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)

A case for primary gastrointestinal stromal tumor (GIST) is described with reference to its ultrastructural characteristics and mutation within the exon 11 of c-kit gene. A forty-seven years old woman complaining of dysphasia was examined by endoscopy, which depicted a submucosal tumor (70 mm in diameter) with ulcerations at the fundus of the stomach. Histopathologically, the tumor cells had large nuclei and eosinophilic cytoplasm and were frequently during mitosis phase. The tumor cells were immunopositive for KIT, CD 34 and vimentin, suggesting their fibroblast-like characteristics. In contrast, desmin and S-100, a smooth muscle and an enteroglial marker, were not immunopositive within the cells. At least 30 % of the tumor cells possessed MIB-I and 20 % of them possessed p53, which are compatible with fast development of the tumor. By electron microscopy, the tumor cells possessed large oval nuclei, abundant mitochondria, caveolae and smooth endoplasmic reticulums, while no gap junctions were seen on the cells: The tumor cells thus possessed interstitial cells-like characteristics at least in part. DNA mutation search for the tumor cells however realized no gain-of-function mutation within the exon 11 of the c-kit gene, suggesting existence of other mechanism for neoplasmic growth of the tumor cells classified as gastrointestinal stromal tumors.
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PMID:A case for gastrointestinal stromal tumor (GIST) with reference to its ultrastructure and 'gain-of-function' mutation. 1471 34

The understanding of mesenchymal neoplasms of the gastrointestinal tract has evolved dramatically over the last two decades since gastrointestinal stromal tumor (GIST) was described as the most common stromal tumor arising anywhere from the esophagus to the ano-rectum. Although morphologically similar to other benign and malignant smooth muscle and neural stromal neoplasms, GIST constitutes a distinct group of rare gastrointestinal tract tumors that originate from the interstitial cells of Cajal, regulators of gut peristalsis that normally express CD117, which is the product of the c-KIT proto-oncogene that encodes a tyrosine kinase receptor that regulates cellular proliferation in GISTs. Virtually all GISTs occur from mutations of the c-KIT oncogene and exhibit consistent expression of c-KIT (CD117), which is considered the most specific criterion for a diagnosis of GIST. Gastrointestinal stromal tumors vary in their behavior and several features have to be considered to assess their malignant potential. The advent of sophisticated imaging techniques for the evaluation and sampling of stromal tumors of the gastrointestinal tract has resulted in improved detection of GISTs. The identification of a novel tumor-specific target in c-KIT resulted in the development of a tyrosine kinase-inhibitor (imatinib mesylate) that provides an encouraging option for treating GISTs. This article reviews recent advances in the understanding of the cell biology, diagnosis, and therapy of GISTS.
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PMID:Recent advances in cell biology, diagnosis, and therapy of gastrointestinal stromal tumor (GIST). 1472 14

GIST is a rare neoplasm, the majority of GISTs are located in the stomach and small intestine. Most GISTs are diagnosed histopathologically after resection because of submucosal location. A 37-year-old female patient presented with a 2-weeks history of generalized weakness, nausea accompanied by intermittent passage of black, tarry stools. Esophagogastroduodenoscopy and ERCP showed a large round mass measuring 5 cm in diameter in the ampulla of Vater with ulcer crack. Endoscopic multiple biopsies from the mass including ulcer base were taken. Light microscopic findings showed spindle-shaped and epitheloid tumor cells having high cellularity and frequent mitotic figures. On immunohistochemical stainings, the tumor cells were positive for CD34 and smooth muscle actin. Based on these preoperative findings, a diagnosis of malignant GIST of the ampulla of Vater was made probably. After operation, immunohistochemical studies revealed positive reaction for c-kit and vimentin, as well as focally reactive for CD34 and smooth muscle actin. We report a case of GIST in the ampulla of Vater presenting with melena that was diagnosed preoperatively and postoperatively.
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PMID:Malignant gastrointestinal stromal tumor of the ampulla of Vater: a case report. 1474 56

GIST anatomical concept, recently elucidate, they are characterized by the expression of the protooncogene C Kit The diagnosis is relatively easy but prognosis evaluation is not usually possible. The treatment is based on the surgical resection. The rewardable clinical response of tumors that express C-Kit to treatment with the tyrosine kinase inhibitor STI 571 is a triumph of molecular pharmacology.
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PMID:[Gastrointestinal stromal tumors. Current data]. 1498 24

Gastrointestinal stromal tumor (GIST) is a distinct group of mesenchymal neoplasms recently shown to exhibit differentiation toward interstitial cells of Cajal. Although previous studies have shown that the clinical outcome of patients with GIST is associated with mitotic activity, the proliferation index determined by the Ki-67 labeling index, immunophenotype (CD34 and/or p53) and mutation in exon 11 of the c-kit, a definitive discrimination between benign and malignant GIST has not yet been established. We report a patient in whom malignant GIST in the abdomen recurred five times. In this case, the primary GIST and the five recurrent GIST were associated with c-kit immunoreactivity, but the mitotic index of the GIST tended to be increasingly higher with subsequent recurrences. Mutational analysis of the c-kit revealed that the primary and recurrent GIST were mutant-negative. These data indicated that 'morphologically appearing benign' tumors with lower proliferative parameters may also have the capacity of metastasis and recurrence.
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PMID:Immunohistopathological and molecular genetic features of a case in which gastrointestinal stromal tumor recurred five times. 1498 43

