The conventional laboratory approach to study the mechanisms of drug resistance has been the selection of drug-resistant cell lines by continuous exposure to cytotoxic agents. Such lines, which are selected for resistance to a single agent, frequently display cross-resistance to a number of cytotoxic agents that are unrelated in both structure and proposed mechanism of action. Multidrug-resistant cells display reduced drug accumulation, which is the result of overexpression of a surface glycoprotein (P170). Although resistance to multiple antitumor agents is a common clinical problem in the treatment of cancer, the precise role of the P-glycoprotein-mediated mechanism in human tumors remains to be established. Many alterations in multidrug-resistant cells selected in vitro have been identified. The concomitant expression of multiple phenotypic differences, which appear to be favored by continued and prolonged drug exposure, makes analysis of critical individual resistance pathways more difficult. However, multiple factors may also be involved in the development of clinical resistance. Recent studies have identified alterations in DNA topoisomerase II activity and function as an alternative mechanism that contributes to the multidrug-resistance phenomenon or is responsible for a different type of drug resistance. The precise nature of these changes remains unclear. Available evidence supports the view that expression of the enzyme is an important determinant of cell sensitivity to DNA topoisomerase poisons, but that other changes involved in regulation of enzyme function and/or in the cellular processing of drug-induced DNA damage may be critical in determining the differential pattern of cell response to antitumor agents.
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http://dx.doi.org/10.1016/0024-3205(91)90333-7 | DOI Listing |
AIDS Res Ther
January 2025
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
The global HIV epidemic remains a major public health challenge, with DTG playing a key role in ART regimens due to its efficacy and tolerability. This study evaluated virological outcomes and resistance mutations in patients on DTG in Mozambique through a retrospective cohort study in seven DREAM centers. Data from 29,601 patients (98.
View Article and Find Full Text PDFGenome Med
January 2025
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Background: Klebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Background: Drug resistance constitutes one of the principal causes of poor prognosis in breast cancer patients. Although cancer cells can maintain viability independently of mitochondrial energy metabolism, they remain reliant on mitochondrial functions for the synthesis of new DNA strands. This dependency underscores a potential link between mitochondrial energy metabolism and drug resistance.
View Article and Find Full Text PDFAnn Clin Microbiol Antimicrob
January 2025
Laboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.
Background: Mycobacterium abscessus (MABS) causes difficult-to-treat pulmonary and extra-pulmonary infections. A combination therapy comprising amikacin, cefoxitin, and a macrolide agent is recommended, but its antimicrobial activity and clinical efficacy is uncertain. Inducible resistance to macrolides (macrolides-iR) has been associated with poor clinical response in pulmonary infections, whilst for extra-pulmonary infections data are scarce.
View Article and Find Full Text PDFBMC Complement Med Ther
January 2025
Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand.
Background: Plant flavonoids such as quercetin are useful for both the therapeutic and preventive care of a variety of illnesses. Nevertheless, their antitumor efficacy against KON oral cancer is still unknown. Therefore, the aim of this investigation was to examine quercetin's anti-growth, anti-migrative, and anti-invasive characteristics.
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