Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Cyclohexanes: Six-carbon alicyclic hydrocarbons.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Endostatins: Angiostatic proteins that are formed from proteolytic cleavage of COLLAGEN TYPE XVIII.SesquiterpenesNeovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.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.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.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.Angiogenesis Inducing Agents: Agents that induce or stimulate PHYSIOLOGIC ANGIOGENESIS or PATHOLOGIC ANGIOGENESIS.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.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.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.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.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.Vascular Endothelial Growth Factor Receptor-2: A 200-230-kDa tyrosine kinase receptor for vascular endothelial growth factors found primarily in endothelial and hematopoietic cells and their precursors. VEGFR-2 is important for vascular and hematopoietic development, and mediates almost all endothelial cell responses to VEGF.Vascular Endothelial Growth Factors: A family of angiogenic proteins that are closely-related to VASCULAR ENDOTHELIAL GROWTH FACTOR A. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells.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.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.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.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.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.Human Umbilical Vein Endothelial Cells: Endothelial cells that line venous vessels of the UMBILICAL CORD.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.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.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.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.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).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.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.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Isocoumarins: Compounds that differ from COUMARINS in having the positions of the ring and ketone oxygens reversed so the keto oxygen is at the 1-position of the molecule.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.Angiostatic Proteins: Proteins that specifically inhibit the growth of new blood vessels (ANGIOGENESIS, PHYSIOLOGIC).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.Capillaries: The minute vessels that connect the arterioles and venules.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Kringles: Triple-looped protein domains linked by disulfide bonds. These common structural domains, so-named for their resemblance to Danish pastries known as kringlers, play a role in binding membranes, proteins, and phospholipids as well as in regulating proteolysis. Kringles are also present in coagulation-related and fibrinolytic proteins and other plasma proteinases.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 Line, Tumor: A cell line derived from cultured tumor cells.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Mice, Inbred C57BLThrombospondins: 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.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).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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Blood Vessels: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).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.Calreticulin: A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.Transplantation, Heterologous: Transplantation between animals of different species.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.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.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.PhthalazinesMicrovessels: The finer blood vessels of the vasculature that are generally less than 100 microns in internal diameter.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Collagen Type IV: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.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.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.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.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.Mice, Inbred BALB CReverse 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.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.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.Lung Neoplasms: Tumors or cancer of the LUNG.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.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.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.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.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.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.IndazolesLaminin: 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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Epoxy Compounds: Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.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)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.Drugs, Investigational: Drugs which have received FDA approval for human testing but have yet to be approved for commercial marketing. This includes drugs used for treatment while they still are undergoing clinical trials (Treatment IND). The main heading includes drugs under investigation in foreign countries.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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).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.Proteoglycans: Glycoproteins which have a very high polysaccharide content.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.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)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.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Kidney Neoplasms: Tumors or cancers of the KIDNEY.Spiro Compounds: A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.Sulfonamides: A group of compounds that contain the structure SO2NH2.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.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).Carcinoma, Renal Cell: A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.Aorta: The main trunk of the systemic arteries.Fibrosarcoma: A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Clinical Trials as Topic: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.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.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)Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.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.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Colonic Neoplasms: Tumors or cancer of the COLON.Microcirculation: The circulation of the BLOOD through the MICROVASCULAR NETWORK.Cell Adhesion: Adherence of cells to surfaces or to other cells.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.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).Dacarbazine: An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Retinal Neovascularization: Formation of new blood vessels originating from the retinal veins and extending along the inner (vitreal) surface of the retina.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.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.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.Wound Healing: Restoration of integrity to traumatized tissue.Antineoplastic Agents, Alkylating: A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.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.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Carcinoma, Non-Small-Cell Lung: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.Retinal Vessels: The blood vessels which supply and drain the RETINA.Lymphangiogenesis: 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.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.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.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.Combined Modality Therapy: The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.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.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.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.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Melanoma, Experimental: Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.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.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.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.
Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect. (1/4006)
Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor gene p53 is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here, we investigated the antiangiogenic effect of the wild-type p53 (wt-p53) gene transfer on a human non-small cell lung cancer cell line. Mutant p53-expressing H226Br non-small cell lung cancer cells were transduced with the wt-p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semiquantitative reverse transcription-PCRs for the detection of altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by s.c. inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor, and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1, resulting in reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wt-p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wt-p53 gene is antiangiogenic, which may explain, in part, the mechanism of the bystander effect induced by the wt-p53 gene transfer on adjacent tumor cells. (+info)Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth. (2/4006)
Several angiogenesis inhibitors are fragments of larger proteins that are themselves not active as angiogenesis inhibitors. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In the present study, we examined whether the full-length calreticulin molecule shares the antiangiogenic and antitumor activities of vasostatin. Similar to vasostatin, calreticulin selectively inhibited endothelial cell proliferation in vitro, but not cells of other lineages, and suppressed angiogenesis in vivo. When inoculated into athymic mice, calreticulin inhibited Burkitt tumor growth comparably with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids inhibited endothelial cell proliferation in vitro and Burkitt tumor growth in vivo comparably with vasostatin. An internal calreticulin fragment encompassing amino acids 120-180 also inhibited endothelial cell proliferation in vitro and angiogenesis in vivo comparably with calreticulin and vasostatin. These results suggest that the antiangiogenic activities of vasostatin reside in a domain that is accessible from the full-length calreticulin molecule and localize to calreticulin N-terminal amino acids 120-180. Thus, calreticulin and calreticulin fragments are inhibitors of angiogenesis that directly target endothelial cells, inhibit angiogenesis, and suppress tumor growth. This information may be critical in designing targeted inhibitors of pathological angiogenesis that underlies cancer and other diseases. (+info)Inhibition of angiogenesis and intrahepatic growth of colon cancer by TAC-101. (3/4006)
We demonstrated in this study that inhibition of intra-hepatic growth of colon cancer by TAC-101 is mediated by inhibition of angiogenesis. In vitro experiments showed that TAC-101 inhibited the proliferation of murine hepatic sinusoidal endothelial (HSE) cells induced by coculture with murine colon 26-L5 (L5) cells. HSE cell proliferation was also enhanced by conditioned medium of L5 cells (CM-L5), and this enhancement of proliferation was abrogated by anti-vascular endothelial growth factor antibody. CM-L5 also induced in vitro tube formation of HSE cells on Matri-gel, and this activity of CM-L5 was abrogated by TAC-101 in a concentration-dependent manner. On the other hand, p.o. administration of TAC-101 inhibited tumor-induced angiogenesis in vivo and decreased the weights of L5 tumors in the mouse liver. Reverse transcriptase-PCR analysis using in vivo tumor tissue suggested that repression of vascular endothelial growth factor expression by TAC-101 was associated with the antiangiogenic activity. TAC-101 alone and 5-fluorouracil (5-FU)/D,L-leucovorin (LV) significantly inhibited the intrahepatic growth of L5 tumors (P = 0.002 and 0.001, respectively), whereas 5-FU alone did not (P = 0.088). When TAC-101 was administered with 5-FU/LV, marked enhancement of antitumor activity was observed (95% inhibition; P<0.001). This enhanced antitumor effect was also observed in experiments using Co-3 human colon adenocarcinoma. Concurrent treatment with TAC-101 and 5-FU/LV and sequential treatment with 5-FU/LV followed by TAC-101 resulted in significant augmentation of antitumor activity against Co-3 (overall P = 0.007 and 0.015, respectively). These findings indicate that TAC-101 inhibits tumor angiogenesis and suggest that it may be effective against hepatic metastasis of colon cancer. (+info)A pharmacokinetically guided Phase II study of carboxyamido-triazole in androgen-independent prostate cancer. (4/4006)
We conducted a Phase II clinical trial of the antiproliferative, antimetastatic, and antiangiogenic agent carboxyamido-triazole (CAI), using pharmacokinetic assessment to guide drug dosing. Fifteen patients who had stage D2 androgen-independent prostate cancer with soft tissue metastases were enrolled. Because CAI previously had been shown to decrease prostate-specific antigen secretion in vitro, this marker was not used to assess disease status. The dose of CAI used in this study was calculated so that plasma steady-state maximum concentrations between 2.0 and 5.0 microg/ml would be maintained. Following the initial dosage adjustment, 93% (14 of 15) of patients were within the predicted range. Fourteen of 15 patients were evaluable for response. All of the 14 evaluable patients demonstrated progressive disease at approximately 2 months. Twelve patients progressed by computed tomography and or bone scan at 2 months, whereas two patients demonstrated clinical progression at 1.5 and 2 months. One patient was removed from study at 6 weeks due to grade II peripheral neuropathy lasting >1 month. Although no clinical responses were noted, a 27.7% decrease in serum vascular endothelial growth factor concentration was observed. CAI does not possess clinical activity in patients with androgen-independent prostate cancer and soft tissue metastases. Pharmacokinetically guided dosing, although found to be feasible using a Bayesian approach, was not found to be of practical benefit. Although plasma CAI concentrations were maintained within the designated range, grade III toxicity requiring drug discontinuation was still observed. (+info)Angiogenesis inhibitor endostatin is a distinct component of elastic fibers in vessel walls. (5/4006)
Theendothelial cell inhibitor endostatin (22 kDa) is part of the carboxyl-terminal globular domain of collagen XVIII and shows a widespread tissue distribution. Immunohistology of adult mouse tissues demonstrated a preferred localization in many vessel walls and some other basement membrane zones. A strong immunogold staining was observed across elastic fibers in the multiple elastic membranes of aorta and other large arteries. Staining was less strong along sparse elastic fibers of veins and almost none was observed in the walls of arterioles and capillaries. Strong evidence was also obtained for some intracellular and basement membrane associations. Immunogold double staining of elastic fibers showed a close colocalization of endostatin with fibulin-2, fibulin-1, and nidogen-2, but not with perlecan. Reasonable amounts of endostatin could be extracted from aorta and skin by EDTA, followed by detergents, with aorta being the richest source of the inhibitor identified so far. Solubilizations with collagenase and elastase were approximately fivefold less efficient. Immunoblots of aortic extracts detected major endostatin components of 22-25 kDa whereas skin extracts also contained some larger components. Solid-phase assays demonstrated distinct binding of recombinant mouse endostatin to the fibulins and nidogen-2, consistent with their tissue colocalization. Together, the data indicate several different ways for endostatin to be associated with the extracellular matrix, and its release may determine biological activation. This also defines a novel function for some elastic tissues. (+info)Antiangiogenic activity of prostate-specific antigen. (6/4006)
