肿瘤干细胞研究进展

肿瘤是由功能异质性的细胞群体组成的。有研究认为肿瘤起源于干细胞，是一种千细胞疾病。只有小部分肿瘤干细胞才有成瘤及维持恶性显型的作用。由此可推论：肿瘤治疗的关键应是针对肿瘤干细胞的治疗。肿瘤干细胞研究对肿瘤发生发展机制的阐明、治疗新靶点的发现等将产生深远影响。     

肿瘤干细胞研究进展

肿瘤干细胞是存在于肿瘤组织中的一小部分具有干细胞性质的细胞群体,它具有自我更新的能力,是形成不同分化程度肿瘤细胞和肿瘤不断扩大的源泉.人们对肿瘤干细胞的认识开始于研究肿瘤组织的克隆起源,通过镶嵌性联同工酶标记,已证实了肿瘤细胞的单克隆源性[1],进而逐渐形成肿瘤干细胞的概念.随着干细胞研究的不断深入,有关知识的不断积累,又为肿瘤干细胞理论注入了很多新的观念.目前对肿瘤干细胞的研究越来越热,很多实验证实肿瘤干细胞的存在,人们也在不断探索肿瘤干细胞的起源.通过这些方面的研究,人们对肿瘤发生发展过程的认识将会提高到一个新的阶段,对肿瘤的诊断和治疗以及预后判断将产生深远影响,将为战胜这一顽疾提供新的方法.     

肿瘤干细胞与肿瘤的诊断、转归和预后的关系

肿瘤干细胞(cancer stem cells,CSCs)是近年来干细胞研究和肿瘤研究的热点之一,它具有强大的自我更新和致瘤能力以及不断分化的潜能。目前研究发现肿瘤治疗后易复发、预后差、具有强耐药性与肿瘤中存在肿瘤干细胞有密切的关系。且肿瘤干细胞学说认为,肿瘤很可能是肿瘤干细胞产生的,并且已有学者和专家在造血系统肿瘤和多种实体瘤中分离并鉴定出肿瘤干细胞。对肿瘤干细胞、肿瘤干细胞与肿瘤的发生、发展、诊断、治疗及预后之间的关系作一综述。     

乏氧与肿瘤干细胞干性、异质性和血管生成的关系

摘 要：缺氧诱导因子（HIFs）是肿瘤干细胞适应乏氧及营养缺乏的主要调节因子。活化的HIFs可以诱导肿瘤干细胞的干性维持、异质性和血管生成,对肿瘤干细胞介导肿瘤的自我更新、多分化潜能及可塑性、血管生成及侵袭和转移能力、治疗抗性起到重要作用。因此,研究HIFs与肿瘤干细胞干性、异质性和血管生成的关系,将为肿瘤的治疗提供新的思路。     

肿瘤干细胞与肿瘤的诊断、转归和预后的关系

肿瘤干细胞（cancerstemcells,CSCs）是近年来干细胞研究和肿瘤研究的热点之一,它具有强大的自我更新和致瘤能力以及不断分化的潜能。目前研究发现肿瘤治疗后易复发、预后差、具有强耐药性与肿瘤中存在肿瘤干细胞有密切的关系。且肿瘤干细胞学说认为,肿瘤很可能是肿瘤干细胞产生的,并且已有学者和专家在造血系统肿瘤和多种实体瘤中分离并鉴定出肿瘤干细胞。对肿瘤干细胞、肿瘤干细胞与肿瘤的发生、发展、诊断、治疗及预后之间的关系作一综述。     

胃癌干细胞鉴定和治疗的研究进展

胃癌是最常见的消化道恶性肿瘤。近年来,随着对干细胞和肿瘤研究的不断深入,越来越多的证据表明,肿瘤来源于干细胞,肿瘤干细胞在胃癌发病机制中的作用日益受到重视。但是在对胃癌干细胞的筛选方面仍没有非常精准的方法,如何针对胃癌干细胞进行治疗仍是现在研究的热点。本文对胃癌干细胞的研究进展作一综述,将有助于加深对胃癌干细胞的认识,并为从根本上控制胃癌的发生和发展提供线索。      

