Musashil和Notch信号通路在脑缺血后神经发生中的作用

Musashil是一种进化保守的RNA结合蛋白,在维持干细胞状态、分化以及肿瘤发生方面起重要作用.Notch信号通路在脑缺血后神经干细胞的增殖中起重要作用.文章简要介绍Musashil和Notch的结构和分子生物学特征,并对Musashil和Notch信号通路在脑缺血再灌注后神经发生中的相互作用进行了综述.     

老年胶质瘤患者术后组织中乙醛脱氢酶、Musashi-1和血管内皮生长因子表达的临床意义

<正>胶质瘤病变发展过程中常出现多种蛋白的表达失调。乙醛脱氢酶-1(ALDH1)在肿瘤的发生、血管生成和细胞增殖中起到重要的促进作用〔1〕。Musashi-1是一种保守的神经RNA结合蛋白,可在祖细胞中表达,也被认为是干细胞的标志物,近来研究认为其可能与多种癌症相关〔2〕。血管内皮生长因子(VEGF)是最经典的血管内皮生长因子,对肿瘤和新生组织中的血管形成有重要价值〔3〕。本实验探讨胶质瘤老年患者术后肿瘤组织中ALDH1、Musashi-1和VEGF的表达及三者的关系。     

CD133和CD90在肝细胞癌中的表达及其意义

存在于肿瘤组织中的少数具有干细胞性质的细胞群体被称为肿瘤干细胞(CSCs),可促进肿瘤的发生和发展,也是肿瘤耐药性、复发及转移的根源.有报道CD133和CD90可能为肿瘤干细胞表面标志物,但CD133和CD90在肝癌中的表达及其意义报道尚少.本研究采用免疫组织化学方法检测不同肝组织中CD133及CD90蛋白的表达水平,探讨其在肝癌中的表达情况及其与肝癌生物学特性及预后的关系.     

未来肝癌治疗的新靶点-肝癌干细胞

肿瘤起源于干细胞的假说正在各种人类肿瘤中得到证实,肿瘤不单是一种基因病,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.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.但至今为止,确切的肝癌干细胞的标志物没有找到,而且没有分离出肝癌干细胞.     

CD133和CD90在肝细胞癌中的表达及其意义

存在于肿瘤组织中的少数具有干细胞性质的细胞群体被称为肿瘤干细胞(CSCs),可促进肿瘤的发生和发展,也是肿瘤耐药性、复发及转移的根源.有报道CD133和CD90可能为肿瘤干细胞表面标志物,但CD133和CD90在肝癌中的表达及其意义报道尚少.本研究采用免疫组织化学方法检测不同肝组织中CD133及CD90蛋白的表达水平,探讨其在肝癌中的表达情况及其与肝癌生物学特性及预后的关系.     

结直肠癌相关基因甲基化生物标志物的研究进展

结直肠癌（CRC）的发生是结肠上皮细胞恶性转化过程中的遗传学和表观遗传学改变累积的结果。基因甲基化被认为是肿瘤发展过程中常见的分子改变,且往往发生在肿瘤早期,并可以在患者的粪便和血液中被检测到,因此,基因甲基化状态的改变可作为肿瘤标志物用于结直肠癌的早期临床诊断。此文对与结直肠癌早期检测、转移及预后相关的基因甲基化的分子标志物作一综述。     

胃癌干细胞研究进展

胃癌干细胞(gastric cancer stem cells,GCSCs)是胃癌细胞中具有引发肿瘤生长和维持自我更新及转移潜能的一小群细胞,不能被目前的化疗、放疗等抗癌治疗措施杀灭。GCSCs可能来源于胃干细胞和骨髓干细胞(bone marrow stem cells,BMSCs),其分子标志物主要是CD44、CD133等,并受多种信号转导通路的调控,GCSCs的存在是肿瘤药物耐受的主要机制,并导致胃癌的复发与转移。有证据表明肿瘤本质是一种干细胞疾病,GCSCs研究已经成为胃癌研究新热点。本文就近年来GCSCs的起源、分子标志物、信号转导通路及药物耐受方面的研究进展作一概述。     

肝癌干细胞的调控机制及靶向治疗的研究进展

随着肿瘤干细胞(cancer stem cells,CSCs)在人类许多实体肿瘤中得到证实,肝癌被认为很可能也是一种干细胞疾病.肝癌中是否存在肝癌干细胞(liver cancer stem cells,LCSCs)一直是近来研究热点.CSCs学说认为,肿瘤的发生、发展、转移、复发与耐药均与CSCs有密切关系.因此,确认并分离鉴定LCSCs对于早期预防及早期诊断、有效治疗及改善预后有着极为重要的作用.本文就LCSCs的来源、表面标志、信号转导与调控、治疗策略等方面的相关研究作一综述.     

