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 so-called interstitial cells of Cajal myenteric plexus (ICC-MP), interstitial cells of Cajal intramuscular (ICC-IM) and interstitial cells of Cajal deep muscular plexus (ICC-DMP) are the three types of ICC endowed within the intestinal muscle coat where they play different roles in gut motility. Studies on ICC ontogenesis showed ICC-MP in the human ileum by 7-9 weeks while information on ICC-IM and ICC-DMP in foetuses and newborns are not exhaustive. Functional recordings in the fasting state of prematurely born babies aged 28-37 weeks showed immature ileal motility. To gain more information on the time of appearance of the three ICC types in the human ileum and on the steps of the acquisition of mature features, we studied by c-kit immuno-histochemistry foetuses aged 17-27 weeks and newborns aged 36-41 weeks. In parallel, the maturative steps of enteric plexuses and muscle layers were immunohistochemically examined by using anti-neuron specific enolase (NSE), anti-S-100 and anti-alpha smooth muscle actin (alphaSMA) antibodies. The appearance and differentiation of all the ICC types were seen to occur in concomitance with those of the related nerve plexuses and muscle layers. ICC-MP appeared first, ICC-IM and ICC-DMP later and their differentiation was incomplete at birth. In conclusion, the ICC-MP, the intestinal pacemaker cells, in spite of absence of food intake, are already present during the foetal life and the ICC-IM appear by pre-term life, thus ensuring neurotransmission. The ICC-DMP and their related nerve plexus and smooth muscle cells, i.e. the intestinal stretch receptor, begin to differentiate at birth. These findings might help in predicting neonatal ileal motor behaviour and in interpreting the role of ICC abnormalities in the pathophysiology of intestinal motile disorders of neonates and young children.
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PMID:Morphology of the interstitial cells of Cajal of the human ileum from foetal to neonatal life. 1763 40

Solitary fibrous tumor (SFT) is an unusual mesenchymal neoplasm that most often arises in the pleura; however, it has recently been described in a number of extrapleural sites. This report describes an extremely rare case of a benign SFT arising in the pancreas. A 41-year-old woman presented in the clinic with right upper abdominal pain. Subsequent ultrasonographic studies revealed a 1.5x1.5x1.4 cm hypoechoic mass within the pancreatic body, which was later confirmed on both helical computerized tomography and magnetic resonance imaging studies. An endocrine tumor was clinically suspected. Laparoscopic enucleation of the mass was performed. Microscopically, the tumor was composed of bland uniform spindle cells arranged between collagen bundles. On immunohistochemical studies, these spindle cells were positive for CD34 and bcl-2 but negative for cytokeratin (AE1+AE3 and Cam5.2), smooth muscle actin, desmin, S-100, and c-kit. Based on the light microscopic morphology and immunohistochemical staining profile, the diagnosis of SFT was rendered.
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PMID:Solitary fibrous tumor of the pancreas: a case report. 1765 47

The neovascularization of tissues is accomplished by two distinct processes: de novo formation of blood vessels through the assembly of progenitor cells during early prenatal development (vasculogenesis), and expansion of a pre-existing vascular network by endothelial cell sprouting (angiogenesis), the main mechanism of blood vessel growth in postnatal life. Evidence exists that adult bone marrow (BM)-derived progenitor cells can contribute to the formation of new vessels by their incorporation into sites of active angiogenesis. Aim of this study was to investigate the in vitro self-organizing capacity of human BM mononuclear cells (BMMNC) to induce vascular morphogenesis in a three-dimensional (3D) matrix environment in the absence of pre-existing vessels. Whole BMMNC as well as the adherent and non-adherent fractions of BMMNC were embedded in fibrin gels and cultured for 3-4 weeks without additional growth factors. The expression of hematopoietic-, endothelial-, smooth muscle lineage, and stem cell markers was analyzed by immunohistochemistry and confocal laser-scanning microscopy. The culture of unselected BMMNC in 3D fibrin matrices led to the formation of cell clusters expressing the endothelial progenitor cell (EPC) markers CD133, CD34, vascular endothelial growth factor receptor (VEGFR)-2, and c-kit, with stellar shaped spreading of peripheral elongated cells forming tube-like structures with increasing complexity over time. Cluster formation was dependent on the presence of both adherent and non-adherent BMMNC without the requirement of external growth factors. Developed vascular structures expressed the endothelial markers CD34, VEGFR-2, CD31, von Willebrand Factor (vWF), and podocalyxin, showed basement-membrane-lined lumina containing CD45+ cells and were surrounded by alpha-smooth muscle actin (SMA) expressing mural cells. Our data demonstrate that adult human BM progenitor cells can induce a dynamic self organization process to create vascular structures within avascular 3D fibrin matrices suggesting a possible alternative mechanism of adult vascular development without involvement of pre-existing vascular structures.
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PMID:Vascular morphogenesis by adult bone marrow progenitor cells in three-dimensional fibrin matrices. 1817 24

