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)

Transgenic mice carrying either a 1.008 or a 4.225 kb of the mouse c-kit 5'-flanking sequences linked to the oncogenic large T antigen (TAg) region of the simian virus 40 (SV40) genome were generated to test if the c-kit promoter could be used to develop useful mouse models. Both constructs promote tumourigenesis in the pituitary and the thyroid with high efficiency. The cell types from which each of these tumours derives were identified. Tumours of the pituitary derive from alpha-MSH-expressing cells located in the intermediate lobe. Transformed cells of the thyroid were calcitonin-positive, implying that the tumours derive from C cells or their precursors. Chromogranin A and neuron-specific enolase, general neuroendocrine cell markers, were expressed in both tumour types. Furthermore a variety of tumours appeared in the transgenic mice. Several of them stained positively for chromogranin A and/or neuron-specific enolase. This suggests a previously unsuspected tissue-specificity of the c-kit 5' flanking sequences for neuroendocrine cells. The Kit-TAg transgenic mouse lines may represent a valuable model for the study of the development and the biology of neuroendocrine tumours.
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PMID:Multiple neuroendocrine tumours in transgenic mice induced by c-kit-SV40 T antigen fusion genes. 917 64

The purpose of this work was to study the expression in gastrointestinal stromal tumors (GISTs) of various antigens, including the protein tau associated with enteric neuronal differentiation; to compare their expression with that of c-kit, known to be associated with interstitial cell of Cajal differentiation; and to correlate their expression with the observation of ultrastructural features of gastrointestinal autonomic nerve tumors. Twenty-six GISTs of the stomach and 16 GISTs of the small bowel were included in the study group. Thirty-five tumors served as controls. Tissue sections were immunostained with vimentin, CD34, desmin, specific smooth muscle actin, S100 protein, neuron-specific enolase, PGP9.5, neurofilament, bcl-2 oncoprotein, synaptophysin, chromogranin A, c-kit, and tau. Twenty-one of these tumors were also analyzed ultrastructurally. Of the 42 GISTs, 28 were predominantly spindled, 7 were predominantly epithelioid, and 7 were a mixture of epithelioid and spindle cells. Ten primary GISTs were classified as benign, 9 as borderline, and 23 as malignant. Metastatic dissemination was present at primary surgery in 1 case and eventually developed in 6 patients. Six disease-related deaths were counted. In normal submucous and myenteric plexuses of stomach and small bowel, ganglion cell bodies and nerve fibers strongly expressed tau. Twenty (76.9%) GISTs of the stomach and 12 (75%) of the small bowel expressed tau. Tau often showed intense, diffuse staining patterns in both spindled and epithelioid tumors. Ten (100%) of the 10 benign GISTs, 7 (77.8%) of the borderline GISTs, and 15 (65.2%) of the 23 frankly malignant GISTs expressed tau. Thirty-six GISTs expressed at least 2 different neuronal markers. A coexpression of the neuronal markers and c-kit was observed in 90% of GISTs. The expression of tau was observed in 12 of the 15 GISTs with dense core granules, considered as the definitive finding for a diagnosis of gastrointestinal autonomic nerve tumors. Ten of these also expressed c-kit; 9 were malignant. Tau also immunostained other intra-abdominal tumors, including neuroendocrine carcinomas, paragangliomas and desmoplastic round cell tumors. This immunohistochemical study shows that GISTs are specific tumors of the digestive tract and are nearly always characterized by simultaneous neuronal and interstitial cell of Cajal differentiation. Although the loss of tau expression is observed only in borderline and malignant tumors, its prognostic value is not clear cut.
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PMID:Expression of microtubule-associated protein tau by gastrointestinal stromal tumors. 1172 54

Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic agents. The aim of the study was to determine if members of the anthraquinone family could be used as adjuncts to increase the growth inhibiting effect of anticancer agents in MCC. An adherent variant of MCC was derived from a previously established MCC cell line suspension. Cells were characterized by immunocytochemical methods using specific antibodies against epithelial (low molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron-specific enolase, neurofilament protein, chromogranin A and synaptophysin) antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5-fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin potentiated their inhibitory effect, especially when low concentrations of the anticancer compounds were used. The antiproliferative action of STI 571 may be associated with the presence of anti-c-kit antibodies. The combined use of anticancer agents, especially at low concentrations, and aloe-emodin may be considered a preferable means for treating MCC.
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PMID:Combined effect of aloe-emodin and chemotherapeutic agents on the proliferation of an adherent variant cell line of Merkel cell carcinoma. 1465 28

