NOTCH1, which is frequently mutated in T cell acute lymphoblastic leukemia, has been an elusive therapeutic target. In this issue of Cancer Cell, Roti and colleagues demonstrate that inhibiting SERCA calcium pumps preferentially impairs the maturation of the most common class of oncogenic Notch1 mutants, thus uncovering a potential therapeutic avenue.
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http://dx.doi.org/10.1016/j.ccr.2013.02.020 | DOI Listing |
Nat Med
January 2025
Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.
View Article and Find Full Text PDFEur J Neurosci
January 2025
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
In corticostriatal nerve terminals, glutamate release is stimulated by adenosine via A receptors (ARs) and simultaneously inhibited by endocannabinoids via CB receptors (CBRs). We previously identified presynaptic AR-CBR heterotetrameric complexes in corticostriatal nerve terminals. We now explored the possible functional interaction between ARs and CBRs in purified striatal GABAergic nerve terminals (synaptosomes) and compared these findings with those on the release of glutamate.
View Article and Find Full Text PDFNPJ Parkinsons Dis
January 2025
Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.
Parkinson's disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson's disease includes increased neuropathic pain, the prevalence of which is 4 to 5 times higher than the general rate. By studying a mouse model of Parkinson's disease induced by 6-hydroxydopamine, we assessed the impact of dopamine depletion on pain modulation.
View Article and Find Full Text PDFPathogens
December 2024
Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.
Natural killer (NK) and CD8 T cell function is compromised in human immunodeficiency virus type 1 (HIV-1) infection by increased expression of inhibitory receptors such as TIGIT (T cell immunoreceptor with Ig and ITIM domains). Blocking inhibitory receptors or their ligands with monoclonal antibodies (mAb) has potential to improve antiviral immunity in general and facilitate HIV eradication strategies. We assessed the impact of TIGIT engagement and blockade on cytotoxicity, degranulation, and interferon-gamma (IFN-γ) production by CD8 T cells from persons living with HIV (PLWH).
View Article and Find Full Text PDFCancers (Basel)
December 2024
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
Pembrolizumab has recently emerged as a PD-1 blockade immunotherapy treatment for lung cancer. It is critical that such treatment strategies for lung cancer should be chosen not only on the basis of histopathological features and the expression of targetable cell surface proteins (such as PD-1), but should rather be selected based on other determinants of treatment success or risk factors for poor prognosis. One method to forecast cancer trajectory is the identification of biomolecular signatures such as microRNAs (miRNAs), non-protein-coding RNA molecules that play a regulatory role in gene expression by modulating the translation or stability of messenger RNA.
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