血小板在肿瘤转移中的作用

血小板是巨核细胞产生的无核细胞碎片,其主要功能是参与凝血和止血。近年来,越来越多的研究和临床证据表明,血小板还参与并促进了肿瘤转移。当肿瘤细胞从原位肿瘤组织脱落进入血管后,血小板是其第一个接触到的宿主细胞。作为肿瘤转移微环境中的重要成员,血小板与肿瘤细胞之间相互作用和相互影响。一方面,肿瘤细胞能通过诱导血小板活化和聚集来调节血小板功能;另一方面,血小板能够通过直接接触和释放生物活性介质的方式,促进肿瘤转移。大量的研究结果表明,血小板主要通过以下几条途径促进肿瘤转移:1)降低血液流体剪切力对肿瘤细胞造成的机械损伤;2)帮助肿瘤细胞逃避免疫监视;3)促进肿瘤细胞在血管内的迁移和停滞;4)促进肿瘤细胞上皮间质转化;5)促进肿瘤细胞外渗;6)构建适合肿瘤细胞生存的转移生态位。因此,靶向血小板与肿瘤细胞相互作用成为潜在的肿瘤治疗策略。本文以国内外最新研究进展为基础,综述血小板在肿瘤转移不同阶段发挥的作用,以及抗血小板药物在肿瘤治疗中的应用。     

乳腺癌血行肺转移模型家兔血小板与凝血功能变化研究

目的 研究乳腺癌血行肺转移模型家兔血小板与凝血功能的变化规律。方法 取健康雌性新西兰白兔12只,随机分为2组：正常组和模型组,模型组家兔左侧第3乳房乳垫注射VX2组织悬液,再经耳缘静脉注射VX2细胞悬液,构建乳腺癌血行肺转移家兔模型。观察42 d内家兔精神状态、饮食情况,监测体重和肿瘤大小,检测血小板相关参数PLT、MPV、PDW、PCT和凝血相关指标PT、APTT、TT、FIB及D-二聚体;实验终点ELISA法检测血清CD63、CD62P、TXB₂及血浆GMP-140水平;取肿瘤组织和肺用10%甲醛固定、石蜡包埋、切片、HE染色,光学显微镜下观察肿瘤和肺组织形态变化。结果 家兔乳垫注射VX2组织悬液附加静脉注射VX2细胞悬液,能成功构建乳腺癌血行肺转移家兔模型,肺转移率100%,模型家兔血液处于高凝状态,14～42 d内,PLT、MPV、PCT均明显增加;10～30 d内,PT、APTT、TT均明显缩短,且FIB、D-二聚体含量均明显增加;血清CD63、CD62P、TXB₂及血浆GMP-140水平明显增高;模型家兔乳腺中肿瘤细胞增多、排列疏...     

参杞合剂对高转移肺癌细胞体外作用的研究

参杞合剂(SQ)是以传统中药参杞片为基础,辅以黄芪、当归、莪术、白花蛇舌草煎制而成,据报道其在小鼠体内、外有抗瘤、抑瘤之功效。但其是否对人类肿瘤也有同样功效尚不可知。本实验通过研究参杞合剂对人高转移肺癌细胞(PG)生长调控的作用及其表面粘附分子(CD44、CD55)表达的影响,初步探讨其对人类肿瘤作用的相关机制,为今后开发抗肿瘤新药提供理论依据。     

RhoC、Rho-GDIα在肺癌细胞系中过表达并与转移相关

目的 分析Rhoc及其调节蛋白GDP解离抑制因子α(Guanine dissociation inhibitor,GDIα)在肺癌细胞中的表达及其与肺癌细胞转移能力间的关系.方法 应用Western blot、RT-PCR分别检测正常支气管上皮细胞、不同的肺癌细胞系中的RhoC、Rho-GDIa蛋白及RNA的表达.结果 RhoC、Rho-GDIα在人支气管上皮细胞、肺腺癌细胞系、肺巨细胞癌细胞系均有表达,免疫荧光显示均表达于细胞浆.RhoC、Rho-GDIα在肺癌中的表达高于人支气管上皮细胞.在高转移能力的肺巨细胞癌亚系BEl RhoC、Rho-GDIα的表达均高于低转移能力的肺巨细胞癌亚系LH7.结论 RhoC、RhoGDIα在肺癌细胞系中过表达并与转移能力相关.     

