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 tumors have until recently had a uniformly poor prognosis with lack of effective drug therapies. These tumors usually have activating mutations in either KIT or PDGFR-alpha tyrosine kinase receptors. Over the past decade, imatinib (Gleevec), a selective tyrosine kinase inhibitor has become the standard of care for the first-line treatment of patients with unresectable and metastatic disease. For patients with imatinib-resistant disease or intolerant to the side effects of imatinib, sunitinib (Sutent), a multitargeted tyrosine kinase inhibitor was recently approved. For earlier-stage disease, status post-complete surgical excision, preliminary data seem encouraging for the role of adjuvant imatinib in prolonging patients' disease-free interval. The impact of neoadjuvant drug therapy needs to be further classified and explored. With additional evaluation of other tyrosine kinase inhibitors and novel therapies against other molecular markers, the treatment paradigm for this malignancy should continue to evolve.
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PMID:New therapeutic options in gastrointestinal stromal tumors. 1840 63

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 (GISTs) are the most common gastrointestinal mesenchymal tumors. Computed tomography (CT) often shows exophytic gastrointestinal masses with cystic changes, necrosis or fistula formation, and heterogeneous enhancement. After Gleevec therapy, the primary tumor, its metastases, and its recurrences can develop cystic changes and decrease in size, these findings can be satisfactorily monitored by CT. We report on 42 patients with proven GISTs, five presenting with metastases and nine patients with recurrence or development of metastases after surgery and chemotherapy.
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PMID:Value of CT in the diagnosis and follow-up of gastrointestinal stromal tumors. 1850 43

Gastrointestinal stromal tumors (GISTs) generally arise from primary activating mutations in the KIT or PDGFRA genes that result in constitutive activation of receptor tyrosine kinase activity. Imatinib provides targeted therapy for GIST by inhibiting the KIT and PDGFR-alpha tyrosine kinases. Clinical benefit is achieved in approximately 85% of patients with unresectable or metastatic disease, with a median progression-free survival of 20 to 24 months. The mechanisms of acquired resistance to imatinib are heterogeneous, with most involving the emergence of secondary mutations in KIT exons 13, 14, or 17. In patients failing or intolerant to imatinib, the multitargeted agent sunitinib achieves durable disease control in approximately 50% of cases. Experimental treatment options beyond those currently available consist of other KIT-targeting tyrosine kinase inhibitors, such as nilotinib, or agents targeting alternative pathways, such as antiangiogenic agents, mammalian target of rapamycin, RAF kinase, and chaperone inhibitors.
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PMID:Novel approaches to imatinib- and sunitinib-resistant GIST. 1877 61

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumours of the digestive tract. They can arise anywhere in the gastrointestinal tract, from oesophagus to anus, and rarely from peritoneal cavity or mesentery. GIST usually remain asymptomatic for a long time. Therefore 10 to 20% are found incidentally at endoscopy or at time of surgery for others reasons and metastases are found in 15 to 50% of cases at diagnonis. Histologicaly, they are characterized by a cellular proliferation constituted of either spindle or epithelioid cells. Diagnosis has to be confirmed by immunohistochemistry, with positivity of KIT in 95% of cases, or by molecular biology, with "gain of function" mutations of KIT or PDGFRA in 85% of cases. Primary localization, mitotic activity and tumor size are the main prognostic factors. Metastases occur in 30 to 50% of patients with GIST. GIST are highly resistant to conventional chemotherapy and results obtained with new targeted therapies like Imatinib constitute one of the major progress in oncology during the decade.
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PMID:[GIST: definition, physiopathology]. 1906 Aug 40

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant dermal neoplasm characterized by slow infiltrative growth, little metastatic potential but a high tendency to recur locally after surgical excision. DFSP is associated with a high cure rate. The optimal therapy is complete surgical resection. The recurrence potential of DFSP is directly related to the extent of resection. The need for wide excision margins has been amply documented. Wide local excision is a frequently used practice. Mohs micrographic surgery with continuous histological margin control is further propagated to reduce local recurrence rates. In more than 90% of DFSP, a specific chromosomal aberration is described, involving Chromosomes 17 and 22. It leads to a constitutive activation of the platelet-derived growth factor receptor (PDGFR) followed by continuous stimulation of the tumor cell growth. The use of targeted inhibitors of PDGFR is a good therapeutic option in the treatment strategy of unresectable locally advanced, recurrent or metastatic disease. With Imatinib, a selective PDGFR tyrosin kinase inhibitor, partial and complete remissions of DFSP could be achieved. This article reviews the current opinion and literature about DFSP and resulting therapy strategies.
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PMID:Current treatment options in dermatofibrosarcoma protuberans. 1920 37

