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The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic(More)
Soft tissue sarcomas are rare tumours of the connective tissue. The knowledge of this rare entity is necessary for an accurate diagnosis. The incidence in Europe is about 3,6/100 000 per year. The first line treatment consists of a wide resection of the tumour, possibly combined with an adjuvant radiation therapy. A chemotherapy can be indicated and has to(More)
Resistance to chemotherapy in cancer is common. As gene expression profiling has been shown to anticipate chemotherapeutic resistance, we sought to identify cellular pathways associated with resistance to facilitate effective combination therapy. Gene set enrichment analysis was used to associate pathways with resistance in two data sets: the NCI-60 cancer(More)
Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-Kras(G12D); Trp53(Flox/Flox) mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we(More)
The field of oncology is experiencing a paradigm shift from broad-spectrum cytotoxic therapies to more specific molecularly based targeted therapies. The activity of imatinib mesylate in chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST) has reinforced our faith in translational research and its potential impact on the cure of cancer(More)
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to mdi-cate this fact. Abstract The spontaneous mouse waved I (wal) mutation is allelic with the transforming growth factor a (TGF-a) gene and produces(More)
Recent advances in sarcoma genomics have identified novel mutations in the PI3K pathway in human sarcomas. Here, we use a mouse model of primary soft-tissue sarcoma for preclinical testing of doxorubicin and inhibitors of the PI3K pathway: BKM120 (PI3K inhibitor) and BEZ235 (a dual PI3K/mTOR inhibitor). Doxorubicin-treated tumors (n = 15) showed a partial(More)
Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma.(More)
Rhabdomyosarcomatous dedifferentiation of GIST following tyrosine kinase inhibitor (TKI) therapy is rare, with only a handful of cases previously reported in the literature. Herein we present a case of metastatic GIST initially treated with imatinib that developed radiographic evidence of progression after 8 months of standard dose therapy with continued(More)
Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signatures can accurately predict clinical(More)
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