Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal neoplasm of the gastrointestinal tract. Now, there is widespread scientific and clinical interest in GIST because of identifying in principal pathogenetic defects and development of a specific molecular inhibitor of GIST. GISTs have a gain-of-function mutation in the c-kit protooncogene. Mutation results in constitutive activation of the Kit receptor tyrosine kinase, which induces malignant cell proliferation. Imatinib (gleevec) is an oral agent that selectively inhibits c-Kit, whose efficacy proves that a specific inhibitor can counteract the effects of a genetic defect responsible for cancer. Although STI571 was first applied to GIST, it has already revolutionized the treatment of patients with metastases. Now so many molecular target agents are under development in clinical trials.
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PMID:[GIST]. 1848 9

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They originate from the myenteric ganglion cells, termed the interstitial Cajal cells. The majority, i.e. 95% of GIST, show expression of the membrane receptor protein CD117 with a tyrosine kinase activity c-kit. Gastrointestinal stromal tumors constitute less than 1% of all digestive tract tumors. They may be benign or malignant (30%), and occur in every part of the gastrointestinal tract, however the stomach is the most common localization. They develop with the same prevalence in men and in women, usually above the age of 50 years. The peak incidence is observed between the fifth and the sixth decade of life. Symptoms are not typical and depend on the localization and the tumor size. About 10-30% of GIST are completely asymptomatic, and are discovered accidentally during the endoscopy or X-rays evaluation as well as during surgical interventions performed for various reasons. The malignant tumors metastasize most commonly to the liver and peritoneum. The metastases are rarely found in the lungs, pleura and bones. The detection of GIST is based on imaging, endoscopy, histological and immunohistochemical examinations. A useful and promising diagnostic procedure is positron emission tomography. The final diagnosis is mostly based on the pathologic findings of the removed tumor. The prognosis of GIST depends on its size, mitotic activity in 50 high power fields and mucosal infiltration. Radical surgery is the best treatment of GIST.
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PMID:Gastrointestinal stromal tumors: epidemiology, clinical picture, diagnosis, prognosis and treatment. 1857 21

Uveal melanoma is the most common primary intraocular malignancy in adults. Overall mortality rate remains high because of the frequent development of metastatic disease, especially hepatic metastasis. While traditional systemic chemotherapies provide only marginal benefit to patients, local treatments for hepatic metastases, such as immunoembolization, have improved patient prognoses. Progress has also been made in identifying potential targets in the pathways involved in apoptosis, proliferation, invasion, metastasis, and angiogenesis of uveal melanoma. Among these pathways, the c-Kit, c-Met, and IGF-1R signal pathways and the PTEN-related PI3K-Akt pathway are the most important targets. Clinical trials using blockades of these pathways in conjunction with strategies to facilitate apoptosis is a direction for future clinical trials. Application of these approaches in the adjuvant setting after primary therapy for high-risk uveal melanoma patients is also a future consideration to improve the clinical outcome of this disease.
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PMID:The biology and management of uveal melanoma. 1870 73

Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. One hundred one patients (54 women and 47 men) with a mean age of 64.1 years (range, 17-94 years) were surgically treated for a GIST within a 10-year period. Of these patients, 28 (28%) were affected by metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97 GIST patients (96%). In patients with high-risk GIST, the expression of p16 expression was highly predictive for poor prognosis, i.e., the development of recurrence or metastases (P = .006) and poor survival (P = .004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041). The disease-specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85% and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high-risk classification were confirmed as relevant predictors for unfavorable prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases, the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for "very high risk GIST."
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PMID:p16 expression differentiates high-risk gastrointestinal stromal tumor and predicts poor outcome. 1881 51

