BibSonomyburst/user/kanefendt/LineBibSonomy RSS feed for /user/kanefendt/Line2012-02-16T11:12:06+01:00http://www.bibsonomy.org/bibtex/2ef0f98aaa58251a4ab8b2c0be419ef9e/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; A Administration Agents Angiogenesis Animals Antineoplastic Antitumor Assays Blood Cell Dose-Response Drug Endothelial Factor Female Growth Humans Hypoxia Indoles Inducing Line Mice Model Neoplasms Organ Outcome Placenta Pregnancy Proteins Pyrroles RANGE Receptor-2 Relationship Research Schedule Scid Specificity Treatment Tumor Tyrosine Vascular Xenograft administration blood dosage drug effects metabolism pathology pharmacology protein response therapy toxicity <span class="authorEditorList"><a href="/author/Ebos">J. M. Ebos</a>, <a href="/author/Lee">C. R. Lee</a>, <a href="/author/Christensen">J. G. Christensen</a>, <a href="/author/Mutsaers">A. J. Mutsaers</a>, and <a href="/author/Kerbel">R. S. Kerbel</a> </span><em>Proc.Natl.Acad.Sci.U.S.A</em> <em>104(43):17069-17074</em> (<em>2007</em>)Fri Feb 05 11:28:39 CET 2010Proc.Natl.Acad.Sci.U.S.A4317069-17074Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy1042007& A Administration Agents Angiogenesis Animals Antineoplastic Antitumor Assays Blood Cell Dose-Response Drug Endothelial Factor Female Growth Humans Hypoxia Indoles Inducing Line Mice Model Neoplasms Organ Outcome Placenta Pregnancy Proteins Pyrroles RANGE Receptor-2 Relationship Research Schedule Scid Specificity Treatment Tumor Tyrosine Vascular Xenograft administration blood dosage drug effects metabolism pathology pharmacology protein response therapy toxicity Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes. However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered proteihttp://www.bibsonomy.org/bibtex/2ac1d1b6812b2c96f4f5978564cf44933/kanefendtkanefendt2010-02-05T11:28:39+01:0080 Adenocarcinoma Adult Aged Antibodies C Cell Chemistry D Disease-Free Endothelial Factor Growth Humans Immunohistochemistry Laboratories Line Lymphatic Messenger Metastasis Middle Neoplasms Prognosis RNA Receptor-3 Research Stomach Survival Tumor Vascular analysis and blood genetics identify methods mortality over supply <span class="authorEditorList"><a href="/author/Juttner">S. Juttner</a>, <a href="/author/Wissmann">C. Wissmann</a>, <a href="/author/Jons">T. Jons</a>, <a href="/author/Vieth">M. Vieth</a>, <a href="/author/Hertel">J. Hertel</a>, <a href="/author/Gretschel">S. Gretschel</a>, <a href="/author/Schlag">P. M. Schlag</a>, <a href="/author/Kemmner">W. Kemmner</a>, and <a href="/author/Hocker">M. Hocker</a> </span><em>J.Clin.Oncol.</em> <em>24(2):228-240</em> (<em>2006</em>)Fri Feb 05 11:28:39 CET 2010J.Clin.Oncol.2228-240Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma24200680 Adenocarcinoma Adult Aged Antibodies C Cell Chemistry D Disease-Free Endothelial Factor Growth Humans Immunohistochemistry Laboratories Line Lymphatic Messenger Metastasis Middle Neoplasms Prognosis RNA Receptor-3 Research Stomach Survival Tumor Vascular analysis and blood genetics identify methods mortality over supply PURPOSE: Vascular endothelial growth factor (VEGF)-D and its homolog VEGF-C influence lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3), and have been implicated in lymphatic tumor spread. Nodal dissemination of gastric adenocarcinomas critically determines clinical outcome and therapeutic options of affected patients. Therefore, we analyzed expression and prognostic significance of VEGF-D along with VEGF-C, and VEGFR-3 in gastric adenocarcinomas. MATERIALS AND METHODS: VEGF-C, VEGF-D, and VEGFR-3 were analyzed in 91 R(0)-resected primary gastric adenocarcinomas, corresponding noncancerous gastric mucosa, and lymph node metastases employing immunohistochemistry and/or in situ hybridization. Blood and lymph vessel densities were assessed after staining with CD31 and LYVE-1-specific antibodies. RESULTS: VEGF-D and VEGF-C were detected in 67.0% and 50.5% of gastric cancers, respectively. Healthy gastric mucosa was negative for VEGF-C and in 12.5% positive for VEGF-D. Presehttp://www.bibsonomy.org/bibtex/2da3316c6e820f72389299eecdae161d6/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; 3 50 Angiogenesis Benzenesulfonates Bone Cell Cells Concentration Diseases Endothelial Factor Growth Hematologic Hematopoietic Human Humans Indoles Inhibitors Inhibitory Kinase Line Marrow Myelopoiesis Phosphorylation Platelet-Derived Protein Proteins Proto-Oncogene Pyridines Pyrimidines Pyrroles Receptors Research Specificity Stem Substrate Sulfonamides Tumor Tyrosine Vascular antagonists c-kit chemically drug effects enzymology fms-Like induced inhibitors methods pharmacology protein <span class="authorEditorList"><a href="/author/Kumar">R. Kumar</a>, <a href="/author/Crouthamel">M. C. Crouthamel</a>, <a href="/author/Rominger">D. H. Rominger</a>, <a href="/author/Gontarek">R. R. Gontarek</a>, <a href="/author/Tummino">P. J. Tummino</a>, <a href="/author/Levin">R. A. Levin</a>, and <a href="/author/King">A. G. King</a> </span><em>Br.J.Cancer</em> <em>101(10):1717-1723</em> (<em>2009</em>)Fri Feb 05 11:28:39 CET 2010Br.J.Cancer101717-1723Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors1012009& 3 50 Angiogenesis Benzenesulfonates Bone Cell Cells Concentration Diseases Endothelial Factor Growth Hematologic Hematopoietic Human Humans Indoles Inhibitors Inhibitory Kinase Line Marrow Myelopoiesis Phosphorylation Platelet-Derived Protein Proteins