BACKGROUND: Measurement of serum levels of prostate-specific antigen (PSA) is widely used as a screening tool for prostate cancer. However, PSA is not prostate specific, having been detected in breast, lung, and uterine cancers. In one study, patients whose breast tumors had higher levels of PSA had a better prognosis than patients whose tumors had lower PSA levels. To test the hypothesis that PSA may have antiangiogenic properties, we evaluated the effects of PSA on endothelial cell proliferation, migration, and invasion, which are key steps in angiogenesis, the process by which tumors develop a blood supply. METHODS: To assess the antiproliferative effects of PSA, we treated bovine endothelial cells and human endothelial cell lines (HUVEC and HMVEC-d) with purified human PSA (0.1-10 microM) and then stimulated them with 10 ng/mL fibroblast growth factor-2 (FGF-2). Effects on FGF-2- or vascular endothelial growth factor (VEGF)-stimulated endothelial cell migration, invasion, and tube formation were measured by use of one cell line only (HUVEC). PSA was administered to mice at 9 microM for 11 consecutive days after intravenous inoculation of B16BL6 melanoma cells to assess its ability to inhibit the formation of lung colonies (i.e., metastatic tumors). RESULTS: PSA inhibited endothelial cell proliferation, migration, and invasion at IC(50) (i. e., the concentration at which inhibition was 50%) values ranging from 0.3-5 microM. In addition, PSA inhibited endothelial cell responses to both angiogenic stimulators tested, FGF-2 and VEGF. In a mouse model of metastatic disease, daily PSA treatment resulted in a 40% reduction in the mean number of lung tumor nodules compared with phosphate-buffered saline treatment (two-sided P =.003). CONCLUSION: To our knowledge, this is the first report that PSA may function in tumors as an endogenous antiangiogenic protein. This function may explain, in part, the naturally slow progression of prostate cancer. Our findings call into question various strategies to inhibit the expression of PSA in the treatment of prostate cancer. (+info)Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action. (7/4006)
Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to mammalian cells. While this makes it difficult to discover antifungal agents without toxic side effects, it also has enabled detailed studies of drug action in simple genetic model systems. We review here studies on the antifungal actions of antineoplasmic agents. Topics covered include the mechanisms of action of inhibitors of topoisomerases I and II; the immunosuppressants rapamycin, cyclosporin A, and FK506; the phosphatidylinositol 3-kinase inhibitor wortmannin; the angiogenesis inhibitors fumagillin and ovalicin; the HSP90 inhibitor geldanamycin; and agents that inhibit sphingolipid metabolism. In general, these natural products inhibit target proteins conserved from microorganisms to humans. These studies highlight the potential of microorganisms as screening tools to elucidate the mechanisms of action of novel pharmacological agents with unique effects against specific mammalian cell types, including neoplastic cells. In addition, this analysis suggests that antineoplastic agents and derivatives might find novel indications in the treatment of fungal infections, for which few agents are presently available, toxicity remains a serious concern, and drug resistance is emerging. (+info)Tumor development under angiogenic signaling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy. (8/4006)
The effects of the angiogenic inhibitors endostatin, angiostatin, and TNP-470 on tumor growth dynamics are experimentally and theoretically investigated. On the basis of the data, we pose a quantitative theory for tumor growth under angiogenic stimulator/inhibitor control that is both explanatory and clinically implementable. Our analysis offers a ranking of the relative effectiveness of these inhibitors. Additionally, it reveals the existence of an ultimate limitation to tumor size under angiogenic control, where opposing angiogenic stimuli come into dynamic balance, which can be modulated by antiangiogenic therapy. The competitive influences of angiogenically driven growth and inhibition underlying this framework may have ramifications for tissue size regulation in general. (+info)VEGFMetastasisInhibitsTumorsInhibit angiogenesisEndostatinCancerTherapiesKinase inhibitorsFormation of new blood vesselsProcess of angiogenesisInhibition of angiogenesisTherapyTherapeuticMacular degenerationPhysiologicalAngiogenicMechanismsSelectiveBlood vesselEndogenous angiogenesis inhibitorsCheckpoint inhibitorsTyrosine kinase inReceptorsVivo angiogenesisEndothelial cell migration and angiogenesisCancersClinicalAntiangiogenicTherapeuticsSmall moleculeEfficacyPotent inhibitorIntegrinsJudah FolkmanBevacizumabTumourStimulatorsOncogenes and tumor supprAction of angiogenesisVasculatureGrowth and angiogenesisTumor Induced AngiogenesisPaclitaxelLymphangiogenesis
- Inhibition of the VEGF pathway has become the focus of angiogenesis research as approximately 60% of malignant tumors express high concentrations of VEGF. (wikipedia.org)
- Strategies to inhibit the VEGF pathway include antibodies directed against VEGF or VEGFR, soluble VEGFR/VEGFR hybrids, and tyrosine kinase inhibitors. (wikipedia.org)
- The most widely used VEGF pathway inhibitor on the market today is Bevacizumab . (wikipedia.org)
- It inhibits angiogenesis by blocking the pro-angiogenic activities of VEGF and FGF-basic. (sigmaaldrich.com)
- SU 5416 is a vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 inhibitor. (sigmaaldrich.com)
- by blocking angiogenesis growth factors (substances, such as VEGF, which promote the process of developing new blood vessels). (cancerindex.org)
- VEGF inhibitors in renal cell carcinoma. (cancerindex.org)
- The arrival of targeted therapies-vascular endothelial growth factor (VEGF) pathway inhibitors and mammalian target of rapamycin (mTOR) inhibitors-and programmed death 1 (PD-1) inhibitors has transformed the management of renal cell carcinoma (RCC). (cancerindex.org)
- It then discusses the pivotal trials that have investigated VEGF inhibitors in metastatic RCC, as well as in adjuvant and neoadjuvant settings. (cancerindex.org)
- Finally, it addresses some practical considerations and future directions in the use of VEGF inhibitors in RCC. (cancerindex.org)
- Noting that placental growth factor [PIGF, a member of the VEGF family that binds VEGF receptor 1 (VEGFR-1)] is not required for normal development and maintenance of the vasculature but has been implicated in pathological angiogenesis, Fischer et al . (sciencemag.org)
- VEGF is a key molecular target for specific polyphenols found in tea, apples and cocoa which potently inhibit VEGF signalling and angiogenesis at physiological concentrations. (greenmedinfo.com)
- In a mouse corneal neovascularization assay, this compound inhibited VEGF-induced angiogenesis. (nih.gov)
- s3f also inhibited VEGF 165 , as well as bFGF-induced in vivo angiogenesis as determined by the alginate micro-encapsulation and Matrigel plug assays. (aacrjournals.org)
- Indeed, s3a was found to inhibit capillary sprouting in an in vitro assay of angiogenesis and VEGF 165 -induced migration of endothelial cells. (aacrjournals.org)
- Cediranib inhibits the potent angiogenesis factor VEGF which is known. (bio-medicine.org)
- Cediranib inhibits the potent angiogenesis factor VEGF, which is known to be abundantly present in glioblastomas and play a critical role in tumor blood vessel formation. (bio-medicine.org)
- Jain also notes that it will be important to identify biomarkers that may indicate which patients are most likely to benefit from treatment with angiogenesis inhibitors and to identify the mechanisms by which glioblastomas and other tumors resist anti-VEGF therapies. (bio-medicine.org)
- Although VEGF has growth factor activity for some cancers, its bigger role in cancer spread is to promote angiogenesis by aiding multiplication and survival of the endothelial cells that form the new blood vessels. (oasisofhope.com)
- PD-1/PD-L1 checkpoint inhibitors have been associated with promising activity as monotherapy in patients with HCC, and VEGF inhibition with bevacizumab has shown "modest activity" in this population. (onclive.com)
- Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic factors that can drive tumor angiogenesis ( 6 , 7 ), although platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) also play an important role. (aacrjournals.org)
- In contrast, to inhibit lymph angiogenesis, so far there are only a few experimental approaches (e.g., the use of a VEGF R1R2 -Trap 5 or of a blocking anti-VEGFR3-antibody 9 ) but there is no U.S. Food and Drug Administration (FDA)-approved substance available yet. (arvojournals.org)
- Introduction of non-platinum based PARP inhibitors and VEGF inhibitors in second and third-line settings has changed the treatment regime for ovarian cancer dramatically. (marketresearch.com)
- VEGF or other angiogenesis factors produced by tumor cells or nearby cells can cause the development of blood vessels that feed the growing tumor. (cancerquest.org)
