乳腺癌细胞促血管生成能力及MMP-9 表达与其淋巴道转移的关系

 目的　本研究旨在通过检测血管内皮细胞生长因子(VEGF) ,基质金属蛋白酶-9 (MMP-9) 在乳腺癌细胞中的表达情况及计数微血管密度(Microvascular density , MVD) 值来探讨它们与乳腺癌浸润和转移的关系。方法　采用免疫组织化学SP 法检测75 例乳腺浸润癌(有淋巴结转移者39 例,无淋巴结转移者36 例) 中VEGF、MMP-9 、CD34 的表达,并用多因素COX 比例风险模型分析患者的预后。结果　VEGF 、MMP-9 和MVD 在淋巴结转移组与无转移组的表达均具有显著性差异( P < 0. 05) , 与乳腺癌淋巴结转移呈正相关。MVD 值高者生存时间短。结论　乳腺癌淋巴道转移与VEGF、MMP-9 表达及MVD 值有关,检测这几种蛋白表达将有助于判断乳腺癌的转移潜能及预后。     

COX-2、VEGF在胃癌中的表达及其预后意义

目的 :研究COX 2、VEGF表达对胃癌的预后意义。方法 :收集我院 1990～ 1999年早、中期胃癌 2 81例 ,对有完整存档蜡块资料的 2 32例进行免疫组织化学染色。检测COX 2、VEGF及MVD在胃癌组织中的表达 ,并分析其预后意义。结果 :胃癌组织中COX 2、VEGF阳性表达的MVD值均显著高于COX 2、VEGF阴性表达者(P <0 0 1) ;COX 2、VEGF阳性表达及MVD值与胃癌淋巴结转移、血管浸润均密切相关 (P <0 0 1) ;COX 2、VEGF阳性表达者五年生存率明显低于阴性者 (P <0 0 1)。多因素分析显示 ,VEGF表达、淋巴结转移、COX 2表达、浸润深度、血管浸润均为胃癌独立的预后因素。结论 :COX 2、VEGF在胃癌组织呈过度表达状态 ,与胃癌的生长和浸润转移关系密切 ,可以作为反映胃癌生物学行为和判断预后的有效指标。     

胃癌微血管密度与VEGF表达的关系138例分析

[目的]探讨胃癌微血管密度与VEGF表达的临床病理意义。[方法]采用超敏SP法检测138例胃癌患者微血管密度（MVD）和VEGF表达,结合临床病理学特征进行相关分析。[结果]胃癌组织MVD平均为45．77±11．31,MVD与肿瘤浸润深度、淋巴结状态相关（P〈0．05）;VEGF表达阳性率为85．5％（118／138）,VEGF阳性表达与组织学分化型、淋巴结转移、血管浸润相关。MVD在VEGF阳性表达组显著高于阴性表达组（P=0．008）：MVD值与VEGF表达状态显著相关。[结论]MVD值与VEGF激活在胃癌发展进程中发挥重要作用．联合检测MVD和VEGF表达可作为胃癌生物学行为和预后的判断指标。     

胃癌组织中环氧化酶-2的表达与微血管密度和VEGF的关系

目的 :探讨环氧化酶 -2 (COX 2 )在胃癌组织中的表达及其与微血管密度(microvesseldensity ,MVD)和血管内皮生长因子 (vascularendothelial growthfactor ,VEGF)的关系。方法 :采用免疫组织化学法 ,检测 43例胃癌患者手术切除标本中COX 2和VEGF的表达 ,并计数MVD。结果 :COX 2在胃癌组织的阳性表达率为60 5 % ,明显高于对照组 ,P <0 0 1;并且与胃癌淋巴结的转移和临床分期有关 ,与肿瘤大小、浸润深度、分化程度均无关。COX 2和VEGF表达一致符合率为 5 3 5 % ,两者表达有显著相关性 ,P <0 0 1。COX 2阳性和VEGF阳性组MVD值 (2 2 0 8± 3 69、2 2 12± 3 5 0 )均高于COX 2阴性和VEGF阴性组 (17 68± 3 5 0、16 15± 3 2 3 ) ,P <0 0 5 ;COX 2和VEGF均为阳性者的MVD值最高 (2 2 86± 3 40 ) ,P <0 .0 5。结论 :COX 2、VEGF的表达以及MVD的测定可作为判断胃癌恶性潜能的重要生物指标。COX 2、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测COX 2、VEGF的表达对了解肿瘤血管形成的机制有一定的作用     