Proto-Oncogene Pyridines Pyrimidines Pyrroles Receptors Research Specificity Stem Substrate Sulfonamides Tumor Tyrosine Vascular antagonists c-kit chemically drug effects enzymology fms-Like induced inhibitors methods pharmacology protein BACKGROUND: Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. METHODS: Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. RESULTS: Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopanhttp://www.bibsonomy.org/bibtex/2b27000713c04489b8399bb1ffbbb30d3/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Adult Angiogenesis Animals Antibodies BALB Blood C Cell Cells Dipeptides Down-Regulation Endothelial Endothelium Expression Factor Factors Female Gene Growth Humans Inbred Inhibitors Laboratories Ligands Line Lymphangiogenesis Mice Monoclonal Neoplasms Neoplastic Neovascularization Notch Pathologic Proliferation Receptor-3 Receptors Regulation Research Signal Transduction Transgenic Tumor Tyrosine Vascular Vessels antagonists blood cells drug effects genetics inhibitors metabolism pharmacology supply therapy <span class="authorEditorList"><a href="/author/Tammela">T. Tammela</a>, <a href="/author/Zarkada">G. Zarkada</a>, <a href="/author/Wallgard">E. Wallgard</a>, <a href="/author/Murtomaki">A. Murtomaki</a>, <a href="/author/Suchting">S. Suchting</a>, <a href="/author/Wirzenius">M. Wirzenius</a>, <a href="/author/Waltari">M. Waltari</a>, <a href="/author/Hellstrom">M. Hellstrom</a>, <a href="/author/Schomber">T. Schomber</a>, <a href="/author/Peltonen">R. Peltonen</a>, <a href="/author/Freitas">C. Freitas</a>, <a href="/author/Duarte">A. Duarte</a>, <a href="/author/Isoniemi">H. Isoniemi</a>, <a href="/author/Laakkonen">P. Laakkonen</a>, <a href="/author/Christofori">G. Christofori</a>, <a href="/author/Yla-Herttuala">S. Yla-Herttuala</a>, <a href="/author/Shibuya">M. Shibuya</a>, <a href="/author/Pytowski">B. Pytowski</a>, <a href="/author/Eichmann">A. Eichmann</a>, <a href="/author/Betsholtz">C. Betsholtz</a>, and <a href="/author/Alitalo">K. Alitalo</a> </span><em>Nature</em> <em>454(7204):656-660</em> (<em>2008</em>)Fri Feb 05 11:28:39 CET 2010Nature7204656-660Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation4542008& Adult Angiogenesis Animals Antibodies BALB Blood C Cell Cells Dipeptides Down-Regulation Endothelial Endothelium Expression Factor Factors Female Gene Growth Humans Inbred Inhibitors Laboratories Ligands Line Lymphangiogenesis Mice Monoclonal Neoplasms Neoplastic Neovascularization Notch Pathologic Proliferation Receptor-3 Receptors Regulation Research Signal Transduction Transgenic Tumor Tyrosine Vascular Vessels antagonists blood cells drug effects genetics inhibitors metabolism pharmacology supply therapy Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFRhttp://www.bibsonomy.org/bibtex/294c1263be4532fda2056dce70ae83ab4/kanefendtkanefendt2010-02-05T11:28:39+01:001 Adenocarcinoma Autocrine Breast C Carcinoma Cell Colorectal Communication Endothelial Expression Factor Gene Growth Human Humans Hypoxia Hypoxia-Inducible Line Lung Neoplasms Neoplastic Oxygen Receptor-1 Receptor-2 Receptor-3 Regulation Subunit Survival Tumor Up-Regulation Vascular alpha cells genetics metabolism pathology physiology protein <span class="authorEditorList"><a href="/author/Simiantonaki">N. Simiantonaki</a>, <a href="/author/Jayasinghe">C. Jayasinghe</a>, <a href="/author/Michel-Schmidt">R. Michel-Schmidt</a>, <a href="/author/Peters">K. Peters</a>, <a href="/author/Hermanns">M. I. Hermanns</a>, and <a href="/author/Kirkpatrick">C. J. Kirkpatrick</a> </span><em>Int.J.Oncol.</em> <em>32(3):585-592</em> (<em>2008</em>)Fri Feb 05 11:28:39 CET 2010Int.J.Oncol.3585-592Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines3220081 Adenocarcinoma Autocrine Breast C Carcinoma Cell Colorectal Communication Endothelial Expression Factor Gene Growth Human Humans Hypoxia Hypoxia-Inducible Line Lung Neoplasms Neoplastic Oxygen Receptor-1 Receptor-2 Receptor-3 Regulation Subunit Survival Tumor Up-Regulation Vascular alpha cells genetics metabolism pathology physiology protein Adaptation to hypoxia, a universal hallmark of carcinomas, is a critical step for tumor cell survival and growth. One of the principal regulators of hypoxia-responsive pathways is the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha). Currently, it is known that tumoral production of members of the vascular endothelial growth factor (VEGF)-family (VEGFs) may promote tumor growth and progression by acting on carcinoma cells that express the cognate receptors (VEGFRs). However, the influence of hypoxia in the formation of such a tumoral VEGF/VEGFR loop is not completely understood. In the present study we examined the potential existence of a HIF-1 alpha/VEGF/VEGFR autocrine loop on commonly occurring carcinomas. The experiments were performed on five colorectal carcinoma cell lines, one breast (MCF7) and one lung (A549) adenocarcinoma cell line under normoxic and oxygen stress conditions using HIF-1 alpha-EIA, VEGFs-ELISA as well as RT-PCR and immunofluorescence for VEhttp://www.bibsonomy.org/bibtex/279245c6069a71953b9a702ad2d4030f0/kanefendtkanefendt2010-02-05T11:28:39+01:00Adolescent Adult Aged Bone C Cell Chain Child Cytoplasm D Endothelial Expression Factor Female Gene Growth Human Humans Immunohistochemistry Line Lymphatic Male Messenger Metastasis Middle Neoplasm Neoplasms Neoplastic Osteosarcoma Polymerase RNA Reaction Receptor-3 Regulation Research Up-Regulation Vascular Vessels cells genetics metabolism pathology protein <span class="authorEditorList"><a href="/author/Park">H. R. Park</a>, <a href="/author/Min">K. Min</a>, <a href="/author/Kim">H. S. Kim</a>, <a href="/author/Jung">W. W. Jung</a>, and <a href="/author/Park">Y. K. Park</a> </span><em>Pathol.Res.Pract.