肿瘤干细胞疫苗的研究进展

目前已知的绝大多数癌症治疗方法如化疗、放疗、免疫靶向治疗等主要以肿瘤细胞为靶目标,但很多肿瘤并不能被完全治愈且治疗后伴随很多并发症。一群高度耐药的肿瘤细胞能够使肿瘤重新聚集并转移到新的部位,使肿瘤继续发生发展。如果可以基于它们的表型或功能特征来鉴定具有干细胞样特征的癌细胞,从而找到肿瘤干细胞特异性抗原制成干细胞疫苗,进而激活机体内特异的免疫应答,以达到靶向清除肿瘤干细胞的目的,就能一定程度上控制肿瘤的复发及转移,杀灭肿瘤干细胞甚至可以消除肿瘤对放化疗的拮抗性及耐药性。因此肿瘤干细胞疫苗即靶向肿瘤干细胞的主动免疫疗法的研究与发展对恶性难治性肿瘤的治疗有着重要意义,本篇综述将对近年来肿瘤干细胞及其疫苗的发现、发展与研究结果进行概述。     

乙醛脱氢酶在肿瘤干细胞鉴定中的作用

摘 要：肿瘤干细胞被认为是肿瘤复发和转移的根源,其鉴定尤为重要。当前肿瘤干细胞鉴定的主要方法有利用干细胞表面标志鉴定、细胞增殖和分化能力的鉴定、动物体内致瘤性鉴定、化疗耐药性的鉴定、放疗抵抗性的鉴定等。乙醛脱氢酶是细胞质中调节乙醛代谢的一种重要酶类,其在肿瘤干细胞中显示出很高的活性,可作为肿瘤干细胞鉴定的标志物。研究乙醛脱氢酶在肿瘤干细胞鉴定中的作用将有利于肿瘤的诊断、治疗和预后评估。     

肿瘤干细胞相关机制及靶向肿瘤干细胞治疗研究进展

肿瘤干细胞(cancer stem cells,CSCs)是肿瘤细胞中存在的小部分具有无限自我更新和多向分化潜能的细胞亚群,是肿瘤形成、复发、恶性转移和耐受放化疗性的细胞学根源.肿瘤干细胞的相关研究为肿瘤的治疗提供了新的思路,肿瘤干细胞靶向治疗可能成为肿瘤根治的希望.然而,目前对肿瘤干细胞的调控机制还不甚清楚,基于调控肿瘤干细胞的抗肿瘤治疗还有待成熟.本综述旨在总结近年来有关调控肿瘤干细胞及相关肿瘤治疗的主要研究进展,并对基于肿瘤干细胞调控的抗肿瘤治疗进行讨论和展望.     

肺癌干细胞标志物研究现状

摘 要：肿瘤干细胞是近年肿瘤领域研究热点,其理论的提出为肿瘤的治疗提供了新的思路及靶点。肺癌是当今社会威胁人类健康的主要恶性肿瘤,深入研究肺癌干细胞有望提高其治疗有效率。而肺癌干细胞的识别是其研究的第一步,找到行之有效的肺癌干细胞标志物十分必要。全文对目前肺癌干细胞标志物研究现状作一综述。     

肿瘤干细胞及肿瘤靶向治疗的研究进展

研究发现引起肿瘤复发或转移的根源是肿瘤中一少部分具有无限增殖能力的肿瘤干细胞,其在体内长期存在并不断自我更新,使肿瘤快速增殖且侵袭、转移能力增加,药物敏感性减弱,成为临床治疗的难题。因此,深入了解肿瘤干细胞进而寻找抑制肿瘤干细胞的方法对临床靶向治疗肿瘤具有重要意义。本文从肿瘤干细胞的发现过程、生物学特性、鉴别及培养方法等方面进行了阐述,根据其特点总结针对肿瘤干细胞治疗肿瘤的方法,并重点综述抗生素治疗肿瘤干细胞的研究进展。     

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)     

肿瘤干细胞相关研究进展

干细胞具有自我更新和多向分化的特征.随着对干细胞进一步了解及肿瘤基础研究的不断深入,越来越多证据表明肿瘤中极少数细胞具有干细胞特征,肿瘤干细胞概念随之产生,且已从血液肿瘤、乳腺癌及神经系统肿瘤中分离出肿瘤干细胞.这些细胞具有治疗抵抗特性,能够耐受传统的细胞毒化疗和放射治疗.肿瘤生长正是这些具有特殊表型细胞分化增殖的结果.许多学者认为,肿瘤复发、转移以及耐药等均与肿瘤干细胞相关,肿瘤治疗关键应该针对肿瘤干细胞.这一全新的治疗概念给肿瘤治疗带来希望,同时对传统肿瘤治疗模式提出了巨大挑战.肿瘤干细胞的发现、自身特点以及对肿瘤治疗可能影响的研究具有重要意义.     

