大肠癌干细胞研究进展

随着肿瘤下细胞研究的深入,近年来学者提出了大肠癌起源的干细胞学说,并借助干细胞分离技术,将其成功分离.本篇旨在回顾基于肿瘤干细胞概念提出的大肠癌起源假说和大肠癌干细胞在大肠癌进展的作用,大肠癌干细胞分离技术及其在体内和体外的功能特征,与大肠癌干细胞相关的信号通路及大肠癌耐药机制研究.     

人膀胱癌组织中肿瘤干细胞样细胞的分离培养及PIWIL2表达

目的从人膀胱移行细胞癌（BTCC）组织中分离培养肿瘤干细胞样细胞（CSLC）,鉴定其生物学特性,并研究PIWIL2在CSLC中的表达和意义。方法收集12例不同临床分期BTCC患者组织标本,通过酶消化和原代培养相结合等方法处理,采用无血清悬浮培养法分离培养获得含CSLC的悬浮细胞球,流式细胞仪检测细胞表面分子标志CD133和CD44的表达,免疫磁珠分选系统分离CD133＋CD44＋细胞;采用半定量逆转录聚合酶链反应检测PIWIL2mRNA在CSLC中的表达;裸鼠皮下接种CS-LC,观察其成瘤能力。结果成功地从人膀胱癌组织分离培养获得可悬浮生长、稳定传代的CSLC,CSLC高表达CD133和CD44,裸鼠皮下接种1×104、1×105个CSLC均可全部成瘤,PIWIL2mRNA在CSLC的表达显著高于正常膀胱组织细胞。结论采用无血清悬浮培养法成功从人膀胱癌组织中分离获得CSLC,具有肿瘤干细胞特性,能高度表达PIWIL2,为靶向肿瘤干细胞的治疗提供了实验依据。     

Investigations of prostate epithelial stem cells and prostate cancer stem cells

Although both prostate epithelial stem cells and prostate cancer stem cells are implicated in the differentiation of the normal prostate gland and carcinogenesis of prostate cancer, there has, until recently, been little information regarding their biology. This review summarizes the recent advancements in cell biological research including various in vitro culture systems that have offered the characterization and isolation of prostate epithelial stem cells and prostate cancer stem cells. In addition, the stromal niche or microenvironment of stem cells plays an essential role in proliferation and differentiation of normal stem cells. Stroma surrounding cancer cells, which also provide another unique niche, may involve the initiation and development of cancer stem cells. Investigation of stem cells and their microenvironments in the prostate should lead to the elucidation of biological features and the development of novel treatments for prostate cancer.     

Future perspectives of prostate cancer therapy

We summarize several recent laboratory advances to tackle the problem of tumor-stroma-immune cell microenvironment interaction with the hope of developing and advancing new concepts and therapeutic strategies for prostate cancer therapy by improving bone and soft tissue metastases in prostate cancer patients. Given the emerging enthusiasm for immunotherapy in prostate cancer due to (I) improved understanding of the role of immune cells in the tumor microenvironment, (II) approval by the FDA of an immunotherapeutic drug to treat prostate cancer, and (III) recognition of immunotherapy as a novel approach to treat solid tumors by the Nobel Prize Committee (for discovery of dendritic cells that are used in immunotherapy), the field of tumor immunology is poised for growth in the next decade with the hope of developing new immunomodulatory drugs which will compliment and perhaps eventually replace traditional chemotherapeutic drugs. In this article, we provide a timely review of recent advances in the field of immunotherapy for prostate cancer, lessons learned from successes and failures, the contributory factors in the tumor microenvironment that could be rendered hostile to cancer cells, an exciting area of future research.     

