Phosphoproteomics
Ontology highlight
ABSTRACT:
TISSUE(S): ['prostate']
SUBMITTER: Xin Li
PROVIDER: OEX00028406 | NODE | 2024-07-11
REPOSITORIES: NODE
Similar Datasets
Project description:Aberrant activation of PI3K pathway is frequently observed in triple negative breast cancer (TNBC). However single agent PI3K inhibitors have shown limited anti-tumor activity. To investigate biomarkers of response and resistance mechanisms, we tested 17 TNBC patient-derived xenograft (PDX) models representing diverse genomic backgrounds and varying degrees of PI3K pathway signaling activities for their tumor growth response to the pan-PI3K inhibitor BKM120. Baseline and post-treatment PDX tumors harvested following 3 days of BKM120 or vehicle administration were subjected to reverse phase protein array (RPPA) to identify protein markers associated with tumor growth response. While BKM120 consistently reduced PI3K pathway activity, as demonstrated by reduced levels of phosphorylated AKT, percentage tumor growth inhibition (%TGI) ranged from 35% in the least sensitive to 84% in the most sensitive PDX model at the completion of approximately 3-4 weeks of treatment. Several biomarkers showed significant association with resistance, including elevated baseline levels of growth factor receptors (EGFR, pHER3 Y1197), PI3Kp85 regulatory subunit, anti-apoptotic protein BclXL, EMT (Vimentin, MMP9, IntegrinaV), NFKB pathway (IkappaB, RANKL), and intracellular signaling molecules including Caveolin, CBP, and KLF4, as well as treatment-induced increase in the levels of phosphorylated forms of Aurora kinases. Sensitivity to BKM120 was associated with higher baseline levels of proapoptotic markers (Bak and Caspase 3) and a greater number of markers differentially changed following BKM120 therapy. Interestingly, markers indicating PI3K pathway signaling activation or PTEN loss at baseline were not significantly correlated to %TGI. These results provide important insights into biomarker development for PI3K inhibitors in TNBC.
2021-01-27 | GSE149720 | GEO
Project description:Sjögren's Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition. The presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male non-obese diabetic (NOD) and male non-obese insulitis resistant (NOR) mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Sources of Ig in tears were investigated using scRNA-Seq of the LG (GSE132420). Data were analyzed by R package Limma and Seurat. Analysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models. Igha and Ighg2b expressing cells were identified in the plasma cell cluster of NOD.H2b LG. NOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.
2025-01-28 | GSE286504 | GEO
Project description:Male Non-Obese Diabetic (NOD) mice develops autoimmune dacryoadenitis beginning 6-8 weeks of age including lymphocytic infiltration of the lacrimal glands, reduced tear production, increased cysteine tear proteases and restructuring of extracellular membrane structural proteins. Autoantigens with high antibody reactivity in serum of disease model mice may have diagnostic potential for Sjögren's Disease. Serum was collected from mice at early (8 weeks,), intermediate (24 weeks) and advanced (33 weeks) stage of autoimmune dacryoadenitis. Serum was also collected from healthy control BALB/c mice at 8 and 28 weeks of age. Approximately 0.8 mL of blood was collected by cardiac puncture into serum separator tubes. Following cold centrifugation, serum was collected. 10 uL of serum per sample was used to determine reactivity against 94 autoantigens using proteinarray. Additionally, effect of age on the level of reactivity was also studied to determine if aging was a confounding the observed up or downregulation of serum autoantibodies.
2025-01-28 | GSE286503 | GEO
Project description:Male Non-Obese Diabetic (NOD) derived NOR mice develop autoimmune dacryoadenitis by 16 weeks of age including lymphocytic infiltration of the lacrimal glands, reduced tear production, and increased cysteine tear proteases. Unlike the NOD mice, the NOR mice do not develop diabetes and studies designed with the NOR mice are expected to not have diabetes development counfounding the results observed for Sjogren's development. Autoantigens with high levels of reactivity in serum and/or tears of diseased mice may have diagnostic potential. Serum was collected from mice at 16 weeks old male NOR mice along with age matched male healthy BALBc controls. Approximately 0.8 mL of blood was collected by cardiac puncture into serum separator tubes. Following cold centrifugation, serum was collected. Tears were collected following topical stimulation of the lacrimal gland with carbachol. For tear samples, tears were pooled from 1, 2 or 3 mice, respectively to generate three samples. This was done mainly to optimize the number of mice required to obtain sufficient sample for the assay as well as to assess the sensitivity of mouse tears for the proteinarray. 1 to 10 uL of tear or 10 uL of serum per sample was used to determine reactivity against 94 autoantigens using proteinarray.
2025-01-28 | GSE286502 | GEO
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.
2019-12-17 | GSE141930 | GEO
Project description:β-cell specific Mettl14 knock-out mice display reduced N6-methyladenosine (m6A) levels and recapitulate human Type II diabetes (T2D) islet phenotype with early diabetes onset and mortality secondary to decreased β-cell proliferation and insulin degranulation. To gain insights into the role of m6A in regulating the IGF1/insulin -> AKT - > PDX1 pathway and to dissect the signaling networks modulating AKT phosphorylation, we subjected freshly isolated islets from control and Mettl14 knock-out mice to phospho-antibody microarrays.
2019-08-09 | GSE132111 | GEO
Project description:This study uses proteome microarray technology/data to identify predictive biomarkers of neutralizing antibody response and potential new correlates of protective immunity in rubella virus serology.
2017-09-23 | GSE104148 | GEO
Project description:Human serum samples were probed onto human protein microarrays in order to ascertain the number and diversity of naturally ocurring self-reactive IgG autoantibodies.
2013-04-25 | GSE39087 | GEO
Project description:DNA sequence is a major determinant of the binding specificity of transcription factors (TFs) for their genomic targets. However, eukaryotic cells often express, at the same time, TFs with highly similar DNA binding motifs but distinct in vivo targets. Currently, it is not well understood how TFs with seemingly identical DNA motifs achieve unique specificities in vivo. Here, we used custom protein binding microarrays to analyze TF specificity for putative binding sites in their genomic sequence context. Using yeast TFs Cbf1 and Tye7 as our case study, we found that binding sites of these bHLH TFs (i.e., E-boxes) are bound differently in vitro and in vivo, depending on their genomic context. Computational analyses suggest that nucleotides outside E-box binding sites contribute to specificity by influencing the 3D structure of DNA binding sites. Thus, local shape of target sites might play a widespread role in achieving regulatory specificity within TF families.
2013-03-29 | GSE44436 | GEO
Project description:Global kinase activity induced by cytokines IL-32g and IL-17A/F were determined using peptide arrays representing phophorylation targets The objective of this study was to identify common and unique phosphorylation targets of pro-inflammatory cytokines IL-32 and IL-17. These cytokines are associated with the pathogenesis and severity of chronic inflammatory disorders, therefore signaling intermediates of these cytokines could be beneficial as alternate theraputic targets that may likely influence different inflammatory pathways.
2011-04-16 | GSE28649 | GEO