- This increase in VEGF results in shifting the balance of angiogenesis inducers and inhibitors, thereby switching on angiogenesis. (ewg.org)
- Keywords: CCR7, esophageal squamous carcinoma, angiogenesis, VEGF Introduction Esophageal squamous cell carcinoma (ESCC) is usually one of the most aggressive tumors and is usually also the most common cause of esophagus malignancy deaths WZ8040 worldwide . (acancerjourney.info)
- Tumor angiogenesis WZ8040 is usually a result of an imbalance between pro-angiogenic factors, such as the vascular endothelial growth factor (VEGF) family and inhibitors of angiogenesis, including endostatin, angiostatin and other related molecules . (acancerjourney.info)
- VEGF-A regulates the sprouting and proliferation of endothelial cells and can stimulate tumor angiogenesis. (acancerjourney.info)
- A number of currently-used anti-angiogenesis drugs function by inhibiting pro-angiogenic factors, for example the monoclonal antibody bevacizumab binds to VEGF-A and prevents it from binding to the VEGF receptors, and sunitinib and sorafenib are small molecules that attach to VEGF-R and prevent the binding of VEGF-A . (acancerjourney.info)
- VEGF promotes angiogenesis by aiding multiplication and survival of the endothelial cells needed to form new blood vessels. (oasisofhopecancercenter.com)
- We also utilize NF-kappaB inhibitors and EGFR inhibitors because they both boost tumor production of VEGF and other angiogenic growth factors. (oasisofhopecancercenter.com)
- Inhibition of tumor angiogenesis based on administration of recombinant humanized antibodies targeting A-VEGF was the first clinically approved angiogenesis-based therapy and has been used in the treatment of several cancers, including breast, colorectal and lung cancers, but the overall effectiveness of this approach is debated [ 3 ]. (mdpi.com)
- PURPOSE It has been recently shown that the catecholamine neurotransmitter dopamine (DA) strongly and selectively inhibits vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-induced angiogenesis. (semanticscholar.org)
- VEGF Signal Transduction in Angiogenesis. (indigo.ca)
- Some common components of human diets also act as mild angiogenesis inhibitors and have therefore been proposed for angioprevention, the prevention of metastasis through the inhibition of angiogenesis. (wikipedia.org)
- Tumor growth and metastasis depend on blood supply and blood vessel formation (angiogenesis). (cochrane.org)
- The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. (nature.com)
- In sum, C11 is a novel selective FGFR1 inhibitor that exhibits potent activity against breast cancer metastasis and angiogenesis. (nature.com)
- Cancer progression and metastasis depend on recruitment of new capillaries from preexisting vessels, a process known as angiogenesis ( 1 ). (aacrjournals.org)
- Publications] Masaki Tamura, Toru Yanase, and kenichi Tanaka: 'Angiogenesis inhibitor and inhibition of metastasis' Hematology and Incology. (nii.ac.jp)
- Angiogenesis, the process of new blood vessel formation, is critical for tumor progression, invasion, and metastasis in solid tumors. (oncologynurseadvisor.com)
- Angiogenesis has been shown to be essential for growth and metastasis of solid tumors. (wikidoc.org)
- In particular, the presence of regional attack, distant metastasis and tumor-induced angiogenesis show highly malignant potential in esophageal carcinoma patients . (acancerjourney.info)
- Plenty of researches demonstrate that tumor induced angiogenesis is usually required to maintain malignant ESCC growth and metastasis, and constitutes an important hallmark of ESCC progression . (acancerjourney.info)
- Chemokines and their receptors play important functions in metastasis and tumor growth, however, the role of chemokine receptors in angiogenesis has only recently been discovered . (acancerjourney.info)
- Angiogenesis is required for tumor growth and metastasis, and targeting angiogenesis is a novel anticancer strategy. (aacrjournals.org)
- In mouse models of Lewis lung carcinoma (LLC) and hepatoma H22, when given as a single dose, AARP is highly effective for reducing tumor growth, angiogenesis, and metastasis, and increasing survival time. (aacrjournals.org)
- Taken together, our findings suggest AARP is a highly effective, safe, and more potent antiangiogenic agent for blocking tumor angiogenesis and metastasis, and warrants further testing for clinical applications. (aacrjournals.org)
- However, angiogenesis is now widely recognized as one of the hallmarks of cancer, a crucial step in the transition of tumors from a dormant state to a malignant state, and playing an essential role in tumor growth, invasion and metastasis [ 1 ]. (mdpi.com)
- Controlling tumor angiogenesis and metastasis of C26 murine colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models, Cancer Research 59, 1252-1258, Mar. 15, 1999. (freepatentsonline.com)
- An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels ( angiogenesis ). (wikipedia.org)
- Endostatin is an endogenous inhibitor of angiogenesis, and in vitro inhibits the migration of endothelial cells. (sigmaaldrich.com)
- inhibits endothelial cell proliferation and angiogenesis. (sigmaaldrich.com)
- Withaferin A also inhibits angiogenesis by binding to vimentin and F-actin. (sigmaaldrich.com)
- A new paper 1 reports that a common and readily available prescription drug for athlete's foot, itraconazole, inhibits both mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2) in endothelial cells, suppressing growth and proliferation and, hence, angiogenesis. (life-enhancement.com)
- Topical or systemic application of bevacizumab inhibits both inflammation-induced angiogenesis and lymphangiogenesis in the cornea. (arvojournals.org)
- One such class of drugs inhibits angiogenesis (the development of new blood vessels), which is essential for tumour growth. (ox.ac.uk)
- 1. An antagonist that inhibits angiogenesis by modifying protein-protein interactions between matrix metalloproteinase 9 (MMP-9) and a β1-containing integrin, wherein said antagonist comprises an antibody reagent which specifically binds to a polypeptide consisting of the sequence of SEQ ID NO: 1. (freepatentsonline.com)
- 5. The antagonist of claim 1 wherein said antagonist inhibits angiogenesis. (freepatentsonline.com)
- 11. An antagonist that inhibits angiogenesis by modifying protein-protein interactions, wherein said antagonists comprises an antibody reagent which specifically binds to a polypeptide consisting of the sequence of SEQ ID NO: 1. (freepatentsonline.com)
- One of the most recent methods that is being developed for the delivery of anti-angiogenesis factors to tumour regions in cancer sufferers is using genetically modified bacteria that are able to colonize solid tumors in vivo. (wikipedia.org)
- Scientists have studied the effect of angiogenesis inhibitors on certain kinds of tumors and cells. (hopkinsmedicine.org)
- An angiogenesis inhibitor medicine, bevacizumab, has been approved by the FDA to aid in the treatment of glioblastoma, colorectal cancer, non-small cell lung cancer, liver (hepatocellular) carcinoma, neuroendocrine tumors, and metastatic renal cell cancer. (hopkinsmedicine.org)
- The tumors that did develop from s3f-expressing HEK293 cells developed at a much slower rate and had a significantly lower concentration of tumor-associated blood vessels, indicating that s3f is an inhibitor of tumor angiogenesis. (aacrjournals.org)
- Therefore, there is a need to develop more selective inhibitors to suppress tumors through selective targeting of FGFRs. (nature.com)
- Because tumors that are unable to elicit angiogenesis remain in a dormant state and fail to grow beyond a few millimeters in size ( 2 ), the multistep process of angiogenesis has fostered an intense search for agents that might inhibit this process ( 3 ). (aacrjournals.org)
- The beneficial effects of anti-angiogenesis drugs in the treatment of the deadly brain tumors called glioblastomas appear to result primarily from reduction of edema the swelling of brain tissue and not from any direct anti-tumor effect, according to a study from Massachusetts General Hospital (MGH) researchers. (bio-medicine.org)
- Angiogenesis is the process whereby new blood vessels form, in response to chemical signals produced by wounded tissue or by tumors. (oasisofhope.com)
- Axitinib significantly inhibited angiogenesis in rat 9L tumors grown s.c. in scid mice but only moderately delayed tumor growth. (aacrjournals.org)
- Angiogenesis is crucial for the growth of malignant tumors and metastases ( 1 , 2 ). (aacrjournals.org)
- Angiogenesis is a crucial element in the development and dissemination of great tumors. (columbiagypsy.net)
