他细胞,这类细胞具有类似成体组织干细胞（tissue stem cells）的特性称之为肿瘤干细胞（cancer stem cells）.肿瘤干细胞被认为在肿瘤的生长、转移、复发中发挥着重要作用.有证据表明在胃癌组织中存在胃癌干细胞（gastric cancer stem cells）,但是对胃癌干细胞的来源仍然不是十分明确.对肿瘤干细胞的研究有助于癌症的治疗,改变目前药物针对所有癌细胞的治疗策略.     

干细胞、肿瘤干细胞与肿瘤

干细胞是一种具有自我更新、无限增殖和多向分化能力的细胞.而多数肿瘤是由不同增殖潜能的不均一性细胞构成.随着对干细胞的研究不断深入,使人们对肿瘤的发生机制重新进行了审视,并在造血系统、脑、肺、乳腺等部位肿瘤中发现极少量的具有与干细胞非常类似生物学特性的细胞,称之为肿瘤干细胞,它们很可能是肿瘤细胞的起源.肿瘤干细胞的提出.使得靶向性杀伤肿瘤干细胞从而使根治肿瘤和防止肿瘤复发和转移成为可能.所以研究肿瘤干细胞的起源及其与肿瘤的发生关系,成为当前研究和治疗肿瘤领域的新热点.本文就肿瘤干细胞的存在证据、干细胞与肿瘤干细胞的异同点及它们与肿瘤发生之间的关系作简要的综述.     

肿瘤干细胞鉴定方法

肿瘤干细胞假说是近年来提出的关于肿瘤发生的新理论,该理论认为肿瘤组织中仅有一小部分细胞可以产生肿瘤并且维持肿瘤生长。在体内外如何鉴定这种具有启动以及保持肿瘤生长的细胞类型,成为肿瘤基础及应用研究的关键问题。目前已经在白血病、乳腺癌、神经胶质瘤等肿瘤中成功鉴定并分离出肿瘤干细胞,这对于肿瘤的临床治疗具有重要意义。本文主要从肿瘤干细胞的鉴定及其在临床研究中的应用等方面进行综述。     

影响骨髓间充质干细胞增殖的调节因素及其信号转导途径

骨髓间充质干细胞是一类骨髓来源的成体干细胞,其生长、增殖行为受到多种环境因素的影响.胞外基质、细胞因子、机械刺激等理化因素对骨髓间充质干细胞的生长和增殖起着重要的调节作用,这些调节因素通过不同的信号转导途径影响骨髓间充质干细胞增殖,但又常常出现交叉对话、相互影响.就胞外基质、细胞因子和机械刺激影响骨髓间充质干细胞的增殖及其相应信号转导途径的研究进展作一简要综述.     

肿瘤干细胞的研究进展

肿瘤干细胞(cancer/tumor stem cell,CSC/TSC)假说认为肿瘤组织中存在极少量的瘤细胞充当着干细胞的角色,它们具有自我更新能力、无限增殖能力,且能驱动肿瘤的形成和生长。近年来,随着在血液肿瘤和实体瘤中相继发现CSC/TSC存在的相关证据,对CSC/TSC的生物学特性的认识不断深入,对肿瘤的复发、转移、耐药性等特点也有了新的观点和研究方向,就近年来该方面的进展作一综述。     

肿瘤干细胞靶向治疗研究进展

肿瘤干细胞是存在于肿瘤组织中的一小部分具有自我更新、多向分化和无限增殖能力的细胞,其控制着肿瘤的生长、分化,并且与 肿瘤的耐药性、转移以及复发密切相关。简述近年来国内外学者针对肿瘤干细胞的靶向治疗产品,包括抗体、多肽以及靶向药物的研究进展。 肿瘤干细胞的靶向治疗为临床肿瘤治疗提供了新的希望。     

microRNAs参与肿瘤干细胞的调节

肿瘤干细胞存在于多种类型肿瘤中,并与肿瘤的发生发展密切相关。肿瘤干细胞和胚胎干细胞在生物学特征上存在许多共同点,如自我更新,多潜能性分化等等。然而,肿瘤干细胞和胚胎干细胞又存在很大差异,主要表现在耐药性、致瘤力和转移活性上。肿瘤干细胞在临床研究中具有不可替代的重要性,然而其分子水平上的调节机制尚未被完整揭示。作为内源性非编码小RNA的一部分,miRNAs在细胞发生发展的调节过程中扮演着重要角色。大量研究表明,miRNAs参与肿瘤干细胞的调节,并参与肿瘤的发生与进展。探索miRNAs在肿瘤干细胞基因表达调控中的作用及作用机制,有助于肿瘤特异性生物学标志物及治疗靶点的确定。本文就miRNAs与肿瘤干细胞调节的相关研究进展进行综述。     

