New anti-angiogenesis agents: review of the clinical experience with carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin-12.


:Angiogenesis was postulated to be a critical prognostic factor and therapeutic focus for malignancy more than two decades ago. Recent studies indicate quantitative assessments of microvessel count to be an independent prognostic variable for disease-free and overall survival in a wide variety of tumors, and that angiogenesis may be a feasible target against which to intervene pharmacologically. Several new and old agents have been found to have anti-angiogenic activity and have reached clinical trial. This review will focus on four agents under investigation in the US: carboxyamido-triazole (CAI), thalidomide, TNP-470 and interleukin (IL)-12. CAI, originally identified for its anti-invasive capacity, has been shown to inhibit tumor and endothelial cell proliferation by inhibition of calcium uptake. It is administered orally, is generally well tolerated, and has been shown to induce disease stabilization and occasional reductions in tumor mass. Thalidomide was shown to inhibit growth factor-induced neovessel formation, a process that can also explain its earlier devastating clinical toxicity. It is administered orally, and is currently in phase II clinical trials for prostate cancer, glioblastoma multiforme and breast cancer. TNP-470 is a fumagillin analog that has been shown in in vivo models to be a potent inhibitor of angiogenesis at concentrations that are cytostatic to endothelial cells and tumor cells. Lastly, IL-12 may exert its anti-angiogenic effects through activation of interferon-gamma to up-regulate interferon-inducible protein-10, an anti-angiogenic cytokine. Phase I clinical trials of IL-12 have shown disease stabilization in several tumor types in response to s.c. administration or using genetically engineered IL-12-expressing patient fibroblasts. These promising new agents join the matrix metalloproteinase inhibitors as important new drugs in the anti-cancer armamentarium.






Masiero L,Figg WD,Kohn EC




Has Abstract


1997-01-01 00:00:00














  • CXCR4(+) dendritic cells promote angiogenesis during embryo implantation in mice.

    abstract::Early pregnancy is characterized by decidual adaption to the developing embryo involving angiogenesis and vascular growth. Failure of decidual vascular expansion is linked to diseases of pregnancy. Dendritic cells (DC) have been associated with vascular growth during early gestation, though it is unknown whether their...


    pub_type: 杂志文章


    authors: Barrientos G,Tirado-González I,Freitag N,Kobelt P,Moschansky P,Klapp BF,Thijssen VL,Blois SM

    更新日期:2013-04-01 00:00:00

  • Identification of HIF-2α-regulated genes that play a role in human microvascular endothelial sprouting during prolonged hypoxia in vitro.

    abstract::During prolonged hypoxic conditions, endothelial cells change their gene expression to adjust to the low oxygen environment. This process is mainly regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Although endothelial cells do not form sprouts during prolonged hypoxic culturing, silencing of HIF-2α parti...


    pub_type: 杂志文章


    authors: Nauta TD,van den Broek M,Gibbs S,van der Pouw-Kraan TC,Oudejans CB,van Hinsbergh VW,Koolwijk P

    更新日期:2017-02-01 00:00:00

  • Antiangiogenic therapy promoted metastasis of hepatocellular carcinoma by suppressing host-derived interleukin-12b in mouse models.

    abstract::Antiangiogenic therapy, specially sorafenib, has become the standard of care for patients with advanced hepatocellular carcinoma (HCC), however, the improvement in survival time is not satisfactory. Previous studies have found that, in some circumstances, antiangiogenic therapy promoted tumor metastasis and the mechan...


    pub_type: 杂志文章


    authors: Zhu XD,Sun HC,Xu HX,Kong LQ,Chai ZT,Lu L,Zhang JB,Gao DM,Wang WQ,Zhang W,Zhuang PY,Wu WZ,Wang L,Tang ZY

    更新日期:2013-10-01 00:00:00

  • Matrix Gla protein regulates differentiation of endothelial cells derived from mouse embryonic stem cells.

    abstract::Matrix Gla protein (MGP) is an antagonist of bone morphogenetic proteins and expressed in vascular endothelial cells. Lack of MGP causes vascular abnormalities in multiple organs in mice. The objective of this study is to define the role of MGP in early endothelial differentiation. We find that expression of endotheli...


    pub_type: 杂志文章


    authors: Yao J,Guihard PJ,Blazquez-Medela AM,Guo Y,Liu T,Boström KI,Yao Y

    更新日期:2016-01-01 00:00:00

  • Cyclic GMP protects endothelial progenitors from oxidative stress.