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal tract, and of these, GISTs involving the rectum are uncommon. This report describes a case of effective neoadjuvant therapy for a rectal GIST expressing the c-kit gene, where a laparoscopic ultralow anterior resection was successfully performed, thus preserving the anus. A 57-year-old woman visited our hospital due to constipation and was found by a digital examination to have a soft mass on the right wall of the rectum. Computed tomography revealed an 8.0 x 5.0-cm mass with an unclear margin adjacent to the rectum. A biopsy specimen was positive for CD34 and the c-kit gene product, but it was not positive for smooth muscle actin or S-100 protein, and thus the tumor was diagnosed as GIST. An abdominoperineal resection is generally essential for large rectal GISTs; however, she refused this operation. Neoadjuvant treatment with Imatinib decreased the tumor size (4.0 x 3.5 cm) and the anus was preserved by a laparoscopic ultralow anterior resection with direct coloanal anastomosis. She had no evidence of disease for 24 months postoperatively. To preserve the anus, a rectal GIST expressing the c-kit gene is best treated with Imatinib as neoadjuvant therapy.
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PMID:Neoadjuvant imatinib in a gastrointestinal stromal tumor of the rectum: report of a case. 1823 81

Microglandular adenosis (MGA) of the breast is widely known as a benign lesion that can mimic invasive carcinoma. In situ and invasive carcinomas have been described as arising in MGA, but which cases of MGA will progress to carcinoma is unclear. Criteria for distinguishing uncomplicated MGA, MGA with atypia (AMGA), and carcinoma arising in MGA (MGACA) are not standardized. The primary objective of this study was to illustrate the clinical, histopathologic, and immunophenotypical characteristics of MGA, AMGA, and MGACA in an effort to provide criteria for distinguishing the 3 types. We retrospectively identified 108 cases seen at M.D. Anderson Cancer Center between 1983 and 2007 that had a diagnosis of MGA. Of the 108 cases, 65 cases had available material for review. Inclusion criteria were glands of MGA expressing S-100 protein and lacking myoepithelial layer (smooth muscle actin negative). Eleven out of 65 cases qualified to have an MGA component; myoepithelial layer was detected in the remaining 54 cases and were classified as adenosis. Out of the 11 MGA patients, there were 3 patients with uncomplicated MGA, 2 had AMGA, and 6 had MGACA. Staining indices for the cell cycle markers p53 and Ki-67 were used to compare the 3 tumor categories. Additional staining for other tumor markers [estrogen and progesterone receptors, HER2, epidermal growth factor receptor (EGFR), c-kit, CK5/6, and CK18] were performed. Patient demographics, tumor radiologic features, and clinical follow-up data were collected for all cases. Multiple invasive histologic components were identified in each of the MGACA cases. All invasive MGACAs had a duct-forming component. In addition, basal-like component was present in 2 cases, aciniclike in 2, matrix producing in 4, sarcomatoid in 1, and adenoid cystic in 1. All tumors had strong and diffuse CK8/18 and EGFR expression but no estrogen receptor, progesterone receptor, HER2 (ie, triple negative), or CK5/6 expression. C-kit was focally expressed in 2 of the MGACAs. Ki-67 and p53 labeling indices was < 3% in all MGAs, 5% to 10% in the AMGAs, and > 30% in MGACAs. In a follow-up ranging from 14 days to 8 years, none of the MGA cases recurred. One of the AMGA cases recurred as invasive carcinoma in a background of AMGA after 8 years following incomplete excision of the lesion. Three out of 6 MGACA cases (50%) required multiple consecutive resections ending up with mastectomy due to involved margins by invasive or in situ carcinoma. Two out of 6 MGACA cases (34%) developed metastasis and died of disease. Our data showed that Ki-67 and p53 expression, in conjunction with the morphologic features, could be a reliable marker to distinguish MGA from AMGA and MGACA. Although 11 tumors were only included in our study, 64% of the tumors were carcinomas arising in MGA. This high incidence of MGACA may not represent the actual frequency of MGAs progressing into carcinoma and is likely due to referral bias in our institution. Nonetheless, the high association of carcinoma with MGA necessitates complete excision of MGA to rule out invasion. Although all the MGACA cases were triple negative and express EGFR (basal-like features), all the cases in our study showed a luminal type of differentiation by CK8/18 expression, indicating that MGACA may not fit well into the current proposed molecular classification of breast cancer.
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PMID:Clinical, histopathologic, and immunohistochemical features of microglandular adenosis and transition into in situ and invasive carcinoma. 1830 Jul 93

