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Life Sciences Dec 2020Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and... (Review)
Review
Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and radiotherapy are the most common sarcoma treatments. However, sarcomas' response rates to chemotherapy are quite low and sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multi-drug resistance (MDR). Cancer cellular plasticity plays pivotal roles in cancer initiation, progression, therapy resistance and cancer relapse. Moreover, cancer cellular plasticity can be regulated by a multitude of factors, such as genetic and epigenetic alterations, tumor microenvironment (TME) or selective pressure imposed by treatment. Recent studies have demonstrated that cellular plasticity is involved in sarcoma progression and chemoresistance. It's essential to understand the molecular mechanisms of cellular plasticity as well as its roles in sarcoma progression and drug resistance. Therefore, this review focuses on the regulatory mechanisms and pathological roles of these diverse cellular plasticity programs in sarcoma. Additionally, we propose cellular plasticity as novel therapeutic targets to reduce sarcoma drug resistance.
Topics: Antineoplastic Agents; Cell Plasticity; Disease Progression; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Sarcoma; Tumor Microenvironment
PubMed: 33069737
DOI: 10.1016/j.lfs.2020.118589 -
Biomedicine & Pharmacotherapy =... Jun 2023Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically,... (Review)
Review
Multi-drug resistance (MDR) in cancer cells, either intrinsic or acquired through various mechanisms, significantly hinders the therapeutic efficacy of drugs. Typically, the reduced therapeutic performance of various drugs is predominantly due to the inherent over expression of ATP-binding cassette (ABC) transporter proteins on the cell membrane, resulting in the deprived uptake of drugs, augmenting drug detoxification, and DNA repair. In addition to various physiological abnormalities and extensive blood flow, MDR cancer phenotypes exhibit improved apoptotic threshold and drug efflux efficiency. These severe consequences have substantially directed researchers in the fabrication of various advanced therapeutic strategies, such as co-delivery of drugs along with various generations of MDR inhibitors, augmented dosage regimens and frequency of administration, as well as combinatorial treatment options, among others. In this review, we emphasize different reasons and mechanisms responsible for MDR in cancer, including but not limited to the known drug efflux mechanisms mediated by permeability glycoprotein (P-gp) and other pumps, reduced drug uptake, altered DNA repair, and drug targets, among others. Further, an emphasis on specific cancers that share pathogenesis in executing MDR and effluxed drugs in common is provided. Then, the aspects related to various nanomaterials-based supramolecular programmable designs (organic- and inorganic-based materials), as well as physical approaches (light- and ultrasound-based therapies), are discussed, highlighting the unsolved issues and future advancements. Finally, we summarize the review with interesting perspectives and future trends, exploring further opportunities to overcome MDR.
Topics: Humans; Antineoplastic Agents; Drug Resistance, Neoplasm; Drug Resistance, Multiple; ATP-Binding Cassette Transporters; Neoplasms; Pharmaceutical Preparations
PubMed: 37031496
DOI: 10.1016/j.biopha.2023.114643 -
Pathology Apr 2015Enterobacteriaceae are responsible for a large proportion of serious, life-threatening infections and resistance to multiple antibiotics in these organisms is an... (Review)
Review
Enterobacteriaceae are responsible for a large proportion of serious, life-threatening infections and resistance to multiple antibiotics in these organisms is an increasing global public health problem. Mutations in chromosomal genes contribute to antibiotic resistance, but Enterobacteriaceae are adapted to sharing genetic material and much important resistance is due to 'mobile' resistance genes. Different mobile genetic elements, which have different characteristics, are responsible for capturing these genes from the chromosomes of a variety of bacterial species and moving them between DNA molecules. If transferred to plasmids, these resistance genes are then able to be transferred 'horizontally' between different bacterial cells, including different species, and well as being transferred 'vertically' during cell division. Carriage of several resistance genes on the same plasmid enables a bacterial cell to acquire multi-resistance in a single step and means that spread of one resistance gene may be co-selected for by use of antibiotics other than those to which it confers resistance. Many different mobile genes conferring resistance to each class of antibiotic have been identified, complicating detection of the factors responsible for a particular resistance phenotype, especially when changes in chromosomal genes may also confer or contribute to resistance. Understanding the mechanisms of antibiotic resistance, and the means by which these mechanisms can evolve and disseminate, is important for developing ways to efficiently track the spread of resistance and to optimise treatment.
