MTA1与肿瘤淋巴管血管生成

肿瘤淋巴管血管生成在肿瘤发生及进展中发挥着重要作用。肿瘤转移相关基因1(MTA1)是近年来新发现的一个与肿瘤发生、发展密切相关的基因,既往研究显示,MTA1在肿瘤血管生成、促进肿瘤侵袭及转移中发挥着重要作用,但其在肿瘤淋巴管生成中的作用尚不清楚。该文对MTA1在肿瘤淋巴管血管生成及其促进肿瘤侵袭转移机制的研究进展予以综述。     

乏氧微环境影响肿瘤发生发展的研究进展

<正>随着近年来在细胞和分子水平对肿瘤认识的不断加深,肿瘤微环境在肿瘤发生、发展中的作用日益受到关注,与之相关的肿瘤治疗策略的不断更新改善,肿瘤微环境已逐渐成为医学领域的研究热点之一。肿瘤微环境最早于1993年提出,作为肿瘤发生,发展直接所处的环境,除为肿瘤提供基本生长条件外,还在肿瘤细胞耐药和抑制宿主免疫功能等机制中发挥重要作用^[1]。肿瘤发生早期时,微环境生化组分发生改变,极易形成乏氧状态,形成乏氧微环境;     

BNIP3基因与人类肿瘤的关系

随着肿瘤分子生物学研究的不断深入，人们越来越认识到细胞凋亡紊乱在肿瘤发生、发展过程中的重要作用。细胞凋亡即程序性的细胞死亡，是细胞由控制的有序的死亡。细胞凋亡减少可引起肿瘤的发生，细胞逃避凋亡而促进肿瘤细胞的恶化及演进。细胞凋亡不仅在肿瘤发生和发展中有重要意义，     

瘦素与卵巢癌研究进展

瘦素是脂肪细胞分泌的脂肪因子,参与调控机体的脂肪代谢。近年来发现瘦素在肿瘤发生发展中起重要作用,能促进多种肿瘤的增殖,血管生成,凋亡调节和转移等。本文就其生物学特性和在肿瘤中的作用做一综述。     

肿瘤相关成纤维细胞对肿瘤免疫调控作用的研究进展

肿瘤相关成纤维细胞（CAF）是肿瘤微环境中的重要组分,它通过分泌多种生长因子、趋化因子以及蛋白酶,调控肿瘤微环境中固有免疫细胞和适应性免疫细胞的募集和功能的发挥。此外,CAF分泌的胞外基质在塑造肿瘤微环境免疫抑制特性以及低氧形成的过程中也发挥着重要的促进作用。本文综述了肿瘤微环境中CAF对固有免疫细胞和适应性免疫细胞的浸润以及功能发挥的调控机制,同时针对以CAF为靶细胞进行药物开发的相关问题进行了展望,为进一步研究CAF的功能和临床应用提供科学依据。     

COX-2、EGFR和E-cad对肿瘤发展及预后意义的研究进展

COX-2表达不仅可以增强肿瘤细胞的增殖活动、抑制肿瘤细胞的程序性死亡、促进微血管的形成,在促进肿瘤的发生、发展、侵袭、转移及恶化过程中具有十分重要的作用。肿瘤发病的机制中,EGFR信号传导通路的改变发挥着重要的作用。E-钙黏蛋白在恶性肿瘤中与EMT、DNA甲基化有关。本文叙述了COX-2、EGFR和E-钙黏蛋白在肿瘤发生、发展过程作用及在肿瘤中的表达情况。     

炎症促进肿瘤发生发展的研究进展

炎症在肿瘤发生、发展中的作用受到广泛关注。慢性炎症或组织损伤导致的持续性炎症反应通过基因损伤或促炎性因子促进细胞转化,从而诱发慢性炎症以及肿瘤生长。在肿瘤发展的不同阶段,炎症反应发挥了决定性作用,包括肿瘤的发生、发展、恶性转化、浸润和转移等。炎症也影响了免疫监视和对治疗的反应。该文就炎症促进肿瘤发生、发展的研究进展予以综述。     

NF-κB在感染和炎症促进肿瘤发生及发展中的作用

早在十九世纪,Virchow就提出慢性感染和炎症可能引起肿瘤,然而,直到最近,流行病学的调查显示慢性感染和炎症是各种肿瘤发生的重要因素以后,炎症和肿瘤之间的相互关系的研究才得以深入.本文就NF-κB在慢性感染和炎症促进肿瘤发生和发展中的作用及其机制作一综述.     

