Combinations of anticancer agents may have synergistic anti-tumor effects, but enhanced hematological toxicity often limit their clinical use. We examined whether microarray profiles could be used to compare early molecular responses following a single dose of agents administered individually with that of the agents administered in a combination. Six patterns of co-expressed genes were detected at the 1-hour time point which indicate regulatory expression of genes dependent on the order of the administration. When topotecan is given first, several signal transduction transcription factors associated with cancer or inactivation of a tumor suppressor were co-regulating gene expression. These results suggest alterations in histone biology, chromatin remodeling, DNA repair, bone regeneration, and respiratory and oxidative phosphorylation are among the prominent pathways modulated in bone marrow from animals treated with an oxaliplatin/topotecan combination.
Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity.
Sex, Age, Specimen part, Time
View SamplesBackground. Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is not well characterized. Markers of these processes may provide a deeper understanding of the underlying mechanisms. Objective. To identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. Design. RNA from subcutaneous abdominal adipose tissue from nine obese subjects was obtained and analyzed at baseline, after weight reduction on a low calorie diet (LCD), and after a period of group therapy in order to maintain weight stability. Results. Subjects lost 18.8 + 5.4% of their body weight during the LCD and maintained this weight during group therapy. Insulin sensitivity (HOMA) improved after weight loss with no further improvement during weight maintenance. Cyclin-dependent kinase inhibitor 2B (CDKN2B) and JAZF zinc finger 1 (JAZF1), associated with type 2 diabetes, were downregulated. We could also confirm the downregulation of candidates for obesity and related traits, such as tenomodulin (TNMD) and matrix metallopeptidase 9 (MMP9), with weight loss. The expression of other candidates, such as cell death-inducing DFFA-like effector A (CIDEA) and stearoyl-CoA desaturase (SCD) were upregulated during weight loss but returned to baseline levels during weight maintenance. Conclusion. Genes in the adipose tissue are differentially expressed during weight loss and weight maintenance after weight loss. Genes that show sustained regulation may be of potential interest as markers of the beneficial effects of weight loss whereas others seem to be primarily involved in the process of weight loss itself.
Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance.
Sex, Age
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesGene expression profiles were compared between regulatory T cells (Treg) and Effector CD4+ T cells in healthy B6 mice and sick mice with scurfy mutation.
Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset.
Sex, Specimen part
View SamplesMulticiliated cells are crucial for fluid and ion transport in epithelia of a variety of organs and their impaired development and function are seen in human diseases affecting the brain, respiratory, and reproductive tracts. Multiciliogenesis requires activation of a specialized transcription program coupled to complex cytoplasmic events that lead to large-scale centriole amplification to generate multicilia. Yet, it remains unclear how these events are coordinated to initiate multiciliogenesis in epithelial progenitors. Here we identify an unsuspected mechanism orchestrated by the transcription factor E2f4 essential to integrate these processes. We show that after inducing a transcriptional program of centriole biogenesis, E2f4 translocates to the cytoplasm to become a core component of structures classically identified as fibrous granules (FG), acting as organizing centers for deuterosome assembly and centriole amplification. Remarkably, loss of cytoplasmic E2f4 prevents FG aggregation, deuterosome assembly and multicilia formation even when E2f4s transcriptional function is preserved. Moreover, in E2f4-deficient cells multiciliogenesis is rescued only if both nuclear and cytoplasmic E2f4 activities are restored. Thus, E2f4 integrates previously unrelated nuclear and cytoplasmic events of the multiciliated cell program.
Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis.
Specimen part
View SamplesGenomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Disease, Disease stage
View SamplesGenomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Disease, Disease stage
View SamplesTranscriptomic profiling of human breast tumors.
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Age, Specimen part
View SamplesPseudomonas aeruginosa is a virulent opportunistic pathogen responsible for high morbity in COPD, burns , implanted medical devices and cystic fibrosis.
Anr and its activation by PlcH activity in Pseudomonas aeruginosa host colonization and virulence.
No sample metadata fields
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