78例肺癌脑转移患者临床分析

目的：探讨与肺癌脑转移预后相关的影响因素,为更好的治疗肺癌脑转移提供参考依据。方法：回顾性分析2002年~2009年唐都医院收治的78例肺癌脑转移的临床资料。结果：患者年龄、性别、病理类型、脑转移灶数目、颅外有无转移性病灶、患者的行为状态（PS评分）对患者生存期无显著影响（P〉0.05）。但放疗＋化疗治疗组疗效显著优于单纯放疗组及单纯化疗组（P〈0.05）,症状消失者（CR）或明显缓解者（PR）生存较无明显改善者（SD）或加重者（PD）生存期显著延长。结论：对肺癌脑转移患者应采取放疗联合化疗综合方案治疗,同时,应及时关注其症状缓解情况并指导治疗。     

肺癌转移抑制相关基因研究进展

肺癌是发病率和死亡率增长最快、对人类健康威胁最大的恶性肿瘤之一。侵袭转移是肺癌患者死亡的首要原因。研究表明,在肺癌中发挥转移抑制作用的相关基因主要有nm23、KAI1、TIMP、Cadherin以及MRP-1等。本文对近年来这些基因的研究进展及其对肺癌侵袭转移的抑制作用作一综述     

78 例肺癌脑转移患者临床分析

目的:探讨与肺癌脑转移预后相关的影响因素,为更好的治疗肺癌脑转移提供参考依据。方法:回顾性分析2002年~2009年唐都医院收治的78例肺癌脑转移的临床资料。结果:患者年龄、性别、病理类型、脑转移灶数目、颅外有无转移性病灶、患者的行为状态(PS评分)对患者生存期无显著影响(P>0.05)。但放疗+化疗治疗组疗效显著优于单纯放疗组及单纯化疗组(P<0.05),症状消失者(CR)或明显缓解者(PR)生存较无明显改善者(SD)或加重者(PD)生存期显著延长。结论:对肺癌脑转移患者应采取放疗联合化疗综合方案治疗,同时,应及时关注其症状缓解情况并指导治疗。     

TGF-β/Smads在肺癌中的表达研究

转化生长因子TGF-β／Smads是细胞增殖的抑制因子。它可以促进细胞外基质的增生和原发性肿瘤的转移。选择20例肺癌组织标本及8种不同转移能力的肺癌细胞系,通过荧光免疫组织化学染色法进行RⅡ和Smsds蛋白定位及表达分析。初步探讨了TGF-β／Smads信号传导通路与肺癌发生和转移的关系。     

微RNA调节肺癌转移的分子机制

微RNA(microRNA,miRNA)是一类长约22 nt的非编码小分子RNA,在转录后水平上通过基因沉默调节靶基因的活性。近年来,miRNA与肿瘤转移关系的研究成为探讨肿瘤转移调控机制的热点。越来越多的研究提示miRNA在肿瘤转移过程中发挥着重要作用。肺癌转移是影响肺癌预后的关键,是一种复杂的多因素、多步骤、多基因参与调控的过程。研究miRNA对肺癌转移的作用有助于我们找到阻断肺癌转移的靶点。本文就miRNA和肺癌转移关系的研究进展作一综述。     

血小板、基质金属蛋白酶与肿瘤转移

血小板除参与正常的止血过程外还具有很多病理和生理作用。血小板活化后可以分泌基质金属蛋白酶（matrix metalloproteinases,MMPs）。MMPs属于Zn^2＋和Ca^2＋依赖的内肽酶家族,能特异性与细胞外基质成分相结合并降解细胞外基质。MMPs降解基底膜中的主要成分Ⅳ型胶原,是肿瘤转移发生必不可少的关键步骤。血小板能够与肿瘤细胞结合并促进肿瘤转移,而MMPs在血小板促进肿瘤转移过程中发挥了重要的作用。     

