Flt-4在不同级别脑星形细胞瘤中的表达意义

目的：探讨不同组织病理分级的脑星形细胞瘤中血管内皮生长因子受体3（Flt-4又称VEGFR-3）的表达意义。 方法： 采用免疫组织化学方法，检测50例不同级别脑星形细胞瘤患者手术切除标本中Flt-4、血管内皮生长因子（VEGF）的表达，并用抗FⅧ因子抗体标记瘤组织血管内皮细胞，计算肿瘤内微血管密度（IMVD）。 结果： Flt-4、VEGF总阳性表达率分别为52%（26/50）、60%（30/50）。Flt-4、VEGF均与脑星形细胞瘤病理分级呈显著正相关（等级相关系数分别为0.359、0.360,P＜0.05）。 结论： 脑星形细胞瘤中有Flt-4表达，主要表达于血管内皮细胞和部分肿瘤细胞，Flt-4既可是内皮细胞自分泌产生，部分还可来自瘤细胞的旁分泌；脑星形细胞瘤中Flt-4阳性表达的脉管是血管；Flt-4的表达与星形细胞瘤的病理分级相关     

血管内皮生长因子和E26转录因子在乳腺癌中的表达及意义

目的 试图揭示血管内皮生长因子（VEGF）和E26转录因子（E26 transformation-specificl,ETS-1)在乳腺癌组织中的表达规律,探讨其在血管生成和肿瘤浸润转移中的作用机制。方法 应用原位杂交和免疫组织化学链霉素抗生物系－过氧化物酶复合物法（SP）法,检测48例乳腺癌组织中VEGF和ETS－1的mRNA和蛋白的表达。结果 乳腺癌细胞高表达VEGF mRNA和蛋白,阳性率分别为75％（36／48）,70．8％（34／48）,而血管内皮细胞几乎不表达;ETS－1既表达在乳腺癌细胞,也表达在血管内皮细胞。癌细胞中mRNA和蛋白表达阳性率分别为85．4％（41／48）,79．2％（38／48）;VEGF和ETS－1高表达组的血管密度明显高于低表达组（均P＜0．01）;VEGF和ETS－1的表达与组织学分级和淋巴结转移密切相关,并且高表达组的微血管密度明显高于低表达组（P＜0．01）。结论 VEGF和ETS－1可促进乳腺癌血管形成,同时也促进肿瘤的浸润和转移;检测VEGF和ETS－1的表达可做为乳腺癌恶性度,浸润转移等生物学行为的参考指标。     

内痔粘膜及血管上皮细胞VEGF/FGF2的表达与内痔分期的相关性分析

目的 通过观察人体内痔不同分期粘膜及血管内皮细胞生长因子（VEGF）及碱性成纤维细胞生长因子（FGF2）的表达，探讨内痔的发生及发展机制。 方法 收集南方医院肛肠科门诊手术切除的Ⅰ、Ⅱ、Ⅲ期内痔标本134例（Ⅰ期42例，Ⅱ期45例，Ⅲ期47例），内痔周围正常肠壁组织40例作为对照，采用HE染色观察组织的病理学变化，采用免疫组织化学方法检测血管内皮细胞VEGF及FGF2的表达。 结果 正常组及Ⅰ期内痔黏膜层被覆上皮完整，未见扩张血管；Ⅱ期内痔黏膜层被覆上皮破坏，黏膜肌层破坏，黏膜层内见新生血管；Ⅲ期内痔黏膜层被覆上皮破坏，见血管管壁增厚迂曲，管腔扩张；与正常粘膜成纤维细胞相比VEGF在粘膜层成纤维细胞表达水平明显升高，并随分期增高而增高（F=883.961，P<0.01），FGF2也存在相同表达（F=656.013，P<0.01）；与正常组相比VEGF在血管内皮细胞表达水平明显升高，并随分期增高而增高（F=776.561，P<0.01），FGF2在血管内皮细胞的表达水平存在相同趋势（F=1066.458，P＜0.01）。 结论 VEGF及FGF2在内痔的形成过程中具有促进血管内皮细胞和粘膜下成纤维细胞增生的作用，同时可作为内痔发生发展的分子标志物。     

