鼻咽癌细胞凋亡与血管生成的关系

摘要：为了探讨鼻咽癌（NPC）细胞凋亡及瘤内血管生成与患者预后的关系,采用TdT酶介导的生物素化dUTP缺口末端标记技术（TUNEL）和免疫组化S-P法,分别检测20例正常鼻咽粘膜组织及73例NPC组织的细胞凋亡率（Apoptosis Rate AR）、瘤内微血管密度（MVD）及血管内皮细胞生长因子（VEGF）的表达。其中,NPC复发转移组24例,未复发组49例。结果表明,正常鼻咽粘膜AR显著高于NPC（P〈0．01）,NPC复发转移组的MVD及VEGF显著高于未复发组（P〈0．05）,而AR则显著低于未复发组（P〈0．05）,MVD与VEGF、MVD与AR呈正相关（P〈0.05）。在NPC发展过程中,细胞凋亡明显受到抑制,VEGF是血管生成的重要因子,并通过促进血管生成影响患者的预后,说明细胞凋亡与NPC患者的预后有关系。     

乳腺癌血管内皮生长因子-C和微血管密度的表达及其意义

探讨乳腺癌血管内皮生长因子-C(VEGF-C)、肿瘤血管生成的表达与淋巴结转移的生物学行为关系,应用免疫组化PV9000二步法检测50例乳腺癌组织VEGF-C和微血管密度(MVD)的表达。结果表明,淋巴结转移组的VEGF-C和MVD明显高于淋巴结无转移组(p<0.05)。其中,VEGF-C阳性表达组33例,MVD值为31.67±7.85;VEGF-C阴性表达组17例,MVD值为26.84±7.03,两者之间具有相关性,差异显著(p=0.03)。乳腺癌的淋巴结转移与VEGF-C的表达、微血管密度密切相关。由此可见,VEGF-C在乳腺癌的淋巴管、血管生成中起着重要的作用,VEGF-C和MVD与乳腺癌淋巴结转移有关,并可能协同作用淋巴结转移过程。     

淋巴管密度、微血管密度与VEGF在胃癌中的生物学意义

目的:探讨血管内皮生长因子(VEGF)和与淋巴管密度(LVD)和微血管密度(MVD)之间的关系以及在胃癌组织中的临床病理意义.方法:应用免疫组化SP法检测29例正常胃组织、43例不典型增生胃组织和48例胃癌中VEGF的表达水平,同时标记D2-40和CD105,计数淋巴管密度(LVD)、微血管密度(MVD).结果:(1)在胃癌组织内的VEGF,MVD,LVD较正常胃组织、不典型增生胃组织明显增高,且均有统计学差异(P0.05);(2)胃癌组织中VEGF的表达在有淋巴结转移组高于无转移组;浸润深度T3、T4组也高于T1、T2组,有统计学差异(P0.05);MVD在有淋巴结转移组高于无转移组;浸润深度T3、T4组也高于T1、T2组,有统计学差异(P0.05);LVD在有淋巴结转移组高于无转移组;浸润深度T3、T4组也高于T1、T2组且高、中分化组LVD高于低分化组有统计学差异(P0.05);(3)胃癌组织中,VEGF的阳性表达率为77%,在VEGF阳性组中的MVD计数明显高于在阴性组中的计数,有统计学差异(P0.05),而在LVD则无统计学差异((P0.05).结论:VEGF可能通过促进胃癌的血管形成而参与癌细胞的浸润转移,VEGF和MVD、LVD的检测可作为胃癌转移的指标.     