</em> <em>204(8):575-582</em> (<em>2008</em>)Fri Feb 05 11:28:39 CET 2010Pathol.Res.Pract.8575-582Expression of vascular endothelial growth factor-C and its receptor in osteosarcomas2042008Adolescent Adult Aged Bone C Cell Chain Child Cytoplasm D Endothelial Expression Factor Female Gene Growth Human Humans Immunohistochemistry Line Lymphatic Male Messenger Metastasis Middle Neoplasm Neoplasms Neoplastic Osteosarcoma Polymerase RNA Reaction Receptor-3 Regulation Research Up-Regulation Vascular Vessels cells genetics metabolism pathology protein Vascular endothelial growth factor-C (VEGF-C) and its receptor, vascular endothelial growth factor receptor-3 (VEGFR-3), have been implicated as important factors in the formation of lymphatic vessels, but its role in osteosarcomas has not yet been fully investigated. This study aims to define the expression of VEGF-C and VEGFR-3 in primary and metastatic osteosarcomas and their relationship to various clinicopathologic parameters. Thirty-three primary osteosarcomas and two pulmonary metastatic samples were immunostained for VEGF-C and VEGFR-3. In addition, VEGF-C and vascular endothelial growth factor-D (VEGF-D) mRNA expression levels in three different human osteosarcoma cell lines and control fibroblasts were evaluated by real-time quantitative polymerase chain reaction (PCR). Both VEGF-C and VEGFR-3 were expressed mainly in the cytoplasm of the tumor cells. Of the 35 patients with osteosarcoma, 16 patients (45.7%) showed strong positive reaction with VEGF-C. Four cases (11.4%) werehttp://www.bibsonomy.org/bibtex/28f225e24df5de7cf493d587492f3a1cb/kanefendtkanefendt2010-02-05T11:28:39+01:00Antibodies Antibody Blood Blotting Cell Cells Chain Chemistry Cytometry Endothelial Factor Flow Growth Humans Immunohistochemistry Line Lymphatic Messenger Neoplasms Northern Polymerase RNA Reaction Receptor-3 Reproducibility Results Reverse Separation Specificity Transcriptase Tumor Vascular Vessels Western analysis blood genetics immunology methods of pathology supply <span class="authorEditorList"><a href="/author/Petrova">T. V. Petrova</a>, <a href="/author/Bono">P. Bono</a>, <a href="/author/Holnthoner">W. Holnthoner</a>, <a href="/author/Chesnes">J. Chesnes</a>, <a href="/author/Pytowski">B. Pytowski</a>, <a href="/author/Sihto">H. Sihto</a>, <a href="/author/Laakkonen">P. Laakkonen</a>, <a href="/author/Heikkila">P. Heikkila</a>, <a href="/author/Joensuu">H. Joensuu</a>, and <a href="/author/Alitalo">K. Alitalo</a> </span><em>Cancer Cell</em> <em>13(6):554-556</em> (<em>2008</em>)Fri Feb 05 11:28:39 CET 2010Cancer Cell6554-556VEGFR-3 expression is restricted to blood and lymphatic vessels in solid tumors132008Antibodies Antibody Blood Blotting Cell Cells Chain Chemistry Cytometry Endothelial Factor Flow Growth Humans Immunohistochemistry Line Lymphatic Messenger Neoplasms Northern Polymerase RNA Reaction Receptor-3 Reproducibility Results Reverse Separation Specificity Transcriptase Tumor Vascular Vessels Western analysis blood genetics immunology methods of pathology supply http://www.bibsonomy.org/bibtex/2df8b4bb1902ba2e95f20a9161cb38d39/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Animals C Cell Chain Dexamethasone Endothelial Expression Factor Gene Glucocorticoids Growth Heterologous Human Humans Japan Line Lymphangiogenesis Lymphatic Male Metastasis Mice Neoplasms Neoplastic Polymerase Prostate Prostatic Reaction Receptor-3 Regulation Reverse Transcriptase Transplantation Tumor Vascular cells control drug effects genetics pathology pharmacology prevention protein <span class="authorEditorList"><a href="/author/Yano">A. Yano</a>, <a href="/author/Fujii">Y. Fujii</a>, <a href="/author/Iwai">A. Iwai</a>, <a href="/author/Kawakami">S. Kawakami</a>, <a href="/author/Kageyama">Y. Kageyama</a>, and <a href="/author/Kihara">K. Kihara</a> </span><em>Clin.Cancer Res.</em> <em>12(20 Pt 1):6012-6017</em> (<em>2006</em>)Fri Feb 05 11:28:39 CET 2010Clin.Cancer Res.20 Pt 16012-6017Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells122006& Animals C Cell Chain Dexamethasone Endothelial Expression Factor Gene Glucocorticoids Growth Heterologous Human Humans Japan Line Lymphangiogenesis Lymphatic Male Metastasis Mice Neoplasms Neoplastic Polymerase Prostate Prostatic Reaction Receptor-3 Regulation Reverse Transcriptase Transplantation Tumor Vascular cells control drug effects genetics pathology pharmacology prevention protein PURPOSE: Glucocorticoids such as prednisone, hydrocortisone, and dexamethasone are known to provide some clinical benefit for patients with hormone-refractory prostate cancer. However, the underlying mechanisms by which glucocorticoids affect hormone-refractory prostate cancer progression are not well established as yet. Our previous study has shown that glucocorticoids inhibit tumor angiogenesis possibly by down-regulation of vascular endothelial growth factor (VEGF) and interleukin 8. Here, we hypothesized that the therapeutic effect of dexamethasone on hormone-refractory prostate cancer can be partly attributed to a direct inhibition of lymphangiogenesis through the glucocorticoid receptor by down-regulating