乙酰肝素酶在胃癌中表达的临床意义

目的　探讨胃癌组织中乙酰肝素酶(Hpa)表达状况与肿瘤微血管密度(MVD)和胃癌临床病理特征的关系。方法　应用免疫组化SABC法检测60例胃癌组织中Hpa表达及计数MVD。结果　Hpa表达和胃癌组织浸润深度、TNM分期和淋巴结转移有关,Hpa阳性表达组MVD值(4 8.8±11.3 )显著高于Hpa阴性表达组MVD值(4 1.5±11.9) (P <0 .0 5 )。结论　Hpa可促进肿瘤微血管生成,加速肿瘤浸润和转移。     

非小细胞肺癌组织中血管内皮生长因子的表达与微血管密度的关系

 目的　探讨非小细胞肺癌 (NSCLC)组织中血管内皮生长因子 (VEGF)表达和微血管密度(MVD)的关系。方法　采用免疫组化S P法对 76例NSCLC标本中VEGF表达和MVD进行了检测。结果　在NSCLC中鳞癌的VEGF表达阳性率显著高于腺癌 (P <0 .0 5 ) ;VEGF表达阳性率和MVD值与肿瘤组织学分化程度有关 ,低分化癌VEGF表达阳性率和MVD值显著高于中、高分化癌 (P <0 .0 5 ) ;淋巴结转移阳性组NSCLC的VEGF表达阳性率和MVD值显著高于阴性组 (P <0 .0 5 )。结论　VEGF可引起瘤内MVD增多 ,促进肿瘤的生长和转移 ;检测VEGF表达强度 ,可作为判定NSCLC转移潜能和评价预后的指标     

肿瘤相关巨噬细胞与胃癌血管生成及转移关系

[目的]探讨肿瘤相关巨噬细胞（TAMs）浸润与胃癌血管生成及转移的关系。[方法]采用免疫组织化学法检测51例胃癌组织微血管密度（MVD）、TAMs和血管内皮生长因子（VEGF）的表达。[结果]TAMs的表达在高分化癌组织中明显低于中-低分化组（P〈0．05）；淋巴结转移组高于无淋巴结转移组（P〈0．05）；TAMs与VEGF及MVD均呈正相关（r=0．74，P〈0．01：r=0．58，P〈0．05）。[结论]胃癌组织中TAMs在血管生成及肿瘤转移中可能起重要作用。     

乳腺癌VEGF的表达和微血管形成的关系及意义

目的 :探讨血管内皮生长因子 (VEGF)与肿瘤内微血管形成的关系 ,以及微血管密度 (MVD)与乳腺癌淋巴结转移和预后的关系。方法 :采用免疫组化 S- P法对 4 0例人乳腺浸润性导管癌组织中的 VEGF和 MVD进行检测。结果 :VEGF阳性者 MVD值显著高于阴性者 ,VEGF表达和MVD与乳腺癌淋巴结转移关系密切。结论 :VEGF与乳腺癌血管生成密切相关 ,VEGF和 MVD表达的增高对乳腺癌淋巴结转移有促进作用 ,MVD和 VEGF均可作为反映乳腺癌生物学行为的指标之一     

胃癌组织中H-ras和VEGF的表达与血管生成的关系及其临床意义

目的:探讨胃癌组织H-ras表达与血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)表达和血管生成的关系。方法:应用免疫组织化学ABC法对60例胃癌组织进行H-ras、VEGF表达和微血管密度(micro-vasculardensity,MVD)检测。结果:MVD与胃癌病灶的大小、浸润深度、淋巴结转移和TNM分期密切相关,t值分别为-2·18、-3·46、-4·52和-3·85,P值分别为0·040、0·001、0·001和0·004;VEGF亦与胃癌病灶的大小、浸润深度、淋巴结转移和TNM分期密切相关,χ2值分别为12·80、11·49、10·43和11·52,P值分别为0·002、0·001、0·005和0·003。H-ras的表达与胃癌分化和Lauren分型相关,χ2值分别为11·85和8·87,P值分别为0·001和0·003;并与VEGF的表达相关,χ2=10·79,P=0·001。生存分析显示,MVD和VEGF的表达均影响胃癌的预后,但仅MVD是影响预后的独立因素;H-ras的表达对胃癌的预后影响较小。结论:激活的H-ras可上调VEGF的表达,参与胃癌血管生成的调节,并影响胃癌组织的分化。     

