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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 PDFNovel Therapies for Sleep Disorder Breathing.
Am J Respir Crit Care Med
January 2025
Beth Israel Deaconess Medical Center, Pulmonary, Critical Care and Sleep Medicine, Boston, Massachusetts, United States.
Single-cell and spatial transcriptomics illuminate bat immunity and barrier tissue evolution.
Mol Biol Evol
January 2025
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection.
View Article and Find Full Text PDFMAPK pathway activating alteration and immunotherapy efficacy in squamous cell lung carcinoma: results from the randomized, prospective SQUINT trial.
Clin Cancer Res
January 2025
Istituti Fisioterapici Ospitalieri, Italy.
Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.
Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.
High risk of drug-resistant tuberculosis in IGRA-negative contacts: should preventive treatment be considered?
Infection
January 2025
Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Center, Parkallee 35, Borstel, Germany.
Purpose: Deciding whether to provide preventive treatment to contacts of individuals with multidrug-resistant (MDR) tuberculosis is complex.
Methods: We present the diagnostic pathways, clinical course and outcome of tuberculosis treatment in eight siblings from a single family. Tuberculosis disease was diagnosed by Mycobacterium tuberculosis culture and molecular detection of M.
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