Bendamustine is a commonly-used drug to treat CLL patients. Because drug-responses among the patients are heterogeneous, we wanted to find candidate genes to predict sensitivity to the compound
No associated publication
Specimen part, Disease, Disease stage
View SamplesAcadesine is a nucleoside analogue with known antileukemic effects in different neoplasms. We investigated the activity of acadesine ne exerts a cytotoxic effect in MCL and synergizes with rituximab supporting clinical examination of this strategy for MCL patients
Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma.
Cell line, Treatment
View SamplesNuclear lamin B1 constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of lamin B1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion; in addition we observed an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrate that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that lamin B1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S-phase due to activation of Chk1 and telomere attrition. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.
Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories.
Cell line
View SamplesPhosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL.
Dual PI3K/mTOR inhibition is required to effectively impair microenvironment survival signals in mantle cell lymphoma.
Specimen part, Disease, Disease stage, Treatment
View SamplesCombination of GSI with fludarabine has a synergistic antileukemic effect in primary NOTCH1-mutated CLL cells
The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells.
Specimen part
View Samplesmmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as operationally tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter fingerprint of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for ?d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+CD25+ T-cells and Vd1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.
Multiparameter immune profiling of operational tolerance in liver transplantation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesWe analysed the RNA profile of IPSC-derived dopaminergic neurons from idiophatic and genetic form (LRRK2) of Parkinsons disease (PD). Both, idiopathic and genetic form of the disease show similar expression alterations and were merged in one whole PD group. We found 437 differentially expressed genes (DEGs) in the PD group as a whole. Up-regulated DEGs (n=254) encompassed genes involved in neural functions and transcription factor functions whereas down-regulated DEGs (n=183) affected basic homeostasis. These data point towards the presence of gene - and also protein - expression changes in DAn from PD patients which co-occur simultaneously along with DNA methylation changes.
Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson's disease patients.
Sex, Specimen part, Disease, Disease stage
View SamplesThe aim of this study was to perform a genome-wide transcriptional analysis (mRNA + microRNA) during in vitro mucociliary differentiation of primary human basal stem/progenitors cells (BSCs) cultured at the air-liquid interface (ALI) system.
No associated publication
Sex, Age, Specimen part, Subject, Time
View SamplesHepatic fibrosis, the wound-healing response to repeated liver injury, ultimately leads to cirrhosis. There is an urgent need to develop effective antifibrotic therapies. Ghrelin (encoded by Ghrl) is an orexigenic hormone that has pleiotrophic functions including protection against cell death1. Here we investigate whether ghrelin modulates liver fibrosis and protects from acute liver injury. Recombinant ghrelin reduced the fibrogenic response to prolonged bile duct ligation in rats. This effect was associated with decreased liver injury and myofibroblast accumulation as well as attenuation of the altered gene expression profile. Ghrelin also reduced fibrogenic properties in cultured hepatic stellate cells. Moreover, Ghrl-/- mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. Ghrelin also protected rat livers from acute liver injury and reduced the extent of oxidative stress and the inflammatory response. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis and hepatic expression of the ghrelin gene correlated with expression of fibrogenic genes. Finally, in patients with chronic hepatitis C, single nucleotide polymorphisms of the ghrelin gene (-994CT and 604GA) influenced the progression of liver fibrosis. We conclude that ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy.
Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans.
No sample metadata fields
View Samples