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)

10,090 dissections of dogs exhibited 2631 neoplastic processes of which 309 involved the heart in the form of eu- and heteropic tumours. The most common primary and/or secondary heart tumour type was hemangiosarcoma (n = 187), followed by paraganglioma (n = 46), carcinoma (n = 33), malignant lymphoma (n = 12), thyroid heart base tumour (n = 9), melanoma (n = 7), mast cell tumour (n = 3) and blastoma (n = 2). The tumour diagnoses were immunohistochemically proved by various antibodies to cytokeratins, vimentin, GFAP, NSE, von Willebrand factor, CD3, CD45RA, S100, thyroglobulin as well as histochemically with argyrophilic, Fontana-Masson and heterochromatic reactions. The odds ratio (OR) for breed and tumour prevalences were determined: German shepherds showed the highest OR for hemangiosarcomas and boxers for paragangliomas.
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PMID:Systemic, metastatic, eu- and heterotope tumours of the heart in necropsied dogs. 869 31

YU-311 is a monoclonal antibody that reacts with a human leukemia cell line resistant for cytosine arabinoside and that identifies a 92 kDa membrane protein. The reactivity of YU-311 in normal organs, various non-hematopoietic tumors and in mast cell tumors in formalin-fixed, paraffin-embedded specimens was examined using immunohistochemical methods. In normal organs, YU-311 reacted with fundic glands of the stomach, the intercalated duct of the pancreas, the distal portion and the loop of Henle of renal tubules and tissue mast cells. Benign neoplasms of various organs showed no immunoreaction with YU-311, except for mast cell tumors. Some types of malignant neoplasms were occasionally positive against YU-311, suggesting neoplasms arising from or differentiating along normal YU-311-positive counterparts. Some other types of malignancies were rarely positive for YU-311, although their normal counterparts showed no immunoreactivity with YU-311. None of the non-epithelial tumors reacted with YU-311, except for one case of malignant melanoma. In contrast, normal tissue mast cells and their related tumors, such as urticaria pigmentosa or solitary mastocytoma, were constantly positive for YU-311. None of the non-hematopoietic human tumor cell lines examined in the present study was reactive with YU-311. These findings indicate that YU-311 is a good marker of some types of tumors and mast cell tumors and that an aberrant expression of YU-311 rarely occurs.
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PMID:Reactivity of antibody YU-311 in formalin-fixed, paraffin-embedded specimens of normal organs, non-hematopoietic tumors, and mast cell tumors. 929 30

Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel factor (S1) result in strikingly similar defects in mast cell and melanocyte development. Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with S1 results in activation of MAP kinase, which in turn phosphorylates Mi at a consensus target serine. This phosphorylation upregulates Mi transactivation of the tyrosinase pigmentation gene promoter. In addition to modulating pigment production, such signalling may regulate the expression of genes essential for melanocyte survival and development. The pathway represents a new application of the general MAP kinase machinery in transducing a signal between a tissue-specific receptor at the cell surface and a tissue-specific transcription factor in the nucleus.
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PMID:MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. 944 Jun 96

Mast cell participation in immune responses, tumor progression, and vascularization has been studied extensively in vitro. In situ investigation of mast cells in routinely processed tissues is hampered by difficulty in reliable detection of mast cells. We studied the tissue density of mast cells using a morphometric point-counting technique in 1 microm-thick, Giemsa-stained, tissue sections from epon-embedded samples of skin biopsies. This technique has been demonstrated to be an accurate and reproducible method for determining mast cell density. Mast cell density in 15 cases of invasive melanoma was compared to that of 9 cases of benign melanocytic nevi and 4 cases of melanoma in situ. Mast cell density was greatest in invasive melanoma (mean density = 0.61 vol.%). The mean density of mast cells in nevi and in situ melanoma was 0.33 and 0.5 respectively. Six of 15 cases of melanoma had mast cell densities > 0.6, whereas mast cell density did not exceed 0.6 in any cases of melanoma in situ or benign melanocytic nevi (p < 0.02). Our findings confirm an increase in mast cell tissue density in some cases of invasive melanoma when compared to mast cell density in benign nevi and in situ melanoma.
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PMID:Increased mast cell density in invasive melanoma. 950 38

The c-kit gene product (CD117) is known to be expressed by a variety of normal human tissue cell types, including breast epithelium, germ cells, melanocytes, immature myeloid cells, and mast cells. To further characterize the expression of this antigen, 117 normal human tissues and 576 human tumors were studied by paraffin section immunohistochemistry. Varying degrees of CD117 expression were identified in various normal cells and in 53% of all tumors studied. In most cases (42% of total), CD117 expression was weak. Expression was most common in mast cell disease (100%), testicular germ cell tumors (100%), endometrial carcinomas (100%), papillary and follicular thyroid carcinomas (100%), small cell carcinomas (91%), malignant melanomas (90%), and ovarian epithelial carcinomas (87%). Strong immunoreactivity was only identified in cases of mast cell disease (11 of 11 cases), serous ovarian carcinoma (3 of 16), malignant melanoma (2 of 40), small cell lung carcinoma (one of seven), and adenoid cystic carcinoma (one of one). Although the pattern of reactivity was primarily cytoplasmic, a membrane staining pattern was seen in a subset of cases, and strong membrane staining was identified in normal mast cells and all cases of mast cell disease. The lack of tumor specificity of weak expression of this antigen limits its diagnostic utility in most cases. However, the strong membrane reactivity for CD117 identified in mast cells may be useful in the diagnosis of mast cell disorders.
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PMID:Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders. 959 74

