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)

We report a case of gastrointestinal stromal tumor (GIST) with multiple hepatic metastases that responded to tyrosine kinase inhibitor STI571. A 30-year-old woman underwent total gastrectomy on July 10, 1998, with a diagnosis of submucosal tumor of the stomach. Pathological analysis of the primary lesion revealed strong expression of c-kit, and it was diagnosed as GIST. The patient underwent tumor excision due to peritoneal recurrence on May 1, 2000 and November 13, 2000. On August 8, 2001, multiple liver metastases were detected by abdominal CAT scan. Treatment with STI571 at a dose of 400 mg/day for 28 days was initiated on September 14, 2000. CAT scan showed rapid tumor shrinkage after 3 weeks of treatment (reduction rate of 56%) and the response continued after 7 weeks of treatment (reduction rate of 71%). Thus, we evaluated the response as PR. Leukocytopenia, edema, diarrhea and nausea were observed; however, all toxicities were mild and tolerable. This case suggests the efficacy of STI571 for metastatic GIST.
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PMID:[A patient with metastatic gastrointestinal stromal tumor who responded to STI571]. 1197 48

The nonepithelial, nonlymphoid tumors of the gastrointestinal tract are heterogeneous in terms of clinical presentation, behavior, pathology, and genetic features. Concepts regarding these tumors have changed rapidly over the past decade as nomenclature has evolved. Many of these tumors have no muscle differentiation, and designations such as leiomyoma or leiomyosarcoma are inappropriate for many of these neoplasms. With an improved understanding of the biology of these tumors, gastrointestinal stromal tumor (GIST) is used as a specific term for tumors of the gastrointestinal tract that lack markers of myogenic differentiation, but stain positive for vimentin, and express CD34 and CD117, the product of the c-kit oncogene. Both benign and malignant types are recognized. In addition to myogenic tumors and GIST, gastrointestinal autonomic nerve tumors (GANT) are also recognized. Complete en bloc surgical resection, when possible, is the cornerstone of therapy. Metastasis tends to occur to the liver and within the peritoneal cavity, especially in patients whose tumors have ruptured spontaneously or been violated by the surgeon. Incomplete surgical resection and metastatic disease indicate a dismal prognosis in the majority of patients. Recurrent or metastatic disease is often resected, but this has an uncertain impact on outcome. Operation may palliate patients with intestinal obstruction or other symptoms. For patients with unresectable disease, the results with systemic chemotherapy have been dismal. Treatment with doxorubicin/ifosfamide combinations is of dubious value. Hepatic arterial embolization, with and without intra-arterial chemotherapy, results in regression of liver metastases in selected patients. Regression has also been seen using intrahepatic arterial infusion of doxorubicin without embolization. The impact of such treatment on outcome, however, is poorly studied. Aggressive surgical resection of peritoneal metastases with intraperitoneal chemotherapy has been advocated, but requires formal study in large trials.
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PMID:Gastrointestinal stromal tumors. 1205 70

This paper reviews data on the prognosis of gastrointestinal stromal tumors (GISTs). These tumors are specific KIT-expressing and KIT-signaling-driven mesenchymal tumors, many of which have KIT-activating mutations. GISTs occur in the entire gastrointestinal (GI) tract and may also arise from the omentum, mesenteries, and retroperitoneum. They range from small benign tumors to sarcomas at all sites of occurrence. A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Understanding the natural history of GIST before introduction of STI-571 will help assess the impact and position of this new treatment. The frequency of benign versus malignant GISTs varies between sites. Benign GISTs outnumber malignant GISTs in the stomach, whereas malignant GISTs are more common in the intestines. Tumors that have metastasized at presentation have a very poor prognosis. Traditionally, the 3 key prognostic factors have been mitotic rate, tumor size, and site. Tumors that are small (< or =2 cm) and show mitotic activity not exceeding 5 mitoses per 50 high-power fields (HPFs) have an excellent prognosis, probably independent of site, although this has not been shown specifically for all sites. In the stomach, most epithelioid GISTs are benign, provided that mitotic counts do not exceed 5/50 HPFs. However, a small proportion of tumors apparently lacking mitotic activity do metastasize. Tumors with a mitotic rate >5/50 HPFs usually have a malignant behavior. The Ki67 index may help identify tumors with malignant potential, but large site-specific series are not yet available. Genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential.
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PMID:Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. 1209 72

