Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.Angiogenesis Inducing Agents: Agents that induce or stimulate PHYSIOLOGIC ANGIOGENESIS or PATHOLOGIC ANGIOGENESIS.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.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.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.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.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.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.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.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.Angiogenesis Modulating Agents: Agents that modulate the PHYSIOLOGIC ANGIOGENESIS process. This is accomplished by endogenous ANGIOGENIC PROTEINS and a variety of other chemicals and pharmaceutical agents.Human Umbilical Vein Endothelial Cells: Endothelial cells that line venous vessels of the UMBILICAL CORD.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.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.Capillaries: The minute vessels that connect the arterioles and venules.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).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.Blood Vessels: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).Allantois: An extra-embryonic membranous sac derived from the YOLK SAC of REPTILES; BIRDS; and MAMMALS. It lies between two other extra-embryonic membranes, the AMNION and the CHORION. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.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.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.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.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.Thrombospondin 1: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis.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.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).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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Chorion: The outermost extra-embryonic membrane surrounding the developing embryo. In REPTILES and BIRDS, it adheres to the shell and allows exchange of gases between the egg and its environment. In MAMMALS, the chorion evolves into the fetal contribution of the PLACENTA.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)Microvessels: The finer blood vessels of the vasculature that are generally less than 100 microns in internal diameter.Mice, Inbred C57BLHypoxia-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.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.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Endostatins: Angiostatic proteins that are formed from proteolytic cleavage of COLLAGEN TYPE XVIII.Microcirculation: The circulation of the BLOOD through the MICROVASCULAR NETWORK.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).Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Retinal Neovascularization: Formation of new blood vessels originating from the retinal veins and extending along the inner (vitreal) surface of the retina.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.Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.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.Wound Healing: Restoration of integrity to traumatized tissue.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.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.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.Cyclohexanes: Six-carbon alicyclic hydrocarbons.Angiostatins: Circulating 38-kDa proteins that are internal peptide fragments of PLASMINOGEN. The name derives from the fact that they are potent ANGIOGENESIS INHIBITORS. Angiostatins contain four KRINGLE DOMAINS which are associated with their potent angiostatic activity.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.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Transplantation, Heterologous: Transplantation between animals of different species.Proteoglycans: Glycoproteins which have a very high polysaccharide content.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.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.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.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Retinal Vessels: The blood vessels which supply and drain the RETINA.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.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.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.Mice, Inbred BALB CLymphangiogenesis: The formation of LYMPHATIC VESSELS.Angiopoietins: A family of structurally-related angiogenic proteins of approximately 70 kDa in size. They have high specificity for members of the TIE RECEPTOR FAMILY.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.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.Angiostatic Proteins: Proteins that specifically inhibit the growth of new blood vessels (ANGIOGENESIS, PHYSIOLOGIC).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)Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.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.Matrix Metalloproteinase 9: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.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).Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.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.Thrombospondins: A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.Anoxia: Relatively complete absence of oxygen in one or more tissues.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.Collagen Type XVIII: A non-fibrillar collagen found in BASEMENT MEMBRANE. The C-terminal end of the alpha1 chain of collagen type XVIII contains the ENDOSTATIN peptide, which can be released by proteolytic cleavage.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.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.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.SesquiterpenesPhosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cell Adhesion: Adherence of cells to surfaces or to other cells.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.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.Thymidine Phosphorylase: An enzyme that catalyzes the transfer of 2-deoxy-D-ribose from THYMIDINE to orthophosphate, thereby liberating thymidine.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cell Growth Processes: Processes required for CELL ENLARGEMENT and CELL PROLIFERATION.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.Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Paracrine Communication: Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS on surrounding cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.Matrix Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.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.Aorta: The main trunk of the systemic arteries.Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Nitric Oxide Synthase Type III: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.Enzyme-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.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)Lung Neoplasms: Tumors or cancer of the LUNG.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.)Breast Neoplasms: Tumors or cancer of the human BREAST.Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.Tumor Burden: The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.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.Vascular 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.Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.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.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.Endothelium: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Surgical Sponges: Gauze material used to absorb body fluids during surgery. Referred to as GOSSYPIBOMA if accidentally retained in the body following surgery.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.Receptors, Vitronectin: Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.Collateral Circulation: Maintenance of blood flow to an organ despite obstruction of a principal vessel. Blood flow is maintained through small vessels.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.Ribonuclease, Pancreatic: An enzyme that catalyzes the endonucleolytic cleavage of pancreatic ribonucleic acids to 3'-phosphomono- and oligonucleotides ending in cytidylic or uridylic acids with 2',3'-cyclic phosphate intermediates. EC 3.1.27.5.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.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.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.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.Semaphorins: A family of proteins that mediate axonal guidance. Semaphorins act as repulsive cues for neuronal GROWTH CONES and bind to receptors on their filopodia. At least 20 different molecules have been described and divided into eight classes based on domain organization and species of origin. Classes 1 and 2 are invertebrate, classes 3-7 are vertebrate, and class V are viral. Semaphorins may be secreted (classes 2, 3, and V), transmembrane (classes 1, 4, 5, and 6), or membrane-anchored (class 7). All semaphorins possess a common 500-amino acid extracellular domain which is critical for receptor binding and specificity, and is also found in plexins and scatter factor receptors. Their C termini are class-specific and may contain additional sequence motifs.Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Ephrin-B2: A transmembrane domain containing ephrin that binds with high affinity to EPHB1 RECEPTOR; EPHB3 RECEPTOR; and EPHB4 RECEPTOR. Expression of ephrin-B2 occurs in a variety of adult tissues. During embryogenesis, high levels of ephrin-B2 is seen in the PROSENCEPHALON; RHOMBENCEPHALON; developing SOMITES; LIMB BUD; and bronchial arches.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.PhthalazinesTumor 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.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Oligopeptides: Peptides composed of between two and twelve amino acids.Laser-Doppler Flowmetry: A method of non-invasive, continuous measurement of MICROCIRCULATION. The technique is based on the values of the DOPPLER EFFECT of low-power laser light scattered randomly by static structures and moving tissue particulates.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Integrin alphaV: An alpha integrin with a molecular weight of 160-kDa that is found in a variety of cell types. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds. Integrin alphaV can combine with several different beta subunits to form heterodimers that generally bind to RGD sequence-containing extracellular matrix proteins.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.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.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.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.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.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.Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Plasminogen: Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Receptors, Notch: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Colonic Neoplasms: Tumors or cancer of the COLON.Receptor, EphB4: An eph family receptor found in a variety of adult and embryonic tissues. Unlike the majority of proteins in this class there is little or no expression of EphB4 receptor in the BRAIN. It has been found at high levels in developing mammary glands and in invasive mammary tumors.Chemokine CXCL12: A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.Tumor Microenvironment: The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.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.Mammary Neoplasms, Experimental: Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Receptors, TIE: A family of structurally-related tyrosine kinase receptors that are expressed predominantly in ENDOTHELIAL CELLS and are essential for development of BLOOD VESSELS (NEOVASCULARIZATION, PHYSIOLOGIC). The name derives from the fact that they are tyrosine kinases that contain Ig and EGF domains.Rats, Nude: A mutant strain of Rattus norvegicus without a thymus and with depressed or absent T-cell function. This strain of rats may have a small amount of hair at times, but then lose it.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
Endometriotic disease: the role of peritoneal fluid. (1/782)
