肿瘤干细胞的研究进展

肿瘤干细胞学说认为肿瘤组织中存在极少量瘤细胞,在肿瘤中充当干细胞的角色,具有无限增生的潜能,在启动肿瘤形成和生长中起着决定性的作用。肿瘤干细胞的研究最初在白血病中获得突破,寻找到急性粒细胞白血病的干细胞表型,随后的研究证明白血病干细胞的免疫表型在许多方面与造血干细胞相似。随着对干细胞研究的深入,研究领域已经扩展到实体瘤,首次寻找和证实实体瘤肿瘤干细胞的实验是在乳腺癌的研究中进行的,研究发现了具备干细胞特性的细胞表面抗原。随后实体瘤的干细胞研究在脑肿瘤及前列腺肿瘤等中开展,并得到了初步的结果。近来肿瘤干细胞的研究集中到针对肿瘤干细胞的治疗中。本文对肿瘤干细胞最近的研究情况进行综述。     

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。     

大剂量化疗合并自体造血干细胞移植治疗晚期实体瘤进展

大剂量化疗合并自体造血干细胞移植治疗晚期实体瘤进展苏州医学院附属一院（苏州市２１５００６）张军宁综述许昌韶审校早在１９５８年，Ｋｕｒｎｉｃｋ等（１）首先提出自体骨髓移植治疗放化疗所致骨髓再生障碍的设想，直至１９７８年，Ｂｌｏｏｄ杂志才首先报道了大剂量...     

实体瘤诱导分化研究进展

 实体瘤诱导分化研究进展钱军综述秦叔逵审校诱导分化(INDUCTTONOFDIFF ERENTIATION)是指恶性肿瘤细胞在体内外分化诱导剂存在下，重新分化向正常方向逆转的现象。目前，国内外文献资料中出现许多这样的术语，如肿瘤逆转(REVERSION)。     

自体造血干细胞移植治疗恶性实体瘤的新进展

近年来自体造血干细胞移植（ＡＳＣＴ）在实体瘤的治疗上积累了一定的经验,针对实体瘤ＡＳＣＴ的疗效、适应症及其在综合治疗中的位置等需要回答的问题进行了相应的研究,得出了一些新的结果。１非霍奇金淋巴瘤（ＮＨＬ）１．１复发耐药者ＤＨＡＰ、ＶＩＭ等常规的解救方...     

肿瘤干细胞真的存在吗?

肿瘤干细胞是个令人激动的概念,其假说似乎回答了肿瘤起源的问题.然而从肿瘤中分离出的细胞是否为真正的肿瘤干细胞还存在理论、技术和数学方面的疑问.本文分析肿瘤干细胞不存在的可能性.     

实体瘤患者外周血造血干细胞的动员与保存

目的 :探讨一种适于晚期恶性肿瘤治疗的自体外周血造血干细胞移植方法。方法 :单用rG -CSF(75μg,q12h×2d)作动员剂 ,用血细胞分离机一次性收集单个核细胞(MNC),4℃贮存。观察WBC、MNC计数、细胞活力及细胞分类 ;用流式细胞仪进行细胞表型检测。结果 :小剂量rG -CSF动员后 ,外周血WBC达(18.71±6.54)×109/L。一次可收集MNC(1.87±0.66)×108/kg。CD34、CD14、CD3 及CD22 细胞分别为4.39 %、3.85 %、4.63 %及3.76 %。CD34 细胞平均约为8.2×106/kg。4℃贮存48～56小时MNC存活率为94.3 %。结论 :对实体瘤尚无骨髓转移的患者 ,用此方法可获得足以重建造血功能的干细胞。     

两日预处理方案自体造血干细胞移植治疗恶性实体瘤

目的：探索应用两日预处理方案自体造血干细胞移植治疗实体瘤的疗效与安全性。方法：13例实体瘤患者,中位年龄50岁（14-65岁）,预处理方案9例采用60Co全身照射7.9-8.3Gy加联合化疗,4例不含全身照射。化疗方案组合包括环磷酰胺、顺铂、5-氟脲嘧啶（CDF）,环磷酰胺、阿糖胞苷、足叶乙甙（CAE）,环磷酰胺、阿霉素、顺铂、足叶乙甙（CADE）。全部预处理在48小时内完成,评价疗效及相关毒性反应。结果：13例完全缓解8例（61.5%）,部分缓解2例（15.4%）,总体治疗反应率76.9%;移植相关死亡2例（15.4%）,未缓解或复发4例（30.8%）。中位随访时间14个月,最长无病生存期26个月。结论：两日预处理方案自体造血干细胞移植可有效杀伤肿瘤组织,疗效与非两日预处理方案近似,不增加预处理相关危险因素。     

