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Drug Resistance Updates : Reviews and... Jan 2023The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor... (Review)
Review
The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.
Topics: Humans; B7-H1 Antigen; Drug Resistance; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Drug Resistance, Neoplasm
PubMed: 36527888
DOI: 10.1016/j.drup.2022.100907 -
The Yale Journal of Biology and Medicine Mar 2017Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of... (Review)
Review
Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of penicillin in humans, and is therefore an occasion to reflect upon the extraordinary impact that penicillin has had on the lives of millions of people since. This perspective presents a historical account of the discovery of the wonder drug, describes the biological nature of penicillin, and considers lessons that can be learned from the golden era of antibiotic research, which took place between the 1940s and 1960s. Looking back at the history of penicillin might help us to relive this journey to find new treatments and antimicrobial agents. This is particularly relevant today as the emergence of multiple drug resistant bacteria poses a global threat, and joint efforts are needed to combat the rise and spread of resistance.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Humans; Penicillins
PubMed: 28356901
DOI: No ID Found -
Molecules (Basel, Switzerland) Jan 2022Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally... (Review)
Review
Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.
Topics: Animals; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Nanoparticle Drug Delivery System
PubMed: 35163878
DOI: 10.3390/molecules27030616 -
International Microbiology : the... Nov 2021We are living in a society of fear, where the objectivity in estimating risks is distorted by the media and the interested parties. During more than half of a century,... (Review)
Review
We are living in a society of fear, where the objectivity in estimating risks is distorted by the media and the interested parties. During more than half of a century, the feeling of antibiotic resistance as an apocalyptic phenomenon able to push our society to the high mortality rates caused by infectious diseases in the dark pre-antibiotic ages has been steadily rising. However, at the current status of modern medicine, at least in the high-medium income countries, mortality by lack of efficacy of the antibiotic armamentarium in the therapy of infections is a problem, but not a catastrophe. The threat of antibiotic resistance has many other aspects than failures of therapy in the individual patient. Among them, the increase in the frequency of severe and potentially lethal infections, as bacteremia, the population biology alterations of the healthy microbiota, the global acceleration of bacterial evolution by selecting natural genetic tools mediating microbial interactions, and, most importantly, by modifying the equilibrium and composition of environmental microbial communities. All these threats have huge implications for human health as members of a Biosphere entirely rooted in a menaced microbiosphere.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Microbiota
PubMed: 34028624
DOI: 10.1007/s10123-021-00184-y -
Current Opinion in Pharmacology Oct 2020Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible... (Review)
Review
Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible for the development of MDR in cancer tissues. Further, exosomes and its constituents also play a vital role in limiting the efficacy of chemotherapeutic agents. Exosomes are well known for their role in developing resistance in addition to promoting tumor advancement and metastasis. This review discusses the role of exosomes in the development of drug resistance along with their allied mechanisms. This review also discusses the upregulation and downregulation of various exosomal components, which can be effectively employed as diagnostic biomarkers in the treatment of cancer. The essential applications of exosomes to treat drug-resistant cancer have also been discussed.
Topics: Animals; Antineoplastic Agents; Biomarkers; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Exosomes; Humans; Neoplasms; Nucleic Acids; Proteins
PubMed: 33053492
DOI: 10.1016/j.coph.2020.08.017 -
Microbial Drug Resistance (Larchmont,... Jan 2021
Topics: Anti-Infective Agents; Drug Industry; Drug Resistance, Microbial; Genes, Bacterial; Humans
PubMed: 33464170
DOI: 10.1089/mdr.2020.29000.igb -
Essays in Biochemistry Feb 2017The evolution of antifungal resistance among fungal pathogens has rendered the limited arsenal of antifungal drugs futile. Considering the recent rise in the number of... (Review)
Review
The evolution of antifungal resistance among fungal pathogens has rendered the limited arsenal of antifungal drugs futile. Considering the recent rise in the number of nosocomial fungal infections in immunocompromised patients, the emerging clinical multidrug resistance (MDR) has become a matter of grave concern for medical professionals. Despite advances in therapeutic interventions, it has not yet been possible to devise convincing strategies to combat antifungal resistance. Comprehensive understanding of the molecular mechanisms of antifungal resistance is essential for identification of novel targets that do not promote or delay emergence of drug resistance. The present study discusses features and limitations of the currently available antifungals, mechanisms of antifungal resistance and highlights the emerging therapeutic strategies that could be deployed to combat MDR.
