4f965bf7-dcdc-48d5-983a-dff00cc26b95 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006369 | EGA |
REPOSITORIES: EGA
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Project description:Purpose: DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown.
Patients and Methods: We performed whole genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 hours and 6 weeks) surgery. In a separate cohort (n=189) we identified the presence of ctDNA TP53 mutations in pre-operative plasma in a retrospective cohort, and determined its association with biochemical- and metastasis-free survival.
Results: Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2-4.8, p = 0.014)). Conclusions: CtDNA is uncommonly detected in localised prostate cancer but its presence portends more rapidly progressive disease.
| EGAS00001004636 | EGA
Project description:Cellular Thermal Shift Assay (CETSA) to interrogate interactions between Kalihinol analog Med6-189 and Plasmodium falciparum proteins.
2022-11-08 | MSV000090667 | MassIVE
Project description:The proteins in an MCF-7 cell line were probed for tamoxifen (TAM) and n-desmethyl tamoxifen (NDT) induced stability changes using the Stability of Proteins from Rates of Oxidation (SPROX) technique in combination with two different quantitative proteomics strategies. Together the SILAC- and iTRAQ-SPROX experiments described here enabled over 1000 proteins to be assayed for TAM- and NDT- induced protein stability changes, and a total of 163 and 200 protein hits were identified in the TAM and NDT studies, respectively. A subset of high confidence hits were assessed for experimental links to the ER using a STRING analysis. TAM was shown to induce stabilization of Y-box binding protein 1 (YBX1), a protein recently shown to bind the estrogen receptor. TAM was shown to directly interact with purified recombinant YBX1 with Pulse Proteolysis (PP). These results support YBX1 as a direct protein target of TAM. Proteins with altered expression levels with TAM and NDT treatment were identified with SILAC quantitation. In total, 799 and 671 proteins were probed for TAM- and NDT- induced expression changes, respectively, and 49 and 30 proteins had altered expression. This work also involved the use of a novel data analysis strategy to identify protein targets of ligands using the SPROX technique.
2019-11-08 | PXD006747 | Pride
Project description:The proteins in an MCF-7 cell line were probed for tamoxifen (TAM) and n-desmethyl tamoxifen (NDT) induced stability changes using the Stability of Proteins from Rates of Oxidation (SPROX) technique in combination with two different quantitative proteomics strategies. Together the SILAC- and iTRAQ-SPROX experiments described here enabled over 1000 proteins to be assayed for TAM- and NDT- induced protein stability changes, and a total of 163 and 200 protein hits were identified in the TAM and NDT studies, respectively. A subset of high confidence hits were assessed for experimental links to the ER using a STRING analysis. TAM was shown to induce stabilization of Y-box binding protein 1 (YBX1), a protein recently shown to bind the estrogen receptor. TAM was shown to directly interact with purified recombinant YBX1 with Pulse Proteolysis (PP). These results support YBX1 as a direct protein target of TAM. Proteins with altered expression levels with TAM and NDT treatment were identified with SILAC quantitation. In total, 799 and 671 proteins were probed for TAM- and NDT- induced expression changes, respectively, and 49 and 30 proteins had altered expression. This work also involved the use of a novel data analysis strategy to identify protein targets of ligands using the SPROX technique.
2019-11-08 | PXD006732 | Pride
Project description:This study aims to compared ctDNA methylation status induced by ionizing to different ograns. SD rats were irradiated with local radaition to brain, lung or skin. Serum was collected and subjiected to ctDNA extraction. ctDNA were then treated by methylation-sensive bisulfite and sequencing.