内痔粘膜及血管上皮细胞VEGF/FGF2的表达与内痔分期的相关性分析

目的 通过观察人体内痔不同分期粘膜及血管内皮细胞生长因子（VEGF）及碱性成纤维细胞生长因子（FGF2）的表达,探讨内痔的发生及发展机制。 方法 收集南方医院肛肠科门诊手术切除的Ⅰ、Ⅱ、Ⅲ期内痔标本134例（Ⅰ期42例,Ⅱ期45例,Ⅲ期47例）,内痔周围正常肠壁组织40例作为对照,采用HE染色观察组织的病理学变化,采用免疫组织化学方法检测血管内皮细胞VEGF及FGF2的表达。 结果 正常组及Ⅰ期内痔黏膜层被覆上皮完整,未见扩张血管;Ⅱ期内痔黏膜层被覆上皮破坏,黏膜肌层破坏,黏膜层内见新生血管;Ⅲ期内痔黏膜层被覆上皮破坏,见血管管壁增厚迂曲,管腔扩张;与正常粘膜成纤维细胞相比VEGF在粘膜层成纤维细胞表达水平明显升高,并随分期增高而增高（F=883.961,P<0.01）,FGF2也存在相同表达（F=656.013,P<0.01）;与正常组相比VEGF在血管内皮细胞表达水平明显升高,并随分期增高而增高（F=776.561,P<0.01）,FGF2在血管内皮细胞的表达水平存在相同趋势（F=1066.458,P＜0.01）。 结论 VEGF及FGF2在内痔的形成过程中具有促进血管内皮细胞和粘膜下成纤维细胞增生的作用,同时可作为内痔发生发展的分子标志物。     

VEGF/VEGFR在膀胱癌中表达的研究

目的：探讨血管内皮细胞生长因子（VEGF）和血管内皮细胞生长因子受体（VEGFR）KDR在膀胱移行细胞癌（TCC）患者的组织标本及正常膀胱黏膜组织中的定位及表达情况.方法：分别采用免疫组化SABC法和TUNEL法检测60例膀胱癌组织,并以40例正常膀胱黏膜组织作为对照,比较两种不同组织中VEGF及KDR的阳性表达率和表达强度的差异.结果：在60例膀胱TCC中,VEGF和KDR分别有53例和51例呈阳性表达,平均表达率分别为88%和85%,随肿瘤病理分期和细胞分级的增高其表达水平上调.但在40例正常对照组中无一例表达.两者分别比较,差异均极显著（P＜0.01）.结论：VEGF可能通过膀胱移行细胞上的相应受体而发挥一定的生物学作用.膀胱TCC患者的肿瘤组织中KDR的表达可能直接诱发了肿瘤血管的形成.     

网状血管内皮瘤1例报道并文献复习

目的探讨网状血管内皮瘤(retiform hemangioendothelioma,RH)的临床病理学特征、诊断、鉴别诊断及预后。方法采用免疫组化法检测RH组织中CD31、CD34、FⅧRAg、D2-40的表达,并复习相关文献。结果镜下见肿瘤主要由细长、分支状类似睾丸网的血管网组成,内皮细胞呈鞋钉样,侵犯皮肤附属器和皮下脂肪组织。免疫表型:瘤细胞表达CD31、CD34、FⅧRAg,不表达D2-40。背景中的淋巴细胞表达CD3。结论 RH是一种极少见的具有复发倾向的低度恶性血管源性肿瘤。少数病例可出现转移及死亡。RH应与血管肉瘤、Dabska瘤、鞋钉样血管瘤、梭形细胞血管瘤等鉴别。     

人脑星形细胞瘤COX-2和VEGF表达及其相关性的研究

目的 探讨环氧化酶-2（COX-2）和血管内皮生长因子（VEGF）在人脑星形细胞瘤中的表达及其与肿瘤临床病理分级的关系。方法 通过免疫组化SP法测定COX-2和VEGF在50例人脑星形细胞瘤和10例正常脑组织中的表达。结果 COX-2、VEGF在人脑星形细胞瘤中的表达高于正常脑组织（P＜0.001）。COX-2和VEGF与人脑星形细胞瘤临床病理分级显著相关（P＜0.05）。人脑星形细胞瘤中COX-2与VEGF的表达存在相关性。结论 COX-2和VEGF参与人脑星形细胞瘤的发生、发展且与其恶性表型有关；COX-2可能与人脑星形细胞瘤的血管形成有关。     

