Disease relevance of Gastrointestinal Stromal Tumors

• BACKGROUND & AIMS: Imatinib, a tyrosine kinase inhibitor of BCR-ABL, KIT, and platelet-derived growth factor receptor, is used in patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST) [1].
• Oncogenic mutations of the receptor tyrosine kinase KIT occur in gastrointestinal stromal tumors (GISTs), some cases of acute myelogenous leukemia (AML), and systemic mastocytosis (SM) [2].
• Case 3. Resection of originally inoperable liver metastases of gastrointestinal stromal tumor after imatinib mesylate therapy [3].
• Soft tissue sarcomas. Case 3. Gastrointestinal stromal tumor and Carney's triad [4].
• Double diagnosis in cancer patients and cutaneous reaction related to gemcitabine: CASE 1. Synchronous mucosa-associated lymphoid tissue lymphoma and gastrointestinal stromal tumors of the stomach [5].

High impact information on Gastrointestinal Stromal Tumors

• Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor [6].
• Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors [7].
• Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors [8].
• Gastrointestinal stromal tumors (GISTs) are often associated with activating KIT mutations, affecting regulatory domains of the KIT tyrosine kinase [9].
• PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor [10].

Chemical compound and disease context of Gastrointestinal Stromal Tumors

• Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate [11].
• One patient with gastrointestinal stromal tumor who had rapid progression during SU5416 treatment was subsequently treated with another KIT inhibitor, imatinib mesylate, and had a partial response lasting >36 months [12].
• Chromosome 22q alterations and expression of the NF2 gene product, merlin, in gastrointestinal stromal tumors [13].
• PATIENTS AND METHODS: Serial blood samples were collected over a 2-weeks period in a patient who was receiving daily 400 mg oral imatinib mesylate for the treatment of a gastrointestinal stromal tumor metastatic to the liver while on hemodialysis [14].
• Adverse reactions during imatinib and lansoprazole treatment in gastrointestinal stromal tumors [15].

Biological context of Gastrointestinal Stromal Tumors

• High-resolution amplicon melting analysis was used to scan for c-kit-activating mutations in exons 9, 11, 13, and 17 in 29 neoplasms diagnosed as gastrointestinal stromal tumors (GISTs) [16].
• Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in gastrointestinal stromal tumors [17].
• Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor [18].
• Specific mutation in exon 11 of c-kit proto-oncogene in a malignant gastrointestinal stromal tumor of the rectum [19].
• This study demonstrated that STI571 induces cell death in the gastrointestinal stromal tumor cell line, GIST-T1 [20].

Anatomical context of Gastrointestinal Stromal Tumors

• Imatinib also inhibits the c-abl, platelet-derived growth factor (PDGF) receptor, abl-related gene (ARG) and stem-cell factor (SCF) receptor tyrosine kinases, and has been used clinically to inhibit the growth of malignant cells in patients with CML and gastrointestinal stromal tumors (GISTs) [21].
• A mouse model of gastrointestinal stromal tumor (GIST) has been developed by a knock-in gene targeting strategy, which introduced a Kit gene K641E mutation, originally identified in sporadic human GISTs and in the germ line of familial GIST syndrome patients [22].
• Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal [23].
• Disease-causing human mutations that activate SCF-independent constitutive expression of c-Kit are found in acute myelogenous leukemia, human mast cell disease, and gastrointestinal stromal tumors [24].
• It is also a potent inhibitor of the Kit receptor tyrosine kinase, and has demonstrated activity clinically against the Kit-driven gastrointestinal stromal tumor (GIST) and experimentally in small-cell lung cancer cell lines [25].

Gene context of Gastrointestinal Stromal Tumors

• Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins [26].
• The present study describes seven gastrointestinal stromal neoplasms that presented clinicopathological features typical of GISTs but showed absence of CD117 expression as detected by immunohistochemistry [27].
• Prognostic role of E2F1 and members of the CDKN2A network in gastrointestinal stromal tumors [28].
• c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue) [29].
• Gastrointestinal stromal tumors (GISTs) coexpress CD34 and the Kit tyrosine-kinase receptor (CD117) [30].

Analytical, diagnostic and therapeutic context of Gastrointestinal Stromal Tumors

• Imatinib has also been shown to be the only effective drug therapy in the treatment of patients with metastatic gastrointestinal stromal tumors expressing the stem cell factor (SCF) receptor Kit [31].
• Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs) [32].
• Two gastrointestinal stromal tumors that were desmin negative in paraffin-embedded material had detectable antigen in frozen sections [33].
• BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs) [34].
• Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate [35].

References