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

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.
 ...
PMID:Malignant gastrointestinal stromal tumor of the ampulla of Vater: a case report. 1474 56

Melanotic schwannomas (MS) are tumors of Schwann cell origin characterized by cytoplasmic deposition of melanin. The authors present the case of a 61-year-old man who experienced progressive weakness of the lower extremities over 2 years. This was followed by acute deterioration, which prompted his presentation. MRI of the spine revealed an intradural, extramedullary lesion at the level of T7 with severe spinal cord compression. More caudally, there was involvement of the lumbar spine with drop metastases to the conus medullaris and cauda equina. The patient underwent thoracic laminectomy for tumor resection. A diagnosis of MS was made based on histologic morphology, immunohistochemical profile, and ultrastructural findings. In this report, the authors describe a MS with expression of CD117 (c-kit) and review the literature pertaining to this condition.
 ...
PMID:Melanotic schwannoma with drop metastases to the caudal spine and high expression of CD117 (c-kit). 1569 Jan 31

Gastrointestinal stromal tumors (GISTs) historically have differed from other soft-tissue sarcomas in demonstrating a particularly grim prognosis. GISTs have an extraordinarily high rate of recurrence after surgical resection and are highly resistant to radiation and standard chemotherapy. The discovery that constitutive activation of the c-kit gene drives malignant behavior in GISTs exposed a weakness that was soon exploited through the application of the novel targeted therapy imatinib, a small-molecule tyrosine kinase inhibitor of Bcr-Abl, KIT, and the platelet-derived growth factor receptor-alpha and -beta. Imatinib had shown unparalleled results in patients with advanced chronic myelogenous leukemia (remission rates approaching 98%), and the first GIST patients treated with imatinib demonstrated dramatic response rates unseen with other therapeutic modalities. Thousands of patients worldwide with advanced GIST have been treated with imatinib, with the demonstration of significant response rates, prolongation of survival, and improvement in quality of life. Studies of imatinib in both the neoadjuvant and adjuvant settings are now being conducted to evaluate whether low rates of cure with surgical resection alone can be improved. Additionally, multiple new targeted agents are being tested in patients with imatinib-resistant GIST. The gains that have been made in the treatment of GIST through the use of imatinib have helped to open the door to a new era of development of targeted therapeutic agents in oncology. Whether this new era of targeted therapy will provide the same advances in more common malignancies will be determined only through the ongoing application and development of clinical trials.
 ...
PMID:Gastrointestinal stromal tumors and the evolution of targeted therapy. 1616 51

PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting vascular endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor receptor tyrosine kinase and the c-kit protein tyrosine kinase. The objective of this Phase I study was to evaluate the safety, tolerability, biologic activity and pharmacologic profile of PTK/ZK administered orally, twice daily, on a continuous dosing schedule in patients with primary refractory or relapsed acute myeloid leukemia (AML), secondary AML, poor-prognosis de novo AML or advanced myelodysplastic syndrome (MDS). Acute myeloid leukemia patients for whom PTK/ZK monotherapy was ineffective could receive PTK/ZK combined with standard induction chemotherapy. Sixty-three patients received PTK/ZK at doses of 500-1000 mg orally b.i.d. Safety and pharmacokinetic data were collected. Responses were evaluated according to standard bone marrow and peripheral blood criteria. At 1000 mg b.i.d., dose-limiting toxicities of lethargy, hypertension, nausea, emesis and anorexia were observed. Other adverse events related to PTK/ZK were dizziness, weakness, fatigue, diarrhea and pruritus; these were generally mild and reversible. Pharmacokinetic data showed that steady state was reached by day 14, there was no accumulation with repeat dosing and there was no significant increase in exposure at steady state beyond the maximum tolerated dose (MTD). Complete remission was observed in five of 17 AML patients treated with PTK/ZK combined with chemotherapy. In conclusion, the MTD of PTK/ZK is 750 mg orally b.i.d. The drug is generally well tolerated and can be given in combination with chemotherapy for patients with MDS and AML.
 ...
PMID:Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. 1661 23

A 46-year-old woman was admitted to the hospital with complaints of chronic diarrhoea, vomiting and severe muscle weakness. Clinical examination showed a lethargic, malnourished, dehydrated patient with ascites and bilateral leg oedema. Laboratory evaluation revealed mild normochromic normocytic anaemia and severe hypoproteinaemia with hypoalbuminaemia. Upper gastrointestinal endoscopy showed a thickened, friable duodenal mucosa with multiple erosions. Colonoscopy revealed nodular, pseudopolypoid lesions with patchy erosions in the left hemicolon. Haematoxylin-eosin stained sections from biopsies of endoscopically abnormal bowel segments showed multi-focal aggregates of large, histiocyte-like cells with abundant pale cytoplasm in the lamina propria. These cells were negative on PAS, Ziehl-Neelsen, Giemsa and toluidine blue stains. Their immunophenotype was CD68 (+), c-kit/CD117 (+) and mast cell tryptase (+), which is consistent with mast cells. A trephine biopsy showed diffuse replacement of the bone marrow by atypical, monomorphic, frequently spindle-shaped mast cells. No associated haematopoietic malignancy was detected. The final diagnosis was aggressive systemic mastocytosis with involvement of the gastrointestinal tract complicated by protein-losing enteropathy. This association has not been reported previously. The patient has been treated with prednisolone and interferon-alpha and has since recovered.
 ...
PMID:Aggressive systemic mastocytosis complicated by protein-losing enteropathy. 1684 41