A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the stomach 10 years ago, was found to have a left lung tumor on chest X-ray and computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of gastric leiomyosarcoma. On admission, another tumor was detected at left occipital region by brain CT and was thought to be meningioma. Left lower lobectomy and brain tumor resection were performed serially. The histologic and immunohistochemical findings showed that both tumors were metastases of gastrointestinal stromal tumor (GIST) of the stomach after long disease-free interval. Compared with the primary tumor, cellular density, mitotic figures, bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This case suggest that GIST may recurrent as pulmonary metastasis after long disease-free interval and should be follow up longer after resection. Patient prognosis with pulmonary metastases is considered to be reflected more exactly in biological malignant potential of metastatic tumor rather than that of primary tumor.
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PMID:[Resection for pulmonary metastasis of gastrointestinal stromal tumor of the stomach at 10 years after gastrectomy; report of a case]. 1223 15

Although gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal neoplasm of the gastrointestinal tract, until recently it has been an obscure disease. Now, there is widespread scientific and clinical interest in GIST because its principal pathogenetic defect has been identified and a specific molecular inhibitor of GIST has been developed. Most GISTs contain a gain-of-function mutation in the c-kit proto-oncogene. Mutation results in constitutive activation of the Kit receptor tyrosine kinase, which induces cellular proliferation. STI571 is an oral agent that selectively inhibits Kit. It is a landmark development in cancer treatment and marks a new era of targeted molecular therapy. Its efficacy proves that a specific inhibitor can counteract the effects of a genetic defect responsible for neoplasia. Although STI571 was first applied to GIST only 2 years ago, it has already revolutionized the treatment of patients with metastatic disease and is also currently being tested as an adjuvant therapy after the resection of primary GIST.
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PMID:The GIST of targeted cancer therapy: a tumor (gastrointestinal stromal tumor), a mutated gene (c-kit), and a molecular inhibitor (STI571). 1241 3

Gastrointestinal stromal tumours (GISTs) are the most common form of mesenchymal tumour of the gastrointestinal tract. Clinically, they range from small indolent tumours curable with surgery alone to aggressive cancers. Making a distinction between an indolent and a malignant GIST is unreliable with conventional histopathological techniques. The presence of metastases at the time of diagnosis confirms malignancy, but all GISTs should be regarded as having malignant potential. GISTs characteristically express the KIT protein, a transmembrane tyrosine kinase receptor for stem-cell factor. Most GISTs have a mutation in the KIT proto-oncogene that translates into a gain-of-function constitutive activation of the KIT kinase. KIT activation seems to be an early tumour-promoting event in pathogenesis. Commonly, malignant GISTs show high-level primary resistance to conventional chemotherapy. Imatinib mesylate is an orally administered selective inhibitor of certain tyrosine kinases including KIT. Most patients with advanced malignant GISTs achieve clinical benefit and significant antitumour responses with imatinib mesylate. Responses have been durable, and most patients tolerate the drug well at clinically effective doses. Imatinib mesylate is the first effective systemic therapy for advanced GIST.
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PMID:Management of malignant gastrointestinal stromal tumours. 1242 67

Gastrointestinal stromal tumor (GIST) is a rare, but potentially aggressive tumor. We present an asymptomatic 64-year-old man with an incidental 9-cm GIST that arose in the posterior mediastinum. Wide surgical excision was performed with rotation of an intercostal muscle flap to buttress a surgically created esophageal wall defect. The patient is now free of disease 26 months postoperative. This tumor is defined by the carcinogenic over-expression of KIT-protein, a tyrosine kinase receptor. Accurate diagnosis of gastrointestinal stromal tumor is imperative, as specific medical therapy is now available for potential control of recurrent or metastatic disease.
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PMID:Gastrointestinal stromal tumor of the posterior mediastinum. 1246 32

