Iron plays a central role in the regulation of many cellular functions. Dysregulation of its metabolism leads an iron overload situation and iron depletion leads to an inhibition of cell proliferation. Recent reports demonstrated that ICL670 (Novartis) acts as a potent NF-kappa-B inhibitor and improves hematological data in a subset of MDS patients (Cilloni et al, Haematologica, s1: 238, 2007). However, the precise mechanism of anti-cancer effect of ICL670 is still uncertain.
The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1.
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View SamplesHeat shock protein 90 (Hsp90) is essential for the stability and the function of many client proteins, such as ERB2, C-RAF, CDK4, HIF-1 aplha and AKT. Recent reports demonstrated that inhibition of Hsp90 modulates multiple functions required for survival of human cancer, such as myeloma (Mitsiades et al, Blood:107, 1092, 2006), The aim of this study is evaluate the effect of Hsp90 inhibition, and to identify molecular pathways responsible for anti-proliferative effect on ATL cells. For Hsp90 inhibition, Geldanamycin derivates, 17AAG (17-allylamino -17-demethoxygeldanamycin) and 17DMAG (17-(dimethylaminoethylamino) 17-demethoxygeldanamycin) were used in this study. Interleukin 2-independent ATL cell lines (MT-2 and MT-4) and an interleukin 2-dependent ATL cell line (TaY-E10) were incubated, with or without Hsp90 inhibitors.
Anti-proliferative activity of heat shock protein (Hsp) 90 inhibitors via beta-catenin/TCF7L2 pathway in adult T cell leukemia cells.
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View SamplesAdult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform gene expression profiling.
Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells.
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View SamplesAn branched-chain amino acids auxotroph eca39 mutant fission yeast exhibits an unusual adaptive growth phenotype on solid minimal media containing Ile, Leu and Val when other strains are growing nearby.
The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
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View SamplesCumulus cells (CCs) are biologically distinct from other follicular cells and perform specialized roles, transmitting signals within the ovary and supporting oocyte maturation during follicular development. The Affymetrix 3 IVT express protocol was used to prepare cRNA (one-cycle amplification) with a starting concentration of 100 ng of total RNA
Human cumulus cells molecular signature in relation to oocyte nuclear maturity stage.
Specimen part
View SamplesIn humans, the embryonic genome activation (EGA) program is functional by day 3 after fertilization. The 6-8 cell stage embryo (day 3 post-fertilization) starts the process of compaction that leads to the generation of the tightly organized cell mass of the morula and is followed by differentiation of the morula into a blastocyst. The transition from day 3 embryos to day 5 blastocysts is likely to be controlled by many and specific changes in the expression of different genes. We used mRNA amplification technique and compared the transcriptomes of day 3 human embryos and trophectoderm (TE) cells from day 5 human blastocysts to identify transcripts that are differentially expressed during the embryo-to-TE transition and involved in the TE specification.
Transcriptome analysis during human trophectoderm specification suggests new roles of metabolic and epigenetic genes.
Specimen part
View SamplesThe cumulus cells niche that surrounds the oocyte is essential for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. The cells cultured from the human oocyte cumulus niche (hCC) could be used as feeders for the propagation of human pluripotent stem cells in vitro.
Cultured Cells from the Human Oocyte Cumulus Niche Are Efficient Feeders to Propagate Pluripotent Stem Cells.
Specimen part
View SamplesThe first week of human pre-embryo development is characterized by the induction of totipotency and then pluripotency. The understanding of this delicate process will have far reaching implication for in vitro fertilization and regenerative medicine. Human mature MII oocytes and embryonic stem (ES) cells are both able to achieve the feat of cell reprogramming towards pluripotency, either by somatic cell nuclear transfer or by cell fusion, respectively. Comparison of the transcriptome of these two cell types may highlight genes that are involved in pluripotency initiation. Therefore, based on a microarray compendium of 205 samples, produced in our laboratory or from public databases, we compared the gene expression profile of mature MII oocytes and human ES cells (hESC) to that of somatic tissues. We identified a common oocyte/hESC gene expression profile, which included a strong cell cycle signature, a large chromatin remodelling network (TOP2A, DNMT3B, JARID2, SMARCA5, CBX1, CBX5) and 18 different zinc finger transcription factors, including ZNF84. Strikingly, a large set of genes was found to code for proteins involved in the ubiquitination and proteasome pathway. Upon hESC differentiation into embryoid bodies, the transcription of this pathway declines. In vitro, we observed a selective sensitivity of hESC to the inhibition of the activity of the proteasome, resulting in loss of pluripotency and cell growth at doses without any detectable effects on differentiated cells. Taken together, these results suggest that the proteasome pathway may play a role in initiating and maintaining pluripotency during early development and in hESC.
A gene expression signature shared by human mature oocytes and embryonic stem cells.
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View SamplesPluripotent stem cells, which are capable to generate any cell type of the human body, such as human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPS) are a very promising source of cells for regenerative medicine. However, the genesis, the in vitro amplification and the differentiation of these cells still need improvement before clinical use. This study aimed to improve our knowledge on these critical steps in pluripotent stem cell generation. We derived new hESC lines, generated hiPS and compared these cell types with human foreskin fibroblasts and partially reprogrammed fibroblasts.
A gene expression signature shared by human mature oocytes and embryonic stem cells.
Specimen part, Cell line
View SamplesThe trophoblast cell lineage is specified as early as the blastocyst stage, leading to the individualization of trophectoderm from pluripotent cells of the inner cell mass. We used a double in vitro transcription mRNA amplification technique and compared trophectoderm with pluripotent stem cells.
Dissecting the first transcriptional divergence during human embryonic development.
Specimen part
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