    abstract::Endothelial progenitor cells (EPCs) play a critical role in the repair of damaged blood vessels and/or in the growth of new ones in ischemic tissues. Elevated levels of oxygen radicals, which accumulate in the ischemic tissue, could compromise the angiogenic potential of EPCs. To determine if oxidative stress alters t...


    pub_type: 杂志文章


    authors: Curatola AM,Xu J,Hendricks-Munoz KD

    更新日期:2011-09-01 00:00:00

  • Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer.

    abstract::Cancer cells sustain their metabolic needs through nutrients and oxygen supplied by the bloodstream. The requirement for tumor angiogenesis has been therapeutically exploited in the clinical setting mainly by means of inhibition of the vascular endothelial growth factor family of ligands and receptors. Despite promisi...


    pub_type: 临床试验,杂志文章


    authors: Bocci M,Sjölund J,Kurzejamska E,Lindgren D,Marzouka NA,Bartoschek M,Höglund M,Pietras K

    更新日期:2019-02-01 00:00:00

  • Recombinant human prothrombin kringles have potent anti-angiogenic activities and inhibit Lewis lung carcinoma tumor growth and metastases.

    abstract::Prothrombin, a protein involved in blood coagulation, is a plasma glycoprotein composed of the Gla domain, two adjacent kringle domains, and a serine protease domain. Kringles are triple-disulfide-loop folding domains, which are found in several other blood proteins. In this study, we showed that recombinant human pro...


    pub_type: 杂志文章


    authors: Kim TH,Kim E,Yoon D,Kim J,Rhim TY,Kim SS

    更新日期:2002-01-01 00:00:00

  • Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta-analysis.

    abstract:BACKGROUND:Vasculogenic mimicry (VM) is the formation of vascular channels by tumor cells or tumor cell-derived, trans-differentiated cells in highly aggressive, solid tumors. However, the disease features and prognostic value of VM for overall survival of cancer patients remain controversial. METHOD:To systematically...


    pub_type: 杂志文章,meta分析


    authors: Yang JP,Liao YD,Mai DM,Xie P,Qiang YY,Zheng LS,Wang MY,Mei Y,Meng DF,Xu L,Cao L,Yang Q,Yang XX,Wang WB,Peng LX,Huang BJ,Qian CN

    更新日期:2016-04-01 00:00:00

  • Anti-secretogranin III therapy of oxygen-induced retinopathy with optimal safety.

    abstract::Retinopathy of prematurity (ROP) with pathological retinal neovascularization is the most common cause of blindness in children. ROP is currently treated with laser therapy or cryotherapy, both of which may adversely affect the peripheral vision with limited efficacy. Owing to the susceptibility of the developing reti...


    pub_type: 杂志文章


    authors: Tang F,LeBlanc ME,Wang W,Liang D,Chen P,Chou TH,Tian H,Li W

    更新日期:2019-08-01 00:00:00

  • Multiple angiogenesis stimulators in a single malignancy: implications for anti-angiogenic tumour therapy.

    abstract::Anti-angiogenesis is likely to develop into a novel therapeutic approach for patients with solid malignancies. Most current clinical trials evaluate anti-angiogenic drugs aimed primarily against single angiogenesis stimulators. Here, we show that a single solid malignancy, i.e., a human embryonal rhabdomyosarcoma, pro...


    pub_type: 杂志文章


    authors: Pavlakovic H,Havers W,Schweigerer L

    更新日期:2001-01-01 00:00:00

  • Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia.

    abstract::Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Faughnan ME,Gossage JR,Chakinala MM,Oh SP,Kasthuri R,Hughes CCW,McWilliams JP,Parambil JG,Vozoris N,Donaldson J,Paul G,Berry P,Sprecher DL

    更新日期:2019-02-01 00:00:00

  • Contrasting effects of sunitinib within in vivo models of metastasis.

    abstract::Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metastases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastas...


    pub_type: 杂志文章


    authors: Welti JC,Powles T,Foo S,Gourlaouen M,Preece N,Foster J,Frentzas S,Bird D,Sharpe K,van Weverwijk A,Robertson D,Soffe J,Erler JT,Pili R,Springer CJ,Mather SJ,Reynolds AR

    更新日期:2012-12-01 00:00:00

  • Plants and their active compounds: natural molecules to target angiogenesis.