Peritoneal fluid and the intraovarian milieu are a specific microenvironment. Peritoneal fluid originates mainly as an ovarian exudation product caused by increased vascular permeability, with cyclic variation in volume and steroid hormones which are always higher than in plasma. It contains large amounts of macrophages and their secretion products, and has a large exchange area with plasma through the peritoneum, which is highly permeable for small molecules. Diffusion becomes virtually zero for molecules with a molecular weight of >100000 Da. In women with the luteinized unruptured follicle (LUF) syndrome, concentrations of oestrogens and progesterone are much lower in the luteal phase. Endometriosis is associated with sterile low-grade inflammation, increased concentrations of activated macrophages and many of their secretions, such as cytokines, growth factors and angiogenic factors. Concentrations of CA-125 and of glycodelins are also increased, secreted locally by the endometrial cells. Natural killer (NK) cell function declines, possibly mediated by glycodelins or local intercellular adhesion molecule (ICAM) -1 shedding. The ovary is also a specific microenvironment, with steroid hormone concentrations 1000-fold higher in follicles than in plasma. Endometrial and superficially implanted cells are influenced by peritoneal fluid concentrations so that local environment, rather than inherent cellular differences could explain differences between superficial endometriosis and eutopic endometrium. Differences between superficial implants and endometriotic disease, deep infiltrating or cystic ovarian endometriosis, may thus arise via different endocrine environments. Superficial endometrial implants are regulated by peritoneal fluid factors, whereas deep endometriosis and cystic ovarian endometriosis are influenced by blood or ovarian factors. The endometriotic disease theory considers superficial endometriotic implants and their remodelling as a physiological process in most women, and concentrates on the causes of severe endometriosis such as differences in the eutopic endometrium from women with and without endometriosis (which may indicate hereditary differences), the invasiveness of some endometriotic cells in vitro, focal 'shielding' of endometriotic foci by adhesions, and inhibition of NK activity by ICAM-1 and glycodelins. Endometriotic disease is thus seen as a benign tumour. The type of cellular lesion, hereditary and immunological environments and local hormone concentrations in the ovary and in peritoneal fluid, will decide expression as cystic ovarian endometriosis, deep endometriosis or adenomyosis externa, and whether the latter is associated with adhesions. (+info)Stimulation of tumour growth by wound-derived growth factors. (2/782)
The goal of this work was to determine the molecular basis for the induction of tumour vascularization and progression by injury. Magnetic resonance imaging (MRI) studies demonstrated that administration of wound fluid derived from cutaneous injuries in pigs reduced the lag for vascularization and initiation of growth of C6 glioma spheroids, implanted in nude mice, and accelerated tumour doubling time. The former effect can be attributed to the angiogenic capacity of wound fluid as detected in vivo by MRI, and in vitro in promoting endothelial cell proliferation. The latter effect, namely the induced rate of tumour growth, is consistent with the angiogenic activity of wound fluid as well as with the finding that wound fluid was directly mitogenic to the tumour cells, and accelerated growth of C6 glioma in spheroid culture. Of the multiple growth factors present in wound fluid, two key factors, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) and platelet-derived growth factor (PDGF), were identified as the dominant mitogens for C6 glioma, and inhibition of their activity using specific neutralizing antibodies suppressed the mitogenic effect of wound fluid on DNA synthesis in C6 glioma. This study suggests that the stimulatory effect of injury on tumour progression can possibly be attenuated by therapeutic targeting directed against a limited number of specific growth factors. (+info)Hypoxia-induced up-regulation of angiogenin in human malignant melanoma. (3/782)
Angiogenesis is essential for tumor progression and metastasis, however, the angiogenesis regulators that are biologically relevant for human melanoma are still unknown. In this study, we analyzed the expression of the potent angiogenic factor angiogenin (ANG) in human melanoma in vitro and in vivo. Four different human melanoma cell lines and two normal melanocytes were kept either under normoxic or hypoxic conditions. After 24 h of hypoxic culture conditions, ANG was up-regulated in the melanoma cell lines but not in normal melanocytes. Induction levels correlated with the metastatic potential of the cell lines. These data were confirmed by Northern blot analysis. In contrast, induction of vascular endothelial growth factor by hypoxia was equally strong in the examined highly aggressive melanoma cell lines and in one nonaggressive cell line. Other angiogenic factors tested as well as the melanoma growth stimulatory activity (Gro-alpha) showed no up-regulation. Thus, in the present study, hypoxia-induced up-regulation in melanoma cells was only observed for ANG and vascular endothelial growth factor. Immunohistochemical studies showed that 8 of 10 melanomas and all 15 metastases were positive for ANG, particularly in the vicinity of small vessels, whereas all benign nevi were negative. Reverse transcription-PCR detected only weak ANG mRNA in nevi but strong signals in primary melanomas and metastases. In conclusion, we demonstrate for the first time enhanced expression of ANG in highly metastatic cell lines as well as in melanomas and metastases in vivo, suggesting that ANG expression is associated with the metastatic potential. (+info)Effect of NO, vasodilator prostaglandins, and adenosine on skeletal muscle angiogenic growth factor gene expression. (4/782)
Exercise training results in several muscle adaptations, one of which is angiogenesis. Acutely, exercise leads to release of nitric oxide, prostacyclin (PGI2), and adenosine (A) in the skeletal muscles. In this paper, we asked whether any of these locally released vasodilators, as well as other known dilator prostaglandins (PGE1 and PGE2), have the potential to increase angiogenic growth factor gene expression in resting skeletal muscle. Seven groups of 5-7 female Wistar rats (age 8-12 wk, weight 250 +/- 10 g) were anesthetized and instrumented for carotid artery pressure and electromagnetic femoral artery blood flow measurement. One group acted as control while the other groups each received one of the following six agents by constant arterial infusion (dose in microg/min): A (200), nitroprusside (NP, 4.2), acetylcholine (100), PGE1 (1.9), PGE2 (1.7), and PGI2 (1.7). Each agent reduced peripheral vascular resistance to a similar extent (at least twofold). Densitometric mRNA/18S levels for vascular endothelial growth factor (VEGF) were increased 50% by NP and acetylcholine, were unaffected by PGE1 and PGE2, and were reduced 40% by PGI2. For basic fibroblast growth factor, only PGI2 had any effect, reducing mRNA/18S approximately 25%. For transforming growth factor-beta1, A, NP, and PGE1 led to reduced mRNA/18S, whereas PGE2 slightly increased mRNA/18S. For the principal putative angiogenic growth factor, VEGF, these data suggest that naturally secreted vasodilators in contracting skeletal muscle could be involved in regulation of gene expression, namely, nitric oxide in a positive and PGI2 in a negative direction. (+info)Vascular endothelial growth factor is bound in amniotic fluid and maternal serum. (5/782)
To study vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) concentrations and their possible binders, serum from 22 non-pregnant and 55 pregnant women (15 at weeks 10-13; 40 at term), umbilical vein (n = 24) and artery (n = 13) and amniotic fluid (a pool of 50 at weeks 15-17; 11 at term) were assessed for VEGF and PlGF by an enzyme-linked immunosorbent assay. In amniotic fluid and maternal serum VEGF concentrations were <16 ng/ml and added VEGF was not recovered. VEGF was detected in serum from mothers post-partum (137 +/- 142 ng/l, mean +/- SD), umbilical artery (421 +/- 288 ng/l) and vein (502 +/- 339 ng/l) and non-pregnant controls (182 +/- 147 ng/l), and added VEGF was fully recovered. PlGF was detected in pregnancy serum (52 +/- 23 ng/l early pregnancy; 439 +/- 217 ng/l term pregnancy) and in amniotic fluid (early pregnancy 56 ng/l; term pregnancy 30 +/- 18 ng/l). PlGF was fully recovered in all samples. Gel filtration and isoelectric focusing revealed that in maternal serum and amniotic fluid [125I]VEGF was bound to a protein with an Mr of 400-700 kDa and an isoelectric point of approximately 8. This protein was not identical with alpha-2-macroglobulin (by an immunofluorometric assay), pregnancy zone protein or pregnancy associated plasma protein-A (by immunodiffusion). In conclusion, VEGF-binding activity is present in amniotic fluid and maternal blood. It disappears after delivery and is not detectable in fetal or non-pregnant serum. (+info)Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients. (6/782)
We have compared the platelet number and the serum concentration of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and interleukin-6 (IL-6) in 80 blood samples of 50 patients with advanced cancer. We have also measured the mitogenic effect of patient sera on endothelial cells in vitro in order to estimate the biological activity of serum VEGF. Serum VEGF concentration correlated with platelet number (r = 0.61; P < 10(-4)). Serum IL-6 levels correlated with platelet count (r = 0.36; P < 10(-3)), with serum VEGF levels (r = 0.55; P < 10(-4)) and with the calculated load of VEGF per platelet (r = 0.4; P = 3 x 10(-4)). Patients with thrombocytosis had a median VEGF serum concentration which was 3.2 times higher (P < 10(-4)) and a median IL-6 serum level which was 5.8 times higher (P = 0.03) than in other patients. Serum bFGF did not show an association with any of the other parameters. Patient sera with high VEGF and bFGF content stimulated endothelial cell proliferation significantly more than other sera (P = 4 x 10(-3)). These results support the role of platelets in the storage of biologically active VEGF. Platelets seem to prevent circulating VEGF from inducing the development of new blood vessels except at sites where coagulation takes place. IL-6, besides its thrombopoietic effect, also seems to affect the amount of VEGF stored in the platelets. This is in accordance with the indirect angiogenic action of IL-6 reported previously. The interaction of IL-6 with the angiogenic pathways in cancer might explain the stimulation of tumour growth occasionally observed during IL-6 administration. It also conforms to the worse outcome associated with high IL-6 levels and with thrombocytosis in several tumour types and benign angiogenic diseases. (+info)Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblast growth factor action. (7/782)
Monocyte/macrophages play important roles in regulating tissue growth and angiogenesis through the controlled release of heparin-binding growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor, and heparin binding epidermal growth factor. The action of these potent growth mediators is known to be regulated by adsorption to heparan sulfate proteoglycans (HSPGs) on the surface and within the extracellular matrix of other neighboring cells, which respectively promote or restrict interactions with their signal-transducing receptors on target cells. Here we report on the nature of HSPGs inducibly expressed on the surface of macrophages that confer these cells with the capacity to regulate endogenous growth factor activity. We reveal that activated human macrophages express only a single major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan) as the result of de novo RNA and protein synthesis. In addition, we demonstrate this macrophage HSPG selectively binds the macrophage-derived growth factors FGF-2, vascular endothelial growth factor and heparin binding EGF and can present FGF-2 in a form that transactivates receptor-bearing BaF32 cells. These results define a novel and unique proteoglycan profile for macrophages and imply a key role for syndecan-2 in the delivery of sequestered growth factors by inflammatory macrophages for productive binding to their appropriate target cells in vivo. (+info)Aberrant cutaneous expression of the angiogenic factor midkine is associated with neurofibromatosis type-1. (8/782)
Neurofibromatosis type 1 is a common autosomal dominant disorder (incidence 1:3500) characterized by lesions that include neural crest derivatives such as Schwann cells and melanocytes. A critical event in the pathogenesis of neurofibromatosis type 1 is the heterozygous germ-line loss of the tumor suppressor gene NF1. Additional genetic and/or epigenetic events have been posited, including various alterations in growth factor expression. By in situ hybridization and immunohistochemistry, we demonstrate aberrant expression of the angiogenic and tumorigenic growth factor midkine in the skin of patients with neurofibromatosis type 1, but not normal individuals. We demonstrate that midkine expression is independent of the presence of neurofibromas, and thus appears to be associated with mutations in the NF1 gene. Furthermore, midkine-containing culture media is shown to stimulate the growth of human endothelial and neurofibroma-derived cells. In conclusion, we introduce the skin as a source of dysregulated growth factors in neurofibromatosis type 1, and suggest the further study of the angiogenic factor midkine in neurofibromatosis type 1 pathogenesis. (+info)Cadmium may inhibit angiogenesis. As a stress agent, inducing apoptosis and blocking it, Cd can have both helpful and harmful ... Cadmium is a heavy metal and can also induce apoptosis. The first study in humans was an open pilot trial conducted in Russia ... Huff J; Lunn RM; Waalkes MP; Tomatis L; Infante PF (2007). "Cadmium-induced cancers in animals and in humans". Int J Occup ... Cadmium (metallotherapeutic drug, metal-based drug) can induce apoptosis (programmed tumor cell death) in various cell types. ...