黑色素瘤细胞诱导骨髓间充质干细胞向血管内皮细胞分化的初步研究

目的 体外观察和分析小鼠黑色素瘤细胞B16诱导小鼠骨髓间充质干细胞(BMSC)向血管内皮细胞分化的现象和过程,初步分析肿瘤细胞分泌血管生长因子(VEGF)-a在该诱导过程中的时序关系.方法 利用Transwell系统进行BMSC与B16细胞共培养,利用免疫荧光、蛋白印迹、透射电镜等技术观察BMSC经B16诱导后向内皮细胞分化的过程,利用ELISA检测培养液内VEGF-a的水平.结果 BMSC表型鉴定为CD44+/CD73+/CD90+/CD105+/CD166+/CD34-/CIM5-/CD133-,经B16诱导后出现内皮细胞标志物VEGFR-1、VEGFR-2和第八因子(FⅧ)的表达并随时间延长而增强,共培养48 h后VEGFR-1、VEGFR-2及FⅧ均可见明显表达,72 h时VEGFR-2表达量较48 h时增加了1倍,FⅧ表达量增加了约3倍.共培养体系培养基中可检测到由B16细胞分泌的VEGF-a量随时间增多.结论 B16细胞可能通过分泌VEGF-a来诱导BMSC具备血管内皮细胞表型,提示BMSC在肿瘤血管生成中起了重要的作用.     

肝脏恶性血管源性肿瘤中ERG、Fli-1、CD34、CD31、FⅧRAg的表达特征北大核心CSCD

目的 探讨ERG、Fli-1、CD34、CD31、第八因子相关抗原（FⅧRAg）在肝脏血管源性恶性肿瘤中的表达特征及意义.方法 对解放军总医院病理科1986年1月至2014年1月检出的63例肝脏血管源性恶性肿瘤及31例肝脏其他恶性肿瘤,采用免疫组织化学EnVision法检测ERG、Fli-1、CD34、CD31、FⅧRAg的表达情况.结果 63例肝脏血管源性恶性肿瘤包括24例血管肉瘤、38例上皮样血管内皮瘤和1例Kaposi肉瘤.其中,ERG表达率为100.0%（63/63）,Fli-1表达率为96.8%（61/63）,CD34表达率为87.3%（55/63）,CD31表达率为81.0%（51/63）,FⅧRAg表达率为41.3%（26/63）.在31例肝脏其他恶性肿瘤中,1例表达ERG（3.2%）,6例表达Fli-1（19.4%）,6例表达CD34（19.4%）,3例表达CD31（9.7%）,1例表达FⅧRAg（3.2%）.肝脏血管源性恶性肿瘤中,ERG、Fli-1、CD34、CD31、FⅧRAg的灵敏度分别为100.0%、96.8%、87.3%、81.0%和41.3%,特异度分别为96.8%、80.6%、80.6%、90.3%和96.8%.结论 在诊断肝内血管来源恶性肿瘤的各种标志物中, ERG的灵敏度和特异度优于Fli-1、CD34、CD31和FⅧRAg,有一定的诊断价值.     

