雷公藤甲素对血管生成的抑制作用

利用体外培养人脐静脉内皮细胞,经不同浓度的雷公藤甲素(0、5、10、20、30μg/L)处理后,MTT法显示雷公藤甲素可抑制内皮细胞的增殖,5μg/L雷公藤甲素的抑制率达29.15%;琼脂凝胶立体细胞培养系统检测发现内皮细胞经雷公藤甲素作用后,其游走能力降低;鸡胚尿囊膜试验观察到雷公藤甲素可有效抑制血管的生成;荧光定量RT-PCR检测发现雷公藤甲素可下调内皮细胞u-PAmRNA的表达。因此认为,雷公藤甲素可能在基因水平上干扰内皮细胞u-PAmRNA的表达,减少u-PA蛋白的生成,从而有效地抑制血管内皮细胞的增殖和移行,这可能是雷公藤甲素抑制血管生成的主要机制之一。     

以抑制肿瘤新生血管为靶点的抗肿瘤药物研究进展

恶性肿瘤的生长和转移与肿瘤区域的血管密切相关,肿瘤区域的新生毛细血管是肿瘤赖以生长和生存的物质基础,肿瘤细胞需要新生血管为迅速生长的肿瘤提供营养物质和排出废物。早在七十年代初就有人提出把抑制肿瘤血管形成作为肿瘤治疗的一种途径,以后这种以肿瘤血管为靶标的治疗策     

单克隆抗体药物抑制肿瘤血管新生机制的研究进展（文献综述）

血管新生与肿瘤的发生、生长、转移密切相关。在过去的十年里我们对血管新生这一复杂过程的认识有了飞速的发展,此过程包括：内皮干细胞的迁移、内皮细胞的迁移和侵入、内皮细胞的增殖、内皮细胞在管状结构中的组织、循环系统的形成、血管的成熟、血管的退化。随着对这些过程和参与这些过程的分子的认识加深,     

雷公藤内酯醇抗肿瘤作用机理研究进展

雷公藤（Tripterygium wilfordii Hook．F）系卫矛科雷公藤属木质藤本植物,分布于长江流域以南各地及西南地区。雷公藤作为一种传统中药,可治疗类风湿性关节炎、红斑狼疮等自身免疫性疾病。20世纪70年代,Kupchan等首先从台湾产雷公藤中分离出雷公藤内酯醇（triptolide）、雷公藤内酯酮（triptonide）和雷公藤内酯二醇（tripdiolide）3个活性二萜类化合物。     

血管新生抑制剂的研究进展

肿瘤的发生和转移依赖于血管新生 ,这一概念的提出为肿瘤及血管新生相关性疾病的治疗提供了新的方法。基于对肿瘤血管新生机制、血管新生抑制剂的作用机制及特点的研究 ,目前已开发出了多种血管新生抑制剂 ,其中多数已进入了临床实验     

血管紧张素家族的新成员——血管紧张素（1—7）

Ａｎｇ（１－７）作为新发现的肾素－血管紧张素家族成员，具有广泛的生物学活性。Ａｎｇ（１－７）的作用机制尚未完全阐明，对其进行深入研究将有助于揭示肾素－血管紧张素系统在高血压发病中的确切机制，并有可能为某些高血压的治疗带来新的方法。     

低分子量肝素体外抗肿瘤血管新生作用

目的探讨低分子量肝素（low moleeular weight heparin,LMWH）对肿瘤血管新生的作用。方法采用四唑盐比色实验（MTT）及体外人前列腺癌高转移细胞（PC-3M）和人脐静脉内皮细胞（human umbilical vein endothelial cells,HUVECs）共孵育系统检测HUVECs增殖和小管形成。结果500mg／L LMWH能够显著抑制内皮细胞的增殖（P〈0．05）;PC-3M能够激活HUVECs,使细胞拉长、排列成管状结构;LMWH能够显著抑制PC-3M刺激的HUVECs小管形成,并呈剂量依赖性。结论LMWH具有体外抑制肿瘤血管新生的作用。     

