Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Receptors, Vascular Endothelial Growth Factor: A family of closely related RECEPTOR PROTEIN-TYROSINE KINASES that bind vascular endothelial growth factors. They share a cluster of seven extracellular Ig-like domains which are important for ligand binding. They are highly expressed in vascular endothelial cells and are critical for the physiological and pathological growth, development and maintenance of blood and lymphatic vessels.Vascular Endothelial Growth Factor Receptor-2: A 200-230-kDa tyrosine kinase receptor for vascular endothelial growth factors found primarily in endothelial and hematopoietic cells and their precursors. VEGFR-2 is important for vascular and hematopoietic development, and mediates almost all endothelial cell responses to VEGF.Vascular Endothelial Growth Factors: A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells.Vascular Endothelial Growth Factor Receptor-1: A 180-kDa VEGF receptor found primarily in endothelial cells that is essential for vasculogenesis and vascular maintenance. It is also known as Flt-1 (fms-like tyrosine kinase receptor-1). A soluble, alternatively spliced isoform of the receptor may serve as a binding protein that regulates the availability of various ligands for VEGF receptor binding and signal transduction.Endothelial Growth Factors: These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.Receptor, Epidermal Growth Factor: A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.Receptors, Growth Factor: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Vascular Endothelial Growth Factor Receptor-3: A vascular endothelial cell growth factor receptor whose expression is restricted primarily to adult lymphatic endothelium. VEGFR-3 preferentially binds the vascular endothelial growth factor C and vascular endothelial growth factor D and may be involved in the control of lymphangiogenesis.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.PhthalazinesVascular Endothelial Growth Factor C: A vascular endothelial growth factor that specifically binds to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 and VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3. In addition to being an angiogenic factor it can act on LYMPHATIC VESSELS to stimulate LYMPHANGIOGENESIS. It is similar in structure to VASCULAR ENDOTHELIAL GROWTH FACTOR D in that they both contain N- and C-terminal extensions that were not found in other VEGF family members.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Neuropilin-1: Dimeric cell surface receptor involved in angiogenesis (NEOVASCULARIZATION, PHYSIOLOGICAL) and axonal guidance. Neuropilin-1 is a 140-kDa transmembrane protein that binds CLASS 3 SEMAPHORINS, and several other growth factors. Neuropilin-1 forms complexes with plexins or VEGF RECEPTORS, and binding affinity and specificity are determined by the composition of the neuropilin dimer and the identity of other receptors complexed with it. Neuropilin-1 is expressed in distinct patterns during neural development, complementary to those described for NEUROPILIN-2.Vascular Endothelial Growth Factor D: A vascular endothelial growth factor that specifically binds to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 and VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-3. In addition to being an angiogenic factor it can act on LYMPHATIC VESSELS to stimulate LYMPHANGIOGENESIS. It is similar in structure to VASCULAR ENDOTHELIAL GROWTH FACTOR C in that they both contain N- and C-terminal extensions that were not found in other VEGF family members.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.QuinazolinesCell Line, Tumor: A cell line derived from cultured tumor cells.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Human Umbilical Vein Endothelial Cells: Endothelial cells that line venous vessels of the UMBILICAL CORD.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Fibroblast Growth Factor 2: A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Lymphangiogenesis: The formation of LYMPHATIC VESSELS.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Vascular Endothelial Growth Factor B: A vascular endothelial growth factor expressed in a variety of tissues. It binds with high specificity to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 and NEUROPILIN-1.Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Antigens, CD31: Cell adhesion molecules present on virtually all monocytes, platelets, and granulocytes. CD31 is highly expressed on endothelial cells and concentrated at the junctions between them.Receptors, Platelet-Derived Growth Factor: Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.Receptors, Fibroblast Growth Factor: Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Angiogenesis Inducing Agents: Agents that induce or stimulate PHYSIOLOGIC ANGIOGENESIS or PATHOLOGIC ANGIOGENESIS.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Umbilical Veins: Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Receptor, Platelet-Derived Growth Factor beta: A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Angiopoietin-1: The first to be discovered member of the angiopoietin family. It may play a role in increasing the sprouting and branching of BLOOD VESSELS. Angiopoietin-1 specifically binds to and stimulates the TIE-2 RECEPTOR. Several isoforms of angiopoietin-1 occur due to ALTERNATIVE SPLICING of its mRNA.Receptor, TIE-2: A TIE receptor tyrosine kinase that is found almost exclusively on ENDOTHELIAL CELLS. It is required for both normal embryonic vascular development (NEOVASCULARIZATION, PHYSIOLOGIC) and tumor angiogenesis (NEOVASCULARIZATION, PATHOLOGIC).Capillaries: The minute vessels that connect the arterioles and venules.Pregnancy Proteins: Proteins produced by organs of the mother or the PLACENTA during PREGNANCY. These proteins may be pregnancy-specific (present only during pregnancy) or pregnancy-associated (present during pregnancy or under other conditions such as hormone therapy or certain malignancies.)Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Lymphatic Vessels: Tubular vessels that are involved in the transport of LYMPH and LYMPHOCYTES.Lung Neoplasms: Tumors or cancer of the LUNG.Corneal Neovascularization: New blood vessels originating from the corneal veins and extending from the limbus into the adjacent CORNEAL STROMA. Neovascularization in the superficial and/or deep corneal stroma is a sequel to numerous inflammatory diseases of the ocular anterior segment, such as TRACHOMA, viral interstitial KERATITIS, microbial KERATOCONJUNCTIVITIS, and the immune response elicited by CORNEAL TRANSPLANTATION.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Mice, Inbred C57BLBlood Vessels: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).Piperidines: A family of hexahydropyridines.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Receptors, Mitogen: Glycoprotein molecules on the surface of B- and T-lymphocytes, that react with molecules of antilymphocyte sera, lectins, and other agents which induce blast transformation of lymphocytes.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Transplantation, Heterologous: Transplantation between animals of different species.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Neuropilins: Neuropilins are 140-kDa vertebrate cell surface receptors that bind neuronal guidance molecules during neural development and axonal outgrowth, and modulate VEGF-mediated angiogenesis. NEUROPILIN-1 and NEUROPILIN-2 differ in their binding specificities, and are distributed complementarily in regions of the developing nervous system. Neuropilins are receptors for secreted CLASS 3 SEMAPHORINS as well as for vascular endothelial growth factors, and may form hetero- or homodimers. They may also interact synergistically with plexins and with VEGF RECEPTORS to form receptor complexes with distinct affinities and specificities. Neuropilin binding specificity is determined by CUB and coagulation-factor-like domains in the extracellular portion of the molecule, while a MAM domain is essential for SIGNAL TRANSDUCTION.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.IndazolesEnzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Neuropilin-2: Transmembrane receptor for CLASS 3 SEMAPHORINS and several vascular endothelial growth factor isoforms. Neuropilin-2 functions either as a homodimer or as a heterodimer with NEUROPILIN-1. The binding affinity of neuropilin-2 varies for different class 3 semaphorin isoforms and is dependent on the composition of the dimer. The protein also forms receptor complexes with plexins and with VEGF RECEPTORS, which alters the binding characteristics of the receptor.Angiopoietin-2: An angiopoietin that is closely related to ANGIOPOIETIN-1. It binds to the TIE-2 RECEPTOR without receptor stimulation and antagonizes the effect of ANGIOPOIETIN-1. However its antagonistic effect may be limited to cell receptors that occur within the vasculature. Angiopoietin-2 may therefore play a role in down-regulation of BLOOD VESSEL branching and sprouting.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Chorioallantoic Membrane: A highly vascularized extra-embryonic membrane, formed by the fusion of the CHORION and the ALLANTOIS. It is mostly found in BIRDS and REPTILES. It serves as a model for studying tumor or cell biology, such as angiogenesis and TISSUE TRANSPLANTATION.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Mice, Inbred BALB CBreast Neoplasms: Tumors or cancer of the human BREAST.Microcirculation: The circulation of the BLOOD through the MICROVASCULAR NETWORK.Carcinoma, Renal Cell: A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Kidney Neoplasms: Tumors or cancers of the KIDNEY.Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Hypoxia-Inducible Factor 1: A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Receptor, Fibroblast Growth Factor, Type 2: A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in craniosynostotic syndromes (e.g., APERT SYNDROME; and CROUZON SYNDROME).Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Receptor, Fibroblast Growth Factor, Type 1: A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Anoxia: Relatively complete absence of oxygen in one or more tissues.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.Receptor, erbB-2: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.Glioma: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces.raf Kinases: A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Ischemia: A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.Carcinoma, Non-Small-Cell Lung: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.Retinal Neovascularization: Formation of new blood vessels originating from the retinal veins and extending along the inner (vitreal) surface of the retina.Angiogenic Proteins: Intercellular signaling peptides and proteins that regulate the proliferation of new blood vessels under normal physiological conditions (ANGIOGENESIS, PHYSIOLOGICAL). Aberrant expression of angiogenic proteins during disease states such as tumorigenesis can also result in PATHOLOGICAL ANGIOGENESIS.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Receptors, Nerve Growth Factor: Cell surface receptors that bind NERVE GROWTH FACTOR; (NGF) and a NGF-related family of neurotrophic factors that includes neurotrophins, BRAIN-DERIVED NEUROTROPHIC FACTOR and CILIARY NEUROTROPHIC FACTOR.Nerve Growth Factors: Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Carcinoma, Lewis Lung: A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Integrin alphaVbeta3: An integrin that binds to a variety of plasma and extracellular matrix proteins containing the conserved RGD amino acid sequence and modulates cell adhesion. Integrin alphavbeta3 is highly expressed in OSTEOCLASTS where it may play role in BONE RESORPTION. It is also abundant in vascular smooth muscle and endothelial cells, and in some tumor cells, where it is involved in angiogenesis and cell migration. Although often referred to as the vitronectin receptor there is more than one receptor for vitronectin (RECEPTORS, VITRONECTIN).Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Receptor, Fibroblast Growth Factor, Type 3: A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Culture Media, Conditioned: Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).Wound Healing: Restoration of integrity to traumatized tissue.Cornea: The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed)Hemangiosarcoma: A rare malignant neoplasm characterized by rapidly proliferating, extensively infiltrating, anaplastic cells derived from blood vessels and lining irregular blood-filled or lumpy spaces. (Stedman, 25th ed)Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Transforming Growth Factors: Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.Tumor Burden: The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.Nitric Oxide Synthase Type III: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.Retinal Vessels: The blood vessels which supply and drain the RETINA.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Colonic Neoplasms: Tumors or cancer of the COLON.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Triazines: Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Transforming Growth Factor beta1: A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Proto-Oncogene Proteins c-kit: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Receptor, Platelet-Derived Growth Factor alpha: A PDGF receptor that binds specifically to both PDGF-A chains and PDGF-B chains. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.Placenta: A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Liver Neoplasms: Tumors or cancer of the LIVER.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Aorta: The main trunk of the systemic arteries.Pericytes: Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.Pre-Eclampsia: A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease.Sulfonamides: A group of compounds that contain the structure SO2NH2.Hindlimb: Either of two extremities of four-footed non-primate land animals. It usually consists of a FEMUR; TIBIA; and FIBULA; tarsals; METATARSALS; and TOES. (From Storer et al., General Zoology, 6th ed, p73)Ki-67 Antigen: A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.