Topics: Antifungal Agents; Drug Resistance, Fungal; Drug Resistance, Multiple; Drug Therapy, Combination; Membrane Transport Proteins; Molecular Targeted Therapy
PubMed: 28258238
DOI: 10.1042/EBC20160067 -
Microbiology Spectrum Apr 2018is a major foodborne pathogen and has become increasingly resistant to clinically important antimicrobials. To cope with the selection pressure from antimicrobial use... (Review)
Review
is a major foodborne pathogen and has become increasingly resistant to clinically important antimicrobials. To cope with the selection pressure from antimicrobial use in both veterinary and human medicine, has developed multiple mechanisms for antibiotic resistance, including modification or mutation of antimicrobial targets, modification or inactivation of antibiotics, and reduced drug accumulation by drug efflux pumps. Some of these mechanisms confer resistance to a specific class of antimicrobials, while others give rise to multidrug resistance. Notably, new antibiotic resistance mechanisms continuously emerge in , and some examples include the recently discovered multidrug resistance genomic islands harboring multiple genes involved in the resistance to aminoglycosides and macrolides, a novel Cfr(C) conferring resistance to phenicols and other drugs, and a potent multidrug efflux pump CmeABC variant (RE-CmeABC) that shows a significantly enhanced function in multidrug resistance and is associated with exceedingly high-level resistance to fluoroquinolones. These newly emerged resistance mechanisms are horizontally transferable and greatly facilitate the adaptation of in the food-producing environments where antibiotics are frequently used. In this article, we will discuss how resists the action of various classes of antimicrobials, with an emphasis on newly discovered mechanisms.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Campylobacter; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Gene Transfer, Horizontal; Genomic Islands; Humans; Membrane Transport Proteins; Mutation
PubMed: 29623873
DOI: 10.1128/microbiolspec.ARBA-0013-2017 -
The Science of the Total Environment Jun 2019Aquatic ecosystems subjected to anthropogenic pressures are places of rapid evolution of microbial communities and likely hotspots for selection and emergence of... (Review)
Review
Aquatic ecosystems subjected to anthropogenic pressures are places of rapid evolution of microbial communities and likely hotspots for selection and emergence of antibiotic resistant bacteria. In urban settings, water quality and the risk of infection are generally assessed in sewers and in effluents of wastewater treatment plants. Physical and chemical parameters as well as the presence of antibiotics, antibiotic-resistant bacteria and genes of resistance are driven by urban activities, with adverse effects on aquatic ecosystems. In this paper we review the environmental pressures exerted on bacterial communities in urban runoff waters and discuss the impact of these settings on antibiotic resistance. Considering the worrisome epidemiology of infectious diseases and estimated mortality due to antimicrobial resistance in the coming decades, there is an urgent need to identify all environmental reservoirs of resistant bacteria and resistance genes to complete our knowledge of the epidemiological cycle and of the dynamics of urban antibiotic resistance.
Topics: Bacteria; Cities; Drug Resistance, Bacterial; Drug Resistance, Microbial; Microbiota; Wastewater
PubMed: 30826682
DOI: 10.1016/j.scitotenv.2019.02.183 -
Advances in Experimental Medicine and... 2019ATP-binding cassette (ABC) transporters are involved in active pumping of many diverse substrates through the cellular membrane. The transport mediated by these proteins... (Review)
Review
ATP-binding cassette (ABC) transporters are involved in active pumping of many diverse substrates through the cellular membrane. The transport mediated by these proteins modulates the pharmacokinetics of many drugs and xenobiotics. These transporters are involved in the pathogenesis of several human diseases. The overexpression of certain transporters by cancer cells has been identified as a key factor in the development of resistance to chemotherapeutic agents. In this chapter, the localization of ABC transporters in the human body, their physiological roles, and their roles in the development of multidrug resistance (MDR) are reviewed. Specifically, P-glycoprotein (P-GP), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP/ABCG2) are described in more detail. The potential of ABC transporters as therapeutic targets to overcome MDR and strategies for this purpose are discussed as well as various explanations for the lack of efficacy of ABC drug transporter inhibitors to increase the efficiency of chemotherapy.
Topics: ATP-Binding Cassette Transporters; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms; Tissue Distribution
PubMed: 31571174
DOI: 10.1007/978-981-13-7647-4_12