It also inhibits VEGF-induced angiogenesis in a murine implant model. It has potential as an anticancer agent targeting ... It efficiently inhibited growth factor-induced EGFR and ErbB2 phosphorylation in tumors for >72 h, a phenomenon correlating ... growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. ...
Fulda S, Debatin KM (September 2004). "Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent ... whereby mice given the vaccine had less angiogenesis from the tumour challenge than the control mice that were not given any of ... In acquiring the humoral response to tumour antigens such as survivin, CD4+ T cells are activated to induce B cells to produce ... Although the details are not here, survivin was shown to also inhibit cytochrome c and caspase-8-induced activation of caspases ...
In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, ... Lenalidomide is one of the novel drug agents used to treat multiple myeloma. It is a more potent molecular analog of ... In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulation. ... Compared to placebo, lenalidomide is effective at inducing a complete or "very good partial" response as well as improving ...
It has been observed that it not only induces apoptosis but can also inhibit the cell cycle, and has marked anti-angiogenesis ... Arsenic is a fairly ancient human therapeutic agent, however it has only recently returned to the forefront of cancer treatment ... TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a ... It has been hypothesized that it acts as a survival factor in tumor cell lines, preventing therapeutic-induced apoptosis and ...
... angiogenesis modulating agents MeSH D27.505.696.377.077.077 --- angiogenesis inducing agents MeSH D27.505.696.377.077.099 --- ... fertility agents, male MeSH D27.505.696.875.610 --- luteolytic agents MeSH D27.505.696.875.650 --- menstruation-inducing agents ... fertility agents, male MeSH D27.505.954.705.610 --- luteolytic agents MeSH D27.505.954.705.650 --- menstruation-inducing agents ... luteolytic agents MeSH D27.505.696.875.360.276.500 --- menstruation-inducing agents MeSH D27.505.696.875.360.276.727 --- sperm ...
Another agent involved in autocrine cancer signaling is vascular endothelial growth factor (VEGF). VEGF, produced by carcinoma ... Paracrine signaling is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, ... Evidence from cell lines and primary breast cancer cultures in vitro". Angiogenesis. 8 (3): 197-204. doi:10.1007/s10456-005- ... An example of an autocrine agent is the cytokine interleukin-1 in monocytes. When interleukin-1 is produced in response to ...
"ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells". FEBS Letters. 570 ( ... "The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis". Nature. 428 (6980): 328-32. doi: ... and induce apoptosis. This protein contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling ... "The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis". Nature. 428 (6980): 328-32. doi: ...
... inducing cell proliferation and release of cytokines(IL-6 and IL-8, potent bone resorptive agents) and stimulating bone ... Mammalian heparanase: involvement in cancer metastasis, angiogenesis and normal development. Cancer Biology, Vol. 12, 2002: pp ... A macrobiotic diet is neither effective nor safe as it could hypothetically induce weight loss due to severe dietary ... Matrix metalloproteinases (MMPs) MMP-2 is the main metalloprotease secreted by breast-cancer cells or induced in the adjacent ...
... has been shown to inhibit HCC-induced proliferation and angiogenesis. Sorafenib has also been shown to provide a significant ... Based on these results, researchers concluded that this class of agents may be effective in the treatment of HCC. Brivanib is ... The trial drug is one of the first agents to demonstrate promising antitumor activity in advanced HCC patients treated with ... Doxorubicin (trade name Adriamycin; also known as hydroxydaunorubicin), the most widely used agent in HCC, has shown a 4% to ...
While the mechanisms of bleeding induced by anti-VEGF agents are complicated and not yet totally understood, the most accepted ... An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis ... Angiogenesis Inhibitors for Cancer - from The Angiogenesis Foundation, 23 June 2009. *Angiogenesis Inhibitors for Eye Disease ... downregulate angiogenesis stimulators and inhibit cell migration of endothelial cells. IL-12. stimulate angiogenesis inhibitor ...
... is under investigation as an anti-angiogenic agent in pilot and clinical trials. The drug may inhibit tumor angiogenesis in ... The Cu-SPH complex was found to induce apoptosis in A549, H322 and H1299 lung cancer cells. A copper intrauterine device (IUD) ... Research has been ongoing over the past two decades to determine whether copper is a causative or a preventive agent of ... In humans, the liver is the primary organ of copper-induced toxicity. Other target organs include bone and the central nervous ...
It has played a significant role in more recent tumor models used in metastatic and angiogenesis studies as it is a highly ... Some of Margaret Reed Lewis' research in the mechanics of cancer included myeloid infiltration and strangulation-induced ... one of the earliest tumors that could be transplanted and used to determine if a compound had potential as an anticancer agent ...
2004). "Withaferin A is a potent inhibitor of angiogenesis". Angiogenesis. 7 (2): 115-122. doi:10.1007/s10456-004-1026-3. PMID ... 3-azidoWA acts as a tumor suppressor by inducing Par-4, TIMP-1 and by reducing the levels of pAkt and pERK that are activated ... Therefore, withaferin A can be a potential therapeutic agent for the treatment of cervical cancer without major side effects. ... It can induce oxidative stress, alter gene expression, depolarize mitochondria. Withaferin A also down regulates VEGF gene ...
... induces cancer cell death through a variety of mechanisms. Even now, all the antineoplastic pathways it employs are ... Taurolidine has been used as an antimicrobial agent in the clinical setting since the 1970s and thus far appears nontoxic. The ... It has been shown to enhance apoptosis, inhibit angiogenesis, reduce tumor adherence, downregulate pro-inflammatory cytokine ... Taurolidine is an antimicrobial agent used in an effort to prevent catheter infections. It however is not approved for this use ...
... (tentative trade name Aptosyn) is an antineoplastic agent. It acts by inhibiting the enzyme cyclic guanosine ... Exisulind inhibits the enzyme cGMP-PDE, overexpressed in precancerous and cancerous colorectal cells, and induces apoptosis in ... Preclinical evidence suggests that exisulind also inhibits angiogenesis. Sulindac [No authors listed] (2004). "Exisulind: ... "Inhibition of Angiogenesis by Sulindac and its Sulfone Metabolite (FGN-1): a Potential Mechanism for Their Antineoplastic ...
Rapamycin has also shown to induce p53-independent apoptosis in certain types of cancer. Tumor angiogenesis rely on ... The response rate in solid tumors where rapalogs have been used as a single-agent therapy have been modest. Due to partial mTOR ... Rapamycin induces dephosphorylation of 4EBP1 as well, resulting in an increase in p27 and a decrease in cyclin D1 expression. ... mTORi-induced ILD often is asymptomatic (with ground glass abnormalities on chest CT) or mild symptomatic (with a non- ...
Combining ABT-737 with second agents that inactivate Mcl-1 may reduce this effect. ABT-737 has demonstrated single-agent ... mTOR inhibitors lead to cell cycle arrest in the G1 phase and also inhibits tumor angiogenesis by reducing synthesis of VEGF. A ... A synthetic retinoid that induces apoptosis of cancer cells and acts synergistically with chemotherapeutic drugs by triggering ... Reduced susceptibility to apoptosis increases the resistance of cancer cells to radiation and cytotoxic agents. B-cell lymphoma ...
