Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA115905 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background: Development of target specific therapeutics greatly benefits from simultaneous identification of biomarkers to determine aspects of bioactivity, drug safety and efficacy or even treatment outcome. This is particularly important when targeting pleiotropic factors such as the TGFbeta system. TGFbeta has become a prime target for cancer therapeutics since inhibition of TGFbeta signaling simultaneously attacks the tumor and its microenvironment. Methods: Here we introduce blood transcriptomics followed by a defined set of validation assays as a promising approach to identify novel biomarkers for monitoring TGFbeta therapy. Findings: Our initial genome-wide analysis of transcription in peripheral blood revealed 12 candidate genes specifically regulated in peripheral blood by the TGFbeta receptor I kinase inhibitor LY2109761. In subsequent in vitro and in vivo molecular and immunological analyses, the combined monitoring of gene regulation of three genes, namely TMEPAI, OCIAD2, and SMAD7 was established as novel biomarkers for anti-TGFbeta based therapies. Interpretation: Overall, the proposed algorithm of biomarker identification is easily adapted towards other drug candidates for which gene regulation can be established in peripheral blood. CD4+ T cells were serum-deprived for 12 hours followed by 8 hours incubation with the indicated compounds, total of 22 samples.
2010-07-20 | E-GEOD-15468 | biostudies-arrayexpress
Project description:Background: Development of target specific therapeutics greatly benefits from simultaneous identification of biomarkers to determine aspects of bioactivity, drug safety and efficacy or even treatment outcome. This is particularly important when targeting pleiotropic factors such as the TGFbeta system. TGFbeta has become a prime target for cancer therapeutics since inhibition of TGFbeta signaling simultaneously attacks the tumor and its microenvironment. Methods: Here we introduce blood transcriptomics followed by a defined set of validation assays as a promising approach to identify novel biomarkers for monitoring TGFbeta therapy. Findings: Our initial genome-wide analysis of transcription in peripheral blood revealed 12 candidate genes specifically regulated in peripheral blood by the TGFbeta receptor I kinase inhibitor LY2109761. In subsequent in vitro and in vivo molecular and immunological analyses, the combined monitoring of gene regulation of three genes, namely TMEPAI, OCIAD2, and SMAD7 was established as novel biomarkers for anti-TGFbeta based therapies. Interpretation: Overall, the proposed algorithm of biomarker identification is easily adapted towards other drug candidates for which gene regulation can be established in peripheral blood.
2010-07-20 | GSE15468 | GEO
Project description:We aimed to identify peripheral blood biomarkers that predict the response of advanced HCC to anti-PD-1 therapy.
2022-08-03 | GSE202145 | GEO
Project description:Treatment of latent tuberculosis infection (LTBI) in individuals at greatest risk for reactivation is an important component of TB control and elimination strategies. However, blood biomarkers for monitoring LTBI treatment have not been identified. We performed a microarray analysis to identify the gene expression profile in whole blood from healthy individuals reactive to the tuberculin skin test (TST) with/without a positive in-house interferon-γ release assay (IGRA) before and after isoniazid (INH) prophylactic therapy.
2018-11-22 | GSE122837 | GEO
Project description:In this study we wanted to identify baseline predictors of successful anti-TNF and vedolizumab therapy in patients with inflammatory bowel disease (based on tissue transcriptomics and CD4/CD14 transcriptomics)
2023-10-31 | E-MTAB-7914 | biostudies-arrayexpress
Project description:About 40% IBD patients treated with anti-TNF antibodies do not respond to therapy. Baseline biomarkers of response are therefore of interest. By combining computational deconvolution of gene expression and meta-analysis approaches we identified cellular biomarkers in tissue (validated in 2 cohorts by IHC of biopsies), and investigated associated gene biomarkers in blood. This dataset provides data from the validation cohort III (blood).
2018-02-01 | GSE107865 | GEO
Project description:Systemic mastocytosis is a heterogeneous group of mast cell-driven diseases, diagnosed by bone marrow sampling. However, there are a limited number of available blood disease biomarkers. We performed a single-cell transcriptomics screen alongside a plasma proteomics screen to identify such potential biomarkers.
2023-02-27 | GSE222830 | GEO
Project description:This trial studies the monitoring of therapy and progression by collecting blood, urine, and stool from participants with colorectal cancer that has spread to other places in the body or cannot be removed by surgery. Studying samples of blood, urine, and stool from participants with colorectal cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.
| 2275883 | ecrin-mdr-crc
Project description:Large-scale immune monitoring is becoming routinely used in clinical trials to identify determinants of treatment responsiveness, particularly to immunotherapies. Flow cytometry remains one of the most versatile and high throughput approaches for single-cell analysis; however, manual interpretation of multidimensional data poses a challenge to capture full cellular diversity and provide reproducible results. We present FlowCT, a semi-automated workspace empowered to analyze large datasets that includes pre-processing, normalization, multiple dimensionality reduction techniques, automated clustering and predictive modeling tools. As a proof of concept, we used FlowCT to compare the T cell compartment in bone marrow (BM) vs peripheral blood (PB) of patients with smoldering multiple myeloma (MM); identify minimally-invasive immune biomarkers of progression from smoldering to active MM; define prognostic T cell subsets in the BM of patients with active MM after treatment intensification; and assess the longitudinal effect of maintenance therapy in BM T cells. A total of 354 samples were analyzed and immune signatures predictive of malignant transformation in 150 smoldering MM patients (hazard ratio [HR]: 1.7; P <.001), and of progression-free (HR: 4.09; P <.0001) and overall survival (HR: 3.12; P =.047) in 100 active MM patients, were identified. New data also emerged about stem cell memory T cells, the concordance between immune profiles in BM vs PB and the immunomodulatory effect of maintenance therapy. FlowCT is a new open-source computational approach that can be readily implemented by research laboratories to perform quality-control, analyze high-dimensional data, unveil cellular diversity and objectively identify biomarkers in large immune monitoring studies.
2021-09-26 | GSE166711 | GEO
Project description:B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). We describe the case of a MM patient, enrolled in the CARTITUDE-1 trial (NCT03548207), who developed a progressive movement disorder with features of parkinsonism approximately three months after BCMA-targeted ciltacabtagene autoleucel CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We demonstrate BCMA expression on neurons and astrocytes in the basal ganglia of the patient. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting this may be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade ≥3 parkinsonism on the phase 2 cilta-cel trial and of grade 3 parkinsonism in the idecabtagene vicleucel (ide-cel) package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies.
2021-08-27 | GSE182527 | GEO