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)

Metastases continue to be the chief cause of morbidity and mortality for many tumors, including brain metastases of lung and mammary adenocarcinoma. Stress appears to increase metastases, but the mechanism is not understood. Recent evidence suggests that local inflammation is conducive for cancer growth and a unique immune cell, the mast cell, accumulates in the stroma surrounding tumors and is critically located at the blood-brain-barrier (BBB). Mast cells express receptors for and can be stimulated by corticotropin-releasing hormone (CRH), secreted under stress, to release mediators such as histamine, IL-8, tryptase and vascular endothelial growth factor (VEGF), which disrupt the BBB permitting metastases. Stress and mast cells could serve as new targets for drug development to prevent brain metastases, especially since CRH receptor antagonists and brain mast cell inhibitors have recently been developed.
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PMID:Impact of stress and mast cells on brain metastases. 1919 17

Various studies have shown the role of mast cells in chronic inflammatory states and in tumor growth. The study is designed to have an idea of the relationship of mast cell density (MCD) to gastric ulcer and cancer, to verify whether mast cell accumulation occurred in the two conditions especially in Indian patients and thus postulate that therapeutic strategies against mast cell mediators could be useful in treatment. Also, we want to review literature and attempt to explain our findings. A total of 240 patients, who underwent their first endoscopy and biopsy for a span of 21/2 years were studied retrospectively. Out of these, 210 cases that were either gastric ulcers or cancer were chosen for this MCD study. Biopsies were sectioned and stained routinely. Toluidine blue stain and copper grid was used to calculate MCD. Student's t-Test was used to calculate the statistical significance of MCD. MCD in benign ulcers was much higher than in control subjects. MCD in well-differentiated cancers showed MCD higher than control. Poorly-differentiated adenocarcinoma showed lower MCD than well-differentiated adenocarcinoma. It was concluded that the accumulation of mast cells in gastric ulcers is an inflammatory response. MCD is increased in well-differentiated gastric cancers, which may be a mast cell mediated immune response or mast cells may have a role in tumor angiogenesis and produce factors for tumor progression. Poorly-differentiated adenocarcinoma apparently lacks mast cell mediated anti-tumor response in some unexplained way.
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PMID:Evaluation of endoscopic biopsy in gastric lesions with a special reference to the significance of mast cell density. 1913 73

The study included 85 inpatients and outpatients in whom composition of inflammatory infiltrate from gastric mucosa (GM) was determined at the Oncological Research Institute, Tomsk Research Centre of the Siberian Division, Russian Academy of Medical Sciences. The patients were allocated to 4 groups depending on nosological form of the disease. Group 1 comprised 21 patients with grade II-III GM epithelial dysplasia, group 2 - 24 patients having stomach cancer (histologically confirmed adenocarcinoma), group 3 - 19 patients with stage II-III mucinous gastric carcinoma, group 4 - 20 allegedly healthy subjects without signs of gastrointestinal pathology. It was shown that dysplastic processes in GM are associated with an increase of neutrophil, eosinophil, macrophage, and mast cell count along with a drop in the number of lymphocytes and plasmocytes. Stroma of invasive stomach cancer underwent intense inflammatory infiltration accompanied by a rise in the number of lymphocytes, plasmocytes, and neutrophils. Mucinous gastric carcinoma was characterized by an increase of the number of neutrophils and macrophages. Patients having adenocarcinoma of the stomach showed enhanced plasmocytic infiltration by plasmocytes with a low number of eosinophils and mast cells. It is concluded that characteristics of inflammatory GM infiltrate may be useful for the objective assessment of stomach cancer risk in patients with GM dysplasia, formation of a high oncological risk group, adequate dynamic monitoring and treatment of these patients.
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PMID:[Characteristic of inflammatory infiltrate of gastric mucosa in patients with grade II-III gastric dysplasia and of stomach cancer]. 1917 95