We report a patient with diffuse peritoneal metastases of GIST who was administered STI571 (a tyrosine kinase inhibitor). She was a 45-year-old woman who underwent surgery for a mass that was suspected to be an ovarian tumor. The postoperative diagnosis was GIST developing from the small intestine. Two years later, multiple peritoneal metastases were noted and a complete macroscopic resection was done. Six months after the second operation, she needed a third operation and complete macroscopic resection was repeated. Only 4 months after the third operation, she underwent a fourth operation. We resected massive peritoneal metastases, but diffuse metastases remained. Therefore, we started to administer STI571 at 400 mg/day. She has been free from peritoneal masses for 9 months after the fourth operation. We recommend STI571 for uncontrolled diffuse peritoneal metastases of GIST.
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PMID:[A patient with diffuse peritoneal metastases of GIST who was administered STI571]. 1248 66

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The concept of GIST and the definition of GIST pathology have evolved greatly over the past 5 years. GIST has been shown to share immunohistochemical, ultrastructural and histogenic similarities with the interstitial cells of Cajal. Both GIST and the interstitial cells of Cajal express KIT, the receptor tyrosine kinase that is the protein product of the c-kit proto-oncogene. KIT is universally phosphorylated in GISTs. Sequencing of c-kit complementary DNA from human GIST cells has demonstrated a high frequency of mutations that lead to constitutive activation of the KIT tyrosine kinase in the absence of stimulation by its physiologic ligand (stem cell factor). This, in turn, causes uncontrolled stimulation of downstream signaling cascades with aberrant cellular proliferation and resistance to apoptosis. Historically, malignant GIST has been highly refractory to conventional cytotoxic therapy. Signal transduction inhibition as cancer therapy was first tested successfully with imatinib mesylate (formerly known as STI571), a selective small-molecule tyrosine kinase inhibitor, with the initial target being blockade of Bcr-Abl, the oncogene with tyrosine kinase activity responsible for the pathogenesis of chronic myelogenous leukemia (CML). Imatinib was subsequently shown to block activity of the KIT tyrosine kinase as well, and in laboratory studies this led to apoptotic death of GIST cells. The first GIST patient to receive imatinib exhibited dramatic benefit despite far-advanced metastatic disease that was previously refractory to all chemotherapy. Subsequently, multicenter clinical trials have been performed to assess the safety, efficacy and biologic activity of imatinib in patients with advanced GIST. The results from these studies have established imatinib as an effective new therapeutic alternative for the majority of patients with advanced GIST, a solid tumor for which no prior chemotherapy has ever shown antitumor efficacy. This work provides proof of concept to the hypothesis that selective inhibition of aberrant signal transduction can provide important anticancer activity, if the proper signaling pathways are identified and blocked.
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PMID:Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). 1252 73

Stromal tumors of the rectum are rare. The most common symptoms are rectal bleeding, pain, constipation and obstruction. A case report of a 61 years old female admitted with acute bleeding due to malignant stromal tumor of the rectum is described. Upon admission the clinical and laboratory findings necessitance blood transfusion. Preoperative assessments revealed a large tumor located in the rectal wall with extension to the adjacent tissues. The histologic features of needle biopsy was compatible with gastrointestinal stromal tumor. Abdominoperineal excision of the rectum was performed. The definitive histological examination showed a gastrointestinal stromal tumor (GISTs), spindle cell type with mucosal invasion, vast necrosis and highly mitotic activity. The tumor cells coexpressed CD34 and smooth muscle actin and were negative for staining desmin and S-100 protein. Adjuvant chemotherapy was given. The patient died 7 months after the operation due to widespread metastases. We decided to describe a rare malignant stromal tumor of the rectum with uncommon clinical presentation.
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PMID:[Acute rectal bleeding from malignant stromal tumor]. 1253 96


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