Project description:Protein microarray was used to identify proteins with elevated interactions with serum autoantibodies in a responding patient with rhabdomyosarcoma before and after multiple doses of HER2 CAR T cell therapy. Elevated signals were observed for multiple proteins interacting with serum autoantibodies following multiple doses of HER2-CAR T cell treatment when compared to pre-treatment serum.
Project description:Introduction: Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH), however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signalling pathways with the risk for BPD or PH. Methods: We prospectively enrolled infants with gestational age <34 weeks gestation and collected blood samples during their first week of life. BPD and PH were assessed at 36 weeks postmenstrual age. Samples were assayed for each of the 1121 peptides included in the SOMAscanTM technology, with subsequent pathway analysis. Results: Of 102 study infants, 82 had BPD and 13 had PH. Multiple angiogenic proteins (PF-4, VEGF121, ANG-1, BMP10, HGF, ANG2) were associated with the subsequent diagnosis of BPD, and FGF-19, PF-4, CTAP-III and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH. Conclusion: We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research.
Project description:Established that 11 human anti-Plasmodium vivax Duffy Binding protein II monoclonal antibodies are not cross reactive with other plasmodium antigens as represented by PfPv500.1 array.
Project description:Aberrant secretion of cytokines contributes to pathogenesis of leukemia and is considered a prognostic signature for recurrence of AML. We asked whether molecular targeting of TIFA can perturb NF-κB-dependent secretion of leukemic cytokines and attain better therapeutic efficacy. We performed cytokine antibody array to profile cytokines secreted by U937 cells in response to TIFA dominant-negative fragments and cytarabine treatment.
Project description:The identification of target antigens recognized by monoclonal antibodies that have been derived from oligoclonal band IgG of CSF samples from multiple sclerosis patients.
Project description:Ewing Sarcoma is caused by a pathognomonic genomic translocation that places an N-terminal EWSR1 gene in approximation with one of several ETS genes (typically FLI1). This aberration, in turn, alters the transcriptional regulation of more than five hundred genes and perturbs a number of critical pathways that promote oncogenesis, cell growth, invasion, and metastasis. Among them, translocation-mediated up-regulation of the insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) are of particular importance since they work in concert to facilitate IGF-1R expression and ligand-induced activation, respectively, of proven importance in ES transformation. When used as a single agent in Ewing sarcoma therapy, IGF-1R or mTOR inhibition leads to rapid counter-regulatory effects that blunt the intended therapeutic purpose. Therefore, identify new mechanisms of resistance that are used by Ewing sarcoma to evade cell death to single-agent mTOR inhibition might suggest a number of therapeutic combinations that could improve its clinical activity.
Project description:Ewing Sarcoma is caused by a pathognomonic genomic translocation that places an N-terminal EWSR1 gene in approximation with one of several ETS genes (typically FLI1). This aberration, in turn, alters the transcriptional regulation of more than five hundred genes and perturbs a number of critical pathways that promote oncogenesis, cell growth, invasion, and metastasis. Among them, translocation-mediated up-regulation of the insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) are of particular importance since they work in concert to facilitate IGF-1R expression and ligand-induced activation, respectively, of proven importance in ES transformation. When used as a single agent in Ewing sarcoma therapy, IGF-1R or mTOR inhibition leads to rapid counter-regulatory effects that blunt the intended therapeutic purpose. Therefore, identify new mechanisms of resistance that are used by Ewing sarcoma to evade cell death to single-agent IGF-1R inhibition might suggest a number of therapeutic combinations that could improve its clinical activity.
Project description:Invasive lobular carcinoma (ILC) is the second most frequent histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for 5-15% of all breast cancers. Although clinical outcomes of ILC and IDC seem similar, the molecular processes underlying ILC are still largely unknown. To explore this, we have performed a comprehensive proteomics analysis of a large ILC patient cohort. These data are generated in the context of the RATHER consortium (http://www.ratherproject.com/)