微血管密度及血管内皮生长因子在贲门癌中的表达及其意义

 目的　探讨贲门癌组织中微血管密度及血管内皮生长因子 (VEGF)的表达与其生物学行为的关系。方法　对 4 8例具有较完整临床病理资料的贲门癌组织 ,进行了CD34、VEGF免疫组织化学SP法检测 ,分析VEGF和微血管密度 (MVD)与贲门癌的分化程度、临床分期、淋巴结转移的关系。结果　VEGF阳性表达与MVD均与癌组织分化程度、临床分期、淋巴结转移有相关性(P <0 .0 5 ) ,并且在VEGF阳性表达的肿瘤中 ,MVD明显高于阴性者 (P <0 .0 5 )。结论　VEGF与贲门癌的血管生成密切相关 ,对肿瘤生长、浸润和转移有促进作用。VEGF和MVD可作为预测贲门癌生物学行为指标之一。     

Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecularly targeted anti-cancer agents being used to attack malignancy in a rational manner. A large body of preclinical data indicates that FTase inhibitors block cancer cell proliferation through both cytostatic and cytotoxic effects. Interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they may target unique aspects of cancer cell pathophysiology. The development of FTase inhibitors was predicated on the discovery that the Ras oncoproteins must be post-translationally modified to transform cells. However, recent work indicates that the anti-neoplastic effects of FTase inhibitors depend on altering the post-translational modifications of non-Ras proteins as well. In particular, a critical target protein that responds to FTase inhibition by blocking tumor cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In this review, we survey the biological foundations for the clinical development of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.     

Telomerase and human tumorigenesis

Human cancer cells, unlike their normal counterparts, have shed the molecular restraints to limited cell growth and are immortal. Exactly how cancer cells manage this at the molecular level is beginning to be understood. Human cells must overcome two barriers to cellular proliferation. The first barrier, referred to as senescence, minimally involves the p53 and Rb tumor-suppressor pathways. Inactivation of these pathways results in some extension of lifespan. However, inactivation of these pathways is insufficient for immortalization. As normal cells undergo repeated rounds of DNA replication, their telomeres shorten due to the inability of traditional DNA polymerases to completely replicate the end of the chromosomal DNA. This shortening continues until the cells reach a second proliferative block referred to as crisis, which is characterized by chromosomal instability, end-to-end fusions, and cell death. Stabilization of the telomeric DNA through either telomerase activation or the activation of the alternative mechanism of telomere maintenance (ALT) is essential if the cells are to survive and proliferate indefinitely. Conversely, loss of telomere stabilization by an already-immortalized cell results in loss of immortality and cell death. Together this indicates that telomere maintenance is a critical component of immortality. In this review we attempt to describe our current understanding of the role of telomere maintenance in senescence, crisis, and tumorigenesis.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

LMP1 structure and signal transduction

The oncogenic Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has structural features and functions reminiscent of a constitutively active TNF family receptor. LMP1 aggregates at the plasma membrane and initiates the activation of signalling pathways, such as NF- kappa B, the mitogen-activated protein kinases JNK and p38, the small GTPase Cdc42 and the JAK/STAT cascade. The constitutive engagement of these signals and the characteristic molecular interactions that regulate them provide the basis for the molecular explanation of the transforming properties of this key EBV protein.     

肝癌细胞,癌旁肝细胞转铁蛋白合成及分泌速率的研究

目的　研究肝癌细胞转铁蛋白 ( Tf)合成量及合成后分泌速率的变化 ,探讨肝癌组织中膜结合性 Tf含量降低的原因。方法　采用同位素掺入及免疫共沉淀的方法测定了肝癌细胞及癌旁肝细胞 Tf的合成及分泌速率。结果　与癌旁肝细胞相比 ,尽管肝癌细胞 Tf的合成量没有明显变化 ,但其合成 Tf后的分泌速率加快 ,从而使 Tf的贮存量减少。结论　以上结果可能有利于肝癌细胞的生长与增殖 ,并解释了肝癌组织中膜结合性 Tf含量降低的原因。     

ABCG2在肺癌中表达的定量研究

目的 观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义.方法 常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度.结果 ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜.在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P＜0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零.癌周肺组织表达的PU值高于各型肺癌(P＜0.05).ABCG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P＞0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P＞0.05),与肺癌分化程度有关(P＜0.001).分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P＞0.05).结论 ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一.     

