MP
Ontology highlight
ABSTRACT:
SUBMITTER: Liangting Liu
PROVIDER: OEX00019150 | NODE | 2022-06-25
REPOSITORIES: NODE
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Project description:Hypoxia regulates fibroblast function by changing intracellular signaling and secretion factors, which influences the states of nearby cells. In this work, we investigated the effects of conditioned medium (CM) from human adult dermal fibroblasts (HDFs) cultured in normoxic and hypoxic conditions on cervical cancer (HeLa) cells. The HeLa cells showed decreased cell viability, in-creased apoptosis, and cell cycle arrest in response to CM from hypoxic-cultured HDFs (H-CM) compared with CM from normoxic-cultured HDFs (N-CM). Among the proteins up-regulated (> 2-fold) in H-CM compared with N-CM, LTBR decreased the viability of HeLa cells. Among the intracellular proteins down-regulated (> 2-fold) in HeLa cells treated with H-CM compared with N-CM, the most enriched biological process GO term and KEGG pathway were protein deubiq-uitination and hsa05166:HTLV-I infection, respectively. In the protein–protein interaction net-work of intracellular proteins with altered expression (> 2-fold), 1 up-regulated (TNF) and 8 down-regulated (ESR1, MCL1, TBP, CD19, LCK, PCNA, CHEK1, and POLA1) hub proteins were defined. Among the down-regulated hub proteins, the most enriched biological process GO term and KEGG pathway were leading strand elongation and hsa05166:HTLV-I infection, respectively. This study reveals that H-CM had enhanced anti-cancer effects on cervical cancer cells compared with N-CM, and it induced intracellular signaling patterns related to those enhanced anti-cancer effects.
2022-03-04 | GSE185978 | GEO
Project description:Histone deacetylase inhibitors (HDACi) are currently used as anticancer drugs; however, no clinical trials proved efficacy in pancreatic adenocarcinoma (PDAC). Ivaltinostat, a novel intravenous HDACi, presented cell growth inhibition and improved chemo-sensitivity in PDAC. This phase I/II study demonstrated ivaltinostat with gemcitabine and erlotinib can be administered safely to improve survivals in patients with untreated advanced PDAC. In addition, we proposed potential blood markers to predict response to ivaltinostat treatment based on correlative studies.
2021-11-29 | GSE189724 | GEO
Project description:Akt is a Ser/Thr protein kinase that regulates cell growth, metabolism and is considered a therapeutic target for cancer. Regulation of Akt by membrane recruitment and post-translational modifications (PTMs) has been extensively studied. The most well-established mechanism for cellular Akt activation involves phosphorylation on its activation loop on Thr308 by PDK1 and on its C-terminal tail on Ser473 by mTORC2. Other C-terminal tail PTMs have been identified, but their functional impacts have not been well-characterized. We use expressed protein ligation (EPL) as a tool to produce semisynthetic Akt proteins to dissect the enzymatic functions of these PTMs. We performed kinase assays employing human protein microarrays to investigate global substrate specificity of Akt, comparing phosphorylated vs. O-GlcNAcylated Ser473 forms.
2021-08-13 | GSE181983 | GEO
Project description:Breastfeeding provides defense against infectious disease during early life. The mechanisms underlying this protection are complex but likely include the vast array of immune cells and components, such as immunoglobulins, in milk. Simply characterizing the concentrations of these bioactives, however, provides only limited information regarding their potential relationships with disease risk in the recipient infant. Rather, understanding pathogen and antigen specificity profiles of milk-borne immunoglobulins might lead to a more complete understanding of how maternal immunity impacts infant health and wellbeing. Milk produced by women living in 11 geographically dispersed populations was applied to a protein microarray containing antigens from 16 pathogens, including diarrheagenic E. coli, Shigella spp., Salmonella enterica serovar Typhi, Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis and other pathogens of global health concern, and specific IgA and IgG binding was measured. Our analysis identified novel disease-specific antigen responses and suggests that some IgA and IgG responses vary substantially within and among populations. Patterns of antibody reactivity analyzed by principal component analysis and differential reactivity analysis were associated with either lower-to-middle-income countries (LMICs) or high-income countries (HICs). Antibody levels were generally higher in LMICs than HICs, particularly for Shigella and diarrheagenic E. coli antigens, although sets of S. aureus, S. pneumoniae, and some M. tuberculosis antigens were more reactive in HICs. Differential responses were typically specific to canonical immunodominant antigens, but a set of nondifferential but highly reactive antibodies were specific to antigens possibly universally recognized by antibodies in human milk. This approach provides a promising means to understand how breastfeeding and human milk protect (or do not protect) infants from environmentally relevant pathogens. Furthermore, this approach might lead to interventions to boost population-specific immunity in at-risk breastfeeding mothers and their infants.