2021-12-23 | GSE163763 | GEO
Project description:The systemic delivery of tamoxifen (Tam) to activate inducible CreERT2-loxP transgenic mouse systems is now widely used in neuroscience studies. This critical technological advancement allows temporal control of DNA-cre recombination, avoidance of embryonically lethal phenotypes, and minimization of residual cell labeling encountered in constitutively active drivers. Despite its advantages, the use of Tam has the potential to cause long-lasting, uncharacterized side effects on the transcriptome and epigenome in the CNS, given its mixed estrogen receptor (ER) agonist/antagonist actions. With the welcome focus on including both sexes in biomedical studies and efforts to understand sex differences, Tam administration could also cause sexually divergent responses that would confound studies. To examine these issues, epigenetic and transcriptomic profiles were compared in C57BL/6J female and male hippocampus, cortex, and retina 1 month after a five- day Tam treatment typical for cre induction, or vehicle control (sunflower seed oil). Cytosine methylation and hydroxymethylation levels, in both CG and non-CG contexts, were unchanged as determined by oxidative bisulfite sequencing. Long-lasting Tam transcriptomic effects were also not evident/minimal. Furthermore, there is no evidence of sexually divergent responses with Tam administration and Tam did not alter sex differences evident in controls. Combined with recently reported data that Tam alone does not cause long-lasting changes in behavior and neurogenesis, our findings provide confidence that Tam can be used as a cre-recombinase inducer without introducing significant confounds in transcriptomic and epigenomic neuroscience studies, particularly those focused on genomic and transcriptomic aspects of the aging brain.
2019-08-13 | GSE135752 | GEO
Project description:The systemic delivery of tamoxifen (Tam) to activate inducible CreERT2-loxP transgenic mouse systems is now widely used in neuroscience studies. This critical technological advancement allows temporal control of DNA-cre recombination, avoidance of embryonically lethal phenotypes, and minimization of residual cell labeling encountered in constitutively active drivers. Despite its advantages, the use of Tam has the potential to cause long-lasting, uncharacterized side effects on the transcriptome and epigenome in the CNS, given its mixed estrogen receptor (ER) agonist/antagonist actions. With the welcome focus on including both sexes in biomedical studies and efforts to understand sex differences, Tam administration could also cause sexually divergent responses that would confound studies. To examine these issues, epigenetic and transcriptomic profiles were compared in C57BL/6J female and male hippocampus, cortex, and retina 1 month after a five- day Tam treatment typical for cre induction, or vehicle control (sunflower seed oil). Cytosine methylation and hydroxymethylation levels, in both CG and non-CG contexts, were unchanged as determined by oxidative bisulfite sequencing. Long-lasting Tam transcriptomic effects were also not evident/minimal. Furthermore, there is no evidence of sexually divergent responses with Tam administration and Tam did not alter sex differences evident in controls. Combined with recently reported data that Tam alone does not cause long-lasting changes in behavior and neurogenesis, our findings provide confidence that Tam can be used as a cre-recombinase inducer without introducing significant confounds in transcriptomic and epigenomic neuroscience studies, particularly those focused on genomic and transcriptomic aspects of the aging brain.
2019-08-01 | GSE135208 | GEO
Project description:Circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients are still not well-defined. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high PBatial and temporal heterogeneity. Though ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based in total ctDNA quantification, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.
2023-12-18 | GSE244989 | GEO
Project description:Glioblastomas (GBMs) are highly invasive brain tumors replete with brain- and blood-derived macrophages, collectively known as tumor-associated macrophages (TAMs). Targeting TAMs has been proposed as a therapeutic strategy but has thus far yielded limited clinical success in slowing GBM progression, due in part to an incomplete understanding of TAM function in GBM. Here, by using an engineered hyaluronic acid-based 3D invasion platform, patient-derived GBM cells, and multi-omics analysis of GBM tumor microenvironments, we show that M2-polarized macrophages stimulate GBM stem cell (GSC) mesenchymal transition and invasion. We identify TAM-derived transforming growth factor beta induced (TGFβI/BIGH3) as a pro-tumorigenic factor in the GBM microenvironment. In GBM patients, BIGH3 mRNA expression correlates with poor patient prognosis and is highest in the most aggressive GBM molecular subtype. Inhibiting TAM-derived BIGH3 signaling with a blocking antibody or small molecule inhibitor suppresses GSC invasion. Our work highlights the utility of 3D in vitro tumor microenvironment platforms to investigate TAM-cancer cell crosstalk and offers new insights into TAM function to guide novel TAM-targeting therapies.
2023-12-21 | GSE251777 | GEO