For over 40 years, in vitro assays have been used to understand the complex system of hematopoiesis. Now, several of these assays are undergoing resurgence as scientists in academia and industry are discovering how these assays can be utilized in drug discovery and development. These assays use primary cells from various hematopoietic tissues in multiple species to provide high content information. While conditions in the human body cannot be completely reproduced in vitro, hematopoietic colony-forming cell assays are proving to be a clinically relevant tool to evaluate potential toxic effects of new compounds. The ability to use these assays as a replacement of, or in conjunction with, high-throughput screening assays and high priced in vivo assays can improve the success of the decision-making process, saving time and costs during drug development.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2217/17460751.2.6.947 | DOI Listing |
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.
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 PDFJCI Insight
January 2025
Dianne Hoppes Nunnally Laboratory Research Division, Joslin Diabetes Center, Boston, United States of America.
Background: We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).
Methods: Joslin "Medalists" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging.
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 PDFJ 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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!