Loss of the VEGF(164) and VEGF(188) isoforms impairs postnatal glomerular angiogenesis and renal arteriogenesis in mice. (1/2034)

Vascular endothelial growth factor (VEGF) is transcribed in the VEGF(120), VEGF(164), or VEGF(188) isoforms, which differ in receptor binding, matrix association, and angiogenic activity. This vascular growth factor has been implicated in the development of the renal vasculature, but the role of the distinct VEGF isoforms remains unknown. In the present report, renal angiogenesis and arteriogenesis were studied in VEGF(120/120) mice, expressing only the short VEGF(120) isoform. In VEGF(120/120) mice, ingrowth and survival of capillaries in glomeruli, remodeling of peritubular capillaries, vascular coverage by pericytes, and branching of renal arteries were all severely impaired, causing abnormal glomerular filtration and impairing renal function. The arterial branching defect might be related to a reduced expression of renin, a presumed renal arterial branching factor. Glomerulosclerosis and tubular dilation possibly resulted from renal ischemia caused by vascular defects. Thus, VEGF(164) and VEGF(188) not only mediate angiogenesis, but they also play an essential role in renal branching arteriogenesis.  (+info)

Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability. (2/2034)

Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, comprising at least five cytokines specifically involved in the regulation of vascular and/or lymphatic endothelium differentiation. Several lines of evidence indicate a role for PlGF in monocyte chemotaxis and in potentiating the activity of VEGF, but the exact function of this cytokine is not fully understood. To define the biological role of PlGF in vivo, we have produced a transgenic mouse model overexpressing this factor in the skin by using a keratin 14 promoter cassette. Our data indicate that PlGF has strong angiogenic properties in both fetal and adult life. PlGF overexpression results in a substantial increase in the number, branching and size of dermal blood vessels as well as in enhanced vascular permeability. Indeed, intradermally injected recombinant PlGF was able to induce vessel permeability in wild-type mice. The analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular endothelial growth factor receptor 2/flk-1 indicates that the two receptors are induced in the skin endothelium of transgenic mice suggesting that both are involved in mediating the effect of overexpressed PlGF.  (+info)

Peritubular capillary regression during the progression of experimental obstructive nephropathy. (3/2034)

Injury to the renal microvasculature may be a major factor contributing to the progression of renal disease. Although severe disruption of peritubular capillaries (PTC) could lead to marked tubulointerstitial scarring, elucidation of that process remains incomplete. This study investigated the morphologic changes in PTC and their likely regulation by vascular endothelial growth factor (VEGF) during the progression of tubulointerstitial injuries. Unilateral ureteral obstruction was induced in Wistar rats by ligation of the left ureter, and the kidneys were then collected at selected times. PTC lumina and the expression of VEGF and its receptor Flk-1 were immunohistochemically detected. Morphologic changes in PTC endothelial cells were examined by using Ki67 staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, and electron-microscopic studies. In the first week of the disease period, immunohistochemical labeling of tubular VEGF intensified, with accompanying deformation and dilation of adjacent thrombomodulin (TM)-positive PTC lumina; an angiogenic response of endothelial cells was demonstrated with Ki67 and TM double-staining. During the subsequent 2 wk, tubular VEGF labeling decreased until it was virtually absent, an effect confirmed by Western blotting. Concomitantly, labeling of the VEGF receptor Flk-1 in PTC endothelial cells decreased and PTC lumina began to regress, demonstrating endothelial cell apoptosis (as detected in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling and electron-microscopic studies). By the end of week 4, the numbers of TM-positive PTC lumina were significantly decreased in areas of marked tubulointerstitial scarring. These results suggest that PTC regression, involving an early, unsustained, angiogenic response followed by progressive endothelial cell apoptosis, could be a potential factor contributing to tubulointerstitial scarring in this unilateral ureteral obstruction model.  (+info)

Angiotensin II regulation of vascular endothelial growth factor and receptors Flt-1 and KDR/Flk-1 in cyclosporine nephrotoxicity. (4/2034)

BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in angiogenesis, wound healing and inflammation. VEGF exerts its effect via the tyrosine kinase receptors Flt-1 and KDR/Flk-1. We have previously shown that VEGF is up-regulated in a chronic cyclosporine (CsA) nephrotoxicity model. Our current study examined the role of angiotensin II (Ang II) blockade with enalapril (E) or losartan (L) on VEGF in this model. METHODS: Pair-fed salt-depleted rats were administered vehicle, CsA, CsA + nilvadipine, CsA + hydralazine/hydrochlorthiazide (HCTZ), CsA + E or CsA + L, and were sacrificed at 7 or 28 days. Physiologic and histologic changes were studied in addition to the mRNA expression of VEGF and its receptors Flt-1 and KDR/Flk-1 by Northern blot, and the protein expression of VEGF by Western blot. RESULTS: While all groups achieved similar blood pressures and creatinine clearances, the amelioration in nephrotoxicity was observed only with Ang II blockade. VEGF mRNA and protein expressions increased with CsA and became significantly reduced with Ang II blockade. Flt-1 expression was similar in all groups; it decreased early and remained low. On the other hand, KDR/Flk-1 mRNA expression was higher at seven days in all groups, except in the +E and +L groups where it was significantly lower, and then became further down-regulated at 28 days. CONCLUSIONS: The increased VEGF expression in chronic CsA nephrotoxicity seems to be related to up-regulation of Ang II. In addition, VEGF probably exerted its effect via the KDR/Flk-1 receptor. The actions of VEGF in this model remain speculative, but may be related to its effect on macrophage infiltration or matrix deposition.  (+info)

Exogenous Slit2 does not affect ureteric branching or nephron formation during kidney development. (5/2034)

In an attempt to elucidate the role of Slit2 in vertebrate kidney development, the effect of adding exogenous human Slit2 protein (hSlit2) to developing murine metanephric kidney explants was examined. To confirm the activity of the recombinant Slit2 protein, neurons from 8 day old chick sympathetic nerve chain dorsal root ganglia were cultured with hSlit2 protein, which induced significant neurite branching and outgrowth. Using kidney explants as a model system, metanephric development in the presence of hSlit2 protein was examined. Addition of hSlit2 up to a final concentration of 1 microg/ml had no detectable effect on the formation of nephrons or on branching morphogenesis of the ureteric tree after 2 or 4 days in culture, as assessed via immunofluorescence for the markers WT1 and calbindin 28K respectively. Similarly, maturation of the nephrogenic mesenchyme occurred in a phenotypically normal fashion. In situ analysis of the Slit receptors, Robo1 and Robo2, the vasculogenic markers VEGFA and Flk-1, and the stromal cell marker BF2 displayed no difference in comparison to controls.  (+info)

The type 2 vascular endothelial growth factor receptor recruits insulin receptor substrate-1 in its signalling pathway. (6/2034)

Vascular endothelial growth factor (VEGF) isoforms exert their biological effects through receptors that possess intrinsic tyrosine kinase activity. Whether VEGF binding to its receptors recruits insulin receptor substrate (IRS) family of docking proteins to the receptor is not known. Following incubation of mouse kidney proximal tubular epithelial cells with VEGF, we observed an increase in tyrosine phosphorylation of several proteins, including one of approximately 200 kDa, suggesting possible regulation of phosphorylation of IRS proteins. VEGF augmented tyrosine phosphorylation of IRS-1 in kidney epithelial cells and rat heart endothelial cells in a time-dependent manner. In the epithelial cells, association of IRS-1 with type 2 VEGF receptor was promoted by VEGF. VEGF also increased association of IRS-1 with the p85 regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase), and PI 3-kinase activity in IRS-1 immunoprecipitates was increased in VEGF-treated cells. Incubation of epithelial cells with antisense IRS-1 oligonucleotide, but not sense oligonucleotide, reduced expression of the protein and VEGF-induced PI 3-kinase activity in IRS-1 immunoprecipitates. Additionally, VEGF-induced protein synthesis was also impaired by antisense but not sense IRS-1 oligonucleotide. These data provide the first evidence that binding of VEGF to its type 2 receptor promotes association of IRS-1 with the receptor complex. This association may account for some of the increase in VEGF-induced PI 3-kinase activity, and the increase in de novo protein synthesis seen in renal epithelial cells.  (+info)

Anti-vascular endothelial growth factor receptor 2 antibody reduces tumorigenicity and metastasis in orthotopic prostate cancer xenografts via induction of endothelial cell apoptosis and reduction of endothelial cell matrix metalloproteinase type 9 production. (7/2034)

PURPOSE: Vascular endothelial growth factor (VEGF), which is produced by tumor cells, is a potent endothelial cell mitogen. The aim of the present study was to evaluate the response of orthotopic prostate cancer xenografts and prostate cancer bone metastasis to anti-VEGF receptor (flk-1) antibody (DC101) treatment. EXPERIMENTAL DESIGN: Orthotopic prostate cancer models (PC-3M-MM2 and LNCaP-LN3 prostate carcinoma cells) and a prostate cancer bone metastasis model (PC-3M-MM2) were used for these experiments. Early and established tumors were treated with saline, paclitaxel, DC101, or a DC101-plus-paclitaxel combination for 5 weeks (PC-3M-MM2) and 12 weeks (LNCaP-LN3). At the end of therapy, tumors were removed and weighed. Apoptosis, tumor cell proliferation, and angiogenesis- and metastasis-related gene expression were evaluated using immunohistochemistry, in situ hybridization, and terminal deoxynucleotidyl transferase-ediated nick end labeling (TUNEL). RESULTS: After treatment of early tumors (PC-3M-MM2), median prostate tumor weights (+/-SE) were 1230 +/- 210 mg in untreated controls, 482 +/- 121 mg in mice treated with paclitaxel (P = 0.009), 148 +/- 27 mg in mice treated with DC101 (P < 0.001), and 48 +/- 10 mg in mice treated with the combination of DC101 and paclitaxel (P < 0.001). Lymph node metastasis occurred in 7 of the 9 control mice, 5 of the 9 paclitaxel-treated animals, 5 of the 12 DC101-treated animals, and 2 of the 11 animals in the combination therapy group. Treatment with DC101 alone or in combination with paclitaxel reduced tumor-induced neovascularity measured by microvessel density and tumor cell proliferation (by proliferating cell nuclear antigen) and enhanced apoptosis (measured by TUNEL) in tumor cells and endothelial cells compared with controls. In the tibial prostate cancer metastasis model, significant inhibition of tumor growth was observed. In the LNCaP-LN3 orthotopic prostate cancer model, tumors occurred in 7 of the 10 control mice, 4 of the 10 paclitaxel-treated animals, 5 of the 10 DC101-treated animals, and 2 of the 11 animals in the combination therapy group (P < 0.05). The efficacy of DC101 was much greater in the treatment of early tumors, which suggests that tumor burden may be a critical factor in determining the response to DC101. In vitro and in vivo analysis of endothelial cell function showed reduced matrix metalloproteinase type 9 production in endothelial cells treated with DC101. CONCLUSIONS: This study confirms the principle of tumor growth inhibition by targeting angiogenesis within tumors and supports the use of anti-VEGF receptor agents.  (+info)

A novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to its kinase domain receptor. (8/2034)

Vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, plays an essential role in both physiological and pathological angiogenesis. The VEGF receptor KDR/Flk-1 (a kinase domain receptor) mediates various biological activities of VEGF related to proliferation, differentiation, and migration of endothelial cells. Here we present a novel peptide designated K237-(HTMYYHHYQHHL), which was isolated from a phage-displayed peptide library, binding to KDR with high affinity and specificity. By interfering with the VEGF-KDR interaction, the peptide K237 inhibited proliferation of cultured primary human umbilical vein endothelial cells induced by recombinant human VEGF(165) in a dose-dependent and cell type-specific manner. The peptide also exerted an anti-angiogenesis activity in vivo as revealed using the chick embryo chorioallantoic membrane angiogenesis assay. Moreover, the peptide K237 significantly inhibited the growth of solid tumors implanted beneath the breasts and their metastases to lungs in severe combined immunodeficient mice. Taken together, these findings suggest that the peptide K237 can functionally disrupt the interaction between VEGF and the KDR receptor and cause potent biological effects that include the inhibition of angiogenesis and tumor growth. As a consequence, this peptide (and its future derivatives) may have use as a potential cancer therapy.  (+info)

*Soluble fms-like tyrosine kinase-1

Kendall R, Thomas K. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor ... vascular endothelial growth factor) and PlGF (placental growth factor). sFlt-1 thereby blunts the beneficial effects of these ... which is produced by a variety of tissues.These proteins act as a receptor of vascular endothelial growth factor (VEGF), a ... potent angiogenic growth factor. (Another VEGF receptor is KDR). sFlt-1 (soluble fms-like tyrosine kinase-1 - also known as ...