a major lymphangiogenic factor, VEGF-C. EXPERIMENTAL DESIGN: The effects of dexamethasone on the expression of VEGF-C and its receptor, VEGF receptor-3 (VEGFR-3), were examined using an androgen-independent human prostate cancer cell line, DU145, which expresses glucocorticoid rhttp://www.bibsonomy.org/bibtex/2938204526bc0b026f9e8e9af0e63c628/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; A Adrenal Animals Aorta C Cattle Cell Cells Cortex Cultured Endothelial Endothelium Enzyme Enzymologic Ester Expression Factor Factors Gene Growth II Inhibitors Kinase Kinases Line Lymphokines Methyl NG-Nitroarginine Nitric Oxide Penicillamine Pharmacokinetics Protein Protein-Tyrosine Proteins Receptor Receptors Recombinant Regulation Signal Substances Synthase Transduction Type Tyrosine Up-Regulation Vascular analogs cells derivatives drug effects metabolism pharmacology protein <span class="authorEditorList"><a href="/author/Shen">B. Q. Shen</a>, <a href="/author/Lee">D. Y. Lee</a>, and <a href="/author/Zioncheck">T. F. Zioncheck</a> </span><em>J.Biol.Chem.</em> <em>274(46):33057-33063</em> (<em>1999</em>)Fri Feb 05 11:28:39 CET 2010J.Biol.Chem.4633057-33063Vascular endothelial growth factor governs endothelial nitric-oxide synthase expression via a KDR/Flk-1 receptor and a protein kinase C signaling pathway2741999& A Adrenal Animals Aorta C Cattle Cell Cells Cortex Cultured Endothelial Endothelium Enzyme Enzymologic Ester Expression Factor Factors Gene Growth II Inhibitors Kinase Kinases Line Lymphokines Methyl NG-Nitroarginine Nitric Oxide Penicillamine Pharmacokinetics Protein Protein-Tyrosine Proteins Receptor Receptors Recombinant Regulation Signal Substances Synthase Transduction Type Tyrosine Up-Regulation Vascular analogs cells derivatives drug effects metabolism pharmacology protein The mechanism by which vascular endothelial growth factor (VEGF) regulates endothelial nitric-oxide synthase (eNOS) expression is presently unclear. Here we report that VEGF treatment of bovine adrenal cortex endothelial cells resulted in a 5-fold increase in both eNOS protein and activity. Endothelial NOS expression was maximal following 2 days of constant VEGF exposure (500 pM) and declined to base-line levels by day 5. The elevated eNOS protein level was sustained over the time course if VEGF was co-incubated with L-N(G)-nitroarginine methyl ester, a competitive eNOS inhibitor. Addition of S-nitroso-N-acetylpenicillamine, a nitric oxide donor, prevented VEGF-induced eNOS up-regulation. These data suggest that nitric oxide participates in a negative feedback mechanism regulating eNOS expression. Various approaches were used to investigate the role of the two high affinity VEGF receptors in eNOS up-regulation. A KDR receptor-selective mutant increased eNOS expression, whereas an Flt-1http://www.bibsonomy.org/bibtex/2f877fdd017e4a982a2b7aa3216a89ebb/kanefendtkanefendt2010-02-05T11:28:39+01:00A Alternative Blood Cell Cells Complex Cultured Cytokines Endothelial Endothelium Expression Factor Factors GPIIb-IIIa Gene Glycoprotein Growth Hematopoiesis Human Humans Immunohistochemistry Kinase Kinases Laboratories Line Lymphokines Megakaryocytes Neovascularization Physiologic Platelet Platelets Protein-Tyrosine Receptor Receptors Research Splicing Thrombin Vascular analysis cells cytology genetics metabolism pharmacology protein secretion <span class="authorEditorList"><a href="/author/Mohle">R. Mohle</a>, <a href="/author/Green">D. Green</a>, <a href="/author/Moore">M. A. Moore</a>, <a href="/author/Nachman">R. L. Nachman</a>, and <a href="/author/Rafii">S. Rafii</a> </span><em>Proc.Natl.Acad.Sci.U.S.A</em> <em>94(2):663-668</em> (<em>1997</em>)Fri Feb 05 11:28:39 CET 2010Proc.Natl.Acad.Sci.U.S.A2663-668Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets941997A Alternative Blood Cell Cells Complex Cultured Cytokines Endothelial Endothelium Expression Factor Factors GPIIb-IIIa Gene Glycoprotein Growth Hematopoiesis Human Humans Immunohistochemistry Kinase Kinases Laboratories Line Lymphokines Megakaryocytes Neovascularization Physiologic Platelet Platelets Protein-Tyrosine Receptor Receptors Research Splicing Thrombin Vascular analysis cells cytology genetics metabolism pharmacology protein secretion We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors. Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growth factor (VEGF). Megakaryocytes (CD41a+) were generated by ex vivo expansion of hematopoietic progenitor cells with kit-ligand and thrombopoietin for 10 days and further purified with immunomagnetic microbeads. Using reverse transcription-PCR, we showed that megakaryocytic cell lines (Dami, HEL) and purified megakaryocytes expressed mRNA of the three VEGF isoforms (121, 165, and 189 amino acids). Large quantities of VEGF (> 1 ng/10(6) cehttp://www.bibsonomy.org/bibtex/2fdc813c8de774f99db38d80c7745dbef/kanefendtkanefendt2010-02-05T11:28:39+01:005 Activation Alleles Animals C Cell Chemistry Chromosomes Data Dominant Endothelial Enzyme Factor Factors Female Fusion Genes Growth Half-Life Human Humans Infant Kinase Kinases Laboratories Line Lymphedema Male Mice Missense Models Molecular Mutation Newborn Pair Pedigree Phosphorylation Protein Protein-Tyrosine Proteins Receptor Receptor-3 Receptors Recombinant Research Sequence Signal Stability Structure Surface Transcriptional Transduction Tyrosine Vascular congenital drug effects genetics metabolism pharmacology protein secondary <span class="authorEditorList"><a href="/author/Karkkainen">M. J. Karkkainen</a>, <a href="/author/Ferrell">R. E. Ferrell</a>, <a href="/author/Lawrence">E. C. Lawrence</a>, <a href="/author/Kimak">M. A. Kimak</a>, <a href="/author/Levinson">K. L. Levinson</a>, <a href="/author/McTigue">M. A. McTigue</a>, <a href="/author/Alitalo">K. Alitalo</a>, and <a href="/author/Finegold">D. N. Finegold</a> </span><em>Nat.Genet.