Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considera ...[more]
Project description:Comparison of DNA copy number changes between human sarcomas and corresponding xenografts, as well as between xenograft serial passages. Array CGH was performed using a homemade 1 Mb BAC/PAC microarray on 15 cases with a total of 36 samples.
Project description:Investigation of transcription profile of spontaneous Cefotaxime resistant R6 mutants containing mutations in pbp2x, ciaH, pbp2a and mutants with different mosaic pbp2x, pbp1a genes.
Project description:Mutations in Hedgehog (Hh) pathway genes, leading to constitutive activation of Smoothened (Smo), occur in sporadic medulloblastoma, the most common brain cancer in children. Antagonists of Smo induce tumor regression in mouse models of medulloblastoma and hold great promise for targeted therapy for this tumor. However, acquired resistance has emerged as one of the major challenges of targeted cancer therapy. Here, we describe novel mechanisms of acquired resistance to Smo antagonists in medulloblastoma. NVP-LDE225, a potent and selective Smo antagonist, inhibits Hh signaling and induces tumor regressions in allograft models of medulloblastoma that are driven by mutations of Patched (Ptch), a tumor suppressor in the Hh pathway. However, after long-term treatment, evidence of acquired resistance was observed. Genome-wide profiling of resistant tumors revealed distinct mechanisms to evade the inhibitory effects of Smo antagonists. Chromosomal amplification of Gli2, a downstream effector of Hh signaling, reactivated Hh signaling and restored tumor growth. Analysis of pathway gene-expression signatures selectively deregulated in resistant tumors identified increased phosphoinosite-3-kinase (PI3K) signaling as another potential resistance mechanism. Probing the functional relevance of increased PI3K signaling, we showed that the combination of NVP-LDE225 with the dual PI3K/mTOR inhibitor NVP-BEZ235 markedly delayed the development of resistance. Our findings have important clinical implications for future treatment strategies in medulloblastoma. mRNA profiling: RNA was prepared from tumours from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and hybridized on Affymetrix Mouse Genome 430 2.0 RNA expression array. The dosage terminology (BID & QD) reflects the dosing schedule, where BID = twice a day, QD = once a day. aCGH: DNA was prepared from tumors from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and hybridized on Agilent mouse CGH 244K Array.
Project description:Hypersensitivity reactions to medications constitute a growing problem in the clinical practice. In order to study the molecular basis underlying the pathogenesis of non-immediate hypersensitivity reactions to drugs, we characterized the gene expression profiles of PBMCs isolated from patients during the acute phase and upon resolution of the clinical symptoms using a cDNA array technology. Eighty five genes were found to be differentially expressed during the acute phase of drug-induced delayed hypersensitivity reactions. Furthermore, ninety two genes with distinct expression patterns during the acute phase of severe and benign diseases were identified. Keywords: Comparison between disease and healty status Expression profiles of 11835 genes were analyzed in peripheral blood mononuclear cells from 13 patients with different clinical entities . Two samples were analyze from each patient. The first blood sample was drawn during the acute phase of the disease. The second blood sample was obtained upon resolutin of the clinical symptoms. The ratio between gene expression levels in both samples was calculated for each patient.