*Vascular endothelial growth factor A

"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor ... Vascular endothelial growth factor A has been shown to interact with: ADAMTS1, CTGF, and NRP1, Vascular endothelial growth ... This gene is a member of the platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) family and encodes ... "Assignment of vascular endothelial growth factor (VEGF) and placenta growth factor (PLGF) genes to human chromosome 6p12-p21 ...

*NEDD4

"Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation". J. Biol. Chem. 279 (25): 26754-61. ... signalling by regulating the amount of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) on the cell ... such as HER3 and HER4 EGF receptors, and ACK. The fibroblast growth factor receptor 1 (FGFR1) undergoes NEDD4 mediated ... In vivo NEDD4 is involved in the regulation of a diverse range of processes, including insulin-like growth factor signalling, ...

*FER1L3

"Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function". J Biol Chem. 282 (42): 30745-53. doi ... 9 (2): 217-26. doi:10.1093/hmg/9.2.217. PMID 10607832. Britton S, Freeman T, Vafiadaki E, Keers S, Harrison R, Bushby K, Bashir ...

*Ramucirumab

It is directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2 it works as a receptor ... antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority ... versus 2%), headache (9% versus 3%), and high blood pressure (16% versus 8%). In studies, no interactions were observed with ...

*VEGF receptor

Proteopedia Vascular_Endothelial_Growth_Factor_Receptor - the Vascular Endothelial Growth Factor Receptor Structure in ... VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1 ... "Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor ... Holmes K, Roberts OL, Thomas AM, Cross MJ (Oct 2007). "Vascular endothelial growth factor receptor-2: structure, function, ...

*Annexin A5

"Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1". Biochemical and ... Platelets also expose PS and PE on their surface when activated, which serves as binding site for various coagulation factors. ... Annexin A5 has been shown to interact with Kinase insert domain receptor and Integrin, beta 5. GRCh38: Ensembl release 89: ... "Cloning and expression of cDNA for human vascular anticoagulant, a Ca2+-dependent phospholipid-binding protein". European ...

*GTF2IRD1

2005). "Vascular endothelial growth factor receptor-2: counter-regulation by the transcription factors, TFII-I and TFII-IRD1". ... Vullhorst D, Buonanno A (2003). "Characterization of general transcription factor 3, a transcription factor involved in slow ... General transcription factor II-I repeat domain-containing protein 1 is a protein that in humans is encoded by the GTF2IRD1 ... 2000). "A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome". Eur ...

*Ischemia-reperfusion injury of the appendicular musculoskeletal system

Plasminogen activator inhibitor-1 inhibits angiogenic signaling by uncoupling vascular endothelial growth factor receptor-2- ... 23(10): p. 1305-19 Kapitsinou, P.P., et al., Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury. J ... Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, ... the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. ...

*Intrabody (protein)

"Intrabody-based strategies for inhibition of vascular endothelial growth factor receptor-2: effects on apoptosis, cell growth, ... 303 (1-2): 19-39. doi:10.1016/j.jim.2005.05.004. PMID 16045924. Serruys, B; Van Houtte, F; Verbrugghe, P; Leroux-Roels, G; ... 341 (1-2): 30-40. doi:10.1016/j.jim.2008.10.012. PMID 19038261. Zhou, C; Przedborski, S (2009). "Intrabody and Parkinson's ...

*Foretinib

... is an inhibitor of the kinase enzymes c-Met and vascular endothelial growth factor receptor 2 (VEGFR-2). c-Met ... 2009). "Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF ... and VEGF receptor tyrosine kinases". Cancer Research. 69 (20): 8009-16. doi:10.1158/0008-5472.CAN-08-4889. PMID 19808973. ... c-Met and VEGFR-2 inhibitor, Oncolytic". Drugs Fut. 35 (11): 893-901. doi:10.1358/dof.2010.35.11.1529012 (inactive 2017-01-15 ...

*Vandetanib

... mainly the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET- ... Vandetanib is an inhibitor of vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and RET tyrosine ... It acts as a kinase inhibitor of a number of cell receptors, ... multicentre phase 2 trial. "US Label" (PDF). FDA. July 2016. ... Starkey, Jonathan (August 2, 2011). "AstraZeneca (finally) lands name for cancer drug". Delaware Inc. Fourcade, Marthe (27 July ...

*Pegdinetanib

"Anti-tumor effect of CT-322 as an adnectin inhibitor of vascular endothelial growth factor receptor-2". MAbs. 2 (2): 199-208. ... is an investigational anti-cancer drug that acts as a selective antagonist of vascular endothelial growth factor receptor 2 ( ... 17 (2): 363-371. doi:10.1158/1078-0432.CCR-10-1411. PMID 21224368. Mamluk, R.; Carvajal, I. M.; Morse, B. A.; Wong, H.; ... VEGFR-2), hindering vascularization of tumors. It is a genetically engineered peptide derivative based on the monobody ...

*Vascular endothelial growth factor

"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor ... Proteopedia Vascular_Endothelial_Growth_Factor - the Vascular Endothelial Growth Factor Structure in Interactive 3D. ... Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced ... Ribatti D (2005). "The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a ...

*Apatinib

"Novel Vascular Endothelial Growth Factor Receptor Inhibitor YN968D1 (Apatinib) Against advanced Malignancies: Phase I/II Study ... 2010). "Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in ... is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2 (VEGFR2, also known ... specifically apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel ...

*Cediranib

... (AZD-2171; tentative trade name Recentin) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor ... Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer". Cancer Research. 65 (10 ... an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients ... doi:10.1016/S1470-2045(14)70391-2. PMC 4294183 . PMID 25218906. Combination of Targeted Drugs May Significantly Increase ...

*Targeted therapy

2010). "Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in ... receptor expressed in some types of breast cancer Alemtuzumab Cetuximab target the epidermal growth factor receptor (EGFR). It ... Gefitinib (Iressa, also known as ZD1839), targets the epidermal growth factor receptor (EGFR) tyrosine kinase and is approved ... Erlotinib (marketed as Tarceva). Erlotinib inhibits epidermal growth factor receptor, and works through a similar mechanism as ...

*Kinase insert domain receptor

... (KDR, a type III receptor tyrosine kinase) also known as vascular endothelial growth factor ... "Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism ... Petrova TV, Makinen T, Alitalo K (1999). "Signaling via vascular endothelial growth factor receptors". Exp. Cell Res. 253 (1): ... Matsumoto T, Mugishima H (2006). "Signal transduction via vascular endothelial growth factor (VEGF) receptors and their roles ...

*Neuropilin 1

"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor ... "Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain". The ... NRP1 is a membrane-bound coreceptor to a tyrosine kinase receptor for both vascular endothelial growth factor (VEGF; MIM 192240 ... Whitaker GB, Limberg BJ, Rosenbaum JS (July 2001). "Vascular endothelial growth factor receptor-2 and neuropilin-1 form a ...

*Contact normalization

These include podoplanin (PDPN), vascular endothelial growth factor receptor 2/kinase insert domain receptor (VEFR2/KDR), and ... Tumor cells need to overcome this form of growth inhibition before they can become malignant or metastatic. Induction of a ... Intimate junctional contact between tumor cells and normal cells is needed for this form of growth control. Contact ... is a process by which intercellular junctions mediate signals that allow normal cells to inhibit the transformed growth of ...

*Periostin

... by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 ... Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a protein that in humans is encoded by the POSTN gene. Periostin ... "Entrez Gene: POSTN periostin, osteoblast specific factor". Gillan L, Matei D, Fishman DA, Gerbin CS, Karlan BY, Chang DD (Sep ... Periostin is a gla domain vitamin K dependent factor. Periostin is a secreted extracellular matrix protein that was originally ...

*Sp4 transcription factor

"Vascular endothelial growth factor receptor-2 expression is induced by 17beta-estradiol in ZR-75 breast cancer cells by ... Transcription factor Sp4 is a protein that in humans is encoded by the SP4 gene. Sp4 transcription factor has been shown to ... "Entrez Gene: SP4 Sp4 transcription factor". Rotheneder H, Geymayer S, Haidweger E (Nov 1999). "Transcription factors of the Sp1 ... promoter by the early growth response-1 (EGR-1) and Sp-family transcription factors". Nucleic Acids Research. 31 (3): 1097-107 ...

*Neuropilin 2

"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor ... Gluzman-Poltorak Z, Cohen T, Shibuya M, Neufeld G (2001). "Vascular endothelial growth factor receptor-1 and neuropilin-2 form ... 2002). "Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma". ... "Vascular endothelial growth factor (VEGF) and its receptors". FASEB J. 13 (1): 9-22. PMID 9872925. Kolodkin AL, Levengood DV, ...

*Pathophysiology of Parkinson's disease

Most notably, vascular endothelial growth factor (VEGF) and VEGF receptors are thought to be disregulated in neurodegenerative ... doi:10.1038/nrn3114 Hao, T., & Rockwell, P. (2013). Signaling through the vascular endothelial growth factor receptor VEGFR-2 ... Gap junctions in endothelial cells in the BBB help prevent large or harmful molecules from entering the brain by regulating the ... Cell receptor disruption can also affect the ability for cells to adhere to one another with adherens junctions. Without new ...

*EPAS1

... and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1)". The Journal of ... "Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells". Genes & ... Endothelial PAS domain-containing protein 1 (EPAS1, also known as hypoxia-inducible factor-2alpha (HIF-2alpha)) is a protein ... It is a type of hypoxia-inducible factor, a group of transcription factors involved in body response to oxygen level. The gene ...

*Catenin

Yi ZY, Feng LJ, Xiang Z, Yao H (2011). "Vascular endothelial growth factor receptor-1 activation mediates epithelial to ... conditional inactivation of the β-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular ... to specifically have vascular endothelium cells deficient in β-catenin showed disrupted adhesion between vascular endothelial ... homeostasis and growth, also make it susceptible to alterations that can lead to abnormal cell behavior and growth. Any changes ...

