肿瘤血管生成抑制剂研究进展

肿瘤生长、侵袭、转移和复发是血管生成依赖性的,以肿瘤血管生成的各个环节为靶点,研制血管生成抑制剂,可有效地抑制肿瘤的转移和复发,成为肿瘤防治的新途径。本文就目前已进入临床试验的30多种血管生成抑制剂研究进展作一综述。     

肿瘤血管生成抑制剂研究进展

肿瘤生长、侵袭、转移和复发是血管生成依赖性的,以肿瘤血管生成的各个环节为靶点,研制血管生成抑制剂,可有效地抑制肿瘤的转移和复发,成为肿瘤防治的新途径.本文就目前已进入临床试验的30多种血管生成抑制剂研究进展作一综述.     

血管生成抑制剂

血管生成（ａｎｇｉｏｇｅｎｅｓｉｓ）即新生的血管形成，是肿瘤赖以发展及转移的重要条件［１］。血管生成包括：１）内皮细胞向邻近组织基质内浸润；２）迁移；３）伸展；４）增生；５）内皮细胞之间的相联；６）血管腔的形成［２］。如以上一个或数个环节被抑制，血管...     

肿瘤血管生成抑制剂研究进展张晓实综述

实体瘤的生长和转移依赖血管生成.新生血管为肿瘤细胞提供充分的氧气和营养,新生血管的内皮细胞表达多种生长因子,刺激肿瘤细胞增殖.肿瘤血管缺乏周细胞,基底膜不完整,肿瘤细胞易于进入血液循环[1].     

新型内源性血管生成抑制剂Tumstatin

内源性血管生成抑制剂是抗血管生成治疗最有潜力的药物蛋白。Tumstatin是最近发现的一种新型高效的内源性血管生成抑制剂，可特异性地作用于内皮细胞，诱导内皮细胞凋亡，起到抗血管生成作用。现就其研究进展作一综述。     

肿瘤血管生成抑制剂的临床研究新进展

血管生成 ( angiogenesis)是指在已形成的血管的基础上形成新血管的过程 ,它是肿瘤持续生长和发生转移的必要前提。在生长初期 ,肿瘤细胞可以通过扩散从细胞间隙获得氧气和营养 ,但当肿瘤增至1～ 2 mm3时 ,内部的细胞通过扩散已不能获得足够的氧气和营养满足其继续生长和分裂的需要 ,肿瘤内部形成缺氧状态 ,这时缺氧作为一种环境信号启动了瘤细胞中血管内皮生长因子 ( vascular endo-thelial growth factor,VEGF)、碱性成纤维细胞生长因子 ( basic fibroblast growth factor,b FGF)等血管生成正调控因子的表达 ,使肿瘤具有了促血管生成表…     

肿瘤血管生成抑制剂TNP—470的研究进展

血管生成抑制剂ＴＮＰ－４７０具有强有力的抗肿瘤生长及抗肿瘤转移能力，本文对其作用机理、研究应用等方面的进展及存在的问题作一综述。     

肿瘤新生血管生成抑制药物研究进展

新生血管生成抑制药物可以从不同途径阻断新生血管的生成,达到治疗肿瘤的目的.目前新牛血管生成抑制药物可分为阻断促血管生成因子作用通路的物、直接抑制内皮细胞药物、抑制基底膜降解的药物、抑制细胞整合素的药物、表皮生长因子受体抑制剂和其他种类,有较好的应用前景.     

血管生成抑制剂研究新进展

肿瘤生长与转移是血管生成依赖性的,抗肿瘤血管生成可致恶性肿瘤消退,而且低毒,不易产生获得性耐药。本文综述血管生成抑制剂治疗肿瘤的新进展。     

肿瘤血管形成及其抑制因子研究进展

血管新生是从已形成的血管网络芽生出新的血管.肿瘤的生长、浸润和转移是一个依赖于血管的过程抑制新生血管的生成可使肿瘤细胞进入休眠状态并诱导死亡.     

CANSTATIN, A ENDOGENOUS INHIBITOR OF ANGIOGENESIS AND TUMOR GROWTH

Canstatin is a novel inhibitor of angiogenesis and tumor growth, derived from the C-terminal globular non-collageneous (NCI) domain of the α2 chain of type Ⅳ collagen. It inhibits endothelial cell proliferation and migration in a dose-dependent manner, and induces endothelial cell apoptosis. In vivo experiments show that canstatin significantly inhibits solid tumor growth. The canstatin mediated inhibition of tumor is related to apoptosis. Canstatin- induced apoptosis is associated with phosphatidylinositol 3-kinase/Akt inhibition and is dependend upon signaling events transduced trough membrane death receptor.     

SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis

Neuroblastoma (NB), a common pediatric neoplasm, consists of two main cell populations: neuroblastic/ganglionic cells and Schwann cells. NB tumors with abundant Schwannian stroma display a more benign clinical behavior than stroma-poor tumors. Recent studies suggest that Schwann cells influence NB tumor growth via secreted factors that induce differentiation, suppress proliferation, and inhibit angiogenesis. Two angiogenesis inhibitors, pigment epithelium-derived factor and tissue inhibitor of metalloproteinase-2, have been detected in Schwann cell secretions. Here, we isolated another Schwann cell-derived secreted inhibitor of angiogenesis, a 43-kDa protein identified as SPARC (secreted protein acidic and rich in cysteine), an extracellular matrix protein. We found SPARC to be critical for the antiangiogenic phenotype of cultured Schwann cells. We also show that purified SPARC potently inhibits angiogenesis and significantly impairs NB tumor growth in vivo. SPARC may be an effective candidate for the treatment of children with clinically aggressive, Schwannian stroma-poor NB tumors.     

