血管内皮生长因子与肿瘤放射治疗

实体肿瘤生长、浸润和转移必须有肿瘤血管形成,血管形成是在一系列血管生长因子的调控下实现的,血管内皮生长因子(VEGF)是最重要的血管形成因子.肿瘤放疗能影响肿瘤组织及血液中VEGF的表达水平,VEGF表达水平又能预示肿瘤放疗的疗效,因此肿瘤放疗与抗VEGF治疗的结合将是一个具有诱人前景的肿瘤治疗方案.     

血管内皮生长因子与肿瘤放射治疗

实体肿瘤生长、浸润和转移必须有肿瘤血管形成，血管形成是在一系列血管生长因子的调控下实现的，血管内皮生长因子（VEGF）是最重要的血管形成因子。肿瘤放疗能影响肿瘤组织及血液中VEGF的表达水平，VEGF表达水平又能预示肿瘤放疗的疗效，因此肿瘤放疗与抗VEGF治疗的结合将是一个具有诱人前景的肿瘤治疗方案。     

VEGF和MVD在大肠癌组织中的表达及其临床意义

肿瘤的生长和转移依赖肿瘤血管的形成,血管内皮生长因子(Vascularendothelial growth factor,VEGF)在肿瘤血管形成过程中发挥重要作用[1].本研究采用免疫组织化学方法,对57例大肠癌组织标本中VEGF的表达水平及肿瘤血管密度(MVD)进行检测,探讨了VEGF在结直肠癌血管形成过程中的作用,及其与大肠癌患者预后的关系.     

血管内皮生长因子与肿瘤

血管形成是肿瘤生长和转移的重要条件，而血管内皮生长因子(VEGF)对肿瘤的血管形成具有很突出的作用，就VEGF与肿瘤予以综述。     

血管内皮生长因子和Notch信号通路与肿瘤血管生成

血管内皮生长因子(VEGF)和Notch信号通路是血管发育及肿瘤血管生成的重要机制.阻断VEGF可抑制肿瘤生长和血管生成.Notch能抑制内皮形成尖端细胞,减少血管生成.实验证明,两条通路相互作用,联合阻断VEGF和Notch信号通路可协同抑制肿瘤生长.对VEGF和Notch通路的研究,将为肿瘤临床治疗提供新的方法.     

抗VEGF单抗Avastin(bevacizumab)在肿瘤治疗中的应用研究进展

VEGF调节肿瘤血管形成,刺激血管形成新生血管以供应肿瘤生长的需要。Avastin是一种人源性的抗VEGF单抗,可选择性与VEGF发生高亲和力结合从而阻断VEGF的生物活性,在临床前期和各种临床试验中已显示了良好的疗效,最近被美国FDA批准用于一线治疗晚期结直肠癌。     

血管内皮生长因子在肿瘤中表达的研究进展

肿瘤的发生、发展大体可分肿瘤细胞的克隆性增殖阶段和继之的血管形成支持肿瘤持续生长阶段。因此，目前阻断血管形成成为探索抑制肿瘤的新途径。血管内皮生长因子(Vascular eadothelial growth factor，VEGF)是一个重要的血管形成因子，许多肿瘤细胞分泌该因子，其可诱导肿瘤血管形成，从而支持肿瘤的生长。近年来国外对VEGF进行了一系列研究，但国内报道不多。本文就VEGF在肿瘤中的表达及临床意义方面作一综述。     

肿瘤血管的靶向治疗—血管内皮生长因子-白喉毒素结合物抑制肿瘤生长

实体瘤的生长和转移依赖新生血管的建立,该过程由肿瘤细胞分泌的生血管因子所启动,抑制血管生成因子的产生和作用,可抑制新生血管形成,控制肿瘤生长。血管内皮生长因子/血管通透因子(VEGF/VPF)是体内一个重要的肿瘤血管生成因子,在新生血管形成和肿瘤发展中扮演一个重要角色。原位杂交研究显示,VEGF/VPF两个主要受体flt-1和flk-l/KDR在肿瘤血管内皮细胞中过度表达,而VEGF受体在相邻正常组织血管内皮中几乎不能检测出,所以,VEGF可将毒     

VEGF／VEGFR信号通路抑制剂疗效预测的研究进展

血管生成是肿瘤转移的基础,新生血管形成是肿瘤复发转移不可或缺的条件。血管内皮生长因子（VEGF）及其受体（VEGFR）是肿瘤血管形成过程中的重要调节因子。VEGF／VEGFR信号通路抑制剂已经成功进入临床应用阶段,但只有一部分患者能够从中获益。探索能够可靠预测VEGF／VEGFR信号通路抑制剂疗效的评价指标,将会给肿瘤患者带来更大的临床获益。本文将对VEGF/VEGFR信号通路抑制剂疗效预测指标的研究进展作一综述。     