*Itraconazole

Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling". Journal of Medicinal Chemistry. ... It stopping fungal growth by affecting the cell membrane or affecting their metabolism. Itraconazole was approved for medical ... 26 October 2006 Mellaerts R, Aerts A, Caremans TP, Vermant J, Van den Mooter G, Martens JA, Augustijns P (2010). "Growth of ... Aftab BT, Dobromilskaya I, Liu JO, Rudin CM (2011). "Itraconazole Inhibits Angiogenesis and Tumor Growth in Non-Small Cell Lung ...
Buy KDR elisa kit, Fish Kinase Insert Domain Receptor/Vegfr2 ELISA Kit-AAI31823.1 (MBS018513) product datasheet at MyBioSource, ELISA Kits
Definition of vascular endothelial growth factor receptor-2 in the Definitions.net dictionary. Meaning of vascular endothelial growth factor receptor-2. What does vascular endothelial growth factor receptor-2 mean? Information and translations of vascular endothelial growth factor receptor-2 in the most comprehensive dictionary definitions resource on the web.
(a type III receptor tyrosine kinase) is a VEGF receptor. KDR is the human gene encoding it. KDR has also been designated as CD309 (cluster of differentiation 309). PBB Summary section title = summary text = ee also* Cluster of differentiation *…
These reference sequences exist independently of genome builds. Explain. These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above. ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
Impaired lymphangiogenesis is a complication of chronic complex diseases, including diabetes. VEGF-C/VEGFR3 signaling promotes lymphangiogenesis, but how this pathway is affected in diabetes remains poorly understood. We previously demonstrated that loss of epsins 1 and 2 in lymphatic endothelial cells (LECs) prevented VEGF-C-induced VEGFR3 from endocytosis and degradation. Here, we report that diabetes attenuated VEGF-C-induced lymphangiogenesis in corneal micropocket and Matrigel plug assays in WT mice but not in mice with inducible lymphatic-specific deficiency of epsins 1 and 2 (LEC-iDKO). Consistently, LECs isolated from diabetic LEC-iDKO mice elevated in vitro proliferation, migration, and tube formation in response to VEGF-C over diabetic WT mice. Mechanistically, ROS produced in diabetes induced c-Src-dependent but VEGF-C-independent VEGFR3 phosphorylation, and upregulated epsins through the activation of transcription factor AP-1. Augmented epsins bound to and promoted degradation of ...
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) ...
The therapeutic application of adult stem cells is farther along in clinical development than any of the other stem cell approaches. Adult stem cells exist in the bone marrow and the circulation or as residents within a specific tissue.9 Therapies aimed at neovascularization to date have included bone marrow-derived and circulating stem cell approaches. The use of adult stem cells for vascular regeneration was presaged by Asaharas discovery of the vasculogenic EPC subpopulation in 1997 and has culminated in recent clinical trials.13. Parenthetically, the widely used term "EPC" is a misnomer. The surface markers that are commonly used for identification of human EPCs include markers that are not specific for endothelial lineage, such as CD133 and KDR (kinase insert domain receptor).10 In addition, methods for harvesting, purifying, and culturing EPCs are not standardized. Thus, semantic confusion is compounded by methodological variation. Casual readers of the literature may not recognize that ...
KDR - KDR (untagged)-Human kinase insert domain receptor (a type III receptor tyrosine kinase) (KDR) available for purchase from OriGene - Your Gene Company.
A systematic yet unbiased screening approach in the context of activated Wnt signaling in human cells has enabled the discovery of novel candidate kinase regulators of the Wnt/β-cat pathway. Whereas the Wnt pathway has been extensively pursued with the use of model organism-based genetic screens, recent observations have found newer positive functions of two classic negative regulators of the Wnt pathway, APC (28) and GSK3β (29), highlighting the inherent epistatic bias of conventional assays (30). By interrogating Wnt signaling at the level of transcriptional activation in human STF293 cells with the use of targeted RNA interference, we hoped to identify novel candidate repressors as well as activators of the Wnt/β-cat pathway, which could be further investigated in cell-specific contexts. Additionally, when establishing a screening strategy, there may be concern that the multitude of altered functional pathways and additional dysregulated kinases in colon cancer cell lines could confound ...
Sigma-Aldrich offers abstracts and full-text articles by [Michael T Dellinger, Stryder M Meadows, Katherine Wynne, Ondine Cleaver, Rolf A Brekken].
Background: Ovarian cancer (OVCA) is a lethal malignancy of women with high rate of death among gynecological cancers. Due to the lack of an effective early detection test, OVCA in most cases are detected at late stage. Interleukin (IL)-16 is a cytokine involved in multiple immunopathobiological processes including inflammatory responses and production of proangiogenic cytokines. IL-16 is expressed by malignant epithelium and secreted in serum. Ovarian malignant transformation is followed by neovascularization and vascular endothelial growth factor receptor-2 (VEGFR-2) is a marker of tumor associated neovascularization (TAN). Thus, IL-16 and VEGFR-2 represent markers of OVCA at early stage may constitute an early detection test for OVCA.. Objectives: The goal of this study was to determine whether IL-16 expression is associated with ovarian malignant transformation and to examine association between serum IL-16 levels and VEGFR-2 expression by TAN vessels during ovarian tumor ...
6176 Over the past several years, it has become evident that angiogenesis plays a central role in tumor progression. One treatment approach which attempts to block tumor growth through the disruption of the anigogenic process, is the use of DNA vaccines encoding proteins that are over-expressed during angiogenesis. Two such proteins are vascular endothelial growth factor receptor-2 (Flk1) and platelet derived growth factor receptorβ (PDGFRβ). To assess the efficacy of inhibiting tumor growth by targeting cells expressing these proteins, BALB/c mice were immunized orally with attenuated salmonella thyphimurium carrying plasmid DNA encoding for empty vector, Flk1, PDGFRβ, or both Flk1 and PDGFRβ followed by i.v. tumor challenge with the colon carcinoma cell line CT26. Following challenge, disease severity was significantly reduced in all treatment groups except empty vector vaccinated control mice. Mice immunized with the PDGFRβ vaccine demonstrated a small, but statistically significant ...
Ramucirumab is an IgG1 monoclonal antibody specific for the vascular endothelial growth factor receptor-2. Ramucirumab, 8 mg/kg every 2 weeks, administered as monotherapy (REGARD) or in combination with paclitaxel (RAINBOW), was safe and effective in patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer. We evaluated exposure-efficacy and exposure-safety relationships of ramucirumab from two randomized, placebo-controlled phase III trials. Sparse pharmacokinetic samples were collected, and a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (Cmin,ss). Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the ramucirumab exposure (Cmin,ss)-efficacy relationship to overall survival (OS) and progression-free survival (PFS). Logistic regression analyses were used to evaluate exposure-safety relationships. Analyses included 321 ramucirumab + paclitaxel and 335 placebo + ...
Kinase insert domain receptor (KDR) is one of two main receptors for vascular endothelial growth factor (VEGF). KDR is a type III receptor tyrosine kinase that is the main mediator of VEGF-induced proliferation, survival, migration, and differentiation in endothelial cells. KDR is also known as fetal liver kinase 1 (Flk1), protein-tyrosine kinase receptor flk-1, vascular endothelial growth factor receptor 2 (VEGFR2), CD309, and tyrosine kinase growth factor receptor. Binding of VEGFA, VEGFC, or VEGFD to KDR initiates several signaling cascades, including pathways that involve protein kinase C (PKC), mitogen-activated protein (MAP) kinases, and AKT1 kinase. Mutations in the KDR gene are associated with infantile capillary hemangiomas.. ...
Here, we have studied vascular endothelial growth factor receptor-3 (VEGFR-3) expression in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). Immunohistochemistry revealed that in two-thirds of 34 patients, VEGFR-3 was expressed in situ by both tumor and stromal cells irrespective of the disease stage. The natural VEGFR-3 ligand, VEGF-C, partially protected malignant T-cell lines from growth inhibition by the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA). Whereas the malignant T cells did not produce VEGF-C in vitro, its expression was induced during tumor formation in vivo in a xenograft mouse model of MF. In conclusion, malignant and stromal cells express high levels of VEGFR-3 in all stages of MF. Moreover, malignant T cells trigger enhanced VEGF-C expression in fibroblasts, suggesting that cross-talk between tumor and stromal cells plays a role in lymphangiogenesis and possibly disease progression ...
Asahara et al7 first described early EPCs that mainly consisted of CD34-derived cells and looked as described by Risau and Flamme17 after epiblast induction: round cells at the center and spindle-shaped cells at the periphery with an EC-like phenotype. In consecutive studies, Dil-ac-LDL/lectin-positive cells uptake and lectin labeling emerged as a crucial hallmark to identify putative EPCs after 4 to 7 days.18 These cells express endothelial markers kinase insert domain receptor ([KDR]/vascular endothelial growth factor [VEGF] receptor 2), vascular endothelial cadherin, and von Willebrand factor,19 but cluster formation ceased to be evaluated as criterion. Because of their angiogenic properties and the fact that they are circulating at the time of their isolation, Hirschi et al20 suggested the term "circulating angiogenic cells" to describe this subset of early EPCs. The cultivation of mononuclear cells for 7 days and final assessment of Dil-acetylated-LDL/lectin-positive cells are the standard ...
vegfr3, vascular, endothelial, growth, factor, receptor, 3, VEGFR3 | Vascular endothelial growth factor receptor 3, AS10 1574, Q86W07
Rationale: Fetal Liver Kinase-1 (FLK1) has a recognized role in endothelial cell (EC) formation, migration, and angiogenesis; although, its mechanism of action is not well known.. Hypothesis: NANOG regulates FLK1 expression and therefore EC proliferation and angiogenesis.. Results: We demonstrate that the transcription factor NANOG is expressed in cultured human umbilical cord endothelial cells (HUVECs) and a subset of tumor cell lines. NANOG and FLK1 expression are increased in response to WNT3A stimulation. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA) revealed three NANOG binding sites in the FLK1-promoter DNA sequence. We propose that NANOG binding to these sites activate the FLK1-promoter, thereby its expression in a subset of ECs. Accordingly, FLK1-promoter luciferase assay showed the ability for WNT to activate these three sites and consequently up-regulate EC proliferation. NANOG knockdown resulted in a decrease in FLK1 mediated EC proliferation in ...
Vascular endothelial growth factor (VEGF) signals through VEGF receptor 2 (VEGFR2) to regulate arterial morphogenesis. Noting that mice lacking the scaffolding protein synectin show decreased arterial morphogenesis and that synectin-/- arterial endothelial cells (AECs) have an impaired response to VEGF, Lanahan et al. investigated the role of synectin in VEGFR2 signaling. Comparison of wild-type and synectin-/- AECs revealed no difference in the abundance of total or cell-surface VEGFR2, and their stimulation with VEGF-A elicited similar degrees of VEGFR2 tyrosine residue 1054 (Y1054) phosphorylation, indicating similar VEGFR2 activation. However, VEGF-A-dependent phosphorylation of VEGFR2 Y1175, a residue critical for vasculogenesis, was decreased in synectin-/- AECs, as were downstream signaling events [including extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation]. Full-length synectin rescued phosphorylation of Y1175 and ERK1/2, whereas mutants unable to bind myosin-VI did ...
We present an analysis of a stochastic model of the vascular endothelial growth factor (VEGF) receptor. This analysis addresses the contribution of ligand-binding-induced oligomerization, activation of src-homology 2 domain-carrying kinases and receptor internalization in the overall behaviour of the VEGF/VEGF receptor (VEGFR) system. The analysis is based upon a generalization of a Wentzel-Kramers-Brillouin (WKB) approximation of the solution of the corresponding master equation. We predict that tumour-mediated overexpression of VEGFRs in the endothelial cells (ECs) of tumour-engulfed vessels leads to an increased sensitivity of the ECs to low concentrations of VEGF, thus endowing the tumour with increased resistance to anti-angiogenic treatment. ...
Abstract Postnatal CD34(+) cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assa..
Two critical processes for the growth of solid tumors are tumor cell proliferation and angiogenesis. Increased expression of growth factors and their receptors, particularly EGFR, have been implicated in the progression of gastric cancer (11, 12). Gastric cancer progression is also associated with increased angiogenesis mediated by VEGF/VEGFR (5, 6). This study was undertaken to determine whether targeted therapy directed at these two pathways would have a significant effect on tumor growth in an orthotopic model of gastric cancer. A previous study showed that combining anti-VEGFR and anti-EGFR therapies was more effective than either therapy alone. Therefore, we investigated the ability of ZD6474, a small tyrosine kinase inhibitor with activity against both VEGFR and EGFR, to inhibit gastric cancer growth. In vitro studies confirmed that ZD6474 inhibited both EGFR and VEGFR2 phosphorylation in the presence of EGF or VEGF, respectively. In addition, ZD6474 showed selective inhibition of ...
Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM in cell-free assays. Phase 3.
Kinase insert domain receptor (KDR) is one of two main receptors for vascular endothelial growth factor (VEGF). KDR is a type III receptor tyrosine kinase that is the main mediator of VEGF-induced proliferation, survival, migration, and differentiation in endothelial cells. KDR is also known as fetal liver kinase 1 (Flk1), protein-tyrosine kinase receptor flk-1, vascular endothelial growth factor receptor 2 (VEGFR2), CD309, and tyrosine kinase growth factor receptor. Binding of VEGFA, VEGFC, or VEGFD to KDR initiates several signaling cascades, including pathways that involve protein kinase C (PKC), mitogen-activated protein (MAP) kinases, and AKT1 kinase. Mutations in the KDR gene are associated with infantile capillary hemangiomas.. ...
