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 human genome project has revolutionized technology for the study of DNA. Several of this year's papers have applied these techniques to the study of testicular cancer, especially the use of double-fluorescence in situ hybridization to identify the germ cell tumor marker isochrome 12p in tissue sections, and loss-of-heterozygosity studies to demonstrate a candidate suppressor gene on the long arm of the same chromosome that may be a ligand for the c-kit protooncogene. The report of a solitary case of a patient with a tumor (in a solitary testis) who was treated by partial orchiectomy and then fathered two children emphasizes the need for more information on fertility of patients with carcinoma in situ before the highly effective low-dose radiation to the testis can be accepted. The confirmation of the occurrence of acute myeloid leukemia as a late effect of etoposide and stomach cancer as a late effect of radiotherapy for stage I seminoma has drawn attention to the need to reduce treatment in good-risk patients. Results of trials substituting cisplatin with carboplatin and a trial eliminating bleomycin are particularly disappointing, and the 10% lower cures with the experimental regimen in these studies is an object lesson of the risks involved in such studies. Two other issues that continue to be debated include the increasing recognition of the value of lactate dehydrogenase-1 for identifying poor-risk patients, and the benefits of referral to a unit specializing in testicular cancer. There is an increasing trend to use high-dose chemotherapy for previously untreated patients who have poor risk factors. who have poor risk factors.
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PMID:Testicular cancer. 808 Aug 58

We report herein the case of a 70-year-old man who was found to have a gastrointestinal stromal tumor (GIST) in the stomach following sigmoid colon resection. Preoperative gastroscopic and barium examinations revealed a submucosal tumor, measuring 10 cm, on the upper part of the stomach. Using computed tomography (CT) images (i.e., computed tomographic volumetry) the doubling time of this tumor was calculated, accurately, as 3.3 months, which suggested a high growth rate and malignancy. A laparotomy and partial gastric resection were performed. Histologically, the tumor consisted of spindle-shaped cells with oval nuclei. In immunohistochemical studies, the tumor cells were positive with respect to c-kit, CD34, and vimentin, but negative with respect to smooth muscle actin and S-100 protein. There were 15-16 mitoses per 50 high-power fields (HPFs), and the Ki-67 antigen (MIB-1) index was 25.5% in the most active areas, which also indicated malignancy. The final pathological diagnosis of this tumor was malignant GIST. The patient was found to have hepatic metastasis 27 months after the surgery, and he subsequently received a hepatic subsegmentectomy. To our knowledge, there are very few reports concerning the growth rate of GISTs. Computed tomographic volumetry is useful for the follow-up of small or irregularly shaped gastric submucosal tumors, and for making decisions regarding surgical intervention.
Gastric Cancer 2004
PMID:A gastrointestinal stromal tumor in the stomach: usefulness of computed tomographic volumetry. 1561 75

Gastrointestinal stromal tumors (GISTs) are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal (ICCs). The frequent occurrence of activating mutations involving exon 11 of c-Kit gene in sporadic GISTs indicates an important role in genesis of this tumor type. In the present study we examined c-Kit gene mutations in a series of GISTs and also in ICCs of surrounding normal tissues. Samples from 18 patients were monitored immunohistochemically for c-Kit expression and microdissected for sequencing analysis of exons 9, 11, 13, and 17 of the c-Kit gene. It was revealed to be mutated in exon 11 or adjacent introns in 9 out of the total of 18 (50.0%) GISTs. In 6 (33.3%) cases, mutations in ICCs were also detected in the same exon. With stomach GISTs, 8 of 16 (50.0%) cases harbored mutations and 4 had mutations in background ICCs (25.0%). In contrast counterpart ICCs in gastric cancer cases harbored no c-Kit gene mutations (0 out of 24=0%) (P<0.02). ICCs undergoing c-Kit mutation as a possible early initiation step in GIST tumorigenesis may thus have pre-neoplastic potential.
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PMID:Frequent c-Kit gene mutations not only in gastrointestinal stromal tumors but also in interstitial cells of Cajal in surrounding normal mucosa. 1629 6

