Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.
Napoleone Ferrara,Karen Carver-Moore,Helen Hsifei Chen,Mary Dowd,Lucy Lu,K. Sue O'Shea,Lyn Powell-Braxton,Kenneth J. Hillan,Mark W. Moore +8 more
TL;DR: The unexpected finding that loss of a single VEGF allele is lethal in the mouse embryo between days 11 and 12 was reported, and angiogenesis and blood-island formation were impaired, resulting in several developmental anomalies.
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Abstract: ANGIOGENESIS is required for a wide variety of physiological and pathological processes1. The endothelial cell-specific mitogen vascular endothelial growth factor (VEGF)2,3 is a major mediator of pathological angiogenesis4–6. Also, the expression of VEGF and its two receptors, Flt-1 and Flk-1/KDR, is related to the formation of blood vessels in mouse and rat embryos7–10. Mice homozygous for mutations that inactivate either receptor die in utero between days 8.5 and 9.5 (refs 11,12). However, ligand(s) other than VEGF might activate such receptors13,14. To assess the role of VEGF directly, we disrupted the VEGF gene in embryonic stem cells. Here we report the unexpected finding that loss of a single VEGF allele is lethal in the mouse embryo between days 11 and 12. Angiogenesis and blood-island formation were impaired, resulting in several developmental anomalies. Furthermore, VEGF-null embryonic stem cells exhibit a dramatically reduced ability to form tumours in nude mice.
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Citations
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VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development
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TL;DR: The cloning and characterization of mouse VEGF-C is reported, which is produced as a disulfide-linked dimer of 415 amino acid residue polypeptides, sharing an 85% identity with the human VEGf-C amino acid sequence, suggesting one of the functions of VEGC-C may be in the regulation of angiogenesis of the lymphatic vasculature.
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Cytokines in cancer immunity and immunotherapy
TL;DR: This review defines the contrasting roles that cytokines play in promoting tumor immunity, inflammation, and carcinogenesis and discusses the more promising aspects of clinical cytokine use in cancer patients.
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Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling.
TL;DR: The cellular mechanisms and the molecular regulation of angiogenesis in the pathological state are summarized and the differences of physiological and pathological angiogenic elaborated.
425
Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue.
Sarah Tzu Feng Hsiao,Azar Z Asgari,Zerina Lokmic,Rodney Sinclair,Gregory J. Dusting,Shiang Y. Lim,Rodney J. Dilley +6 more
TL;DR: VEGF-A and V EGF-D were 2 of the major growth factors secreted by ASCs that supported endothelial tubulogenesis and ASCs maybe preferred over other MSC populations for augmenting therapeutic approaches dependent upon angiogenesis.
417
•Journal Article
Selective Inhibition of Vascular Endothelial Growth Factor (VEGF) Receptor 2 (KDR/Flk-1) Activity by a Monoclonal Anti-VEGF Antibody Blocks Tumor Growth in Mice
Rolf A. Brekken,Jay P. Overholser,Victor Stastny,Johannes Waltenberger,John D. Minna,Philip E. Thorpe +5 more
TL;DR: 2C3 has potent antitumor activity, inhibiting the growth of newly injected and established human tumor xenografts in mice and highlighting the dominant role of VEGFR2 in mediating VEGF-induced vascular permeability increase and tumor angiogenesis.
415
References
Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice.
Fouad Shalaby,Janet Rossant,Janet Rossant,Terry P. Yamaguchi,Terry P. Yamaguchi,Marina Gertsenstein,Xiang-Fu Wu,Xiang-Fu Wu,Martin L. Breitman,Martin L. Breitman,Andre C. Schuh +10 more
TL;DR: The generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells is reported, indicating that FlK-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.
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Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo
TL;DR: It is demonstrated that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.
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Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders
Lloyd Paul Aiello,Robert L. Avery,Paul G. Arrigg,B A Keyt,Henry D. Jampel,Sweta Shah,Louis R. Pasquale,Hagen Thieme,Mami Iwamoto,John Edward Park +9 more
TL;DR: The data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
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•Journal Article
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
TL;DR: T tumors have "borrowed" fundamental mechanisms that developed in multicellular organisms for purposes of tissue defense, renewal, and repair and taught us something new about angiogenesis, namely, that vascular hyperpermeability and consequent plasma protein extravasation are important, perhaps essential, elements in its generation.
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