In this study we investigate the mechanism of drug addiction Overall design: Drug was withdrawn from wt / MAPK1 KO / JUNB KO double drug resistant mel888 (DR Mel888) cells, and gene expression profiling was performed upon drug withdrawal
Cancer drug addiction is relayed by an ERK2-dependent phenotype switch.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing.
Specimen part
View SamplesThe therapeutic landscape of melanoma is rapidly changing. While targeted inhibitors yield significant responses, their clinical benefit is often limited by the early onset of drug resistance. This motivates the pursuit to establish more durable clinical responses, by developing combinatorial therapies. But while potential new combinatorial targets steadily increase in numbers, they cannot possibly all be tested in patients. Similarly, while genetically engineered mouse melanoma models have great merit, they do not capture the enormous genetic diversity and heterogeneity typical in human melanoma. Furthermore, whereas in vitro studies have many advantages, they lack the presence of micro-environmental factors, which can have a profound impact on tumor progression and therapy response. This prompted us to develop an in vivo model for human melanoma that allows for studying the dynamics of tumor progression and drug response, with concurrent evaluation and optimization of new treatment regimens. Here, we present a collection of patient-derived xenografts (PDX), derived from BRAFV600E, NRASQ61 or BRAFWT/NRASWT melanoma metastases. The BRAFV600E PDX melanomas were acquired both prior to treatment with the BRAF inhibitor vemurafenib and after resistance had occurred, including six matched pairs. We find that PDX resemble their human donors’ melanomas regarding biomarkers, chromosomal aberrations, RNA expression profiles, mutational spectrum and targeted drug resistance patterns. Mutations, previously identified to cause resistance to BRAF inhibitors, are captured in PDX derived from resistant melanomThis melanoma PDX platform represents a comprehensive public resource to study both fundamental and translational aspects of melanoma progression and treatment in a physiologically relevant setting. Overall design: RNA sequencing of 4 melanoma PDX samples to validate the effects of a structural variant on BRAF mRNA in BRAF inhibitor resistant melanoma.
BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts.
No sample metadata fields
View SamplesHere we show that biotin-labelled miR-34a can be loaded to AGO2, and AGO2 immunoprecipitation can pulldown biotinylated miR-34a (Bio-miR pulldown). RNA-sequencing (RNA-seq) of the Bio-miR pulldown RNAs efficiently identified miR-34a mRNA targets, which could be verified with luciferase assays. In contrast to the approach of Bio-miR pulldown, RNA-seq of miR-34a overexpression samples had limited value in identifying direct targets of miR-34a. It seems that pulldown of 30 -Biotin-tagged miRNA can identify bona fide microRNA targets at least for miR34a. Overall design: biotin-labelled miR-34a pulldown and RNA sequencing of miR-34a overexpression samples
Comparing two approaches of miR-34a target identification, biotinylated-miRNA pulldown vs miRNA overexpression.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesDisseminated prostate cancer cells colonize the skeleton to progress into macroscopic lesions only if they successfully adapt to the bone microenvironment. We previously reported that the ability of prostate cancer cells to generate skeletal tumors in animal models correlated with the expression of the alpha-receptor for Platelet-Derived Growth Factor (PDGFRa). In this study we aimed to identify PDGFRa-regulated genes responsible for the acquisition of a bone-metastatic prostate phenotype. We performed genome-wide expression comparative analyses of human prostate cancer cell lines that differ for PDGFRa expression and propensity to establish tumors in the skeleton of animal models. We investigated the genes that were differentially regulated in the highly bone-metastatic PC3-ML cells and their low-metastatic counterpart PC3-N cells, and the genes differentially regulated between PC3-N and PC3-N with overexpression of PDGFRa (PC3NRa). We have previously shown that DU-145 cells lack PDGFRa and fail to survive longer than three days as disseminated tumor cells after homing to the mouse bone marrow. Interestingly, and in contrast to PC3-N cells, the exogenous expression of PDGFRa did not promote metastatic bone-tropism of DU-145 cells in our model. Thus, we examined the genes that were differentially regulated between DU-145 and DU-145(Ra) and excluded them from our candidate genes. Finally, to refine our findings and compensate for PC3 and DU-145 genetic disparity, we performed a comparative analysis of the genes differentially regulated between two bone metastatic single-cell progenies that were derived from PC3-ML cells.
Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features.
Cell line
View SamplesResponse of A549 cells treated with Aspergillus fumigatus wild type germinating conidia (WT_GC) or PrtT protease deficient mutant conidia (PrtT-GC) or inert acrylic 2-4 micron beads (Beads) for 8h
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesResponse of A549 cells treated with Aspergillus fumigatus wild type culture filtrate (WT-CF) or PrtT protease deficient mutant culture filtrate (PrtT-CF) for 8h
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesResponse of A549 cells treated with Aspergillus fumigatus germinating conidia (WT-GC) or culture filtrate (WT-CF) for 8h
PrtT-regulated proteins secreted by Aspergillus fumigatus activate MAPK signaling in exposed A549 lung cells leading to necrotic cell death.
Specimen part, Cell line, Treatment
View SamplesMicroarrays were used to examine gene expression changes that may be present in the fallopian tube epithelium of morphologically normal BRCA1 mutation positive and negative subjects. Fallopian tube epithelia has been implicated as an early point of origin for serous carcninoma. By examining the early events present in the microenvironment of this tissue between BRCA1 mutation carriers and non-carriers, we hoped to elucidate mechanisms that may lead to the development of epithelial ovarian cancer.
Identification of abrogated pathways in fallopian tube epithelium from BRCA1 mutation carriers.
Specimen part
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