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In situ RAS:RAF binding correlates with response to KRASG12C inhibitors in KRASG12C--mutant non-small cell lung cancer.
Clin Cancer Res
January 2025
Moffitt Cancer Center, Tampa, Florida, United States.
Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.
View Article and Find Full Text PDFThe effects of aerobic exercise and heat stress on the unbound fraction of caffeine.
Front Physiol
January 2025
Human Physiology Research Unit, Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.
Introduction: The fraction of drug circulating in the blood that is not bound to plasma proteins ( ) is considered pharmacologically active since it readily binds to its receptor. evidence suggests that changes in temperature and pH affect the affinity of drug binding to plasma proteins, resulting in changes in . In light of the well-established effects of exercise on body temperature and blood pH, we investigated whether an increase in blood temperature and decrease in pH facilitated through passive heating and exercise translated to a change in the of caffeine.
View Article and Find Full Text PDFLong-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection.
Front Immunol
January 2025
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Introduction: Serum levels of interleukin-6 (IL-6) are increased in COVID-19 patients. IL-6 is an effective therapeutic target in inflammatory diseases and tocilizumab, a monoclonal antibody that blocks signaling via the IL-6 receptor (IL-6R), is used to treat patients with severe COVID-19. However, the IL-6R exists in membrane-bound and soluble forms (sIL-6R), and the sIL-6R in combination with soluble glycoprotein 130 (sgp130) forms an IL-6-neutralizing buffer system capable of neutralizing small amounts of IL-6.
View Article and Find Full Text PDFBoundaries and cross-linking densities modulate domain sizes of polydomain nematic elastomers.
Soft Matter
January 2025
Department of Physics, Tohoku University, Sendai 980-8578, Japan.
When nematic liquid crystal elastomers (LCEs) crosslinked at their isotropic phase are quenched to the nematic phase, they show polydomain patterns, in which nematic microdomains with different orientations self-organize into a three-dimensional mosaic with characteristic correlation patterns. The orientational correlation length of the domain, which is usually in the micrometer range, is believed to emerge as a result of a competition between liquid crystalline ordering and frozen network inhomogeneity. Although polydomain patterns show potentials as the basic platform for optical, memory, and mechanical devices, no study exists regarding how they are modulated by experimentally accessible parameters.
View Article and Find Full Text PDFFunctional analysis of the type II toxin-antitoxin system ParDE in Streptococcus suis serotype 2.
BMC Vet Res
January 2025
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
Streptococcus suis (S. suis) is a major pathogen in swine and poses a potential zoonotic threat, which may cause serious diseases. Many toxin-antitoxin (TA) systems have been discovered in S.
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