To further elucidate mechanisms involved in mast cell accumulation at sites of cutaneous inflammation, we have studied the ability of human leukemic mast cells (HMC-1 cells) to express functionally active IL-8 receptors. Expression of mRNA for both types of IL-8 receptors (CXCR1 and CXCR2) was demonstrated by PCR and of both proteins by flow cytometry. Binding and competition studies with 125I-labeled IL-8 and its homologue melanoma growth stimulating activity (125I-labeled MGSA) revealed two specific binding sites for IL-8, K1 = 1.1 x 10(11) M(-1) and K2 = 5 x 10(7) M(-1); and for MGSA, K1 = 2.8 x 10(10) M(-1) and K2 = 5 x 10(7) M(-1). This finding was supported by a dose-dependent rise of cytosolic free calcium concentration ([Ca2+]i) induced by both chemokines and to a lesser extent by the homologue neutrophil-activating peptide-2 (NAP-2). A significant migratory response of human leukemic mast cells (HMC-1) was observed with all three chemokines at a range from 10(-8) M to 10(-9) M. Moreover, the formation of cellular F-actin was induced in a rapid, dose-dependent fashion, with a maximally 1.7-fold increase at 10(-7) M. Using postembedding immunoelectron microscopy, we could show the expression of CXCRI on the cytoplasmatic membrane of isolated human skin mast cells whereas CXCR2 was located in mast cell-specific granules. These findings demonstrate for the first time the functional expression of both types of IL-8 receptors on human mast cells, suggesting a role for their ligands during mast cell activation and recruitment.
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PMID:Expression and functional activity of the IL-8 receptor type CXCR1 and CXCR2 on human mast cells. 972 62

1. The development into tumours of skin cells transformed by ultraviolet (UV) B radiation of wavelengths 290-320 nm is enhanced by the ability of UVB to suppress an immune response that would otherwise destroy them. Ultraviolet B-induced immunomodulation may be by multiple mechanisms, but generally manifests in an antigen-presenting cell defect and an altered cytokine environment in the draining lymph nodes. 2. Immune responses to microbial or self-antigens may be dysfunctional by similar mechanisms following UVB exposure. 3. Earliest-acting intermediates in the initiation of UVB-induced immunosuppression are the UVB absorbers (photoreceptors) of the skin, notably DNA resulting in immunoregulatory cytokine production, and trans-urocanic acid (UCA), which, upon isomerization to its cis isomer, signals downstream immunosuppressive events. 4. In mice, dermal mast cells are critical to UVB-induced systemic immunomodulation. In mice, there is a functional link as well as a linear relationship between the prevalence of histamine-staining dermal mast cells and the log of the dose of UVB required for 50% immunosuppression. Studies with histamine receptor antagonists support histamine as the main' product of mast cells involved. Histamine acts in large part via a prostanoid-dependent pathway. 5. Approximately 50% of humans and greater than 90% of patients with non-melanoma skin cancer are UVB susceptible for suppression of a contact hypersensitivity response. Neither cytokine polymorphisms nor UVB-induced levels of cis-UCA in irradiated skin have been linked to UVB susceptibility. Patients with basal cell carcinomas (BCC) have an increased dermal mast cell prevalence in non-sun-exposed buttock skin. We propose that mast cells function in humans, as in mice, by initiating immunosuppression and, thereby, allowing a permissive environment for BCC development.
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PMID:Sunlight, immunosuppression and skin cancer: role of histamine and mast cells. 1115 22