Gastric gastrointestinal stromal tumors (GIST) commonly present as an incidental finding on upper gastrointestinal endoscopy. Advances in endoscopic technology have allowed some to perform attempted excision of these lesions endoscopically. The oncologic implications of such an approach remain unclear. A-74-year-old man initially presented with an incidental finding of a 1.6 x 1.8-cm c-kit-positive gastrointestinal stromal tumor with low mitotic activity in the gastric fundus. The patient underwent an attempted endoscopic resection of this mass resulting in incomplete excision and gastric perforation. There was immediate conversion to a celiotomy and the patient underwent partial gastrectomy; there was no evidence of metastatic GIST. Three years later, the patient was noted to have an asymptomatic large pelvic mass (4 x 7 cm) on CT scan and was referred for evaluation. Subsequent surgical exploration revealed a single mass adherent to the pelvic sidewall that was resected. Subsequent pathology demonstrated a c-kit-positive GIST consistent with metastatic disease. Eighteen months later, the patient remains free of disease. Complications from endoscopic resection of gastric GIST may be associated with peritoneal dissemination of disease. This should be considered when formulating a strategy for management of gastric GIST. Complete transperitoneal excision (either open or laparoscopic) with clear margins and without tumor rupture remains the gold standard for management of gastric GIST.
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PMID:Is endoscopic resection of gastric gastrointestinal stromal tumors safe? 1909 34

Gastrointestinal stromal tumors (GISTs) are a rare and heterogeneous group of spindle cell neoplasms that have also been reported outside of gastrointestinal (GI) tract. These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec). We report two cases of gastrointestinal stromal tumor identified on prostatic biopsies, where a primary prostatic sarcoma was considered in the differential diagnosis. In one of the cases, there was extensive local disease involving prostate, rectum, and pelvic wall, as well as metastatic disease that quickly lead to the patient's death despite aggressive treatment with imatinib mesylate and conventional chemotherapy. In the other case, the tumor was mostly confined to the rectum but also focally extended into the prostate capsule. The patient underwent resection and was alive without disease 18 months after surgery. In both cases, tissue samples from prostate and the rectum showed a malignant spindle cell neoplasm, which was positive for CD117 (c-kit). Given their unique clinical management, gastrointestinal stromal tumors should be considered in the differential diagnosis of spindle cell lesions on prostatic needle biopsies and CD117 should be added to the immunohistochemical panel in the work-up of such lesions to avoid misinterpreting them as primary prostatic neoplasms.
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PMID:Gastrointestinal stromal tumors presenting as a prostatic mass. 1922 92

The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.
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PMID:[Gastric mesenchymal tumours (GIST)]. 1925 69

A 5-year-old female miniature dachshund presenting with persistent vomiting and diarrhea had two concurrent rare pathological conditions: systemic candidiasis and mesenteric mast cell tumor with multiorgan metastases. Neoplastic mast cells formed mass in the mesentery of the cecal-colonic region and were also found in the liver, spleen, kidneys, lungs, adrenal grands, ovaries, bone marrow and other tissues. The cells had intracytoplasmic granules with metachromasia and were immunohistochemically positive for c-kit and histamine. Granulomatous lesions with fungal organisms were present in the heart, lungs, kidneys, pancreas, subserosal and surrounding adipose tissue of the duodenum, thyroid glands and mesenteric mass, and phagocytosed organisms were detected in the liver and bone marrow. Bacteriologically and immunohistochemically, the fungi were consistent with Candida albicans.
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PMID:Systemic candidiasis and mesenteric mast cell tumor with multiple metastases in a dog. 1926 39

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

Gastrointestinal stromal tumor (GIST) is the most common form of sarcoma and can vary in size and clinical outcome from an incidental finding at the time of surgery to life-threatening metastatic disease. Surgery is the standard of care for primary disease, and the oral drug imatinib is the standard of care for metastatic disease. Sunitinib was approved in the United States in early 2006 for GIST refractory to imatinib. The pathology of GIST, surgical options for primary and metastatic disease, and findings leading to the use of imatinib and sunitinib for GIST are reviewed in this manuscript, with attention to the mutation statuses of c-kit and PDGF receptor that lead to imatinib sensitivity or resistance.
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PMID:Gastrointestinal Stromal Tumors (GIST) and Their Management. 1936 Jan 54


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