MVD及VEGF表达与鼻咽癌侵袭转移关系的研究

为探讨微血管密度（ＭＶＤ）及血管内皮生长因子（ＶＥＧＦ）的表达与鼻咽癌（ＮＰＣ）侵袭转移关系,在分子水平干预肿瘤血管生成,预防ＮＰＣ复发和转移打下基础,采用免疫组织化学Ｓ－Ｐ法检测了７３例ＮＰＣ,１５例鼻咽良性肿瘤、２０例无瘤鼻咽部石蜡标本组织中的ＭＶＤ及ＶＥＧＦ表达,ＮＰＣ中转移组４９例,非转移组２４例。     

再生障碍性贫血中VEGF和MVD的相关性研究

目的：研究再生障碍性贫血患者血管内皮生长因子（VEGF）的表达,微血管的生成与疾病病理临床改变的关系。方法：用免疫组织化学染色方法检测35g4再生障碍性贫血患者和35例正常人的骨髓蜡块的VEGF表达情况,并用CD34标记血管内皮细胞,对VEGF和微血管密度（MVD）的表达进行平均光密度测定。结果：再生障碍性贫血骨髓的VEGF表达低下,MVD也降低,与正常对照组比较有显著差异（P〈0．05）。VEGF和MVD的表达呈显著正相关（r=0．988,P〈0．01）。结论：VEGF在再生障碍性贫血中的下调可能和MVD的改变有着密切的关系,针对血管生成的治疗可成为再生障碍性贫血治疗的另一新途径。     

口腔鳞癌组织中组织因子的表达与血管生成的关系

目的:研究口腔鳞癌(OSCC)和口腔正常黏膜中组织因子(tissue factor TF)的表达及其与微血管密度(MVD)和淋巴结转移的关系,了解OSCC中TF在肿瘤血管生成中的作用,为OSCC的研究及其治疗提供理论依据.方法:应用免疫组织化学SABC方法,检测了42例OSCC和10例正常口腔黏膜中TF的表达情况和CD34抗体标记的MVD值.结果:(1)在OSCC组织中TF的阳性表达为64.29%,显著高于在正常口腔黏膜组织中的表达(10.00%;P＜0.01);(2)TF与肿瘤的淋巴结转移密切相关(P＜0.01);(3)TF的表达与MVD值之间存在显著相关性(r=0.611,P＜0.001).结论:TF在OSCC中参与了肿瘤的血管生成,对OSCC的生长、浸润和转移有促进作用,但其是否可作为反映OSCC生物学行为的客观指标仍有待研究.     

白藜芦醇诱导VEGF表达促进缺血再灌注小鼠新生血管形成

研究白藜芦醇能否诱导小鼠缺血,再灌注后缺血区域新生血管形成及其与血管内皮细胞生长因子(VEGF)表达的相关性,用90只雄性BALB/c小鼠随机分为单纯缺血组、白藜芦醇组及假手术组,采用大脑中动脉线栓法制作局灶性脑缺血模型,免疫组化法测定微血管密度,Western blot检测VEGF蛋白表达.结果白藜芦醇处理组与单纯缺血对照组微血管计数存在差异,并且有统计学意义(P<0. 05),白藜芦醇处理组在各时间点VEGF蛋白表达水平均较高(P<0.05).说明白藜芦醇可以诱导脑缺血后VEGF早期表达,促进缺血区域新生血管形成,发挥脑保护作用.     

光动力疗法对兔肝癌肿瘤微血管密度及血管内皮细胞生长因子的影响

目的：研究光动力疗法对兔肝＇VX2移植癌模型的抑瘤作用及其可能的机制,为临床应用 PDT 治疗肝癌提供依据;方法用15只新西兰白兔制成VX2细胞肝癌模型。以血卟啉衍生物（HPD）为光敏剂观察PDT的抑瘤效果,应用免疫组化染色检测VEGF及MVD的表达水平;结果 PDT对肿瘤明显的杀伤作用;PDT组中VEGF及Mr＇VD的表达水平显著的低于对照组（p〈0.05）;结论 PDT可抑制兔肝VX2移植癌中肿瘤灶VEGF的生成,减少肿瘤灶内MVD。PDT抗肿瘤血管形成是其抑制肿瘤生长的一个重要机制。     