For example, the Hsp90 inhibitor geldanamycin has been used as an anti-tumor agent. The drug was originally thought to function ... Davies TH, Ning YM, Sánchez ER (February 2002). "A new first step in activation of steroid receptors: hormone-induced switching ... angiogenesis, and metastasis. Hsp90 plays apparently conflicting roles in the cell, as it is essential for both the creation ... Hence inhibition of Hsp90 may induce apoptosis through inhibition of the PI3K/AKT signaling pathway and growth factor signaling ...
Currently have been suggested few approaches in development of novel therapeutic agents with better properties Discovery agents ... They induce mitotic arrest in the G2-M phase of the cell cycle, resulting in apoptosis. Epothilone A and epothilone B exhibit ... It is known that some compounds can inhibit the formation of new blood vessels (inhibit the process of angiogenesis) or shut ... Play media Agents which act as inhibitors of tubulin, also act as inhibitors of cell division. Microtubule exists in a ...
Another example occurs in activated T cell lymphocytes, i.e., when a T cell is induced to mature by binding to a peptide:MHC ... An example of an autocrine agent is the cytokine interleukin-1 in monocytes. When interleukin-1 is produced in response to ... Evidence from cell lines and primary breast cancer cultures in vitro". Angiogenesis. 8 (3): 197-204. doi:10.1007/s10456-005- ... Another agent involved in autocrine cancer signaling is vascular endothelial growth factor (VEGF). VEGF, produced by carcinoma ...
GHK-Cu has been found to induce a systemic enhancement of healing in rats, mice, and pigs; that is, the GHK-Cu peptide injected ... In the late 1980s, copper peptide GHK-Cu started attracting attention as a promising wound healing agent. Pioneers in this ... angiogenesis, and wound closure in both wound chambers and full thickness wounds. Biotinylated GHK-Cu was incorporated into a ... 2005:549-563 Uno H, Kurata S "Chemical agents and peptides affect hair growth. J Invest Dermatol. 1993; 101(1 Suppl):143S-147S ...
McDougall, S.R, Anderson, A.R.A., Chaplain, M.A.J. Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: ... the completed or ongoing clinical trials in which the FGF-1 protein is used as the therapeutic agent to stimulate angiogenesis ... Angiogenesis inhibitor can be endogenous or come from outside as drug or a dietary component. Angiogenesis may be a target for ... Sprouting angiogenesis was the first identified form of angiogenesis. It occurs in several well-characterized stages. First, ...
... disulfide (MoS2) is used as a solid lubricant and a high-pressure high-temperature (HPHT) antiwear agent. It forms ... It has also been found to have an inhibitory effect on angiogenesis, potentially by inhibiting the membrane translocation ... Copper reduction or deficiency can also be deliberately induced for therapeutic purposes by the compound ammonium ... antiangiogenic agent: Phase I study". Clinical Cancer Research. 6 (1): 1-10. PMID 10656425. Institute of Medicine (2000). " ...
It was also shown in vivo that S1P synergizes with angiogenic factors such as FGF-2 and VEGF in inducing angiogenesis and ... Fingolimod, a drug which internalizes the receptor, is approved as a disease modifying agent in MS. There are other Sphingosine ... is strongly induced in endothelial cells during tumor angiogenesis and a siRNA against S1PR1 was able to inhibit angiogenesis ... Liu CH, Thangada S, Lee MJ, Van Brocklyn JR, Spiegel S, Hla T (April 1999). "Ligand-induced trafficking of the sphingosine-1- ...
Rahmanian M, Heldin P (February 2002). "Testicular hyaluronidase induces tubular structures of endothelial cells grown in three ... and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyaluronidase is also used for ... Hyaluronidases are also thought to play a role in the process of angiogenesis, although most hyaluronidase preparations are ...
ALE is a novel growth-rich therapeutic agent that is cell-free and easy to produce. Besides, it is also able to induce ... In vivo, the therapeutic effect of this agent was investigated on wound healing in C57BL/6 mice, and wound healing rate, vessel ... Moreover, when added as a cell culture supplement, ALE effectively induced tube formation of HUVECs and lipid accumulation in ... and adipose tissue has been demonstrated to induce tissue repair and regeneration in various ischemic and impaired conditions. ...
Angiogenesis Inducing Agents. LinkOut - more resources. Other Literature Sources. *Cited by Patents in - The Lens ... The prevascular tumor does not induce angiogenesis, is limited in size, and rarely metastasizes. The vascularized tumor induces ... The role of angiogenesis in tumor growth.. Folkman J1.. Author information. 1. Department of Surgery, Harvard Medical School, ... Thus, angiogenesis is necessary but not sufficient for tumor growth and metastasis. Neovascularization of a tumor requires that ...
... in endothelial cell migration and angiogenesis, we have used two in vitro model systems involving coculture of endothelial ... Anti-Inflammatory Agents, Non-Steroidal / pharmacology * Antineoplastic Agents / pharmacology * Caco-2 Cells ... Cyclooxygenase regulates angiogenesis induced by colon cancer cells Cell. 1998 May 29;93(5):705-16. doi: 10.1016/s0092-8674(00) ... NS-398 does not inhibit production of angiogenic factors or angiogenesis induced by COX-2-negative cells. Treatment of ...
Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process whereby capillary sprouts are formed ... Angiogenesis Inducing Agents / physiology* * Animals * Arteriovenous Anastomosis / physiopathology * Capillaries / growth & ... Continuous and discrete mathematical models of tumor-induced angiogenesis Bull Math Biol. 1998 Sep;60(5):857-99. doi: 10.1006/ ... Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process whereby capillary sprouts are formed ...
Antineoplastic Agents. Angiogenesis Inhibitors. Angiogenesis Modulating Agents. Growth Substances. Physiological Effects of ... Pilot Study of Sunitinib Tumor Levels in Patients Not on Enzyme-Inducing Anti-Epileptic Drugs Undergoing Debulking Surgery for ... Sunitinib Tumor Levels in Patients Not on Enzyme-Inducing Anti-Epileptic Drugs Undergoing Debulking Surgery for Recurrent ... Patient must be on no anti-epileptic drugs (AED) or AED that are non-enzyme inducing (NEIAED) ...
Angiogenesis Inducing Agents. Grant support. *R01 CA142657/CA/NCI NIH HHS/United States ... Targeting angiogenesis and the tumor microenvironment.. Samples J1, Willis M, Klauber-Demore N. ...
Angiogenesis Inducing Agents. Angiogenesis Modulating Agents. Growth Substances. Physiological Effects of Drugs. ...
Angiogenesis Inducing Agents. Angiogenesis Modulating Agents. Growth Substances. Physiological Effects of Drugs. ... systemic treatment with corticosteroid agents or cytotoxic drugs in the past 3 months before inclusion ... and/or presence of a diabetes treated by oral agent, insulin or diet ...
EDB fibronectin and angiogenesis- a novel mechanistic pathway. Angiogenesis 2005;8:183-196pmid:16308732. ... Curr Med Chem Anticancer Agents 2002;2:667-681pmid:12678719. OpenUrlCrossRefPubMed ... Oxygen-induced retinopathy (OIR) mice.. We induced OIR in mice as previously described (16), modified from the original ... Inhibition of angiogenesis and angiogenesis-dependent tumor growth by the cryptic kringle fragments of human apolipoprotein(a) ...
... angiogenesis-targeted nanomedicine approach to deliver adipose tissue browning agents and simultaneously stimulate angiogenesis ... IRGD- and P3-NP-Rosi induced adipose tissue transformation and angiogenesis and up-regulated both BAT and angiogenesis markers ... by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis- ... 2004) Angiogenesis inhibitor, TNP-470, prevents diet-induced and genetic obesity in mice. Circ Res 94(12):1579-1588. ...
... to its suppression of tumor-induced angiogenesis and, more importantly, to develop novel therapeutic agents against ACC. ... ISL Prevents ACC-Induced Angiogenesis Ex Vivo and In Vivo.. To verify the preventive effect of ISL on ACC-induced angiogenesis ... D, effect of ISL on ACC-induced angiogenesis in the CAM assay in vivo. E, effect of ISL on ACC-induced vessel formation in the ... 2002) TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C ( ...
Pharmacological Actions : Angiogenesis Inducing Agents, Neuroprotective Agents. [+] In this review, all the available data on ... Curcumin induces neurogenesis and neuroprotection and may provide a novel therapeutic agent for both regenerative medicine and ... Pharmacological Actions : Anti-Inflammatory Agents, Heme oxygenase-1 up-regulation, Neuroprotective Agents, NF-kappaB Inhibitor ... Pharmacological Actions : Anti-Inflammatory Agents, Interleukin-1 beta downregulation, Neuroprotective Agents, Tumor Necrosis ...
Angiogenesis Inducing Agents. 1. 1. *. Research Articles 1. *. Cumulative Knowledge Score 1. ...
Angiogenesis Inducing Agents / administration & dosage, pharmacology, therapeutic use*. Animals. Arterial Occlusive Diseases / ... 0/Angiogenesis Inducing Agents; 0/Recombinant Proteins; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth ...
