前列腺干细胞抗原与前列腺癌

前列腺干细胞抗原是近年来新发现的存在于上皮细胞表面的一种糖蛋白 ,具有很高的前列腺组织特异性。在人正常前列腺及良、恶性病变组织中均有表达 ,尤其在激素非依赖前列腺癌及转移灶中表达增高。研究显示 ,前列腺干细胞抗原可能在前列腺癌发病机制研究、早期诊断以及前列腺癌的靶向免疫治疗等方面具有重要意义。     

前列腺癌干细胞与雄激素受体信号通路的新进展

雄激素是维持前列腺生长和发育的重要激素，在前列腺相关疾病的病理生理中发挥着重要的作用。前列腺癌从激素依赖型转变为激素抵抗型前列腺癌的过程中，雄激素受体（androgen receptor，AR）一直是受关注的焦点，有观点认为，AR是前列腺癌出现从激素依赖型向激素抵抗型转变的关键分子。另有观点认为前列腺癌是从前列腺干细胞起源，并且，前列腺癌中含量极少的前列腺癌干细胞在前列腺癌激素剥夺治疗后复发和维持肿瘤生长过程中发挥了重要作用。这两种理论是否能够获得统一，还需进一步研究。     

前列腺干细胞抗原与相关癌症的研究进展

前列腺干细胞抗原 (PSCA)为一种细胞表面抗原 ,在正常前列腺中表达 ,在前列腺癌、膀胱癌及胰腺癌组织中过度表达。PSCA在前列腺癌监测中敏感性优于PSA。PSCA可用于制备蛋白疫苗和基因疫苗 ,为癌症诊断与治疗提供新的方向与思路 ;进一步研究可以明确其有效性与安全性。     

前列腺干细胞抗原与前列腺癌

前列腺干细胞抗原是近年来新发现的存在于上皮细胞表面的一种糖蛋白，具有很高的前列腺组织特异性，在人正常前列腺及良，恶性病变组织中均有表达，尤其在激素非依赖前列腺癌及转移灶中表达增高。研究显示，前列腺干细胞抗原可能在前列腺癌发病机制研究，早期诊断以及前列腺癌的靶向免疫治疗等方面具有重要意义。     

前列腺肿瘤干细胞分离及鉴定技术研究进展

肿瘤干细胞假说是近年来提出的关于前列腺癌发生的新理论,为诊断及治疗前列腺癌提供了全新的视角.该假说提出肿瘤干细胞是前列腺癌的起源细胞,并可能是前列腺癌对内分泌治疗产生耐受的根源.分离纯化一直是前列腺肿瘤干细胞研究的难题,近年来一些新的分选技术如免疫磁珠法和免疫流式分选开始应用于前列腺肿瘤干细胞.对分离纯化获得的潜在的肿瘤干细胞进行鉴定,是研究肿瘤干细胞生物学特性的重要环节,本文就相关进展进行综述.     

有应用前景的前列腺癌相关肿瘤标志物

前列腺癌是男性泌尿系统最常见的恶性肿瘤之一,其病死率为男性癌症死亡的第二位。前列腺癌的早期诊断主要是前列腺特异性抗原筛查,但该指标特异性低。目前有许多敏感性、特异性更高的肿瘤标志物(TM)被发现,现就近年研究较多、有应用前景的几种TM(前列腺癌抗原3、早期前列腺癌抗原、前列腺特异性膜抗原、α-甲酰基辅酶A消旋酶和血管内皮生长因子)予以综述。     

