1121-51 SU11218, a platelet-derived growth factor receptor and vascular endothelial growth factor receptor 2 inhibitor blocks adventitial angiogenesis and prevents intimal hyperplasia after coronary stenting in a porcine model

The aim of the study was to evaluate selected angiogenic factors in patients with essential thrombocythemia (ET) depending on JAK2V617F, calreticulin gene (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations. Sixty ET patients and 20 healthy volunteers were enrolled in the study. The following tests were performed: vascular endothelial growth factor- A (VEGF-A), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1),soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), platelet-derived growth factor( PDGF-BB), and stromal-derived factor-1α (SDF-1α). We observed an increased PDGF-BB level in patients with ET compared to the controls. Patients with CALR mutation had significantly higher concentration of PDGF-BB and lower concentration of SDF-1α than patients with JAK2V617F mutation. High concentration of PDGF-BB and low concentration of SDF-1α in patients with CALR(+) ET may indicate a contribution of these chemokines in disturbed Ca2+ metabolism in platelets.

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Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro

British Journal of Cancer ◽

10.1038/bjc.2012.459 ◽

2012 ◽

Vol 107 (10) ◽

pp. 1702-1713 ◽

Cited By ~ 24

Author(s):

C Pfister ◽

H Pfrommer ◽

M S Tatagiba ◽

F Roser

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase

Cancer Science ◽

10.1111/cas.12101 ◽

2013 ◽

Vol 104 (4) ◽

pp. 486-494 ◽

Cited By ~ 9

Author(s):

Yoshiko Awazu ◽

Akio Mizutani ◽

Yoshinori Nagase ◽

Shuntarou Tsuchiya ◽

Kazuhide Nakamura ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Growth Factor Receptor ◽

Selective Inhibitor ◽

Platelet Derived Growth Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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Die Häufigkeit von Anti-VEGF-A-Injektionen und Ödemrezidiven hängt vom Grad der begleitenden lokalen zellulären Entzündung ab

Karger Kompass Ophthalmologie ◽

10.1159/000458732 ◽

2017 ◽

Vol 3 (2) ◽

pp. 70-71

Author(s):

Olaf Strauss

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Adhesion Molecule ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Intercellular Adhesion Molecule ◽

Vascular Endothelial ◽

Intercellular Adhesion Molecule 1 ◽

Endothelial Growth Factor ◽

Zentrale Netzhautdicke

Wir maßen die Konzentrationen von Zytokinen und Wachstums-/Entzündungsfaktoren im Kammerwasser von 46 Patienten mit retinalem Venenastverschluss (VAV) und Makulaödem (MÖ), die mit einer intravitrealen Ranibizumab-Injektion (IRI) behandelt wurden. Patienten mit rezidivierendem MÖ erhielten bei Bedarf eine weitere IRI. Die Anzahl der IRI-Behandlungen korrelierte signifikant mit dem Alter, dem Visus c.c. bei Studienbeginn, der zentralen Netzhautdicke bei Studienbeginn sowie den Konzentrationen von 5 Zytokinen/Faktoren im Kammerwasser bei Studienbeginn (löslicher VEGFR-1 (vascular endothelial growth factor receptor 1), PDGF-AA (platelet-derived growth factor-AA), lösliches ICAM-1 (intercellular adhesion molecule 1), IL-6 (Interleukin 6) und IL-8). Die multivariate lineare Regressionsanalyse mit schrittweiser Auswahl bestätigte, dass Alter, zentrale Netzhautdicke bei Studienbeginn und PDGF-AA-Wert bei Studienbeginn unabhängige Determinanten der Anzahl der IRI-Behandlungen waren. Diese Ergebnisse deuten darauf hin, dass Entzündungsfaktoren möglicherweise das erneute Auftreten von MÖ bei VAV-Patienten beeinflussen können und dass der PDGF-AA-Wert ein hilfreicher Indikator dafür sein könnte, wie viele IRI-Behandlungen für die Beherrschung des MÖ erforderlich sein werden.

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A novel pyrrolo[3, 2-d]pyrimidine derivative, as a vascular endothelial growth factor receptor and platelet-derived growth factor receptor tyrosine kinase inhibitor, shows potent antitumor activity by suppression of tumor angiogenesis

Cancer Science ◽

10.1111/j.1349-7006.2012.02238.x ◽

2012 ◽

Vol 103 (5) ◽

pp. 939-944 ◽

Cited By ~ 7

Author(s):

Yoshiko Awazu ◽

Akio Mizutani ◽

Yoshinori Nagase ◽

Hidehisa Iwata ◽

Yuya Oguro ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Antitumor Activity ◽

Receptor Tyrosine Kinase ◽

Kinase Inhibitor ◽

Growth Factor Receptor ◽

Pyrimidine Derivative ◽

Platelet Derived Growth Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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The platelet-derived growth factor receptor as a target for vascular endothelial growth factor-mediated anti-angiogenetic therapy in head and neck cancer

International Journal of Oncology ◽

10.3892/ijo_00000147 ◽

1992 ◽

Cited By ~ 1

Author(s):

Bran

Keyword(s):

Vascular Endothelial Growth Factor ◽

Head And Neck Cancer ◽

Growth Factor ◽

Head And Neck ◽

Neck Cancer ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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Phase I Dose Escalation Study of Telatinib, a Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor 2 and 3, Platelet-Derived Growth Factor Receptor β, and c-Kit, in Patients With Advanced or Metastatic Solid Tumors

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.8193 ◽

2009 ◽

Vol 27 (25) ◽

pp. 4169-4176 ◽

Cited By ~ 29

Author(s):

Ferry A.L.M. Eskens ◽

Neeltje Steeghs ◽

Jaap Verweij ◽

Johan L. Bloem ◽

Olaf Christensen ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Phase I ◽

Kinase Inhibitor ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Vascular Endothelial ◽

Dose Escalation Study ◽

Grade 3 ◽

Endothelial Growth Factor

PurposeTelatinib (BAY 57-9352) is an orally available tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -2, VEGFR-3, platelet-derived growth factor receptor-β, and c-Kit. This phase I dose escalation study was conducted to evaluate the safety and tolerability of telatinib, with additional pharmacokinetic, pharmacodynamic, and efficacy assessments.Patients and MethodsPatients with solid tumors refractory to standard therapies or with no standard therapy available were enrolled. Doses of continuously administered telatinib were escalated from 20 mg once daily to 1,500 mg twice daily.ResultsFifty-three patients were enrolled. Most frequently observed drug-related adverse events were nausea (26.4%; grade ≥ 3, 0%) and hypertension (20.8%; grade 3, 11.3%; grade 4, 0%). Two dose-limiting toxicities were observed: one poorly controlled hypertension (600 mg twice daily), and one grade 2 weight loss, anorexia, and fatigue (1,500 mg twice daily). A formal maximum-tolerated dose was not reached. Telatinib was rapidly absorbed, with median time to peak concentration (tmax) lower than 3 hours after dose. A nearly dose-proportional increase in exposure was observed with substantial variability. Telatinib half-life averaged 5.5 hours. Biomarker analyses showed dose-dependent increase in VEGF levels and decrease in plasma soluble VEGFR-2 levels, with a plateau at 900 mg twice daily. A decrease in tumor blood flow (Ktransand IAUC60) was observed with dynamic contrast-enhanced magnetic resonance imaging. Best tumor response was stable disease, observed in 50.9% of patients.ConclusionTelatinib was safe and well tolerated up to 1,500 mg twice daily. Based on pharmacodynamic and pharmacokinetic end points, telatinib 900 mg twice daily is the recommended dose for subsequent phase II studies.

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