Project description:Mice bearing murine A223 SCC tumors were treated with bintrafusp alfa, targeting both TGF-beta and PD-L1, then processed for single-cell sequencing to identify cell population signaling changes that characterize responders to therapy.
Project description:To investigate blood transcriptional changes induced by omalizumab treatment and to determine variations between omalizumab responders and non-responders.
Project description:Endothelial, inflammatory, cellular, interferon gamma and calcineurin inhibitor related genes were analyzed in 10 therapy responders and 6 non responders in chronic active antibody mediated rejection (caABMR) in kidney transplantation.
Project description:Background: Results obtained from our previous study using a label-free quantitation (LF) proteomic approach in which dynamic range compression was used to profile lower abundance proteins, demonstrated few proteins that were differentially abundant within the synovial fluid (SF) when comparing Autologous Chondrocyte Implantation (ACI) responders and non-responders at baseline (1). This study builds upon our previous findings by assessing higher abundance proteins within these SFs; providing a more global proteome analysis from which we can understand more fully the biology underlying ACI success or failure. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics was used to assess SFs from ACI responders (mean Lysholm improvement of 33; n=14) and non-responders (mean Lysholm decrease of 14; n=13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins were investigated using pathway analyses and the iTRAQ proteomic dataset was combined with our published proteomic dataset of dynamically compressed SFs, from which an interactome network model of systemic protein interactions was generated. Results: iTRAQ proteomics has confirmed our previous finding that there is a marked proteome shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥2.0 fold change between Stages I and II in responders and non-responders, respectively) and has highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, that were not found in the LF study; 16 of which were altered at baseline. Two protein abundance changes (Complement C1S subcomponent and Matrix metalloproteinase 3 (MMP3), have been biochemically validated. Combination of the iTRAQ and LF proteomic datasets has generated in-depth SF proteome information that has been used to generate interactome networks representing ACI success or failure, from which functional pathways that are dysregulated in ACI non-responders have been identified. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome have been identified. A holistic overview of the SF proteome in responders and non-responders to ACI has been profiled providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.
Project description:Ustekinumab provides clinical benefit to psoriasis patients, but precise cellular and molecular changes underlying its therapeutic utility are not yet fully understood. To assess differences between ustekinumab responders vs. non responders in modulating specific inflammatory pathways and provide reference data for exploring molecular effects of next-generation interleukin(IL)-17 and IL-23-antagonists in psoriasis.
Project description:The goal of this study was to gain a better understanding of the genetic background of gonadal maturation of the European eel and to use gene expression profiles to identify predictive markers for broodstock selection that can be measured in blood samples. Three-year-old farmed silver female European eels were injected with 20 mg salmon pituitary extract (SPE) once per week and sampled after 4 weekly hormone injections. Four responders (gonadosomatic index > 1.5) and two non-responders (gonadosomatic index < 1.0) were selected for Illumina RNAseq analysis to identify early markers of responsiveness to gonadotropin treatment. Deep-sequencing transcriptome analysis of ovarian samples derived from four responsive and two non-responsive eels after four weekly injections with gonadotropins.
Project description:Analysis of gene-expression changes in treatment responders vs non-responders to two different treatments among subjectrs participating in LiTMUS. Results provide information on pathways that may be involved in the clinical response to Lithium in patients with bipolar disorder.
Project description:As hepatitis B virus is widely spread, WHO recommend vaccination from infancy to reduce acute infection and chronic carriers. However current subunit vaccines are not 100% efficacious and leaves 5-10% persistent non-responders unprotected. To handle large inter-individual variability in immune response after the first Engerix-B vaccination, we employed whole blood early gene expression signatures at day 3 and 7. Immune related pathways are differential expressed in the responders group mostly at day 3 and at day 7 in the non-responders. A notable difference between both groups are significant differential expressed genes at day 0, before vaccination, showing the inter-individual variation. The granulin precursor (GRN) was significant downregulated in responders while upregulated in non-responders. Further absolute granulocytes numbers were significant higher in non-responders. So there is a certain diversity in basic innate immune system.