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Project description:Engineered cytokine-based approaches for immunotherapy of cancer are poised to enter the clinic, with IL-12 being at the forefront. However, little is known about potential mechanisms of resistance to cytokine therapies. We found that orthotopic murine lung tumors were resistant to systemically delivered IL-12 fused to murine serum albumin (MSA, IL12-MSA) due to low IL-12R expression on tumor-reactive CD8+ T cells. IL2-MSA increased binding of IL12-MSA by tumor-reactive CD8+ T cells, and combined administration of IL12-MSA and IL2-MSA led to enhanced tumor-reactive CD8+ T cell effector differentiation, decreased numbers of tumor-infiltrating CD4+ regulatory T (Treg) cells, and increased survival of lung tumor-bearing mice. Predictably, the combination of IL-2 and IL-12 at therapeutic doses led to significant dose-limiting toxicity. Administering IL-12 and IL-2 analogs with preferential binding to cells expressing IL12rb1 and CD25, respectively, led to a significant extension of survival in mice with lung tumors while abrogating dose-limiting toxicity. These findings suggest that IL-12 and IL-2 represent a rational approach to combination cytokine therapy whose dose-limiting toxicity can be overcome with engineered cytokine variants.
2024-01-26 | PXD044740 | Pride
Project description:Human post-portem Multiple System Atrophy (MSA) and control aged brains were examined for mRNA expression of iron-related genes
2024-08-17 | GSE241198 | GEO
Project description:Genome-wide methylation profiling of DNA extracted from the prefrontal cortex of post-mortem MSA patients (n=41) or normal, healthy controls (CTRLs; n=37). The Illumina Infinium MethylationEPIC BeadChip was used, investigating app. 850,000 CpG sites throughout the genome
2020-03-10 | GSE143157 | GEO
Project description:Iron-related gene expression in MSA
| PRJNA1006714 | ENA
Project description:Multiple system atrophy (MSA) is a fatal rapidly progressive Ia-synucleinopathy, characterized by prominent Ia-synuclein accumulation in oligodendrocytes. In this study we investigated miRNA expression in the substantia nigra and striatum of MSA transgenic mice (Tg(Plp1-SNCA)1Haa) and wild type controls. This forms part of a larger study in which we investigated miRNA-mRNA regulatory network in substantia nigra and striatum of MSA transgenic mice in pre-motor stage of neurodegenration.
2016-03-15 | E-MTAB-3993 | biostudies-arrayexpress
Project description:Mannose-specific interactions of Lactobacillus plantarum 299v with jejunal epithelium were investigated using an in situ pig small intestinal segment perfusion (SISP) model. L. plantarum 299v wildtype strain was compared to two isogenic mutant strains either lacking the gene encoding for the mannose-specific adhesin (msa) or sortase (srtA; responsible for anchoring of cell surface proteins like Msa to the cell wall). Salmonella typhimurium served as a positive control for gene expression analysis. Scrapings from jejunal segments were collected after perfusion with bacterial suspensions or PBS (control) for 4 or 8 hours, and host gene expression was assessed using a home-made cDNA porcine microarray. Keywords: host-microbe interaction, Lactobacillus plantarum, mannose-specific adhesion A Small Intestinal Segment Perfusion (SISP) test was performed using 4 pigs. 10 segments were prepared in the jejunum of each pig and perfused with Lactobacillus plantarum 299v wildtype, Lactobacillus plantarum 299v msa mutant strain, Lactobacillus plantarum 299v srtA mutant strain, Salmonella typhimurium or PBS (control) for 4 or 8 hours. Pooled samples from each treatment at each timepoint were used for microarray analysis. 8 comparisons were done: L. plantarum wildtype vs control (4 hours), L. plantarum wildtype vs control (8 hours), L. plantarum msa mutant vs control (4 hours), L. plantarum msa mutant vs control (8 hours), L. plantarum srt mutant vs control (4 hours), L. plantarum srt mutant vs control (8 hours), S. typhimurium vs control (8 hours), samples taken at the beginning of the experiment vs control (8 hours). Dye-swaps were performed for each comparison.
2010-05-25 | E-GEOD-9209 | biostudies-arrayexpress
Project description:RNA was extracted from each brain of 3 wild-type and 3 MSA Transgenic mice at the age of 16 weeks and microarray analysis was performed on each sample.
2022-06-10 | GSE205662 | GEO