VEGF、bFGF与抗肿瘤血管新生治疗

1 血管新生与肿瘤 血管新生与肿瘤生长有非常密切的关系,实体瘤要超过 2 mm2以上,必须要有新生血管的支持才能与肿瘤宿主的血管系统保持一定的连续性,而且肿瘤的转移和转移部位的生长也有赖于肿瘤组织血管新生。因此,血管新生是肿瘤增生、扩散和微转移灶发展的重要条件之一。开发新生血管生成抑制剂成为目前肿瘤治疗研究的一个新策略。主要优势在于:（1）血管生成抑制剂针对的是血管内皮细胞,血管内皮细胞遗传特性比较稳定,不易产生耐药性,也     

多抗甲素抗肿瘤作用及其机理研究

多抗甲素(Polyactin A,PAA)是α-溶血性链球菌(alpha-hemolytic stre-ptococci)33#菌株经深层培养,提取精制所得的α-甘露聚糖肽物质,是我国新近开发的一种抗生素,具有直接的抗肿瘤效应和刺激机体免疫反应的作用。药理实验表明在体内外对小鼠S-180,艾氏腹水瘤等肿瘤均有抑制作用。临床上配合放疗、化疗用于肺癌、     

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Why angiogenesis inhibition? Commentary.

Over the last several decades, cancer research and therapy have focused primarily on tumor cells. However, in 1971 it was proposed that a solid tumor cannot grow without recruiting endothelial cells. The hypothesis was that if one can block the formation of an adequate capillary network, tumor growth could be inhibited. Antiangiogenesis research is undoubtedly very fashionable today but compounds effective in clinical trials have not been reported so far. The goal of this commentary is to discuss two questions: what are the limitations of the old, established antitumor paradigm? Second, what are the advantages of the antiangiogenesis paradigm? At this time it is important to convince more scientists that the inhibition of angiogenesis is a valid concept against tumor growth. A stronger momentum of the antiangiogenesis movement will hopefully result in finding more effective compounds against cancer growth.     

Targeting angiogenesis in cancer therapy

Angiogenesis is an essential process in tumor growth. The concept of angiogenesis, when proposed by Folksman in 1971, had a great impact on cancer research and therapy, as the survival and proliferation of cancer depend on angiogenesis, which could be a target of cancer therapy. In subsequent decades, numerous antiangiogenic agents were developed, and some of them have been applied clinically. However, angiogenesis includes a complex and multistep process that has not been sufficiently elucidated. In this review, we focus on signaling pathways related with tumor angiogenesis and several antiangiogenic agents approved by the United States Food and Drug Administration or under investigation.     

Synergistic inhibition of lung cancer cell invasion,tumor growth and angiogenesis using aptamer-siRNA chimeras

Early metastasis is one of the major causes of mortality among patient with lung cancer. The process of tumor metastasis involves a cascade of events, including epithelial-mesenchymal transition, tumor cell migration and invasion, and angiogenesis. To specifically suppress tumor invasion and angiogenesis, two nucleolin aptamer-siRNA chimeras (aptNCL-SLUGsiR and aptNCL-NRP1siR) were used to block key signaling pathways involved in lung cancer metastasis that are pivotal to metastatic tumor cells but not to normal cells under ordinary physiologic conditions. Through nucleolin-mediated endocytosis, the aptNCL-siRNA chimeras specifically and significantly knocked down the expressions of SLUG and NRP1 in nucleolin-expressing cancer cells. Furthermore, simultaneous suppression of SLUG and NRP1 expressions by the chimeras synergistically retarded cancer cell motility and invasive ability. The synergistic effect was also observed in a xenograft mouse model, wherein the combined treatment using two chimeras suppressed tumor growth, the invasiveness, circulating tumor cell amount, and angiogenesis in tumor tissue without affecting liver and kidney functions. This study demonstrates that combined treatment of aptNCL-SLUGsiR and aptNCL-NRP1siR can synergistically suppress lung cancer cell invasion, tumor growth and angiogenesis by cancer-specific targeting combined with gene-specific silencing.     

