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)

This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.
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PMID:Mast cells and cutaneous malignancies. 1625 17

Imatinib mesylate (Gleevec, also known as STI-571), is an approved oral treatment for patients with chronic myeloid leukemia (CML). It blocks the activity of Abelson cytoplasmic tyrosine kinase (ABL), c-Kit and the platelet-derived growth factor receptor (PDGFR). As an inhibitor of PDGFR, imatinib mesylate appears to have utility in the treatment of a variety of dermatological diseases. Imatinib has been reported to be an effective treatment for FIP1L1-PDGFRalpha+ mast cell disease, hypereosinophilic syndrome, and dermatofibrosarcoma protuberans. One report notes its effectiveness for treating HIV related Kaposi's sarcoma; imatinib has not been effective for the treatment of melanoma.
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PMID:A comprehensive review of imatinib mesylate (Gleevec) for dermatological diseases. 1648 79

Retinoids show antitumor effects on human acute promyelocytic leukemia and other tumors via retinoid receptors. In dogs, the role of retinoid receptors in inhibiting tumor development remains unclear. To evaluate the correlation between the degree of expression of retinoic acid receptor alpha (RARalpha) mRNA and the antiproliferative effects of all-trans retinoic acid (ATRA) treatments, expression analysis of RARalpha mRNA and cell growth inhibition assay were performed on 17 established canine tumor cell lines, including 6 mammary gland tumor (MGT) cell lines, 3 osteosarcoma cell lines, 5 melanoma cell lines, and 3 mast cell tumor (MCT) cell lines. Among the cell lines investigated, all 3 MCT cell lines showed high expression of RARalpha, and the most effective cell growth inhibition was observed in ATRA-treated MCT cell lines. However, remarkable antiproliferative effects of ATRA treatments were not observed on other tumor cell lines with moderate or low RARalpha mRNA expression. As a result of the relationship between RARalpha mRNA expression and ATRA treatment with regression analysis, statistically significant correlation was suggested. Furthermore, real-time quantitative polymerase chain reaction analysis of RARalpha was performed on MCT tissue samples of dogs with spontaneous disease, and 5 of 9 tissues showed high expression. These results suggest that ATRA may be an effective antitumor agent for MCT in dogs, and that prior measurement of expression of RARalpha mRNA may be a good indicator of the effectiveness of ATRA treatment.
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PMID:Relationship between retinoic acid receptor alpha gene expression and growth-inhibitory effect of all-trans retinoic acid on canine tumor cells. 1659 93

Previous studies have demonstrated that treatment with activin A and TGF-beta(1), members of the TGF-beta family, stimulated maturation of mouse bone marrow-derived cultured mast cells (BMMC), which was characterized by morphology and gene expression of mouse mast cell proteases (mmcps). In order to gain a better understanding of activin A- and TGF-beta(1)-induced maturation in mast cells, we investigated the genes that were up-regulated in response to treatment with these two members of the TGF-beta family. The cDNA microarray analyses indicated that in BMMC, five genes were induced by treatment with 4 nM activin A for 2 h. Tocopherol-associated protein (Tap) was one of the induced genes, and the Tap induction in response to activin A treatment was confirmed by real-time RT-PCR analyses. Treatment with TGF-beta(1) at 200 pM but not BMP-2 at 4 nM also increased Tap gene transcript in BMMC. Activin A-induced Tap expression was detected in BMMC but not in RAW264 macrophage-like cells, B16 melanoma cells or P19 embryonic carcinoma cells. Treatment with >1 muM SB431542, an inhibitor of activin and TGF-beta type I receptors ALK4/5, reduced responsiveness of Tap expression to TGF-beta(1), whereas <0.5 microM SB431542 effectively reduced TGF-beta(1)-induced expression of mmcp-1 and mmcp-7. These results suggest that inhibitory effects of SB431542 are different between TGF-beta-induced genes. Reporter assays indicated that Tap expression enhances transcription mediated by the activin/TGF-beta pathway. Thus, the present results suggest that Tap induction in response to activin/TGF-beta occurs predominantly in mast cells and serves as a positive regulator in activin/TGF-beta signaling.
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PMID:Identification of tocopherol-associated protein as an activin/TGF-beta-inducible gene in mast cells. 1687 93

