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)

Mast cells are likely to play a role in angiogenesis under pathological conditions. Solid tumor growth is dependent on angiogenesis, but the influence of mast cells on angiogenesis in non-Hodgkin's lymphoma, (NHL) is not clear. We investigated mast cell number and vessel count in 61 cases of NHL. We also evaluated expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), both important cytokines for angiogenesis. The number of mast cells was greater in T-cell lymphomas than in B-cell lymphomas. Of the T-cell lymphomas, the greatest number of mast cells was observed in the angioimmunoblastic T-cell lymphoma (AIL). In all NHLs, significant correlation was found between vessel count and the number of mast cells (p < 0.0001) and between vessel count and the number of VEGF-expressing cells (p < 0.05) but not between vessel count and bFGF-expressing cells. Strong correlation was detected between the number of mast cells and the number of VEGF-expressing cells (p < 0.0001) in all NHLs. Double fluorescence staining of VEGF mRNA and mast cell tryptase revealed that mast cells expressed VEGF mRNA. Our data suggest that mast cells play a very important role in angiogenesis by expressing VEGF in NHL, especially in AIL.
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PMID:Angiogenesis and mast cells in non-Hodgkin's lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma. 1169 1

Mast cells have a clear-cut pathologic role in allergy, participating in a number of chronic inflammatory conditions, in helmintic parasitosis, and in some solid tumor reactions, but also in physiological situations, such as wound healing and innate immunity. Mast cells release a large number of proinflammatory, immunoregulatory, and tissue regulatory mediators after activation induced by either IgE-dependent or IgE-independent mechanisms. While much information has been gathered on the immunological mast cell activation both in rodent and human systems, only minimal knowledge exists on the non-immunological activation especially in human mast cells. Mast cell IgE-independent activation occurs through G(i3alpha) which has been identified as the pertussis toxin (Ptx)-sensitive heterotrimeric G protein that interacts with cationic secretagogues inducing PLC-independent mast cell exocytosis. Mast cell IgE-independent activation in allergy probably occurs when mast cells encounter eosinophils, the main inflammatory cells of the allergic reactions that persist throughout the late phase and when the inflammatory condition becomes chronic. This review summarizes regarding the influence of eosinophils on mast cell activation, thus demonstrating that IgE-independent activation has a relevant role in pathophysiological processes as well as in mast cell IgE-dependent activation.
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PMID:Effects of eosinophils on mast cells: a new pathway for the perpetuation of allergic inflammation. 1221 10

Mast cells are tissue dwelling cells that have a clear-cut pathologic role in allergy. Besides that, they participate in several chronic inflammatory conditions, helminitic parasitosis, and in some solid tumor reactions, but also in physiological situations, such as wound healing and innate immunity. Mast cells produce and release various mediators after activation induced by either IgE-dependent or IgE-independent mechanisms. Although much information has been gathered on the immunological (IgE-dependent) mast cell activation both in vivo and in vitro, not much is known about the non-immunological (IgE-independent) activation particularly in human mast cells. Mast cell IgE-independent activation is mediated through Gi3alpha which has been identified in rat mast cells as the pertussis toxin (Ptx)-sensitive heterotrimeric G protein that interacts with cationic secretagogues inducing PLC-independent mast cell exocytosis. Mast cell IgE-independent activation in allergy most likely occurs when mast cells encounter eosinophils, the main inflammatory cells that persist throughout the late and chronic phases of the allergic reaction. This review summarizes the influence of eosinophils on mast cell activation demonstrating that IgE-independent activation has a significant role in pathophysiological processes.
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PMID:IgE-Independent Activation of Human Mast Cells Indicates their Role in the Late Phase Reaction of Allergic Inflammation. 1525 66