Cancer stem cells switch on tumor neovascularization

Recent studies on cancer stem cells (CSCs), a special subpopulation of tumor cells, promote our understanding of tumorigenesis, neovascularization, invasion, drug resistance and tumor recurrence, which establishes new concepts for cancer diagnosis and treatment. Therefore, the biological features and behaviors of CSCs have become an exciting frontier of cancer research. CSCs initiate tumor neovascularization and promote invasion with yet to be defined mechanisms. In this review, we provide evidence for the role of CSCs in tumor vascularization and discuss the potential mechanisms and therapeutic significance based on the interaction between CSCs and their vascular niches.     

免疫微环境对肿瘤干细胞影响研究进展

肿瘤干细胞是肿瘤组织中一小群特殊的未分化的细胞,由于其对化疗药耐受及致瘤潜能,被认为是造成肿瘤发生、复发和转移的根源,所以深入了解肿瘤干细胞特性对提高肿瘤治疗效率有着重要临床意义.肿瘤微环境中的免疫细胞及其分泌的分子与肿瘤干细胞之间存在复杂的相互作用,可以维持肿瘤干细胞的干性及自我更新能力.目前,肿瘤免疫微环境对肿瘤干细胞的影响、肿瘤干细胞对免疫微环境的塑造作用以及靶向肿瘤干细胞或免疫微环境等研究,是肿瘤干细胞研究领域的热点问题.本文就免疫微环境对肿瘤干细胞的影响、靶向肿瘤干细胞及微环境治疗的研究进展进行了综述.     

肿瘤干细胞的光动力治疗研究进展

肿瘤干细胞(cancerstem cells,CSCs)是在肿瘤组织中具有干细胞特性的细胞亚群,它具有正常干细胞的多向分化潜能,能够无限增值和自主分化为各种具有异质性的肿瘤细胞。CSCs在肿瘤的发生、生长、转移中起着重要作用。同时,CSCs对目前大多数治疗如化疗、放疗不敏感,甚至具有耐药性,这也就导致了恶性肿瘤在治疗后容易复发。鉴于此,针对肿瘤干细胞的治疗日益受到关注,光动力疗法(photodynamictherapy,PDT)由于其微创性,不良反应少,靶向性强等特点在肿瘤的治疗研究中不断得到发展。本文将从CSCs的特性入手,结合PDT治疗的最新进展,探讨PDT治疗在肿瘤干细胞治疗中的应用。     

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines

Cancer stem cells (CSCs) are defined as a subset of slow cycling and undifferentiated cells that divide asymmetrically to generate highly proliferative, invasive, and chemoresistant tumor cells. Therefore, CSCs are an attractive population of cells to target therapeutically. CSCs are predicted to contribute to a number of types of malignancies including those in the blood, brain, lung, gastrointestinal tract, prostate, and ovary. Isolating and enriching a tumor cell population for CSCs will enable researchers to study the properties, genetics, and therapeutic response of CSCs. We generated a protocol that reproducibly enriches for ovarian cancer CSCs from ovarian cancer cell lines (SKOV3 and OVCA429). Cell lines are treated with 20 µM cisplatin for 3 days. Surviving cells are isolated and cultured in a serum-free stem cell media containing cytokines and growth factors. We demonstrate an enrichment of these purified CSCs by analyzing the isolated cells for known stem cell markers Oct4, Nanog, and Prom1 (CD133) and cell surface expression of CD177 and CD133. The CSCs exhibit increased chemoresistance. This method for isolation of CSCs is a useful tool for studying the role of CSCs in chemoresistance and tumor relapse.     