- Tumors that do not produce (or cause other cells to produce) angiogenesis factors can not grow. (cancerquest.org)
- Approximately 50 years ago, Judah Folkman raised the concept of inhibiting tumor angiogenesis for treating solid tumors. (mdpi.com)
- In case of tumors, angiogenesis is a rate-limiting step in the development and progression of tumors because tumor growth is generally limited to 1 to 2 mm 3 in the absence of a blood supply ( 3 ). (aacrjournals.org)
- Angiogenesis is a physiological process implicated in growth, invasion and metastization of tumors. (frontiersin.org)
- The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of receptor tyrosine kinase antagonists/inhibitors, especially ErbB receptor antagonists, more preferably EGF receptor (Her 1) antagonists and anti-angiogenic agents, preferably integrin antagonists, optionally together with agents or therapy forms that have additive or synergistic efficacy when administered together with the combination of antagonists/inhibitors, such as chemotherapeutic agents and or radiation therapy. (patentsencyclopedia.com)
- Because these agents inhibit angiogenesis, they should have at least additive benefit in combination with standard chemotherapy and radiation therapy [24, (nih.gov)
- Therapies that inhibit angiogenesis are attracting fresh interest in combination regimens with immune checkpoint immunotherapy in tumor types such as hepatocellular carcinoma, urothelial carcinoma, and endothelial cancer. (onclive.com)
- There are known substances that both stimulate angiogenesis and stop, or inhibit, angiogenesis. (chemocare.com)
- An important cancer fighting strategy is to inhibit angiogenesis. (oasisofhopecancercenter.com)
- Kringle 5 has been shown to inhibit angiogenesis by inducing the cell-cycle arrest, autophagy, and apoptosis of proliferating endothelial cells ( 8, 9 ). (aacrjournals.org)
- Such antagonists inhibit angiogenesis, tumor growth and disease states. (freepatentsonline.com)
- Collagen XVIII is cleaved to form endostatin, and this system might act as the negative control of angiogenesis. (sigmaaldrich.com)
- Here, we present the effects of oral rifampicin on human cancer progression and its antiangiogenic properties, which were comparable to the angiogenesis inhibitor endostatin. (aacrjournals.org)
- Furthermore, we found that rifampicin exerts its antiangiogenic effect through inhibition of the expression of angiogenesis-associated genes in a manner comparable to the action of endostatin, an endogenous angiogenesis inhibitor known to down-regulate a variety of growth- and angiogenesis-related genes in a wide range of endothelial lineage cells ( 8 , 9 ). (aacrjournals.org)
- 1997) Endostatin An Endogenous Inhibitor of Angiogenesis and Tumor Growth. (scirp.org)
- Aim: To construct the human endostatin gene, which is the angiogenesis inhibitor, into non-fusion expression vector in Escherichia coli. (elsevier.com)
- Conclusion: The cloned Endostatin gene of 552 bp has almost the same gene sequence with the endostain cDNA of collagen XVIII in GenBank, which indicates that human endostatin gene obtains non-fused expression in Escherichia coli, it lays an experimental methodological foundation for the anti-angiogenesis therapy with endostatin gene. (elsevier.com)
- Other angiogenesis inhibitors, including angiostatin and endostatin, have also been tested in clinical trials [ 4 ], without as yet reaching wide marketing approval. (mdpi.com)
- Two of the most potent endogenous antiangiogenic inhibitors, angiostatin and endostatin are the most well-studied in the angiogenesis literature ( 5 ). (aacrjournals.org)
- Angiogenesis inhibitors were once thought to have potential as a " silver bullet " treatment applicable to many types of cancer , but the limitations of anti-angiogenic therapy have been shown in practice. (wikipedia.org)
- Nonetheless, inhibitors are used to effectively treat cancer, macular degeneration in the eye, and other diseases that involve a proliferation of blood vessels. (wikipedia.org)
- Endogenous inhibitors are attractive targets for cancer therapy because they are less toxic and less likely to lead to drug resistance than some exogenous inhibitors. (wikipedia.org)
- Angiogenesis inhibitors have different side effects from most conventional cancer chemotherapy medicines because they work very differently. (hopkinsmedicine.org)
- The Foundation promotes angiogenesis research and aiming to improve treatments for patients with angiogenesis related disease (including cancer). (cancerindex.org)
- Vitamin C therapy can down-regulate angiogenesis and inflammation promoting cytokines in some cancer patients. (greenmedinfo.com)
- There is currently no reliable evidence from randomized controlled trials demonstrating that the benefits of angiogenesis-inhibitors outweigh their risks in treating advanced thyroid cancer. (cochrane.org)
- There is currently no reliable evidence available from randomized controlled trials regarding the benefits and harms of the use of angiogenesis-inhibitors for treating advanced thyroid cancer. (cochrane.org)
- To evaluate the benefits and risks of angiogenesis-inhibitors for metastatic thyroid cancer when given alone, or in combination with chemotherapy or radiotherapy. (cochrane.org)
- We planned to include randomized controlled trials that compared angiogenesis-inhibitors with other treatments, no treatment, or placebo in participants who had pathologically confirmed advanced thyroid cancer. (cochrane.org)
- In order to take advantage of both the COX-dependent and COX-independent benefits of NSAIDs and selective COX-2 inhibitors, will require evaluation of these agents in neoplastic disease settings, using cancer-specific biomarkers. (nih.gov)
- The reported success of selective COX-2 inhibitors in cancer prevention could be related to angiogenesis inhibition . (nih.gov)
- Angiogenesis is an important therapeutic target in cancer, and to fully exploit its therapeutic potential, combination chemotherapeutic/antiangiogenic regimens should be optimized and delivered earlier to more patients. (aacrjournals.org)
- Research in angiogenesis has strong implications in cancer therapy as angiogenesis is one of the hallmarks of cancer. (scbt.com)
- The National Cancer Institute (NCI) will sponsor phase III trials to test the efficacy of AE-941/Neovastat, an angiogenesis inhibitor developed by AEterna Laboratories Inc., a Canadian biotechnology corporation, in the treatment of cancer. (cancernetwork.com)
- In our work to date with patients, AEterna s AE-941/Neovastat has demonstrated to be an interesting angiogenesis inhibitor for the treatment of cancer. (cancernetwork.com)
- Angiogenesis plays a crucial role in the growth and spread of cancer. (oasisofhope.com)
- Agiogenic inhibitors have become an important part of treatment for many type of cancer as they stop tumor from growing their own blood vessels. (oasisofhope.com)
- The promising but still limited efficacy of angiogenesis inhibitors as monotherapies for cancer treatment indicates a need to integrate these agents into existing therapeutic regimens. (aacrjournals.org)
- Taken together, these findings clearly support the pharmacological roles of marmesin in regulating angiogenesis, and warrant further evaluation and development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer. (sigmaaldrich.com)
- This phase I, accelerated titration study investigated the maximum tolerated dose, safety, pharmacokinetic profile, and pharmacodynamics of BIBF 1120, a novel, orally available angiokinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor receptors, in 61 patients with advanced cancer. (aacrjournals.org)
- Angiogenesis inhibitors offer a novel approach for cancer therapy ( 5 ). (aacrjournals.org)
- Cancer Angiogenesis Inhibitor Market Research Report Forecast 20172022 is a valuable source of insightful data for business strategists. (bioportfolio.com)
- This Cancer Angiogenesis Inhibitor market study provides comprehensive data which enhances the understanding, scope and application of this report. (bioportfolio.com)
- Are substances that inhibit the growth of new blood vessels (angiogenesis inhibitors), alone or in combination with conventional chemotherapy, likely to improve outcomes for women with ovarian cancer? (cochrane.org)
- However, there is currently no evidence that angiogenesis inhibitors improve OS, nor is there enough evidence to justify the routine use of angiogenesis inhibitors in treating women with ovarian cancer. (cochrane.org)
