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

The growth rate of Cloudman S91 melanoma cells was compared in groups of normal and immunologically compromised DBA/2 mice that had undergone thymectomy and treatment with antilymphocyte serum. Tumor growth was markedly accelerated in the immunosuppressed animals. Other groups of normal and immunosuppressed animals were treated with daily injections of either histamine, the H-2 antihistamine cimetidine, the H-1 antihistamine pyrilamine; or the mast cell stabilizer proxicromil. Histamine treatment accelerated tumor growth, but only in normal animals and had little effect on tumor growth in immunocompromised hosts. Cimetidine treatment tended to increase tumor growth in normal hosts but this was statistically significant in only 1 of 3 experiments. In contrast, treatment with cimetidine, pyrilamine, or proxicromil always resulted in significant retardation of tumor growth in immunosuppressed animals. These data are consistent with the notion that thymectomy and treatment with antilymphocyte serum results in enhanced tumor growth that is in part due to activation of histamine-dependent suppressor cells. In this system, histamine activation of suppressor cells may be reversed by treatment with either antihistamines or proxicromil, a drug that prevents mast cell release of histamine. However, since the effects of these drugs seem to depend on the immune status of the host, thorough evaluation of immunoregulatory function and careful testing to determine whether histamine blockers reduce or promote tumor growth would seem indicated when immunomodulatory treatment with these drugs is contemplated.
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PMID:The effect of histamine, antihistamines, and a mast cell stabilizer on the growth of cloudman melanoma cells in DBA/2 mice. 686 77

The functional status of a population of mast cells taken from the subcutaneous connective tissue of rats with lymphosarcoma of Pliss and those suffering from aseptic inflammation was evaluated. The experiment established such manifestations of remote influence on the mast cell population, at early stages of tumorigenesis, as faster rates of tumor growth and mast cells maturation and enhanced degranulation. Initial signs of functional exhaustion of the mast cells population was seen as a paraneoplastic syndrome.
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PMID:[Functional status of mast cells in subcutaneous connective tissue of rats with lymphosarcoma of Pliss]. 778 45

Immunoglobulin E (IgE) that specifically binds to antigens present on carcinoma cells may represent a useful tool to combat carcinomas. Induction of an inflammatory response at the tumor site by tumor-specific IgE may result in reduced tumor growth and tumor regression. Local mast cells may be activated to release TNF-alpha and other mediators that attract inflammatory cells, such as eosinophils and macrophages, to the tumor site. It may even be expected that eosinophils perform IgE-mediated lysis of tumor cells. The G250 IgE binds an antigen present on renal cell carcinoma. Mast cells were assayed for activation by G250 IgE in vitro in the presence of G250-positive tumor cells, by determination of the release of TNF-alpha and histamine. In parallel, G250 IgG1, IgG2a, and IgG2b, bound to tumor cells, were tested for their ability to activate mast cells. Tumor-specific IgE was capable of activating mast cells in the presence of tumor cells. This activation was specific and required the presence of the antigen on the tumor cell surface and recognition of the tumor cell by the IgE. G250 IgE mediated mast cell activation when present in the medium as well as being preloaded on either tumor cells or mast cells. Preincubation of mast cells with irrelevant IgE did not block specific G250 IgE-mediated mast cell activation. Upon activation, mast cells released histamine and TNF-alpha, as was detected in cytotoxicity assays with TNF-alpha-sensitive target cells (WEHI). G250 IgG2a also induced efficient mast cell activation, comparable to the effect of G250 IgE. Mast cells can be triggered to release mediators such as TNF-alpha by IgE in the presence of tumor cells expressing specific antigen. Whether mast cell activation contributes to antitumor effects observed during antibody-based immunotherapy of tumors deserves further investigation.
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PMID:Target-specific activation of mast cells by immunoglobulin E reactive with a renal cell carcinoma-associated antigen. 878 Jan 64

Aggregation of the high affinity IgE receptor (FcepsilonRI) in a mast cell line resulted in activation of the p42 and the stress-activated p38 mitogen-activated protein (MAP) kinases. Selective inhibition of these respective kinases with PD 098059 and SB 203580 indicated that p42 MAP kinase, but not p38 MAP kinase, contributed to the production of the cytokine, tumor necrosis factor-alpha, and the release of arachidonic acid in these cells. Neither kinase, however, was essential for FcepsilonRI-mediated degranulation or constitutive production of tumor growth factor-beta. Studies with SB 203580 and the p38 MAP kinase activator anisomycin also revealed that p38 MAP kinase negatively regulated activation of p42 MAP kinase and the responses mediated by this kinase.
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PMID:Mitogen-activated protein (MAP) kinase regulates production of tumor necrosis factor-alpha and release of arachidonic acid in mast cells. Indications of communication between p38 and p42 MAP kinases. 914 63