</em> <em>25(2):153-159</em> (<em>2000</em>)Fri Feb 05 11:28:39 CET 2010Nat.Genet.2153-159Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema2520005 Activation Alleles Animals C Cell Chemistry Chromosomes Data Dominant Endothelial Enzyme Factor Factors Female Fusion Genes Growth Half-Life Human Humans Infant Kinase Kinases Laboratories Line Lymphedema Male Mice Missense Models Molecular Mutation Newborn Pair Pedigree Phosphorylation Protein Protein-Tyrosine Proteins Receptor Receptor-3 Receptors Recombinant Research Sequence Signal Stability Structure Surface Transcriptional Transduction Tyrosine Vascular congenital drug effects genetics metabolism pharmacology protein secondary Primary lymphoedema is a rare, autosomal dominant disorder that leads to a disabling and disfiguring swelling of the extremities and, when untreated, tends to worsen with time. Here we link primary human lymphoedema to the FLT4 locus, encoding vascular endothelial growth factor receptor-3 (VEGFR-3), in several families. All disease-associated alleles analysed had missense mutations and encoded proteins with an inactive tyrosine kinase, preventing downstream gene activation. Our study establishes that VEGFR-3 is important for normal lymphatic vascular function and that mutations interfering with VEGFR-3 signal transduction are a cause of primary lymphoedemahttp://www.bibsonomy.org/bibtex/2e0c24eb6bc035e5246ea5789b096d844/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Animal Animals Cell Chloroform Concentration Glands Guanidine Guanidines Humans Hydrogen-Ion Line Mammary Phenol Phenols RNA Rats Solutions analysis cells isolation purification <span class="authorEditorList"><a href="/author/Chomczynski">P. Chomczynski</a>, and <a href="/author/Sacchi">N. Sacchi</a> </span><em>Anal.Biochem.</em> <em>162(1):156-159</em> (<em>1987</em>)Fri Feb 05 11:28:39 CET 2010Anal.Biochem.1156-159Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction1621987& Animal Animals Cell Chloroform Concentration Glands Guanidine Guanidines Humans Hydrogen-Ion Line Mammary Phenol Phenols RNA Rats Solutions analysis cells isolation purification A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue sampleshttp://www.bibsonomy.org/bibtex/27828c679111652379662d16686c669d3/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Acid Amino Base Blood Cell Cells Chemistry Cloning Conformation Data Development Differentiation Distribution Dna Down-Regulation Embryonic Endothelial Epithelial Expression Factor Fetal Gene Growth Homology Human Humans Immunoglobulins Kinase Kinases Leukemia Line Lung Molecular Nucleic Protein Protein-Tyrosine Receptor-3 Receptors Research Sequence Species Specificity Surface Teratoma Tissue Tyrosine Vascular Vessels and blood cells genetics isolation pathology protein purification <span class="authorEditorList"><a href="/author/Pajusola">K. Pajusola</a>, <a href="/author/Aprelikova">O. Aprelikova</a>, <a href="/author/Korhonen">J. Korhonen</a>, <a href="/author/Kaipainen">A. Kaipainen</a>, <a href="/author/Pertovaara">L. Pertovaara</a>, <a href="/author/Alitalo">R. Alitalo</a>, and <a href="/author/Alitalo">K. Alitalo</a> </span><em>Cancer Res.</em> <em>52(20):5738-5743</em> (<em>1992</em>)Fri Feb 05 11:28:39 CET 2010Cancer Res.205738-5743FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines521992& Acid Amino Base Blood Cell Cells Chemistry Cloning Conformation Data Development Differentiation Distribution Dna Down-Regulation Embryonic Endothelial Epithelial Expression Factor Fetal Gene Growth Homology Human Humans Immunoglobulins Kinase Kinases Leukemia Line Lung Molecular Nucleic Protein Protein-Tyrosine Receptor-3 Receptors Research Sequence Species Specificity Surface Teratoma Tissue Tyrosine Vascular Vessels and blood cells genetics isolation pathology protein purification The fms-like tyrosine kinase 4 (FLT4) complementary DNA was cloned from a human HEL erythroleukemia cell library by polymerase chain reaction-amplification. We previously reported a partial sequence of FLT4 and showed that the FLT4 gene maps to chromosomal region 5q33-qter (O. Aprelikova, K. Pajusola, J. Partanen, E. Armstrong, R. Alitalo, S. Bailey, J. McMahon, J. Wasmuth, K. Huebner, and K. Alitalo, Cancer Res., 52: 746-748, 1992). Here we present the full-length sequence of the predicted FLT4 protein. The extracellular domain of FLT4 consists of 7 immunoglobulin-like loops, including 12 potential glycosylation sites. On the basis of structural similarities FLT4 and the previously known FLT1 and kinase insert domain-containing receptor tyrosine kinase/fetal liver kinase 1 (KDR/FLK1) receptors constitute a subfamily of class III tyrosine kinases. FLT4 was expressed as 5.8- and 4.5-kilobase mRNAs which were found to differ in their 3' sequences and to be differentially expressed in thehttp://www.bibsonomy.org/bibtex/268da99870febb32cf06b671fe61b7474/kanefendtkanefendt2010-02-05T11:28:39+01:0080 A Adult Aged Arteries Artery Cell Cells Coronary Disease Endothelial Epithelial Factor Female Growth Human Humans Immediate-Early Intercellular Laboratories Line Macrophages Male Messenger Middle Monocytes Neuregulin-1 Peptides Proteins RNA Signaling Vascular and blood cells genetics metabolism methods over pathology physiopathology protein response secretion <span class="authorEditorList"><a href="/author/Panutsopulos">D. Panutsopulos</a>, <a href="/author/Arvanitis">D. L. Arvanitis</a>, <a href="/author/Tsatsanis">C. Tsatsanis</a>, <a href="/author/Papalambros">E. Papalambros</a>, <a href="/author/Sigala">F. Sigala</a>, and <a href="/author/Spandidos">D. A. Spandidos</a> </span><em>J.Vasc.Res.