We show here (presumably for the first time) a special type of cell in the human and rat exocrine pancreas. These cells have phenotypic characteristics of the enteric interstitial cells of Cajal (ICC). To identify pancreatic interstitial cells of Cajal (pICC) we used routine light microscopy, non-conventional light microscopy (less than 1 mum semi-thin sections of Epon-embedded specimens cut by ultramicrotomy and stained with Toluidine blue), transmission electron microscopy (TEM), and immunocytochemistry. The results showed that pICC can be recognized easily by light microscopy, particularly on semi-thin sections, as well as by TEM. Two-dimensional reconstructions from serial photos suggest a network-like spatial distribution of pICC. pICC represent 3.3+/-0.5% of all pancreatic cells, and seem to establish close spatial relationships with: capillaries (43%), acini (40%), stellate cells (14%), nerve fibres (3%). Most of pICC (88%) have 2 or 3 long processes (tens of mum) emerging from the cell body. TEM data show that pICC meet the criteria for positive diagnosis as ICC (e.g. numerous mitochondria, 8.7+/-0.8% of cytoplasm). Immunocytochemistry revealed that pICC are CD117/c-kit and CD34 positive. We found pICC positive (40-50%) for smooth muscle alpha-actin or S-100, and, occasionally, for CD68, NK1 neurokinin receptor and vimentin. The reactions for desmin and chromogranin A were negative in pICC. At present, only hypotheses and speculations can be formulated on the possible role of the pICC (e.g., juxtacrine and/or paracrine roles). In conclusion, the quite-established dogma: "ICC only in cavitary organs" is overpassed.
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PMID:Interstitial cells of Cajal in pancreas. 1620 21

Solid tumors of the pancreas are usually neoplastic. We report on two adult patients, each with a solid tumor of the pancreas that presented with an unusual histology and seemed to follow a benign course. The tumors, one located in the body and one in the tail, were well demarcated and composed of irregularly arranged but well-differentiated acini and small intralobular and interlobular ducts embedded in predominantly hypocellular fibrotic tissue that contained fascicles of cytologically bland spindle cells. Islets were lacking, but immunohistochemical staining for chromogranin A and insulin revealed individual scattered insulin-producing cells distributed between acinar and ductal cells. The spindle cell component tissue showed coexpression of CD34, c-kit (CD117) and bcl-2. The follow-up (2 and 4 years) of the patients was uneventful. We propose to designate the tumors as 'cellular hamartoma resembling gastrointestinal stromal tumor.
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PMID:Cellular hamartoma resembling gastrointestinal stromal tumor: a solid tumor of the pancreas expressing c-kit (CD117). 1580 85

Nonsmall cell neuroendocrine carcinoma (NSCNEC) of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. In this study, we present the clinicopathologic and immunohistochemical features of 11 such cases seen at The University of Texas M.D. Anderson Cancer Center in a 16-year period (1990 to 2005). Patients ranged in age from 22 to 63 years (mean 46.7). The most common presentation was abdominal/pelvic pain (6 cases), followed by ascites (2 cases), pelvic mass, vaginal bleeding, and abdominal bloating (1 case each). Tumors were mostly unilateral, cystic, or solid/cystic and ranged in size from 5 to 26 cm (mean 16.2). In 8 cases, NSCNEC was associated with other epithelial neoplasms, including mucinous neoplasms of low malignant potential, mucinous carcinoma, endometrioid carcinoma, mixed endometrioid and mucinous carcinoma, and a high-grade carcinoma, not otherwise specified. In 2 cases, the tumor was associated with a mature cystic teratoma; one of them also containing an invasive moderately differentiated adenocarcinoma. A single case was associated with a benign ovarian cyst. The latter case had a dermoid cyst in the contralateral ovary. NSCNEC represented anywhere from 10% to 90% of the ovarian tumor. Microscopically, the neuroendocrine component was usually composed of large and/or intermediate oval to round cells. In 2 cases, the intermediate cells were intermixed with small cells. Three cases had also spindle cells. The neoplastic cells were mostly arranged in a solid pattern, nests, or trabeculae. All tumors had a brisk mitotic activity. Immunoperoxidase studies for keratin cocktail, cytokeratin (CK) 7, CK20, CAM 5.2, chromogranin A, synaptophysin, NSE, CD56, and c-kit were performed and the cases stained as follows: keratin cocktail 6/6, CK7 4/5, CK20 3/5, CAM 5.2 3/3, chromogranin A 8/11, synaptophysin 9/9, NSE 1/1, CD56 4/8, and c-kit 5/7. According to the International Federation of Gynecology and Obstetrics staging system, 4 cases were stage I tumors, 3 cases were stage III tumors, and 4 cases were stage IV tumors. Seven patients were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy. One patient had a bilateral salpingo-oophorectomy with omentectomy and appendectomy followed by chemotherapy; 1 patient had a total abdominal hysterectomy with right salpingo-oophorectomy followed by chemotherapy; one had a bilateral salpingo-oophorectomy followed by chemotherapy, and one had a right salpingo-oophorectomy with appendectomy followed by chemotherapy. Five patients died of disease at 2, 3, 9, 20, and 36 months. One patient is alive with disease at 8 months and 5 are alive without evidence of disease at 11, 28, 37, 66, and 68 months. Four of 5 patients who died of disease had either stage III or IV tumors and 3 of 5 patients who are alive without evidence of disease have stage I tumors. In summary, ovarian NSCNEC is an aggressive tumor with a tendency to present at advanced stage and cause death within a mean of 17 months after diagnosis; however, some patients, particularly those with stage I disease and/or those who have received platinum-based therapy, may have a more favorable prognosis.
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PMID:Ovarian nonsmall cell neuroendocrine carcinoma: a clinicopathologic and immunohistochemical study of 11 cases. 1746 Apr 63