奥沙利铂联合氟尿嘧啶和甲酰四氢叶酸治疗局部进展期胃癌临床研究

目的:评价奥沙利铂、5氟尿嘧啶(5FU)和甲酰四氢叶酸(CF)联合新辅助化疗治疗局部进展期胃癌的近期疗效和毒副反应。方法:选择2000年3月～2004年4月我科住院的胃癌患者42例入组,术前接受化疗,方案为:奥沙利铂130mg/m2,d1;5FU500mg/m2,d1～d3;CF300mg/d,d1～3。每3个周为1个周期,共2个周期。观察新辅助化疗后肿瘤原发病灶的缓解情况,并观察毒副反应。结果:42例患者中有38例获得手术切除,其中26例获得根治性切除,19例肿瘤原发病灶明显缩小,14例肿瘤TNM分期降低。毒副反应主要为白细胞减少、腹泻、恶心、呕吐、脱发、肝功能异常,经对症及营养支持治疗后均能缓解。结论:奥沙利铂联合5FU与CF新辅助化疗在局部进展期胃癌的治疗中近期疗效显著,耐受性良好。     

血清与脑脊液唾液酸含量测定对脑瘤与脊髓瘤诊断价值的比较

检测脑瘤与脊髓肿瘤患者血清和脑脊液中唾液酸的含量，比较两者对脑瘤与脊髓瘤的诊断价值。方法应用ＳＡ快速比色测定盒对１１３例脑肿瘤和２４例脊髓肿瘤患者血清及ＣＳＦ唾认酸含量进行测定，分别进行组间比较。结论血清和ＣＳＦ中ＳＡ含量可和为脑瘤与脊髓瘤的诊断指标之一，而ＣＳＦ中ＳＡ含量的测定对脑瘤与脊髓瘤的诊断更具临床价值。     

食管平滑肌瘤的诊断及外科治疗

目的　探讨食管平滑肌瘤的诊断及外科治疗特点。方法　对 14 1例食管平滑肌瘤患者的术前影像学、内窥镜资料及外科治疗结果进行回顾性分析。结果　食管平滑肌瘤患者的主要症状为吞咽不顺 (6 4 .5 % )及胸部或上腹部疼痛 (2 0 .6 % ) ,平均病史 15 .7个月。 11例术前误诊为食管恶性肿瘤、纵隔或腹膜后肿瘤。 13例行食管部分切除术 ,其中 2例肿瘤巨大 ,3例术中仍误诊为食管恶性肿瘤 ,8例并存食管癌或贲门癌。 12 8例行肿瘤摘除术 ,13例术中黏膜破裂并予以修补。肿瘤单发 130例 ,多发 11例。瘤体呈类圆形、马蹄形或不规则形 ,包绕食管周经 <1/ 2者 75例 ,>1/ 2者 5 9例 ,累及全周者 7例。肿瘤呈息肉状管腔内生长 1例 ,管壁外生长 2例 ,其余均管壁内生长。本组无手术死亡 ,手术并发症发生率 3.6 %。结论　食管平滑肌瘤易误诊为食管恶性肿瘤或纵隔肿瘤 ,应注意鉴别诊断。术式选择应尽可能行肿瘤摘除术。食管镜检查疑为平滑肌瘤时应避免活检。食管平滑肌瘤患者食管癌发病率较高 ,其原因有待探讨     

Signalling events regulating lymphoid growth and survival

Epstein-Barr virus (EBV) uses many different strategies to induce lymphocyte proliferation and survival. In the different states of EBV infection and latency, several genes play specific roles in the induction of cell growth and cell survival proteins. EBNA2A, EBNA-LP and EBNA3C all modulate early events in the G1 phase of the cell cycle. Furthermore, interleukin-6 and interleukin-10, which are induced following EBV infection, appear to be important for growth. They activate signalling pathways that have been shown to link directly to proliferation. Latent membrane protein 1 (LMP1) induces a number of anti-apoptotic proteins via NF- kappa B, and LMP2A also appears to contribute to lymphocyte survival. This paper describes some of the many cellular pathways modulated by EBV that interact with the signalling machinery and thus make lymphocytes survive and grow.