Project description:doxorubicin is commonly used for hematological malignancies. Since some of PTCL patients resistance to dox and die due to refractory disease or relapse, enhanced knowledge about drug response mechanisms is required to improve treatment outcome. we found an increased expression of HDAC3 in T lymphoma H9 cells following dox exprosure, we compared the gene expression profiles of H9 cells pre/post treated with doxorubicin to explore the potential mechanism of the high expression of HDAC3
Project description:Although diffuse large B-cell lymphoma (DLBCL) is a very heterogeneous disease, patients are as standard treated with a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Since approximately 40% of patients die due to refractory disease or relapse, enhanced knowledge about drug response mechanisms is required to improve treatment outcome. Therefore, this study assesses parameters that possibly influence doxorubicin response. Doxorubicin-induced impact on the number of living cells was evaluated for four human DLBCL cell lines, illustrating differences in intrinsic sensitivity levels. Six cell lines were subjected to gene expression profiling upon exposure to two distinct drug concentrations (0.00061 μg/mL and 2.5 μg/mL) for 2, 12, and 48 hours. Variation in gene expression compared to baseline was determined with a mixed-effects model, and gene ontology enrichment analysis was performed using the webtools GOrilla and REVIGO. Only few genes were differentially expressed after short exposure and/or exposure to the low concentration, suggesting lack of drug efficacy under these conditions. In contrast, 12-hour exposure to the high concentration induced several changes. In sensitive cell lines, doxorubicin affected the expression of genes involved in ncRNA metabolism, DNA repair, and cell cycle process mechanisms. In resistant cell lines, the expression of genes implicated in metabolic processes were altered. Thus, we observed a differential response rate to doxorubicin in distinct DLBCL cell lines and demonstrated that doxorubicin-induced alterations in gene expression and resulting ontologies vary with drug concentration, exposure duration, and intrinsic sensitivity level.
Project description:Microarray data on H9 hESC-derived cardiomyocytes (d30) treated with 0, 0.1, 1, or 10 uM of doxorubicin for 24 h Establish effects of increasing doses of doxorubicin on control H9 hESC-derived cardiomyocytes
Project description:Microarray data on H9 hESC-derived cardiomyocytes (d30) treated with 0, 0.1, 1, or 10 uM of doxorubicin for 24 h Establish effects of increasing doses of doxorubicin on control H9 hESC-derived cardiomyocytes Monolayers of cells in a 24-well plate were treated for 24 h
Project description:RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of combining ZD0473 and doxorubicin in treating patients who have advanced solid tumors or lymphoma.
Project description:The standard treatment for patients with diffuse large B-cell lymphoma (DLBCL) is the immunochemotherapy-based R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). Resistance to treatment, intrinsic or acquired, is observed in approximately 40% of patients with DLBCL, who thus require novel interventions to survive. To identify biomarkers for cytotoxic response assessment, microRNAs (miRNAs) associated with doxorubicin sensitivity were determined by combining global miRNA expression profiling with systematic dose-response screens in 15 human DLBCL cell lines. One candidate, miR-34a, was tested in functional in vitro studies and in vivo in a retrospective clinical cohort. High expression of miR-34a was observed in cell lines sensitive to doxorubicin, and upregulation of miR-34a is documented here to increase doxorubicin sensitivity in in vitro lentiviral transduction assays. High expression of miR-34a had a prognostic impact using overall survival as outcome. With risk stratification of DLBCL samples based on resistance gene signatures (REGS), doxorubicin-responsive samples had statistically significant upregulated miR-34a expression. Classification of the DLBCL samples into subset-specific B cell-associated gene signatures (BAGS) revealed differentiation-specific expression of miR-34a. Our data further support FOXP1 as a target of miR-34a, suggesting that downregulation of FOXP1 may sensitize DLBCL cells to doxorubicin. We conclude that miRNAs, in particular miR-34a, may have clinical utility in DLBCL patients as both predictive and prognostic biomarkers.
Project description:Transcriptional profiling of human CTCL cell line H9 comparing cells transfected with vehicle control with ShBCL11B cells. Previous study have shown the involvements of BCL11b/BCL11B in T cell development and hematopoietic malignancies of T-cell origin. Objective was to explore the action of BCL11B in the pathogenesis of cutaneous T-cell lymphoma(CTCL).