Rhabdoid Tumors (RT) are highly aggressive tumors that are frequently localized in the central nervous system (CNS) where they are termed atypical teratoid and rhabdoid tumors (ATRT). We generated conditional Smarcb1-deficient mouse model leads to CNS Smarcb1-deficient tumors.
The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.
Specimen part
View SamplesWe used microarrays to compared gene expression profilings in various tumors of the kidney.
Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic Alterations in Renal Medullary Carcinomas.
Specimen part
View SamplesWe used microarrays to compare gene expression profilings in various SMARCB1-deficient tumors.
Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other SMARCB1-deficient cancers.
Specimen part
View SamplesWe used microarrays to compared gene re-expression of SMARCB1 in I2A SMARCB1-deficient rhabdoid tumor cell line.
High-Throughput Drug Screening Identifies Pazopanib and Clofilium Tosylate as Promising Treatments for Malignant Rhabdoid Tumors.
Specimen part
View SamplesAlpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinsons disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. To gain a better understanding of the consequences of excessive SNCA expression on basal ganglia function, we performed transcriptome analysis of striatal tissue from male Thy1-aSyn-mice and wt littermates. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.
Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons.
Sex, Age, Specimen part
View SamplesCoexpression of alpha-synuclein and p25alpha in an oligodendroglial cell line elicites a degenerative response that relies on aggregation and phosphorylation of alpha-synuclein at Ser129
Prodegenerative IκBα expression in oligodendroglial α-synuclein models of multiple system atrophy.
Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-infected brain: novel analysis of retrospective cases.
Sex, Age, Specimen part
View SamplesMajor depressive disorder (MDD) is a clinically defined entity with little understanding as to the underlying pathological substrate. Biologically, MDD is characterized by disruption of neurotransmitters, especially serotonin and noradrenaline, which are the main targets of antidepressants. We previously demonstrated significant reduction of glial cell number in the cingulate and dorsolateral prefrontal cortical regions. Unfortunately, individuals living with HIV still have very high rates of MDD, despite the fact that mortality rates have fallen sharply with effective antiretroviral treatment. It is possible that in this treatment era, living with chronic HIV infection may result in long-term neuropathological changes that predispose to MDD. For example, it is known that HIV is associated with a range of inflammatory pathologies, neuronal loss, and dendrite-synaptic damage. In HIV, these neurodegenerative changes have been linked to neurocognitive impairments, however it is also possible that these changes potentiate MDD.
Evidence for Alteration of Gene Regulatory Networks through MicroRNAs of the HIV-infected brain: novel analysis of retrospective cases.
Sex, Age, Specimen part
View SamplesA significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at transcriptomic level and compared to patient’s early primary tumours to identify new therapeutic targets associated with endocrine resistance in the metastatic setting.
PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance.
Disease, Disease stage, Treatment
View SamplesThe full complement of molecular pathways contributing to Parkinsons disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and -synuclein toxicity, we investigated a yeast model expressing -synuclein. Polyamines were found to enhance the toxicity of -synuclein, and an unbiased genome-wide screen for modifiers of -synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing -synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis.
Polyamine pathway contributes to the pathogenesis of Parkinson disease.
Sex, Age, Subject
View Samples