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Multimodal integration of blood RNA and ctDNA reflects response to immunotherapy in metastatic urothelial cancer.
JCI Insight
January 2025
Medical Oncology Department, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands.
Background: Previously, we demonstrated that changes in circulating tumor DNA (ctDNA) are promising biomarkers for early response prediction (ERP) to immune checkpoint inhibitors (ICI) in metastatic urothelial cancer (mUC). In this study, we investigated the value of whole blood immunotranscriptomics for ERP-ICI and integrated both biomarkers into a multimodal model to boost accuracy.
Methods: Blood samples of 93 patients were collected at baseline and after 2-6 weeks of ICI for ctDNA (N=88) and immunotranscriptome (N=79) analyses.
Aerobic exercise prevents renal osteodystrophy via irisin-activated osteoblasts.
JCI Insight
January 2025
Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Renal osteodystrophy is commonly seen in patients with chronic kidney disease (CKD) due to disrupted mineral homeostasis. Given the impaired renal function in these patients, common anti-resorptive agents, including bisphosphonates, must be used with caution or even contraindicated. Therefore, an alternative therapy without renal burden to combat renal osteodystrophy is urgently needed.
View Article and Find Full Text PDFElevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.
J Clin Invest
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.
View Article and Find Full Text PDFReporting of concomitant and rescue topical therapies in atopic dermatitis randomised controlled trials evaluating a systemic treatment: a scoping review.
Br J Dermatol
January 2025
Centre of Evidence Based Dermatology, School of Medicine, Faculty of Medicine & Health Sciences, University of Nottingham, UK.
Background: Randomised controlled trials (RCTs) evaluating new systemic treatments for atopic dermatitis (AD) have increased dramatically over the last decade. These trials often incorporate topical therapies either as permitted concomitant or rescue treatments. Differential use of these topicals post-randomisation introduces potential bias as they may nullify or exaggerate treatment responses.
View Article and Find Full Text PDFMonocytes and interstitial macrophages contribute to hypoxic pulmonary hypertension.
J Clin Invest
January 2025
Department of Medicine, University of California San Francisco, San Francisco, United States of America.
Hypoxia is a major cause of pulmonary hypertension (PH) worldwide, and it is likely that interstitial pulmonary macrophages contribute to this vascular pathology. We observed in hypoxia-exposed mice an increase in resident interstitial macrophages, which expanded through proliferation and expressed the monocyte recruitment ligand CCL2. We also observed an increase in CCR2+ macrophages through recruitment, which express the protein thrombospondin-1 that functionally activates TGF-beta to cause vascular disease.
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