Angiogenesis Inducing Agents (2). Angiogenesis Inhibitors (29) • Agents and endogenous substances that antagonize or inhibit ... Anti-Angiogenesis Effect (0) see Angiogenesis Inhibitors. Anti-Anxiety Agents (86) • Agents that alleviate ANXIETY, tension, ... Anti-Mycobacterial Agents (0) see Anti-Bacterial Agents. Anti-Obesity Agents (24) • Agents that increase energy expenditure and ... Antithrombotic Agents (0) see Fibrinolytic Agents. Antithyroid Agents (10) • Agents that are used to treat hyperthyroidism by ...
0 (Angiogenesis Inducing Agents); 0 (Estrogen Receptor beta); 0 (Iridoid Glucosides); 0 (Phytoestrogens); 0 (Platelet ... In addition, results from quantitative PCR and western blot suggested AU induced angiogenesis via vascular endothelial cell ... RESULTS: MC induced a significant (p < 0.05) MCF-7 cell proliferation at a concentration of 0.1 M, but did not inhibit the ... In the study, hindlimb ischemia was induced by ligation of femoral artery on the right leg of ovariectomized mice. AU treatment ...
The agent strengthens the antitumor effect of an angiogenesis-inhibiting substance and serves to reduce the dose and ... And use of the agent in concert with an anti-neoplastic agent brings about further strong and long-lasting antitumor effects. ... The present invention relates to an intravascular embolizing agent containing an angiogenesis-inhibiting substance and an ... since the tumor regenerates by the formation of collateral artery caused by secretion of the tumor-induced angiogenesis factor ...
Nanofibers; Peptides; Tissue Scaffolds; Angiogenesis Inducing Agents; Hemostatics Academic: 336-716-4498. ...
VEGF is a vascular permeability-inducing agent and an important stimulator of angiogenesis. TBARS is a biomarker of lipid ... Induced Sputum: Induced sputum is a non-invasive test used to collect cells from lung airways for examining acute lung ... Heart Rate Vari-ability (HRV) Changes: A proposed mechanism of PM-induced cardiovascular effects is autonomic dysfunction, or ... Respiratory inflammatory responses (induced sputum), pulmonary function (flow-volume curves) and nasal/respiratory symptom ...
... may be useful agents for preventing tumor-induced angiogenesis.. 1. Introduction. Angiogenesis is defined as the process of ... Folkman first observed that the angiogenesis is required for tumor growth in 1971 [1]. Tumor-induced neovessels carry oxygen ... M. R. Ahn, K. Kunimasa, T. Ohta et al., "Suppression of tumor-induced angiogenesis by Brazilian propolis: major component ... K. Kunimasa, M.-R. Ahn, T. Kobayashi et al., "Brazilian propolis suppresses angiogenesis by inducing apoptosis in tube-forming ...
Rg3 treatment induced apoptosis and inhibited angiogenesis. They contributed to the tumor shrinkage. Rg3 initialized the tumor ... Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen. ... Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) ,i,in vitro,/i,. ... i,Aim,/i,. Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. ...
Wakabayashi K. NSAIDs as cancer preventive agents. Asian Pac. J. Cancer Prev., 1: 97-113, 2000. ... Peroxisome proliferator-activated receptor γ ligands are potent inhibitors of angiogenesis in vitro and in vivo. J. Biol. Chem. ... AOM-induced ACF, and DSS/AOM-induced ACF. PPARγ ligands could induce growth arrest and differentiation in human colon cancer ... inhibited DDS-induced colitis and AOM-induced ACF. In addition, both ligands inhibited DSS/AOM-induced ACF formation, which are ...
None of the lymphatics illustrated had been injected with carbon or other agents. (a and b) Fibrin clot (*) within giant ... We now report that, in addition to inducing angiogenesis, VEGF-A164 also induces a strong lymphangiogenic response. This ... Both VEGF-C and VEGF-D induce angiogenesis as well as lymphangiogenesis under appropriate circumstances (10, 15, 16) but VEGF-A ... Several recent papers (14, 18, 19) have reported that human Ad-VEGF-A165 induces angiogenesis but not lymphangiogenesis in ...
Anaesthetic agents were confirmed to play a role on the tumor angiogenesis. The effect of sevoflurane on tongue squamous cell ... Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation ... We concluded that sevoflurane attenuates hypoxia-induced VEGF level via DNA methylation of the promoter region in TSCC cell. ... Results showed that sevoflurane attenuated the hypoxia-induced VEGF level without altering the HIF-1α after exposure for 24 and ...
Keywords: Angiogenesis Inducing Agents, Carcinoma, Hepatocellular, Chemokine CXCL12, Plumbaginaceae, Receptors, CXCR4. Full ... CONCLUSIONS: The effect of PL on the SDF-1-CXCR4/CXCR7 axis has become an attractive target for inhibiting angiogenesis in ... The study further demonstrated that PL not only abolishes SDF-1-induced formation of endothelial tubes, but also inhibits ... Plumbagin Restrains Hepatocellular Carcinoma Angiogenesis by Stromal Cell-Derived Factor (SDF-1)/CXCR4-CXCR7 Axis. Jing Zhong, ...
VEGFProliferationInhibitorsBlood vesselsAngiogenicNeovascularizationPromote angiogenesisVascular EndothHuman umbilical vein endothelial cellsCapillaryIschemicHepatocellular carcinomaRole in modulating aApoptosis in endothelial cellsVesselsMiceStimulatesVitro angiogenesisGrowth factor-inducedPhysiological and pathologicalIschemia-inducedTherapeutic angiogenesisRetinalInduction of apoptosisChemotherapeutic agentsEpidermal GrowthSynthesisClinicalCaspase-dependentProgressionPathwaysEpithelialDiet-inducedMediatesCarcinoma
- In a further mimic coculture study, ISL effectively suppressed the ability of ACC cells to induce in vitro proliferation, migration, and tube formation of human endothelial hybridoma (EAhy926) cells as well as ex vivo and in vivo angiogenesis, whereas it exerted no effect on EAhy926 cells when added directly or in the presence of vascular endothelial growth factor (VEGF). (aspetjournals.org)
- The data also showed that the specific suppression of tumor angiogenesis by ISL was caused by down-regulation of mammalian target of rapamycin (mTOR) pathway-dependent VEGF production by ACC cells, correlating with concurrent activation of c-Jun NH 2 -terminal kinase (JNK) and inhibition of extracellular signal-regulated kinase (ERK). (aspetjournals.org)
- Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. (rupress.org)
- Using an adenoviral vector engineered to express murine VEGF-A 164 , we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A-expressing tumors. (rupress.org)
- We now report that, in addition to inducing angiogenesis, VEGF-A 164 also induces a strong lymphangiogenic response. (rupress.org)
- Another member of the VPF/VEGF family, placenta growth factor (PlGF), also has a role in pathological angiogenesis, interacting with VEGFR-1 but not VEGFR-2 ( 9 ). (rupress.org)
- Mutation or loss of these cytokines or their receptor (VEGFR-3) leads to impaired lymphatic development and human disease whereas overexpression of VEGF-C or VEGF-D induces increased lymphangiogenesis in animal systems. (rupress.org)
- Both VEGF-C and VEGF-D induce angiogenesis as well as lymphangiogenesis under appropriate circumstances ( 10 , 15 , 16 ) but VEGF-A is thought not to induce lymphangiogenesis ( 14 , 17 - 19 ). (rupress.org)
- When murine VEGF-A 164 was introduced into adult mouse tissues by means of an adenoviral vector, angiogenesis developed according to a characteristic series of steps ( 20 , 21 ). (rupress.org)
- Within a matter of hours, infected host cells expressed VEGF-A 164 , inducing microvascular hyperpermeability, extravasation of plasma and plasma proteins, deposition of extravascular fibrin gel and edema. (rupress.org)
- We here report the unanticipated finding that, in addition to angiogenesis, VEGF-A also induces proliferation of lymphatic endothelium, resulting in the formation of greatly enlarged and poorly functioning lymphatic channels. (rupress.org)
- Unlike angiogenesis, the lymphangiogenic response became VEGF-A independent, as, once formed, the newly formed "giant" lymphatics persisted indefinitely, long after VEGF-A expression and tissue edema had ceased. (rupress.org)
- Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region. (sigmaaldrich.com)
- Results showed that sevoflurane attenuated the hypoxia-induced VEGF level without altering the HIF-1α after exposure for 24 and 72 h. (sigmaaldrich.com)
- The attenuation effect of sevoflurane on hypoxia-induced VEGF level could be blocked by 5-Aza. (sigmaaldrich.com)
- We concluded that sevoflurane attenuates hypoxia-induced VEGF level via DNA methylation of the promoter region in TSCC cell. (sigmaaldrich.com)
- The treatment of the hepatoma cell line SMMC-7721 with SDF-1 resulted in enhanced secretion of the angiogenic factors, IL-8 and VEGF, and shows that these stimulatory effects are abolished by PL. The study further demonstrated that PL not only abolishes SDF-1-induced formation of endothelial tubes, but also inhibits expression of CXCR4 and CXCR7, and partially prevents activation of angiogenic signaling pathways. (medscimonit.com)
- It also inhibits VEGF-induced angiogenesis in a murine implant model. (wikipedia.org)
- We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. (nih.gov)
- We found that the activation of the VEGFR2 signaling pathway induced by VEGF was enhanced by arnebin‑1. (spandidos-publications.com)
- Of all the known pro-angiogenic molecules, VEGF is the most important mediator that promotes angiogenesis ( 12 - 14 ). (spandidos-publications.com)
- Conclusion In vitro data for SN on cardiac cells suggest induction of angiogenesis and upregulation of VEGF. (ahajournals.org)
- Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. (biomedcentral.com)
