Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The currently accepted models of metastasis are inconsistent with many clinical observations of the natural history of cancer and its response to therapy. Specifically, the authors suggest that it is time for a "paradigm shift." It is time to reject the "local, regional, systemic hypothesis" of cancer and replace it with a hypothesis more consistent with the clinical facts, specifically, that cancer exists in many different forms (i.e. localized disease arising from locally acting carcinogens, which can spread locally and should be treated locally, and cancer that arises as localized disease but evolves to more malignant invasive disease [the current model of metastasis]). The other forms of cancer are systemic disease, which is induced by systemic carcinogens, and cancer arising in multiple cells and multiple sites, giving rise to a picture described as metastatic cancer. The importance of this paradigm shift is that more attention would be focused on identifying systemically acting carcinogens as they relate to etiology and to molecular abnormalities in the neoplastic cells that might be targeted clinically. Recent advances in cancer treatment have demonstrated that molecules that target cancer cell molecular abnormalities (rather than tissue of origin, lymph node, or metastasis) such as bcr-abl or mutations in a cellular receptor such as c-kit or epidermal growth factor possess curative potential. In addition, more attention should be devoted to distinguishing between local tumors and systemic disease, using sophisticated molecular biologic techniques. Perhaps most important, there is a need to devise therapeutic strategies that would treat cancer as a systemic illness and hopefully have a substantial impact on overall cancer mortality.
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PMID:Metastasis--an alternative hypothesis. 1573 96

Systemic mast cell disorders in most instances appear to be clonal disorders of the mast cell and its progenitor. Symptoms result from a pathological release of mast cell mediators and a destructive mast cell infiltration. Cutaneous mastocytosis is most frequently seen in children and may regress. Systemic mastocytosis (SM) is a persistent disease. A somatic c-kit mutation at codon 816 is often detectable in haematopoietic cells. The clinical course of mastocytosis is variable, ranging from indolent to aggressive. Five categories of disease are recognized: Indolent SM, aggressive SM, SM with associated clonal haematological non-mast cell-lineage disease (AHNMD) and mast cell leukaemia (MCL). In SM-AHNMD, additional genetic abnormalities have been reported. Patients with cutaneous or indolent systemic disease are treated symptomatically. Patients with aggressive disease are candidates for cytoreductive therapy. The use of 'Kit-targeting' tyrosine kinase inhibitors are best selected following a mutational analysis of c-kit. For instance, the D816V mutation appears to be associated with relative resistance against imatinib. However, imatinib has been used with success in patients with SM-hypereosinophilic syndrome (HES) and the FIPL1/PDGFRA fusion gene and in a patient with mastocytosis with a mutation outside of codon 816. The value of bone marrow transplantation remains under investigation.
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PMID:Mastocytosis. 1660 39

Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.
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PMID:Phenotypic and genotypic characteristics of mastocytosis according to the age of onset. 1840 1

The term "mastocytosis" denotes a heterogeneous group of disorders characterised by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Symptoms result from MC chemical mediator's release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem to contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently encountered, especially in systemic disease. We present a literature review of mastocytosis and a rare case report of an 18 month-old-girl with a bullous dermatosis, respiratory distress and anaphylaxis, as clinical manifestations of mastocytosis. The developments of accepted classification systems and novel useful markers allowed a re-evaluation and updating of the classification of mastocytosis. In paediatric age cutaneous forms of disease prevail and may regress spontaneously. SM is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow. The clinical course in these patients is variable. Today diagnostic criteria for each disease variant are reasonably well defined. There are, however, peculiarities, namely in paediatric age, that makes the diagnostic approach difficult. Systemic disease may pose differential diagnostic problems resulting from multiple organ systems involvement. Conversely, the "unexplained" appearance of those symptoms with no skin lesions should raise the suspicion of MC disease. This case is reported in order to stress the clinical severity and difficult diagnostic approach that paediatric mastocytosis may assume.
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PMID:Mastocytosis: a rare case of anaphylaxis in paediatric age and literature review. 1868 Jul 4

Mastocytosis is a heterogeneous entity that may present as either a cutaneous or systemic disease. Progression of pediatric cutaneous mastocytosis (CM) is uncommon, but in adults, this condition persists and often progresses to systemic disease. Mast cell proliferation and differentiation from stem cell precursors depend on a number of factors, including a mast cell tyrosine kinase receptor (kit) and its ligand (the stromal cell-derived cytokine stem cell factor). A gain-of-function mutation in codon 816 of c-kit is frequently present in mast cells of patients with systemic mastocytosis (SM). The diagnostic approach for a patient with suspected mast cell disease includes a thorough skin examination, a skin biopsy, a serum tryptase level, and bone marrow aspiration and biopsy. The treatment is directed toward avoidance of triggers of mast cell mediator release and management of symptoms. Aggressive cases are managed with cytoreductive therapies, such as interferon alfa-2b and cladribine. Research has been directed at more specific treatment modalities, including specific kit tyrosine kinase inhibitors.
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PMID:Systemic mastocytosis: classification, pathogenesis, diagnosis, and treatment. 1927 68

The term urticaria pigmentosa (UP) denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MC) in the skin. Symptoms result from MC chemical mediator's release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently found, especially in systemic disease. The aim of this paper is to provide a current overview for a better understanding of the symptoms associated with this disease, to describe its classification, recent advances in its pathophysiology and its treatment.
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PMID:[Urticaria pigmentosa: a current approach]. 1976 74

Mastocytosis arises from clonal mast cell expansion and the resultant accumulation of mast cells in cutaneous and sometimes extracutaneous tissues. Recent studies have demonstrated that c-kit mutations seem to be more prevalent in pediatric mastocytosis than previously assumed, but what determines disease evolution and severity in the individual patient remains elusive. For the large majority of children, mastocytosis is a self-limited cutaneous disease that spontaneously regresses before they reach adult age. Rarely, children develop systemic disease progression that is the hallmark of adult-onset disease. Therefore, invasive diagnostic testing, including performing a bone marrow biopsy, is not routinely recommended and usually reserved for children that present with signs of systemic involvement and persistently elevated serum tryptase levels. Despite its often-transient nature and limited skin involvement, some children experience challenging disease-associated symptoms due to spontaneous or trigger-induced mast cell degranulation. Anticipation of and preparation for potential complications can in many instances avoid symptomatic exacerbations. Proper symptomatic treatment and supportive care can often improve the child's quality of life. Cytoreductive therapy is usually not indicated given the natural history of spontaneous disease resolution.
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PMID:Primary mast cell disorders in children. 2415 Jul 53