血管内皮细胞生长因子抑制剂对成骨肉瘤生长的影响

通过动物接种方法研究血管内皮细胞生长因子 (VEGF)抗体对骨肉瘤生长的抑制作用。将OS 732骨肉瘤细胞以 1 0 70 / (mL·只 )的剂量接种于BALB/C型裸鼠腋窝部皮下 ,并分成 4组 :A组于接种次日于瘤体局部注射VEGF抗体 ,B组于接种后 2周瘤体局部注射抗体 ,C组于接种次日于瘤体局部注射PBS ,D组不注射抗体。VEGF注射剂量为 2 0 0 μg/ (只·次 ) ,每周 3次 ,共 3周。 4周后处死A、C2组裸鼠 ,6周后处死B、D 2组裸鼠。每组均取出瘤组织作病理切片。计算肿瘤体积及肿瘤内微血管密度 ,并对结果进行分析。结果显示 ,A组的肿瘤体积小于B、C、D 3组 ,在接种后 2 5d与D组有统计学差异 (P <0 .0 5 ) ;B、C、D 3组间无统计学差异。 4组肿瘤内微血管密度的比较 ,无统计学差异。提示 ,VEGF抗体对骨肉瘤早期的生长有明显的抑制作用 ,可作为转移病灶的预防及治疗方法之一。     

颊鳞状细胞癌组织中血管内皮生长因子的表达

目的 :研究颊鳞状细胞癌 (颊癌 )组织中血管内皮生长因子 (VEGF)表达与颊癌细胞生长、转移及预后的关系。方法 :用免疫组织化学法对 37例颊癌标本进行染色 ,观察VEGF的阳性表达率 ,并结合病理和随访资料作统计分析。结果 :37例颊癌组织中VEGF的总阳性表达率为 91 .89% ,有淋巴结转移者VEGF强阳性占 69.2 3 % ,无淋巴结转移者VEGF强阳性占 33 .33 % (χ2 =6 .48,P <0 .0 1 ) ;VEGF和肿瘤浸润深度密切相关 (r =4.54 ,P <0 .0 1 ) ;5a生存组VEGF阳性率低于 5a内死亡组 (χ2 =3 .90 ,P <0 .0 5) ;COX分析结果表明VEGF可作为独立的预后判断指标 (风险比 =2 .90 ,χ2 =7.95 ,P <0 .0 1 )。结论 :VEGF在颊癌生长转移中发挥重要作用 ,可以作为颊癌预后的指标     

血浆VEGF CA153 CA125检测对乳腺癌的诊断价值

目的:探讨血管内皮细胞生长因子、CA153联合检测在乳腺癌诊断中的价值.方法:采取56例乳腺癌患者血浆标本作实验组,102例乳腺良性疾病血浆标本作对照组.VEGF采用生化比色法测定,CA153用化学发光免疫法检测.结果:VEGF、CA153对乳腺癌的敏感性分别为60.7%、58.9%,特异性分别为98.4%、96.3%,准确性分别为89.8%、88.1%.VEGF及CA153联合检测乳腺癌的敏感性为92.8%,特异性为88.8%,准确性为89.8%.联合检测与单项指标检测相比,敏感性明显提高.结论:血浆VEGF、CA153单项检测对乳腺癌的诊断均有较大意义,联合检测血浆VEGF及CA153能提高乳腺癌的诊断敏感性.     

Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression

To elucidate the role of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in tumour angiogenesis and malignant progression, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though their in vitro growth rate and intrinsic productivity of another angiogenic factor, basic fibroblast growth factor (bFGF), were not changed by transfection, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcinoma QG90 cells having lower bFGF productivity acquired tumorigenicity as well as significant in vivo angiogenesis-inducing ability, secondly, tumorigenic colorectal carcinoma RPMI4788 cells having higher potency for bFGF production could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not produce detectable bFGF, acquired tumorigenicity even in the absence of oestrogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These results suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF productivity of tumour cells.     

抗人喉癌/抗VEGF双功能抗体制备及应用研究

目的：研制抗人喉癌／抗血管内皮因子（VEGF）双功能克隆抗体，用于喉癌抗血管生成治疗。方法：采用二次杂交瘤技术制备抗人喉癌／抗VEGF双功能抗体。经酶联免疫吸附试验法和SP法检测喉癌及癌前病患者血清及癌组织中VEGF的含量表达。结果：获得6株分泌抗人喉癌／抗VEGF双功能抗体的杂交瘤，经免疫组化证实与喉癌细胞特异性结合率为93％，而与血管内皮细胞结合率为89％。血清中VEGF含量表达，喉癌组与癌前病组及正常对照组相比差异均显著。IgG亚型鉴定为IgG2aBSAb抗体效价为1：25 600倍（ELISA法）。结论：二次杂交瘤法制备的双功能抗体具有均匀性、可控性、效价高、稳定性好，可用于喉癌抗血管生成治疗，动态检测可作为判断喉癌预后的客观指标。     

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice

We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.     