Recombinant Human soluble Vascular Endothelial Growth Factor Receptor-1 domain D1-4 is produced as a non-chimeric protein in a monomeric form.
A large number of pseudogenes have been found to be transcribed in human cancers. However, only a few pseudogenes are functionally characterized. Here, we identified a transcribed pseudogene of vascular endothelial growth factor receptor-1 (VEGFR1), or fmsrelated tyrosine kinase 1 (FLT1), in human colorectal cancer (CRC) cells. Interestingly, this pseudogene (designated as FLT1P1) was found to be transcribed bidirectionally and functionally modulated cognate VEGFR1 protein expression in the cells. Mechanistically, expression of FLT1P1 antisense transcript not only inhibited the VEGFR1 expression, but also inhibited non-cognate VEGF-A expression through interaction with miR-520a. Perturbation of FLT1P1 expression by RNA interference (RNAi) markedly inhibited tumor cell proliferation and xenograft tumor growth. This study identifies FLT1P1 antisense as a critical regulator of VEGFR1 and VEGF-A expression in CRC cells, and highlights its role in regulation of the pathogenesis of CRC. Implications: ...
The vascular endothelial growth factor (VEGF) family of vascular growth factors in mammals is composed of 5 proteins (VEGFs A-D) and of a closely related placenta growth factor. VEGFs act by binding to 3 closely related receptor tyrosine kinases (VEGFR1-3) and 2 nonkinase receptors, neuropilin (NRP) 1 and 2.1 Specificity of the biological activity of various VEGFs is determined, in part, by preferential binding of certain VEGFs to specific VEGFRs. Thus, VEGF-A and -B and placenta growth factor bind to VEGFR1, VEGF-A, and -C to VEGFR2, and VEGF-C and -D predominantly bind to VEGFR3.2 Specificity is further determined by differential expression of VEGF receptors, with VEGFR1 and VEGFR2 being the predominant isoforms in blood endothelial cells (EC). VEGFR3 is initially expressed during early embryonic development by both blood and lymphatic endothelial cells (LECs) later on becoming largely restricted to LECs.3 However, its expression can be reinduced in blood ECs during angiogenesis,4 and it may ...
The presence of leading tip ECs in growing luteal vessel was identified by immunofluorescent analysis of Dll4 in the ovaries of hormonally stimulated female mice. The effects of Dll4 inhibition on luteal vessels functionality and related corpus luteum function were assessed by administering a Dll4 blocking antibody or placebo to hormonally stimulated female mice.. Main Outcome Measure(s): ...
SIK2 is a multifunctional kinase of the AMPK family which plays a role in CREB1-mediated gene transcription and was recently reported to have therapeutic potential in ovarian cancer. factor and proto-oncogene it was posited that the effects of SIK2 on cell proliferation and viability might be mediated by changes in gene expression. To test this gene expression array profiling was performed and whilst SIK2 knockdown or GW2580 over-expression of LAMNB2 the kinase-dead mutant affected established CREB1 target genes; the overlap with transcripts regulated by forskolin (FSK) the adenylate cyclase/CREB1 pathway activator was incomplete. Implications This study demonstrates that targeting SIK2 genetically or therapeutically could have pleiotropic results on cell routine development and transcription element activation that ought to become accounted for when characterizing SIK2 inhibitors. cells (Agilent Systems) and had been purified using HiSpeed Plasmid Midi Package (Qiagen) relating to ...
Sigma-Aldrich offers abstracts and full-text articles by [Attila Varga, Pál Gyulavári, Zoltán Greff, Krisztina Futosi, Tamás Németh, Laura Simon-Szabó, Krisztina Kerekes, Csaba Szántai-Kis, Diána Brauswetter, Márton Kokas, Gábor Borbély, Anna Erdei, Attila Mócsai, György Kéri, Tibor Vántus].
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key drivers of blood and lymph vessel formation in development, but also in several pathological processes. VEGF-C signaling through VEGFR-3 promotes lymphangiogenesis, which is a clinically relevant target for treating lymphatic insufficiency and for blocking tumor angiogenesis and metastasis. The extracellular domain of VEGFRs consists of seven Ig homology domains; domains 1-3 (D1-3) are responsible for ligand binding, and the membrane-proximal domains 4-7 (D4-7) are involved in structural rearrangements essential for receptor dimerization and activation. Here we analyzed the crystal structures of VEGF-C in complex with VEGFR-3 domains D1-2 and of the VEGFR-3 D4-5 homodimer. The structures revealed a conserved ligand-binding interface in D2 and a unique mechanism for VEGFR dimerization and activation, with homotypic interactions in D5. Mutation of the conserved residues mediating the D5 interaction (Thr446 and Lys516) ...
Vascular endothelial growth factor (VEGF) and its high-affinity receptor, fetal liver kinase 1 (FLK1, also called VEGFR2 or KDR), are essential for formation of the vasculature. Mice lacking a single Vegf allele die at E10.5 owing to defects in the differentiation of endothelial cells and severe disorganization of the vasculature (Carmeliet et al., 1996; Ferrara et al., 1996). Similarly, homozygous Flk1-null embryos die at E8.5-9.5 with severe reduction in endothelial cell number and complete disruption of subsequent vascular development (Shalaby et al., 1995). Since FLK1 is amongst the earliest markers of the endothelial lineage, characterization of transcription mechanisms regulating Flk1 gene expression will help to advance our understanding of the regulatory pathways controlling vascular development.. Mouse transgenic studies have shown that endothelial-specific expression of Flk1 is regulated by an enhancer in the first intron, which contains binding elements for the transcription factors ...
Milroy disease (MD) is an autosomal dominantly inherited primary lymphedema. In 1998, the gene locus for MD was mapped to 5q35.3 and variants in the VEGFR3 (FLT4) gene, encoding vascular endothelial growth factor receptor 3 (VEGFR3), were identified as being responsible for the majority of MD cases. Several reports have since been published detailing pathogenic FLT4 mutations. To date, a total of 58 different variants in FLT4, 20 of which are unpublished, have been observed in 95 families with MD. A review of published mutations is presented in this update. Furthermore, the unpublished variants are presented including clinical data. Comparison of clinical features in patients and their families with the same mutations reveals incomplete penetrance and variable expression, making genotype-phenotype correlations difficult. Most mutations are missense, but a few deletions and one splicing variant have also been reported. Several animal models have confirmed the role of VEGFR3 in lymphangiogenesis ...
The dysregulation of receptor tyrosine kinases (RTKs) in multiple cell types during chronic inflammation is indicative of their pathogenic role in autoimmune diseases. Among the many RTKs, vascular endothelial growth factor receptor (VEGFR) stands out for its multiple effects on immunity, vascularization, and cell migration. Herein, we examined whether VEGFR participated in the pathogenesis of type 1 diabetes (T1D) in nonobese diabetic (NOD) mice. We found that RTK inhibitors (RTKIs) and VEGF or VEGFR-2 antibodies reversed diabetes when administered at the onset of hyperglycemia. Increased VEGF expression promoted islet vascular remodeling in NOD mice, and inhibition of VEGFR activity with RTKIs abrogated the increase in islet vascularity, impairing T-cell migration into the islet and improving glucose control. Metabolic studies confirmed that RTKIs worked by preserving islet function as treated mice had improved glucose tolerance without affecting insulin sensitivity. Finally, examination of ...
Smith, Neil R., Baker, Dawn, James, Neil H., Ratcliffe, Kirsty, Jenkins, Martin, Ashton , Susan E., Sproat, Graham, Swann, Ruth, Gray, Neil, Ryan, Anderson, Jürgensmeier, Juliane M. and Womack, Chris (2010) Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 are localised primarily to vasculature in human primary solid cancers. Clinical Cancer Research, 16 (14). pp. 3548-3561. ISSN 1078-0432 ...
FLT3 (pour « Fms-like tyrosine kinase 3 ») est un récepteur de tyrosine kinase. Son gène est le FLT3. Il est appelé aussi CD 135 ou FLK2 (pour « fetal liver kinase-2 ») Il est exprimé par les cellules souches hématopoïétiques. Sa stimulation diminue lapoptose et active la prolifération de ces dernières. Le TNF alpha et le TGF bêta inhibent son action. Il est également exprimé dans le cœur et aurait un rôle de protection, notamment, en cas dischémie myocardique. Son inhibition via certains antimitotiques pourrait être ainsi une explication à la cardiotoxicité de ces derniers. Son gène est muté dans un tiers des leucémies aiguës myéloblastiques et indicateur de formes plus agressives. Plusieurs antimitotiques ciblent le FLT3 et sont utilisés dans le traitement des leucémies aiguës. ↑ a et b (en) Veiby OP, Jacobsen FW, Cui L, Lyman SD, Jacobsen SE, « The flt3 ligand promotes the survival of primitive hemopoietic progenitor cells with myeloid as well as B lymphoid ...
VEGF Receptor 2山羊多克隆抗体(ab10972)可与小鼠, 大鼠, 狗样本反应并经WB, IHC, ICC, Neut, Flow Cyt, I-ELISA, BL, ICC/IF实验严格验证,被9篇文献引用…
VEGF Receptor 2兔多克隆抗体(ab5475)可与小鼠, 人样本反应并经WB实验严格验证,被6篇文献引用。所有产品均提供质保服务,中国75%以上现货。
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Is of particular interest to analyze which of these functions are controlled by the sets of maternally and MedChemExpress ZK-36374 paternally expressed genes,
A vascular endothelial growth factor expressed in a variety of tissues. It binds with high specificity to VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 and NEUROPILIN-1 ...
Vascular endothelial growth factor (VEGF) activated angiogenesis is crucial for endochondral ossification occurring during bone tissue development and bone tissue repair. are likely involved in matrix mineralization. Within this paper we analyzed the consequences of hypoxia (1% O2) and VEGF over the appearance of AnxA2 in osteoblastic MC3T3-E1 cells. Hypoxia desferrioxamine (hypoxia mimetic) and recombinant VEGF all elevated AnxA2 mRNA and proteins amounts in osteoblastic cells. The hypoxia-induced upsurge in AnxA2 was inhibited with a preventing antibody to VEGF-R1 nevertheless VEGF120 a VEGF-R1 agonist showed no impact upon appearance. This shows that VEGF induction of Annexin A2 isnt mediated VEGF-R1 agonism by itself but by VEGF-R1 and Neuropilin-1 or Neuropilin-2 heterodimers. Additionally we demonstrated that VEGF-stimulated changes in AnxA2 expression with a pathway involving MEK and Src kinase. These data show that AnxA2 manifestation in osteoblasts can be beneath the control of VEGF ...
Relationship Between Vascular Endothelial Growth Factor and Left Ventricular Dimension in Patients With Acute Myocardial Infarction.Relationship Between Vascular Endothelial Growth Factor and Left Ventricular Dimension in Patients With Acute Myocardial Infarction. ...
In the early 1970s (1) , Folkman hypothesized that solid tumor growth and metastasis are critically dependent on angiogenesis, the formation of new blood vessels from preexisting vasculature. Over the past few decades, many mediators of angiogenesis have been characterized, providing new and important targets for drug discovery research. Considerable effort has been directed toward the development of pharmacological agents that modulate specific pathways associated with angiogenesis.. Among the many known triggers of tumor angiogenesis, VEGF6 has emerged as a relatively specific effector (2 , 3) . In fact, VEGF expression has been observed in many human tumor types (4, 5, 6, 7, 8, 9, 10) , is up-regulated in response to hypoxia (11 , 12) , and has been specifically linked with tumor neovascularization (13, 14, 15) . Tumor cells engineered to express VEGF constitutively exhibit enhanced tumor growth and angiogenic phenotypes (16) . Conversely, treatments with anti-VEGF monoclonal antibodies have ...
Yasuhara, T., Shingo, T., Kobayashi, K., Takeuchi, A., Yano, A., Muraoka, K., Matsui, T., Miyoshi, Y., Hamada, H. and Date, I. (2004), Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinsons disease. European Journal of Neuroscience, 19: 1494-1504. doi: 10.1111/j.1460-9568.2004.03254.x ...
Naturally-occurring endogenous electric fields (EFs) have been detected at skin wounds damaged tissue sites and vasculature. cells also align and elongate in an EF. Inhibition of vascular endothelial growth factor (VEGF) receptor signalling completely abolished the EF-induced directional migration of the progenitor cells. We conclude that EFs TC-H 106 are an effective signal that guides EPC migration through VEGF receptor signalling and genetic studies with mouse models. Progenitor cell marker CD133 and endothelial cell markers VEGFR-2 and von Willebrand Factor (vWF) were TC-H 106 used to confirm the endothelial progenitor cell nature. These combined proteins are the markers used to identify EPCs. We confirmed that the three cell lines (MFLM-4 AEL-deltaR1 and AEL-deltaR1/Runx1) are all positive with specific stem cell marker-CD133 and endothelial cell markers-vWF and VEGFR-2 (Fig. 1). Figure 1 Expression of progenitor markers 2.2 Directed migration of the progenitor cells by EFs MFLM-4 cells ...
QSAR model predictions should not be trusted if the query compound is outside of the applicability domain of the model (i.e., if the query compound is dissimilar to the training dataset compounds). more.. ...
Vascular endothelial growth factor (VEGF) and platelet (PF-4) factor 4 inputs modulate human microvascular endothelial signaling in a three-dimensional matrix migration context. ...
TRC105 (carotuximab) is a monoclonal antibody to endoglin (CD105), an essential angiogenic target highly expressed on tumor vessels that is distinct from VEGFR. Endoglin is also expressed directly on tumor cells in angiosarcoma and is upregulated following VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR.. Pazopanib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR tyrosine kinase inhibitors (TKIs) and could represent a major advance in the treatment of angiosarcoma. Together, the use of TRC105 with ...
TRC105 (carotuximab) is a monoclonal antibody to endoglin (CD105), an essential angiogenic target highly expressed on tumor vessels that is distinct from VEGFR. Endoglin is also expressed directly on tumor cells in angiosarcoma and is upregulated following VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR.. Pazopanib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR tyrosine kinase inhibitors (TKIs) and could represent a major advance in the treatment of angiosarcoma. Together, the use of TRC105 with ...