Topics: Drug Resistance, Bacterial; Drug Resistance, Microbial; Drug Resistance, Multiple; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Interspersed Repetitive Sequences
PubMed: 25764207
DOI: 10.1097/PAT.0000000000000237 -
European Journal of Medicinal Chemistry Aug 2021Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells... (Review)
Review
Clinically, chemotherapy is the mainstay in the treatment of multiple cancers. However, highly adaptable and activated survival signaling pathways of cancer cells readily emerge after long exposure to chemotherapeutics drugs, resulting in multi-drug resistance (MDR) and treatment failure. Recently, growing evidences indicate that the molecular action mechanisms of cancer MDR are closely associated with abnormalities in saccharides. In this review, saccharides affecting cancer MDR development are elaborated and analyzed in terms of aberrant aerobic glycolysis and its related enzymes, abnormal glycan structures and their associated enzymes, and glycoproteins. The reversal strategies including depletion of ATP, circumventing the original MDR pathway, activation by or inhibition of sugar-related enzymes, combination therapy with traditional cytotoxic agents, and direct modification on the sugar moiety, are ultimately proposed. It follows that abnormal saccharides have a significant effect on cancer MDR development, providing a new perspective for overcoming MDR and improving the outcome of chemotherapy.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Molecular Structure; Neoplasms; Polysaccharides
PubMed: 33933752
DOI: 10.1016/j.ejmech.2021.113487 -
The Journal of Hospital Infection Dec 2021Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant... (Review)
Review
Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Dysbiosis; Gastrointestinal Microbiome; Humans; Pharmaceutical Preparations
PubMed: 34492304
DOI: 10.1016/j.jhin.2021.09.001 -
ACS Nano Jul 2022Antibiotic resistance has become a serious threat to human health due to the overuse of antibiotics. Different antibiotics are being developed to treat resistant... (Review)
Review
Antibiotic resistance has become a serious threat to human health due to the overuse of antibiotics. Different antibiotics are being developed to treat resistant bacteria, but the development cycle of antibiotics is hard to keep up with the high incidence of antibiotic resistance. Recent advances in antimicrobial nanomaterials have made nanotechnology a powerful solution to this dilemma. Among these nanomaterials, gold nanomaterials have excellent antibacterial efficacy and biosafety, making them alternatives to antibiotics. This review presents strategies that use gold nanomaterials to combat drug-resistant bacteria. We focus on the influence of physicochemical factors such as surface chemistry, size, and shape of gold nanomaterials on their antimicrobial properties and describe the antimicrobial applications of gold nanomaterials in medical devices. Finally, the existing challenges and future directions are discussed.
Topics: Humans; Gold; Nanostructures; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Bacteria; Anti-Infective Agents
PubMed: 35776694
DOI: 10.1021/acsnano.2c02269 -
Nutrients Oct 2019Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the... (Review)
Review
Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the side effects have been raised, and development of alternative therapy is inevitable. The purpose of this study is to prove the efficacy of dietary substances as a source of anti-tumor drugs by identifying their carcinostatic activities in specific pathological mechanisms. According to numerous studies, dietary substances were effective through following five mechanisms; apoptosis, anti-angiogenesis, anti-metastasis, microRNA (miRNA) regulation, and anti-multi-drug-resistance (MDR). About seventy dietary substances showed the anti-prostate cancer activities. Most of the substances induced the apoptosis, especially acting on the mechanism of caspase and poly adenosine diphosphate ribose polymerase (PARP) cleavage. These findings support that dietary compounds have potential to be used as anticancer agents as both food supplements and direct clinical drugs.