肿瘤微环境中上皮–间质转化与肿瘤干细胞的调控

肿瘤微环境是一个复杂的组织样结构,具有丰富的表型和功能异质性。不同浓度的趋化因子、细胞因子与组成肿瘤微环境的细胞间相互作用,可激活上皮–间质转化(epithelial-mesenchymal transition,EMT)相关的信号通路及控制肿瘤干细胞(cancer stem cells,CSCs)的生成。EMT的异常激活会促进肿瘤细胞的可塑性,赋予上皮细胞间充质特性,并与癌细胞获得侵袭性的特征密切相关。CSCs是一类具有高致瘤潜能的细胞群,其能很容易地适应周围环境的变化,与肿瘤内其他细胞相比具有较强的抗药性。该文对肿瘤微环境中EMT与CSC的作用机制及相关信号通路的研究进展进行综述。     

Cancer stem cell, niche and EGFR decide tumor development and treatment response: A bio-computational simulation study

Recent research in cancer biology has suggested the hypothesis that tumors are initiated and driven by a small group of cancer stem cells (CSCs). Furthermore, cancer stem cell niches have been found to be essential in determining fates of CSCs, and several signaling pathways have been proven to play a crucial role in cellular behavior, which could be two important factors in cancer development. To better understand the progression, heterogeneity and treatment response of breast cancer, especially in the context of CSCs, we propose a mathematical model based on the cell compartment method. In this model, three compartments of cellular subpopulations are constructed: CSCs, progenitor cells (PCs), and terminal differentiated cells (TCs). Moreover, (1) the cancer stem cell niche is, considered by modeling its effect on division patterns (symmetric or asymmetric) of CSCs, and (2) the EGFR signaling pathway is integrated by modeling its role in cell proliferation, apoptosis. Our simulation results indicate that (1) a higher probability for symmetric division of CSC may result in a faster expansion of tumor population, and for a larger number of niches, the tumor grows at a slower rate, but the final tumor volume is larger; (2) higher EGFR expression correlates to tumors with larger volumes while a saturation function is observed, and (3) treatments that inhibit tyrosine kinase activity of EGFR may not only repress the tumor volume, but also decrease the CSCs percentages by shifting CSCs from symmetric divisions to asymmetric divisions. These findings suggest that therapies should be designed to effectively control or eliminate the symmetric division of CSCs and to reduce or destroy the CSC niches.     

Cancer stem cells: Road to therapeutic resistance and strategies to overcome resistance

Unlike other normal cells, a subpopulation of cells often termed as “stem cells” are long-lived and generate cellular progeny throughout life. Cancer stem cells (CSCs) are rare immortal cells within a tumor that can both self-renew by dividing and giving rise to many cell types that constitute the tumor. CSCs also have been shown to be involved in fundamental processes of cell proliferation and metastatic dissemination. CSCs are generally resistant to chemotherapy and radiotherapy, a subset of remaining CSCs after therapy can survive and promote cancer relapse and resistance to therapies. Understanding the biological characteristics of CSCs, the pathways leading to their sustainability and proliferation, and the CSCs role in drug resistance is crucial for establishing novel tumor diagnostic and therapeutic strategies. In this review, we address the pathways that regulate CSCs, the role of CSCs in the resistance to therapy, and strategies to overcome therapeutic resistance.     

Cancer cells stemness: A doorstep to targeted therapy

Recent advances in research on cancer have led to understand the pathogenesis of cancer and development of new anticancer drugs. Despite of these advancements, many tumors have been found to recur, undergo metastasis and develop resistance to therapy. Accumulated evidences suggest that small population of cancer cells known as cancer stem cells (CSC) are responsible for reconstitution and propagation of the disease. CSCs possess the ability to self-renew, differentiate and proliferate like normal stem cells. CSCs also appear to have resistance to anti-cancer therapies and subsequent relapse. The underlying stemness properties of the CSCs are reliant on multiple molecular targets such as signaling pathways, cell surface molecules, tumor microenvironment, apoptotic pathways, microRNA, stem cell differentiation, and drug resistance markers. Thus an effective therapeutic strategy relies on targeting CSCs to overcome the possible tumor relapse and chemoresistance. The targeted inhibition of these stem cell biomarkers is one of the promising approaches to eliminate cancer stemness. This review article summarizes possible targets of cancer cell stemness for the complete treatment of cancer.