PM2.5引起的肿瘤新生血管形成和转移研究进展

 PM_2.5指直径≤2.5 μm 的颗粒物质,它很容易穿过呼吸道屏障,进入血液循环,可诱发肺癌等多种恶性肿瘤,已成为恶性肿瘤新的诱因。近年研究揭示,PM_2.5可刺激肿瘤细胞合成和分泌血管内皮生长因子（VEGF）,促进血管内皮细胞介导的肿瘤血管新生;并可激活肿瘤细胞,使其通过血管生成拟态直接形成肿瘤血管;还能使肿瘤干细胞向肿瘤内皮细胞转化,促进肿瘤新生血管形成。此外,PM_2.5可促进肿瘤细胞及其他多种细胞分泌趋化因子和白细胞介素,招募骨髓和血液中白细胞进入肿瘤组织,诱发局部慢性炎症反应,诱导上皮细胞-间充质细胞转化（EMT）的发生,增加肿瘤细胞干性、迁移和转移能力;还可破坏血管稳态,增加血管通透性,为肿瘤细胞的转移打开方便之门。PM_2.5在肿瘤的新生血管形成和转移中起了重要作用,然而,至今对其作用机制知之甚少。因此,进一步深入研究PM_2.5诱导的肿瘤新生血管形成及转移机制,能为PM_2.5引起的恶性肿瘤防治提供可靠的理论依据和新的应对策略。     

血管内皮生长因子与肿瘤新生血管的关系

目的：综述血管内皮生长因子(VEGF)与肿瘤新生血管的关系及近年来的研究现状。方法：通过对近年来血管内皮生长因子促进肿瘤血管生成方面的相关献的回顾、总结VEGF及VEGF与肿瘤新生血管的关系。结果：血管生成在肿瘤生长中占有重要地位，而VEGF在促进肿瘤血管生成因素中起到最关键的作用。结论：VEGF是目前发现的最重要的刺激微血管因子，针对VEGF的抗血管生成治疗可能给恶性肿瘤的治疗带来新的契机。     

Overexpression of N-cadherin is correlated with metastasis and worse survival in colorectal cancer patients

N-cadherin is related to the progression and metastases of several solid carcinomas. However, it was still unclear whether N-cadherin is overexpressed in colorectal malignant tumors that have stronger malignant tendency. In this study, we used immunohistochemistry to detect the expression patterns of N-cadherin in both the primary tumors and their normal mucosa tissues of 120 patients with colorectal cancer. We revealed that N-cadherin was expressed in 78.3% (94/120) of colorectal tumor tissues and in only 9.2% (11/120) of paired distant normal mucosa tissues with a significant difference (P=0.000). The low, moderate, and high expression of N-cadherin protein was 42.5%, 30.8%, and 26.7%, respectively. N-cadherin overexpression was associated with advanced TNM stage, lymph nodes metastasis and distant metastasis (P<0.05). Patients with N-cadherin overexpressed showed the obvious lower overall survival rate than those with moderate and low expression, and patients with low expression had a better survival rate than those with moderate and high expression (P<0.05). In conclusion, high N-cadherin expression may lead to tumor aggressiveness and metastatic potential in colorectal cancer, and may prove to be a possible prognostic factor.     

恶性肿瘤患者与健康人血清Cu、Zn、Ca、Mg、Se含量及Cu／Zn比值的对比分析

用ＩＣＰ－ＡＥＳ法测定了４４例恶性肿瘤患者和３３例健康人血清Ｃｕ、Ｚｎ、Ｃａ、Ｍｇ、Ｓｅ含量．结果显示：恶性肿瘤组血清Ｃａ、Ｓｅ含量低于健康组，血清Ｃｕ含量高于健康组，两组相比较，均有非常显著差异（Ｐ＜０．０１）．提示上述元素可能与恶性肿瘤的发生、发展有一定关系．     

Inducible nitric oxide synthase expression is related to angiogenesis,bcl—2 and cell proliferation in hepatocellular carcinoma

