Multidrug resistance protein 7 (MRP7, ABCC10) is a recently discovered member of the ATP-binding cassette (ABC) family which are capable of conferring resistance to a variety of anticancer drugs, including taxanes and nucleoside analogs, in vivo. MRP7 is highly expressed in non-small cell lung cancer cells, and Mrp7-KO mice are highly sensitive to paclitaxel, making MRP7 an attractive chemotherapeutic target of non-small cell lung cancer. However, only a few inhibitors of MRP7 are currently identified, with none of them having progressed to clinical trials. We used MRP7-expressing cells to investigate whether tariquidar, a third generation inhibitor of P-glycoprotein, could inhibit MRP7-mediated multidrug resistance (MDR). We found that tariquidar, at 0.1 and 0.3 µM, significantly potentiated the sensitivity of MRP7-transfected HEK293 cells to MRP7 substrates and increased the intracellular accumulation of paclitaxel. We further demonstrated that tariquidar directly impaired paclitaxel efflux and could downregulate MRP7 protein expression in a concentration- and time-dependent manner after prolonged treatment. Our findings suggest that tariquidar, at pharmacologically achievable concentrations, reverses MRP7-mediated MDR through inhibition of MRP7 protein expression and function, and thus represents a promising therapeutic agent in the clinical treatment of chemoresistant cancer patients.
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ACS Infect Dis
December 2024
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Carbapenemase producing (CPEs) represent a group of multidrug resistant pathogens for which few, if any, therapeutics options remain available. CPEs generally harbor plasmids that encode resistance to last resort carbapenems and many other antibiotics. We previously performed a high throughput screen to identify compounds that can disrupt the maintenance and replication of resistance conferring plasmids through use of a synthetic screening plasmid introduced into K-12 cells.
View Article and Find Full Text PDFEur J Intern Med
December 2024
Department of Biomedical Sciences, IRCCS Humanitas Research Hospital, 20089 Milano, Italy.
Background And Aim: The aim of the present study was to evaluate the prevalence and to identify the independent predictors of multi-drug resistance among a cohort of patients admitted to emergency department for urinary tract infections (UTI), and to assess the impact of antimicrobial resistance on the clinical outcomes.
Methods: We conducted a prospective multicentre study enrolling all adult patients admitted to one of the eight emergency departments participating in the study with a microbiologically confirmed diagnosis of UTI from February 2023 to July 2024. The primary outcome evaluated was 30-day mortality; secondary outcomes included 7-day mortality and clinical response.
Anticancer Res
January 2025
Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
Background/aim: Ovarian cancer (OC) is one of the leading gynecological causes of death among women. The current standard treatment for OC is debulking surgery followed by platinum-based chemotherapy treatments; however, despite initial success to treatment many patients experience relapses. Currently, there are no available tests to predict sensitivity or resistance to chemotherapy.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary; Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen 4032, Hungary; Dean's office, Faculty of Pharmacy, University of Debrecen, Debrecen 4032, Hungary. Electronic address:
ABCB1/MDR-1/P-glycoprotein (Pgp) is an ABC transporter responsible for cancer cell multi-drug resistance. It is expressed in cytotoxic T lymphocytes (CTL). Eliminating sensitive cancer cells during high-dose chemotherapy can also damage immune cells.
View Article and Find Full Text PDFJ Infect Public Health
December 2024
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address:
Background: Currently, antimicrobial agents are widely used in both animals and agriculture, causing the crisis of multidrug-resistant (MDR) bacteria. In this study we surveyed for 4 important antimicrobial-resistant bacteria: extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and Salmonella spp., and methicillin-resistant Staphylococcus aureus (MRSA) from the environment around chicken and pig farms.
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