P2Y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin and Sepsis-Associated Liver Injury and Mortality

Authors

Athis R Arunachalam
Sanju S Samuel
Arunmani Mani
Janielle P Maynard
Kelsey M Stayer
Eric Dybbro
Subapradha Narayanan
Aalekhya Biswas
Saliha Pathan
Krishnakant Soni
Abu Hena Mostafa Kamal
Chandra Shekar R Ambati
Nagireddy Putluri
Moreshwar S Desai
Sundararajah Thevananther

Publication Date

11-1-2023

Journal

Cells

DOI

10.3390/cells13121005

PMID

38920635

PMCID

PMC11201841

PubMedCentral® Posted Date

6-8-2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Mice, Animals, Lipopolysaccharides, Gene Deletion, Liver, Cytokines, Sepsis, Bacterial Infections, Bacteremia, Nucleotides, Arginine, Receptors, Purinergic, Amino Acids, Mice, Inbred C57BL, Receptors, Purinergic P2Y2, Mice, Knockout, patient-derived cells, PCa, CR

Abstract

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).