Journal ArticleDOI
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Peter Carmeliet,Valérie Ferreira,Georg Breier,Saskia Pollefeyt,Lena Kieckens,Marina Gertsenstein,Michaela Fahrig,Ann Vandenhoeck,Kendraprasad Harpal,Carmen Eberhardt,Cathérine Declercq,Judy Pawling,Lieve Moons,Desire Collen,Werner Risau,Andras Nagy,Andras Nagy +16 more
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TLDR
It is reported that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES)16,17, and even more impaired in homozygous D1-VEGF- deficient (VDGF-/-) T-ES embryos, resulting in death at mid-gestation.Abstract:
The endothelial cell-specific vascular endothelial growth factor (VEGF) and its cellular receptors Flt-1 and Flk-1 have been implicated in the formation of the embryonic vasculature. This is suggested by their colocalized expression during embryogenesis and the impaired vessel formation in Flk-1 and Flt-1 deficient embryos. However, because Flt-1 also binds placental growth factor, a VEGF homologue, the precise role of VEGF was unknown. Here we report that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES) and even more impaired in homozygous VEGF-deficient (VEGF-/-) T-ES embryos, resulting in death at mid-gestation. Similar phenotypes were observed in F1-VEGF+/- embryos, generated by germline transmission. We believe that this heterozygous lethal phenotype, which differs from the homozygous lethality in VEGF-receptor-deficient embryos, is unprecedented for a targeted autosomal gene inactivation, and is indicative of a tight dose-dependent regulation of embryonic vessel development by VEGF.read more
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Role of vascular endothelial growth factor in regulation of physiological angiogenesis
TL;DR: Evidence accumulating over the last decade has established the fundamental role of vascular endothelial growth factor (VEGF) as a key regulator of normal and abnormal angiogenesis, and numerous clinical trials are presently testing the hypothesis that inhibition of VEGF may have therapeutic value.
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Induction of Pancreatic Differentiation by Signals from Blood Vessels
TL;DR: A role for blood vessels as a source of developmental signals during pancreatic organogenesis is demonstrated and results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development.
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An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination.
TL;DR: Analysis of embryos carrying different combinations of these alleles revealed requirements for Fgf8 gene function during gastrulation, as well as cardiac, craniofacial, forebrain, midbrain and cerebellar development.
Journal ArticleDOI
Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis
Ralf H. Adams,George A. Wilkinson,Cornelia Weiss,Francesca Diella,Nicholas W. Gale,Urban Deutsch,Werner Risau,Rüdiger Klein +7 more
TL;DR: EphrinB ligands induce capillary sprouting in vitro with a similar efficiency as angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), demonstrating a stimulatory role of ephrins in the remodeling of the developing vascular system.
Journal ArticleDOI
Phase II Trial of Bevacizumab and Irinotecan in Recurrent Malignant Glioma
James J. Vredenburgh,Annick Desjardins,James E. Herndon,Jeannette M. Dowell,David A. Reardon,Jennifer A. Quinn,Jeremy N. Rich,Sith Sathornsumetee,Sridharan Gururangan,Melissa Wagner,Darell D. Bigner,Allan H. Friedman,Henry S. Friedman +12 more
TL;DR: The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity and no central nervous system hemorrhages occurred.
References
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Journal ArticleDOI
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.
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.
Journal ArticleDOI
Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
Guo-Hua Fong,Janet Rossant,Janet Rossant,Marina Gertsenstein,Martin L. Breitman,Martin L. Breitman +5 more
TL;DR: It is reported that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation, and it is suggested that the FlT-1 signalling pathway may regulate normal endothelium cell-cell or cell-matrix interactions during vascular development.
Journal ArticleDOI
Derivation of completely cell culture-derived mice from early-passage embryonic stem cells
TL;DR: Fully potent early passage R1 cells and the R1-S3 subclone should be very useful not only for ES cell-based genetic manipulations but also in defining optimal in vitro culture conditions for retaining the initial totipotency of ES cells.
Journal ArticleDOI
The fms-Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth Factor
TL;DR: Findings show that flt encodes a receptor for VEGF-VPF, a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation.