Angiostatic Proteins: Proteins that specifically inhibit the growth of new blood vessels (ANGIOGENESIS, PHYSIOLOGIC).Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Chemokine CXCL10: A CXC chemokine that is induced by GAMMA-INTERFERON and is chemotactic for MONOCYTES and T-LYMPHOCYTES. It has specificity for the CXCR3 RECEPTOR.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.Endostatins: Angiostatic proteins that are formed from proteolytic cleavage of COLLAGEN TYPE XVIII.Platelet Factor 4: A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.Receptors, CXCR3: CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.Pregnadienediols: Doubly unsaturated pregnane derivatives with two hydroxy groups substituted anywhere on the rings or side chains.Chemokine CXCL11: A CXC chemokine that is induced by GAMMA-INTERFERON. It is a chemotactic factor for activated T-LYMPHOCYTES and has specificity for the CXCR3 RECEPTOR.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.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.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.Benzenesulfonates: Organic salts and esters of benzenesulfonic acid.Phenylurea Compounds: Compounds that include the amino-N-phenylamide structure.Kidney Neoplasms: Tumors or cancers of the KIDNEY.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.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.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.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)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 Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.Epigenomics: The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.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.BerlinEndometriosis: A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.GermanyNewspapers: Publications printed and distributed daily, weekly, or at some other regular and usually short interval, containing news, articles of opinion (as editorials and letters), features, advertising, and announcements of current interest. (Webster's 3d ed)Mass Media: Instruments or technological means of communication that reach large numbers of people with a common message: press, radio, television, etc.Germany, EastDrug Information Services: Services providing pharmaceutic and therapeutic drug information and consultation.National Library of Medicine (U.S.): An agency of the NATIONAL INSTITUTES OF HEALTH concerned with overall planning, promoting, and administering programs pertaining to advancement of medical and related sciences. Major activities of this institute include the collection, dissemination, and exchange of information important to the progress of medicine and health, research in medical informatics and support for medical library development.Counterfeit Drugs: Drugs manufactured and sold with the intent to misrepresent its origin, authenticity, chemical composition, and or efficacy. Counterfeit drugs may contain inappropriate quantities of ingredients not listed on the label or package. In order to further deceive the consumer, the packaging, container, or labeling, may be inaccurate, incorrect, or fake.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Government Agencies: Administrative units of government responsible for policy making and management of governmental activities.MEDLARS: A computerized biomedical bibliographic storage and retrieval system operated by the NATIONAL LIBRARY OF MEDICINE. MEDLARS stands for Medical Literature Analysis and Retrieval System, which was first introduced in 1964 and evolved into an online system in 1971 called MEDLINE (MEDLARS Online). As other online databases were developed, MEDLARS became the name of the entire NLM information system while MEDLINE became the name of the premier database. MEDLARS was used to produce the former printed Cumulated Index Medicus, and the printed monthly Index Medicus, until that publication ceased in December 2004.Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Osteonectin: Non-collagenous, calcium-binding glycoprotein of developing bone. It links collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for Secreted Protein, Acidic and Rich in Cysteine.Tumor Microenvironment: The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cysteine-Rich Protein 61: A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It may play an important role in the development of branched CAPILLARIES during EMBRYOGENESIS.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.

Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. (1/25)

Platelet factor-4 (PF-4)/CXCL4 was the first chemokine described to inhibit neovascularization. Here, the product of the nonallelic variant gene of CXCL4, PF-4var1/PF-4alt, designated CXCL4L1, was isolated for the first time from thrombin-stimulated human platelets and purified to homogeneity. Although secreted CXCL4 and CXCL4L1 differ in only three amino acids, CXCL4L1 was more potent in inhibiting chemotaxis of human microvascular endothelial cells toward interleukin-8 (IL-8)/CXCL8 or basic fibroblast growth factor (bFGF). In vivo, CXCL4L1 was also more effective than CXCL4 in inhibiting bFGF-induced angiogenesis in rat corneas. Thus, activated platelets release CXCL4L1, a potent regulator of endothelial cell biology, which affects angiogenesis and vascular diseases.  (+info)

BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan. (2/25)

Endorepellin, the C-terminal domain of the heparan sulfate proteoglycan perlecan, possesses angiostatic activity. The terminal laminin-like globular (LG3) domain of endorepellin appears to possess most of the biological activity on endothelial cells. LG3 protein has been detected in the urine of patients with end-stage renal disease and in the amniotic fluid of pregnant women with premature rupture of fetal membranes. These findings suggest that proteolytic processing of endorepellin and the generation of LG3 might have biological significance. In this study, we have identified specific enzymes of the bone morphogenetic protein-1 (BMP-1)/Tolloid family of metalloproteases that cleave LG3 from recombinant endorepellin at the physiologically relevant site and that cleave LG3 from endogenous perlecan in cultured mouse and human cells. The BMP-1/Tolloid family of metalloproteases is thereby implicated in the processing of a major basement membrane proteoglycan and in the liberation of an anti-angiogenic factor. Using molecular modeling, site-directed mutagenesis and angiogenic assays, we further demonstrate that LG3 activity requires specific amino acids involved in Ca(2+) coordination.  (+info)

Angiostatic peptides use plasma fibronectin to home to angiogenic vasculature. (3/25)

A group of angiogenesis inhibitors are derived from fragments of extracellular matrix or blood proteins. Endostatin, antithrombin, and anastellin are members of this group of substances. The plasma adhesion proteins fibronectin and vitronectin serve as cofactors for these three antiangiogenic proteins. Anginex is a synthetic 33-amino acid peptide that was originally modeled to reproduce the beta-sheet structure of antiangiogenic proteins. Here, we show that anginex initiates fibronectin polymerization and is inactive in mice that lack plasma fibronectin. Anginex shares these characteristics with anastellin. Fluorescein-labeled anginex and anastellin specifically localized in angiogenic vessels in vivo. This localization was dependent on plasma fibronectin and inhibited by an Arg-Gly-Asp peptide. Thus, anginex shares with several physiological angiogenesis inhibitors a dependence on plasma adhesion proteins. The role of the adhesion protein interaction apparently is to form integrin-binding complexes that deliver the antiangiogenic proteins to sites of angiogenesis. This functional convergence of several antiangiogenic factors has important implications for antiangiogenic therapies.  (+info)

Identification of CD36 molecular features required for its in vitro angiostatic activity. (4/25)

Thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, acts directly on endothelial cells (EC) via CD36 to inhibit their migration and morphogenesis induced by basic fibroblast growth factor. Here we show that CD36 triggered by TSP-1 inhibits in vitro angiogenesis stimulated by vascular endothelial growth factor-A (VEGF-A). To demonstrate that the TSP-1 inhibitory signal was mediated by CD36, we transduced CD36 in CD36-deficient endothelial cells. Both TSP-1 and the agonist anti-CD36 mAb SMO, which mimics TSP-1 activity, reduced the VEGF-A165-induced migration and sprouting of CD36-ECs. To address the mechanisms by which CD36 may exert its angiostatic function, we investigated the functional components of the C-terminal cytoplasmic tail by site-directed mutagenesis. Our results indicate that C464, R467, and K469 of CD36 are required for the inhibitory activity of TSP-1. In contrast, point mutation of C466 did not alter TSP-1 ability to inhibit EC migration and sprouting. Moreover, we show that activation of CD36 by TSP-1 down-modulates the VEGF receptor-2 (VEGFR-2) and p38 mitogen-associated protein kinase phosphorylation induced by VEGF-A165, and this effect was specifically abolished by point mutation at C464. These results identify specific amino acids of the C-terminal cytoplasmic tail of CD36 crucial for the in vitro angiostatic activity of TSP-1 and extend our knowledge of regulation of VEGFR-2-mediated biological activities on ECs.  (+info)

T2-TrpRS inhibits preretinal neovascularization and enhances physiological vascular regrowth in OIR as assessed by a new method of quantification. (5/25)

PURPOSE: A carboxyl-terminal fragment of tryptophan tRNA synthetase (T2-TrpRS) has demonstrated potent angiostatic activity during retinal developmental neovascularization in vivo. The effects of T2-TrpRS on pathologic neovascularization were tested and compared with a potent VEGF antagonist using the mouse model of oxygen-induced retinopathy (OIR). METHODS: C57BL/6J mice were transiently exposed to hyperoxic conditions (75% O2) between postnatal day 7 (P7) and P12 and then returned to room air. Retinas were isolated, blood vessels stained with isolectin Griffonia simplicifolia, images of retinal whole-mounts acquired, and the area of vascular obliteration and extent of preretinal neovascularization quantified. This method was compared to the commonly used method of OIR quantification in which the number of pre-inner limiting membrane (ILM) nuclei is counted in serial sections of whole eyes. To assess the angiostatic activity of T2-TrpRS, mice were injected intravitreally at P12 with either T2-TrpRS, a VEGF aptamer, or vehicle (PBS) alone, and the effects on area of obliteration and on preretinal neovascular tuft formation were assessed. RESULTS: Using a modified method of quantification in the mouse OIR model based on images of isolectin-stained retinal wholemounts, we were able to assess reliably and consistently both vascular obliteration and preretinal neovascular tuft formation in the same specimen. T2-TrpRS demonstrated potent angiostatic activity, reducing the appearance of pathologic neovascular tufts by up to 90%. Surprisingly, T2-TrpRS also enhanced physiological revascularization of the obliterated retinal vasculature, reducing these areas by up to 60% compared with PBS-injected eyes. In contrast, the VEGF antagonist, while similarly reducing preretinal neovascular tuft formation, did not enhance revascularization of the obliterated areas. CONCLUSIONS: Use of a rapid, quantifiable method to assess the effect of T2-TrpRS on retinal angiogenesis in the OIR model demonstrates the importance of a quantification system that permits simultaneous analysis of a drug's effect on vascular obliteration as well as on preretinal neovascularization. The results obtained using this method suggest enhanced clinical value for compounds such as T2-TrpRS that not only inhibit pathologic neovascularization, but also facilitate physiological revascularization of ischemic tissue.  (+info)

Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the alpha2beta1-integrin receptor. (6/25)

Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported alpha2beta1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an alpha2beta1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/alpha2beta1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in alpha2beta1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.  (+info)

Clinical implications of angiogenesis in cancers. (7/25)

Angiogenesis plays an important role in the growth and progression of cancer. The regulation of tumor angiogenesis depends on a net balance of angiogenic factors and antiangiogenic factors, which are secreted by both tumor cells and host-infiltrating cells. Numerous studies have indicated that assessment of angiogenic activity by either microvessel density or expression of angiogenic factors in cancer can provide prognostic information independent of conventional clinicopathological factors such as tumor staging. Some studies also suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy or radiotherapy. However, the most important clinical implication of tumor angiogenesis is the development of a novel strategy of anticancer therapy targeting tumor vessels instead of cancer cells. Antiangiogenic therapy aims to inhibit the growth of tumor, and current evidence suggests that it works best in combination with conventional cytotoxic chemotherapy. Recently, a monoclonal antibody against vascular endothelial growth factor, which is one of the most potent angiogenic factors, has been approved for clinical use in colorectal cancer patients after a clinical trial confirmed that combining the antibody with standard chemotherapy regimen could prolong patient survival. The clinical implications of angiogenesis in cancer are reviewed in this article.  (+info)

Stimulation of angiostatic platelet factor-4 variant (CXCL4L1/PF-4var) versus inhibition of angiogenic granulocyte chemotactic protein-2 (CXCL6/GCP-2) in normal and tumoral mesenchymal cells. (8/25)

Chemokines affect inflammation and cancer through leukocyte attraction and angiogenesis. Here, we demonstrate that CXCL4L1/platelet factor-4 variant (PF-4var), a highly angiostatic chemokine, is poorly chemotactic for phagocytes and is inducible in monocytes by inflammatory mediators but remained undetectable in macrophages and neutrophils. In addition, CXCL4L1/PF-4var production by mesenchymal tumor cells was evidenced in vitro and in vivo by specific ELISA and immunohistochemistry. CXCL4L1/PF-4var, but not CXCL4/PF-4, was coinduced with the angiogenic chemokine CXCL6/granulocyte chemotactic protein-2 (GCP-2) by cytokines, e.g., IL-1beta and IL-17, in sarcoma cells, but not in diploid fibroblasts. Furthermore, the induction of CXCL6/GCP-2 in endothelial cells by IL-1beta was enhanced synergistically by TNF-alpha but inhibited by IFN-gamma, which synergized with IL-1beta to produce the angiostatic CXCL10/IFN-gamma-induced protein-10. These findings indicate that the equilibrium between angiostatic and angiogenic factors during inflammation and tumor progression is rather complex and differs depending on the chemokine, cell type, and stimulus. Selective intervention in the chemokine network may drastically disturb this delicate balance of angiogenesis and tissue repair. Application of angiostatic CXCL4L1/PF-4var without attraction of protumoral phagocytes may be beneficial in cancer therapy.  (+info)