- A. Rossi, P. Maione, M. L. Ferrara, P. C. Sacco, C. Schettino, M. A. Bareschino and C. Gridelli, " Angiogenesis Inhibitors and Vascular Disrupting Agents in Non-Small Cell Lung Cancer", Current Medicinal Chemistry (2009) 16: 3919. (eurekaselect.com)
- PARP inhibitors are anticipated to be the fastest growing drug class in the ovarian cancer market through the forecast period. (marketresearch.com)
- Although data have shown that angiogenesis inhibitors significantly improve overall and progression-free survival compared with non-angiogenesis inhibitor-containing therapies, efficacy may be affected by non-small cell lung cancer (NSCLC) histologic subtype. (oncologynurseadvisor.com)
- We aimed at assessing the overall efficacy of angiogenesis inhibitor (AI)-containing regimens in the treatment of advanced non-small-cell lung cancer (NSCLC) according to histological types. (oncologynurseadvisor.com)
- Integrin Antagonists and Other Low Molecular Weight Compounds as Inhibitors of Angiogenesis New Drugs in Cancer Therapy. (docme.ru)
- HIGHLIGHTS Integrin Antagonists and Other Low Molecular Weight Compounds as Inhibitors of Angiogenesis: New Drugs in Cancer Therapy** Athanassios Giannis* and Frank Riibsam Angiogenesis (neovascularization), the process by which new blood capillaries are formed from an already existing blood vessel, is of fundamental importance for a number of physiological and pathological events including embryogenesis, wound healing, chronic inflammation. (docme.ru)
- Due to the observation that an adequate blood supply is necessary for tumor growth, Folkman postulated in the early 1970s that inhibitors of angiogenesis are of potential use in cancer therapy. (docme.ru)
- Angiogenesis inhibitors for the treatment of ovarian cancer. (ox.ac.uk)
- OBJECTIVES: To compare the effectiveness and toxicities of angiogenesis inhibitors in the treatment of ovarian cancer. (ox.ac.uk)
- SELECTION CRITERIA: Randomised controlled studies comparing angiogenesis inhibitors with either standard chemotherapy or no treatment, in women with ovarian cancer. (ox.ac.uk)
- We identified five abstracts of completed RCTs of four different angiogenesis-inhibiting agents, with a total of 3701 participants.Meta-analysis of two trials found no statistically significant difference in overall survival (OS) between women with newly-diagnosed advanced ovarian cancer who received concurrent and maintenance bevacizumab compared to those who received chemotherapy (carboplatin and paclitaxel) alone. (ox.ac.uk)
- More research is needed to identify which cancers may be best treated with targeted therapies such as monoclonal antibodies or anti-angiogenesis drugs and to identify additional targets for more types of cancer. (chemocare.com)
- Angiogenesis is associated with tumor development and malignancy and is a validated target for cancer treatment. (eurekaselect.com)
- Abnormal angiogenesis is not limited to cancer. (cancerquest.org)
- 5 The process of angiogenesis in cancer is shown in the animation below. (cancerquest.org)
- The process of blood vessel formation is termed angiogenesis.This process is a very active area of research in cancer treatment for several reasons. (cancerquest.org)
- Tumour angiogenesis and the levels of plasminogen activator inhibitor type I (PAI-I) are both informative prognostic markers in breast cancer. (lu.se)
- To evaluate the interrelationship of angiogenesis and the PAI-I level in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. (lu.se)
- We conclude that the PAI-I level and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-I is not only based on its involvement in angiogenesis. (lu.se)
- Cancer growth inhibitors block certain chemical signals within cells, which slows down or stops the growth of the cancer. (macmillan.org.uk)
- So it may also be called a cancer growth inhibitor. (macmillan.org.uk)
- Cancer growth inhibitors make it difficult for cancer cells to receive these signals. (macmillan.org.uk)
- In contrast, cancer cells always have angiogenesis switched on. (ewg.org)
- WO9916755A1 ] The present invention relates to compounds which inhibit tyrosine kinase enzymes, compositions which contain tyrosine kinase inhibiting compounds and methods of using tyrosine kinase inhibitors to treat tyrosine kinase-dependent diseases/conditions such as angiogenesis, cancer, atherosclerosis, diabetic retinopathy or autoimmune diseases, in mammals. (epo.org)
- Mareedu N, Escalante CP (2017) Angiogenesis Inhibitor Induced Thromboembolism in Cancer Patients. (clinmedjournals.org)
- But, angiogenesis also plays a crucial role in the promoting the growth and spread of cancer. (oasisofhopecancercenter.com)
- Angiogenesis inhibitors (AIs) have become established as an effective cancer treatment. (cdc.gov)
- The National Cancer Institute's Angiogenesis Core Facility seek parties interested in in-licensing a new set of non-cytotoxic antiangiogenic small molecules. (cancer.gov)
- The National Cancer Institute's Angiogenesis Core Facility is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a new set of non-cytotoxic antiangiogenic small molecules. (cancer.gov)
- Deregulation of angiogenesis plays a role in many human diseases, including cancer, age-related macular degeneration, diabetic retinopathy, and endometriosis. (cancer.gov)
- Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis. (semanticscholar.org)
- However, persistent and upregulated angiogenesis is often found to be a critical causal factor in certain pathologic conditions such as cancer, atherosclerosis, and diabetic retinopathy ( 2, 3 ). (aacrjournals.org)
- Thus, interfering with angiogenesis is a promising strategy in cancer therapy to delay tumor growth by preventing a tumor from developing its own blood supply system ( 3 , 5 ). (aacrjournals.org)
- The fact that these effects are carried out at lower concentrations than those required for other inhibitors of angiogenesis makes AD0157 a new promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies. (mdpi.com)
- Currently, angiogenesis inhibitors are likely to change the face of medicine, arising as an attractive approach for the treatment of cancer and other angiogenesis-dependent diseases, with some antiangiogenic compounds approved by the Food and Drug Administration (FDA) for the treatment of cancer, blindness and other angiogenesis-dependent diseases, encouraging expectations in their therapeutic potential [ 3 , 4 ]. (mdpi.com)
- The phase III CONFIRM clinical trials demonstrated that metastatic colorectal cancer patients with elevated serum lactate dehydrogenase (LDH) had improved outcome when the vascular endothelial growth factor receptor (VEGFR) inhibitor PTK/ZK (Vatalanib) was added to FOLFOX4 chemotherapy. (qub.ac.uk)
- Lenz, H-J. / Intratumoral expression profiling of genes involved in angiogenesis in colorectal cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib) . (qub.ac.uk)
- Based on these achievements targeted drug development programs have been implemented to interfere with tumor angiogenesis as an attractive strategy in cancer treatment. (weltbild.de)
- Although tumor growth can be stunted by a variety of single angiogenesis inhibitors ( 2 ), combination antiangiogenesis protocols can be more effective than single-agent therapies ( 3 , 4 ). (aacrjournals.org)
- The addition of angiogenesis kinase inhibitors, such as sorafenib, sunitinib, vandetanib, and lenalidomide, to the treatment therapies for patients with advanced non-small cell lung adenocarcinoma improves survival outcomes, a study published in the journal OncoTargets and Therapy has shown. (oncologynurseadvisor.com)
- HCC is a typical blood vessel-rich tumor, and anti-angiogenesis-related therapies have become the standard treatment for patients with advanced HCC[1- (researchsquare.com)
- Targeted therapies involve production of components such as monoclonal antibodies or anti-angiogenesis drugs may best be used in the short term, combination with traditional therapies. (chemocare.com)
- Michele Moschetta, Marta Cesca, Francesca Pretto and Raffaella Giavazzi, " Angiogenesis Inhibitors: Implications for Combination with Conventional Therapies", Current Pharmaceutical Design (2010) 16: 3921. (eurekaselect.com)
- We developed a network walking algorithm to extract connectivity information from the interactome and applied it to simulate the level of network perturbation by three multi-targeted anti-angiogenic kinase inhibitors. (biomedcentral.com)
- To date, the US Food and Drug Administration has approved 4 oral tyrosine kinase inhibitors (TKIs) and 1 anti-angiogenic antibody for the treatment of advanced HCC. (researchsquare.com)