- To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE. (biomedcentral.com)
- RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. (biomedcentral.com)
- Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. (biomedcentral.com)
- Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and their receptors are important targets in cancer therapy based on angiogenesis inhibition. (aacrjournals.org)
- VEGF is a key driver of angiogenesis in many tumors where VEGF signaling promotes endothelial cell survival, proliferation, and migration ( 14 ). (aacrjournals.org)
- Inhibition of VEGF together with PDGF is a promising strategy for suppressing angiogenesis in tumors. (aacrjournals.org)
- Vascular endothelial growth factor (VEGF) is the most potent angiogenic mitogen, and has been associated with angiogenesis. (molvis.org)
- Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains, which can induce VEGF expression. (molvis.org)
- The aims of the present study were to evaluate the heparanase expression and its relationship with VEGF in the retina of oxygen-induced retinopathy (OIR) mice, and to investigate the effect of the heparanase inhibitor phosphomannopentaose sulfate (PI-88) in the OIR retinas. (molvis.org)
- Many molecules are involved in angiogenesis, of which vascular endothelial growth factor (VEGF) is one of the best studied. (molvis.org)
- Activation of mTOR stimulates translation of oncogenic proteins such as c-Myc and hypoxia-inducible factor 1α (HIF-1α), which results in an increase in genes that promote angiogenesis (vascular endothelial growth factor (VEGF), proliferation (cyclin D1), and cell survival (survivin) (refs. (aacrjournals.org)
- One disadvantage to agents targeting angiogenesis is that they can induce a tumor to increase production of vascular endothelial growth factor (VEGF). (medpagetoday.com)
- In randomised clinical trials, anti-VEGF has been reported as an essential agent for the treatment of advanced gastric cancer. (biomedcentral.com)
- This review aims at assessing the treatment outcome of anti-angiogenesis therapy through the VEGF pathway in the management of patients with advanced gastric cancer. (biomedcentral.com)
- Many clinical trials have confirmed VEGF inhibitors as important therapeutic agents in multiple solid tumors including gastric cancer. (biomedcentral.com)
- Tumors stimulate new blood vessel growth in order to acquire oxygen and nutrients, a process called tumor angiogenesis, by secreting an angiogenic growth factor called VEGF. (eurekalert.org)
- The ability of the R2Fas receptor to switch the function of VEGF from a growth factor to a death factor may allow a new approach to anti-angiogenesis by simultaneously targeting both the VEGF-producing cancer cells and the tumor blood vessels," said Tim Quinn, M.D., assistant professor at the University of California, San Francisco Pediatrics Department. (eurekalert.org)
- Conclusions: Thus, although AMSC from patients with RVD had increased DNA damage and reduced migration, hypoxia stimulated pro-angiogenic responses via increased expression of angiogenic genes, VEGF secretion and induction of the hypoxia-inducible miR-210, while downregulating angiogenesis-related miRNAs. (elsevier.com)
- We tested the hypothesis that adenovirus-mediated intramuscular (IM) gene transfer of the 121-amino-acid form of vascular endothelial growth factor (AdCMV.VEGF 121 ) could stimulate neovascularization in nonischemic skeletal muscle and consequently attenuate the hemodynamic deficit secondary to surgically induced ischemia. (elsevier.com)
- Conclusions - IM administration of AdCMV.VEGF 121 stimulates angiogenesis in normoperfused skeletal muscles, and the newly formed vessels preserve TP after induction of ischemia. (elsevier.com)
- Treatment with AnxA1 2-26 , once a day, from day 3-60 after scaffold implantation improved the take of the implant, induced vessels formation, enhanced gene and protein levels of the vascular growth factor-A (VEGF-A) and fibroblast influx into allograft tissue. (frontiersin.org)
- Moreover, treatment of human umbilical endothelial cells (HUVECs) with AnxA1 2-26 improved proliferation, shortened cycle, increased migration and actin polymerization similarly to those evoked by VEGF-A. The peptide treatment instead only potentiated the tube formation induced by VEGF-A. Collectively, our data showed that AnxA1 2-26 treatment favors the tissue regeneration after skin grafting by avoiding exacerbated inflammation and improving the angiogenesis process. (frontiersin.org)
- To this point, VEGF is one of the most specific and critical regulators of angiogenesis, and it stimulates endothelial proliferation, permeability, survival, and capillary formation ( 4 ). (diabetesjournals.org)
- by blocking angiogenesis growth factors (substances, such as VEGF, which promote the process of developing new blood vessels). (cancerindex.org)
- The concentration of VEGF is increased in human endometrium, and it may be important in physiological and pathological angiogenesis ( 6 ). (spandidos-publications.com)
- Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells. (elsevier.com)
- Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a central role in angiogenesis. (elsevier.com)
- Consistently, an intracellular Ca2+ chelator, BAPTA/AM significantly decreased hypoglycemia-induced VEGF expression and AP-1 DNA-binding activity. (elsevier.com)
- Therefore, these results indicate that increase of intracellular Ca2+ level induces the activation of PKC, which induce the activation of AP-1 leading to the increase of VEGF in glucose-deprived environment. (elsevier.com)
- Furthermore, it provides one link in regulation of VEGF with hypoglycemia as well as information to understand how hypoglycemia induces VEGF expression and subsequently leads to tumor angiogenesis. (elsevier.com)
- 2-4 Recent growing evidence has established the involvement of NO in VEGF-induced angiogenesis. (ahajournals.org)
- NOS inhibitors block VEGF-induced EC migration, proliferation, and tube formation in vitro as well as VEGF-induced angiogenesis in vivo. (ahajournals.org)
- 5,6 VEGF is known to induce Akt/protein kinase B-dependent phosphorylation of eNOS, resulting in activation of eNOS and the subsequent increase in NO production. (ahajournals.org)
- In addition, recombinant PTX3 was neurogenic in vitro when added to neurospheres, which was mediated by IL-1β.In vitro, recombinant PTX3 induced marked endothelial cellular proliferation and promoted formation of tube-like structures of endothelial cell line bEnd.5.Finally, a lack of PTX3 potentiated motor deficits 14 days after MCAo. (nih.gov)
- In vitro, recombinant PTX3 induced marked endothelial cellular proliferation and promoted formation of tube-like structures of endothelial cell line bEnd.5. (nih.gov)
- It has potential as an anticancer agent targeting deregulated tumor cell proliferation as well as angiogenic parameters. (wikipedia.org)
- mTOR is a critical regulator of cellular protein synthesis that influences many aspects of tumor proliferation, including cell cycle progression, angiogenesis, and apoptosis and functions as a downstream effector of the essential phosphatidylinositol 3-kinase (PI3K)-Akt cell survival pathway that is deregulated in many cancers ( 4 ). (aacrjournals.org)
- We measured tumor proliferation, apoptosis, lymphangiogenesis, and angiogenesis by immunohistochemical staining, and examined diaphragm lymphatic vessel network by intraperitoneal injection of a fluorescent dye. (aacrjournals.org)
- TGF-β blockade impaired tumor growth in both models, accompanied by a decreased tumor cell proliferation and angiogenesis. (aacrjournals.org)
- 9-11 Blockade of the RhoA/ROCK pathway effectively corrects blood pressure in a number of animal models of systemic hypertension 8,11 and is a key regulator of vascular smooth muscle proliferation and migration in disease-induced systemic vascular remodeling. (ahajournals.org)
- Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma. (deepdyve.com)
- Stable down-regulation of Slit3 in HCC cell-lines induced cell proliferation in vitro and tumor growth in vivo, while stable Slit3 overexpression repressed these effects. (deepdyve.com)
- Molecular investigations showed that the stable Slit3 repression-induced cell proliferation was associated with a higher expression of β-catenin and a repressed GSK3β activity. (deepdyve.com)
- Angiogenesis, a process of generation of new blood vessels from the pre-existing vasculature, has been demonstrated to be a basic prerequisite for sustainable growth and proliferation of tumour. (cancerindex.org)
- 1 Angiogenesis involves complex steps, including extracellular matrix degradation, migration and proliferation of endothelial cells (ECs), and morphological differentiation of ECs into capillary-like tubes. (ahajournals.org)
- S1P induces migration, proliferation, and cytoskeletal changes of ECs by way of the endothelial differentiation gene ( Edg ), a family of G protein-coupled receptors. (ahajournals.org)
- Taken together, these results demonstrate a critical role of NO in S1P-induced angiogenesis in vivo and in vitro and suggest the divergent roles of NO in S1P-induced angiogenic response among proliferation, migration, and differentiation. (ahajournals.org)
- SSAO inhibitors significantly blocked the catalytic activity of VAP-1 in tumor, attenuated tumor progression, and reduced neo-angiogenesis. (wikipedia.org)
- Angiogenesis and endothelial cell growth and migration induced by basic fibroblast growth factor were not affected by NO synthase inhibitors. (jci.org)
- This monokine and other members of its family are usable as antitumor agents, either directly or as inhibitors of angiogenesis. (bioworld.com)