  • Stimulation by IFN-γ also induces production of the angiostatic chemokines IP-10 and MIG ( 19 , 20 ) and attenuates expression of the angiogenic chemokine IL-8 ( 21 ). (
  • 1,2 By signaling through G protein-coupled chemokine receptors, chemokines govern a variety of cell responses including cell activation and transmigration in leukocytes, as well as in nonhematopoietic cells. (
  • Platelet factor-4 (CXCL4/PF-4), which is released from α-granules of activated platelets, is the first described angiostatic chemokine. (
  • Platelet factor-4 (CXCL4/PF-4) has been identified as a tetrameric heparin-binding protein released from the α-granules of activated platelets long before the term chemokine was introduced ( 1 ). (
  • They are classified into four groups depending on the positioning of the conserved cysteines in the NH 2 -terminal part-CXC, CC, CX 3 C, and C chemokine ligands ( 5 )-and they generally bind to G protein-coupled seven-transmembrane receptors (GPCR) designated CXCR or CCR ( 6 , 7 ). (
  • In contrast, CXCL4/PF-4 belongs to the ELR − CXC chemokine group and is angiostatic ( 10 ). (
  • Interestingly, this impairment was as important as that observed in mice deficient for the well known CC-chemokine monocyte chemoattractant protein-1 (MCP-1). (
  • Recently, exogenous administration of the well-known CC-chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) or a deficiency in its receptor CCR2 have been shown to play a crucial role in monocyte recruitment in the adventitia of growing arteries after vessel occlusion. (
  • CXCL10 ( C-X-C Motif Chemokine Ligand 10) is a 10 kDa protein and member of the CXC family that acts by binding to CXCR3. (
  • In addition, mononuclear cell chemoattractants, such as the CC chemokine CCL2/Monocyte Chemoattractant Protein (MCP)-1, are expressed, leading to monocyte and lymphocyte recruitment in the ischemic area. (
  • We have recently described a marked transient induction of the angiostatic CXC chemokine CXCL10/Interferon-γ inducible Protein (IP)- 10 in the infarct. (
  • Annemiek Nap, a doctor at the University Hospital Maastricht, The Netherlands, told the conference that she and her colleagues tested whether angiostatic therapy (therapy that inhibits the development of blood vessels) could prevent new endometriosis lesions growing and whether it could interfere with the maintenance and growth of existing lesions. (
  • We found that angiostatic therapy inhibits the number of newly developed blood vessels around lesions. (
  • Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. (
  • WNK1 signaling is largely mediated by two downstream protein kinases, OSR1 (oxidative stress responsive 1) and SPAK (STE20/SPS1-related proline-, alanine-rich kinase), sometimes considered redundant in terms of WNK1 function. (
  • With no lysine (K) (WNK) enzymes constitute a family of large (up to 300-kDa) serine/threonine protein kinases with a unique N-terminal kinase domain characterized by the presence of the catalytic lysine replacing a conserved glycine in the phosphate anchor ribbon ( 1 ⇓ - 3 ). (
  • The results suggest that PCBs induce mechanisms against oxidative stress (peroxiredoxins 1 and 2), adaptative changes in the energetic metabolism (enolase 1, glycerol-3-phosphate dehydrogenase, and creatine kinase muscle and brain types), and the implication of the unfolded protein response system (glucose-regulated protein, 58 kDa). (
  • H89 and protein kinase A (PKA) inhibitor peptide prevented rescue of breast cancer cells by PTX, 8-Br-cAMP, and forskolin, suggesting that the effects of cAMP are mediated via PKA-dependent phosphorylation events. (
  • The authors report the generation of a novel transgenic (Tg) mouse that expresses a bioluminescent reporter protein, Nano - lantern , under the control of fetal liver kinase 1 ( Flk1 ). (
  • Yes, GS-101 Aganirsen is a completed novel molecule which is different from the other, because all the drug available anti-VEGF, they have an anti-VEGF action mean while GS-101 is targeting the overexpression of protein which is regulating the overexpression of the VEGF downstream. (
  • However, recent studies suggest that some VEGF neutralizing proteins are not effective in some patients [ 7 , 8 ]. (
  • In contrast to the SSc skin, HIF-1 alpha protein was found to be coexpressed with VEGF in healthy skin samples, indicating that the constitutive VEGF synthesis in the skin is driven by this transcription factor. (
  • Despite the enhanced levels of VEGF, serum samples of SSc patients did not induce angiogen-esis in the vivo chorion allantois membrane assay, indicating that the proangiogenic effects of VEGF may be outweighed by angiostatic factors. (
  • Interestingly, the angiostatic factor endostatin was elevated in a subset of patients and thus may counteract directly the biologic effects of VEGF in SSc patients. (