The Vegf family is composed of several ligands (Vegfa, b, c, d, and e, and Placental growth factor), each of which has a particular preference for 1 of 3 endothelial-expressed receptors (Vegfr-1/Flt1, Vegfr-2/Flk1/Kdr, and Vegfr-3/Flt4).9 Regarding vascular development, Vegfa is the most functionally significant and well-characterized member of the Vegf family. Upon binding to its receptor tyrosine kinase, Vegfr-2, Vegfa can elicit distinct responses, including proliferation, cell survival, permeability, differentiation, and migration.9 These effects are mediated through the activation of several downstream signaling effectors.9 Homozygous deletion of Vegfr-2,26 much like deletion of its ligand,10,11 results in an absence of blood vessels and lethality in mice. Vegfr-3, which becomes almost exclusive to lymphatic ECs during late development,27 is also expressed on vascular endothelial tip cells during embryonic and postnatal angiogenesis, and responds to Vegfc and Vegfd.28,29 Vegfr-3 deletion ...
Notre laboratoire a démontré que la capacité proinflammatoire du vascular endothelial growth factor (VEGF-A165) implique la synthèse endothéliale du facteur dactivation plaquettaire (PAF) via lactivation du récepteur tyrosine kinase homodimérique VEGFR-2/R-2. La synthèse du PAF requiert lactivation de la p38 MAPK et p42/44 MAPK qui activent la phospholipase A2 secrétée de type V (sPLA2-V). Nous avons découvert que la synthèse aigue de prostacycline (PGI2) induite par le VEGF-A165 requiert lactivation des récepteurs hétérodimériques VEGFR-1/R-2. Lactivation sélective des récepteurs du VEGF peut donc agir comme balance dans la synthèse de facteurs pro-(PAF) et anti-(PGI2) inflammatoire. Cependant, les tyrosines impliquées dans la transphosphorylation de VEGFR-2/R-2 menant à la synthèse du PAF sont inconnues. Par mutagenèse dirigée, nous avons effectué des transfections transitoires de cellules endothéliales avec des plasmides codant pour le VEGFR-2 dont les tyrosines ...
Rationale: The density of native (pre-existing) collaterals varies widely and is a significant determinant of variation in severity of stroke, myocardial infarction and peripheral artery disease. However, little is known about mechanisms responsible for formation of the collateral circulation in healthy tissues. Objective: We previously found that variation in VEGF expression causes differences in collateral density of newborn and adult mice. Herein, we sought to determine mechanisms of collaterogenesis in the embryo and the role of VEGF in this process. Methods and Results: Pial collaterals begin forming between embryonic day (E) 13.5 and 14.5 as sprout-like extensions from arterioles of existing cerebral artery trees. Global VEGF-A overexpressing mice (Vegf hi/+) formed more-and Vegf lo/+ formed fewer-collaterals during embryogenesis, in association with differences in vascular patterning. Conditional global reduction of Vegf or Flk1 only during collaterogenesis significantly reduced ...
It has been reported that median survival duration of Indian ALS patients is ~9 years after disease onset which is significantly higher as compared to their Western counterparts who survive for 3-6 years after disease onset [6-8]. Because of this contradicting presentation, we investigated the levels of VEGF-A and CCL2 among the Indian ALS patients.. The increased PBMCs VEGF-A and CCL2 expression in our patients may suggest the pathophysiological involvement of circulating monocytes and lymphocytes in ALS. The elevated PBMCs VEGF-A is in contrast to previous reports where a profound downregulation of VEGF-A mRNA in SOD1G93A ALS mouse and significantly reduced serum and cerebrospinal fluid (CSF) VEGF-A in ALS patients was observed possibly because of genetic changes in promoter regions [15-17]. Increased serum and CSF VEGF-A reported earlier in ALS and in its different clinical subtype with limb onset and extended disease duration are in agreement with current results [18, 19]. However, some ...
3.0.CO;2-P, PMID 11550156. Strausberg RL, Feingold EA, Grouse LH, et al., Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences., in Proc. Natl. Acad. Sci. U.S.A., vol. 99, nº 26, 2003, pp. 16899-903, DOI:10.1073/pnas.242603899, PMC 139241, PMID 12477932. Ota T, Suzuki Y, Nishikawa T, et al., Complete sequencing and characterization of 21,243 full-length human cDNAs., in Nat. Genet., vol. 36, nº 1, 2004, pp. 40-5, DOI:10.1038/ng1285, PMID 14702039. Dunham A, Matthews LH, Burton J, et al., The DNA sequence and analysis of human chromosome 13., in Nature, vol. 428, nº 6982, 2004, pp. 522-8, DOI:10.1038/nature02379, PMC 2665288, PMID 15057823. Shao R, Bao S, Bai X, et al., Acquired expression of periostin by human breast cancers promotes tumor angiogenesis through up-regulation of vascular endothelial growth factor receptor 2 expression., in Mol. Cell. Biol., vol. 24, nº 9, 2004, pp. 3992-4003, DOI:10.1128/MCB.24.9.3992-4003.2004, PMC 387763, PMID ...
This test measures the amount of a substance in your body that helps new blood vessels form. The test can help monitor cancer treatment.
Khushbu K Patel, Hiroyuki Miyoshi, Wandy L Beatty, Richard D Head, Nicole P Malvin, Ken Cadwell, Jun‐Lin Guan, Tatsuya Saitoh, Shizuo Akira, Per O Seglen, Mary C Dinauer, Herbert W Virgin, Thaddeus S Stappenbeck ...
Here, we showed that the majority of sVEGF-R1 is retained in the vicinity of the producing cell in spite of it being a secreted protein. Further, we showed that pericellular retention of this natural VEGF decoy receptor is mediated through its high affinity binding to HS and that its release is controlled at least in part by heparanase.. Existence of tissue depots of sVEGF-R1 provide a basis for the notion that the primary physiological role of sVEGF-R1 is to sequester VEGF locally thereby granting the producing cell protection against unwarranted VEGF signaling. Thus, it can be argued that the abundant presence of sVEGF-R1 in the vessel wall shown here has a functional role in protecting VSMCs from adverse VEGF signaling. Consistent with this proposition is our previous observation that the mRNA transcribed from the VEGF-R1 locus in VSMCs is spliced in a mode yielding exclusively sVEGF-R115 (but not the signaling transmembrane receptor) and results shown here that only sVEGF-R1 protein is ...
Purpose Investigate the systems of rules and part connected with EZH2 manifestation in lung malignancy cells. Summary Our outcomes recommend that VEGF/VEGFR-2 path takes on a part in rules of EZH2 manifestation via At the2N3, HIF-1 and in different malignancy cell lines; particularly, overexpression of an imitate downregulates manifestation of EZH2 (9C11). Although upregulation of …Read More. ...
Mouse Monoclonal Anti-VEGF R2/KDR/Flk-1 Antibody (KDR721) [HRP]. Hemangioblast Marker. Validated: ELISA, IHC-Fr. Tested Reactivity: Human. 100% Guaranteed.
Vegfa - Vegfa (untagged ORF) - Rat vascular endothelial growth factor A (Vegfa), transcript variant 2, (10 ug) available for purchase from OriGene - Your Gene Company.
Vascular Endothelial Growth Factor (VEGF) umschreibt eine Unterfamilie von Waschtumsfaktoren, die als Signalmolekül die Bildung und das Wachstum von Blutgef...
1BJ1: VEGF and the Fab fragment of a humanized neutralizing antibody: crystal structure of the complex at 2.4 A resolution and mutational analysis of the interface.
Immunohistochemical staining of the VEGFR-1 ligands and pVEGFR-1 in the vasculature of CC tissue. (A) Characteristic endothelial VEGF expression. VEGF positive
S and cancers. This study inevitably suffers a couple of limitations. Despite the fact that the TCGA is among the biggest multidimensional studies, the powerful
Purpose : Gremlin is a bone morphogenic protein antagonist and also a direct agonist of vascular endothelial growth factor receptor 2 (VEGFR2), a major proangiogenic receptor. Gremlin was reported to be expressed in the retina of non-diabetic and diabetic mice. However, the role of gremlin in retinal angiogenesis has not been reported. We investigated the angiogenic effect of gremlin in human endothelial cells and examined the expression in a mouse model of oxygen-induced retinopathy (OIR). Methods : Tube formation assays were performed using human umbilical vein endothelial cells (HUVEC) and human retinal microvascular endothelial cells (HRMEC) to determine the angiogenic activity of gremlin compared to VEGF. In brief, HUVEC and HRMEC treated either with VEGF (10 and 100 ng/ml) or gremlin (10 and 100 ng/ml) were seeded and the tubular structures were manually quantified. Also, the effect of adding tanibirumab, a fully human monoclonal antibody against VEGFR2, was examined in HUVEC and HRMEC. ...
Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p<0.01); resistance to ...
Title:Targeting Vascular Endothelial Growth Factor in Neuroblastoma. VOLUME: 2 ISSUE: 1. Author(s):Danielle Hsu, Jason M. Shohet and Eugene S. Kim. Affiliation:Division of Pediatric Surgery, Texas Childrens Hospital, CCC Building, Suite 1210, 6701 Fannin St, Houston, TX 77030, USA.. Keywords:Vascular endothelial growth factor, angiogenesis, clinical trials, neuroblastoma.. Abstract:Angiogenesis is critical to tumor growth and metastasis and is dependent on growth factors, such as vascular endothelial growth factor (VEGF). The most characterized angiogenic factor, VEGF is an endothelial cell mitogen and permeability factor that has been found to be overexpressed in almost all human cancers. In a number of tumor model systems, antagonism of the VEGF pathway results in inhibition of angiogenesis and tumor growth. Specifically, VEGF inhibition has been shown to suppress tumor growth, decrease microvasculature, and induce apoptosis of endothelial cells. This close relationship between hypoxia, ...
OBJECTIVES: - Determine if elevated levels of thrombospondin I serum levels, vascular endothelial growth factor receptor I, fibroblast growth factor, transforming growth factor, and mesothelin portend a poor prognosis in patients with unresectable malignant mesothelioma treated with vatalanib on protocol CALGB-30107. - Determine if elevated levels of thrombospondin I serum levels, vascular endothelial growth factor receptor I, fibroblast growth factor, transforming growth factor, and mesothelin correlate with response or stable disease in these patients. OUTLINE: Serum samples previously obtained from patients on protocol CALGB-30107 are tested for levels of thrombospondin I serum, vascular endothelial growth factor receptor I, fibroblast growth factor, transforming growth factor, and mesothelin using enzyme-linked immunosorbent assays (ELISA). PROJECTED ACCRUAL: A total of 47 specimens will be accrued for this study. ...
Vascular endothelial growth factor A (VEGF-A) is a protein that in humans is encoded by the VEGFA gene. This gene is a member of the platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) family and encodes a protein that is often found as a disulfide linked homodimer. This protein is a glycosylated mitogen that specifically acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis, vasculogenesis and endothelial cell growth, promoting cell migration, and inhibiting apoptosis. Alternatively spliced transcript variants, encoding either freely secreted or cell-associated isoforms, have been characterized. VEGF-A shows prominent activity with vascular endothelial cells, primarily through its interactions with the VEGFR1 and -R2 receptors found in prominently on the endothelial cell membrane. Although, it does have effects on a number of other cell types (e.g., stimulation monocyte/macrophage migration, ...
Angiogenesis, the growth of blood vessel from the existing vasculature, depends on the expression of various growth factors but Vascular Endothelial Growth factor (VEGF) ranks as the key inducer and the central mediator that promotes vascular permeability.
Angiogenesis inhibitors used as part of chemotherapy regimens improve outcomes for patients with several types of malignancies.21,22 However, hypertension has emerged as a common adverse effect of VEGF inhibition. These clinical observations have revealed a somewhat unexpected role for VEGF-associated signaling pathways to modulate BP. However, the mechanisms underlying the control of BP by VEGF have not been precisely defined. Elucidating these mechanisms will provide novel physiological insights but could also have clinical use for developing regimens to minimize the risk of significant hypertension, optimizing targeted antihypertensive drug therapies, and identifying those patients most susceptible to hypertension.. In clinical trials, hypertension has been observed after treatment with neutralizing antibodies against VEGF, as well as small molecules that inhibit multiple tyrosine kinase receptors, including the VEGF receptors and platelet-derived growth factor receptors. However, a precise ...
Vascular endothelial growth factor (VEGF) is definitely 1 of the many essential angiogenic growth factors for tumor angiogenesis. growth angiogenesis in MMP-2 suppressed growth areas was associated with decreased co-localization of MMP-2 and integrin-V3. In overview, these data offer fresh information into the systems root MMP-2-mediated VEGF appearance in lung growth angiogenesis. and versions. Our results reveal that MMP-2 transcriptional inactivation decreased integrin-V3-mediated considerably, PI3E/AKT-induced VEGF appearance, which reduced tumor cell-induced angiogenesis ultimately. Components AND Strategies Cells and Reagents A549 and L1299 lung adenocarcinoma cells had been cultured in RPMI 1640 (ATCC Manassas, Veterans administration) supplemented with 10% fetal bovine serum (Invitrogen, Carlsbad, California), 50 devices/mL penicillin, and 50 g/mL streptomycin (Existence Systems, Inc., Frederick, MD). For human being microvascular skin endothelial cells (HMEC-1), glutamine, EGF buy ...
Previous work showed that connexin 43 (Cx43) reduced the expression of hypoxic-induced factor-1α (HIF-1α) in astrocytes. HIF-1α is a master transcription factor for angiogenesis in tumor. Angiogenesis is essential for tumor progression. Here, we investigated the role of Cx43 in vascular endothelial growth factor (VEGF) production and angiogenesis in murine tumor. In the study, mouse B16F10 and 4T1 cells were overexpressed or knockdown with Cx43. The expression profiles as well as activity of the treated cells were examined. Furthermore, reduced Cx43 expression in B16F10 and 4T1 cells causes increased expression of VEGF and enhanced the proliferation of endothelial cells. On the contrary, the expression of VEGF and the proliferation of endothelial were increased in the conditioned medium of Cx43-knockdown tumor cells. We subcutaneously transplanted Cx43-overexpressing B16F10 cells into mice to evaluate the roles of Cx43 in the tumor angiogenesis. Both tumor size and the number of vessels growing in