Mast cells accumulate within solid tumors and can release many angiogenic factors, suggesting that they may modulate vascularization of tumors. Stem cell factor (SCF) stimulates mast cell migration, proliferation, and degranulation and therefore may influence mast cell behavior within tumors. We investigated the contribution of SCF to tumor angiogenesis by manipulating its level in mammary tumors. Sense or antisense cDNA fragments of rat SCF were ligated into an episomal expression vector. Ethylnitrosourea-induced rat mammary tumor cell lines were transfected with vector containing either control (no insert, C-P), sense (S-P), or antisense (AS-P) SCF DNA. The functional nature of the transfectants was confirmed by measuring SCF in cell lysates and conditioned media. Immunohistochemical analysis of the tumors induced in Berlin-Druckrey rats by these transfected cells demonstrated that mast cell number and microvascular density were significantly higher in S-P tumors and significantly lower in AS-P tumors, compared with C-P tumors. The expression of von Willebrand factor, an endothelial cell marker, showed a similar pattern. AS-P tumors were significantly smaller than either C-P or S-P tumors. These data suggest that SCF modulates tumor growth and angiogenesis via the involvement of mast cells.
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PMID:Modulation of tumor angiogenesis by stem cell factor. 1111 63

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

The aim of the present study was the ultrastructural characteristics of mast cell (MC) involved in host antitumor responses induced by local (i.t.) administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) in the primary focus of methA fibrosarcoma. MC were involved in tumor interstitium remodeling. Numerous mitochondria, well-developed RER and Golgi apparatus, clusters of polyribosomes, considerable polymorphism of granules and differentiated lamellar structures which frequently presented myelinic forms were observed after rhTNF-alpha application. In the study numerous fibres of the fibrous tissue, richly vascularized, occurred in the peripheral and intermediate tumor zones. Cluster of MC and tumor cells were seen on the border of the necrotic foci. However, proteolytic enzymes released by MC cause interstitial lysis, ensuring the place for tumor growth, and are involved in angiogenesis. Thus, it is not clear whether MC contribute to the inhibition of tumor growth or have an adjunctive role in tumor progression.
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PMID:Effect of the cytokine rhTNF-alpha on the population of mast cells in the growth of MethA fibrosarcoma--a TEM study. 1182 Jun 6

The stem cell factor/c-kit tyrosine kinase receptor pathway has been shown to be important for tumor growth and progression in several cancers, including mast cell diseases, gastrointestinal stromal tumor, acute myeloid leukemia, small cell lung carcinoma, and Ewing sarcoma. Studies using the oral agent STI-571 (Gleevec, Novartis), an inhibitor of the tyrosine kinases bcr-abl, c-kit, and PDGFR, have shown significant responses in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. With the aim of identifying additional groups of tumors that may use the stem cell factor/c-kit pathway and secondarily may be responsive to STI-571 treatment, this study surveyed 151 primary tumors from patients treated at St. Jude Children's Research Hospital for immunohistochemical expression of c-kit. Formalin-fixed, paraffin-embedded sections were stained with rabbit polyclonal anti-human c-kit (CD117, Dako) using standard avidin-biotin-peroxidase complex technique, antigen retrieval, and an automated stainer. Strong, diffuse staining for c-kit was seen in a proportion of synovial sarcomas, osteosarcomas, and Ewing sarcomas. Strong, diffuse staining was less common in neuroblastomas, Wilms' tumors, and rhabdomyosarcomas and was negative in alveolar soft part sarcomas and desmoplastic small round cell tumors. Tumors with strong, diffuse staining for c-kit in a pattern similar to gastrointestinal stromal tumor may represent suitable targets for new therapeutic agents.
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PMID:C-kit expression in pediatric solid tumors: a comparative immunohistochemical study. 1191 27

BACKGROUND: Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique.METHODS: Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII.RESULTS: The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis.CONCLUSIONS: All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis.
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PMID:Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis. 1195 67

Recently, some studies reported the presence of mast cells in various malignancies and their role in tumor growth. The aim of the study was to determine the utility of mast cell numbers in evaluating benign and malignant prostate lesions, and to ascertain whether there are variations in the numbers of mast cells with the Gleason grade. The relationship between mast cell numbers and patient age was also investigated. Retrospectively, 104 prostate specimens were examined for the presence of mast cells. The study group consisted of 57 benign prostatic hyperplasias and 47 prostate carcinomas. The paraffin sections were stained with anti-human mast cell tryptase immunohistologically. The numbers of positively staining cells in five high-power fields were counted, and their mean was calculated. There was no relationship found between mast cell numbers and age statistically. The mean mast cell numbers of the intratumoral region were significantly different from those of the peritumoral region (p = 0.0001). While the difference between benign hyperplasia and the intratumoral region was found to be significant (p = 0.0001), no difference between hyperplasia and the peritumoral region was noted (p = 0.762). There was no statistical difference between Gleason score groups (p = 0.452), and there was no interaction between score groups and intraperitumoral regions (p = 0.355).
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PMID:Immunohistological analysis of mast cell numbers in the intratumoral and peritumoral regions of prostate carcinoma compared to benign prostatic hyperplasia. 1204 35


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