Topics: Anticarcinogenic Agents; Apoptosis; Caspase Inhibitors; Diet; Drug Resistance, Multiple; Humans; Male; MicroRNAs; Neoplasm Metastasis; Neovascularization, Pathologic; Phytochemicals; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms
PubMed: 31597327
DOI: 10.3390/nu11102401 -
Journal of Infection and Chemotherapy :... Oct 2014Staphylococcus (S.) aureus silently stays as our natural flora, and yet sometimes threatens our life as a tenacious pathogen. In addition to its ability to outwit our... (Review)
Review
Staphylococcus (S.) aureus silently stays as our natural flora, and yet sometimes threatens our life as a tenacious pathogen. In addition to its ability to outwit our immune system, its multi-drug resistance phenotype makes it one of the most intractable pathogenic bacteria in the history of antibiotic chemotherapy. It conquered practically all the antibiotics that have been developed since 1940s. In 1961, the first MRSA was found among S. aureus clinical isolates. Then MRSA prevailed throughout the world as a multi-resistant hospital pathogen. In 1997, MRSA strain Mu50 with reduced susceptibility to vancomycin was isolated. Vancomycin-intermediate S. aureus (VISA), so named according to the CLSI criteria, was the product of adaptive mutation of S. aureus against vancomycin that had long been the last resort to MRSA infection. Here, we describe the genetic basis for the remarkable ability of S. aureus to acquire multi-antibiotic resistance, and propose a novel paradigm for future chemotherapy against the multi-resistant pathogens.
Topics: Anti-Bacterial Agents; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Multiple, Bacterial; Humans; Origin Recognition Complex; Penicillin-Binding Proteins; Phenotype; Staphylococcal Infections; Staphylococcus aureus
PubMed: 25172776
DOI: 10.1016/j.jiac.2014.08.001 -
Current Opinion in Microbiology Oct 2023Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of... (Review)
Review
Bacterial pathogens are constantly evolving new resistance mechanisms against antibiotics; hence, strategies to potentiate existing antibiotics or combat mechanisms of resistance using adjuvants are always in demand. Recently, inhibitors have been identified that counteract enzymatic modification of the drugs isoniazid and rifampin, which have implications in the study of multi-drug-resistant mycobacteria. A wealth of structural studies on efflux pumps from diverse bacteria has also fueled the design of new small-molecule and peptide-based agents to prevent the active transport of antibiotics. We envision that these findings will inspire microbiologists to apply existing adjuvants to clinically relevant resistant strains, or to use described platforms to discover novel antibiotic adjuvant scaffolds.
Topics: Bacteria; Anti-Bacterial Agents; Drug Resistance, Microbial; Biological Transport; Drug Resistance, Multiple, Bacterial
PubMed: 37329679
DOI: 10.1016/j.mib.2023.102334 -
Current Topics in Medicinal Chemistry 2018The menace of multi-drug resistance by bacterial pathogens that are responsible for infectious diseases in humans and animals cannot be over-emphasized. Many bacteria... (Review)
Review
The menace of multi-drug resistance by bacterial pathogens that are responsible for infectious diseases in humans and animals cannot be over-emphasized. Many bacteria develop resistance to antibiotics by one or more combination of resistance mechanisms namely, efflux pump activation thereby reducing bacteria intracellular antibiotic concentration, synthesizing a protein that protects target site causing poor antibiotic affinity to the binding site, or mutations in DNA and topoisomerase gene coding that alters residues in the binding sites. The ability to use a combination of these resistance mechanisms among others creates a phenomenon known as antimicrobial drug resistance. The development of a new class of antibiotics to address bacterial resistance will require many resources, such as time-consuming effort and high cost associated with commercial risk. Hence, the researchers have adopted a strategic approach to enhance the antibacterial efficacy of existing antibiotics by conjugation or combination of existing antibiotics. A number of peptides have become known as antibacterial, cell-penetrating, or membrane-active agents. Antibiotics-Peptide Conjugates (APCs) are a combination of known antibiotics with a peptide connected through a linker. The rationale is to produce an alternative multifunctional antimicrobial compound that will elicit synergistic antibacterial activities while reducing known shortcomings of antibiotics or peptides, such as cellular penetration, serum instability, cytotoxicity, hemolysis, and instability in high salt conditions. In this review, we overview APCs which are used, as a strategy to combat the menace of multi-drug resistance of bacterial pathogens. Furthermore, we explain the focus area of adopted APC strategies and physicochemical properties data that show how they can be used to improve antibacterial efficacy.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Peptides
PubMed: 30499392
DOI: 10.2174/1568026619666181129141524