The expression of a primary initiator of tumor angiogenic responses, vascular endothelial growth factor (VEGF), may be induced by nitric oxide (NO) in carcinoma cells. However, the net impact of NO on carcinogenesis remains unclear, because manipulation of NO levels has been shown to either stimulate or inhibit tumor growth. We have investigated the relationship between inducible NO synthase (NOS II), VEGF expression, and growth of B16-F1 melanoma over 14 days in wild-type (NOS II+/+) mice and in those in which the gene for NOS II has been deleted (NOS II-/-). B16-F1 tumor growth was measured as wet weight of the excised tissue. Tumor NOS II and VEGF localization were evaluated by immunohistochemistry, and VEGF mRNA levels were measured by Northern blot analysis. In NOS II+/+ mice inoculated with B16-F1 melanoma cells, macroscopic tumors were always observed at 14 days; however, 22% of NOS II-/- mice had no detectable tumor mass. Immunoreactive NOS II was detected in tumor cells of tumors grown in NOS II+/+ but not in NOS II-/- mice. Although immunoreactive VEGF was detected in the granules of tumor-associated mast cells from both NOS II+/+ and NOS II-/- mice, VEGF mRNA expression in tumors from NOS II-/- was half that in NOS II+/+ mice. Neither NOS II inhibition, exogenous NO, nor peroxynitrite influenced DNA synthesis in culture B16-F1 melanoma cells. The NO donor did not alter either VEGF mRNA levels or degranulation in cultures of the mast cell line RBL-2H3, but peroxynitrite increased both VEGF mRNA expression and degranulation. We conclude that host expression of NOS II contributes to induction of NOS II in the tumor and to melanoma growth in vivo, possibly by regulating the amount and availability of VEGF.
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PMID:Nitric oxide synthase II gene disruption: implications for tumor growth and vascular endothelial growth factor production. 1130 6

Varieties of the clinical features of mastocytoses, also called mastocytosis syndrome, are presented. The disease is characterized by excessive accumulation of mast cells, their proliferation and action in the skin and other organs, even in the central nervous system. The mastocytosis syndrome was known as early as the second half of the 19th century under the term urticaria pigmentosa, and was histologically confirmed by the presence in the dermis of metachromatic cells, i.e. Ehrlich mast cells with red-purple cytoplasmic granules visible with Giemsa or toluidine blue stains. The mastocytosis syndrome was then supposed to be a benign chronic dermatosis of childhood with spontaneous regression by adolescence. The clinically pathognomonic symptoms of Darier's sign (urtication of primary skin lesion upon rubbing) and flushing help in the diagnosis of mastocytosis syndrome. In the 1950s, there was a progression in the diagnosis of systemic mastocytosis achieved by scientists and clinicians of various specialties. Upon the discovery of many mast cell released mediators (heparin, histamine, leukotrienes, prostaglandins, proteases, cytokines), receptor functions, relationship to IgE, anaphylatoxin, etc., they were recognized as triggers of various clinical features of the mastocytosis syndrome. In this paper, different forms of cutaneous and systemic mastocytosis are described, with special reference to 'mastocytosis mucocutanea haemorrhagica' observed by one of the authors in a female infant and followed from 6 months till 2.5 years of age. The patient showed practically all the diverse forms of cutaneous mastocytosis: urticaria pigmentosa, papular, nodular, tumorous-like melanoma, vesiculobullous, erythrodermic, telangiectasia eruptiva maculosa perstans. She also suffered from nasal and rectal hemorrhage, conjunctival suggillations, plaque-like infiltrations of the glossal, oropharyngeal and laryngotracheal mucosa, episodes of flushing, and transitory apnea. It is emphasized that the diagnosis of mastocytosis syndrome may be difficult for its mimicking various other diseases. The occurence of mastocytosis syndrome from the neonatal period through adult and old age, and possibilities of symptomatic treatment and prevention of sudden death or fatalities are discussed. Familial occurrence of mastocytosis syndrome and new genetic studies that may prove highly useful for understanding the etiopathogenesis of mastocytosis syndrome are described.
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PMID:Clinical varieties of mastocytoses. 1150 29

An unexplained paradox of malignant melanoma is the apparent failure of the blood within the tumor to clot despite the presence of multiple factors that should promote blood clotting. Here we present histochemical evidence that human and murine melanomas are extensively infiltrated by abundant mast cells. Because mast cells contain the natural anticoagulant heparin, the present studies were aimed at defining the role of mast cell heparin in preventing the blood from clotting within B16 melanoma grafts in C57BL/6 J mice. Mice bearing B16 melanoma grafts were treated with non-specific or specific inhibitors of mast cell heparin (protamine or heparinase, respectively). After the drug treatment there was histologic and functional evidence of selective thrombosis of the blood vessels within the protamine and heparinase treated melanoma grafts. A similar, high degree of thrombosis was also observed in B16 tumors grown in transgenic NDST-2 knockout mice bearing a targeted disruption in the gene coding for mast cell heparin synthesis. The tumors grown in the protamine-treated animals were significantly smaller than the tumors from control (untreated mice). By contrast, the tumors treated with heparinase or grown in the NDST-2 knockout mice were significantly larger than the tumors from control (untreated) mice. We conclude that the intrinsic procoagulant properties of malignant melanoma are neutralized in vivo by the anticoagulant properties of endogenous heparin produced by mast cells that naturally infiltrate the tumor. Our results also suggest that thrombosis and hemostasis within melanoma may play a complex role in modulating the growth of the tumor.
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PMID:Inhibition of thrombosis in melanoma allografts in mice by endogenous mast cell heparin. 1288 84


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