</em> <em>42(6):463-474</em> (<em>2005</em>)Fri Feb 05 11:28:39 CET 2010J.Vasc.Res.6463-474Expression of heregulin in human coronary atherosclerotic lesions42200580 A Adult Aged Arteries Artery Cell Cells Coronary Disease Endothelial Epithelial Factor Female Growth Human Humans Immediate-Early Intercellular Laboratories Line Macrophages Male Messenger Middle Monocytes Neuregulin-1 Peptides Proteins RNA Signaling Vascular and blood cells genetics metabolism methods over pathology physiopathology protein response secretion BACKGROUND: Endothelial cells, monocytes/macrophages, and vascular smooth muscle cells contribute to the establishment and progression of atherosclerotic lesions by expressing growth and inflammatory factors. The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease. METHODS: Twenty-six fresh human coronary artery segments were collected at autopsy. Expression of cysteine-rich 61 (CYR61) and VEGF in response to HRG was studied in the human endothelial cell line EA.hy926, and expression of CYR61 and HRG was evaluated in activated macrophages isolated from peripheral blood of healthy donors. RESULTS: We found that HRG was overexpressed at the protein and mRNA level in all lesions analyzed and gradually increased as the stages of the lesions progressed. Expression of HRG was observed in the intima primarily in macrophages. The same specimens were analyzed for the expression of CYR61, an angiogenetic factor regulated by HRG in brhttp://www.bibsonomy.org/bibtex/202092469557a1e573b6d3861630a2291/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; A Adenocarcinoma Administration Angiogenesis Animals Antibodies Antineoplastic Biological Blood Cell Chemotherapy Colorectal Combined Drug Endothelial Factor Growth Human Humans Inhibitors Line Male Markers Messenger Mice Modality Monoclonal Neoplasms Neovascularization Nude Pathologic Platelets Prostatic Protocols RNA Receptor-2 Research Schedule Scid Therapy Tumor Vascular administration biosynthesis blood dosage genetics immunology metabolism protein supply therapy <span class="authorEditorList"><a href="/author/Bocci">G. Bocci</a>, <a href="/author/Man">S. Man</a>, <a href="/author/Green">S. K. Green</a>, <a href="/author/Francia">G. Francia</a>, <a href="/author/Ebos">J. M. Ebos</a>, <a href="/author/Manoir">J. M. Du Manoir</a>, <a href="/author/Weinerman">A. Weinerman</a>, <a href="/author/Emmenegger">U. Emmenegger</a>, <a href="/author/Ma">L. Ma</a>, <a href="/author/Thorpe">P. Thorpe</a>, <a href="/author/Davidoff">A. Davidoff</a>, <a href="/author/Huber">J. Huber</a>, <a href="/author/Hicklin">D. J. Hicklin</a>, and <a href="/author/Kerbel">R. S. Kerbel</a> </span><em>Cancer Res.</em> <em>64(18):6616-6625</em> (<em>2004</em>)Fri Feb 05 11:28:39 CET 2010Cancer Res.186616-6625Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies642004& A Adenocarcinoma Administration Angiogenesis Animals Antibodies Antineoplastic Biological Blood Cell Chemotherapy Colorectal Combined Drug Endothelial Factor Growth Human Humans Inhibitors Line Male Markers Messenger Mice Modality Monoclonal Neoplasms Neovascularization Nude Pathologic Platelets Prostatic Protocols RNA Receptor-2 Research Schedule Scid Therapy Tumor Vascular administration biosynthesis blood dosage genetics immunology metabolism protein supply therapy A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a signihttp://www.bibsonomy.org/bibtex/2d06f290f7ae2e47b1305848e69910a6a/kanefendtkanefendt2010-02-05T11:28:39+01:00Animals Antibodies Binding Cell Cells Chemistry Conditioned Culture Endothelial Factor Factors Glycosylation Growth Health Human Humans Immunoprecipitation Line Media Mice Molecular Plasma Protein Receptor-2 Research Solubility Tyrosine Vascular Weight blood cells immunology metabolism protein secretion <span class="authorEditorList"><a href="/author/Ebos">J. M. Ebos</a>, <a href="/author/Bocci">G. Bocci</a>, <a href="/author/Man">S. Man</a>, <a href="/author/Thorpe">P. E. Thorpe</a>, <a href="/author/Hicklin">D. J. Hicklin</a>, <a href="/author/Zhou">D. Zhou</a>, <a href="/author/Jia">X. Jia</a>, and <a href="/author/Kerbel">R. S. Kerbel</a> </span><em>Mol.Cancer Res.