2020-12-28 | GSE163902 | GEO
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.
2025-12-10 | GSE302839 | GEO
Project description:Previously, cooperative binding to DNA between the bZIP domain of CREB1 and the ETS domain of GABPα was observed for the composite ETS-CRE motif (A0C1C2G3G4A5A6G7T8G9A10C11G12T13C14A15). Single nucleotide polymorphisms (SNPs) at the beginning and end of the ETS motif (ACCGGAAGT) increased cooperative binding. Here, we use a microarray containing all double nucleotide polymorphisms (DNPs) of the ETS-CRE motif to explore GABPα and CREB1 binding to their canonical motifs and their cooperative binding to the ETS-CRE motif. For GABPα, binding to SNPs predicted binding the DNPs. In contrast, CREB1 binding to DNPs showed cooperativity. Similar results were observed for other ETS and bZIP family members. Cooperative binding between GABPα and CREB1 was typically weaker than expected except for DNPs containing A7 and SNPs at the beginning of the ETS motif.
2020-01-01 | GSE125613 | GEO
Project description:Reciprocal signaling between melanoma brain metastatic (MBM) cells and microglia reprograms the phenotype of both interaction partners, including upregulation of the transcription factor JunB in microglia. Here, we aimed to elucidate the impact of microglial JunB upregulation on MBM progression. For molecular profiling, we employed RNAseq and RPPA. To test microglial JunB functions we generated microglia variants stably overexpressing JunB (JunBhi) or with downregulated levels of JunB (JunBlo). Melanoma-derived factors, namely Leukemia Inhibitory Factor (LIF), controlled JunB upregulation through JAK/STAT3 signaling. The expression levels of JunB in melanoma-associated microglia were heterogeneous. Flow cytometry analysis revealed the existence of basal-level JunB expressing microglia alongside JunB-highly expressing microglia. Proteomic profiling revealed a differential protein expression in JunBhi and JunBlo cells, including in the expression of microglia activation markers Iba-1 and CD150, and in immunosuppressive molecules SOCS3 and PD-L1. Functionally, JunBhi microglia displayed decreased migratory capacity and phagocytic activity. JunBlo microglia reduced melanoma proliferation and migration, while JunBhi microglia supported the ability of melanoma to proliferate in 3-dimensional co-cultures, that was abrogated by targeting LIFRβ in melanoma-microglia spheroids. Altogether, these data highlight a melanoma-mediated heterogeneous effect on microglial JunB expression, which turns these cells into functionally heterogeneous microglia. Targeting JunB highly-expressing microglia may potentially be utilized for MBM theranostics.
2025-10-15 | GSE240905 | GEO
Project description:Purpose: This study uses a high-throughput glycan microarray to evaluate the immunological evolution of antibodies to the glyco-antigen GD2. The goal is to determine germline and affinity mature antibody specificity and affinities/ Results: Affinity mature anti-GD2 antibodies 3F8 and ch14.18 had high affinity and were highly specific for the target GD2. Germline antibodies were also hihgly specific and had surprisingly high affinity. Conclusion: Antibodies to GD2 evolved from highly specific germlines. Highly specific germlines may be critical in evading autoimmunity issues.
2017-08-25 | GSE100308 | GEO
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2016-11-01 | GSE88781 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-06-01 | GSE78124 | GEO