- Angiogenesis Inhibitors. (worldcat.org)
- The combination of low-dose chemotherapy and anti-angiogenic inhibitors suppresses growth of experimental tumors more effectively than conventional therapy or anti-angiogenic agent alone. (biomedcentral.com)
- Angiogenesis inhibitors are substances which prevent this formation of new blood vessels, thereby stopping or slowing the growth or spread of tumours. (cancerindex.org)
- Definition and list of angiogenesis inhibitors. (cancerindex.org)
- An unmoderated mailing list designed mainly for PhD level scientists and medical doctors actively engaged in research on tumor angiogenesis inhibitors and their possible clinical applications. (cancerindex.org)
- This fact has led to the search for novel endogenous or synthetic angiogenesis inhibitors. (jove.com)
- Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process whereby capillary sprouts are formed in response to externally supplied chemical stimuli. (nih.gov)
- Angiogenesis is defined as the process of forming new blood vessels from preexisting ones. (hindawi.com)
- In vivo poststroke angiogenesis was significantly reduced in PTX3 KO mice compared to WT mice 14 days after MCAo, as revealed by reduced vascular density, less newly formed blood vessels and decreased expression of VEGFR2. (nih.gov)
- Angiogenesis is a pivotal process in the growth, invasion, and spread of tumors ( 1 - 3 ) and is used as a therapeutic target in several types of cancer based on the abnormalities of tumor blood vessels ( 4 - 6 ). (aacrjournals.org)
- Angiogenesis is the formation of blood vessels or capillaries from existing blood vessels due to specific signals. (abcam.com)
- Angiogenin induces the growth of new blood vessels. (abcam.com)
- These vascular complications result from an imbalanced inflammation and from the dysregulation of angiogenesis, defined as the formation of new blood vessels from pre-existent ones. (rsc.org)
- Other factors such as angiopoietin-1/2, platelet-derived growth factor BB, matrix metalloproteinases, and fibroblast growth factor also participate in angiogenesis and the maturation of blood vessels ( 4 ). (diabetesjournals.org)
- Angiogenesis is the process which forms new blood vessels. (cancerindex.org)
- However, when a specific angiogenesis promoter is blocked, some cancers eventually grow blood vessels by using a different angiogenesis promoter. (cancerindex.org)
- Angiogenesis, the formation of new blood vessels from preexisting ones, plays an important role not only in normal physiological events such as embryonic development and wound healing but also in pathological conditions such as tumor growth, diabetic retinopathy, and rheumatoid arthritis. (ahajournals.org)
- Regarding opioids, the author notes that one the one hand, opioids have been shown to promote angiogenesis (formation of new blood vessels necessary for tumor growth). (geripal.org)
- Cyclooxygenase regulates colon carcinoma-induced angiogenesis by two mechanisms: COX-2 can modulate production of angiogenic factors by colon cancer cells, while COX-1 regulates angiogenesis in endothelial cells. (nih.gov)
- In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. (pnas.org)
- These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. (pnas.org)
- Introduction The angiogenic neuropeptide Secretoneurin (SN) is upregulated by hypoxia in several tissues like neurones and skeletal muscle cells and SN gene therapy restores tissue integrity, function and perfusion in the mouse hind-limb ischemia model by induction of angiogenesis, arteriogenesis and vasculogenesis. (ahajournals.org)
- This trend of research has yielded a staggering wealth of genes, proteins, and cells that play critical roles in angiogenesis and some have resulted in successful targeted angiogenic therapies. (springer.com)
- 3- O -Acetyloleanolic acid thus exhibits anti-angiogenic effects and induces apoptosis in HUVECs and the results suggest that it has a potential use for suppression of the tumor growth stimulated by angiogenesis. (springer.com)
- Additionally, the implants may contain an angiogenic substance or a thrombus of blood, preloaded or injected after implantation to aid in initiating angiogenesis. (google.com.au)
- an angiogenic substance for promoting angiogenesis associated with the implant. (google.com.au)
- Blocking the receptor for AGEs (RAGE) inhibited low BSA-AGE- and MC extract-induced ERK1/2 phosphorylation and tube formation, indicating the crucial role of RAGE in the pro-angiogenic effects of MC extracts. (rsc.org)
- Clinical studies indicate that some of these anti-angiogenic agents will take a few months before they really start to work effectively, and obviously most patients with advanced cancer don't have that luxury of waiting a few months. (medpagetoday.com)
- Anti-angiogenic agents bear potential as a treatment of cancer. (biomedcentral.com)
- Nowadays, efforts have been directed toward discovering of new anti-angiogenic agents. (biomedcentral.com)
- Thus, our results demonstrate the crucial role of NO in S1P-induced angiogenesis in vivo and in vitro and suggest the divergent roles of NO in the S1P-induced angiogenic response. (ahajournals.org)
- In this study, we demonstrated the inhibitory effect of recombinant human apolipoprotein(a) kringle V (rhLK8) in an animal model of ischemia-induced retinal neovascularization. (diabetesjournals.org)
- Taken together, our data suggested the possible application of rhLK8 in the treatment of retinal neovascularization by suppression of fibronectin-mediated angiogenesis. (diabetesjournals.org)
- These data indicate that NO production induced by vasoactive agents, such as SP, functions as an autocrine regulator of the microvascular events necessary for neovascularization and mediates angiogenesis. (jci.org)
- Since the outer aspects of chronic gly- caemic control, angiogenesis neovascularization, by a wide qRS. (musicaenlamochila.net)
- Momordica charantia (MC, bitter melon) has been shown to prevent AGE formation and to promote angiogenesis in diabetic wounds in animal models. (rsc.org)
- We tested the hypothesis that AMSCs from older patients with atherosclerotic renovascular disease (RVD) differ from normal kidney donors, and whether hypoxia changes their functional and molecular properties to promote angiogenesis. (elsevier.com)
- Poststroke neurogenesis was assessed by nestin, doublecortin (DCX) and bromodeoxyuridine (BrdU) immunostaining, whereas angiogenesis was assessed by BrdU, vascular endothelial growth factor receptor 2 (VEGFR2) and PECAM-1 immunostaining. (nih.gov)
- Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor-induced angiogenesis. (geripal.org)
- CA4P induced time- and dose-dependent antiproliferative activities against human umbilical vein endothelial cells (HUVECs), and caused G2/M arrest accompanied with DNA fragmentation. (cognizantcommunication.com)
- A mathematical model of tumour-induced capillary growth. (springer.com)
- Mathematical modeling of capillary formation and development in tumor angiogenesis: Penetration into stroma. (springer.com)
- A mathematical model of growth factor induced capillary growth in the retina. (springer.com)
- A mathematical model of the first steps of tumour-related angiogenesis: capillary sprout formation and secondary branching. (springer.com)
- In addition to increased vascular resistance, chronic hypoxia induced Rho kinase-dependent capillary angiogenesis. (ahajournals.org)
- Rho kinase also mediated hypoxia-induced capillary angiogenesis, a previously unrecognized but potentially important adaptive response. (ahajournals.org)
- In vitro models and in vivo Matrigel implants show that inhibition of RhoA or ROCK prevents growth factor-induced endothelial cell migration and organization into capillary-like structures 12,13 and vessel formation. (ahajournals.org)
- During wound healing, ALK1 expression is induced in pre-existing arteries supplying the wound area and in newly branching small arteries in contrast to minimal expression in the capillary-like vessels of the wound rim area. (aacrjournals.org)
- These findings suggest that SN gene therapy might be a promising new therapeutic agent to improve ischemic cardiac dysfunction. (ahajournals.org)
- Angiogenesis, the formation of new vessels from pre-existing endothelium, is an important process in the adult organism because it supports the increasing demands for metabolic supplies (nutrients, various growth factors, and molecular oxygen) at sites of tissue repair or regeneration, during processes such as pregnancy, the female reproductive cycle, wound healing, and revascularization of ischemic tissues. (biomedcentral.com)
- Induction of angiogenesis by the methods of the invention can be used in therapeutic angiogenesis in, for example, treatment of ischemic syndromes such as coronary or peripheral arterial disease. (patentgenius.com)
- Implants and associated delivery systems for promoting angiogenesis in ischemic tissue are provided. (google.com.au)
- This invention relates to methods and devices for inducing angiogenesis in ischemic tissue. (google.com.au)
- Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro . (hindawi.com)
- An agaricus extract enhanced doxorubicin-induced apoptosis against drug-resistant human hepatocellular carcinoma (24) . (mskcc.org)
- Activin receptor-like kinase-1 (ALK1) is a type I, endothelial cell-specific member of the transforming growth factor-β superfamily of receptors known to play an essential role in modulating angiogenesis and vessel maintenance. (aacrjournals.org)
- subsequently, the TNF-alpha moiety induces apoptosis in endothelial cells expressing CD13, thereby inhibiting tumor-associated angiogenesis. (cancer.gov)
