Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant CNS neoplasm whichprimarily occurs in children under three years of age. Due to poor outcomes with intense and toxicmultimodality treatment, new therapies are urgently needed. Histone deacetylase inhibitors (HDIs)have been evaluated as novel agents for multiple malignancies and have been shown to function asradiosensitizers. They act as epigenetic modifiers and lead to re-expression of inappropriatelyrepressed genes, proteins, and cellular functions. Due to the underlying chromatin remodeling genemutation in ATRT, HDIs are ideal candidates for therapeutic evaluation. To evaluate the role of HDIsagainst ATRT in vitro, we assessed the effect of drug treatment on proliferation, apoptosis, and geneexpression. Additionally, we examined HDI pretreatment as a radiosensitization strategy for ATRT.MTS and clonogenic assays demonstrated that HDI treatment significantly reduces the proliferativecapacity of BT-12 and BT-16 ATRT cells. Also, the HDI SNDX-275 was able to induce apoptosis in bothcell lines and induced p21Waf1/Cip1 protein expression as measured by Western blot. Evaluation ofdifferential gene expression by microarray and pathway analysis after HDI treatment demonstratedalterations of several key ATRT cellular functions. Finally, we showed that HDI pretreatmenteffectively potentiates the effect of ionizing radiation on ATRT cells as measured by clonogenic assay.These findings suggest that the addition of HDIs to ATRT therapy may prove beneficial, especiallywhen administered in combination with current treatment modalities such as radiation.
Histone deacetylase inhibition decreases proliferation and potentiates the effect of ionizing radiation in atypical teratoid/rhabdoid tumor cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.
Sex, Specimen part, Treatment, Time
View SamplesAs a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 months. We found that most transcriptional changes occur at 1 and 3 months after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 months. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. This data suggests that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.
Sex, Specimen part, Treatment, Time
View SamplesOur findings demonstrate that CDCP1 is a novel modulator of HER2 signalling, and a biomarker for the stratification of breast cancer patients with poor prognosis
Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer.
Cell line
View SamplesThe goal of this study was to identify potential genes regulated by ERG
Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
No sample metadata fields
View SamplesWe have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries.
Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation.
Sex, Age, Specimen part, Subject
View SamplesRecent data from our group, demonstrate that infusion of myelin oligodendrocyte glycoprotein (MOG35-55) peptide, leads to induction of MOG35-55-specific Tregs and subsequent suppression of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis. Amelioration of EAE was accompanied by reduced MOG-specific Th1 and Th17 responses in the draining lymph nodes (dLNs). Phenotypic analysis of the dLNs of MOG-infused mice revealed a significant Treg-mediated reduction in the recruitment of 7AAD-CD3-CD19-CD11c+CD11bhighGr-1+ iDCs compared to non-infused control immunized mice. Focusing on the delineation of novel molecules/genes that are involved in the MOG-specific Treg-mediated suppression of autoimmune responses, we have isolated highly purified iDCs from MOG infused and non-infused control immunized mice.
De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.
Sex, Specimen part
View Sampleswe evaluated the mechanism behind NOTCH activation in prostate cancer
Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence.
Specimen part
View SamplesWe performed a whole-transcriptome analysis of the peripheral blood of untreated patients with stage 1 PD (HoehnYahr scale).
Involvement of endocytosis and alternative splicing in the formation of the pathological process in the early stages of Parkinson's disease.
Specimen part, Disease
View SamplesThe in vitro directed differentiation of pluripotent stem cells (PSCs) through stimulation of developmental signaling pathways can generate mature somatic cell types for basic laboratory studies or regenerative therapies.
Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification.
Treatment
View Samples