Project description:Increasing evidence across malignancies suggests that infiltrating T cells at the site of disease are crucial to tumor control. We hypothesized that marrow-infiltrating immune populations play a critical role in response to donor lymphocyte infusion (DLI), an established and potentially curative immune therapy whose precise mechanism remains unknown. We therefore analyzed marrow-infiltrating immune populations in 29 patients (22 responders, 7 nonresponders) with relapsed chronic myelogenous leukemia who received CD4+ DLI in the pre-tyrosine kinase inhibitor era. We used microarrays to detail the global programme of gene expression underlying T cell infiltration into bone marrow of responders and nonresponders to DLI. mRNA expression profiling of marrow-infiltrating CD3+ positively selected T cells of 4 responders compared to 2 non-responders, before and after DLI, was performed on Affymetrix microarrays.
Project description:Increasing evidence across malignancies suggests that infiltrating T cells at the site of disease are crucial to tumor control. We hypothesized that marrow-infiltrating immune populations play a critical role in response to donor lymphocyte infusion (DLI), an established and potentially curative immune therapy whose precise mechanism remains unknown. We therefore analyzed marrow-infiltrating immune populations in 29 patients (22 responders, 7 nonresponders) with relapsed chronic myelogenous leukemia who received CD4+ DLI in the pre-tyrosine kinase inhibitor era. We used microarrays to detail the global programme of gene expression underlying T cell infiltration into bone marrow of responders and nonresponders to DLI.
Project description:Newly diagnosed chronic phase chronic myeloid leukemia (CML) patients with a major cytogenetic response (MCyR) after 12 months of imatinib therapy have an excellent long-term outcome, while patients without MCyR have a high progression risk. Since patients with primary cytogenetic resistance may benefit from more intensive therapy up-front, we sought to identify biomarkers to predict MCyR. Keywords: Two group comparison to identify trasncriptomic signature that predicts response to therapy CD34+ cells were isolated from cryopreserved mononuclear cells of chronic phase CML patients with a complete cytogenetic response (CCyR) or >65% Ph-positive metaphases after 12 months of imatinib therapy (training set N=36). Gene expression profiles generated on amplified RNA using Affymetrix HG-U133 Plus 2.0 arrays were compared between responders and non-responders, using the criteria ANOVA p<0.1 and fold difference >I1.5I. A minimal response classifier derived from the comparison was used to predict response in a prospectively collected validation set using same criteria for responders/nonresponders (N=23).
Project description:This is a class prediction experiment, where the class is the response status to imatinib (also called Gleevec), a drug used to treat patients with chronic myelogenous leukemia (CML). There are two data sets, a training set (from Leipzig, 8 Responders and 5 Non-Responders) and a validation set (from Mannheim, 8 Responders and 7 Non-Responders). The objective is to identify differentially regulated genes between CML patients who respond and those who do not respond to imatinib and confirm the results in the validation data set. The samples from blood or bone marrow of CML patients were hybridized to Affymetrix HG-U95Av2 chip and RMA was used to generate the normalized signal values.
Project description:Biopsy specimens were collected from rectal cancer before starting preoperative radiotherapy.The expression profiles were determined using Affymetrix Human Genome U95 version 2 arrays.Comparison between the sample groups allow to identify a set of discriminating genes that can be used for characterization of responders and nonresponders to preoperative radiotherapy in rectal cancer. Keywords: repeat
Project description:Biopsy specimens were collected from rectal cancer before starting preoperative radiotherapy.The expression profiles were determined using Affymetrix Human Genome U95 version 2 arrays.Comparison between the sample groups allow to identify a set of discriminating genes that can be used for characterization of responders and nonresponders to preoperative radiotherapy in rectal cancer. Experiment Overall Design: 35-training and 11-test samples were analyzed
Project description:This is a class prediction experiment, where the class is the response status to imatinib (also called Gleevec), a drug used to treat patients with chronic myelogenous leukemia (CML). There are two data sets, a training set (from Leipzig, 8 Responders and 5 Non-Responders) and a validation set (from Mannheim, 8 Responders and 7 Non-Responders). The objective is to identify differentially regulated genes between CML patients who respond and those who do not respond to imatinib and confirm the results in the validation data set. The samples from blood or bone marrow of CML patients were hybridized to Affymetrix HG-U95Av2 chip and RMA was used to generate the normalized signal values. Keywords = chronic myelogenous leukemia Keywords = imatinib Keywords = cytogenetic responses Keywords = Gleevec Keywords = Affymetrix Keywords: other
Project description:Gene signatures were derived to separate responders from nonresponders by tipifarnib treatment. Experiment Overall Design: 58 samples from 58 patients
Project description:Dasatinib has demonstrated efficacy in patients with chronic-phase chronic myeloid leukemia (CML) who had resistance or intolerance to imatinib. However, some patients also develop resistance or intolerance to dasatinib. To identify potential molecular pathways involved in primary resistance to dasatinib in CML, we analyzed gene expression profiles of mononuclear cells of 7 imatinib-resistant patients, collected before and after 1-year dasatinib treatment. Large-scale gene expression was measured with Agilent microarrays covering protein-coding genes and long (>200 nt) noncoding RNAs (lncRNAs). Sets of genes and lncRNAs significantly differentially expressed (>1.5 fold-change; q value ?10%) were identified. Ingenuity Pathway Analysis pointed to a number of functions, canonical pathways and gene networks that were significantly enriched with differentially expressed genes. In addition to protein-coding genes, lncRNAs have been recently implicated in pathways leading to tumorigenesis. Our data point to new possible regulatory elements involved in dasatinib resistance in CML. Dasatinib pre-treatment and 1-yr post-treatment samples from 3 responders (R) or 4 non-responders (NR) chronic myeloid leukemia (CML) patients were investigated. We analyzed expression of Pre-treatment R vs. Pre-treatment NR; Pre-treatment R vs. Post-treatment NR; Pre-treatment NR vs. Post-treatment NR.