In vivo efficacy of novel anticancer agents has been hindered by the inability to deliver effective concentrations of drugs to tumors. The use of macromolecules such as antibodies and polymers for enzyme delivery to tumors has revealed that catalyzing the conversion of a nontoxic prodrug into its cytotoxic form can generate an effective level of cytotoxic agents at tumor sites. This study primarily focuses on the synthesis and characterization of methoxypoly(ethylene glycol)-modified carboxypeptidase A (CPA) for solid tumor targeting. The molecular weight of CPA has been successfully altered from 35 to 40-50 kDa via attachment of a defined number of mPEG moieties. Relatively pure mPEG-CPA conjugates containing one, two, and three mPEG chains were obtained at preparative scale quantities through controlled PEGylation followed by fractionation that involved size-exclusion chromatography. An enhancement in kinetic properties including k(cat) and k(cat)/K(m) towards hippuryl-L-phenylalanine (hipp-L-phe) was observed in mPEG-CPA conjugates. An increase in the V(m) appeared to be responsible for this enhancement. The attachment of mPEG to CPA substantially improved the stability of the enzyme with respect to the specific peptidase activity toward the model substrate. This finding is particularly important in the development of a novel CPA/methotrexate-alpha-peptide system in solid tumor chemotherapy.
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PMID:Methoxypoly(ethylene glycol)-conjugated carboxypeptidase A for solid tumor targeting: part I: synthesis and characterization. 1586 40

There are around 27 species of Amolops amphibian distributed in South-east of Asia. Seven antimicrobial peptides (AMPs) belonging to two different families were purified from skin of rufous-spotted torrent frog, Amolops loloensis, and designated brevinins-ALa, b, c, and d, and temporins-ALa, b, and c. The brevinins-AL family which is structurally related to brevinins-1 from skin secretions of the European frog, Rana brevipoda, is composed of 24 amino acids and has an intra-disulfide bridge at the C-terminus. The temporins-AL family, composed of 13 or 16 amino acid residues, is related with temporins from the skin secretions of R. temporaria. The findings of this study will facilitate the solutions to the taxonomic questions of the ranid genus Amolops and Staurois. In the work of this paper, both brevinins-ALb and temporin-Ma induced mast cell degranulation and histamine release, and had cytotoxic activity toward solid tumor cell line HepG(2). Brevinins-ALb also exerted strong hemolytic activity while temporin-Ma had no such activity.
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PMID:Two families of antimicrobial peptides with multiple functions from skin of rufous-spotted torrent frog, Amolops loloensis. 1700 29

The chimeric BCR-ABL gene, originated by the Philadelphia chromosome, encodes a fusion protein, BCR-ABL, bearing unregulated tyrosine kinase activity, the pivotal pathogenetic step of chronic myeloid leukemia (CML). Imatinib, an inhibitor of the BCR-ABL tyrosine kinase, significantly improves the outcome of patients with CML. Although the majority of CML patients are responsive to imatinib, a subset of patients loses the response and some progress to accelerated- or blast-phase CML. The understanding of mechanisms of imatinib resistance has led to the development of novel BCR-ABL inhibitors; among these, dasatinib emerged as the most promising, being approximately 300-fold more potent than imatinib; it also inhibits SRC family kinases. Preliminary data, after the introduction of dasatinib in clinical trials, in patients with CML, suggest that this drug is safe and well tolerated; furthermore, the majority of patients with imatinib-resistant disease achieved objective responses, although the durability of responses remains to be defined. Recently, dasatinib emerged as a potent inhibitor of imatinib-resistant protein tyrosine kinase (KIT) activation loop mutants and it is able to induce apoptosis in mast cell and leukemic cell lines expressing these mutations. The preclinical data concerning its activity on several human solid tumor lines widen new opportunities for their use outside CML.
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PMID:Dasatinib: a new step in molecular target therapy. 1759 30