Notch signaling from tumor cells: a new mechanism of angiogenesis

Notch signaling is an evolutionarily conserved pathway and plays key roles in embryonic vascular development and angiogenesis. Multiple components of the Notch pathway are expressed in vasculature, and mice deficient for a variety of these components display embryonic lethality with vascular remodeling defects. Alteration of Notch signaling in various endothelial cells generates profound effects on angiogenesis in vitro. New evidence shows that Notch signaling from tumor cells is able to activate endothelial cells and trigger tumor angiogenesis in vitro and in a xenograft mouse tumor model. Selective interruption of Notch signaling within tumors may provide an antiangiogenic strategy.     

Semaphorin-3F is an inhibitor of tumor angiogenesis

The neuropilin-1 (np1) and neuropilin-2 (np2) receptors form complexes with type-A plexins. These complexes serve as signaling receptors for specific class-3 semaphorins. Np1 and np2 function in addition as receptors for heparin-binding forms of vascular endothelial growth factor (VEGF), such as VEGF(165). Human umbilical vein endothelial cells (HUVEC) express tyrosine-kinase receptors for VEGF and basic fibroblast growth factor (bFGF), as well as np1, np2, and several type-A plexins. We have found that semaphorin-3F (s3f), a semaphorin which signals through the np2 receptor, was able to inhibit VEGF(165), as well as bFGF-induced proliferation of HUVECs. Furthermore, s3f inhibited VEGF as well as bFGF-induced phosphorylation of extracellular signal-regulated kinase-1/2. Our experiments indicate that bFGF does not bind to neuropilins, nor does s3f inhibit the binding of bFGF to FGF receptors. It is therefore possible that s3f inhibits the activity of bFGF by a mechanism that requires active s3f signal transduction rather than by inhibition of bFGF binding to FGF receptors. s3f also inhibited VEGF(165), as well as bFGF-induced in vivo angiogenesis as determined by the alginate micro-encapsulation and Matrigel plug assays. Overexpression of s3f in tumorigenic human HEK293 cells inhibited their tumor-forming ability but not their proliferation in cell culture. The tumors that did develop from s3f-expressing HEK293 cells developed at a much slower rate and had a significantly lower concentration of tumor-associated blood vessels, indicating that s3f is an inhibitor of tumor angiogenesis.     

肿瘤血管生成抑制物作用机制及应用研究进展

介绍肿瘤血管生成抑制物血管抑素、内皮抑素、CM-101、TNP-470、反应停、血小板因子-4、白介素-12和基质金属蛋白酶抑制剂等的作用机制应用研究进展.     

抗血管生成药物治疗恶性脑水肿的研究进展

抗血管生成药物通过减少血管通透性和血脑屏障破坏,能有效减轻恶性脑水肿,缓解临床症状,改善患者生命质量。目前多种抗血管生成药物在治疗恶性脑水肿方面取得了积极的疗效,因此被认为是较糖皮质激素治疗恶性脑水肿更为安全、有效的治疗手段。     

Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogenesis with extensive tumor necrosis

PURPOSE: Toward improved glioblastoma multiforme treatment, we determined whether celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, could enhance glioblastoma radiosensitivity by inducing tumor necrosis and inhibiting tumor angiogenesis. METHODS AND MATERIALS: U-87MG cells treated with celecoxib, irradiation, or both were assayed for clonogenic survival and angiogenic factor protein analysis (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor [VEGF]). In vivo, survival of mice intracranially implanted with U-87MG cells and treated with celecoxib and/or irradiation was monitored. Isolated tumors were assessed for tumor necrosis and tumor microvascular density by von Williebrand's factor (vWF) immunohistochemical staining. RESULTS: Celecoxib (4 and 30 microM; 24, 48, and 72 h) enhanced U-87MG cell radiosensitivity by significantly reducing clonogenic survival of irradiated cells. Angiopoietin-1 and VEGF proteins were decreased, whereas angiopoietin-2 expression increased after 72 h of celecoxib alone and when combined with irradiation. In vivo, median survival of control mice intracranially implanted with U-87MG cells was 18 days. Celecoxib (100 mg/kg/day, 2 weeks) significantly extended median survival of irradiated mice (24 Gy total) from 34 to 41 days, with extensive tumor necrosis [24.5 +/- 8.6% of tumor region, compared with irradiation alone (2.7 +/- 1.8%)]. Tumor microvascular density was significantly reduced in combined celecoxib and irradiated tumors (52.5 +/- 2.9 microvessels per mm2 tumor region), compared with irradiated tumors alone (65.4 +/- 4.0 microvessels per mm2). CONCLUSION: Celecoxib significantly enhanced glioblastoma radiosensitivity, reduced clonogenic survival, and prolonged survival of glioblastoma-implanted mice by inhibition of tumor angiogenesis with extensive tumor necrosis.