</em> <em>2(6):315-326</em> (<em>2004</em>)Fri Feb 05 11:28:39 CET 2010Mol.Cancer Res.6315-326A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma22004Animals Antibodies Binding Cell Cells Chemistry Conditioned Culture Endothelial Factor Factors Glycosylation Growth Health Human Humans Immunoprecipitation Line Media Mice Molecular Plasma Protein Receptor-2 Research Solubility Tyrosine Vascular Weight blood cells immunology metabolism protein secretion Angiogenesis and vasculogenesis are regulated in large part by several different growth factors and their associated receptor tyrosine kinases (RTKs). Foremost among these is the vascular endothelial growth factor (VEGF) family including VEGF receptor (VEGFR)-2 and -1. VEGFR ligand binding and biological activity are regulated at many levels, one of which is by a soluble, circulating form of VEGFR-1 (sVEGFR-1). This sVEGFR-1 can act as a competitive inhibitor of its ligand, serve as a possible biomarker, and play important roles in cancer and other diseases such as preeclampsia. Recombinant forms of sVEGFR-2 have been shown to have antiangiogenic activity, but a naturally occurring sVEGFR-2 has not been described previously. Here, we report such an entity. Having a molecular weight of approximately 160 kDa, sVEGFR-2 can be detected in mouse and human plasma with several different monoclonal and polyclonal anti-VEGFR-2 antibodies using both ELISA and immunoprecipitation techniques. In vhttp://www.bibsonomy.org/bibtex/24685622165a738ccc4fae9881358cc91/kanefendtkanefendt2010-02-05T11:28:39+01:00Adenoviridae Animals C Carcinoma Cell Endothelial Factor Female Gene Genetic Growth Human Humans Kidney Line Lung Lymph Lymphangiogenesis Lymphatic Male Melanoma Metastasis Mice Neoplasms Nodes Nude Prostate Prostatic Receptor-3 Renal Techniques Therapy Transfer Tumor Vascular Vectors biosynthesis blood cells genetics immunology methods pathology secondary therapy <span class="authorEditorList"><a href="/author/Lin">J. Lin</a>, <a href="/author/Lalani">A. S. Lalani</a>, <a href="/author/Harding">T. C. Harding</a>, <a href="/author/Gonzalez">M. Gonzalez</a>, <a href="/author/Wu">W. W. Wu</a>, <a href="/author/Luan">B. Luan</a>, <a href="/author/Tu">G. H. Tu</a>, <a href="/author/Koprivnikar">K. Koprivnikar</a>, <a href="/author/VanRoey">M. J. VanRoey</a>, <a href="/author/He">Y. He</a>, <a href="/author/Alitalo">K. Alitalo</a>, and <a href="/author/Jooss">K. Jooss</a> </span><em>Cancer Res.</em> <em>65(15):6901-6909</em> (<em>2005</em>)Fri Feb 05 11:28:39 CET 2010Cancer Res.156901-6909Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor652005Adenoviridae Animals C Carcinoma Cell Endothelial Factor Female Gene Genetic Growth Human Humans Kidney Line Lung Lymph Lymphangiogenesis Lymphatic Male Melanoma Metastasis Mice Neoplasms Nodes Nude Prostate Prostatic Receptor-3 Renal Techniques Therapy Transfer Tumor Vascular Vectors biosynthesis blood cells genetics immunology methods pathology secondary therapy The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that the lymphangiogenic growth factor, vascular endothelial growth factor-C (VEGF-C), and its receptor, VEGF receptor-3 (VEGFR3), may play a pivotal role in the promotion of metastasis to regional lymph nodes. In this study, human prostate and melanoma tumor models that preferentially metastasize to the lymph nodes following s.c. tumor cell implantation were established from lymph node metastases via in vivo selection. Melanoma tumor cell sublines established from lymph node metastasis express higher amounts of VEGF-C than the parental tumor cells. The inhibition of tumor-derived VEGF-C with a soluble VEGFR3 decoy receptor, sVEGFR3-Fc, expressed via a recombinant adeno-associated viral vector, potently blocks tumor-associated lymphangiogenesis and tumor metastasis to the lymph nodes, when the treatment was initiated before the tumor implhttp://www.bibsonomy.org/bibtex/2853643c851098d66d2e16a17fb34377a/kanefendtkanefendt2010-02-05T11:28:39+01:00Agents Animals Antibodies Antigen Antineoplastic Antitumor Assay Assays Biological Carcinoma Cell Chemistry Colonic Enzyme-Linked Epidermal Factor Factors Female G Growth Human Humans Immunoglobulin Immunohistochemistry Immunosorbent Ki-67 Kinase Line MAP Markers Mice Model Monoclonal Neoplasm Neoplasms Nude Pharmacokinetics Phosphorylation Receptor Research Signaling System Time Transplantation Tumor Tyrosine Xenograft analysis biosynthesis drug metabolism methods pathology pharmacology protein response therapy <span class="authorEditorList"><a href="/author/Luo">F. R. Luo</a>, <a href="/author/Yang">Z. Yang</a>, <a href="/author/Dong">H. Dong</a>, <a href="/author/Camuso">A. Camuso</a>, <a href="/author/McGlinchey">K. McGlinchey</a>, <a href="/author/Fager">K. Fager</a>, <a href="/author/Flefleh">C. Flefleh</a>, <a href="/author/Kan">D. Kan</a>, <a href="/author/Inigo">I. Inigo</a>, <a href="/author/Castaneda">S. Castaneda</a>, <a href="/author/Wong">T. W. Wong</a>, <a href="/author/Kramer">R. A. Kramer</a>, <a href="/author/Wild">R. Wild</a>, and <a href="/author/Lee">F. Y. Lee</a> </span><em>Clin.Cancer Res.</em> <em>11(15):5558-5565</em> (<em>2005</em>)Fri Feb 05 11:28:39 CET 2010Clin.Cancer Res.155558-5565Prediction of active drug plasma concentrations achieved in cancer patients by pharmacodynamic biomarkers identified from the geo human colon carcinoma xenograft model112005Agents Animals Antibodies Antigen Antineoplastic Antitumor Assay Assays Biological Carcinoma Cell Chemistry Colonic Enzyme-Linked Epidermal Factor Factors Female G Growth Human Humans Immunoglobulin Immunohistochemistry Immunosorbent Ki-67 Kinase Line MAP Markers Mice Model Monoclonal Neoplasm Neoplasms Nude Pharmacokinetics Phosphorylation Receptor Research Signaling System Time Transplantation Tumor Tyrosine Xenograft analysis biosynthesis drug metabolism methods pathology pharmacology protein response therapy PURPOSE: Epidermal growth factor receptor (EGFR), a protein tyrosine kinase expressed in many types of human cancers, has been strongly associated with tumor progression. Cetuximab is an IgG(1) anti-EGFR chimeric mouse/human monoclonal antibody that has