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A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.
Proc Natl Acad Sci U S A
January 2025
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.
View Article and Find Full Text PDFOlaparib and Radiotherapy Induce Type I Interferon- and CD8+ T Cell-Dependent Sensitization to Immunotherapy in Pancreatic Cancer.
Mol Cancer Ther
December 2024
Department of Radiation Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, Michigan.
PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN)-mediated antitumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote antitumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy.
View Article and Find Full Text PDFCXCL12-targeted immunomodulatory gene therapy reduces radiation-induced fibrosis in healthy tissues.
Mol Cancer Ther
December 2024
Institute of Cancer Research, London, United Kingdom.
Radiation-induced fibrosis (RIF) is a progressive pathology deleteriously impacting cancer survivorship. CXCL12 is an immune-stromal signal implicated in fibrosis and innate response. We hypothesised that modulation of CXCL12 would phenotypically mitigate RIF.
View Article and Find Full Text PDFGreater resting state functional connectivity of the medial prefrontal cortex with the thalamus, caudate, and putamen in individuals who adhere to the Mediterranean style diets.
Eur J Nutr
November 2024
School of Psychology and Clinical Language Sciences, University of Reading, Reading, RG6 6ET, UK.
Purpose: Healthy diets are believed to be associated with a reduced risk of experiencing common mental disorders (CMDs) and related symptomatology (such as ruminative thinking), and with healthier brain chemistry and structure, especially in the frontal regions implicated in CMDs, cognitive control, and food choice. Nevertheless, there is very limited research on the relationship between diet health/quality and brain function. In this study we assessed the associations between adherence to the Mediterranean diet and resting state functional connectivity (rs-FC) of the prefrontal cortex (PFC) with the whole brain and whether this connectivity would be associated with ruminative thinking as a transdiagnostic factor for CMDs.
View Article and Find Full Text PDFLongitudinal Study of Transcriptomic Changes Occurring over Six Weeks of CHOP Treatment in Canine Lymphoma Identifies Prognostic Subtypes.
Vet Sci
November 2024
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
The majority of canine lymphoma patients treated with the standard of care, the CHOP chemotherapy protocol, initially achieve remission but eventually relapse with a multi-drug-resistant phenotype. This study assesses gene expression profiles of canine lymphoma tumor cell populations using RNA-Seq data from 15 matched patient samples taken prior to treatment and again six weeks into treatment with CHOP. Two distinct clusters were present in the t-SNE dimensionality reduction of the gene expression profiles.
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