Context:Multiple genes and proteins have been shown to be important in treatment and prognosis of breast cancer, including the estrogen and progesterone receptors and Her-2 neu. Vascular endothelial growth factor (VEGF) subtypes have been shown to be associated with lympho-vascular invasion, lymph node metastases and prognosis in multiple types of cancer, including colon cancer, gastric cancer and breast cancer. The goal of this project was to observe and quantify the protein expression of VEGF subtypes in human breast cancer, then correlate this with known clinicopathologic information. Design:Ninety grade three (high grade) invasive ductal carcinomas received over a four year period (1997-2001) were selected from our files. Immunohistochemistry was performed on formalin fixed paraffin embedded tissue of both primary tumor and lymph node metastasis when applicable using VEGF-A, VEGF-C, VEGF-D and VEGF-R (the VEGF receptor) antibodies. The staining was graded from zero (no expression) to 3+ (high
The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role
Objective: A major shortcoming of traditional mouse models based on xenografted human glioblastoma cells is that tumor cells do not invade. Another deficit is that genetic alterations, such as amplification of the epidermal growth factor receptor (EGFR), are typically not maintained in glioma cell lines and xenografts derived thereof. These models are therefore of limited value for preclinical therapeutic studies.. Methods: We established a highly invasive orthotopic mouse model using freshly resected glioblastoma tissue, briefly cultured as spheroids and injected into the brains of nude mice. Animals were treated for 4 weeks with either interstitial infusion of a monoclonal antibody against the EGFR (antibody C225) or with intraperitoneal injections of an antibody against the vascular endothelial growth factor receptor-2 (VEGFR-2, antibody DC101). Tumor extension was measured using image analysis on H&E-stained serial sections, defining 36 landmark points at 6 different coronal levels with 6 ...
The vascular endothelial growth factor 165 (VEGF165) is the predominant form of thecomplex VEGF family. This glycoprotein has, among others, an angiogenic effect inmany physiological and pathological events. For this reason, its roles as a biomarker andas a therapeutic drug have been considered. However, very little is known about theexistence of different forms of VEGF165 arising from glycosylation and other potentialPTMs. This aspect is crucial because it is known that for other glycoproteins the ratiobetween these isoforms actually acts as a biomarker for certain diseases and otherphysiological states. In addition, for therapeutic use of glycoproteins it is known that thebiological activity may differ for the various isoforms. In this work CE methods toseparate up to seven peaks without baseline resolution containing various forms ofVEGF165 are developed. Using a computer program previously developed in-house peakassignment could be performed with accuracy close to 100%. In this way, ...
Increasing evidence suggests that cerebral vascular dysfunction is associated with the early stages of Alzheimers disease (AD). Vascular endothelial growth factor (VEGF) is one of the key players involved in the development and maintenance of the vasculature. Here, we hypothesized that VEGF levels in cerebrospinal fluid (CSF) may be altered in AD patients with vascular involvement, characterized by the presence of microbleeds (MB), and in vascular dementia (VaD) patients compared to controls. VEGF levels were determined by electrochemilumiscence Meso Scale Discovery (MULTI-SPOT Assay System) in CSF from age-matched groups of controls with subjective cognitive decline (n = 21), AD without MB (n = 25), AD with MB (n = 25), and VaD (n = 21) patients. The average level of VEGF in the different groups was 2.8 ± 1 pg/ml CSF. Adjusted for age and gender, no significant differences were detected between groups (p | 0.5). However, we detected a significant correlation between the concentration of VEGF in the
Little is known about the presence, frequency, and in vivo proliferative potential of stromal cells within blood-derived hematopoietic transplants. In this study, nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were injected with human CD34(+) peripheral blood cells (PBCs) or cord blood cells (CBCs, either enriched for CD34 or density-gradient separated mononuclear cells). Flow cytometric analysis 5 to 11 weeks after transplantation revealed the presence of a human lymphomyeloid hematopoiesis within the murine bone marrow. Immunohistochemical staining of bone marrow cell suspensions using human-specific antibodies showed human cells staining positive for human fibroblast markers, human von Willebrand factor (vWF) and human KDR (vascular endothelial growth factor receptor-2) in mice transplanted with CD34(+) PBCs or CBCs, with mean frequencies between 0.6% and 2.4%. In stromal layers of bone marrow cultures established from the mice, immunohistochemical staining using ...
Vascular endothelial growth factor (VEGF) plays a crucial role in cancer cell growth and tumor expansion. Inhibition of VEGF overexpression offers a potential target for cancer therapy. Dr. Bai will identify nanoparticle based small interfering RNAs (SiRNAs) for targeting prevention of VEGF expression in lung tumors. This work will aim at providing important new data on a safe and effective therapeutic approach to lung cancer using gene therapy and nanotechnology to improve the effectiveness of the treatment efficacy while limiting the toxicity.
Significantly higher expression of vascular endothelial growth factor (VEGF) and shorter survival after recurrences in premenopausal node negative patients with triple negative breast cancer in CANCER RESEARCH, vol 69, issue 2, pp 128S-129S ...
Objectives: This study is looking at the level of vascular endothelial growth factor (VEGF) circulating in the blood stream of patients diagnosed with e
Rab GTPases are implicated in endosome-to-plasma membrane recycling, but how such membrane traffic regulators control vascular endothelial growth factor receptor 2 (VEGFR2/KDR) dynamics and function are not well understood. Here, we evaluated two different recycling Rab GTPases, Rab4a and Rab11a, in regulating endothelial VEGFR2 trafficking and signalling with implications for endothelial cell migration, proliferation and angiogenesis. In primary endothelial cells, VEGFR2 displays co-localisation with Rab4a, but not Rab11a GTPase, on early endosomes. Expression of a guanosine diphosphate (GDP)-bound Rab4a S22N mutant caused increased VEGFR2 accumulation in endosomes. TfR and VEGFR2 exhibited differences in endosome-to-plasma membrane recycling in the presence of chloroquine. Depletion of Rab4a, but not Rab11a, levels stimulated VEGF-A-dependent intracellular signalling. However, depletion of either Rab4a or Rab11a levels inhibited VEGF-A-stimulated endothelial cell migration. Interestingly, depletion of
Cholangiocarcinoma (CCA) is a form of cancer that easily aggress to contiguous structures. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) are increased in majority species of cancers and suppress tumor progression by blocking VEGF/VEGFR2. Apatinib is a highly selective VEGFR2 antagonist which has inhibitive effect on antiapoptotic and cell growth in CCA. While, the effect of apatinib cell migration and invasion in CCA is still unknown. CCA cell lines QBC939 and TFK-1 were transfected with siKDR to establish the KDR function loss cell model, and recombined human VEGF (rhVEGF) protein was added into the culture medium to enhance the VEGF expression. RT-qPCR and western bloting were used to detect the mRNA and protein expression levels of VEGFR2 to investigate whether it was effectively repressed or activated with rhVEGF or apatinib treatment. Then, MTT, wound healing assay, and transwell matrix assay were applied to measure the effect of apatinib and rhVEGF on cell viability,
Results Compared with placebo, G-CSF had no effect on myocardial ischaemia by cardiac MRI, EST or SAQ/UBQ-H, despite effective EPC mobilisation (peak fold increase: CD34+=19, CD34+CD133+=37, CD34+ vascular endothelial growth factor receptor 2 (VEGFR-2)+=5, CD34+CD133+VEGFR-2+=3; all p,0.05 vs placebo). Plasma levels of stromal cell derived factor 1, angiopoietin 1, interleukin 8 and tumour necrosis factor α decreased after a symptom limited EST while vascular endothelial growth factor and platelet derived growth factor remained unchanged. All cytokines were unchanged following G-CSF. Seven troponin I positive events occurred with G-CSF compared with three with placebo (p=0.289). High sensitivity C reactive protein and N terminal prohormone brain natriuretic peptide increased with G-CSF (both p,0.01 vs placebo). ...
Vascular endothelial growth factor (VEGF) was originally identified as an endothelial cell specific growth factor stimulating angiogenesis and vascular permeability. Some family members, VEGF C and D, are specifically involved in lymphangiogenesis. It now appears that VEGF also has autocrine functions acting as a survival factor for tumour cells protecting them from stresses such as hypoxia, chemotherapy and radiotherapy. The mechanisms of action of VEGF are still being investigated with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins which were not previously associated with angiogenesis. VEGF plays an important role in embryonic development and angiogenesis during wound healing and menstrual cycle in the healthy adult. VEGF is also important in a number of both malignant and non-malignant pathologies. As it plays a limited role in normal human physiology, VEGF is an attractive therapeutic target in diseases where VEGF plays a key role. It was
Historically, VEGFR-1 was assigned a role as a nonsignaling decoy receptor because of the low activity and embryonic dispensability of its tyrosine kinase function. More recently, its role has become more interesting because VEGFR-1 signaling has been reported both to promote (6, 7) and suppress (8) VEGF-A-driven angiogenesis. We report not only that PlGF-1 inhibits inflammatory CNV, extending the scope of VEGFR-1 function, but also what we believe is the unprecedented observation that VEGF-A itself can suppress angiogenesis. Multiple lines of evidence emerging from genetic ablation, antibody neutralization, and receptor-selective ligand activation all strongly support the thesis that the antiangiogenic action of VEGF-A is mediated by VEGFR-1. Previously, VEGF-A has been reported to reduce VEGF-E-induced VEGFR-2 tyrosine kinase phosphorylation in capillary endothelial cells in vitro, raising the provocative hypothesis that VEGF-A could limit its own angiogenic activity through VEGFR-1 (29). We ...
TY - JOUR. T1 - Coffee induces vascular endothelial growth factor (VEGF) expression in human neuroblastama SH-SY5Y cells. AU - Kakio, Shota. AU - Tago, Megumi. AU - Kobata, Kenji. AU - Tamura, Hiroomi. PY - 2016/1/21. Y1 - 2016/1/21. N2 - Recent evidence indicates that hypoxia-inducible vascular endothelial growth factor (VEGF) has neurotrophic and neuroprotective effects on neuronal and glial cells. On the other hand, recent epidemiological studies showed that daily coffee consumption has been associated with a lower risk of several neuronal disorders. Therefore, we investigated the effect of coffee on VEGF expression in human neuroblastoma SH-SY5Y cells. We found that even low concentration of coffee (. AB - Recent evidence indicates that hypoxia-inducible vascular endothelial growth factor (VEGF) has neurotrophic and neuroprotective effects on neuronal and glial cells. On the other hand, recent epidemiological studies showed that daily coffee consumption has been associated with a lower risk ...
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Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema. To assess the role of vascular endothelial growth factor in eosinophilic meningitis, vascular endothelial growth factor was measured in the cerebrospinal fluid (CSF) and blood of 9 patients with eosinophilic meningitis in a cohort study. VEGFCSF was detected in 8 (90%) of 9 eosinophilic meningitis patients (range, 45-2190 pg/mL) at presentation. The mean VEGFCSF at presentation, 1 week, and 2 weeks after admission was 568 pg/mL, 751 pg/mL, and 1031 pg/mL, respectively. There was an association between VEGFCSF, CSF protein, white cell count, and eosinophil counts. The VEGFSERUM fluctuated during the 6-month follow-up period. These results indicate that vascular endothelial growth factor may be associated with blood-brain barrier disruption in patients with eosinophilic meningitis.
TY - JOUR. T1 - Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model. AU - Perry, Kyle A.. AU - Enestvedt, Charles. AU - Hosack, Luke W.. AU - Pham, Thai H.. AU - Diggs, Brian S.. AU - Teh, Swee. AU - Orloff, Susan. AU - Winn, Shelly. AU - Hunter, John. AU - Sheppard, Brett. PY - 2010/5. Y1 - 2010/5. N2 - Background Vascular endothelial growth factor (VEGF) is overexpressed in hepatocellular carcinoma (HCC), and findings have shown that its upregulation in these tumors has an impact on tumor growth. The authors hypothesized that compared with open liver resection, laparoscopic hepatectomy would result in a decreased local angiogenic response in residual tumor cells. Methods Right- and left-lobe hepatomas were induced in Buffalo rats via laparoscopically guided subcapsular injection of Morris hepatoma cells. After 1 week, the animals were randomized to laparoscopic or open left lateral ...
Table of Contents. Table of Contents 2. List of Tables 5. List of Figures 5. Introduction 6. Global Markets Direct Report Coverage 6. Placenta Growth Factor (Vascular Endothelial Growth Factor Related Protein or PGF) Overview 7. Therapeutics Development 8. Placenta Growth Factor (Vascular Endothelial Growth Factor Related Protein or PGF)-Products under Development by Stage of Development 8. Placenta Growth Factor (Vascular Endothelial Growth Factor Related Protein or PGF)-Products under Development by Therapy Area 9. Placenta Growth Factor (Vascular Endothelial Growth Factor Related Protein or PGF)-Products under Development by Indication 10. Placenta Growth Factor (Vascular Endothelial Growth Factor Related Protein or PGF)-Pipeline Products Glance 11. Late Stage Products 11. Early Stage Products 12. Placenta Growth Factor (Vascular Endothelial Growth Factor Related Protein or PGF)-Products under Development by Companies 13. Placenta Growth Factor (Vascular Endothelial Growth Factor Related ...