硫修饰脂质体包裹VEGF反义寡核苷酸对肺癌血管生成及转移的抑制作用

目的：探讨硫修饰脂质体包裹的VEGF反义寡核苷酸对肺癌血管生成和转移的抑制作用。方法：将硫修饰脂质体包裹的VEGF反义寡核苷酸（ASODN）、正义寡核苷酸（SODN）、错义寡核苷酸（MODN）加入培养的Lewis肺癌细胞中，采用免疫组织化学方法检测肺癌细胞中VEGF蛋白表达，观察经ODN处理的条件培养基对牛主动脉内皮细胞增殖的影响。另外，复制小鼠Lems肺癌模型40只，随机分为对照组、VEGFASODN组、VEGFSODN组及VEGFMSODN组，每组10只，接种肿瘤细胞24小时内，给予脂质体、VEGFASODN、VEGFSODN、VEGFMSODN皮下注射，每周2次，连续4周。检测皮下肿瘤的变化和肺转移率，并用免疫组织化学方法检测肿瘤组织微血管密度（MVD），超声检测肿瘤组织Ps、砌变化。结果：ASODN能够下调肺癌细胞中VEGF蛋白的表达，经ASODN处理的条件培养基能显著抑制牛主动脉内皮细胞的增殖。ASODN组小鼠肿瘤生长及肺转移受到显著抑制，MVD、PS、RI与其它各组相比有明显差异（P〈0．01）。结论：硫修饰脂质体包裹的VEGF反义寡核苷酸能够显著抑制肺癌血管生成，进而抑制肿瘤生长及转移。     

Inducible nitric oxide synthase expression in human colorectal cancer: correlation with tumor angiogenesis

To investigate the potential involvement of the nitric oxide (NO) pathway in colorectal carcinogenesis, we correlated the expression and the activity of inducible nitric oxide synthase (iNOS) with the degree of tumor angiogenesis in human colorectal cancer. Tumor samples and adjacent normal mucosa were obtained from 46 surgical specimens. Immunohistochemical expression of iNOS, vascular endothelial growth factor (VEGF), and CD31 was analyzed on paraffin-embedded tissue sections. iNOS activity and cyclic GMP levels were assessed by specific biochemical assays. iNOS protein expression was determined by Western blot analysis. iNOS and VEGF mRNA levels were evaluated using Northern blot analysis. Both iNOS and VEGF expressions correlated significantly with intratumor microvessel density (r(s) = 0.31, P = 0.02 and r(s) = 0.67, P < 0.0001, respectively). A significant correlation was also found between iNOS and VEGF expression (P = 0.001). iNOS activity and cyclic GMP production were significantly higher in the cancer specimens than in the normal mucosa (P < 0.0001 and P < 0.0001, respectively), as well as in metastatic tumors than in nonmetastatic ones (P = 0.002 and P = 0.04, respectively). Western and Northern blot analyses confirmed the up-regulation of the iNOS protein and gene in the tumor specimens as compared with normal mucosa. NO seems to play a role in colorectal cancer growth by promoting tumor angiogenesis.     

Loss of DCC expression in astrocytomas: relation to p53 abnormalities, cell kinetics, and survival

AIMS: Although frequent reduction or loss of DCC (deleted in colorectal carcinomas) has been demonstrated in gliomas, the association with cell kinetics and survival is still unclear. METHODS: A total of 119 astrocytomas, comprising 39 grade IV, 36 grade III, and 44 low grade tumours, were immunohistochemically investigated, along with 26 normal adult brain samples and two fetal brains. The results were compared with p53 abnormalities, Ki-67 labelling index (LI), mitotic index (MI), apoptotic index (AI), and survival. RESULTS: In normal adult and fetal brain tissues, DCC expression was detected in mature and terminally differentiated neuronal cells but not glial elements. In astrocytomas, whereas DCC expression was still clearly shown with low grade malignancy, DCC scores were significantly decreased in high histological grade malignancy, along with an increase in cell kinetics determined by AI, MI, and Ki-67 LI values. In addition, p53 LI values were significantly increased, although a direct link between DCC scores and p53 LI values was not evident. Univariate analysis revealed that high DCC scores and low p53 LI values were closely related to a favourable outcome for astrocytoma, although only the AI was an independent prognostic factor. CONCLUSIONS: The loss of DCC expression may be closely related to changes in cell kinetics and tumour phenotype in astrocytomas, independent of p53 abnormalities.     