We describe here an interstitial Cajal-like cell type (ICLC) in human gallbladder, resembling the archetypal enteric interstitial cells of Cajal. Gallbladder ICLC were demonstrated in fresh preparations (tissue cryosections) using methylene-blue, and fixed specimens in Epon semi-thin sections stained with toluidine blue or transmission electron microscopy (TEM). The positive diagnosis of gallbladder ICLC was further verified by immunohistochemistry: CD117/c-kit, CD34, and another 16 antigens: vimentin, desmin, nestin, alpha-smooth muscle actin, NK-1, S-100, PGP-9.5, tau protein, chromogranin A, NSE, GFAP, CD1a, CD62-P, CD68, estrogen and progesterone receptors. Double immunostaining was performed for CD117, CD34 and CD117 and nestin, respectively. In fresh specimens, the spatial density of gallbladder ICLC was 100-110 cells/mm(2). ICLC mainly appeared beneath the epithelium and in muscularis (about 7%, and approximately 5%, respectively). In toto, ICLC represent in gallbladder approximately 5.5% of subepithelial cells. TEM showed that diagnostic criteria were fulfilled by ICLC. Moreover, TEM indicated that the main ultrastructural distinctive feature for ICLC, the cell processes, develop into the characteristic shape at a relatively early stage of development. It remains to be established if, in humans, ICLC are involved in gallbladder (dis)functions (e.g. pace-making, secretion (auto-, juxta- and/or paracrine), intercellular signaling, or stone formation).
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PMID:Interstitial Cajal-like cells in human gallbladder. 1754 11

Mesenchymal tumors of the pancreas are rare and difficult to classify. We report a case of a solitary mesenchymal tumor in the body of the pancreas. The tumor showed immunocytochemical reactivity for anti-vimentin, anti-alpha-smooth muscle actin, and anti-CD34; however, it was negative immunohistochemically for antibodies to cytokeratins, as well as for the following antibodies: anti-desmin, anti-S-100, anti-chromogranin A, anti-CD117 (c-Kit), anti-CD99, and anti-bcl-2. This tumor could not be classified as a specific type of mesenchymal tumor immunocytochemically.
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PMID:Mesenchymal tumor of the pancreas: report of a case. 1803 May 79

Herein we present a 73-year-old man with primary carcinosarcoma of the liver, a rare malignant tumor of the liver. The case was followed up due to HBV-related liver cirrhosis. Regular check-up by ultrasound demonstrated a hyperechoic tumor in the left lobe of the liver, and he was referred and admitted to our hospital. Dynamic CT studies revealed a mostly hypoenhancing hepatic mass with a peripheral ring enhancement. Surgical resection was performed, and the resected tumor was macroscopically a simple nodular type, 3 cm in diameter, with a dense fibrous capsule. Microscopically, undifferentiated cells were dominant in the tumor, while moderately differentiated hepatocellular carcinoma (HCC) were also observed. A transitional zone was noted between the undifferentiated tumor and HCC. Tumor tissue with adenocarcinoma, osteosarcoma and chondrosarcoma were also detected. Immunohistochemical studies demonstrated that tumor cells were HepPar 1 positive in hepatocellular carcinoma, and CK19 and partly CK7 positive in adenocarcinoma. Moreover, CD56, chromogranin A and c-kit were occasionally positive in undifferentiated tumor cells. The diagnosis of carcinosarcoma was made based on the concomitant presence of HCC and sarcomatous components, yet it is noteworthy that various types of tumor cells were observed.
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PMID:Carcinosarcoma of the liver. 2113 95

Adult onset neuroblastoma arising in the mediastinum, except posterior mediastinum is extremely rare. We report a case of surgically resected neuroblastoma in the superior mediastinum. A 64-year-old male was admitted to a local hospital, after an abnormal shadow had been detected on a chest radiogram on a routine medical checkup. Computed tomography (CT) examination revealed the tumor located in the superior mediastinum. Preoperatively, we suspected malignant lymphoma or lymph node metastasis from an unknown primary site. We resected the mediastinal tumor for both definitive diagnosis and local treatment. The tumor was composed of sheets of small round cells positive for CD56, NSE, chromogranin A, and vimentin, but negative for AE1/3, CK5/6, CK7, CD3, CD20, CD79a, c-kit, S-100, SMA and CD99. N-myc gene amplification was also confirmed and supported diagnosis of neuroblastoma. Chest CT seven months after surgery revealed multiple recurrences in lymph nodes.
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PMID:Adult neuroblastoma arising in the superior mediastinum. 2138 84


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