Isolation of cancer stem cells from adult glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor and is comprised of a heterogeneous population of cells. It is unclear which cells within the tumor mass are responsible for tumor initiation and maintenance. In this study, we report that brain tumor stem cells can be identified from adult GBMs. These tumor stem cells form neurospheres, possess the capacity for self-renewal, express genes associated with neural stem cells (NSCs), generate daughter cells of different phenotypes from one mother cell, and differentiate into the phenotypically diverse populations of cells similar to those present in the initial GBM. Having a distinguishing feature from normal NSCs, these tumor stem cells can reform spheres even after the induction of differentiation. Furthermore, only these tumor stem cells were able to form tumors and generate both neurons and glial cells after in vivo implantation into nude mice. The identification of tumor stem cells within adult GBM may represent a major step forward in understanding the origin and maintenance of GBM and lead to the identification and testing of new therapeutic targets.     

间充质干细胞基因治疗肿瘤新进展

骨髓间充质干细胞(MSC)是骨髓内除造血干细胞和多功能前祖细胞外另一种成体干细胞,具有很强的自我更新能力、多向分化潜能.该细胞具有明显的趋向肿瘤移动并与肿瘤组织楔合的生长特性.虽然骨髓间充质干细胞有向肿瘤干细胞转化的风险,但其作为一种克隆载体可以转导治疗基因在体内获得长期稳定表达,对肿瘤的靶向治疗有着广阔的前景.     

微小RNA在肿瘤干细胞中的研究进展

肿瘤干细胞学说（tumorstemcells,TSCs）认为肿瘤组织中存在一小部分细胞具有干细胞特性,具有自我更新和多向分化的潜能,是肿瘤形成、发展、转移及复发的根本原因。最近的研究发现微小RNA（miRNA）在维持肿瘤干细胞生物学特性方面发挥着重要作用。探讨miRNA参与调控肿瘤干细胞特性的分子机制,具有重要的理论意义。     

脑肿瘤干细胞的研究

大量事实表明,包括脑肿瘤在内,所有肿瘤细胞群落之间在形态和功能上存在很大差异,其异质性与肿瘤干细胞的分化潜能有关.脑肿瘤干细胞的分离和培养获得了成功.脑肿瘤干细胞具有增殖、自我更新以及多向分化的特点;但其在肿瘤组织中所占的比例很低,却是肿瘤保持恶性特征的关键所在.     

Hirntumorstammzellen und Therapieresistenz in malignen Gliomen

The identification of tumor initiating cells or tumor stem cells capable of self-renewal has changed our fundamental view on tumorigenesis and tumor progression. A hierarchical order of different aggressive cell types derived from a small population of brain tumor stem cells is the basis for the heterogeneity in malignant gliomas. The glioma stem cells are extremely resistant to chemotherapy and radiotherapy they survive adjuvant cancer therapy and are the basis for recurrent tumor growth and clinical relapse. Therefore, modern therapies should be targeted against this cell type. It is a major goal to identify brain tumor stem cell markers for imaging and to enhance neuropathological diagnostics.     

实体瘤干细胞研究进展

新近的研究结果表明,肿瘤细胞在成瘤性方面存在不均一性。肿瘤中存在少量具有自我更新和高增殖能力的干细胞,它们在维持肿瘤生长中起决定性作用。该理论首先在血液系统肿瘤中取得突破,并在部分实体瘤如乳腺癌、脑肿瘤、前列腺肿瘤、肺癌、胰腺癌及部分细胞系中成功分离出了肿瘤干细胞。目前实体瘤干细胞的标志研究主要集中于CD133、CD44、CD117和CD34等CD分子。干细胞的识别将为肿瘤病理的认识及肿瘤治疗提供新的思路和方法。     

CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells

Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.