野生型p53诱导的磷酸酶1与肿瘤发生发展及耐药关系的研究进展

野生型p53诱导的磷酸酶1（Wip1）属于丝氨酸/苏氨酸蛋白磷酸酶,是PP2C家族成员。Wip1基因是一种原癌基因,可协同其他癌基因及致癌信号通路促进肿瘤形成,在肿瘤的发生发展中发挥重要作用。本文从抑制DNA损伤应答、抑制INK4a/ARF信号通路及调控肿瘤细胞侵袭、转移和凋亡相关蛋白表达等方面阐述Wip1基因促进肿瘤发生发展的机制,指出Wip1基因促进肿瘤发生发展过程涉及的相关信号转导分子,分析Wip1基因在肿瘤细胞化疗耐药、放疗抵抗中的作用。     

组织微环境对肿瘤发生发展的影响

肿瘤微环境与肿瘤发生发展密切相关.最近的研究证实,肿瘤形成可能是干细胞分化异常导致.而微环境是干细胞稳态调节的关键,干细胞微环境的失调在肿瘤发生中扮演了重要角色.而在肿瘤发展过程中,适宜的微环境将促进肿瘤快速增殖,改变这些特异的微环境可以抑制肿瘤的恶性表型.同时.在肿瘤迁移过程中,微环境也起到了重要作用.这些机制的研究有助于加深对肿瘤的认识,为肿瘤的预防和治疗提供新的理论基础.     

Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role

Background Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.Methods The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF),transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.Results The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line,as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.Conclusion NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.     

Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role

Background  Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.

Methods  The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.

Results  The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.

Conclusion  NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.

     

癌相关成纤维细胞与肿瘤细胞相互作用对肿瘤发生发展的影响

间质细胞与细胞外基质成分构成的肿瘤微环境对肿瘤细胞的生长、浸润和转移具有重要作用.特征性间质改变通常伴随甚至先于上皮细胞的恶变.这一过程中的关键成分--活化的成纤维细胞,又称为肌成纤维细胞或者癌相关成纤维细胞,是肿瘤间质中数量最丰富的细胞类型,它们通过细胞与细胞间相互接触,在各种可溶性因子的媒介作用下,促进上皮细胞恶性转化.文中主要介绍癌相关成纤维细胞及其在肿瘤发生发展中的作用.     

Ameliorated Chrysotille—induced DNA Damage in Human Embryo Lung Cells by Surface Modification of Chrysotile With Rare Earth Compounds

OBJECTIVE: In view of the fact that asbestos is not only a key occupational hazard, but also an important environmental pollutant, it is necessary to develop a proper method to decrease the carcinogenicity of asbestos fibers. This study was designed to determine if the surface modification of chrysotile asbestos fiber (CAF) with rare earth compounds (REC) can ameliorate CAF-induced DNA damages in human embryo lung (HEL) cells. METHODS: After incubation with REC solution at different concentrations at room temperature for 1 h, natural and REC-pretreated CAF was added to cell culture at various doses. At the selected time as the experiment designed, DNA damages of the HEL cells were detected by Unscheduled DNA Synthesis (UDS) and Single Cell Gel Electrophoresis (SCGE) assays. RESULTS: The UDS induced by natural CAF was elevated with the increase of CAF doses. There was a good dose-response relationship between the UDS and the amount of CAF in the medium and the coefficient of correlation (R) was 0.958 at P < 0.05. In REC-pretreated CAF groups, the UDS declined with the increase of REC doses. Both catalase (CAT) and dimethylsulfoxide (DMSO) also reduced the CAF-induced enhancement of UDS. In SCGE assay, CAF induced DNA chain breakage and the magnitude of DNA chain breakage increased in a dose-dependent manner and the coefficient of correlation (R) was 0.992 at p < 0.01, while REC-pretreated CAF significantly decreased the induction of DNA chain breakage in a dose-dependent manner (r = 0.989, p < 0.05). CONCLUSION: It can be concluded that CAF-induced DNA damages in HEL cells may be partly mediated by oxygen derivatives, and the surface modification of CAF with REC might hide critical sites on the fiber surface, thereby reducing the fiber-mediated production of oxygen derivation and lowering the CAF-induced UDS and DNA chain breakage in HEL cells.     