    abstract::Angiogenesis, or new blood vessel formation, is an important process in the pathogenesis of several diseases and thus has been targeted for the prevention and treatment for many disorders. However, the anti-angiogenic agents that are currently in use are mainly synthetic compounds and humanized monoclonal antibodies, ...


    pub_type: 杂志文章,评审


    authors: Lu K,Bhat M,Basu S

    更新日期:2016-07-01 00:00:00

  • Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system.

    abstract::Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-...


    pub_type: 杂志文章


    authors: Herz K,Becker A,Shi C,Ema M,Takahashi S,Potente M,Hesse M,Fleischmann BK,Wenzel D

    更新日期:2018-05-01 00:00:00

  • Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis.

    abstract:OBJECTIVE:Dysregulation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a hallmark of human cancer, occurring in a majority of tumors. Activation of this pathway is critical for transformation and also for the angiogenic switch, which is a key step for tumor progression. The objective of this study was...


    pub_type: 杂志文章


    authors: Harfouche R,Basu S,Soni S,Hentschel DM,Mashelkar RA,Sengupta S

    更新日期:2009-01-01 00:00:00

  • VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities.

    abstract:BACKGROUND:Angiogenesis plays a pivotal role in neoplastic growth and metastasis formation. Vascular endothelial growth factor A (VEGFA) is a major player in physiological and tumour-induced angiogenesis and numerous human tumours have been show to overexpress VEGFA. Moreover increased VEGFA gene expression has been fo...


    pub_type: 杂志文章


    authors: Andreozzi M,Quagliata L,Gsponer JR,Ruiz C,Vuaroqueaux V,Eppenberger-Castori S,Tornillo L,Terracciano LM

    更新日期:2014-07-01 00:00:00

  • Tumor-derived microRNA-494 promotes angiogenesis in non-small cell lung cancer.

    abstract::Angiogenesis, a crucial step in tumor growth and metastasis, is regulated by various pro- or anti-angiogenic factors. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, roles of tumor-derived microRNAs in regulating tumor vasculari...


    pub_type: 杂志文章


    authors: Mao G,Liu Y,Fang X,Liu Y,Fang L,Lin L,Liu X,Wang N

    更新日期:2015-07-01 00:00:00

  • Thymosin beta4 enhances endothelial cell differentiation and angiogenesis.

    abstract::When human umbilical vein endothelial cells (HUVEC) differentiate into capillary-like tubes, there is a five-fold upregulation of the mRNA for thymosin beta4 (Tbeta4) (Grant et al. J Cell Sci 1995; 108: 3685-94 [1]) and this endogenous expression plays an important role in endothelial cell attachment to and spreading ...


    pub_type: 杂志文章


    authors: Grant DS,Rose W,Yaen C,Goldstein A,Martinez J,Kleinman H

    更新日期:1999-01-01 00:00:00

  • TM4SF1: a tetraspanin-like protein necessary for nanopodia formation and endothelial cell migration.

    abstract::Transmembrane-4-L-six-family-1 (TM4SF1) is a tetraspanin-like membrane protein that is highly and selectively expressed by cultured endothelial cells (EC) and, in vivo, by EC lining angiogenic tumor blood vessels. TM4SF1 is necessary for the formation of unusually long (up to a 50 μm), thin (~100-300 nm wide), F-actin...


    pub_type: 杂志文章


    authors: Zukauskas A,Merley A,Li D,Ang LH,Sciuto TE,Salman S,Dvorak AM,Dvorak HF,Jaminet SC

    更新日期:2011-09-01 00:00:00

  • Inhibition of B16 melanoma growth in vivo by retroviral vector-mediated human ribonuclease inhibitor.

    abstract::Human ribonuclease inhibitor (hRI) can inhibit angiogenesis by reversibly binding angiogenin, a member of the RNaseA superfamily, and by suppressing the expression of basic fibroblast growth factor (bFGF). Angiogenesis is necessary for the growth and metastasis of tumors. To study the links between hRI, angiogenesis, ...


    pub_type: 杂志文章


    authors: Wang T,Yang M,Chen J,Watkins T,Xiuyun C

    更新日期:2005-01-01 00:00:00

  • VEGF over-expression in skeletal muscle induces angiogenesis by intussusception rather than sprouting.

    abstract::Therapeutic over-expression of vascular endothelial growth factor (VEGF) can be used to treat ischemic conditions. However, VEGF can induce either normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo, which limits its clinical usefulness. The goal herein was ...


    pub_type: 杂志文章


    authors: Gianni-Barrera R,Trani M,Fontanellaz C,Heberer M,Djonov V,Hlushchuk R,Banfi A

