神经干细胞和脑肿瘤干细胞研究进展

神经干细胞(NSC)是中枢神经系统(CNS)内具有自我更新和多向分化潜能的干细胞,主要存在于脑室下区域(SVZ),NSC通过自我更新和分化维持正常CNS的形态和功能。可塑性(plastici- ty)是NSC的重要特征,由NSC所处的微环境(microenvironment)决定。脑肿瘤干细胞(BTSC)是脑肿瘤中与NSC相似的细胞,是脑肿瘤发生和生长的细胞来源。BTSC可能起源于NSC,是NSC可塑性的表现,导致NSC向BTSC分化的机制可能是微环境作用的结果。     

发育相关的信号通路与脑肿瘤干细胞

许多学者发现存在与脑肿瘤发生和生长有密切相关的细胞亚群。这些细胞显示出干细胞样的特性如可自我更新，永久分化增殖，并且在遗传学和表型上与正常神经干细胞相似故被称为脑肿瘤干细胞（brain tumor stem cells，BTSC）。     

神经干细胞在恶性脑肿瘤基因治疗中的应用现状及前景

神经干细胞(neural stem cell，NSC)是具有增殖能力和分化潜能的细胞。神经干细胞的建立和基因修饰技术的完善，为基因治疗恶性脑肿瘤提供了可能。目前，NSC在恶性脑肿瘤中基因治疗的应用，主要包括构建载体和包装病毒载体。综述了这方面的研究进展和前景。     

干细胞niche与肿瘤干细胞产生和发展的关系

肿瘤干细胞学说认为大部分肿瘤来源于肿瘤干细胞。肿瘤干细胞与正常干细胞一样具有自我更新能力,能够产生肿瘤组织团块中的各种增殖和分化的细胞。肿瘤干细胞可能来源于正常干细胞或分化细胞。干细胞niche是干细胞生存的微环境,通过提供抑制细胞增殖和生长的信号来维持干细胞于静止状态。干细胞niche功能异常会导致niche的数量增加,以及干细胞功能异常和数量增加。肿瘤干细胞可能在异常的niche中存活,打破这种异常的niche就会削弱肿瘤干细胞的自我更新,从而抑制肿瘤的生长。靶向肿瘤干细胞异常微环境的治疗策略可能是癌症治疗的一个方向。     

神经干细胞在恶性脑肿瘤基因治疗中的应用现状及前景

神经干细胞 (neuralstemcell,NSC)是具有增殖能力和分化潜能的细胞。神经干细胞的建立和基因修饰技术的完善 ,为基因治疗恶性脑肿瘤提供了可能。目前 ,NSC在恶性脑肿瘤中基因治疗的应用 ,主要包括构建载体和包装病毒载体。综述了这方面的研究进展和前景     

神经干细胞和脑肿瘤干细胞与胶质瘤发生发展潜在性研究

自从1992年R eyno lds从成年小鼠纹状体中分离到能够不断增殖、具有多向分化潜能的细胞群、提出了神经干细胞(neural stem cell, N SC )的概念以来, N SC的研究已成为神经科研的一个重要领域。从N SC的分离、体外培养、分化调控到移植治疗神经系统疾病,各个方面都有了一定进展。从其发展过程来看,从小鼠到人类胚胎都得到证实后,现在成体干细胞更成为研究的热点。在N SC的研究取得了一定成果的基础上,一些神经肿瘤学者提出了脑肿瘤干细胞(brain tum or stem cell, BTSC )的概念,认为BTSC是脑肿瘤的起源细胞。目前关于BTSC的报道较…     

肿瘤干细胞及其微环境与肿瘤的耐药、复发和转移

 肿瘤干细胞（NSC）是肿瘤发生发展的根源,其特殊的微环境可通过调控NSC或者其自身变化参与肿瘤的耐药、复发和转移。根除NSC和干扰其特殊微环境可能是治疗肿瘤的新策略。     