In this study,we examined the expression of inducible nitric oxide synthase(iNOS) and vascular endothelial growth factor(VEGF) by immunohistochemical staining in 76 tissue sections collected from bepa-tocellular carcinoma(HCC) patients undergoing hepatectomy.Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody.We performed DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expression on the cell cycle of HCC.Most of the HCC cells that invaded stroma were markedly immunostained by iNOS antibody.The iNOS stain intensity of the liv-er tissue close to the tumor edge was stronger than that of HCC tissue,and the strongest was the hepatocytes colser to the tumor tissue.However,iNOS expression in 10 normal hepatic samples was undetectable.VEGF positive expression ratio was 84.8% in iNOS positive expression cases,and the ratio was 35.3% in negative cases.There was significant correlation(P=0.000) between iNOS and VEGF expression.Moreover,iNOS expression was significantly associated with bcl-2 and MVD,but without p53 expression.DNA-flow cytometric analyses showed that combined expression of iNOS and VEGF had significant impact on the cell cycle in HCC.PI(Proliferating Index) and SPF(S-phase fraction)in the combined positive expression of iNOS and VEGF group was significantly higher than that in the combined negative group.The present findings suggested that iNOS expression was significantly associated with angiogenesis,bcl-2 and cell proliferation of HCC.     

晚期头颈恶性肿瘤组织含促血小板聚集物

为探讨头颈恶性肿瘤组织提取液是否含有聚集血小板的物质，将15例头颈恶性肿瘤和14例非恶性肿瘤组织匀浆取组织提取液，分别致聚于头颈恶性肿瘤21例。非肿瘤，非恶性肿瘤33例及健康人16例的血小板，发现，头颈恶性肿瘤组织提取液致聚于头颈恶性肿瘤21例，非肿瘤，非恶性肿瘤33例及健康人16例血小板，发现，头颈恶性肿瘤组织提取液致聚的阳性率比非恶性头颈肿瘤组织提取液致聚的高；头颈恶性肿瘤组织提取液对血小板的聚集作用随病期进展而增强。头颈部恶性肿瘤病人的血小板易受组织提取液激素，其血小板最大聚集率随病期进展的增强，表明，晚期头颈恶性肿瘤组织含促血小板聚集物。这可能是直接引起恶性肿瘤机体血小板聚集增强的原因之一。     

Suppression of murine breast cancer metastasis by selective inhibition of CXCR4 by synthetic polypeptide derived from viral macrophage inflammatory protein II

Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4 (CXCR4) have been implicated in breast cancer metastasis. A significant association between HER2 and CXCR4 expression has been observed in human breast tumor tissues, and overexpression of CXCR4 is essential for HER2-mediated tumor metastasis. Moreover, CXCR4 expression is low in normal breast tissues and high in malignant tumors, suggesting that a blockade of CXCR4 may limit tumor metastasis. The present study investigated the action of a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein II against CXCR4 (NT21MP) in inhibiting metastasis in vitro and in vivo. The results showed that chemotaxis of SKBR3 cells toward SDF-1α was reduced by NT21MP in a dose-dependent manner (P < 0.05). NT21MP inhibited tumor growth at 500 μg/kg and in combination with Herceptin, the anti-HER2 antibody. The in vivo metastatic assay showed that NT21MP significantly inhibited pulmonary metastasis, and the number of metastatic tumor nodes on the surface of the lung was greatly decreased. Compared with the saline-treated control group, PCNA expression was dose-dependently decreased by NT21MP, the percentage of apoptotic cells was increased, and CXCR4 mRNA and protein expression were downregulated. In conclusion, NT21MP inhibits cellular prolifer-ation, promotes apoptosis by downregulating CXCR4 expression, and suppresses the progression of primary and metastatic tumors. CXCR4 may be a useful therapeutic target for breast cancer, and NT21MP may serve as a potential target drug for the treatment of breast cancer metastasis.