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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 -
Chemical Communications (Cambridge,... May 2023Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming... (Review)
Review
Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming decades. Although some of the underlying causes leading up to antibiotic resistance are well understood, many of the molecular processes involved remain elusive. To better appreciate at a molecular level how resistance emerges, customized chemical biology tools can offer a solution. This Feature Article attempts to provide an overview of the wide variety of tools that have been developed over the last decade, by highlighting some of the more illustrative examples. These include the use of fluorescent, photoaffinity and activatable antibiotics and bacterial components to start to unravel the molecular mechanisms involved in resistance. The antibiotic crisis is an eminent global threat and requires the continuous development of creative chemical tools to dissect and ultimately counteract resistance.
Topics: Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial
PubMed: 37039397
DOI: 10.1039/d3cc00759f -
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 -
Sub-cellular Biochemistry 2021Chemotherapy represents the current mainstay therapeutic approach for most types of cancer. Despite the development of targeted chemotherapeutic strategies, the efficacy...
Chemotherapy represents the current mainstay therapeutic approach for most types of cancer. Despite the development of targeted chemotherapeutic strategies, the efficacy of anti-cancer drugs is severely limited by the development of drug resistance. Multidrug resistance (MDR) consists of the simultaneous resistance to various unrelated cytotoxic drugs and is one of the main causes of anticancer treatment failure. One of the principal mechanisms by which cancer cells become MDR involves the overexpression of ATP Binding Cassette (ABC) transporters, such as P-glycoprotein (P-gp), mediating the active efflux of cytotoxic molecules from the cytoplasm. Extracellular vesicles (EVs) are submicron lipid-enclosed vesicles that are released by all cells and which play a fundamental role in intercellular communication in physiological and pathological contexts. EVs have fundamental function at each step of cancer development and progression. They mediate the transmission of MDR through the transfer of vesicle cargo including functional ABC transporters as well as nucleic acids, proteins and lipids. Furthermore, EVs mediate MDR by sequestering anticancer drugs and stimulate cancer cell migration and invasion. EVs also mediate the communication with the tumour microenvironment and the immune system, resulting in increased angiogenesis, metastasis and immune evasion. All these actions contribute directly and indirectly to the development of chemoresistance and treatment failure. In this chapter, we describe the many roles EVs play in the acquisition and spread of chemoresistance in cancer. We also discuss possible uses of EVs as pharmacological targets to overcome EV-mediated drug resistance and the potential that the analysis of tumour-derived EVs offers as chemoresistance biomarkers.
Topics: Antineoplastic Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Extracellular Vesicles; Humans; Neoplasms; Tumor Microenvironment
PubMed: 33779919
DOI: 10.1007/978-3-030-67171-6_9 -
Indian Journal of Dermatology,... 2023Antimicrobial stewardship refers to a well-coordinated program which promotes the scientific and rational use of antimicrobials, reduces the chances of drug resistance... (Review)
Review
Antimicrobial stewardship refers to a well-coordinated program which promotes the scientific and rational use of antimicrobials, reduces the chances of drug resistance and improves patient outcomes. A comprehensive English language literature search was done across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for the period 1990-2022, revealing a large volume of reports of growing resistance to established antifungal therapies, against a backdrop of irrational and unscientific prescriptions. As a result of this, antifungal stewardship, a new kid on the block, has recently garnered attention. This review article is an attempt to summarise the basic concept of stewardship programs, highlighting the dire need to implement the same in the present situation of antifungal resistance and treatment failure.
Topics: Humans; Antifungal Agents; Anti-Infective Agents; Antimicrobial Stewardship; Drug Resistance, Fungal; Drug Resistance
PubMed: 36461808
DOI: 10.25259/IJDVL_91_2022 -
The Psychiatric Clinics of North America Jun 2016Although treatment-resistant schizophrenia (TRS) was described 50 years ago and has a gold standard treatment with clozapine based on well-defined criteria, there is... (Review)
Review
Although treatment-resistant schizophrenia (TRS) was described 50 years ago and has a gold standard treatment with clozapine based on well-defined criteria, there is still a matter of great interest and controversy. In terms of the underlying mechanisms of the development of TRS, progress has been made for the elucidation of the neurochemical mechanisms. Structural neuroimaging studies have shown that patients with TRS have significant reduction of the prefrontal cortex volume when compared with non- TRS. This article updates and enhances our previous review with new evidence mainly derived from new studies, clinical trials, systematic reviews, and meta-analyses.
Topics: Antipsychotic Agents; Clozapine; Cognitive Behavioral Therapy; Drug Resistance; Electroconvulsive Therapy; Humans; Neuroimaging; Prefrontal Cortex; Risk Factors; Schizophrenia; Transcranial Magnetic Stimulation; Treatment Outcome
PubMed: 27216902
DOI: 10.1016/j.psc.2016.01.006 -
Environmental Microbiology Dec 2021
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Microbial
PubMed: 34773441
DOI: 10.1111/1462-2920.15841 -
Revue de L'infirmiere Oct 2023
Topics: Bacteria; Drug Resistance, Multiple, Bacterial
PubMed: 37838375
DOI: 10.1016/j.revinf.2023.08.015 -
Drug Discovery Today Sep 2022Drug resistance to chemotherapy and molecularly targeted therapies is a current challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic... (Review)
Review
Drug resistance to chemotherapy and molecularly targeted therapies is a current challenge in cancer treatments. The underlying mechanisms of resistance to cytotoxic chemotherapeutics and to drugs that target a specific molecule are not understood completely. In recent years, emerging evidence has frequently suggested that the dysregulation of deubiquitinating enzymes (DUBs) plays important roles in the development of drug resistance. We focus on the molecular mechanisms through which DUBs enable cancer cells to escape cell death and survive when exposed to a variety of anti-cancer drugs. Furthermore, this review summarizes the potential application of DUB inhibitors in combination therapies to overcome drug resistance.
Topics: Antineoplastic Agents; Deubiquitinating Enzymes; Drug Resistance; Molecular Targeted Therapy
PubMed: 35760282
DOI: 10.1016/j.drudis.2022.06.009 -
Methods in Molecular Biology (Clifton,... 2022Understanding drug resistance in cancer is paramount to improving patient outcomes, quality of life and reducing toxicities in patients receiving chemotherapy....
Understanding drug resistance in cancer is paramount to improving patient outcomes, quality of life and reducing toxicities in patients receiving chemotherapy. Pharmacogenomic methods seek to understand the interaction of genomic variation and response to chemotherapeutic treatment. This chapter presents a workflow to interrogate multiple genomic inputs and individually assess their relationship with the phenotype of drug resistance using hierarchical clustering to determine the set of features that can best describe what features are associated with drug resistance. Then in a gene-centric manner regulatory features such as miRNAs, SNPs, or DNA methylation can be related back to the differential expression of genes to give understanding to the mechanism underlying resistance. In this chapter, we describe a computational method that can be adapted to a number of different diseases and phenotypes in which there are multiple genomic data types available with concordant phenotypic drug resistance information.
Topics: Drug Resistance; Genomics; Pharmacogenetics; Phenotype; Quality of Life
PubMed: 35867232
DOI: 10.1007/978-1-0716-2513-2_15