CD133在脑瘤干细胞研究与临床应用中的新进展

CD133作为一种在脑肿瘤干细胞（brain tumor stem cell,BTSC）表面广泛表达的跨膜糖蛋白,已被公认为BTSC的特异性标志物,为BTSC的研究奠定了基础,在其分选鉴定、肿瘤分级和预后诊断方面起重要作用。但是,CD133作为BTSC特异性标志物的可靠性仍颇受争议。本文在查阅大量国内外最新文献的基础上,针对CD133的结构、特征,及其在BTSC研究中的具体应用和争议进行综述,并提出几种可能的CD133＋细胞靶向治疗方案。     

结直肠癌干细胞和肿瘤微环境的相互影响及靶向策略

肠癌干细胞是结直肠癌中少量的具有恶性表型特征的未分化致瘤细胞,具有自我更新和分化克隆等独特的特征,被认为是肿瘤复发、耐药、转移的主要原因。肠癌干细胞与肿瘤微环境中各成分之间互相依存,互相影响,了解肿瘤微环境中肿瘤干细胞和其他成分之间的联系,可能对结直肠癌的治疗具有重要作用。本文就肠癌干细胞和肿瘤微环境的关系及靶向治疗进行综述。     

BMPs在脑肿瘤干细胞中的研究进展

骨形成蛋白（bone morphogenetic proteins，BMPs）在神经干细胞的增殖和分化过程中起重要的调节作用：脑肿瘤干细胞是从脑肿瘤中分离得到的干细胞样的肿瘤起源细胞，与神经干细胞有很大的相似性，它们之间存在很多共同的信号传导通路。在神经干细胞增殖分化中起重要调节作用的BMPs信号通路对脑肿瘤干细胞的增殖和分化也起重要的调节作用。     

肝干细胞与肝癌干细胞

正常肝干细胞在致癌因素作用下发生基因突变，获得无限增殖能力成为肿瘤干细胞，肿瘤干细胞分化成各种分化等级、表型不一的肿瘤。在正常肝干细胞转化成肝癌干细胞的过程中保留了一些干细胞表型特征和进一步向相对成熟细胞分化的能力。正常肝干细胞是肝癌重要起源。     

甲状腺干细胞及其与甲状腺肿瘤干细胞的关系

甲状腺干细胞是存在于甲状腺组织内具有自我更新及增殖分化潜能的细胞.甲状腺肿瘤干细胞是甲状腺肿瘤组织中与甲状腺干细胞相似的细胞,是甲状腺肿瘤发生发展的细胞来源.研究表明,甲状腺干细胞是甲状腺肿瘤干细胞的重要来源,其恶变时所处的分化阶段对甲状腺肿瘤的恶性程度有重要影响.     

Leukemia stem cells

Leukemia stem cells (LSCs) might originate from malignant transformation of normal hematopoietic stem cells (HSCs), or alternatively, of progenitors in which the acquired mutations have re-installed a dysregulated self-renewal program. LSCs are on top of a hierarchy and generate leukemia cells with more differentiated characteristics. While most leukemia cells are initially sensitive to chemo- and radiotherapy, LSCs are resistant and are considered to be the basis for disease relapse after initial response. Albeit important knowledge on LSC biology has been gained from xenogeneic transplantation models introducing human leukemia cells into immune deficient mouse models, the prospective identification and isolation of human LSC candidates has remained elusive and their prognostic and therapeutic significance controversial. This review focuses on the identification, enrichment and characterization of human LSC derived from patients with acute myeloid leukemia (AML). Experimental data demonstrating the clinical significance of estimating LSC burden and strategies to eliminate LSC will be summarized. For long-term cure of AML, it is of importance to define LSC candidates and to understand their tumor biology compared to normal HSCs. Such comparative studies might provide novel markers for the identification of LSC and for the development of treatment strategies that might be able to eradicate them.     