Malignant gastrointestinal stromal tumor (GIST) consists a rare neoplasm, developing in small intestine and stomach. The presenting manifastations include weakness, weight loss, nausea, melena and anaemia. The present case refers to a 65 years old female patient with a GIST of the ampulla of Vater presenting with obstructive jaundice. Diagnosis was achieved pre-operatively by biopsies collected through diagnostic ERCP. The tumour was locally excised, with preservation of the ampulla. The histological analysis suggested low grade GIST positive for both CD 117 (c-kit) and CD34. Two years after the surgery the patient remains free of disease. Malignant GIST of the ampulla of the Vater is extremely rare as only few similar cases have been described in the literature. This is the first time a GIST being presented as obstructive jaundice ever reported. Despite the unavailability of EUS-FNA, the diagnosis was set preoperatively and the tumor was resected.
 ...
PMID:Malignant gastrointestinal stromal tumor of the ampulla of Vater presenting with obstructive jaundice. 1685 23

A 10-year-old female Egyptian fruit bat (Rousettus aegyptiacus) was evaluated for weakness and lethargy. Despite clinical improvement after supportive therapy, the bat was found dead the following day. Gross necropsy identified a mass associated with the duodenal wall and right renal cortex. Microscopically, the duodenal and gastric tunica muscularis and serosa and the right renal cortex were effaced by interlacing bundles of neoplastic spindle cells that were diffusely and strongly positive for vimentin and alpha-smooth muscle actin. The neoplastic cells also had mild to moderate cytoplasmic labeling for laminin and S100 and were negative for c-kit and desmin. On the basis of cell morphology and the immunophenotype, this tumor was diagnosed as a gastrointestinal leiomyosarcoma.
 ...
PMID:Gastrointestinal leiomyosarcoma in an Egyptian fruit bat (Rousettus aegyptiacus). 2045 29

We report the case of a 33-year-old man with diplopia, sleepiness, and paresthesia of the left upper limb that were slowly progressive. On admission, he presented with restriction in the vertical movement of the eyes and abduction of the right eye, and horizontal and convergence nystagmus. Slight weakness of the left upper limb, bilateral Babinski sign, and truncal ataxia were also noted. Cerebral magnetic resonance imaging was performed, and gadolinium-enhanced T1-weighted imaging revealed a mass lesion that involved the diencephalon and the corpus callosum, which was invariably enhanced. Specimens obtained using a brain biopsy showed epithelioid granuloma with the presence of foreign body giant cells and lymphocytic infiltration. Prednisolone was administrated because we suspected neurosarcoidosis, but the clinical symptoms worsened with the enlargement of the lesion. A re-evaluation of the biopsy specimens using immunohistochemistry revealed tumor cells of germinoma that were scattered among the lymphocytes and positive for periodic acid-Schiff staining, placental alkaline phosphatase, and c-kit. A combination of chemotherapy and radiation resulted in clinical improvement and marked reduction of the mass lesion in size. We concluded that the possibility of germinoma should be considered in case granulomatous inflammation is observed in brain biopsy specimens.
...
PMID:[Intracranial germinoma masquerading as a granulomatous inflammation, diagnostic failure after brain biopsy]. 2422 69

Thymic carcinoma is a rare, aggressive neoplasm with low 5-year survival rates ranging from 28 to 67%. Initial presentation with spinal or bone metastasis in primary thymic carcinoma is extremely rare. Thymic carcinoma, compared with thymoma, has higher recurrence rates and worse survival. We report one patient, a 29-year-old African-American male, with thymic carcinoma with metastasis to the epidural space (with cord compression), multiple bony structures (T10-L1) and left supraclavicular lymph node. Immunohistochemical staining was CD5 and c-Kit positive, consistent with thymic carcinoma. Patient underwent T12-L1 laminectomy with tumor resection to relieve cord compression and leg numbness/weakness. Patient was deemed a good candidate for rehabilitation. Soon after starting a rehabilitation program, he quickly demonstrated gains in gait distance with little to no assistance. Follow-up appointments with oncology were scheduled, and further planning of radiation and chemotherapy treatments were discussed.
 ...
PMID:Thymic carcinoma with metastasis in a 29-year-old male causing radiculopathy. 2949 45

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by loss of motor neurons in the ventral horn of the spinal cord. Clinical features such as progressively lethal respiratory weakness and associated muscle wasting have been extensively studied but less attention has been given to gastrointestinal (GI) dysfunction, which is common symptomatology in SMA patients with 43% constipation, 15% abdominal pain, and 14% meteorism. In the current study, the PrP92-SMN mouse model of SMA was utilized, to complement previous studies in which cells of the Enteric Nervous system (ENS) were susceptible to Smn (survival motor neuron) deficiency and could possibly be the basis of the observed GI symptoms. Necropsy of our mouse model showed impairment in feces excretion and smaller bladder mass, compared to Wild-Type (WT) animals. Along with the reduction in bladder mass, we also observed a decrease in the size of smooth muscles, due to reduction in Cross-Sectional Area (CSA). Interstitial cells of Cajal (ICC) provide important regulatory functions in the GI tract. To investigate if ICC are implicated in Smn deficient-induced colonic dysmotility, we assessed ICC distribution and abundance, by c-Kit, a well-established marker. SMA mice exhibited fewer c-Kit positive cells with altered localization, compared to WT. In conclusion, the observed histopathological abnormalities of our mouse model, can be secondary to SMN deficiency and could possibly underlie the GI symptoms observed in SMA patients. Future therapeutic approaches for SMA, must address not only CNS symptoms, but also non-motor-neuron-related symptoms. The PrP92-SMN mouse model could be a useful model for assessing therapeutic rescue of GI dysfunction in SMA.
 ...
PMID:Smooth muscle atrophy and colon pathology in SMN deficient mice. 3097 2


1