Between October 2000 and January 2007, 24 horses were presented with suspected squamous cell carcinoma (SCC) of the third eyelid. The hospital's medical records were analysed retrospectively to gain data about the cases, and telephone follow-up was obtained from the owners and referring veterinary surgeons. The resected third eyelid was submitted for histological examination in 21 cases; in the other three cases the tissue was not submitted at the owners' request, for economic reasons. SCC was confirmed in 16 of these 21 cases, three cases were diagnosed histologically as lymphoid hyperplasia, one as a mast cell tumour and one as a sebaceous gland adenocarcinoma. Long-term follow up over a median period of 41 months revealed no recurrence of SCC or associated problems; six of the 16 confirmed SCC cases were euthanased for unrelated reasons during the follow-up period.
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PMID:Third eyelid resection as a treatment for suspected squamous cell carcinoma in 24 horses. 2002 77

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with an extremely low survival rate. It is characterized by a chronic inflammatory process with intense mast cell infiltrate that is associated with reduced survival. The aim of this study was to test the hypothesis that mast cells have an enhancing effect on NSCLC proliferation. To assess the tumor-promoting potential of mast cells, we used the human alveolar basal adenocarcinoma (A549) and the mouse Lewis lung carcinoma (LLC) cell lines, umbilical cord blood-derived mast cells (CBMC) and the mast cell-deficient mouse Sash model. The proliferation rate of A549/LLC cells was markedly increased by mast cells and histamine. Histamine proliferating activity was mediated via H(1), H(2) and H(4) receptors and caused ERK phosphorylation. LLC induced in Sash mice or in wild-type mice treated with the mast cell stabilizer nedocromil sodium displayed an accelerated growth (number of metastic colonies in the lungs, total lung area and lung/total mice weight ratio). In summary, we have shown a significant effect of mast cells and histamine in enhancing NSCLC/LLCX growth in vitro, while in a mouse LLC model in vivo we have found that mast cells are important negative regulators of cancer development. Therefore our results would indicate a pro-tumorogenic effect of the mast cells in vitro on established lung tumor cell lines, and anti-tumorogenic effect in mice at lung cancer induction. In conclusion, mast cell/anti-histamine targeted therapies should carefully consider this dual effect.
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PMID:Mast cells and histamine enhance the proliferation of non-small cell lung cancer cells. 2173 95

Pancreatic ductal adenocarcinoma (PDAC) exists in a complex desmoplastic microenvironment, which includes cancer-associated fibroblasts [also known as pancreatic stellate cells (PSC)] and immune cells that provide a fibrotic niche that impedes successful cancer therapy. We have found that mast cells are essential for PDAC tumorigenesis. Whether mast cells contribute to the growth of PDAC and/or PSCs is unknown. Here, we tested the hypothesis that mast cells contribute to the growth of PSCs and tumor cells, thus contributing to PDAC development. Tumor cells promoted mast cell migration. Both tumor cells and PSCs stimulated mast cell activation. Conversely, mast cell-derived interleukin (IL)-13 and tryptase stimulated PSC proliferation. Treating tumor-bearing mice with agents that block mast cell migration and function depressed PDAC growth. Our findings suggest that mast cells exacerbate the cellular and extracellular dynamics of the tumor microenvironment found in PDAC. Therefore, targeting mast cells may inhibit stromal formation and improve therapy.
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PMID:Dynamic mast cell-stromal cell interactions promote growth of pancreatic cancer. 2363 81

A case of a 58-year-old with fatal anaphylaxis due to multiple bee stings is reported. Supportive evidence for anaphylaxis included post-mortem serum tests, which demonstrated a markedly elevated tryptase level and increased sensitivity to bees on radioallergosorbent test (RAST). At autopsy a previously undiagnosed esophageal adenocarcinoma involving the gastroesophageal (GE) junction was also identified. Histology of the tumor demonstrated significant numbers of mast cells, many of which were degranulating. Increased numbers of mast cells, as in mastocytosis, are known to predispose to an allergic sensitivity to Hymenoptera. The finding of a significant peritumoral mast cell population with degranulating forms in this case, therefore, raises the possibility that death due to anaphylaxis was contributed to by mast cell proliferation in an occult esophageal carcinoma.
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PMID:Multiple bee stings, peritumoral mast cell degranulation and anaphylaxis--is there a relationship? 2391 Aug 39