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 response of gastrointestinal stromal tumors (GISTs) to tyrosine kinase receptor inhibitors (TKR-I) has been a breakthrough for small molecular therapy. We report here on the very different long-term outcome of a synchronous metastatic GIST with complete remission of the primary tumor and progressive liver metastases under TKR-I therapy. In 2003, a 52-year-old patient was diagnosed with gastric GIST and synchronous multiple liver metastases. Therapy with imatinib, 400 mg daily, was started immediately. Fifteen months later, the primary was no longer detectable by endoscopy. In 2006, progression of the liver metastases was observed. Mutation analysis of the initial biopsy specimen from the primary, as well as the biopsy from the three main liver metastases after 3 years of imatinib treatment, revealed the common KIT exon 11 deletion (W557_K558del) in all tumor samples. Two of the metastases had a separate secondary mutation in KIT exon 14 and 17, respectively, while the largest cystic metastatic lesion had no other mutation. Imatinib was then increased to a daily dose of 800 mg, and in April 2007 the treatment was changed to sunitinib. Fifty-two months after initial diagnosis, the patient died of liver failure. At no time point, relapse of the gastric primary tumor was observed. Whilst TKR-Is are commonly very effective in treating GISTs, the present case illustrates their varying effects regarding the clinical behavior and genetic variations within different tumors of the same patient after long-term treatment.
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PMID:Analysis of a case with disappearance of the primary gastrointestinal stromal tumor and progressive liver metastases under long-term treatment with tyrosine kinase inhibitors. 1929 38

During cancer therapy with DNA-damaging drug-agents, the development of secondary resistance to apoptosis can be observed. In the search for novel therapeutic approaches that can be used in these cases, we monitored chemotherapy-induced apoptosis resistance in a syngenic mouse tumor model. For this, syngenic murine colorectal carcinoma cells, which stably expressed a FRET-based caspase-3 activity sensor, were introduced into animals to induce peritoneal carcinomatosis or disseminated hepatic metastases. This syngenic system allowed in vitro, in vivo and ex vivo analysis of chemotherapy induced apoptosis induction by optically monitoring the caspase-3 sensor state in the tumor cells. Tumor tissue analysis of 5-FU treated mice showed the selection of 5-FU-induced apoptosis resistant tumor cells. These and chemo-naive fluorescent tumor cells could be re-isolated from treated and untreated mice and propagated in cell culture. Re-exposure to 5-FU and second line treatment modalities in this ex-vivo setting showed that 5-FU induced apoptosis resistance could be alleviated by imatinib mesylate (Gleevec). We thus show that syngenic mouse systems that stably express a FRET-based caspase-3 sensor can be employed to analyse the therapeutic efficiency of apoptosis inducing chemotherapy.
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PMID:Fluorescence lifetime imaging microscopy of chemotherapy-induced apoptosis resistance in a syngenic mouse tumor model. 1958 98

A young woman was referred to our institution for the appearance of a single pulmonary nodule at a routine follow-up computed tomographic scan of the thorax. She had been operated on 4 years earlier for a parachordoma of the iliopsoas muscle. Wedge resections were accessed through a mini-thoracotomy, and the pathologic examination confirmed the diagnosis of parachordoma lung metastases. Adjuvant chemotherapy (Glivec, 400 mg/daily [imatinib; Novartis, Basel, Switzerland]) was indicated and was administered for 10 months. At the time this case report was written, the patient was alive with no sign of tumor recurrence. We believe that metastatic parachordoma to the lung has been previously reported only once in the English literature. Our case adds evidence that parachordoma, despite its generally indolent behavior, can metastasize to the lung.
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PMID:Pulmonary metastases from parachordoma. 1963 72


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