Mullerian adenosarcomas (MAs) are rare mixed mesenchymal and epithelial neoplasms that occur most commonly in the uterus. Although the epithelial component is typically benign, the mesenchymal component of most adenosarcomas morphologically resembles that observed in endometrial stromal tumors and is responsible for their clinical behavior. Thus, the differential diagnosis usually includes not only low-grade endometrial stromal tumors, but also adenofibroma, carcinosarcoma, and embryonal rhabdomyosarcoma especially in small samples. The objective of this study was to ascertain the immunophenotypic profile of the epithelial and mesenchymal components of MAs and delineate possible differences between conventional mesenchymal areas and areas of sarcomatous overgrowth. Representative sections from 35 MAs, 28 of them without sarcomatous overgrowth (MA-NSO) and 7 with sarcomatous overgrowth (MA-SO), were included in the study. Thirty tumors arose in the uterus, 4 were pelvic, and 1 originated in the colon. Adequate blocks were selected and immunostained for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), CD10, WT1, smooth muscle actin, desmin, AE1/3 cytokeratin, CD34, calretinin, inhibin, c-kit, and Ki-67. The mesenchymal component expressed ER in 21/27 MA-NSOs but in only 1/7 MA-SOs (65% overall). PR was expressed in 21/26 MA-NSOs and 4/7 MA-SOs (76% overall), whereas AR was positive in 10/27 MA-NSOs and 5/7 MA-SOs (35% overall). CD10 was expressed in 23/28 MA-NSOs but in only 2/7 MA-SOs (71% overall), and WT1 positivity was seen in 22/27 MA-NSOs and 6/7 MA-SOs (79% overall). Sixty-seven percent of MAs expressed smooth muscle actin, 32% desmin, including both examples of MA-SOs with rhabdomyoblastic differentiation, and 25% expressed AE1/3 cytokeratin. CD34 expression was found in 35% of the tumors, but it was almost always patchy in distribution and weak in intensity, as was calretinin expression, seen only in 12% of the cases. Expression of c-kit and inhibin in greater than 5% of the tumor cells was not encountered. The median and mean Ki-67 labeling indices were 10% and 12%, respectively (range, <5% to 40%). The median and mean Ki-67 indices were both 5% in MA-NSOs compared with 30% and 28%, respectively, in MA-SOs. The epithelial compartment demonstrated expression for ER (24/32), PR (23/31), and AE1/3 cytokeratin (33/33); rare cases expressed CD10 (4 cases) and AR (1 case). In summary, the immunophenotype of most MAs resembled that of endometrial stromal tumors (positive for ER, PR, WT1, and CD10, with variable expression of muscle markers, AR and cytokeratin). The proliferative rate in the stromal component was strongly related to the presence of sarcomatous overgrowth. ER, PR, and CD10 expression was lost in MA-SOs relative to conventional low-grade stromal areas of mullerian/mesodermal adenosarcomas, reflecting the "dedifferentiation" of this component.
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PMID:Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases. 1846 8

Esophageal striated myogenesis progresses differently from appendicular myogenesis, but the mechanism underlying this process is incompletely understood. Early theories of transdifferentiation of smooth muscle into striated muscle are not supported by transgenic fate-mapping experiments; however, the origin of esophageal striated muscle remains unknown. To better define the process of striated myogenesis, we examined myogenesis in murine fetal cultured esophageal whole-organ explants. Embryonic day 14.5 (E14.5) esophagi maintained a functional contractile phenotype for up to 7 days in culture. Striated myogenesis, as evidenced by myogenin expression, proceeded in a craniocaudal direction along the length of the esophagus. Esophageal length did not change during this process. Complete, but not partial, mechanical disruption of the rostral esophagus inhibited myogenesis distally. Addition of fibroblast growth factor-2 (FGF-2) to the culture media failed to inhibit striated myogenesis, but attenuated smooth muscle actin expression and reduced peristaltic activity. Inhibition of c-kit failed to inhibit peristalsis. These results suggest that striated myogenic precursors are resident along the entire length of the esophagus by day 14.5 and do not migrate along the esophagus after E14.5. Induction of myogenesis craniocaudally appears to require physical continuity of the esophagus and is not inhibited by FGF-2. Finally, peristalsis in E14.5 esophagi appears not to be regulated by interstitial cells of Cajal.
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PMID:Striated myogenesis and peristalsis in the fetal murine esophagus occur without cell migration or interstitial cells of Cajal. 1878 10