  • We investigated this possibility by testing the potential value of restoration and maintenance of angiostatic chemokines in delaying the acquired resistance to VEGFR blockade in murine human tumor xenograft models. (
  • Thus, GD2 is a convenient tumor-specific marker for targeting immune-stimulatory protein domains to tumor cells for the purpose of raising an effective immune response against the tumor cells to destroy them. (
  • While the 14.18 mouse antibody (m14.18 antibody) may assist the targeting of these protein domains to tumor cells, its mouse-derived amino acid sequences can impair the desired therapeutic effect. (
  • Other positive regulators are angiotropin, angiogenin, epidermal growth factor, granulocyte colony-stimulating factor, interleukin-1 (IL-1), IL-6, IL-8, platelet-derived growth factor (PDGF), tumor necrosis factor-α (TNF-α), and matrix proteins such as collagen and the integrins. (
  • Although the therapeutic efficacy of this protein (called IFNγ-NGR) in animal models is greater than that of IFNγ, frequent administrations of IFNγ-NGR may result in lower efficacy and tumor resistance. (
  • zebularine enhances tumor cell chemo- and radiosensitivity and has antimitogenic and angiostatic activities . (
  • Recently, a new class of compounds (angiostatic steroids) have been found to inhibit the formation of new blood vessels (i.e. neovascularization) in the eye. (
  • The angiostatic natural product fumagillin was synthesized in the group of Erik Sorensen, and Barry Sharpless and colleagues parlayed practical catalytic transformations into diverse libraries of organic compounds. (
  • These proteins include an antibody moiety and a cytokine moiety, and are useful for targeting cytokines to diseased cells, such as cancer cells. (
  • It was shown recently that human tyrosyl-tRNA synthetase (TyrRS) can be split into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. (
  • Production of this fragment is reported to be stimulated by IFN-γ, a cytokine that also stimulates production of angiostatic factors. (
  • Recently, we demonstrated that one of the tRNA synthetases-human tyrosyl-tRNA synthetase (TyrRS)-has novel cytokine functions in addition to its role in protein synthesis ( 1 ). (
  • The immunomodulatory, antiproliferative, and angiostatic activities of IFNγ make this cytokine an attractive anticancer agent ( 1 - 4 ). (
  • Besides its angiostatic activity, CXCL4/PF-4 is implicated in different biological processes, such as coagulation, promotion of neutrophil cell adhesion to endothelium, and inhibition of megakaryopoiesis and hematopoiesis ( 11 - 13 ). (
  • During airway growth, the lung acquires a rich blood supply, which is regulated by a balance of proangiogenic growth factors and angiostatic proteins. (
  • With an average of more than 200 publications each year since its founding, the Institute has earned its research identity in the United States and worldwide for its accomplishments in organic synthesis, antibody catalysis, protein structure, and RNA chemistry. (
  • Unlike some of the angiostatic steroids, anecortave acetate appears to be lacking in the pharmacological activities typical of the steroid family (i.e. glucocorticoid, anti-inflammatory, cardiovascular, neurologic, diuretic, etc. (
  • Lyophilized from a 0.2 μm filtered solution in MOPS, NaCl and CHAPS with BSA as a carrier protein. (
  • For further dilution, carrier protein (0.1% BSA or HSA) should be added to avoid loss of bioactivity. (
  • The lyophilized protein, though stable at room temperature for up to 3 weeks, is best stored desiccated at -20°C. Reconstituted protein should be used immediately or stored long-term in undiluted working aliquots at -20°C. For long-term storage it is recommended to add a carrier protein (0.1% HSA or BSA). (
  • Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis. (
  • A semi-quantitative assessment of Endostatin protein expression on immunostained tissue micro arrays (TMA) constructed from breast cancer samples of patients with genotype data was performed. (
  • Serum Endostatin levels and Endostatin protein expression on the tissue micro array were not associated with genotype. (
  • By studying circulating levels and tumour Endostatin protein expression, we have shown that any influence of this polymorphism is unlikely to be through an effect on the levels of protein produced. (
  • Recently, it was found that the variant of CXCL4/PF-4 (CXCL4L1/PF-4var) could exert a more pronounced angiostatic and antitumoral effect than CXCL4/PF-4. (
  • 4 The overexpression of YB-1 in arterial SMCs enhanced CCL5 transcriptional activity, CCL5 mRNA and protein expression, and CCL5-mediated monocyte recruitment. (
  • 01) levels of MMP-2 mRNA and protein when compared with nonactive MM and MGUS patients, whereas MMP-9 expression was similar in all groups. (
  • Thus, complexes of mammalian tRNA synthetases with seemingly disparate proteins may in general be relevant to understanding how their expanded functions are implemented. (