- Tyrosine kinase inhibitors and proteasome inhibitors are examples of small-molecule drugs. (cancer.ca)
- Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. (semanticscholar.org)
- Angiogenesis is the formation of new blood vessels. (hopkinsmedicine.org)
- Angiogenesis inhibitors are substances which prevent this formation of new blood vessels, thereby stopping or slowing the growth or spread of tumours. (cancerindex.org)
- Anti-angiogenesis is the process of stopping the formation of new blood vessels. (chemocare.com)
- The formation of new blood vessels, known as angiogenesis , satisfies these needs. (ewg.org)
- Angiogenesis, the process leading to formation of new blood vessels, is an essential physiological and developmental process. (mdpi.com)
- The complex process of angiogenesis proceeds in the following stages (Figure 1): a) activation of endothelial cells (EC) and pericytes by the growth factors, b) degradation of the basal lamina of the bloodvessel by the action of proteases (collagenases, plasminogen activator), c) migration (and proliferation) of EC and pericytes towards Figure 1. (docme.ru)
- Interestingly, the expression of angiogenic-stimulating factors such as vascular endothelial growth factor or kinase insert domain receptor were suppressed by FK228, whereas that of angiogenic-inhibiting factors such as von Hippel Lindau and neurofibromin2 were induced, suggesting that a gene-transcription effect was involved in the inhibition of angiogenesis by FK228. (nih.gov)
- Angiogenesis inhibitor therapy may stabilize the tumor and prevent it from growing further. (hopkinsmedicine.org)
- However, successful clinical application of angiogenesis inhibitors, irrespective of monotherapy or combination therapy, requires long-term administration, but most of these entering clinical trials are costly, large molecular weight proteins requiring parenteral administration ( 3 , 5 ). (aacrjournals.org)
- How can I get more information about Angiogenesis Inhibitors Therapy at Oasis of Hope? (oasisofhope.com)
- She said the hy pothesi s behind combining angiogenesis inhibitors and immunotherapy is that ablation or "reprogramming" the microenvironment might boost the efficacy of anticancer therapy. (onclive.com)
- This study aimed at confirming whether ACEIs are beneficial in anti-angiogenesis therapy for hepatocellular carcinoma. (researchsquare.com)
- Modern targeted therapy types include the use of monoclonal antibodies and anti-angiogenesis drugs, both of which are described in greater depth here. (chemocare.com)
- Preclinical and clinical evidence substantiates the feasibility of combining angiogenesis inhibitors with conventional anticancer therapy. (eurekaselect.com)
- Bevacizumab (Avastin, MVASI, Zirabev) is a type of targeted therapy called an angiogenesis inhibitor. (cancer.ca)
- Therapy with Angiogenesis Inhibitors (AIs) is a newer targeted approach in treating cancers. (clinmedjournals.org)
- Angiogenesis Inhibitors (AIs) are one of the classes of targeted therapy being used in the treatment of various cancers. (clinmedjournals.org)
- However, the therapeutic use of endogenous inhibitors has disadvantages. (wikipedia.org)
- Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis. (nih.gov)
- Disrupting one or even a few angiogenesis pathways is often insufficient to achieve sustained therapeutic benefits due to the complexity of angiogenesis. (biomedcentral.com)
- Through increased specificity, potency and ocular permeability, novel SRPK1 inhibitors have potential to reach therapeutic levels in posterior eye segments following eye drop administration and improve treatment for patients with wAMD and DME. (arvojournals.org)
- The present invention describes methods for inhibition angiogenesis in tissues using vitronectin αvβ3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing αvβ3 antagonists. (google.com.au)
- Given its high vascularization and immunogenicity, antiangiogenics and immune checkpoint inhibitors (ICI), respectively, are two therapeutic approaches that have shown efficacy in HCC. (biomedcentral.com)
- Several of the angiogenesis inhibitors are also effective in treating an eye disease, macular degeneration. (hopkinsmedicine.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)
- In adults, angiogenesis is only switched on during physiological processes such as wound healing or menstruation, and then only transiently and regulated extremely carefully. (ewg.org)
- Angiogenesis, a physiological process involving the generation of new capillaries from pre-existing vessels, is strictly controlled by a balance of stimulators and inhibitors, being restricted in adults to some processes related to the reproductive cycle and wound repair. (mdpi.com)
- PDGF: impact on physiological and tumor angiogenesis. (weltbild.de)
- Inhibiting angiogenesis requires treatment with anti-angiogenic factors, or drugs which reduce the production of pro-angiogenic factors, prevent them binding to their receptors or block their actions. (wikipedia.org)
- Here, we have identified a novel gene, ARHGAP18, as an endogenous negative regulator of angiogenesis, limiting pro-angiogenic signaling and promoting vascular stability. (centenary.org.au)
- Angiogenesis needs both EC migration into an angiogenic specific niche market and EC proliferation to be able to type new vascular buildings . (columbiagypsy.net)
- Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria caused by anti-angiogenic drugs (AADs) according to diabetic nephropathy guidelines or expert recommendations. (researchsquare.com)
- Under normal physiologic circumstances, angiogenesis is tightly regulated by a balance between angiogenic activators and inhibitors ( 1 ). (aacrjournals.org)
- In the tumor microenvironment, when angiogenic stimulators outbalance angiogenic inhibitors, generating a proangiogenic response and an increased blood vessel density to allow the tumor to progress ( 3 , 4 ). (aacrjournals.org)
- The effects of selective COX-2 inhibitors on angiogenesis may also be due, in part, to COX-independent mechanisms [123- (nih.gov)
- Some of the COX-independent mechanisms for NSAIDs and selective COX-2 inhibitors include activation of protein kinase G, inhibition of NF-kappa B activation, downregulation of the antiapoptotic protein Bcl-XL, inhibition of PPAR delta, and activation of PPAR gamma. (nih.gov)
- However, our knowledge of the precise rules and mechanisms of tumor angiogenesis is usually clearly limited and the recognition of other novel targets of angiogenesis is usually urgently required to improve the treatment outcomes and lengthen survival for malignancy patients . (acancerjourney.info)
- Recent years brought significant progresses in our understanding of the role of chromatin remodeling and epigenetic mechanisms in the regulation of angiogenesis and tumorigenesis. (mdpi.com)
- Tumor angiogenesis is one of the most prominent mechanisms driving tumor development and progression. (weltbild.de)
- Mechanisms: Vasculogenesis and angiogenesis in development. (weltbild.de)
- In preclinical models, a selective inhibitor of COX-2 was shown to potentiate the beneficial antitumor effects of ionizing radiation with no increase in normal tissue cytotoxicity [113- (nih.gov)
- Given the safety and tolerability of the selective COX-2 inhibitors, and the potent antiangiogenic properties of these agents, the combination of antiangiogenic chemotherapy with a COX-2 inhibitor warrants clinical evaluation [118, 121, (nih.gov)
- One or more of these COX-independent effects could contribute to the antiangiogenic properties of NSAIDs and selective COX-2 inhibitors. (nih.gov)
- Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. (nature.com)
- C11 was a selective FGFR1 inhibitor with an IC 50 of 19 nM among a panel of 20 tyrosine kinases. (nature.com)
- Present FGFR inhibitors can be divided into two groups: nonselective FGFR TKIs and selective FGFR TKIs. (nature.com)
- The most frequently prescribed antidepressants are in a group called selective serotonin reuptake inhibitors, or SSRIs, according to Mayo Clinic. (reference.com)
- Endogenous inhibitors are found in the body naturally and involved in the day-to-day process of regulating blood vessel formation. (wikipedia.org)
- During tumor growth, the action of angiogenesis stimulators surpasses the control of angiogenesis inhibitors, allowing for unregulated or less regulated blood vessel growth and formation. (wikipedia.org)
- To achieve this, tumor cells excrete certain proteins that stimulate blood vessel growth into and around the tumor - a process called angiogenesis. (cancerindex.org)