been approved for the treatment of advanced colon cancer. Using human tumor xenografts grown in nude mice, we have determined the in vivo pharmacodynamic response of cetuximab at efficacious doses. Three pharmacodynamic end points were evaluated: tumoral phospho-EGFR, tumoral mitogen-activated protein kinase (MAPK) phosphorylation, and Ki67 expression. EXPERIMENTAL DESIGN: The pharmacodynamic study was conducted in nude mice bearing Geo tumors following a single i.p. administration of 0.25 and 0.04 mg. The tumors were analyzed by immunohistochemistry. The levels of phospho-EGFR were quantitated by an ELISA assay. RESULTS: At 0.25 mg, phospho-EGFR was maximally inhibited by 91% at 24 hours, whereas the level of inhibition decreased to 72http://www.bibsonomy.org/bibtex/21e6f63e4e13c562e65844b4fd1b765ea/kanefendtkanefendt2010-02-05T11:28:39+01:00&amp; Adenoviridae Animals Antitumor Assays Cell Cells Endothelial Endothelium Factor Fusion Genetic Growth Humans Immunoglobulins Laboratories Line Lung Lymph Lymphangiogenesis Lymphatic Metastasis Mice Model Neoplasm Neoplasms Neovascularization Nodes Pathologic Proteins Receptor-3 Recombinant Research Scid Signal Staging Transduction Tumor Vascular Vectors Vessels Xenograft administration antagonists cells control dosage genetics inhibitors pathology physiology prevention protein therapy <span class="authorEditorList"><a href="/author/He">Y. He</a>, <a href="/author/Rajantie">I. Rajantie</a>, <a href="/author/Pajusola">K. Pajusola</a>, <a href="/author/Jeltsch">M. Jeltsch</a>, <a href="/author/Holopainen">T. Holopainen</a>, <a href="/author/Yla-Herttuala">S. Yla-Herttuala</a>, <a href="/author/Harding">T. Harding</a>, <a href="/author/Jooss">K. Jooss</a>, <a href="/author/Takahashi">T. Takahashi</a>, and <a href="/author/Alitalo">K. Alitalo</a> </span><em>Cancer Res.</em> <em>65(11):4739-4746</em> (<em>2005</em>)Fri Feb 05 11:28:39 CET 2010Cancer Res.114739-4746Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels652005& Adenoviridae Animals Antitumor Assays Cell Cells Endothelial Endothelium Factor Fusion Genetic Growth Humans Immunoglobulins Laboratories Line Lung Lymph Lymphangiogenesis Lymphatic Metastasis Mice Model Neoplasm Neoplasms Neovascularization Nodes Pathologic Proteins Receptor-3 Recombinant Research Scid Signal Staging Transduction Tumor Vascular Vectors Vessels Xenograft administration antagonists cells control dosage genetics inhibitors pathology physiology prevention protein therapy Lymphangiogenic growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to promote lymphatic metastasis by inducing tumor-associated lymphangiogenesis. In this study, we have investigated how tumor cells gain access into lymphatic vessels and at what stage tumor cells initiate metastasis. We show that VEGF-C produced by tumor cells induced extensive lymphatic sprouting towards the tumor cells as well as dilation of the draining lymphatic vessels, suggesting an active role of lymphatic endothelial cells in lymphatic metastasis. A significant increase in lymphatic vessel growth occurred between 2 and 3 weeks after tumor xenotransplantation, and lymph node metastasis occurred at the same stage. These processes were blocked dose-dependently by inhibition of VEGF receptor 3 (VEGFR-3) signaling by systemic delivery of a soluble VEGFR-3-immunoglobulin (Ig) fusion protein via adenoviral or adeno-associated viral vectors. However, VEGFR-3-Ig did not suppress lymph http://www.bibsonomy.org/bibtex/270eb5ef3478db1258b031656dde47a5c/kanefendtkanefendt2010-02-05T11:28:39+01:00Biological C Cell Culture D Endothelial Endothelium Factor Factors Growth Humans Kinase Kinases Line Lymphatic Markers Metastasis Movement Neoplasm Neoplasms Neovascularization Pathologic Protein-Tyrosine Receptor Receptor-3 Receptors Research Techniques Vascular Vessels blood pathology physiology physiopathology supply <span class="authorEditorList"><a href="/author/Karkkainen">M. J. Karkkainen</a>, <a href="/author/Makinen">T. Makinen</a>, and <a href="/author/Alitalo">K. Alitalo</a> </span><em>Nat.Cell Biol.</em> <em>4(1):E2-E5</em> (<em>2002</em>)Fri Feb 05 11:28:39 CET 2010Nat.Cell Biol.1E2-E5Lymphatic endothelium: a new frontier of metastasis research42002Biological C Cell Culture D Endothelial Endothelium Factor Factors Growth Humans Kinase Kinases Line Lymphatic Markers Metastasis Movement Neoplasm Neoplasms Neovascularization Pathologic Protein-Tyrosine Receptor Receptor-3 Receptors Research Techniques Vascular Vessels blood pathology physiology physiopathology supply The vascular endothelium is a dynamic tissue with many active functions. Until recently, endothelial cell (EC) biology studies have used cultured ECs from various organs; these cell lines are considered representative of the blood vascular endothelium. Very few lymphatic EC lines have been available, and these were derived from lymphatic tumours or large collecting lymphatic ducts. In the past, lymphatic vessels were defined largely by the lack of erythrocytes in their lumen, a lack of junctional complexes and the lack of a well-defined basement membrane. Now that lymphatic-specific vascular endothelial growth factors (VEGF-C and VEGF-D) and molecular cell surface markers such as the VEGFR-3 receptor have been identified, this definition needs to be updated. Recent developments have highlighted the importance of lymphatic ECs, and they could become the next focus for angiogenesis and metastasis research