  • The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. (
  • Similarly, in the SLN-CFP reporter, Cyan Fluorescent Protein (CFP) was integrated downstream of the coding region of the atrial-specific gene, Sarcolipin (SLN). (
  • The FOXP1 gene encodes a member of the forkhead box transcription factor family that contains a DNA-binding domain and a protein-protein interaction domain. (
  • DOI: and '(ISWI) protein which is the catalytic component of multiple chromatin-remodeling complexes with functions in nucleosome assembly and gene repression (Tsukiyama et al. (
  • For example, interleukin-2, erythropoietin, and growth hormone are all human proteins that are given to humans who already usually make endogenous levels of these proteins. (
  • 01) levels of the angiogenic basic fibroblast growth factor (FGF)-2 in the active MM patients than in nonactive MM and MGUS patients (153 ± 59, 23 ± 17, and 31 ± 18 pg FGF-2/100 μg of protein, respectively). (
  • Using intrinsic protein fluorescence, it was shown that different conditions of pseudotuberculosis bacteria cultivation (temperature, medium, growth phase) led to the changes in spectral properties of porin fluorescence due to the redistribution of the contributions of tyrosine and different classes of tryptophan residues to the total protein emission. (
  • In the present review, we summarize 48 of the significant ECM components including 17 ECM modifying enzymes, seven extracellular angiogenic factors, 13 cell adhesion and cytoskeletal organizers, seven matricellular proteins and growth factors, and four proteoglycans and extra cellular glycoproteins. (
  • 2017-2020 Foundation for Research in Science and the Humanities at the University of Zurich (STwF).Topic: The role of the bromodomain proteins in arthritis susceptibility and synovial biology. (
  • This cascade is precisely controlled by the activity of various regulatory proteins [ 2 ], including members of the Sprouty (SPRY) protein family. (
  • Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. (
  • They not only identified the rat version of LKB1, but also found two proteins that bind to LKB1 and enhance its activity. (
  • Increased MMP2 and MMP9 activity in the ischemic retina has been linked to the proteolytic degradation of pigmented epithelial derived factor (PEDF), a key retinal angiostatic factor. (
  • METHODS: A Phase II trial was initiated to analyze the activity of a continuously administered molecularly targeted treatment regimen (daily pioglitazone [45 mg administered orally] and rofecoxib [25 mg administered orally]) combined with sequentially added angiostatic chemotherapy for patients with previously treated metastatic melanoma (n = 19) or soft tissue sarcoma (n = 21). (
  • RBPJ Inhibitor-1 (RIN1) also blocked the functional interaction of RBPJ with SHARP, a scaffold protein that forms a transcriptional repressor complex with RBPJ in the absence of NOTCH signaling. (
  • At high doses zebularine induced changes in apoptotic proteins in a cell line specific manner manifested by alteration in caspase-3, Bax, Bcl2 and PARP cleavage . (
  • Angiostatic Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • Residues 12-65 of the NH 2 -terminal extension of human TrpRS are homologous to the WHEP-TRP conserved domain protein family (pfam00458) ( 8 ). (
  • Proteomics has been initially used successfully in drug discovery, biomarker identification, and protein-protein interaction studies in human disease processes ( 23 , 24 ). (
  • Subsequently, the feasibility of an eap -based approach was systematically analyzed on the genomic, transcriptional, and protein levels by use of a large collection of human- and veterinary-derived S. aureus and non- S. aureus staphylococcal isolates. (
  • The endosperm varies in ploidy and contains reserves of starch, oils, and proteins, making it an important source of human nutrition. (
  • MicroRNA-18a enhances the interleukin-6-mediated production of the acute-phase proteins fibrinogen and haptoglobin in human hepatocytes. (
  • Myeloid related proteins activate toll-like receptor 4 in human acute coronary syndromes. (
  • CAF-specific proteins can provide important prognostic markers and targets for anticancer drugs. (
  • The Dundee team were looking for a protein that activates AMPK, an enzyme that reduces blood glucose levels and is a target for drugs commonly used in treating Type 2 diabetes. (
  • They hoped that this protein would be a target for new anti-diabetes drugs, and their search ended with an enzyme called LKB1. (
  • He discovered several angiostatic proteins for potential treatment of cancer. (
  • Proteomics data identified several proteins with relevance in the cancer disease which were significantly modulated in CAFs through ITGA11 down-regulation. (
  • He holds numerous patents, including describing the invention of the first engineered dominant negative protein and small molecules for stem cell and cancer applications. (