The role of angiogenesis in cancer

Angiogenesis is the term coined to define the process of new blood vessel formation and has been the subject of intense scientific interest since the discovery of vascular endothelial growth factor (VEGF) in 1989. It is necessary for the growth of the organism, tissue repair and reproductive function. However, pathological angiogenesis is now recognised as an essential feature of conditions such as rheumatoid arthritis, diabetic retinopathy and malignant neoplasia. The development of small molecule inhibitors of this process is regarded as an important therapeutic area in the treatment of human cancers and offers potentially long-term treatment, with significantly fewer side effects than traditional chemotherapeutic treatment regimes.First presented at the European Histopathology Forum, April 2004     

Markers of angiogenesis in ovarian cancer

Tumor development and progression are inherently dependent on the process of angiogenesis. Recently, anti-angiogenic therapy has started to show promise as an effective treatment strategy in many solid tumors including ovarian carcinoma. Unfortunately, lack of effective biomarkers presents a challenge for oncologists in treatment planning as well as monitoring response of new anti-vascular agents. Previously, quantification of angiogenesis by microvessel density analysis provided useful prognostic information, however, its utility following anti-angiogenic therapy remains to be determined. Moreover, since secreted cytokines play an active part in angiogenesis by mediating neovascularization in tumors, investigations have focused on their potential role to serve as candidate biomarkers of disease detection, prognosis, and treatment response. In this article, we review the role of key angiogenesis markers as potential biomarkers in ovarian carcinoma.     

血管生成及其抑制剂在前列腺癌中的研究进展

Angiogenesis plays a key role in progression of prostate cancer. Antigiogenesis becomes a new treament target for prastate cancer. In this review, we focus on the current knowledge of angiogenesis and tumor angiogenesis inhibitor in prastate cancer.     

Mechanistic insights on the inhibition of tumor angiogenesis

Angiogenesis, the growth of new vasculature, is an absolute requirement for the maintenance and progression of the overwhelming majority of the solid tumors. Unraveling the mechanisms that govern this complex biological process has become a central issue not only for understanding of the molecular basis of cancer but also for developing new therapeutic approaches that interfere with neovascularization of the tumor mass. Here we discuss the survival and apoptosis of endothelial cells in the context of vessel formation and regression in response to mediators of angiogenesis produced by tumors. It is the balance between proangiogenic and antiangiogenic molecules in the microenvironment of a vessel in vivo that determines whether the existing vasculature will expand, remain the same, or regress. Here we propose that the vascular endothelial cells themselves interpret and respond to these environmental cues by integrating the activities of the survival and apoptotic pathways within the cell. Thus it is the survival or death of the vulnerable cells that venture out to form new vessels that is the ultimate arbiter of whether neovascularization, as well as the growth of a malignancy that depends on it, succeeds or fails.     

Hematopoietic cancer and angiogenesis

The growth of solid tumors is certainly angiogenesis dependent. However, the role of angiogenesis in the growth and survival of leukemias and other hematological malignancies has only been rendered evident since 1994 in a series of demonstrations showing that the progression of several forms is clearly related to their degree of angiogenesis. Here, we present an overview of the literature concerning the relationship between angiogenesis and disease progression in several hematological malignancies and the recent advances in antiangiogenesis in these diseases and we describe the most important active substances, preclinical and clinical data, and future perspectives.     

Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis

Encapsulation of cytokines within protein microcrystals (polyhedra) is a promising approach for the stabilization and delivery of therapeutic proteins. Here, we investigate the influence of vascular endothelial growth factor (VEGF) microcrystals and endostatin microcrystals on angiogenesis. VEGF was successfully encapsulated into microcrystals derived from insect cypovirus with overexpression of protein disulfide bond isomerase. VEGF microcrystals were observed to increase the phosphorylation of p42/p44 MAP kinase and to stimulate the proliferation, migration, and network and tube formation of human umbilical vein endothelial cells (HUVECs). Endostatin was also successfully encapsulated into microcrystals. Endostatin microcrystals showed antiangiogenesis activities and inhibited the migration, and network and tube formation of HUVECs. Local administration of endostatin microcrystals in mice inhibited both angiogenesis and tumor growth with clear significant differences between treatment and control groups. Endostatin microcrystals only affected angiogenesis, but had no significant effect on lymphangiogenesis compared to controls. Local therapy using endostatin microcrystals offers a potential approach to achieve sustained therapeutic release of antiangiogenic molecules for cancer treatment.