外周血干细胞移植治疗11例急性白血病和恶性实体瘤

目的:观察外周血干细胞移植(PBSCT)治疗急性白血病和恶性实体瘤的临床疗效观察。方法:自1999年11月至2004年3月,用PBSCT治疗急性白血病和恶性实体瘤11例,其中:急性淋巴细胞白血病(ALL)1例;急性非淋巴细胞白血病(ANLL)3例;非霍奇金淋巴瘤(NHL)4例;霍奇金淋巴瘤(HD)1例;乳腺癌1例;恶性黑色素瘤1例。除1例异基因外周血干细胞移植患者采用重组人粒细胞集落刺激因子(rhGCSF,惠尔血)对供者进行动员外,其他患者均为自体外周血干细胞移植,动员方案为化疗 rhGCSF。经2次采集,获得MNC为(5.91±2.34)×108/kg,CD34 细胞为(14.05±6.65)×106/kg,CFUGM(4.80±2.80)×105/kg。预处理方案3例患者采用FTBI加化疗,8例患者采用高剂量化疗方案。结果:所有患者移植后均重建造血。外周血WBC于移植后(6±1)天降至0。PLT于(7±1)天降至30×109/L以下。WBC>1.0×109/L、中性粒细胞>0.5×109/L、PLT>50×109/L,分别为(11±2)天、(11±2)天、(13±3)天。3例患者于移植后1～12个月死于肝功能衰竭或病情复发,2例患者带瘤生存3～5个月,其余患者均无瘤存活3～46个月,疗效仍在近一步随访中。结论:PBSCT对急性白血病和恶性实体瘤是一种安全有效的治疗方法。     

Brain tumor stem cells: The cancer stem cell hypothesis writ large

Brain tumors, which are typically very heterogeneous at the cellular level, appear to have a stem cell foundation. Recently, investigations from multiple groups have found that human as well as experimental mouse brain tumors contain subpopulations of cells that functionally behave as tumor stem cells, driving tumor growth and generating tumor cell progeny that form the tumor bulk, but which then lose tumorigenic ability. In human glioblastomas, these tumor stem cells express neural precursor markers and are capable of differentiating into tumor cells that express more mature neural lineage markers. In addition, modeling brain tumors in mice suggests that neural precursor cells more readily give rise to full blown tumors, narrowing potential cells of origin to those rarer brain cells that have a proliferative potential. Applying stem cell concepts and methodologies is giving fresh insight into brain tumor biology, cell of origin and mechanisms of growth, and is offering new opportunities for development of more effective treatments. The field of brain tumor stem cells remains very young and there is much to be learned before these new insights are translated into new patient treatments.     

Lung cancer stem cells: Progress and prospects

Epithelial stem cells are critical for tissue generation during development and for repair following injury. In both gestational and postnatal stages, the highly branched and compartmentalized organization of the lung is maintained by multiple, resident stem/progenitor cell populations that are responsible for the homeostatic maintenance and injury repair of pulmonary epithelium. Though lung epithelial injury in the absence of oncogenic mutation is more commonly expressed as chronic lung disease, lung cancer is the most common form of death worldwide and poses a highly significant risk to human health. Cancer is defined by the cell of origin, responsible for initiating the disease. The Cancer Stem Cell Hypothesis proposes that cancer stem cells, identified by stem-like properties of self-renewal and generation of differentiated progeny, are responsible for propagating growth and spread of the disease. In lung cancer, it is hypothesized that cancer stem cells derive from several possible cell sources. The stem cell-like resistance to injury and proliferative potentials of bronchioalveolar stem cells (BASCs) and alveolar epithelial type II cells (AEC2), as well as cells that express the cancer stem cell marker glycoprotein prominin-1 (CD133) or markers for side populations make them potential reservoirs of lung cancer stem cells. The abnormal activation of pathways that normally regulate embryonic lung development, as well as adult tissue maintenance and injury repair, including the Wnt, Hedgehog (Hh) and Notch pathways, has also been identified in lung tumor cells. It is postulated that therapies for lung cancer that specifically target stem cell signaling pathways utilized by lung cancer stem cells could be beneficial in combating this disease.     

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.     

实体肿瘤干细胞相关研究进展

肿瘤干细胞学说认为,肿瘤干细胞是肿瘤发生、生长、耐药以及复发、转移的根源.肿瘤不单是一种基因病,而且是一种干细胞病.越来越多的证据提示了多种实体瘤中肿瘤干细胞的存在.     

胰腺肿瘤干细胞研究新进展

胰腺肿瘤尤其是胰腺导管腺癌的恶性程度高,转移性强,预后差。以往研究表明肿瘤干细胞(cancer stem cells,CSC)在胰腺肿瘤的发生、发展过程中起重要作用,深入了解胰腺肿瘤的发病机制将有助于针对性治疗。在胰腺发育过程中,复杂的信号通路和转录因子决定了其前体细胞分化方向,在胰腺发生恶变过程中,这些因素又参与其中,因而往往可以作为追溯CSC的标志。一些研究也应用特定蛋白来筛选胰腺CSC。现就胰腺CSC的来源、鉴定和靶向治疗进行综述。     

Gastric cancer stem cells: A novel therapeutic target

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow-derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer.     

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。     

Circulating cancer stem cells: the importance to select

It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients’ outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, ‘liquid biopsy’, which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients’ clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and characterizing these circulating cancer stem cells, but also highlights current technological limitations.     

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.