靶向于血管内皮生长因子信号传导通路的肿瘤生物治疗

 血管生长(angiogenesis) 在肿瘤的演化过程中非常重要,肿瘤的生长与转移依赖于肿瘤血管的形成。在众多的血管生长因子中,血管内皮生长因子(Vascularendothelialcell growthfactor,VEGF ) 是内皮细胞特异的有丝分裂原,在原发肿瘤的生长、转移肿瘤的形成及血管生长中都起着重要作用[1] 。Flt-1 (fmsiket yrosinekinase ) 与Flk-1PKDR( Kinaseinsertdomain-containin grece ptor ) 是VEGF 的两个高亲和的特异的酪氨酸激酶受体。VEGF 与VEGF 受体结合,通过受体的磷酸化,引起一系列的信号传导,释放各种生长因子与细胞因子,增加血管渗透性,促进内皮细胞的增殖与迁移,最终引起血管增殖。VEGF 信号传导通路在肿瘤的血管生长调控中非常重要,国内外许多研究都希望通过干扰这一通路来调控肿瘤的血管生长。     

Inhibiting Colorectal Carcinoma Growth and Metastasis By Blocking the Expression of VEGF Using RNA Interference

Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The present study was designed to determine the role of VEGF in tumor growth and metastasis using RNA interference (RNAi) technology. Four small interfering RNA (siRNA) sequences for the VEGF gene were cloned into expression plasmids and transfected into human colorectal carcinoma (CRC) SW620 cells. Stable transfection of these plasmids decreased VEGF protein expression, leading to the potent suppression of tumor cell proliferation, migration, invasion, and angiogenesis in vitro. Furthermore, in subcutaneous and intrasplenic/portal injection models involving athymic nude mice, the tumor growth and metastasis of SW620 cells expressing VEGF siRNA were significantly inhibited compared with untransfected cells or cells transfected with control vector alone. Immunohistochemical analyses of tumor sections revealed a decreased vessel density and decreased VEGF expression in the animals where siRNA against VEGF were expressed. These results indicate that RNAi of VEGF can be an effective antiangiogenic strategy for CRC.     

Wide Spectrum of Antitumor Activity of a Neutralizing Monoclonal Antibody to Human Vascular Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is known as an angiogenic factor for tumor angiogene—sis. We developed a neutralizing anti—VEGF monoclonal antibody (MAb), MV833, and examined its antitumor activity against 27 human tumor cell lines transplanted in nude mice. All the tumor cell lines used in this study secreted various amounts of VEGF into culture medium in vitro. However, the growth of the cell lines, including three which expressed VEGF receptor, was not affected by exogenously added MV833 in vitro. All tumor cell lines including colon, lung, breast, pancreas, and melanoma, grew subcutaneously in nude mice. The growth of HeLa/v5, which had been transformed by human VEGF₁₂₁ gene and secreted large amounts of VEGF, was significantly faster than that of the control vector transformant. Although the amounts of VEGF secreted from two HeLa transformants differed greatly, MV833 completely inhibited the growth of both tumors. Moreover, the growth of the other 25 human tumor cell lines transplanted into nude mice was also strongly suppressed by MV833. Neither the amount of VEGF secreted from each tumor cell line in vitro nor the expression of VEGF receptor correlated with the antitumor activity of MV833. MV833, administered when tumor volumes reached 400 mm₃, completely inhibited the growth of some tumor lines. The results show VEGF to be a critical angiogenic factor for many tumors. VEGF—neutralizing antibody could be applicable as an antitumor agent for a wide range of tumors.     

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors

Angiogenesis, or the formation of new blood vessels from preexisting vasculature, plays a major role in tumor growth and metastasis formation. Therefore, inhibiting tumor angiogenesis may be a promising therapeutic strategy. Paracrine stimuli from tumor cells are the main promoters of angiogenesis. They activate endothelial cells to proliferate and migrate, subsequently resulting in new tube formation and blood flow. This complex process involves numerous biological activities. Vascular endothelial growth factor (VEGF) is a potent and specific angiogenic factor. Originally identified for its ability to induce vascular permeability and stimulate endothelial cell growth, VEGF is now known to be a key requirement for tumor growth. Currently, three high-affinity tyrosine kinase receptors for VEGF have been identified, of which VEGF receptor (VEGFR)-Flk-1/KDR (VEGFR-2) is exclusively expressed in vascular endothelial cells. Because the VEGFR-2 system is a dominant signal-transduction pathway in regulating tumor angiogenesis, specific inhibitors of this pathway inhibit metastases, microvessel formation, and tumor-cell proliferation. Induction of apoptosis in tumor cells and endothelial cells has also been observed. The clinical importance of VEGF for tumor growth is supported by the fact that most tumors produce VEGF and that the inhibition of VEGF-induced angiogenesis significantly inhibits tumor growth in vivo. In this review, we discuss the biologic role of VEGF and the therapeutic options for inhibiting VEGF in cancer patients.     

Vascular endothelial growth factor 936 C/T polymorphism in cancer patients.