The term gastrointestinal stromal tumors (GISTs) is defined diagnostically as the main group of mesenchymal tumors with spindle or epithelioid cells arising from the wall of the gastrointestinal tract with immunohistochemical reactivity for CD117 antibody. Previous studies revealed that cells in GISTs express a growth factor receptor with tyrosine kinase activity (termed c-kit), which is the product of the c-kit proto-oncogene. The most specific and practical diagnostic criteria for GISTs are: immunohistochemically determined c-kit (CD117) expression; mitotic score; and tumor size. A small GIST concomitant with early gastric cancer is rarely encountered clinically. Herein we have reported a case of a 1.1-cm GIST detected by esophagogastroduodenoscopy concomitant with a IIc type of early gastric cancer (signet ring cell type). It was detected during a routine physical health examination. To our knowledge, this is the first report of a small GIST concomitant with a signet ring cell type of early gastric cancer.
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PMID:Small gastrointestinal stromal tumor concomitant with early gastric cancer: a case report. 1652 Dec 3

A 57-year-old man with gastrointestinal stromal tumor (GIST) of the stomach with peritoneal dissemination underwent gastrectomy. After surgery, he was treated with 400 mg/day of imatinib, without recurrence, for 26 months. At 26 months, the imatinib dose was reduced because of nausea, and 4 months after the dose reduction, recurrence of GIST was detected, for which surgical resection was performed again. The first surgical specimen had a mutation of exon 11 in the c-kit receptor gene. Intriguingly, the second surgical specimen had a novel mutation of exon 17, in addition to the above-mentioned mutation, in the c-kit receptor gene. Based on the result of molecular analysis, the novel mutation of exon 17, induced by longterm chemotherapy, was judged to have been responsible for the recurrence, which perhaps was triggered by the dose reduction of imatinib.
Gastric Cancer 2006
PMID:Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a novel c-kit mutation after imatinib treatment. 1695 44

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms with an annual incidence of approximately 10 to 20 per 1 million cases. Although pathologists have often observed incidental small GISTs in the stomach resected from patients with gastric cancer, no report on the real incidence of gastric GISTs is available. In this study, 100 whole stomachs resected from patients with gastric cancer were sectioned at 5-mm intervals and hematoxylin and eosin-stained slides (a mean of 130 slides for each case) were examined for microscopic GISTs. KIT (CD117), CD34, and desmin expression of the incidental tumors was evaluated by immunohistochemistry, and genomic DNA extracted from formalin-fixed and paraffin-embedded tumor tissues was analyzed for c-kit gene mutations in exon 11. In 35 of the 100 whole stomachs, we found 50 microscopic GISTs, all of which were positive for KIT and/or CD34 and negative for desmin. Most microscopic GISTs (45/50, 90%) were located in the upper stomach. Two of the 25 (8%) microscopic GISTs had c-kit gene mutations. Fifty-one leiomyomas with positive expression for desmin were observed in 28 of the 100 stomachs. Both leiomyomas and GISTs were found in 12 stomachs. These results indicate that microscopic GISTs are common in the upper portion of the stomach. Considering the annual incidence of clinical GISTs, only few microscopic GISTs may grow into a clinical size with malignant potential. Further studies are required to clarify the genetic events responsible for the transformation of microscopic GISTs to clinical GISTs.
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PMID:High incidence of microscopic gastrointestinal stromal tumors in the stomach. 1699 66