    更新日期:2013-01-01 00:00:00

  • To be or not to be: endothelial cell plasticity in development, repair, and disease.

    abstract::Endothelial cells display an extraordinary plasticity both during development and throughout adult life. During early development, endothelial cells assume arterial, venous, or lymphatic identity, while selected endothelial cells undergo additional fate changes to become hematopoietic progenitor, cardiac valve, and ot...


    pub_type: 杂志文章,评审


    authors: Greenspan LJ,Weinstein BM

    更新日期:2021-01-15 00:00:00

  • Angiogenic desmoplastic histopathological growth pattern as a prognostic marker of good outcome in patients with colorectal liver metastases.

    abstract:BACKGROUND:In patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt end...


    pub_type: 杂志文章


    authors: Galjart B,Nierop PMH,van der Stok EP,van den Braak RRJC,Höppener DJ,Daelemans S,Dirix LY,Verhoef C,Vermeulen PB,Grünhagen DJ

    更新日期:2019-05-01 00:00:00

  • Pharmacological intervention of MKL/SRF signaling by CCG-1423 impedes endothelial cell migration and angiogenesis.

    abstract::De novo synthesis of cytoskeleton-regulatory proteins triggered by the megakaryoblastic leukemia (MKL)/serum response factor (SRF) transcriptional system in response to pro-angiogenic growth factors lies at the heart of endothelial cell (EC) migration (a critical element of angiogenesis) and neovascularization. This s...


    pub_type: 杂志文章


    authors: Gau D,Veon W,Capasso TL,Bottcher R,Shroff S,Roman BL,Roy P

    更新日期:2017-11-01 00:00:00

  • Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells.

    abstract::The role of muscle contraction, prostanoids, nitric oxide and adenosine in the regulation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endothelial cell proliferative compounds in skeletal muscle cell cultures was examined. VEGF and bFGF mRNA, protein release as well as the pr...


    pub_type: 杂志文章


    authors: Jensen L,Schjerling P,Hellsten Y

    更新日期:2004-01-01 00:00:00

  • Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    abstract::Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancre...


    pub_type: 杂志文章


    authors: Sunamura M,Duda DG,Ghattas MH,Lozonschi L,Motoi F,Yamauchi J,Matsuno S,Shibahara S,Abraham NG

    更新日期:2003-01-01 00:00:00

  • Suppression of vascular network formation by chronic hypoxia and prolyl-hydroxylase 2 (phd2) deficiency during vertebrate development.

    abstract::In the adult, new vessels and red blood cells form in response to hypoxia. Here, the oxygen-sensing system (PHD-HIF) has recently been put into focus, since the prolyl-hydroxylase domain proteins (PHD) and hypoxia-inducible factors (HIF) are considered as potential therapeutic targets to treat ischemia, cancers or age...


    pub_type: 杂志文章


    authors: Metikala S,Neuhaus H,Hollemann T

    更新日期:2016-04-01 00:00:00

  • Visualizing vascular permeability and lymphatic drainage using labeled serum albumin.

    abstract::During the early stages of angiogenesis, following stimulation of endothelial cells by vascular endothelial growth factor (VEGF), the vascular wall is breached, allowing high molecular weight proteins to leak from the vessels to the interstitial space. This hallmark of angiogenesis results in deposition of a provision...


    pub_type: 杂志文章,评审


    authors: Vandoorne K,Addadi Y,Neeman M

    更新日期:2010-06-01 00:00:00

  • Endothelial cells expressing low levels of CD143 (ACE) exhibit enhanced sprouting and potency in relieving tissue ischemia.

    abstract::The sprouting of endothelial cells from pre-existing blood vessels represents a critical event in the angiogenesis cascade. However, only a fraction of cultured or transplanted endothelial cells form new vessels. Moreover, it is unclear whether this results from a stochastic process or instead relates to certain endot...


    pub_type: 杂志文章


    authors: Silva EA,Eseonu C,Mooney DJ

    更新日期:2014-07-01 00:00:00

  • The impact of EPLINα (Epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis.

    abstract:BACKGROUND:EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in the regulation of actin dynamics and subsequently in cell motility. EPLIN expression is frequently reduced in a variety of cancer cells and tissues and this loss may account for increased invasive traits in cancer ce...


    pub_type: 杂志文章


    authors: Sanders AJ,Ye L,Mason MD,Jiang WG

    更新日期:2010-12-01 00:00:00