Bovine carboxypeptidase A (CPA) conjugated with biotinylated poly(ethylene glycol) (PEG) has been synthesized and characterized in terms of stoichiometry and half-life of the avidin-biotin-PEG(s)-CPA complex. The half-lives for dissociation are 3.34 days for the avidin-biotin-PEG(3400)-CPA 1:1 complex, 3.65 days for the avidin-biotin-PEG(5000)-CPA 1:1 complex, 3.91 days for the avidin-biotin-PEG(3400)-CPA-PEG(2000) 1:1 complex, and 2.74 days for the avidin-biotin-PEG(5000)-CPA-PEG(2000) 1:1 complex. The slow dissociation demonstrates the stability of complexes using a PEGylated biotin terminus as a linker with avidin. The stoichiometry of the biotin-PEGylated CPA with avidin was determined by the 2,6-ANS method, and the results are consistent with measurements of the stoichiometry using size exclusion chromatography. The stoichiometries are 1:2 for the avidin-biotin-PEG(3400)-CPA complex and the avidin-biotin-PEG(3400)-CPA-PEG(2000) complex, 1:1 for the avidin-biotin-PEG(5000)-CPA complex, and 1:4 for the avidin-biotin-PEG(5000)-CPA-PEG(2000) complex. These findings stress both the importance of the length of a PEG chain as an appropriate spacer between the biotin terminus and a functional group, and the great potential of the avidin-biotin-PEGylated-protein complex as a therapeutic protein delivery system for solid tumor prodrug targeting.
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PMID:Avidin-biotin-PEG-CPA complexes as potential EPR-directed therapeutic protein carriers: preparation and characterization. 1770 54

Oncolytic virotherapy is a new strategy for cancer treatment for humans and dogs. Reovirus has been proven to be a potent oncolytic virus in human medicine. Our laboratory has previously reported that canine mast cell tumor and canine lymphoma were susceptible to reovirus. In this study, canine solid tumor cell lines (mammary gland tumor, osteosarcoma and malignant melanoma) were tested to determine their susceptibility towards reovirus. We demonstrated that reovirus induces more than 50% cell death in three canine mammary gland tumors and one canine malignant melanoma cell line. The reovirus-induced cell death occurred via the activation of caspase 3. Ras activation has been shown to be one of the important mechanisms of reovirus-susceptibility in human cancers. However, Ras activation was not related to the reovirus-susceptibility in canine solid tumor cell lines, which was similar to reports in canine mast cell tumor and canine lymphoma. The results of this study highly suggest that canine mammary gland tumor and canine malignant melanoma are also potential candidates for reovirus therapy in veterinary oncology.
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PMID:The oncolytic effects of reovirus in canine solid tumor cell lines. 2564 33

Mast cell sarcoma (MCS) is a rare form of mastocytosis characterized by the presence of solid tumor(s) comprising malignant mast cells that harbor destructive infiltration capability and metastatic potential. Here, we present an extensive literature review and report on 23 cases of MCS, including 3 new cases from the French National Reference Center for Mastocytosis. From our analysis, it appears that MCS can occur at any age. It can manifest de novo or, to a lesser extent, may evolve from a previously established mastocytosis. Bone tumor is a frequent manifestation, and symptoms of mast cell activation are rare. Histological diagnosis can be difficult because MCS is frequently composed of highly atypical neoplastic mast cells and can thus mimic other tumors. Unexpectedly, the canonical KIT D816V mutation is found in only 21% of MCS; therefore, complete KIT gene sequencing is required. The prognosis of patients with MCS is poor, with a median survival time of less than 18 months, and progression to mast cell leukemia is not unusual. Because conventional chemotherapies usually fail, the role of targeted therapies and bone marrow transplantation warrants further investigation in such aggressive neoplasms.
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PMID:Mast cell sarcoma: new cases and literature review. 2760 77

The prognostic role of tumor-infiltrating tryptase+ mast cells in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 28 published studies with 4224 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating tryptase+ mast cells in human solid tumors. We found that tryptase+ mast cell infiltration significantly decreased overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, tryptase+ mast cell infiltration was significantly associated with worse OS in non-small cell lung cancer, hepatocellular carcinoma and 5-year survival in colorectal cancer. And these cells were inversely associated with DFS in hepatocellular and colorectal cancer. In addition, high density of intratumoral tryptase+ mast cells significantly correlated with lymph node metastasis of solid tumor. In conclusion, Tryptase+ mast cell infiltration leads to an unfavorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances and targeting it may have a potential for effective treatment.
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PMID:Tumor-infiltrating tryptase+ mast cells predict unfavorable clinical outcome in solid tumors. 2902 96


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