Angiogenesis is an essential process in the development, growthand metastasis of malignant tumors [1]. Vascular endothelialgrowth factor (VEGF) plays an important role in the angiogenesis.Increased VEGF expression is associated with tumor growth andmetastasis, whereas inhibition of VEGF signaling results insuppression of both tumor-induced angiogenesis and tumor growth. The human VEGF     

神经菌毛素促进VEGF介导的血管生成作用及其机制研究进展

Neuropilin-1(NRP-1), acted as one important member of NRP family,expressed in endothelial cellsand certain tumour cells and conducted common receptor of Sema 3A,VEGF,PDGF and TGF. Therefore, itplays an important role in axon growth,angiogenesis and tumor growth. VEGF acts as one important regulatingfactor in angiogenesis, also played an important role in tumor angiogenesis, growth and development. Moreand more researches had confi rmed that VEGF could facilitate angiogenesis, tumor growth and developmentas combined with NRP-1. This article mainly summarizes angiogenesis and mechanism of VEGF promotedby NRP-1.     

mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and improves anti-tumor activity against gastric cancer in vivo

VEGF receptor blockage has been reported to increase serum VEGF. We hypothesized that mTOR inhibition by everolimus counteracts VEGF induction by sunitinib resulting in an improved anti-tumor activity of sunitinib. In vitro, sunitinib in combination with everolimus did not outperform the respective monotherapies. In vivo, monotherapies reduced tumor growth by 60%, whereas the combination of sunitinib and everolimus led to an almost complete tumor growth inhibition. This superior anti-tumor activity coincided with attenuation of VEGF peaks. In conclusion mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and results in significant reduction of tumor burden and long-lasting tumor growth control.     

Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an orthotopic murine renal cell cancer model.

PURPOSE: Angiogenesis inhibitors have shown clinical benefit in patients with advanced renal cell cancer, but further therapeutic improvement is needed. Vascular endothelial growth factor (VEGF) Trap is a newly developed VEGF-blocking agent with stronger affinity and broader activity than the anti-VEGF antibody bevacizumab. In this study, we tested the activity of VEGF Trap in an orthotopic murine model of renal cancer with spontaneous lung metastases. EXPERIMENTAL DESIGN: Murine syngeneic renal cell carcinoma cells (RENCA) transfected with a luciferase-expressing vector were injected into the renal capsule of BALB/c mice. I.p. treatment with VEGF Trap or control protein (10 or 25 mg/kg twice weekly) was started shortly after tumor injection to prevent tumor development (prevention model) or after established tumors were formed to inhibit tumor growth and metastasis formation (intervention model). RESULTS: In the prevention model, VEGF Trap inhibited tumor growth by 87 +/- 14% compared with control (P=0.007) and significantly prolonged survival. In the intervention model, VEGF Trap inhibited tumor growth by 74 +/- 9% (P<0.001) and the formation of lung metastases was inhibited by 98% (P<0.004). Microvascular density was reduced by 66% due to VEGF Trap treatment (P<0.001). In addition, VEGF Trap prevented fibrinogen leakage into the tumor microenvironment representative for reduced vascular leaking as shown by immunohistochemical staining. CONCLUSIONS: VEGF Trap is a potent inhibitor of RENCA tumor growth and metastasis formation and blocks the biological function of VEGF in vivo. These results support further clinical development of VEGF Trap for renal cell cancer and other cancer types.     

贝伐单抗治疗转移性结直肠癌

贝伐单抗是一种重组人源化抗血管内皮生长因子(VEGF)的单克隆抗体,可与肿瘤细胞上的VEGF特异性结合,通过抑制肿瘤血管生成而抑制肿瘤生长,临床研究证实其治疗转移性结直肠癌有良好的应用前景.     

Phosphatase and tensin homolog reconstruction and vascular endothelial growth factor knockdown synergistically inhibit the growth of glioblastoma

Glioblastoma (GBM) is a highly malignant tumor with poor prognosis. Two hallmarks of this disease are a high expression of vascular endothelial growth factor (VEGF) and a depletion of the phosphatase and tensin homolog (PTEN). In the present study, combined gene therapy using wild-type PTEN reconstruction and VEGF siRNA was examined for its effectiveness in inhibiting tumor growth and tumorigenicity of PTEN-null GBM cells. In U251 GBM cells, PTEN restoration reduced proliferation, arrested the cell cycle at G0/G1 stage, and promoted apoptosis via inhibition of PIK/AKT signaling pathway. Unexpectedly, anchorage-dependent and -independent colony formation ability and the capacity for wound-healing migration of U251 cells with stable expression of VEGF siRNA were significantly inhibited, suggesting that VEGF also appeared to function as an autocrine growth factor in addition to its well-known pro-angiogenic paracrine function. Further, a combined treatment of PTEN restoration and VEGF siRNA had the best tumor suppression effect. In a xenograft study in null mice, both the restoration of PTEN and the expression of VEGF siRNA could significantly inhibit the growth of U251 GBMs, whereas tumor growth was entirely suppressed by a combination of the two treatments. Therefore, the combination of PTEN expression and VEGF knockdown represents an effective gene therapy strategy for malignant gliomas.