AMACR (P504S)与前列腺癌诊断的研究进展

前列腺癌的发病率在美国己超过肺癌而占男性恶性肿瘤的第一位和癌症死因的第二位[1].随着人均寿命的延长以及诊断技术的提高,我国前列腺癌的发病率也在逐年提高.前列腺癌的早期诊断是临床上关注的焦点.目前前列腺癌的诊断主要依赖直肠指诊、PSA检测和穿刺活检.PSA的灰区存在使得鉴别前列腺良性病变和前列腺癌存在较大困难,而明确前列腺癌的组织学诊断仍然依靠基本的HE染色切片,对于早期前列腺癌的穿刺活检,则可能由于前列腺癌细胞较少而造成漏诊.故有必要寻求一种更客观、可靠的肿瘤特异性标记物.目前在前列腺癌肿瘤标志物的研究方面已经取得了很大的进展,PSA,PSMA已被广泛地运用于前列腺癌的临床诊断和治疗随访中.近年来发现的人血管舒缓素激肽释放酶2和前列腺干细胞抗原(PSCA)也被证实为前列腺癌特异性基因,但它们并不能提高前列腺癌的早期诊断率.现对一种新近确认的前列腺癌的特异性分子标记物α -甲酰-辅酶A-消旋酶(alpha-methylacyl-COA racemase,AMACR,P504S)的研究现状作一综述.     

机器人辅助腹腔镜前列腺癌根治术的进展

正前列腺癌是美国等西方国家男性最常见的恶性肿瘤之一,病死率居男性各种癌症第2位,位列中国泌尿生殖系统癌症的第1位[1]。前列腺癌根据临床分期不同治疗方法各异。针对早期局限性前列腺癌,根治性前列腺切除术是目前使用最为广泛的治疗方法之一[2]。本文将介绍目前较为常见的两种入路机器人辅助腹腔镜前列腺癌根治术     

前列腺癌诊断标志物的研究进展

前列腺癌是男性生殖系统肿瘤的常见病,在欧美等国家前列腺癌是男性发病率最高的恶性肿瘤,占癌症死亡率的第二位[1].随着老龄化人口的发展及诊疗水平的不断提高,前列腺癌在中国的发病率及检出率也呈显著增长趋势,是威胁老年男性健康的一个重要因素[2].目前前列腺癌实验室早期诊断指标主要是血清前列腺特异性抗原(PSA),但是血清PSA作为前列腺特异性而非前列腺癌特异性标志物,在有关前列腺各种检查(直肠指诊和经直肠超声)及非肿瘤状态下(如良性前列腺增生、前列腺炎)也有表达.临床上将PSA＞4 ng/ml作为前列腺癌诊断的临界值,但是当PSA值在4～10 ng/ml 时,前列腺癌的检出率仅在25%左右,活检阴性率占70%～80%,阴性的活检结果并不能完全排除恶性肿瘤存在的可能性[3].因此寻找敏感性、特异性高的生物标志物仍是目前研究的重点,本文就近几年研究较为热点的几种标志物予以综述.     

前列腺癌PSA筛查的价值和争议

前列腺癌作为老年男性最常见的恶性肿瘤,是欧美男性中发病率和死亡率分别高居第一、二位的癌症.2011年,在美国有约24万男性被诊断为前列腺癌,其中3.4万例死于前列腺癌,在男性癌症死亡率中排第二[1].我国前列腺癌发病率较低,但近年来呈明显迅速上升的趋势.文献报道1993年国内前列腺癌发生率为1.71人/10万男性,1997年升至2.0人/10万,2000年为4.55人/10万,2005年则升至7.9人/10万[2].而且,据推测该发病率以每年10％左右的速度攀升.因此,有理由相信前列腺癌在我国也将很快成为威胁老年男性健康的重要疾病.     

前列腺癌干细胞标志物研究进展

前列腺癌是严重影响男性健康的恶性疾病,其发生、发展机理仍未完全明了。近年来前列腺癌干细胞的研究取得了多方面的进展,研究材料涉及人前列腺癌组织、前列腺癌细胞系,以及鼠前列腺癌模型。前列腺癌干细胞的研究为前列腺癌的发生和发展提出了一个全新的理念,对于前列腺癌的治疗具有积极意义。本文就近些年来在前列腺癌干细胞研究中应用于分离鉴定前列腺癌干细胞的标志物情况进行综述。     

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.     

Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: A stem cell model

A stem cell model is presented for the organization of the prostatic epithelium that may explain normal and abnormal growth in the human prostate. This model is based on recent data indicating that: 1) The three basic cell types encountered in the prostatic epithelium—i.e., secretory luminal, basal, and endocrine paracrine (EP) cells—are linked in the precursor progeny relationship. 2) The proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. 3) The proliferative compartment of the prostatic epithelium is androgen-independent but contains androgen-responsive target cells. 4) During the malignant transformation of the prostatic epithelium, the proliferative zone is inverted and shifts to luminal cell types. 5) Formation of neoplastic basement membrane (BM) material is crucial for the development of the invasive phenotype in prostate cancer. 6) The proliferative activities in prostate cancer are exclusively restricted to exocrine cell types, whereas endocrine differentiated tumor cells are postmitotic cells. 7) The majority of exocrine tumor cells are androgen-responsive in contrast to endocrine differentiated cell types that consistently lack the nuclear androgen receptor (AR). In this model, a small stem cell population located in the basal cell layer gives rise to all epithelial cell lineages encountered in the normal, hyperplastic, and neoplastic prostate. The differentiating process from basal cells to secretory luminal cells via intermediate phenotypes is induced by circulating androgens, and largely depends on the presence of androgen-responsive target cells in the basal cell layer. Accordingly, the abnormal growth of the secretory epithelium in benign prostate hyperplasia (BPH) may be related to an increase in the total number of androgen-responsive basal cells in the proliferative compartment. Prostate cancer derives from transformed stem cells located in the basal cell layer that acquire secretory luminal characteristics under androgenic stimulation. During tumor invasion, the malignant phenotypes adhere via specific receptors to newly formed BM-material, which, in turn, may facilitate their passage through the extracellular matrix. The occurrence of endocrine differentiation in prostate cancer reflects the pluripotency of its stem cells. The widespread absence of nuclear AR in endocrine differentiated tumor cells clearly indicates that this phenotype belongs to those cell clones in prostate cancer, that are initially androgen-independent and refractory to hormonal therapy. Accordingly, the progressive emergence of endocrine cell clones during tumor progression may represent one mechanism by which prostate cancer cells escape hormonal control. © 1996 Wiley-Liss, Inc.     

Cell death under epithelial–mesenchymal transition control in prostate cancer therapeutic response

Prostate cancer is a widespread problem among men, with >160 000 new cases in 2017 alone. Androgen deprivation therapy is commonly used in prostate cancer treatment to block androgens required for cancer growth, but disease relapse after androgen deprivation therapy is both common and severe. Changes in androgen receptor signaling from androgen deprivation therapy have been linked to therapeutic resistance and tumor progression. Resistant cells can become reprogrammed to undergo epithelial–mesenchymal transition, a phenotypic switch from benign, epithelial cells to a mobile cell with mesenchymal traits. In these cells, attachment to their epithelial cell layer is no longer required for survival. Anoikis is a form of cell death that occurs when detachment from other cells and the basement membrane occurs. Epithelial cells have been shown to undergo epithelial–mesenchymal transition, avoid anoikis induction and progress to a metastatic phenotype. In prostate cancer progression to advanced disease, epithelial–mesenchymal transition induction (characterized by loss of epithelial cellular attachment protein E‐cadherin) correlates with a higher Gleason score, tumor progression, increased metastasis and higher biochemical recurrence. The concept of interfacing epithelial–mesenchymal transition with anoikis in the tumor microenvironment landscape will be discussed here, with focus on the significance of the functional exchange between the two processes in therapeutic targeting of advanced disease. The current evidence on the impact of loss of cell–cell contact, acquisition of chemoresistance, immune escape and metastatic spread in advanced tumors in response to transforming growth factor‐β on prostate cancer metastasis will be also discussed. The signaling cross‐talk between transforming growth factor‐β and androgen receptor signaling will be interrogated as a new therapeutic platform for the development of combination strategies to impair prostate cancer metastasis.     

