肿瘤血管生成抑制剂的研究现状及我国的发展战略探讨

肿瘤血管生成抑制剂是一类能破坏或抑制血管生成,有效地阻止肿瘤的生长和转移的药物。按作用机制可分为五大类：（１）抑制基底膜降解;（２）直接抑制内皮细胞增殖;（３）抑制血管生长因子活化;（４）抑制内皮细胞特异性整合素／生存信号;（５）其它非特异性作用机制的药物。本文主要介绍了肿瘤血管生成抑制剂的研究现状,并对我国在肿瘤血管生成抑制剂研究方面可采取的战略进行了探讨。     

Homoharringtonine induces apoptosis of endothelium and down－regulates VEGF expression of K562 cells

Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.     

Role of FGF-2／FGFR signaling pathway in cancer and its signification in breast cancer

Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. It has been proved that FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. cancer, atherosclerosis). However, many of the biological activities of FGF-2 have been found to depend on its receptor抯 intrinsic tyrosine kinase activity and second messengers such as the mitogen activated protein kinases. This review will focus on the mechanism of FGF-2/FGFR induced signaling pathway in tumor and human breast cancer.     

VEGF在小鼠膀胱癌肿瘤生长与转移中的作用

探讨VEGF在膀胱肿瘤生长和转移中的作用, 实验结果表明, 反义VEGF₁₂₁表达质粒转染能够明显降低肿瘤细胞产生VEGF. 稳定转染的克隆其VEGF的表达量仅为未转染的亲代细胞的12%及19%. 低水平表达VEGF的肿瘤细胞在体外的生长速度与未转染的亲代细胞间无明显差异, 但在同系小鼠体内的致瘤能力、生长速度及肺、肝等实质器官的转移率等均明显低于亲代细胞. 进一步比较高水平与低水平表达VEGF的肿瘤细胞对体外培养的小鼠血管内皮细胞生长的影响、体内肿瘤组织中微血管数目及通透性等, 证实膀胱癌细胞产生VEGF的能力与其诱导肿瘤新生血管形成的能力一致, 在肿瘤生长与转移过程中起重要作用.     

血管内皮生长因子在小鼠胚胎植入"窗口"的表达和功能

血管内皮生长因子（vascular endothelial growth factor ,VEGF)是一种特异作用于血管内皮细胞,与血管生成密切相关的生长因子,目前已知VEGF参与胚胎植入及胚胎的血管发生,但是仍不清楚VEGF在植入窗口期的表达情况和具体功能,实验应用离体和间接免疫荧光－激光共聚焦扫描等方法对VEGF在胚胎植入窗口的表达和功能进行了研究,研究发现,VEGF的分布在体外培养的处于植入“窗口”期的小鼠胚泡及其扩展的滋养层细胞和子宫上皮细胞单层上;VEGF抗体能够显著降低在体小鼠胚胎的着床数,在共培养体系中,VEGF抗体能够显著降低小鼠胚泡在子宫上皮细胞单层上的黏附率和扩展率,此作用具有剂量依赖关系,实验表明,VEGF是一种在胚胎植入过程中起重要作用的细胞因子,VEGF可能作为植入胚胎及接受性子宫内膜之间的“局部介导者”（local mediator),参与母胎间的信息传递,促进胚胎植入。     

赤魟软骨新生血管抑制组分的制备及其活性的初步研究

以赤魟软骨为原料,对赤魟软骨中新生血管抑制组分的提取方法及其生物学活性进行了初步研究。采用盐酸胍抽提、冷冻离心、透析、冷冻干燥等方法,得到分子量为3～300 kDa的活性组分,研究结果表明:赤魟软骨提取物显著地抑制了鸡胚绒毛尿囊膜血管的生成,并且抑制效果具有一定的浓度依赖性。     

血管内皮细胞生长因子在损伤修复中的作用

近年研究显示血管内皮细胞生长因子能够促进局部组织的血管化,而血管生成是生理及病理性组织生长和损伤愈合的基础,故血管内皮细胞生长因子在损伤修复中有重要的作用.目前认为这一作用主要是促进内皮细胞有丝分裂和使细胞通透性增强,通过和血管内皮细胞的特异性受体结合,产生强大的促进内皮增殖及血管生成作用而实现的.     

Establishment of the model of vascular endothelial cell membrane chromatography and its preliminary application

A model of vascular endothelial cell membrane chromatography was established by using an ECV304 cell membrane stationary phase (ECV304 CMSP) prepared by immobilizing the ECV304 cell membrane onto the surface of silica carrier. The surface and chromatographic characteristics of ECV304 CMSP were studied. The active component from Caulophyllum robustum was screened by using the model of vascular endothelial cell membrane chromatography. The interaction between the active component and membrane receptor was determined by using a replace experiments. The effect of the active component was tested by using tube formation of ECV304 cell. The results indicated that the model of ECV304 cell membrane chromatograph (ECV304 CMC) can stimulate the interaction between drug and receptor in vitro and the retention characteristics of taspine as active component was similar to that of model molecule in the model of ECV304 CMC. And therefore, taspine acted on VEGFR2 and inhibited the tube formation of ECV304 cell induced by VEGF. This model can be used to screen definite active component as a screening model.     

电刺激小脑顶核促脑缺血后血管内皮生长因子表达的意义

探讨电刺激小脑顶核(FNS)对局部脑缺血后血管内皮生长因子(VEGF)表达和毛细血管新生的影响．以线栓法制成大鼠右侧大脑中动脉梗塞模型(MCAO)，大鼠随机分为假手术对照组、MCAO组、电刺激小脑顶(MCAO FNS)干预组，以免疫组织化学法检测VEGF、内皮细胞阳性表达及毛细血管记数，大脑中动脉梗塞后，缺血区神经元变性、坏死，VEGF、内皮细胞在半暗带有少量表达，毛细血管数较对照组增加，经电刺激小脑顶核干预后，VEGF、内皮细胞大量表达，毛细血管数目明显增加，有统计学差异．电刺激小脑顶核可通过促VEGF表达、内皮细胞增殖，从而促进毛细血管新生。     

猪血管脱细胞细胞外基质制备的初步探讨

采用高渗、低渗溶液,结合去污剂—酶联合处理猪腹主动脉,进行组织学检查,从而制备血管脱细胞细胞外基质。结果表明:经该法处理的猪血管细胞全部脱除,细胞外基质保持完好,未见胶原纤维、弹性纤维有断裂现象。作者认为,高渗、低渗溶液结合去污剂—酶联合处理,是制备血管脱细胞细胞外基质理想的方法。