Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palladia(TM) (toceranib phosphate-Pfizer Animal Health) is a novel orally administered receptor tyrosine kinase inhibitor (TKI) approved for treatment of canine mast cell tumors. Receptor tyrosine kinase dysregulation leads to tumor growth, progression, and metastasis. Toceranib's targets include vascular endothelial growth factor receptor (VEGFR-2/Flk-1/KDR), platelet-derived growth factor receptor, and kit. Positron Emission Tomography/Computed Tomography (PET/CT) is used commonly to diagnose, prognosticate, and monitor response to antineoplastic therapy in human patients. In this study, serial PET/CT imaging with (18) F-fluorodeoxyglucose ((18) FDG) was used to assess response to toceranib therapy in dogs with measurable solid malignancies. Six tumor-bearing dogs underwent tumor assessment using both standard RECIST criteria and PET/CT prior to and at a median of 5 weeks postinitiation of toceranib treatment. Toceranib was prescribed initially at a target dose 3.25 mg/kg PO q48 h, with subsequent modifications based on observed toxicity. Treatment was continued in patients achieving stable disease with acceptable drug tolerance. One dog was maintained on drug despite dose modification due to toxicity; measurable clinical and image-based responses were seen after 10 weeks of therapy. All others had stable or progressive disease based on clinical restaging and PET/CT at first recheck. . Due to discordance with anatomic and metabolic imaging, further studies are needed to investigate the role of molecular imaging in assessment of drug response and identify other potential molecular targets of toceranib.
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PMID:Preliminary evaluation of serial (18) FDG-PET/CT to assess response to toceranib phosphate therapy in canine cancer. 2236 Jun 84

Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities and play a critical role in skin allergic reactions, which are manifested with rapid edema and increases of vascular permeability. The exact mechanisms of mast cell tryptase promoting vascular permeability, however, are unclear and, therefore, we investigated the effect and mechanism of tryptase or human mast cells (HMC-1) supernatant on the permeability of human dermal microvascular endothelial cells (HDMECs). Both tryptase and HMC-1 supernatant increased permeability of HDMECs significantly, which was resisted by tryptase inhibitor APC366 and partially reversed by anti-VEGF antibody and SU5614 (catalytic inhibitor of VEGFR). Furthermore, addition of tryptase to HDMECs caused a significant increase of mRNA and protein levels of VEGF and its receptors (Flt-1 and Flk-1) by Real-time RT-PCR and Western blot, respectively. These results strongly suggest an important role of VEGF on the permeability enhancement induced by tryptase, which may lead to novel means of controlling allergic reaction in skin.
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PMID:VEGF is involved in the increase of dermal microvascular permeability induced by tryptase. 2266 7

Angiogenesis, namely, the growth of new blood vessels from pre-existing ones, is an essential process of embryonic development and post-natal growth. In adult life, it may occur in physiological conditions (menstrual cycle and wound healing), during inflammatory disorders (autoimmune diseases and allergic disorders) and in tumor growth. The angiogenic process requires a tightly regulated interaction among different cell types (e.g. endothelial cells and pericytes), the extracellular matrix, several specific growth factors (e.g. VEGFs, Angiopoietins), cytokines and chemokines. Lymphangiogenesis, namely, the growth of new lymphatic vessels, is an important process in tumor development, in the formation of metastasis and in several inflammatory and metabolic disorders. In addition to tumors, several effector cells of inflammation (mast cells, macrophages, basophils, eosinophils, neutrophils, etc.) are important sources of a wide spectrum of angiogenic and lymphangiogenic factors. Human mast cells produce a large array of angiogenic and lymphangiogenic molecules. Primary human mast cells and two mast cell lines constitutively express several isoforms of angiogenic (VEGF-A and VEGF-B) and the two lymphangiogenic factors (VEGF-C and VEGF-D). In addition, human mast cells express the VEGF receptor 1 (VEGFR-1) and 2 (VEGFR-2), the co-receptors neuropilin-1 (NRP1) and -2 (NRP2) and the Tie1 and Tie2 receptors. Immunologically activated human basophils selectively produce VEGF-A and -B, but not VEGF-C and -D. They also release Angiopoietin1 that activates Tie2 on human mast cells. Collectively, these findings indicate that human mast cells and basophils might participate in the complex network involving inflammatory and tumor angiogenesis and lymphangiogenesis.
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PMID:Mast cells and basophils in inflammatory and tumor angiogenesis and lymphangiogenesis. 2594 Oct 82