脂肪量和肥胖相关基因修饰N6-甲基腺嘌呤调控肿瘤发生发展的作用机制研究进展

脂肪量和肥胖相关基因（FTO）最初被认为是一种与成人和儿童的早发及严重肥胖密切相关的肥胖敏感基因，后来研究发现，FTO能够作为RNA的去甲基化酶，在N6-甲基腺嘌呤（m6A）修饰中作为调控因子发挥作用，其功能障碍与多种恶性肿瘤的发生发展有关。FTO可以通过修饰m6A影响细胞周期与细胞增殖、逃避细胞凋亡信号、逃避自体免疫微环境、诱导血管生成、激活肿瘤细胞侵袭和转移，调节肿瘤干细胞干性，从而在肿瘤中发挥促癌因子或抑癌因子的作用，有望成为肿瘤分子诊断的潜在生物标志物及肿瘤治疗的新靶点。     

脑胶质瘤干细胞的体外培养与生物学特性观察

目的体外培养人脑胶质瘤干细胞并观察其生物学特性。方法应用无血清培养技术,从手术中获取的人脑胶质瘤组织培养得到肿瘤干细胞,诱导其分化后与原肿瘤组织细胞进行比较。应用细胞免疫荧光技术鉴定肿瘤干细胞表面标志物。结果分别在间变性星形细胞瘤和胶质母细胞瘤中培养得到悬浮生长的肿瘤干细胞球,其能在体外自我更新、增殖,形成新的克隆性细胞球,保持连续稳定的传代,能表达神经干细胞表面标志物CD 133。在含血清培养基中能够分化为与原肿瘤组织相似的贴壁生长的细胞。结论人脑胶质瘤中存在一定量的肿瘤干细胞,能够自我更新增殖、诱导分化、表达干细胞标志物CD 133。为探讨脑胶质瘤的发病机制奠定了基础。     

CD133在肺癌中的研究与进展

肺癌是世界范围内死亡率最高的恶性肿瘤之一,也是我国常见的恶性肿瘤之一,恶性程度高,发展迅速,治疗困难,总体疗效不理想。肿瘤干细胞是肿瘤组织中一小部分具有自我更新、无限增殖和多向分化能力的肿瘤细胞,它在肿瘤组织中所占比例虽然很少,却与肿瘤起源、发展与转移关系密切,因此肿瘤干细胞被看作是一个根除癌症的潜在目标。CD133是...     

Nestin in gastrointestinal and other cancers: effects on cells and tumor angiogenesis

Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including...     

Pancreatic cancer stem cells: new insights and perspectives

Since the identification of self-renewing cells in the hematopoietic system several decades ago, stem cells have changed the way we study biology and medicine. Solid tumors contain a distinct subpopulation of cells that have stem cell characteristics and are exclusively responsible for tumorigenicity. This discovery has led to the development of the stem cell concept of cancer, which proposes that a subpopulation of self-renewing tumor cells, also termed cancer stem cells, is responsible for tumorigenesis and metastasis. This contrasts with the stochastic model of tumor development, which holds that all tumor cells are capable of tumor initiation. Different subpopulations of cancer stem cells have been identified in pancreatic ductal adenocarcinoma, based on the use of combinations of surface markers that allow their isolation, propagation, and further characterization. Importantly, cancer stem cells are not only capable of self-renewal and differentiation, but may also confer virulence via immune system evasion and multidrug resistance, and potentially via vasculogenic mimicry and transition to migratory and metastasizing derivatives. Therapeutic targeting of this subset of cells and the pathways defining their virulence holds great promise for the development of more effective strategies for the amelioration and eradication of this most lethal form of cancer.     

CD133:A cancer stem cells marker,is used in colorectal cancers

Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and selfrenewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD133, have been of great interest. CD133, a five-transmembrane glycoprotein, is widely used as a marker to identify and isolate colorectal cancer stem cells. This marker has been investigated to better understand the characteristics and functions of cancer stem cells. Moreover, it can also be used to predict tumor progression, patient survival, chemoradiotherapy resistance and other clinical parameters. In this review, we discuss the use of CD133 in the identification of colorectal cancer stem cell, which is currently controversial. Although the function of CD133 is as yet unclear, we have discussed several possible functions and associated mechanisms that may partially explain the role of CD133 in colorectal cancers. In addition, we focus on the prognostic value of CD133 in colorectal cancers. Finally, we predict that CD133 may be used as a possible target for colorectal cancer treatment.     