A 69-year-old man was admitted with a large elastic mass in the upper abdomen. Computed tomography revealed a massive tumor in contact with the liver and gastrointestinal endoscopy revealed a gastric adenocarcinoma. He developed acute renal failure with massive proteinuria and died with a marked enlargement of the tumor. Autopsy revealed a tumor located in the lesser omentum. The tumor was considered to be a Gastrointestinal Stromal Tumor (GIST) because it was positive for c-kit. In addition, crescent formations and immune complexes in glomeruli were observed. We report the first case of GIST complicated by rapidly progressive glomerulonephritis and gastric carcinoma.
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PMID:Malignant gastrointestinal stromal tumor originating in the lesser omentum, complicated by rapidly progressive glomerulonephritis and gastric carcinoma. 1500 50

We report on a case of a stromal tumor, similar to a gastrointestinal stromal tumor, originating from the pancreas. The patient was a 54-year-old woman, who was seen at the Kofu Municipal Hospital because of an abdominal tumor. On abdominal computed tomography and splenic arteriography, the tumor was detected in the pancreatic tail. The patient underwent distal pancreatectomy with splenectomy. Macroscopically, the cut surface of the tumor showed almost completely surrounded by the normal pancreatic tissue. Microscopically, the tumor composed of spindle-shaped cells that were immunoreactive for vimentin, CD34, and c-kit protein. Therefore, the tumor was diagnosed as a stromal tumor of the pancreas. The expression of c-kit protein suggests that this pancreatic stromal tumor may originate from primitive mesenchymal cells which can be a logical candidate for the origin of gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors.
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PMID:Stromal tumor of the pancreas with expression of c-kit protein: report of a case. 1501 91

Eighteen cases of Vanek's tumors are presented. The patients included nine men and nine women between the ages of 45 and 93 years (mean, 66.2 years). Nine cases were clinically diagnosed as polyps of the gastric antrum, five cases as polyps of the stomach (not otherwise specified), one polyp was located in the ileum and the three remaining polyps in the small intestine (not otherwise specified). The thirteen polyps with available size information measured from 0.4 to 5 cm in the greatest diameter (mean, 2.2 cm). Immunohistochemically, the affections were positive for vimentin (18/18) and CD34 (15/18). All the cases negative for CD34 also lacked concentric onion skin-like formations of the spindle cells around glands and vessels. The different immunophenotype and absence of concentric formations could be explained by the existence of two different lesions commonly designated as Vanek's tumor (inflammatory fibroid polyp) or by the hypothesis of various evolutional stages. In the differential diagnosis, it is important to distinguish namely eosinophilic gastroenteritis, gastrointestinal stromal tumor, inflammatory pseudotumor, hemangioendothelioma, and hemangiopericytoma. In contrast to gastrointestinal stromal tumors, genetically no substitution, deletion, or insertion occurred in c-kit exon 11 in all analyzed samples. Likewise, no deletion or insertion in part of c-kit exon 9 was observed.
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PMID:Vanek's tumor (inflammatory fibroid polyp). Report of 18 cases and comparison with three cases of original Vanek's series. 1501 16

The Kit receptor tyrosine kinase is a transmembrane receptor that is expressed in a variety of different tissues and mediates pleiotropic biological effects through its ligand stem cell factor (SCF). Sporadic mutations of Kit as well as autocrine/paracrine activation mechanisms of the SCF/Kit pathway have been implicated in a variety of malignancies, where its primary contribution to metastases is in enhancing tumor growth and reducing apoptosis. For example, Kit is frequently mutated and activated in gastrointestinal stromal tumors (GISTs) and there is ligand-mediated activation of Kit in some lung cancers. Kit is a convenient target in Kit-induced tumors and inhibition of this receptor with the small molecule drug Gleevec (imatinib mesylate, STI571) in GIST has shown dramatic efficacy. Unfortunately, past experience has demonstrated that chemotherapy of cancers with a single drug often leads to resistance of the cancer. Further understanding of the molecular mechanisms underlying Kit-mediated transformation is therefore important and may lead to the identification of further novel drug targets. These Kit-specific signaling pathways may then be targeted to overcome potential drug resistance. This review will focus on our understanding of the molecular mechanisms involved in transformation by Kit. The potential mechanisms by which Kit induces cellular transformation are described. We will also discuss the role and expression of Kit in various malignancies. Ultimately, the understanding of c-Kit biology, biochemistry, and mutational analysis will lead to better therapeutics.
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PMID:Targeting c-Kit mutations: basic science to novel therapies. 1503 37

Most gastrointestinal stromal tumors (GISTs) contain activating mutations of the proto-oncogene c-kit. The GNNK- isoform of c-kit has a greater oncogenic potential than the GNNK+ isoform. We studied tumors from 29 patients with GIST, 19 of whom had c-kit mutations, and compared them to normal cells and HMC-1 mast cell line. c-kit transcripts were quantified by real-time PCR. The ratios of GNNK-/+ isoforms and of wild-type/mutant alleles were determined by RT-PCR and fluorometric quantification. On average, GISTs contained 1.9 times more c-kit transcripts than the HMC-1 cell line and GISTs with c-kit mutations contained 2.8 times more c-kit transcripts than those without (P=0.003). The median GNNK-/+ isoform ratios in GISTs with and without c-kit mutations were 4.4 and 4.1, respectively, and there was no difference in the GNNK-/+ ratios between the GISTs and the control samples. Both mutant and wild-type alleles of c-kit were expressed in similar amounts in 13/15 mutant GISTs. The oncogenic effects of KIT in GISTs are not related to the higher expression level of the GNNK- isoform. The high expression level of both mutated and wild-type allele transcripts of c-kit suggests that interactions between spontaneously activated and normal c-kit receptors are important in GIST tumorigenesis.
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PMID:High expression of both mutant and wild-type alleles of c-kit in gastrointestinal stromal tumors. 1506 76


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