Amputation is commonly performed to both treat and diagnose conditions affecting the digits of dogs. Although histopathologic evaluation of these digits is routinely done, data on the prevalence and prognosis of neoplasms of the digit are scarce. The records of multiple veterinary diagnostic laboratories were searched to identify submissions of amputated digits from dogs. Four hundred twenty-eight separate submissions were reviewed for diagnosis, age, sex, limb of origin, and digits affected, and the original submitting clinics were surveyed to determine clinical outcome of the animal. No diagnosis could be agreed upon in 24 animals, and these were excluded from the study. Kaplan-Meier product-limit method was used to determine the disease-free interval and survival time. Neoplastic disease was identified in 296 of 404 submissions, with exclusively inflammatory lesions composing 108 cases. A total of 30 different neoplastic processes were identified. In 233 (77.7%) of the neoplastic cases, a malignant tumor was identified. Squamous cell carcinoma was the most commonly identified tumor (n = 109, 36.3%), and 11 of 42 dogs for which clinical follow-up information was available developed metastatic disease. Squamous cell carcinoma of the digit appears to have a greater metastatic potential than that occurring elsewhere in the body. Other common diagnoses included melanoma (n = 52, 17.3%), soft-tissue sarcoma (n = 29, 9.7%), and mast cell tumor (n = 20, 6.7%). Melanomas were associated with poor prognoses, with a median survival time of 365 days.
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PMID:Diagnoses and clinical outcomes associated with surgically amputated canine digits submitted to multiple veterinary diagnostic laboratories. 1749 Oct 77

This unit presents an experimental tumor model which has led to pivotal advances in tumor immunology culminating in the preclinical development of human cancer vaccines for melanoma. The model employs the use of the P815 mastocytoma cell line. Although the P815 cell line belongs to the mast cell lineage, it offers several advantages for in vivo experimentation of the tumor-host relationship. It grows progressively in the majority of syngeneic DBA/2 mice and can be implanted either intraperitoneally or subcutaneously. Moreover, immunogeneic variants have been created yielding tumors that are spontaneously rejected BB a behavior that has provided a context in which to study the immunologically relevant molecules and cells that dictate a successful anti-tumor response.
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PMID:The p815 mastocytoma tumor model. 1843 77

Transplant immunosuppressants have been implicated in the increased incidence of non-melanoma skin cancer in transplant recipients, most of whom harbor considerable UVB-induced DNA damage in their skin prior to transplantation. This study was designed to evaluate the effects of two commonly used immunosuppressive drugs, cyclosporine A (CsA) and sirolimus (SRL), on the development and progression of UVB-induced non-melanoma skin cancer. SKH-1 hairless mice were exposed to UVB alone for 15 weeks, and then were treated with CsA, SRL, or CsA+SRL for 9 weeks following cessation of UVB treatment. Compared with vehicle, CsA treatment resulted in enhanced tumor size and progression. In contrast, mice treated with SRL or CsA+SRL had decreased tumor multiplicity, size, and progression compared with vehicle-treated mice. CsA, but not SRL or combined treatment, increased dermal mast cell numbers and TGF-beta1 levels in the skin. These findings demonstrate that specific immunosuppressive agents differentially alter the cutaneous tumor microenvironment, which in turn may contribute to enhanced development of UVB-induced skin cancer in transplant recipients. Furthermore, these results suggest that CsA alone causes enhanced growth and progression of skin cancer, whereas co-administration of SRL with CsA causes the opposite effect. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub
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PMID:Sirolimus reduces the incidence and progression of UVB-induced skin cancer in SKH mice even with co-administration of cyclosporine A. 1878 41

Two patients with metastatic malignant melanoma developed immediate type hypersensitivity-like symptoms while being treated with recombinant interleukin-(IL-)2 immunotherapy. Both patients showed positive skin prick tests to IL-2, enhanced basophil degranulation in vitro and responded to anti-histamines, but laboratory investigations suggested an IgE-independent, pseudoallergic mast cell degranulation against IL-2.
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PMID:Interleukin-2 immediate type hypersensitivity? 1849 78

To investigate the expression of cartilage oligomeric matrix protein (COMP) associated with oncogenesis, samples of serum and tumor tissue were obtained from 25 dogs with tumors. The serum levels of COMP in dogs with tumors were significantly higher than in 38 normal controls and correlated with the concentrations of tumor tissue extracts. Positive bands to COMP antibody were detected on immunoblots of tumor extracts. Immunohistochemistry and in situ hybridization demonstrated positive signals of COMP and its mRNA in the cytoplasm of tumor cells from mammary gland tumors, but not in the normal mammary gland. Positive immunohistochemistry results were also obtained for COMP in mast cell tumor and melanoma cells. Oncogenesis might augment production of COMP and the serum level of COMP in dogs.
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PMID:Gene and protein expression of cartilage oligomeric matrix protein associated with oncogenesis in canine tumors. 1942 Aug 57

Microphthalmia-associated transcription factor (MITF) was initially shown to play a key role in melanocyte differentiation through the direct transcriptional control of TYROSINASE, TYRP1 and DCT genes, encoding the three enzymes involved in melanin synthesis or melanogenesis. Sixteen years after the first description of MITF, more than 40 direct MITF target genes have been described. They play a key role in melanocyte, osteoclast and mast cell specific functions. Furthermore, several MITF target genes, e.g. BCL2, CDK2, CDKN1A, CDKN2A, MET and HIF1A, link MITF to general cellular processes such as growth or survival. In this review, we provide an overview of the MITF-regulated genes. We pay special attention to the MITF target genes in melanocytes and raise questions about target specificity.
Pigment Cell Melanoma Res 2010 Feb
PMID:Fifteen-year quest for microphthalmia-associated transcription factor target genes. 1999 75


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