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Merging metabolic modeling and imaging for screening therapeutic targets in colorectal cancer.
NPJ Syst Biol Appl
January 2025
Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism.
View Article and Find Full Text PDFPatient-Specific Variability in Interleukin-6 and Myeloperoxidase Responses in Osteoarthritis: Insights from Synthetic Data and Clustering Analysis.
J Pers Med
January 2025
Department of Applied Science, South East Technological University, R93 V960 Carlow, Ireland.
This study investigated the inflammatory responses of fibroblast-like synoviocytes (FLS) isolated from osteoarthritis (OA) patients, stimulated with lipopolysaccharide (LPS) and interleukin-6 (IL-6). Both experimental and synthetic data were utilised to investigate the variability in IL-6 and myeloperoxidase (MPO) production and its implications for OA pathogenesis. Synovial biopsies were obtained from OA patients undergoing joint replacement surgery.
View Article and Find Full Text PDFA significant advancement in synthetic biology is the development of synthetic gene circuits with predictive Boolean logic. However, there is no universally accepted or applied statistical test to analyze the performance of these circuits. Many basic statistical tests fail to capture the predicted logic (OR, AND, etc.
View Article and Find Full Text PDFImpact of an Oncology Clinical Pharmacist Intervention on Clinical Trial Enrollment in The US Oncology Network's MYLUNG Consortium.
J Adv Pract Oncol
July 2024
New York Oncology Hematology, Albany, New York.
Introduction: The Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic Consortium™ (MYLUNG) clinical trial platform aims to advance the use of precision medicine in patients with non-small cell lung cancer through a series of prospective and iterative clinical trials. Timely patient accrual onto oncology clinical trials is a known practice challenge and impaired accrual rates can lead to premature trial closure or properly powered trial outcomes. The US Oncology Network recently implemented a clinical pharmacist (ClinReview) initiative to provide remote clinical services to screen patients for enrollment onto MYLUNG Protocol 2.
View Article and Find Full Text PDF2-Cyanopyrimidine-Containing Molecules for N-Terminal Selective Cyclization of Phage-Displayed Peptides.
ACS Chem Biol
January 2025
Texas A&M Drug Discovery Center, Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.
Current methods for the macrocyclization of phage-displayed peptides often rely on small molecule linkers that nonspecifically react with targeted amino acid residues. To expand tool kits for more regioselective macrocyclization of phage-displayed peptides, this study explores the unique condensation reaction between an N-terminal cysteine and nitrile along with the reactivity of an internal cysteine. Five 2-cyanopyrimidine derivatives were synthesized for this purpose and evaluated for their selective macrocyclization of a protein-fused model peptide.
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