High microvascular density is correlated with high VEGF, iNOS and COX-2 expression in penetrating growth-type early gastric carcinomas

AIMS: Early gastric carcinomas have two characteristic growth types, superficial spreading (SUP) and penetrating (PEN). Higher mucosal apoptotic activity and lower p21(WAF1/CIP1) expression and submucosal low proliferative activity have been shown in the former, compared with the latter. In order to cast light on whether angiogenesis contributes to these growth patterns, the present immunohistochemical study was performed with cancer tissues. METHODS AND RESULTS: Of a total of 807 early gastric carcinomas, 30 PEN and 33 SUP type submucosal invasive carcinoma cases were immunohistochemically compared. CD34 positivity, microvascular density (MVD), and expression of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), but not cyclooxygenase 2 (COX-2) were higher in cancer cells in both mucosal and submucosal layers in PEN than in SUP (P < 0.05). Submucosal MVD in PEN type was greater (P < 0.01) in cases with high than with low Ki67 labelling. Significant correlations were shown between MVD and VEGF, iNOS and COX-2, and VEGF and iNOS expression in the PEN type, but only a weak correlation between iNOS and COX-2 expression was evident with the SUP type. CONCLUSIONS: Increased MVD in PEN type has an intimate causal relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type, in contrast, has characteristics of low angiogenesis.     

血管内皮生长因子,微血管密度与乳腺癌淋巴结转移及预后？…

目的　探讨血管内皮生长因子 (VEGF)、微血管密度 (MVD)与乳腺癌淋巴结转移和预后的关系。方法　应用逆转录 聚合酶链反应 (RT PCR)与免疫组织化学SP法 ,检测 92例乳腺癌、12例癌旁组织V组织VEGF表达、MVD以及 2 1例乳腺癌、12例癌旁组织VEGFmRNA的表达。结果　乳腺癌组织 ,VEGF12 1(1.16 %± 0 1% )和VEGF165(1.0 1%± 0 .1% )表达高于癌旁组织 (0 .96 %± 0 .14% )、(0 .88%± 0 .1% ) ,P <0 .0 5～ 0 .0 1。此外 ,MVD与VEGF表达具有显著的正相关关系 (r =0 .70 2 ,P <0 .0 1)。VEGF表达和MVD与乳腺癌淋巴结转移、肿瘤复发关系密切 (P <0 .0 5～ 0 .0 1)。VEGF高表达组和高MVD组的无复发存活时间低于VEGF低表达组和低MVD组 ,差异具有非常显著性 (P <0 0 1)。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、肿瘤复发有促进作用 ;VEGF和MVD对乳腺癌患者的无复发存活时间能起到预测作用     

血管内皮生长因子C及其受体3在非小细胞肺癌组织中的表达及意义

目的　探讨血管内皮生长因子C(VEGF C)和受体 (VEGFR) 3在人非小细胞肺癌(NSCLC)组织中的表达及其与微血管、微淋巴管形成、淋巴转移、预后之间的关系。方法　对 76例人NSCLC及相应癌旁组织行VEGF C、VEGFR 3及CD34免疫组织化学染色链霉素抗生物素蛋白 过氧化物酶 (SP)法检测 ,进行淋巴管密度计数、微血管密度 (MVD)计数 ,并结合临床和病理资料进行分析。结果　NSCLC中 ,VEGF C的表达与肺癌分化程度负相关 (P =0 0 0 9)。VEGF C和VEGFR 3的表达水平与淋巴结转移呈正相关 (分别P =0 0 0 8,P =0 0 13) ,与淋巴浸润呈正相关 (分别P =0 0 2 7,P =0 0 2 0 )。VEGF C的表达与VEGFR 3在肺癌细胞中的表达呈正相关 (P =0 0 0 9)。VEGF C与淋巴管密度 (P =0 0 0 6 )、MVD(P =0 0 4 6 )呈正相关。淋巴管密度与淋巴结转移 (P =0 0 10 )、淋巴浸润 (P =0 0 19)、TNM分期 (P =0 0 15 )呈正相关 ,MVD与血行转移 (P <0 0 0 1)、TNM分期 (P <0 0 0 1)呈正相关。VEGF C阳性表达与生存时间、5年生存率呈负相关 (P <0 0 0 1)。结论　NSCLC中 ,VEGF C通过自分泌方式作用于受体VEGFR 3,促进肺癌组织生长 ,抑制分化。VEGF C促使肺癌内淋巴管形成 ,促进肺癌淋巴结转移。VEGF C和VEGFR 3表达增高、淋巴管密度增加     