The role of blood platelets in tumor angiogenesis

Coagulation abnormalities occur frequently in cancer patients. It is becoming evident that blood platelets have an important function in this process. However, understanding of the underlying mechanisms is still very modest. In this review, we discuss the role of platelets in tumor angiogenesis and growth and suggest their potential significance in malignancies. Platelets contain various pro-and antiangiogenic molecules, which seem to be endocytosed and sequestered in different populations of α-granules. Furthermore, tumor endothelial cells are phenotypically and functionally different from endothelial cells in healthy tissue, stimulating local platelet adhesion and subsequent activation. As a consequence, platelets are able to secrete their angiogenic and angiostatic content, most likely in a regulated manner. The overall effect of these platelet–endothelium interactions appears to be proangiogenic, stimulating tumor angiogenesis. We favor the view that local adhesion and activation of blood platelets and dysregulation of coagulation represent underestimated pathways in the progression of cancer.     

Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer

The carbohydrate determinants, sialyl Lewis A and sialyl Lewis X, which are frequently expressed on human cancer cells, serve as ligands for a cell adhesion molecule of the selectin family, E-selectin, which is expressed on vascular endothelial cells. These carbohydrate determinants are involved in the adhesion of cancer cells to vascular endothelium and thus contribute to hematogenous metastasis of cancer. The initial adhesion mediated by these molecules triggers activation of integrin molecules through the action of several cytokines and leads to the extravasation of cancer cells. Cancer cells also produce humoral factors that facilitate E-selectin expression on endothelial cells. The degree of expression of the carbohydrate ligands at the surface of cancer cells is well correlated with the frequency of hematogenous metastasis and prognostic outcome of patients with cancers. The alteration of glycosyltransferase activities that leads to the enhanced expression of these carbohydrate ligands on cancer cell surface are currently being investigated. This revised version was published online in November 2006 with corrections to the Cover Date.     

sLea/x与肿瘤血源性转移研究进展

肿瘤细胞表面sLea/x的表达水平与组织病理学参数正相关,且是转移性疾病的一个很重要的预后指标[1]。ssLea/x与其配体E-选择素的结合启动了肿瘤血源性转移的发生。sLea/x与其配体的相互作用需要一定的活性构象,而基于模拟sLea/x的生物活性结构而设计的一类小分子化合物,可以有效地抑制sLea/x与其配体的结合,从而发挥抗肿瘤作用。本论文对近年来sLea/x与肿瘤血源性转移关系的研究及相关药物开发进行了综述。     

The role of lipids in cancer progression and metastasis

1. Download : Download high-res image (96KB)
2. Download : Download full-size image

     

Apoptosis and lung cancer: a review

It is important to understand the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death. Defects in apoptosis are implicated in both tumorigenesis and drug resistance, and these defects are cause of chemotherapy failures. These studies should explain the relationship between cancer genetics and treatment sensitivity, and should enable a more rational approach to anticancer drug design and therapy. Lung cancer is a major cause of cancer deaths throughout the world. Small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) represent the two major categories of lung cancer that differ in their sensitivity to undergo apoptosis. The role of apoptosis regulation in lung cancer with major focus on the differential sensitivities of the major subtypes is reviewed.     

The role of the organ microenvironment in the biology and therapy of cancer metastasis

By the time of diagnosis, primary neoplasms are biologically heterogeneous and contain subpopulations of cells with different metastatic potentials. The pathogenesis of a metastasis consists of many sequential steps that must be completed to produce clinically relevant lesions. During any of these steps, tumor cells interact with host factors in the microenvironment that the tumor cells can usurp. Treatment of metastasis can be directed against tumor cells and/or microenvironmental factors that support tumor growth, such as tumor-associated blood vessels.