肺癌干细胞标志物的研究现状

肺癌具有高度异质性,能够抵抗化疗药物治疗,5年生存率小于15%。尽管我们关于肺癌的知识在不断增多,但仍很难确定肺癌的异质性和耐药性的发病基础。肿瘤干细胞模型近年来吸引了很多注意力,通过这种模型可以解释各种肿瘤的异质性、耐药性、休眠、复发和转移。肿瘤干细胞理论较少涉及肺癌研究。本文综述了肺癌干细胞的鉴定方法,包括其细胞表面标志物和生物学特征,还讨论了肺癌干细胞与肺癌预后的关系,从而为消灭肺癌干细胞、攻克肺癌提供理论依据。     

Validation of molecular targets in prostate cancer

As prostate cancer is not a single disease, it is important to identify the pivotal pathway in the patient being treated. The molecular environment is the site of current oncological research to define new therapeutic targets for hormone-refractory disease, offering the potential to eventually individualize treatment through stratification of pathways. Targets may be validated either phenotypically (e.g. androgen receptor, cadherin) or functionally (e.g. prostate cancer-specific genes). In addition, several other candidates are potentially suitable, while others await discovery. Important initial steps have been made in the search for prostate cancer stem cells; identifying stem cells and the stromal, hormonal, and other signalling molecules that influence their behaviour would have important implications for managing prostate cancer. Although individual therapeutic pathways might be ineffective in a particular molecular environment, combinations of approaches might be capable of producing synergistic effects. A multimodal approach thus might be the best solution. Determining where best to search for a molecular target, and validating whether the target is associated with a sufficiently aggressive malignant process to justify further study is difficult, but the potential benefits are enormous.     

前列腺干细胞研究进展

干细胞具有强大的自我更新、多向分化潜能和高度增殖的特性,其在多种疾病的发生和疾病治疗中的作用已越来越受到人们重视。前列腺干细胞包括上皮干细胞和间充质干细胞,其中上皮干细胞表面标记物包括细胞角蛋白、干细胞抗原-1、整合素α2β1、CD49f、CD133、CD117、CD44等,间充质干细胞的标记物包括CD30、CD44、CD133、神经元特异性烯醇化酶和血管内皮生长因子受体-1。前列腺疾病的发生与干细胞的参与密切相关。本文就前列腺干细胞近年来的相关研究进展作一综述。     

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.     

Cellular Quiescence in Mammary Stem Cells and Breast Tumor Stem Cells: Got Testable Hypotheses?

Cellular quiescence is a state of reversible cell cycle arrest and has more recently been shown to be a blockade to differentiation and to correlate with resistance to cancer chemotherapeutics and other xenobiotics; features that are common to adult stem cells and possibly tumor stem cells. The biphasic kinetics of mammary regeneration, coupled to its cyclic endocrine control suggest that mammary stem cells most likely divide during a narrow window of the regenerative cycle and return to a state of quiescence. This would enable them to retain their proliferative capacity, resist differentiation signals and preserve their prolonged life span. There is accumulating evidence that mammary stem cells and other adult stem cells utilize quiescence for this purpose, however the degree to which tumor stem cells do so is largely unknown. The retained proliferative capacity of mammary stem cells likely enables them to accumulate and harbor mutations that lead to breast cancer initiation. However it is currently unclear if these causative lesions lead to defective or deranged quiescence in mammary stem cells. Evidence of such effects could potentially lead to the development of diagnostic systems that monitor mammary stem cell quiescence or activation. Such systems may be useful for the evaluation of patients who are at significant risk of breast cancer. Additionally quiescence has been postulated to contribute to therapeutic resistance and tumor recurrence. This review aims to evaluate what is known about the mechanisms governing cellular quiescence and the role of tumor stem cell quiescence in breast cancer recurrence.