慢性房颤对风湿性心脏病心房肌细胞ELK-1、p-ELK-1表达的影响

目的 研究风湿性心脏病慢性房颤患者心房肌细胞ELK-1、p-ELK-1的表达,探讨房颤发生与ELK-1、p-ELK-1 表达之间的关系.方法 12例风心病换瓣患者分为2组:①慢性房颤组(6例)房颤持续时间均＞6个月,②窦性心律组(6例)为正常心律.手术中切取少许右心房游离壁组织采用免疫组化和间接免疫荧光技术检测心房肌ELK-1、p-ELK-1的表达与分布.结果 ①免疫组化显示ELK-1主要表达在心房肌细胞质和细胞核,慢性房颤心房肌较窦性心律心房肌表达明显减弱;②间接免疫荧光技术显示ELK-1在窦性心律心房肌细胞核表达相对较高,在房颤心房肌细胞核中表达明显受到抑制;p-ELK-1在房颤心房肌、窦性心律心房肌均表达受抑.结论 转录激活因子ELK-1的表达改变可能在慢性房颤心房肌的分子重构中起着重要的作用.     

肝脏中自然杀伤细胞的表型及功能

自然杀伤(NK)细胞是先天性免疫系统的重要组成部分,也是机体抗感染和防止细胞恶性转化的重要免疫调节细胞。与T淋巴细胞不同,NK细胞无需肿瘤特异性抗原识别便可以直接杀伤肿瘤细胞,是肿瘤免疫治疗的重要效应细胞。在肝脏中,NK细胞占很大比例,最近研究表明,NK细胞通过直接作用或生物信号间的协同作用活化树突状细胞或直接影响T细胞来调节T细胞的反应。肝脏NK细胞功能主要是通过激活抑制性受体的表达和炎性细胞因子的分泌调节,特别是与脾脏NK细胞相比,肝内NK细胞对白细胞介素(IL)-12、IL-18反应较低。同时,肝脏中含有较多的抑制性受体NK细胞受体2A抗体,缺乏组织相容性复合体Ⅰ类/Ly49受体。     

Roles of MicroRNAs in Cancer Stem Cells

Cancer stem cells are cells with stem cell characteristics within a tumor. With increased proliferative capabilities, they are able to self-renew and develop into various cell types, and thus play important roles in the formation, development, metastasis, and recurrence of tumors. MicroRNAs are a class of endogenous, small non-protein coding RNA molecules. Through regulating the expression of genes depending on the complementation between the microRNAs and their targets, microRNAs play important roles in various human cancers. This article summarizes recent research advances in the roles of microRNAs in cancer stem cells.     

肿瘤成纤维细胞通过外泌体miR- 21促进膀胱癌细胞侵袭转移

（1. Department of Urology, Nanjing Gaochun People’s Hospital, Nanjing Jiangsu 211300; 2. Department of Urology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing Jiangsu 210029, China）     

外泌体在乳腺癌中的研究进展

外泌体是一类由自体细胞分泌的纳米级囊泡样小体,参与细胞及内环境之间的物质运输和信号传递。外泌体可以通过在肿瘤细胞和细胞外基质间运输细胞内的核酸、蛋白和脂类等物质,影响肿瘤的发生和发展,甚至可以影响肿瘤的治疗。不同类型的肿瘤细胞分泌的外泌体,在肿瘤的发生过程中发挥着不同的作用。近来,与乳腺癌相关的外泌体逐渐成为一项新的研究热点,并发现乳腺癌细胞可以刺激分泌某些特定类型的外泌体,并有望成为早期乳腺癌筛查的新型生物学标志。外泌体传递的核酸、蛋白质等物质在乳腺癌的发生、转移和治疗耐药中起到了重要作用。同时外泌体也可以将抗肿瘤药物转运出乳腺癌细胞导致耐药。但外泌体作为肿瘤药物载体时,表现出极低的免疫原性和生物毒性,将为今后的肿瘤靶向治疗提供可行的技术基础。     

Jagged1与肿瘤的研究进展

Jagged1是存在于哺乳动物细胞膜上Notch受体的主要配体之一,参与调控许多组织的生长发育。研究表明,它对肿瘤发生有很大影响,能单独或通过激活Notch信号通路调控细胞的增殖、分化及凋亡。Jagged1还参与肿瘤新生血管化,在肿瘤的内皮组织中通过活化Notch信号通路促进肿瘤血管形成。