Early chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival. We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa. As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq). Overall design: Tumour biposies from 6 patients were taken before and after treatment with combined ADT and docetaxcel for 6 weeks
Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer.
Specimen part, Subject, Time
View SamplesAndrogen ablation therapy (AAT) is standard treatment for locally-advanced/metastatic prostate cancer (PCa). Many patients develop castration-resistance (CRPCa) after ~2-3 years, with a poor prognosis. The molecular mechanisms underlying CRPCa progression are unclear. mRNA-Seq was performed on tumours from 7 patients with locally-advanced/metastatic PCa before and ~22 weeks after AAT initiation. Differentially regulated genes were identified in treatment pairs. Overall design: Tumour biopsies from 7 patients were taken before and after AAT treatment
Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy.
Specimen part, Subject, Time
View SamplesBacteria respond to osmotic stress by a substantial increase in the intracellular osmolality, adjusting their cell turgor for altered growth conditions. Using E. coli as a model organism we demonstrate here that bacterial responses to hyperosmotic stress specifically depend on the nature of osmoticum used. We show that increasing acute hyperosmotic NaCl stress above ~1.0 Os kg-1 causes a dose-dependent K+ leak from the cell, resulting in a substantial decrease in cytosolic K+ content and a concurrent accumulation of Na+ in the cell. At the same time, isotonic sucrose or mannitol treatment (non-ionic osmotica) results in a gradual increase of the net K+ uptake. Ion flux data is consistent with growth experiments showing that bacterial growth is impaired by NaCl at the concentration resulting in a switch from net K+ uptake to efflux. Microarray experiments reveal that about 40% of up-regulated genes shared no similarity in their responses to NaCl and sucrose treatment, further suggesting specificity of osmotic adjustment in E. coli to ionic- and non-ionic osmotica The observed differences are explained by the specificity of the stress-induced changes in the membrane potential of bacterial cells highlighting the importance of voltage-gated K+ transporters for bacterial adaptation to hyperosmotic stress.
Ion transport and osmotic adjustment in Escherichia coli in response to ionic and non-ionic osmotica.
No sample metadata fields
View SamplesAcute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.
Sex, Specimen part, Race
View SamplesWomen suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. This study used a mouse model to dissociate these factors and found no differences in peripheral afferent neurons or in the spinal cord immune response to neuropathic injury. However, it did identify potential sexual dimorphisms in peripheral adaptive immune responses. Overall design: RNA-seq of naïve FACS-purified DRG neurons and MACS-purified DRG neurons after partial sciatic nerve ligation (day 8): comparison of male versus female samples
Sex differences in peripheral not central immune responses to pain-inducing injury.
Sex, Specimen part, Cell line, Subject
View SamplesRenal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Alteration of human blood cell transcriptome in uremia.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesAcute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
No sample metadata fields
View SamplesDuring mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling.
Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks.
No sample metadata fields
View SamplesTo assess in vitro derived podocytes, we examined the transcriptional changes during human podocyte development and applied that knowledge to pinpoint strengths and limitations of hESC-derived podocytes. Overall design: We performed transcriptionaling profiling of kidney organoids and organoid-derived MAFB-eGFP+ podocytes at various differentiation time points.
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Subject
View SamplesIn order to characterize and benchmark the podocytes-like cells generated through human ES cell differentiation, we generated transcriptional profiles of renal corpuscles from embryonic human kidneys using RNA-Seq. To compare, we also performed RNA-Seq of human immortalized podocyte cell lines before and after thermoswitch. Overall design: We performed RNA-Seq of poly-A selected RNA from hESC-derived kidney organoids, organoid-derived MAFB-eGFP+ podocytes at different time points, and human immortalized podocytes.
In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes.
Specimen part, Subject
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