肿瘤干细胞对恶性肿瘤诊治的意义

恶性肿瘤严重地威胁着人类的健康.多药耐药现象增加了其治疗难度,局部复发和远处转移最终导致了治疗失败,然而遗憾的是机制尚不清楚.研究发现在肿瘤组织中有一个具有自我更新及分化潜能的的细胞亚群,是复发及转移的根源.这部分细胞被称为肿瘤干细胞.随后,人们相继从血液系统肿瘤及多种实体瘤中分离、鉴定了肿瘤干细胞.随着肿瘤干细胞学说的提出及确认,人们对肿瘤的复发、转移及多药耐药现象有了新的认识,从而为恶性肿瘤的治疗及复发转移的预防提供了一个全新的线索.本文就此进行综述.     

蛇葡萄素对人膀胱癌细胞株T24的作用

目的 观察蛇葡萄素对体外人膀胱癌细胞株T24的增殖抑制作用.方法 以浓度为20、10、5、320、160、80、40 mg/L的蛇葡萄素作用于体外培养的人膀胱癌细胞株T24应用噻唑蓝(MTT)的培养检测增殖抑制方法.结果 浓度为20、10、5 mg/L的蛇葡萄素对体外人膀胱癌细胞株T24的增殖抑制率明显高于浓度为320、160、80、40 mg/L的蛇葡萄素.结论 蛇葡萄素对体外人膀胱癌细胞株T24的增殖有抑制作用,而且增殖抑制率与蛇葡萄素的浓度剂量不成正比例,在一定范围内的浓度达到最大的抑制率,不会因浓度增加而抑制率增加.浓度为20、10、5 mg/L更能有效的抑制人膀胱癌细胞株T24的增殖.     

Morphological studies on the effect of taxol on cultured human prostatic cancer cells

The effect of taxol, an experimental antitumor drug, was studied in vitro on human prostatic cancer cells. Different concentrations of taxol, varying from 5μM to 0.01 nM, were used. The effect of taxol was examined by light and electron microscopy. Taxol had a marked cytotoxic effect on prostatic cancer cells down to a 10 nM concentration of taxol when observed by light microscopy. However, by electron microscopy, the specific effect of taxol was seen even with a 1 nM concentration of taxol. Taxol induced the appearance of numerous round cells after a few days and, subsequently, progressive death of the tumor cells. Among the surviving tumor cells, large tumor cells were noted as well as many multinucleated tumor cells. By electron microscopy, the round tumor cells showed mitotic figures with a high amount of cytoplasmic microtubules. Nonmitotic cells were often multinucleated and contained a high number of cytoplasmic microtubules and microtubule-related structures. The results show that taxol, even at very low concentrations, has a highly cytotoxic effect on prostatic cancer cells; and when a very low concentration of taxol is used with no obvious cytotoxic effect at the light microscopic level, specific taxol-induced ultrastructural alterations can be observed.     

腹腔镜下进展期胃癌根治术中腹腔游离癌细胞检测的意义

目的探讨腹腔镜下进展期胃癌根治术对腹腔脱落肿瘤细胞检测的影响,并探讨提高腹腔游离癌细胞检出率的方法。方法选取华中科技大学同济医学院附属协和医院胃肠外科35例初治的进展期胃癌病人,行腹腔镜下胃癌根治术。所有病人分别在术中探查前及关腹前各行一次腹腔冲洗,并收集灌洗液。比较两组灌洗液中肿瘤脱落细胞阳性检出率及肿瘤标志物上皮膜抗原(epithelial membrane antigen,EMA)、癌抗原(carbohydrate antigen,CA)125、CA19-9和癌胚抗原(carcinoembryonic antigen,CEA)的表达情况。结果35例进展期胃癌病人探查前腹水或腹腔灌洗液中涂片细胞学检查中检出阳性率为5.7%(2/35),关腹前为5.7%(2/35),两者统计比较差异无统计学意义(P>0.05)。免疫组织化学法检测探查前与关腹前腹水或腹腔灌洗液中EMA的表达(4/35,3/35)比较,差异无统计学意义(P>0.05);两个时间点CA125的表达(1/35,3/35)比较,差异无统计学意义(P>0.05)。探查前腹水或腹腔灌洗液中,腹腔灌洗液脱落细胞学法游离癌细胞检出阳性率为5.7%(2/35),而免疫组织化学法检测EMA的阳性率为11.4%(4/35),两者比较差异有统计学意义(P=0.010);免疫组织化学法检测CA125的阳性率为8.6%(3/35),与腹腔灌洗液脱落细胞学法(2/35)比较,差异有统计学意义(P=0.005);免疫组织化学法联合检测EMA及CA125的阳性率为11.4%(4/35),与腹腔灌洗液脱落细胞学法(2/35)比较,差异有统计学意义(P=0.010)。结论腹腔镜下进展期胃癌根治术并不会增加癌细胞脱落风险,且肿瘤脱落细胞发生率低。但腹腔镜下胃癌根治术后腹腔游离癌细胞的诊断,需要更为有效的检测方法。     

