98%
921
2 minutes
20
Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-β-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and . However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and (ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and (ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and , ATM-IMI-REL might be a reasonable alternative.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459955 | PMC |
http://dx.doi.org/10.1128/aac.00693-24 | DOI Listing |
Front Immunol
September 2025
Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome, Italy.
Background: Sézary syndrome (SS) is an aggressive and leukemic variant of Cutaneous T-cell Lymphoma (CTCL) with an incidence of 1 case per million people per year. It is characterized by a complex and heterogeneous profile of genetic alteration ns that has so far precluded the development of a specific and definitive therapeutic intervention.
Methods: Deep-RNA-sequencing (RNA-seq) data were used to analyze the single nucleotide variants (SNVs) carried by 128 putative CTCL-driver genes, previously identified as mutated in genomic studies, in longitudinal SS samples collected from 17 patients subjected to extracorporeal photopheresis (ECP) with Interferon-α.
Biochem Biophys Res Commun
August 2025
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA. Electronic address:
Taxol is an antitumor agent that arrests cells in the late G2 and M phases of the cell cycle. Our previous research demonstrated that PARP inhibition enhances Taxol-induced cell death via oxidative stress and free radical production. In this study, we hypothesized that the inhibiting DNA damage response (DDR) kinases would further increase Taxol cytotoxicity by impairing the repair of Taxol-induced DNA damage.
View Article and Find Full Text PDFUnlike visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) can play a protective role against the development of insulin resistance and metabolic dysfunction in obesity. Here, we show that, in obesity, subcutaneous adipose tissue macrophages (ATMs) release small extracellular vesicles (sEVs) that can improve insulin sensitivity, opposite to the effect of visceral ATM sEVs. This functional difference was associated with an increase in the proportion of insulin-sensitizing, resident ATMs in SAT.
View Article and Find Full Text PDFSci Rep
August 2025
Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstrasse 27, Erlangen, 91054, Germany.
Treatment of head and neck squamous cell carcinomas (HNSCC) remains challenging with regards to radioresistance, particularly of Human Papilloma Virus (HPV)-negative tumors. Several new approaches are currently under pre-clinical and clinical investigation. Combination of radiotherapy (RT) and kinase inhibitors of the DNA damage repair system (DDRi), targeting Ataxia Telangiectasia Mutated (ATM) or ATM and Rad3-related (ATR), are promising, but the consequences on tumor cell phenotype are still scarce.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland.
Gastric cancer remains a significant global health challenge, with regional and demographic disparities in incidence, mortality, and treatment outcomes. Despite advances in screening and early detection, prognosis remains poor for many patients, particularly those with advanced disease. Recent insights into DNA damage response pathways have uncovered critical molecular vulnerabilities in gastric tumors, including frequent mutations, loss, deficiency, and oncogene-driven replication stress, which render these cancers highly dependent on the ATR-CHK1 axis for survival.
View Article and Find Full Text PDF