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Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.
Sci Adv
January 2025
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.
View Article and Find Full Text PDFA pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies.
PLoS Pathog
January 2025
Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands.
Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of therapeutics.
View Article and Find Full Text PDFPractitioner, patient and public views on the acceptability of mobile stroke units in England and Wales: A mixed methods study.
PLoS One
January 2025
Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.
Background: Evidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation.
Methods: This study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024.
Ventricular-Arterial Coupling: Changes with aging and implications across cardiovascular conditions.
Blood Press
January 2025
Jagiellonian University Medical College, 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Kraków, Poland.
Purpose: Ventricular-arterial coupling (VAC) is a crucial concept in cardiovascular physiology, representing the dynamic interaction between the left ventricle and the arterial system. This comprehensive literature review explores the changes in VAC with aging and various cardiovascular diseases (CVDs).
Materials And Methods: This literature review covers studies on changes in VAC with age and common CVDs such as arterial hypertension, atrial fibrillation, heart failure with preserved and reduced ejection fraction and aortic stenosis.
Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia.
Blood
January 2025
IDIBAPS, Barcelona, Spain.
Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.
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