Angiogenesis of glioma: evaluation of ultrastructural characteristics of microvessels and tubular bodies (Weibel–Palade) in endothelial cells and immunohistochemical findings with VEGF and p53 protein

Capillary endothelial proliferation is often a prominent feature of malignant gliomas. The understanding of structural and functional characteristics of the vascular microenvironment in gliomas is essential for the design of future therapeutic strategies against this tumor. Electron microscopic analysis of the capillary endothelial proliferation in malignant gliomas indicated that the complex vascular structures within the tumor were composed essentially of immature capillaries. Immature capillaries had a narrow slitlike lumen composed of endothelial cells with their high nuclear:cytoplasmic ratio and the relative paucity of organelles. They resembled capillary buds seen in normal repair tissue. Immature microvessels caused by angiogenesis were found more frequently in marginal zone of the tumors with increased microvessels. The tubular body was an organelle observed in vascular endothelial cells and was used frequently as a marker of the endothelial cell. Tubular bodies were evaluated by quantitative measurement of the mean percent (%) ratio of the number of endothelial cells with tubular bodies to all endothelial cells in microvessels of tumors. In glioblastomas it yielded a value of 32.4% in the margin, about two times as high as that in the center of the tumors. However, it was lower in all locations of astrocytomas. Tubular bodies in endothelial cells could be increased in proportion to neovascularization, and they might serve as a marker for increasing microvessels in astrocytic tumors. Tumor angiogenesis may be regulated by growth factors with angiogenic activities that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation. We found that 86% of 29 glioblastomas and 79% of 14 anaplastic astrocytomas demonstrated immunoreactivity for VEGF in their tumor cells. There tended to be a correlation between VEGF and vascularity. A correlation existed between the grade of immunoreactivity for VEGF and the grade of p53 protein expression in the malignant gliomas. However, the MIB-1 indices did not increase in correlation with increase in the extent of immunoreactivity for VEGF.     

Changes in VEGF expression and in the vasculature during the growth of early-stage ethylnitrosourea-induced malignant astrocytomas in rats

 Vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, may be important as a mediator of brain tumour progression. However, it is still not clear whether VEGF plays a causative role in the early stage of glioma development. We investigated the relationship between VEGF protein expression (as assayed by immunohistochemistry) and different morphological parameters reflecting tumour progression (tumour diameter, vascular density and vascular diameter) in tumours at various stages. As a tumour model, ethylnitrosourea (ENU)-induced rat malignant astrocytoma was used. Tumours were classified by size and level of vascularity estimated by the von Willebrand factor (vWF) staining. Tumours less than 10 mm in diameter were designated early stage neoplastic lesions. All 34 early astroglial tumours were found to be VEGF positive. Increase in the VEGF immunopositive rate of tumour cells correlated significantly with increase in vascular density and vascular diameter. We suggest that VEGF induces angiogenesis and growth of microvessels, promoting growth of the early stage malignant astrocytoma. Received: 7 October 1997 / Accepted: 9 June 1998     

树鼩脑缺血后适应升高海马区rCBF及VEGF的变化

目的 探讨缺血后适应(PC)缓解海马rCBF与血管内皮生长因子(VEGF)的变化及其机制.方法 建立树鼩血栓性局部脑缺血模型,通过激光多普勒血流计测量海马CA1区rCBF含量;用免疫组化法测定海马VEGF的表达.结果 树鼩脑缺血时海马rCBF逐渐降低,以24 h的改变最显著,脑缺血后海马CA1区VEGF阳性细胞数增多,12 h表达最强(P<0.01);缺血PC可显著影响缺血所致的改变:rCBF逐渐增加,72 h最显著(P<0.01),与此同时VEGF的表达除8 h外均比血栓性缺血组增强(P<0.01),12 h组最明显;电镜显示缺血24 h血栓性缺血组的海马线粒体应激及内质网池形成最明显,给予PC后得以缓解.结论 缺血12 h内PC通过明显增强VEGF的表达可能与其改善rCBF有关,从而延长治疗的时间窗.