Interstitial cells of Cajal (ICC) include several types of specialized cells within the musculature of the gastrointestinal tract (GIT). Some types of ICC act as pacemakers in the GIT musculature, whereas others are implicated in the modulation of enteric neurotransmission. Kit immunohistochemistry reliably identifies the location of these cells and provides information on changes in ICC distribution and density. Human stomach specimens were obtained from 7 embryos and 28 foetuses without gastrointestinal disorders. The specimens were 7-27 weeks of gestational age, and both sexes are represented in the sample. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. Enteric plexuses were immunohistochemically examined by using anti-neuron specific enolase and the differentiation of smooth muscle cells (SMC) was studied with anti-alpha smooth muscle actin and anti-desmin antibodies. By week 7, c-kit-immunopositive precursors formed a layer in the outer stomach wall around myenteric plexus elements. Between 9 and 11 weeks some of these precursors differentiated into ICC. ICC at the myenteric plexus level differentiated first, followed by those within the muscle layer: between SMC, at the circular and longitudinal layers, and within connective tissue septa enveloping muscle bundles. In the fourth month, all subtypes of c-kit-immunoreactivity ICC which are necessary for the generation of slow waves and their transfer to SMC have been developed. These results may help elucidate the origin of ICC and the aetiology and pathogenesis of stomach motility disorders in neonates and young children that are associated with absence or decreased number of these cells.
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PMID:Development of c-kit immunopositive interstitial cells of Cajal in the human stomach. 1929 25

Malignant solitary fibrous tumor (MSFT) is a rare neoplasm. Three cases of MSFT with unusual features, including 1 pleural and 2 extrapleural, are reported. A 64-year-old woman with a large right thoracic MSFT and episodes of severe hypoglycemia experienced resolution of her hypoglycemia immediately after resection of the MSFT. A 27-year-old woman with primary retroperitoneal MSFT had pulmonary metastases 10 months after resection of the primary tumor. A 54-year-old man with an intracranial solitary fibrous tumor suffered from multiple pulmonary metastases and local recurrence 21 and 28 months after resection of the primary tumor, respectively. All 3 cases of solitary fibrous tumor displayed malignant features. The tumor cells in each case were positive for CD34 and Bcl-2, but negative for cytokeratin, smooth muscle actin, S-100, and c-kit. In addition, the tumor cells in the case with concomitant hypoglycemia were strongly positive for insulin-like growth factor-II. The histopathologic diagnostic criteria for MSFT, the differential diagnosis with other spindle cell tumors, and the mechanism of MSFT-derived hypoglycemia via insulin-like growth factor-II are discussed.
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PMID:Malignant solitary fibrous tumor: report of 3 cases with unusual features. 1934 55

A 17-year-old, gelded Quarter Horse cross was found to have a large, intra-abdominal mass. Clinical signs included infrequent mild colic, weight loss, and chronic anemia. Surgery revealed a very large, discrete, hemorrhagic, multilobular mass with vascular attachments to the transverse colon, mesocolon, jejunal mesentery, and omentum; the site of origin was the transverse colon. Histologic examination demonstrated dense sheets, fascicles, palisades, and interconnecting streams of neoplastic spindle cells with lesser numbers of admixed multinucleated giant cells. Based on morphology alone, this neoplasm might have been misdiagnosed as a peripheral nerve sheath tumor because many of the morphologic features were suggestive of neural differentiation. Neoplastic cells expressed cluster of differentiation (CD)117 (c-kit), vimentin, desmin, smooth muscle actin, neuron-specific enolase, and S-100 protein and did not express cytokeratin. Based predominantly on the immunohistochemical profile, especially the CD117 positivity, this neoplasm was diagnosed as a gastrointestinal stromal tumor with both myogenic and neurogenic differentiation. The morphology and immunohistochemical profile of this neoplasm were different from published cases of equine gastrointestinal stromal tumors. Unusual aspects included the large size of this neoplasm, the neuroid rather than myxomatous morphology, the presence of multinucleated giant cells, and the expression of desmin.
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PMID:An atypical equine gastrointestinal stromal tumor. 1940 97


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