胰腺星形细胞在胰腺癌中的作用

胰腺癌是常见的消化道恶性肿瘤之一,因早期诊断困难,恶性程度高,手术切除率低,并对化放疗均不敏感,故预后极差.其病理特征之一是肿瘤中有大量的结缔组织形成反应.而胰腺星形细胞(PSCs)在这一反应中起重要作用,并通过与胰腺癌细胞的相互作用,对胰腺癌细胞的增生、侵袭和转移有重要作用.本文就PSCs在胰腺癌发展中的作用及机制作一综述.     

肝癌干细胞的研究进展

肿瘤起源于干细胞的假说正在各种人类肿瘤中得到证实.肿瘤不仅是一种基因病,而且是一种干细胞病,基因突变作用于干细胞,干细胞突变成为肿瘤干细胞,这是肿瘤发生、再生、转移和复发的关键.为证实肝癌干细胞的存在,有两个问题必须提出:(1)肝细胞型肝癌是否来源于肝干细胞?(2)肝细胞型肝癌中是否具有干细胞特征的细胞?最新研究表明:肝细胞型肝癌可能是由肝干细胞未分化或分化不全引起的.对于肝癌细胞的研究我们知道肝细胞型肝癌中的细胞具有干细胞特性,如永生性、可移植性以及对治疗手段的抵抗性.但是,至今为止,确切的肝癌干细胞的标记物没有找到,而且没有分离出肝癌干细胞.     

胃、大肠癌循环癌细胞的检测

目的胃大肠癌循环癌细胞的检测。方法用常规细胞学(HE)和免疫细胞化学(ICC)方法对23例进展期胃、大肠癌切除患者门静脉系血及外周血进行癌细胞的检测。结果 23例患者中常规 HE 染色,阳性2例(8.7%),可疑3例(13%);免疫细胞化学方法,阳性4例(17.4%)。4例阳性患者血中癌细胞浓度在40-1000个/ml 范围内。结论循环癌细胞的检测可能有助于预测肝内微转移灶的发生,判断患者预后,为术后选择辅助治疗提供依据。     

Dendritic cells program non-immunogenic prostate-specific T cell responses beginning at early stages of prostate tumorigenesis

BACKGROUND: Prostate cancer promotes the development of T cell tolerance towards prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines targeting these antigens. Here, we sought to determine the stage of disease progression when T cell tolerance develops, as well as the role of steady state dendritic cells (DC) and CD4(+)CD25(+) T regulatory cells (Tregs) in programming tolerance. METHODS: The response of na?ve HA-specific CD4(+) T cells were analyzed following adoptive transfer into Pro-HA x TRAMP transgenic mice harboring variably-staged HA-expressing prostate tumors on two genetic backgrounds that display different patterns and kinetics of tumorigenesis. The role of DC and Tregs in programming HA-specific CD4 cell responses were assessed via depletion. RESULTS: HA-specific CD4 cells underwent non-immunogenic responses at all stages of tumorigenesis in both genetic backgrounds. These responses were completely dependent on DC, but not appreciably influenced by Tregs. CONCLUSIONS: These results suggest that tolerogenicity is an early and general property of prostate tumors.