Neuroblastoma stem cells - mechanisms of chemoresistance and histonedeacetylase inhibitors

Cancer stem cells (CSCs) form a?small proportion of tumor cells that have stem cell properties: self-renewal capacity, the ability to develop into different lineages and proliferative potential. The interest in CSCs emerged from their expected role in initiation, progression and recurrence of many tumors. They are generally resistant to conventional chemotherapy and radiotherapy. There are two hypotheses about their origin: The first assumes that CSCs may arise from normal stem cells, and the second supposes that differentiated cells acquire the properties of CSCs. Both hypotheses are not mutually exclusive, as it is possible that CSCs have a?diverse origin in different tumors. CD133+ cells (CD133 is marker of CSC in some tumors) isolated from NBL, osteosarcoma and Ewing sarcoma cell lines are resistant to cisplatin, carboplatin, etoposide and doxorubicin than the CD133- ones. Being resistant to chemotherapy, there were many attempts to target CSCs epigenetically including the use of histone deacetylase inhibitors. The diverse influence of valproic acid (histone deacetylase inhibitor) on normal and cancer stem cells was proved in different experiments. We have found an increase percentage of CD133+ NBL cells after their incubation with VPA in a?dose that does not induce apoptosis. Further researches on CSCs and clinical application for their detection are necessary: (i) to define the CSC function in carcinogenesis, cancer development and their role in metastasis; (ii) to find a?specific marker for CSCs in different tumors; (iii) to explain the role of different pathways that determine their behavior and (iv) to explain mechanisms of chemoresistance of CSCs. Keywords: Cancer stem cells; CD133; Neuroblastoma; Histone deacetylase inhibitors.     

Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma

Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC) contains a heterogeneous population of cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We show that a minority population of CD44(+) cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. The tumors that arose from purified CD44(+) cells reproduced the original tumor heterogeneity and could be serially passaged, thus demonstrating the two defining properties of stem cells: ability to self-renew and to differentiate. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to play a role in self-renewal in other stem cell types and to be involved in tumorigenesis. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis.     

Lung metastasis genes couple breast tumor size and metastatic spread

The association between large tumor size and metastatic risk in a majority of clinical cancers has led to questions as to whether these observations are causally related or whether one is simply a marker for the other. This is partly due to an uncertainty about how metastasis-promoting gene expression changes can arise in primary tumors. We investigated this question through the analysis of a previously defined "lung metastasis gene-expression signature" (LMS) that mediates experimental breast cancer metastasis selectively to the lung and is expressed by primary human breast cancer with a high risk for developing lung metastasis. Experimentally, we demonstrate that the LMS promotes primary tumor growth that enriches for LMS(+) cells, and it allows for intravasation after reaching a critical tumor size. Clinically, this corresponds to LMS(+) tumors being larger at diagnosis compared with LMS(-) tumors and to a marked rise in the incidence of metastasis after LMS(+) tumors reach 2 cm. Patients with LMS-expressing primary tumors selectively fail in the lung compared with the bone or other visceral sites and have a worse overall survival. The mechanistic linkage between metastasis gene expression, accelerated tumor growth, and likelihood of metastatic recurrence provided by the LMS may help to explain observations of prognostic gene signatures in primary cancer and how tumor growth can both lead to metastasis and be a marker for cells destined to metastasize.     

Cancer stem cells

There is an increasing evidence supporting the cancer stem cell hypothesis. Normal stem cells in the adult organism are responsible for tissue renewal and repair of aged or damaged tissue. A substantial characteristic of stem cells is their ability for self-renewal without loss of proliferation capacity with each cell division. The stem cells are immortal, and rather resistant to action of drugs. They are able to differentiate and form specific types of tissue due to the influence of microenvironmental and some other factors. Stem cells divide asymmetrically producing two daughter cells -- one is a new stem cell and the second is progenitor cell, which has the ability for differentiation and proliferation, but not the capability for self-renewal. Cancer stem cells are in many aspects similar to the stem cells. It has been proven that tumor cells are heterogeneous comprising rare tumor initiating cells and abundant non-tumor initiating cells. Tumor initiating cells -- cancer stem cells have the ability of self-renewal and proliferation, are resistant to drugs, and express typical markers of stem cells. It is not clear whether cancer stem cells originate from normal stem cells in consequence of genetic and epigenetic changes and/or by redifferentiation from somatic tumor cells to the stem-like cells. Probably both mechanisms are involved in the origin of cancer stem cells. Dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. Isolation and identification of cancer stem cells in human tumors and in tumor cell lines has been successful. To date, the existence of cancer stem cells has been proven in acute and chronic myeloid leukemia, in breast cancer, in brain tumors, in lung cancer and gastrointestinal tumors. Cancer stem cell model is also consistent with some clinical observations. Although standard chemotherapy kills most cells in a tumor, cancer stem cells remain viable. Despite the small number of such cells, they might be the cause of tumor recurrence, sometimes many years after the "successful" treatment of primary tumor. Growth of metastases in distinct areas of body and their cellular heterogeneity might be consequence of cancer stem cell differentiation and/or dedifferentiation and asymmetric division of cancer stem cells. Further characterization of cancer stem cells is needed in order to find ways to destroy them, which might contribute significantly to the therapeutic management of malignant tumors.