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  • Enrollment is currently underway in a Phase 1b/2 DEDUCTIVE study of tivozanib in combination with IMFINZI ® (durvalumab), AstraZeneca's human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with HCC who have not received prior systemic therapy. (businesswire.com)
  • LeTx is a binary toxin ordinarily secreted by Bacillus anthracis and is composed of two proteins: protective antigen (the binding moiety) and lethal factor (the active moiety). (elsevier.com)
  • Results: Significant decrease of serum Ang-2 and the increase of sFlt-1 were observed in women with preeclampsia as compared to healthy pregnant women. (elsevier.com)
  • 4 used murine cancer cell lines to show that treatment with an mAb against VEGFA decreased tumor growth, indicating a potential therapeutic role for VEGFA inhibition in cancer treatment. (asnjournals.org)
  • Conclusions: These data support a role for MKK signaling in tumor growth and vascularization and are consistent with the hypothesis that inhibition of MKK signaling by LeTx or a similar agent may be an effective strategy for the treatment of Kaposi's sarcoma as well as other vascular tumors. (elsevier.com)
  • This study is an important steppingstone in understanding tivozanib's safety and efficacy in HCC, and was the foundation for our ongoing Phase 1b/2 DEDUCTIVE study of tivozanib in combination with IMFINZI ® (durvalumab). (businesswire.com)
  • The serum sFlt-1/Ang-2 ratio was strikingly increased in preeclamptic women in contrast to healthy pregnant women exhibiting lower value similar to non-pregnant women. (elsevier.com)
  • While intermittent hypoxic training (IHT) has been reported to evoke cellular responses via hypoxia inducible factors (HIFs) but without substantial performance benefits in endurance athletes, we hypothesized that repeated sprint training in hypoxia could enhance repeated sprint ability (RSA) performed in normoxia via improved glycolysis and O(2) utilization. (nih.gov)
  • Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models 3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC 4 . (businesswire.com)
  • Before (Pre-) and after (Post-) training, muscular levels of selected mRNAs were analyzed from resting muscle biopsies and RSA tested until exhaustion (10-s sprint, work-to-rest ratio 1:2) with muscle perfusion assessed by near-infrared spectroscopy. (nih.gov)
  • 0.25 in the serum sFlt-1/Ang-2 ratio showed 87.1% sensitivity and 82.8% specificity in differentiating preeclamptic women from healthy pregnant women. (elsevier.com)
  • Conclusion: The serum sFlt-1/Ang-2 ratio is significantly elevated in preeclamptic women as compared to healthy pregnant women. (elsevier.com)
  • Remarkable difference of sFlt-1/Ang-2 ratio between these two groups with excellent specificity and sensitivity suggests the clinical usefulness of the serum sFlt-1/Ang-2 ratio in diagnosing and potentially predicting the onset of preeclampsia. (elsevier.com)
  • The article, titled "A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma," is available online first via this link . (businesswire.com)
  • The recommended Phase 2 dose (RP2D) was determined to be 1.0 mg once daily for 21 days followed by 7 days off treatment on a 28-day cycle. (businesswire.com)
  • 1,2 Tivozanib is being studied in the TIVO-3 trial, which is intended to support a regulatory submission of tivozanib in the U.S. as a treatment for relapsed/refractory RCC. (businesswire.com)
  • ZD6474 in combination with two standard modalities in the treatment of malignant glioma, radiotherapy and chemotherapy, markedly decreased the growth of an intracerebral experimental glioma. (diva-portal.org)
  • The predictive power of MedusaDock in cross-docking and preliminary virtual-screening benchmarks highlights the importance to model both ligand and receptor flexibility simultaneously in computational docking. (elsevier.com)
  • The effects on glioma growth were investigated in the intracerebral BT4C rat glioma model. (diva-portal.org)
  • For the Phase 1b/2 tivozanib study, a total of 27 patients were enrolled. (businesswire.com)
  • Unfortunately, by 2 years, the majority of patients with stage IV lung cancer show disease progression, in spite of whatever promising experimental agent they may have received. (ascopost.com)
  • Median overall survival was 3.5 years for the 260 patients with an oncogenic driver and genotype-directed therapy, compared with 2.4 years for the 318 patients with a driver mutation but no targeted therapy, and approximately 2 years for patients lacking a driver mutation. (ascopost.com)