Eosinophils and mast cells participate in the immune response against Helicobacter pylori, but their involvement in the gastric precancerous process is unclear. This study aimed to estimate eosinophil and mast cell density in antral mucosa in subjects from 2 Colombian populations with contrasting gastric cancer risks. Gastric mucosa biopsies were collected from 117 adult males (72 from a high-risk area and 45 from a low-risk area). A histopathology score was used to quantify severity of the lesions. Quantitation of eosinophils in hematoxylin-eosin-stained sections and mast cells in immunostained sections for CD117/c-Kit was performed. Helicobacter pylori infection and genotyping were assessed in Steiner stain and polymerase chain reaction, respectively. Logistic regression models and semiparametric cubic smoothing splines were used for analysis of the results. Eosinophil density was significantly higher in subjects from the low-risk area as compared with subjects from the high-risk area. In both populations, eosinophil density increased with the histopathology score in the progression of lesions from normal morphology to multifocal atrophic gastritis. Intestinal metaplasia and dysplasia specimens showed further increase in eosinophil density in the high-risk area but an abrupt decrease in the low-risk area. Mast cell density increased in parallel to the histopathology score in both populations. Our results suggest that eosinophils play a dual role in chronic gastritis. In the low-risk area, elevated eosinophil density represents a T helper 2-biased response that may down-regulate the effects of proinflammatory cytokines preventing cancer development. In contrast, in the high-risk area, eosinophils might promote a T helper 1-type response leading to progression of precancerous lesions.
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PMID:Eosinophils and mast cells in chronic gastritis: possible implications in carcinogenesis. 1861 1

The author reports a very rare case of sporadic primary multiple extragastrointestinal stromal tumors (EGISTs) of the omentum associated with different mutations of the exon 11 of the c-kit gene in a 75-year-old man with gastric cancer. During an operation for the cancer, two solid tumors (10 mm and 8 mm) were found in the omentum. Both tumors consisted of cellular spindle cells. Mitotic figures were two and three per 50 high power fields. The tumor cells were positive for KIT, CD34 and vimentin, but negative for desmin, S100 protein, alpha-smooth muscle actin and p53 protein. Ki67 labeling was 2% and 3%. The larger EGIST showed a deletion of codons 552-558 of exon 11 of the c-kit gene, while the smaller EGIST had a point mutation at codon 559 (GTT-->GAT) in exon 11 of the c-kit gene. Exons 9, 13, and 17 of the c-kit gene, and exons 12 and 18 of the platelet derived growth factor receptor alpha genes showed no mutations. The case shows that sporadic multiple EGISTs can occur in the omentum.
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PMID:Primary multiple extragastrointestinal stromal tumors of the omentum with different mutations of c-kit gene. 1908 44

Gastric cancer is a deadly disease for which current therapeutic options are extremely limited. Vascular endothelial growth factor receptors and platelet-derived growth factor receptors regulate gastric cancer cell proliferation, invasion, and tumor angiogenesis. In the present study, we report that sorafenib therapy effectively inhibited tumor growth and angiogenesis in tumor xenografts. These were associated with reduction in the phosphorylation of vascular endothelial growth factor receptor-2 Tyr951, c-Kit Tyr568/570, platelet-derived growth factor receptor-beta Tyr1021, and Akt Ser473 and Thr308, down-regulation of positive cell cycle regulators, increased apoptosis, and up-regulation of p27. Sorafenib treatment also caused up-regulation of p-c-Raf Ser338 and p-extracellular signal-regulated kinase (ERK) Thr202/Tyr204 in gastric cancer xenografts. The combination of sorafenib and MAP/ERK kinase inhibitor AZD6244 enhances the effectiveness of each compound alone. Potential effect of sorafenib/AZD6244 included increase in proapoptotic Bim. Our data show that MAP/ERK kinase inhibition enhances the antitumor activity of sorafenib in vivo, supporting a rationale for multitargeted suppression of the angiogenesis and ERK signaling network in gastric cancer therapy.
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PMID:AZD6244 (ARRY-142886) enhances the therapeutic efficacy of sorafenib in mouse models of gastric cancer. 1972 82

Gastrointestinal stromal tumours (GIST) first described in 1983 are the commonest mesenchymal neoplsams of the digestive tract. The main pathogenetic mechanism is hypersecretion of tyrosin kinase receptor c-kit (CD-117) by GIST cells and its hyperactivation. A rare clinical case of GIST measuring 1.2 CM with concomitant stomach cancer (poorly differentiated carcinoma) is reported. The tumours were discovered intraoperatively. To our knowledge, data on such cases are practically lacking in the literature.
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PMID:[Poorly differentiated stomach adenocarcinoma combined with jejunal stromal tumour. Clinical study]. 2001 58


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