Project description:Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that AR-directed antisense oligonucleotides (AR-ASO) block 5-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduced xenograft tumor burden. RPPA analysis was performed to elucidate how AR signaling regulates cellular programs. To gain a preliminary understanding of the short-term pharmacodynamic effects of AR suppression, a group of JN-DSRCT xenografts was collected 10 days into their AR-ASO treatment for analysis by RPPA to assess early compensatory pharmacodynamic changes. Its blockade has long been of interest in managing prostate cancer, where a compensatory increase in AKT signaling has been reported following AR inhibition. Therefore, these results collectively validate another proof of concept of AR-based antisense activity in DSRCT and suggest a clinical path forward since the AR-ASO (AZD5312) was safe, and often effective, in PC patients (NCT03300505). Our findings have immediate clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.
Project description:We used SOMAscan to measure >1300 analytes in sera from healthy controls and patients with sJIA, MAS, sJIA-LD and other related diseases.
Project description:RPL22 expression is lost is ~30% of MSI-high endometrial cancers, and the consequences of RPL22 loss are still unknown. The purpose of this study was to determine the consequences of RPL22 loss in both the tumor and immune microenvironment of MSI-high endometrial cancers. We determined that the number of CD8+ T cells in RPL22 negative tumors is significantly lower than in RPL22 positive tumors and that beta-2-microglobulin protein is significantly reduced in RPL22 negative tumors.
Project description:Combining variant antigens into a multivalent vaccine is a traditional approach used to provide broad coverage against antigenically variable pathogens, such as polio, human papilloma and influenza viruses. However, strategies for increasing the breadth of antibody coverage beyond the vaccine are not well understood, but may provide more anticipatory protection. Influenza virus hemagglutinin (HA) is a prototypic variant antigen. Vaccines that induce HA-specific neutralizing antibodies lose efficacy as amino acid substitutions accumulate in neutralizing epitopes during influenza virus evolution. Here we studied the effect of a potent combination adjuvant (CpG/MPLA/squalene-in-water emulsion) on the breadth and maturation of the antibody response to a representative variant of HA subtypes H1, H5 and H7. Using HA protein microarrays and antigen-specific B cell labelling, we show when administered individually, each HA elicits a cross-reactive antibody profile for multiple variants within the same subtype and other closely-related subtypes (homosubtypic and heterosubtypic cross-reactivity, respectively). Despite a capacity for each subtype to induce heterosubtypic cross-reactivity, broader coverage was elicited by simply combining the subtypes into a multivalent vaccine. Importantly, multiplexing did not compromise antibody avidity or affinity maturation to the individual HA constituents. The use of adjuvants to increase the breadth of antibody coverage beyond the vaccine antigens may help future-proof vaccines against newly-emerging variants.
Project description:To analyze expression of inflammatory cytokines in Exhaled Breath Condensates from pediatric patients with sickle cell disease, asthma, sickle cell disease and asthma, and controls
Project description:we evaluated cytokine profiling of bone marrow serum samples in AML patients and healthy controls. Protein expression profiling of serum from 9 AML patients and 5 healthy controls was obtained using biotinylated antibody chip. Total 507 cytokines and growth factors were analyzed. Compared with healthy people, AML patients expressed 31 signature proteins, among which, 27 were found significantly higher expressed and 4 proteins were lower.
Project description:The aim of the study was to determine the epitope targeted by four different HumAbs and the cross-reactivity to linear peptide epitopes of 10 different Neisserial Heparin Binding Antigen (NHBA) variants. the HumAbs were diluted at 1:60 and incubated on a custom PepStar Peptide Microarray platform printed with 561 different peptides.
Project description:The aim of the study was to determine the epitope targeted by four different HumAbs and the cross-reactivity to linear peptide epitopes of 5 different Neisserial adesin A (NadA) variants. the HumAbs were diluted at 1:200 and incubated on a custom PepStar Peptide Microarray platform printed with 348 different peptides.
Project description:The aim of the study was to determine the epitope targeted by 5 different HumAbs and the cross-reactivity to linear peptide epitopes of 12 different factor H binding protein (fHbp) variants. The HumAbs were diluted at 1:200 and incubated on a custom PepStar Peptide Microarray platform printed with 363 different peptides.
Project description:The aim of the study was to determine the epitope targeted by a panel of Human Fabs. Fabs were diluted at 1:50 and incubated on a non-commercial Protein Microarray platform printed with fHbp, NHBA and NadA specific recombinant protein fragments and full length fHbp, NHBA and NadA of different variants.