The RET (REarranged during Transfection) receptor tyrosine kinase is targeted by oncogenic rearrangements in thyroid and lung adenocarcinoma. Recently, a RET (exon 12) rearrangement with FGFR1OP [fibroblast growth factor receptor 1 (FGFR1) oncogene partner] (exon 12) was identified in one chronic myelomonocytic leukemia (CMML) patient. We report the molecular cloning and functional characterization of a novel FGFR1OP (exon 11)-RET (exon 11) gene fusion event (named FGFR1OP-RET), mediated by a reciprocal translocation t(6; 10)(q27; q11), in a patient affected by primary myelofibrosis (PMF) with secondary acute myeloid leukemia (AML). The FGFR1OP-RET fusion protein displayed constitutive tyrosine kinase and transforming activity in NIH3T3 fibroblasts, and induced IL3-independent growth and activation of PI3K/STAT signaling in hematopoietic Ba/F3 cells. FGFR1OP-RET supported cytokine-independent growth, protection from stress and enhanced self-renewal of primary murine hematopoietic progenitor and stem cells in vitro. In vivo, FGFR1OP-RET caused a spectrum of disease phenotypes, with >50% of mice showing a fatal myeloproliferative disorder (MPD). Other phenotypes were leukemia transplantable in secondary recipients, dramatic expansion of the mast cell lineage, and reduction of repopulating activity upon lethal irradiation. In conclusion, FGFR1OP-RET chimeric oncogenes are endowed with leukemogenic potential and associated to myeloid neoplasms (CMML and PMF/AML).
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PMID:Functional characterization of a novel FGFR1OP-RET rearrangement in hematopoietic malignancies. 2431 14

Increasing evidence indicates that tumor microenvironment (TME) is crucial in tumor survival and metastases. Inflammatory cells accumulate around tumors and strangely appear to be permissive to their growth. One key stroma cell is the mast cell (MC), which can secrete numerous pro- and antitumor molecules. We investigated the presence and degranulation state of MC in pancreatic ductal adenocarcinoma (PDAC) as compared to acute ancreatitis (AP). Three different detection methods: (a) toluidine blue staining, as well as immunohistochemistry for (b) tryptase and (c) c-kit, were utilized to assess the number and extent of degranulation of MC in PDAC tissue (n=7), uninvolved pancreatic tissue derived from tumor-free margins (n=7) and tissue form AP (n=4). The number of MC detected with all three methods was significantly increased in PDAC, as compared to normal pancreatic tissue derived from tumor-free margins (p<0.05). The highest number of MC was identified by c-kit, 22.2&#x2213;7.5 per high power field (HPF) in PDAC vs 9.7&#x2213;5.1 per HPF in normal tissue. Contrary to MC in AP, where most of the detected MC were found degranulated, MC in PDAC appeared intact. In conclusion, MC are increased in number, but not degranulated in PDAC, suggesting that they may contribute to cancer growth by permitting selective release of pro-tumorogenic molecules.
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PMID:Increased number of non-degranulated mast cells in pancreatic ductal adenocarcinoma but not in acute pancreatitis. 2500 33

Neoplastic cancer cells and cancer stroma (including infiltrating immune cells) determine the biology and prognosis of cancer. Various types of adaptive and innate immune cells are known to infiltrate the cancer stroma. However, the patterns and spatial distribution of immune cell infiltration as well as its association with tumor histology remain poorly understood. To address these issues, we comprehensively analyzed the infiltrating immune cells present in lung adenocarcinoma. The principal types of both adaptive and innate infiltrating immune cells were immunohistochemically evaluated in the predominant histologic components of 111 lung adenocarcinomas. The same analysis was also carried out on 143 samples of histologic subtypes making up more than 20% of tumors. As a result, plasma cells and B cells with interfollicular distribution were almost exclusively observed in invasive histologic subtypes, while an increased number of mast cells were observed in noninvasive histologic subtypes. Cluster analysis revealed four distinct immunosubtypes (CD8, mast cell, macrophage/dendritic cell, and plasma cell subtypes) based on the infiltrating immune cell profiles. These immunosubtypes correlated with histologic subtypes, and univariate and multivariate analyses identified the plasma cell subtype as an independent negative prognostic factor. These plasma cells may be one of the major producers of the immunosuppressive cytokine IL35 in cancer stroma.
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PMID:Comprehensive Immune Profiling of Lung Adenocarcinomas Reveals Four Immunosubtypes with Plasma Cell Subtype a Negative Indicator. 2678 25


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