Local Inflammation Precedes Diaphragm Wasting and Fibrotic Remodelling in a Mouse Model of Pancreatic Cancer.

Background: Cancer cachexia represents a debilitating muscle wasting condition that is highly prevalent in gastrointestinal cancers, including pancreatic ductal adenocarcinoma (PDAC). Cachexia is estimated to contribute to ~30% of cancer-related deaths, with deterioration of respiratory muscles suspected to be a key contributor to cachexia-associated morbidity and mortality. In recent studies, we identified fibrotic remodelling of respiratory accessory muscles as a key feature of human PDAC cachexia.

Identify characteristics of Vietnamese oral squamous cell carcinoma patients by machine learning on transcriptome and clinical-histopathological analysis.

Background/purpose: Oral squamous cell carcinoma (OSCC) is notorious for its low survival rates, due to the advanced stage at which it is commonly diagnosed. To enhance early detection and improve prognostic assessments, our study harnesses the power of machine learning (ML) to dissect and interpret complex patterns within mRNA-sequencing (RNA-seq) data and clinical-histopathological features.

Materials And Methods: 206 retrospective Vietnamese OSCC formalin-fixed paraffin-embedded (FFPE) tumor samples, of which 101 were subjected to RNA-seq for classification based on gene expression.

Structural insights into binding-site access and ligand recognition by human ABCB1.

ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer.

Background: SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.