血管内皮细胞生长因子和血管生成与胃癌发展的关系

目的探讨血管内皮细胞生长因子（ＶＥＧＦ）和血管生成与胃癌发展的关系。方法应用免疫组织化学和原位分子杂交技术,检测５６例人胃癌组织ＶＥＧＦ蛋白表达和微血管密度（ＭＶＤ）及部分胃癌ＶＥＧＦｍＲＮＡ表达,分析ＶＥＧＦ和ＭＶＤ、及其与胃癌组织学分型、浸润深度、生长方式、淋巴结转移、远处转移和预后的关系。结果ＶＥＧＦ阳性者ＭＶＤ值显著高于阴性者（Ｐ＜００１）,ＶＥＧＦ表达和ＭＶＤ与胃癌浸润深度（Ｐ＜００１）、淋巴结转移（Ｐ＜００５）和远处转移（Ｐ＜０．０５）密切相关,而与组织学分型和生长方式无关（Ｐ＞００５）;ＶＥＧＦ表达阳性或ＭＶＤ≥４３的胃癌患者５年生存率较低;ＶＥＧＦｍＲＮＡ表达与ＶＥＧＦ蛋白表达具有一致性,但其分布不同。结论ＶＥＧＦ与胃癌的血管生成密切相关,对胃癌的生长和浸润转移有促进作用,ＶＥＧＦ和ＭＶＤ可作为反映胃癌生物学行为的指标之一     

Expression of pERK and pAKT in human astrocytomas: correlation with IDH1-R132H presence,vascular endothelial growth factor,microvascular characteristics and clinical outcome

Although pERK and pAKT are reportedly activated in various neoplasms, little information is available about their significance in astrocytomas. Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters. Nuclear pERK labelling index (LI) increased with increasing cytoplasmic pERK LI and nuclear and cytoplasmic pAKT LI (p = 0.0019, p = 0.0260 and p = 0.0012, respectively). Accordingly, cytoplasmic pERK increased with increasing levels of nuclear (p = 0.0001) and marginally with cytoplasmic pAKT LI (p = 0.0526). Nuclear and cytoplasmic pERK LI and nuclear pAKT LI were positively correlated with tumour histological grade (p = 0.0040, p = 0.0238 for pERK and p = 0.0004 for pAKT, respectively). VEGF expression was correlated with nuclear pERK (p = 0.0099) and nuclear pAKT LI (p = 0.0002). Interestingly, pERK cytoplasmic LI increased with microvessel calibre (p = 0.0287), whereas pAKT nuclear LI was marginally related to microvessel density (p = 0.0685). The presence of IDH1-R132H was related only to histological grade and lower microvessel calibre. Multivariate survival analysis in the entire cohort selected cytoplasmic pAKT LI (p = 0.045), histological grade, microvessel calibre (p = 0.028), patients' age, gender and surgical excision as independent predictors of survival. Moreover, in glioblastomas, pERK nuclear LI emerged as a favourable prognosticator in the presence of IDH1-R132H. pERK and pAKT in astrocytomas are interrelated and associated with tumour grade and angiogenesis. Moreover, the importance of cytoplasmic pAKT immunoexpression in patients' prognosis and nuclear pERK immunoexpression in glioblastomas is confirmed.     

Overexpression of cyclin A and cyclin B1 proteins in astrocytomas

BACKGROUND: Cyclins are proteins that are expressed during the progression of a normal cell through the cell cycle. In a number of cancers, overexpression of cyclin A and cyclin B1 proteins has been reported, and in some instances the levels of expression correlated well with the grades of malignancy. The expression of cyclin A and cyclin B1 proteins in astrocytoma may be linked to the histologic grade or proliferative activities. OBJECTIVE: To study the expression of cyclin A and cyclin B1 proteins in astrocytomas and correlate the labeling indices (LIs) of cyclin A and cyclin B1 with histologic grade and Ki-67 LI. DESIGN: The surgical biopsy specimens from 65 adults with astrocytomas were reviewed and divided into grades based on the World Health Organization system. The paraffin sections were immunostained using primary antibodies against Ki-67, cyclin A, and cyclin B1. The LIs of these astrocytomas for the 3 different antibodies were determined by computerized image analysis. RESULTS: The cyclin A LI showed good correlation with astrocytoma grade and Ki-67 LI. Both the nuclear and cytoplasmic cyclin B LIs correlated well with the tumor grade but showed poor correlation with Ki-67 LI. CONCLUSIONS: This study suggests that although both cyclin A and B protein expression are related to the grade of malignancy in astrocytomas, cyclin A levels more generally reflect the proliferative state of these tumors. We also provide indirect evidence that cyclin B1 is associated with the aberrant progression through the G2-M phase checkpoint in astrocytomas.     