- Angiogenesis is similar for both genotypes 6 days after MCAo (B), but PTX3 knockout (KO) have less striatal proliferating vessels than wild-type (WT) mice 14 days after MCAo (E), even after normalisation with the total amount of PECAM-1 (E) and (F). Scale bars = 50 μm. (nih.gov)
- However, emerging data suggest that cancer therapy targeting only the tumor-existing vessels or tumor angiogenesis may not eradicate the tumor completely. (biomedcentral.com)
- In vitro neurogenesis and angiogenesis assays were carried out on neurospheres derived from WT or interleukin-1β (IL-1β) KO mice, and mouse endothelial cell line bEnd.5 respectively. (nih.gov)
- AnxA1 2-26 ) on heterologous skin scaffolds transplantation in BALB/c mice, focusing on inflammation and angiogenesis. (frontiersin.org)
- The combination of OGF with taxol (3 mg/kg, weekly) or cisplatin (4 mg/kg, weekly for 2 weeks) for 37 days reduced tumor volumes and weight in contrast to mice receiving individual agents alone. (scirp.org)
- Approach and Results- Thrombus was induced in the inferior vena cava of mice. (ahajournals.org)
- For example, CITED2 was downregulated by insulin by up to 54% in the cultured endothelial cells, whereas CITED2 in cardiac endothelial cells was increased in both diet-induced obese mice and db/db mice. (diabetesjournals.org)
- Isomerized hop extract (IHE), which consists mainly of isohumulones and is required in the beer brewing process, was investigated for its effects on diet-induced obesity in two strains of mice. (nature.com)
- The inhibition of intestinal dietary fat absorption may be the mechanism by which IHE induces its weight-lowering effects in high-fat diet-fed mice. (nature.com)
- The present study was designed to evaluate the efficacy of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis and growth of established Lewis lung carcinoma in mice. (biomedcentral.com)
- The monoclonal antibody portion of the F16-IL2 fusion protein binds to tumor cells expressing the tumor associated antigen (TAA) tenascin-C. In turn, the IL-2 moiety of the fusion protein stimulates natural killer (NK) cells, macrophages and neutrophils and induces T-cell antitumor cellular immune responses thereby selectively killing tenascin-C-expressing tumor cells. (cancer.gov)
- To analyze the signaling pathways involved in S1P-induced angiogenesis and clarify the role of NO in this process, we performed in vivo and in vitro angiogenesis assays. (ahajournals.org)
- In cells, growth factor-induced EGFR and ErbB2 phosphorylation was also efficiently inhibited with IC50s of 11 and 220 nM, respectively. (wikipedia.org)
- An international peer-reviewed journal for original articles and reviews on the cellular and molecular mechanisms that regulate angiogenesis in physiological and pathological conditions. (cancerindex.org)
- Interaction of CITED2 and HIF1 in the regulation of hypoxia/ischemia-induced angiogenesis in insulin resistance and type 2 diabetes. (diabetesjournals.org)
- Therapeutic angiogenesis with VEGF164 for facilitation of guidewire crossing in experimental arterial chronic total occlusions. (biomedsearch.com)
- Mesenchymal stromal/stem cells derived from human umbilical cord (UC-MSCs) uniquely combine properties of embryonic and postnatal MSCs and may be the most acceptable, safe, and effective source for allogeneic cell therapy e.g. for therapeutic angiogenesis. (biomedcentral.com)
- The field of therapeutic angiogenesis is currently expanded by using MSCs from other sources, importantly from the umbilical cord and placenta. (biomedcentral.com)
- rhLK8 induced no definite toxicity on endothelial cells and retinal tissues at the therapeutic dosage. (diabetesjournals.org)
- While each single agent led to a modest decrease in survivin levels, the combination dramatically reduced its expression, which correlated with an induction of apoptosis. (aacrjournals.org)
- In addition, F16-IL2 may potentiate the cytotoxicity of other chemotherapeutic agents. (cancer.gov)
- In addition, this agent is able to sensitize FACT-positive tumor cells to the cytotoxic effects of other chemotherapeutic agents. (cancer.gov)
- Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. (urotoday.com)
- Normal somatic stem cells (SC) are naturally resistant to chemotherapeutic agents due to their expression of various membrane transporter molecules (such as MDR-1), detoxifying enzymes and DNA repair proteins. (chemweb.com)
- In addition, they also have a slow rate of cell turnover and therefore escape from chemotherapeutic agents that target rapidly replicating cells. (chemweb.com)
- We believe that the use of antisense molecules against targets such as survivin are a viable option for the treatment and management of cancer patients, either as a single agent or in combination with chemotherapeutic agents," said Bharvin Patel, Ph.D., of Eli Lilly, and lead investigator of the study. (eurekalert.org)
- Other studies are currently assessing the activity of LY2181308 and chemotherapeutic agents in the cancer model. (eurekalert.org)
- Restoration or overexpression of Slit3 is a potential therapeutic approach to repress the tumor growth and enhance the efficacy of chemotherapeutic agents. (deepdyve.com)
- Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. (uniprot.org)
- Early studies showed that diurnal variations in estrogen secretion in rats could be regulated by changes in melatonin synthesis and release, induced by the daily cycle of light and dark via the efferent limb of the reflex in the sympathetic innervation of the pineal gland. (drugs.com)
- Like other members of the ribonuclease superfamily, angiogenin is a cytotoxic agent that can eliminate cellular protein synthesis. (abcam.com)
- All treatments suppressed DNA synthesis and angiogenesis, whereas exposure to taxol or cisplatin, but not OGF, induced apoptosis. (scirp.org)
- Additive inhibitory effects on DNA synthesis and angiogenesis were recorded in animals treated with both OGF and taxol, or OGF and cisplatin, in comparison to individual compounds alone. (scirp.org)
- May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. (uniprot.org)
- Based on the above concerns, we thought that identification and preclinical/clinical development of novel agents that are nontoxic but can specifically suppress tumor-induced angiogenesis may be a rational approach to develop effective therapies for ACC. (aspetjournals.org)
- Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen. (hindawi.com)
- Check for active clinical trials using this agent. (cancer.gov)
- New treatment options for this disease including the Food and Drug Administration (FDA)-approved agents temsirolimus, everolimus, sorafenib, and sunitinib have improved clinical outcomes. (aacrjournals.org)
- Combretastatin A4 phosphate (CA4P) is currently undergoing clinical trials as a tumor vascular-targeting agent. (cognizantcommunication.com)
- Because a number of agents that target the TGF-β-pathway are in clinical trials, the results of the proposed study could be rapidly translated to the clinic. (aacrjournals.org)
- Therapy with erythropoiesis-stimulating agents (ESAs) is associated with an increase in hemoglobin levels, a reduction in transfusion requirements, and, according to many clinical trialists and experienced clinicians, an improvement in functional status, productivity, and quality of life. (jnccn.org)
- Clinical studies suggest that the incidence of venous thromboembolic events increased after treatment of these patients with antiangiogenic agents. (ahajournals.org)
- In addition, nymphaeol-A dose- and time-dependently induced caspase-dependent apoptosis in tube-forming HUVECs. (hindawi.com)
- The success of these agents has largely been attributed to their ability to disrupt angiogenesis, which plays a critical role in the development and progression of RCC ( 2 , 3 ). (aacrjournals.org)
- few data demonstrate that these dimers are able to induce morphological and functional changes observed during the onset and progression of AMD. (biologists.org)
- Whereas the role of TGF-β in tumor angiogenesis and progression is well understood, its role in lymphatic vessel function remains far from understood. (aacrjournals.org)
- A variety of pharmacological approaches including inhibition of tumor invasion, angiogenesis, signal transduction pathways, and most recently the targeting of tumor stroma, are now under fervent development. (chemweb.com)
- The treatment agent is selected to either disrupt the abnormal nerve pathways and/or. (google.com)
- Although the signaling pathways activated by S1P have been extensively studied in various cell types, the precise signaling mechanism by which S1P elicits angiogenesis is only recently beginning to emerge. (ahajournals.org)
- It has been shown that N-terminal portion of the Annexin A1 protein (AnxA1) with its anti-inflammatory properties induces epithelial mucosa repair and presents potential therapeutic approaches. (frontiersin.org)
- In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. (pnas.org)
- These results suggest that IHE may be helpful in humans in preventing diet-induced obesity and perhaps even metabolic syndrome, the latter of which is known to be associated with obesity. (nature.com)
- Pentraxin 3 mediates neurogenesis and angiogenesis after cerebral ischaemia. (nih.gov)
- In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. (uniprot.org)
- In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. (aacrjournals.org)
- (23) reported aberrant expression of PPARγ in chemically induced colonic carcinoma and human colon cancer cell lines. (aacrjournals.org)