There are strong parallels between the evolutionary origin of species within populations of organisms and new concepts for the origin of cancers within cell populations in the tissues of the body. The analogy is that cancers can be regarded as a new somatic species developing within the host organism. In both cases, understanding the processes involved requires a multi-scale analysis, including higher-level control of genetic and epigenetic changes. A key to developing successful therapeutic strategies will be to identify the processes that control heterogeneity in tissues. These include processes outside the currently dominant theory of evolution, i.e. the Modern Synthesis. Specifically, organisms can partially direct both genetic and epigenetic changes through the harnessing of chance. The loci and rates of mutation and of genome reorganisation are forms of targeted functional reorganisation of genomes. They are more likely to result in functional reorganisations compared to the slow accumulation of point mutations.
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http://dx.doi.org/10.1016/j.pbiomolbio.2021.06.007 | DOI Listing |
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFCell Tissue Res
January 2025
Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Qatar Foundation (QF), Hamad Bin Khalifa University (HBKU), Doha, Qatar.
Impaired insulin secretion contributes to the pathogenesis of type 1 diabetes mellitus through autoimmune destruction of pancreatic β-cells and the pathogenesis of severe forms of type 2 diabetes mellitus through β-cell dedifferentiation and other mechanisms. Replenishment of malfunctioning β-cells via islet transplantation has the potential to induce long-term glycemic control in the body. However, this treatment option cannot widely be implemented in clinical due to healthy islet donor shortage.
View Article and Find Full Text PDFHypertension
January 2025
Cardio-Renal Physiology and Medicine, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, AL (C.E.K., G.C.K., J.S.P.).
The term early life stress encompasses traumatic events occurring before the age of 18 years, such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. Adverse psychological experiences in early life are linked to enduring effects on mental and physical health in adulthood. In this review, we first describe the effects and potential mechanisms of early life stress on the components of the vasculature.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background: Damage-associated molecular patterns (DAMPs) induced by immunogenic cell death (ICD) may be useful for the immunotherapy to patients undergoing pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to predict the prognosis and immunotherapy responsiveness of PDAC patients using DAMPs-related genes.
Methods: K-means analysis was used to identify the DAMPs-related subtypes of 175 PDAC cases.
Front Immunol
January 2025
Integrative Immunobiology Department, Duke University, Durham, NC, United States.
Introduction: The regulation of expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage.
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