人脑星形细胞肿瘤IL-8的表达及其与血管生成的关系

目的：探讨IL-8,VEGF在脑胶质瘤中的表达及与血管生成的关系。方法：应用由45例人脑星形细胞肿瘤和6例正常脑组织组成的组织芯片，采用免疫组织化学技术分别进行IL-8，VEGF，CD34标记并进行半定量，观测在不同病理分级胶质瘤中的表达及与微血管密度（MVD）之间的关系。结果：6例正常脑组织中不表达IL-8，VEGF。45例脑胶质瘤中，27例IL-8呈阳性表达，32例VEGF呈阳性表达，Ⅲ，Ⅳ级脑胶质瘤中IL-8，VEGF的表达比Ⅰ级、Ⅱ级明显增强，IL-8，VEGF评分为强阳性的胶质瘤内MVD明显高于评分为阴性和阳性的MVD（P<0.01）。IL-8表达与MVD呈正相关（rs=0.64，P<0.01）。VEGF表达与MVD之间呈正相关（rs=0.44，P<0.01）。IL-8表达与VEGF表达之间亦呈正相关（rs=0.56，P<0.01）。结论：IL-8，VEGF的表达与胶质瘤病理分级、MVD密切相关，二者在胶质瘤的血管生成中可能相互关联、共同调节肿瘤血管生成。     

Angiogenesis is involved in the pathogenesis of nonrheumatic aortic valve stenosis

Angiogenesis is an essential biological process not only in embryogenesis, but also in the progression of several major diseases, including cancer, diabetes, and inflammation. Excessive vascularization can also contribute to some cardiovascular pathologies, such as atherosclerosis, but contradictory reports still prevail regarding its impact on aortic stenosis. Using immunohistochemical techniques, we assessed the vascular density and distribution of angiogenesis (FVIII) and vascular endothelial growth factor (VEGF) expression as well as the expression of 2 VEGF receptors, Flt-1 and Flk-1, in 55 nonrheumatic and 6 control aortic valves. In the light of the fact that the angiogenic effect of VEGF is mediated by sustained formation of nitric oxide, the samples were also immunostained with 3 nitric oxide synthase (eNOS, iNOS, and nNOS) antibodies. The immunohistochemical findings of VEGF and its receptors were verified by immunoblotting techniques. Vascular density was highest in the cases with moderate valve stenosis, and the mean number of FVIII-positive blood vessels was 1.7 +/- 1.9 vessels/mm(2) in the diseased valves, whereas the normal valves contained no blood vessels. Vascular density was significantly higher in the cases showing chronic inflammation (P = 0.007). Interestingly, the patients receiving statin therapy had significantly lower vascular densities than those not receiving such therapy (P = 0.001). Diseased valves showed distinct VEGF, Flt-1, Flk-1, and eNOS positivity of activated endothelial, stromal fusiform myofibroblastic, and histocytic cells. In contrast, immunoreactivity for iNOS and nNOS was seen only in nonendothelial stromal cells, and their expression was weaker. Enhanced vascular density was significantly associated with increased expression of Flk-1 (P = 0.028 for endothelial and P = 0.009 for stromal cells) and with endothelial eNOS expression (P = 0.024). A similar tendency was also observed for VEGF, but not for Flt-1. Our results show a distinct angiogenic response and the presence of angiogenic factors in nonrheumatic aortic valve stenosis, suggesting that angiogenesis may influence on the evolution of this disease.