Tumor stem cells

Stem cells possess two basic characteristics: they are able to renew themselves and to develop into different cell types. The link between normal stem cells and tumor cells could be examined in three aspects: what are the differences and similarities in the control of self-renewal capacity between stem cells and tumor cells; whether tumor cells arise from stem cells; do tumorous stem cells exist? Since tumor cells also exhibit self-renewal capacity, it seems plausible that their regulation is similar to that of the stem cells. The infinite self-renewal ability (immortalization) is assured by several, so far only partly known, mechanisms. One of these is telomerase activity, another important regulatory step for survival is the inhibition of apoptosis. Other signal transduction pathways in stem cell regulation may also play certain roles in carcinogenesis: e.g. Notch, Sonic hedgehog (SHH), and Wnt signals. Existence of tumor stem cells was suggested since it is simpler to retain the self-renewal capacity than to reactivate the immortality program in an already differentiated cell. Moreover, stem cells live much longer than the differentiated ones, and so they are exposed for a long period of time to impairments, collecting gene errors leading to the breakdown of the regulation. However, it is still an open question whether all cells in the tumor possess the capacity that produces this tissue or not, that is: are there tumor stem cells or there are not. If tumor stem cells exist, they would be the main target for therapy: only these must be killed since the other tumor cells possess limited proliferative capacity, therefore limited life span. The only problem is that during tumor progression stem-like cells can develop continuously and the identification but mainly the prevention of their formation is still a great challenge.(Pathology Oncology Research Vol 10, No 2, 69–73)     

Teratocarcinoma stem cells

Human teratocarcinomas or mixed germ cell tumours are histologically composed of diverse tissues corresponding to somatic and extraembryonic (trophoblastic and yolk sac) like cells, as well as malignant stem cells. In typical teratocarcinomas these stem cells correspond to embryonal carcinoma cells, ie developmentally pluripotent cells equivalent to embryonic cells from the early stages of development. These cells have the capacity to differentiate and give rise to non-proliferating terminally differentiated tissue. Occasionally embryonal carcinoma cells can give rise to more differentiated stem cells which have the phenotype and the restricted developmental potential of choriocarcinoma and yolk sac carcinoma cells, or less commonly to somatic cell malignancies, indistinguishable from typical carcinomas, sarcomas, melanoma or lymphomas. Malignant transformation of benign somatic tissues in teratomas can also give rise to malignant stem cells, which all have a somatic cell phenotype. The biology and the clinical presentation as well as the response to chemotherapy of germ cell tumours depend on the nature of stem cells that form their proliferative compartment and account for the malignancy of these tumours.     

Leukemia stem cells

Leukemia stem cells (LSC) reside within a hierarchy of malignant hematopoiesis and possess the ability to instigate, maintain and serially propagate leukemia in vivo, while retaining the capacity to differentiate into committed progeny that lack these properties. In most cases, LSC appear to share immunophenotypic characteristics with committed hematopoietic progenitors, however have pathologically enhanced self-renewal, mediated through the activation of certain cellular pathways. The presence of a LSC that solely possesses the ability to initiate and sustain leukemia has implications for the treatment of patients with this disease. In this review, we will discuss these issues as well as some of the recent controversies regarding LSC frequency and alternative theories of leukemogenesis.     

Hepatocellular stem cells

The liver has enormous regenerative capacity. Restitution of the liver in response to different injuries involves proliferation of cells at different levels of liver lineage. Mature hepatocytes, which are normally dormant, could undergo rapid replication with a near infinite capacity to proliferate. When the replication of mature hepatocytes is inhibited, a reserve compartment of bipotential hepatic progenitor/stem cells is activated. The degree of activation appears to correlate with the degree of inflammation and stage of chronic liver disease. Deregulation of key regulatory signaling pathways such as transforming growth factor-beta, Wnt, hepatocyte growth factor, insulin-like growth factor, transforming growth factor-alpha and epidermal growth factor in this progenitor/stem cell population could give rise to HCC. Further understanding of these key signaling pathways and the molecular and genetic alterations associated with HCC could provide major advances in new therapeutic and diagnostic modalities.