- New blood vessel formation, known as angiogenesis, is a fundamental event in the process of tumor growth and metastatic dissemination. (eurekaselect.com)
- Since 1980, at least 28 endogenous angiogenesis inhibitors have been identified ( 5 ). (aacrjournals.org)
- Meanwhile, the combined application of immune checkpoint inhibitors and TKIs is the current clinical research trend, and the results are promising[5, (researchsquare.com)
- Signal Transduction inhibitors: Imatinib Mesylate (protein-tyrosine kinase inhibitor), Genefitinib (epidermal growth factor receptor tyrosine kinase inhibitor - EGFR-TK), Cetuximab (epidermal growth factor receptor), Lapatinib (epidermal growth factor receptor (EGFR) and human epidermal receptor type 2 (HER2) tyrosine kinase inhibitor. (chemocare.com)
- Consequently, application of specific strategy, including monoclonal antibody therapeutics and tyrosine kinase inhibitor that may block tumor angiogenesis could prevent the formation of tumor blood vessels and combat ESCC . (acancerjourney.info)
- BAI1 (brain-specific angiogenesis inhibitor 1) is a member of the so-called adhesion-type family of 7-transmembrane receptors ( 3 ). (pnas.org)
- BIBF 1120 is an oral, potent angiokinase inhibitor targeting receptors of the vascular endothelial growth factors, platelet-derived growth factors, and fibroblast growth factors. (aacrjournals.org)
- Fibroblast growth factor 2 (FGF2) induces endothelial cell migration and angiogenesis through two classes of receptors: receptor tyrosine kinases, such as FGF receptor 1 (FGFR1), and heparan sulfate proteoglycans, such as syndecan 4 (S4). (antibodyassay.com)
- Eph receptors and ephrins: role in vascular development and tumor angiogenesis. (weltbild.de)
- The role of the neuropilins and their associated plexin receptors in tumor angiogenesis and tumor progression. (weltbild.de)
- Here, we investigate the effect of HT on in vitro and in vivo angiogenesis. (elsevier.com)
- Inhibition of the mentioned essential steps of in vitro angiogenesis is in agreement with the observed antiangiogenic activity, substantiated by using two in vivo angiogenesis models, the chorioallantoic membrane and the zebrafish embryo neovascularization assays, and by the ex vivo mouse aortic ring assay. (mdpi.com)
- b) result in the production of eicosanoid products TXA2, PGI2, PGE2 that directly stimulate endothelial cell migration and angiogenesis in vivo, and (c) result in enhanced tumor cell, and possibly, vascular endothelial cell survival by upregulation of the antiapoptotic proteins Bcl-2 and/or activation of PI3K-Akt. (nih.gov)
- However, when a specific angiogenesis promoter is blocked, some cancers eventually grow blood vessels by using a different angiogenesis promoter. (cancerindex.org)
- Although new blood vessels can form as part of the body's normal processes, cancers are especially reliant on angiogenesis, as they need a blood supply in order to grow. (cochrane.org)
- Angiogenesis inhibitors prevent cancers from making new blood vessels. (macmillan.org.uk)
- 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)
- Many inhibitors of DNA methylation as well as of histone methylation, have been successfully tested in preclinical studies and some are currently undergoing evaluation in phase I, II or III clinical trials, either as cytostatic molecules-reducing the proliferation of cancerous cells-or as tumor angiogenesis inhibitors. (mdpi.com)
- Antiangiogenic agent, down-regulates the transcription of genes involved in controlling angiogenesis. (sigmaaldrich.com)
- This antiangiogenic chemotherapy regimen could be enhanced by the concurrent administration of an angiogenesis inhibitor [116- (nih.gov)
- Developing a global functional association network among angiogenesis-related genes is much needed to facilitate holistic understanding of angiogenesis and to aid the development of more effective anti-angiogenesis therapeutics. (biomedcentral.com)
- Thus, these compounds would be promising candidates for the development of new anti-angiogenesis therapeutics. (cancer.gov)
- Development of new anti-angiogenesis therapeutics. (cancer.gov)
- Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. (nih.gov)
- RO4396686 is a small molecule KDR, FGFR, and PDGFR inhibitor with good pharmacokinetic properties in rodents. (nih.gov)
- Presently, we investigate the antitumor activity of the small-molecule angiogenesis inhibitor axitinib (AG-013736) and its potential for combination with metronomic cyclophosphamide. (aacrjournals.org)
- Axitinib (AG-013736) is a potent small-molecule inhibitor of the vascular endothelial growth factor receptor ( 15 ). (aacrjournals.org)
- Factors such as continued uptake of approved PARP inhibitors owing to their superior efficacy, long treatment duration, and considerable number of treatment opportunities in first-line advanced settings are likely to propel the growth of the drug class. (marketresearch.com)
- Therefore, researchers sought to evaluate the overall efficacy of angiogenesis inhibitor-containing regimens in the treatment of advanced NSCLC with regard to histologic types. (oncologynurseadvisor.com)
- As it is a potent inhibitor of angiogenesis, it also strongly suppresses tumor growth. (sigmaaldrich.com)
- 2-Methoxyestradiol (2-ME) is a potent inhibitor of endothelial cell proliferation and angiogenesis. (sigmaaldrich.com)
- a& Integrins and angiogenesis. (docme.ru)
- Fluciclatide (GE Healthcare) (AH111585) is a small cyclic peptide containing the RGD tripeptide (figure 1), which preferentially binds with high affinity to α¬vβ3 integrins that are up-regulated in angiogenesis. (clinicaltrials.gov)
- Integrins in Angiogenesis. (indigo.ca)
- It was postulated as long ago as 1971 by Dr. Judah Folkman that prevention of angiogenesis could inhibit tumor growth by starving them of vital nutrients. (cancerquest.org)
- Dr. Judah Folkman is considered the 'father of angiogenesis. (indigo.ca)
- To analyze whether bevacizumab can inhibit inflammatory angiogenesis and lymphangiogenesis in the cornea. (arvojournals.org)
- 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)
- We incorporated tumour growth, angiogenesis and vessel remodelling at tissue level, by coupling tumour cell phenotypes and endothelial cell behaviour in response to local chemical and haemodynamical microenvironment. (cancerindex.org)
- Hypoxia and tumour angiogenesis. (weltbild.de)
- Angiogenesis is regulated by the activity of endogenous stimulators and inhibitors. (wikipedia.org)
- Angiogenesis is controlled by a local balance between stimulators and inhibitors of new vessel growth and is suppressed under normal physiologic conditions. (wikidoc.org)
- The interactome includes the involvement of oncogenes and tumor suppressor genes in angiogenesis. (biomedcentral.com)
- This paper is concerned with the bifurcation phenomenon of a free-boundary problem modeling the tumor growth under the action of angiogenesis and inhibitor. (springer.com)
- In this paper, we study a mathematical model of tumor growth under the action of angiogenesis and inhibitor. (springer.com)
- As a result of angiogenesis, the tumor possesses its own vasculature. (springer.com)
- Assume that the nutrient and the inhibitor are single species consumed by tumor cell through its own vasculature and diffusion from the boundary. (springer.com)
- Tumor angiogenesis is usually the complex processes by generation of a new network of blood vessels develop from an existing vasculature that penetrates into the neoplastic tissue to supply the nutrients and oxygen required to maintain and enable tumor growth and attack . (acancerjourney.info)
- Angiogenesis and Vascular Remodeling: Biology and Architecture of the Vasculature. (indigo.ca)
- Tumor-induced angiogenesis is a process that tumor cells secrete cytokines that stimulate the vascular system to grow toward the tumor. (springer.com)
- Extent of intratumoral angiogenesis, as indicated by microvessel tortuosity and microvessel density, was significantly reduced by paclitaxel in a dose-dependent manner. (nih.gov)
- αPIGF inhibited tumor angiogenesis and lymphangiogenesis, as well as tumor recruitment of proangiogenic macrophages. (sciencemag.org)
- These studies indicate that semaphorins may perhaps be able to function as modulators of vasculogenesis, angiogenesis, and possibly lymphangiogenesis. (aacrjournals.org)
- Objective The study was focused on the effect and mechanism of IFN-α and IFN-γ on the proliferation and migration of the lymphatic endothelial cell (LEC), and further discovering the safe, effective and practical inhibitors of lymphangiogenesis.Materials and Methods LECs were taken from the pig thoracic duct. (dissertationtopic.net)