Statins and bisphosponates (BPs) are two distinct classes of isoprenoid pathway inhibitors targeting HMG-CoA reductase (upstream enzyme) and Farnesyl-pyrophospate synthase (downstream enzyme) respectively. Here we conducted a comparative study of two representatives of these classes, fluvastatin (Fluva) and Zoledronate (Zol), to assess the differences in their in vivo metastatic potentials and pharmacogenomic profiles. Both drugs, being administered after emergence of detectable metastases, appeared to be potent metastasis inhibitors in MDA-MB-231 breast cancer metastasis model. We observed a reduced number of metastatic sites under Fluva, but not Zol treatment. Combinatorial in vivo treatment by Fluva and Zol showed no synergy for these drugs, as reported earlier on the basis of in vitro studies (Budman DR, Oncology 2006), staying in line with similarity of their transcriptomic profiles. Comparison of Zol and Fluva transcriptomic profiles revealed similar patterns of affected genes (describe involved genes functions) through different kinetics (when treated with IC50 determined for 72h treatment, the majority of changes were observed after 24h incubation with Fluva , and only after 48h incubation with Zol at 72h-IC50 or after 24h treatment with its 3 times higher dose). We demonstrated here that targeting different enzymes of the same pathway neither necessarily leads to distinct changes in gene profiles, nor to synergy for in vivo anti-metastatic potential.
Transcriptome analysis and in vivo activity of fluvastatin versus zoledronic acid in a murine breast cancer metastasis model.
Cell line, Time
View SamplesTo determine the modulation of gene expression of C57BL/6 and DBA/2 BMDLs in the presence of living intracellular Leishmania amazonensis amastigotes
Distinct transcriptional signatures of bone marrow-derived C57BL/6 and DBA/2 dendritic leucocytes hosting live Leishmania amazonensis amastigotes.
Specimen part
View SamplesTo determine the modulation of gene expression of mouse BMDCs in the presence of living intracellular Leishmania amazonensis amastigotes
Sorting of Leishmania-bearing dendritic cells reveals subtle parasite-induced modulation of host-cell gene expression.
Sex, Age
View SamplesTo determine the modulation of gene expression of mouse BMDCs in the presence of living intracellular Leishmania amazonensis amastigotes at 24 hr post infection.
<i>Leishmania amazonensis</i> Subverts the Transcription Factor Landscape in Dendritic Cells to Avoid Inflammasome Activation and Stall Maturation.
Specimen part, Time
View SamplesWe address the function of HEXIM, an inhibitor of the general transcriptional elongation regulator P-TEFb which regulates the transcriptional status of many developmental genes, during Drosophila development. We showed that HEXIM knockdown mutants display organs development failure. In the wing disc, it induces apoptosis and affects Hh signaling. The continuous death of proliferative cells is compensated by apoptosis-induced cell proliferation, in a manner similar to that of differentiated cells, together with high levels of Hh and Ci. We completed this analysis with microarrays to characterize the molecular phenotype of HEXIM knockdown during eye differentiation.
Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development.
Specimen part
View SamplesTranscriptional profiles of HCMV or Mock infected neonatal and adult were anayzed
IL-12 and type I IFN response of neonatal myeloid DC to human CMV infection.
Specimen part, Time
View SamplesDisruption of N-linked glycosylation has a broad impact on proper glycosylation of nascent glycoproteins in the endoplasmic reticulum, which affect multiple signalling pathways( by changing the stability of membrane proteins or the signalling ability of membrane receptors) and may be responsible of the fibrotic stage associated to CDG type-I.
Fibrotic response in fibroblasts from congenital disorders of glycosylation.
No sample metadata fields
View SamplesWe derived gene set signature for GSEA investigation study from primary cell culture derived from healthy patients. Cells were exposed or not to cytokine for 24H before RNA collection and microarray analysis
Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer.
Specimen part, Treatment
View SamplesThis work uses a time series in order to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to NO3- provision. The experimental approach has been to monitor genome response to NO3- at 3, 6, 9, 12, 15 and 20 min, using ATH1 chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by very fast (within 3 min) gene expression modulation, involving genes/functions needed to prepare plants to use/reduce NO3-. State-space modeling (a machine learning approach) has been used to successfully predict gene behavior in unlearnt conditions.
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate.
Specimen part, Treatment
View SamplesPrevious studies in our laboratory have shown that low folate diet (control diet with 2mg folate/kg, low folate diet with 0.3mg folate/kg) can induce intestinal tumors in BALB/c mice. In addition, we reported that C57Bl/6J mice did not form tumors under the same conditions.
Differential gene expression and methylation in the retinoid/PPARA pathway and of tumor suppressors may modify intestinal tumorigenesis induced by low folate in mice.
Sex, Specimen part, Treatment
View Samples