scholarly journals Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

2007 ◽  
Vol 71 (3) ◽  
pp. 463-476 ◽  
Author(s):  
Jacek Lubelski ◽  
Wil N. Konings ◽  
Arnold J. M. Driessen
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Atp Hydrolysis ◽  
Vast Number ◽  
Active Efflux ◽  
Bacterial Drug Resistance ◽  
Higher Eukaryotes ◽  
Molecular Mode ◽  
New Strategies

SUMMARY Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria.

scholarly journals The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Carolina Soekmadji ◽  
Colleen C. Nelson
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Advanced Prostate Cancer ◽  
Control Cell ◽  
Extracellular Vesicle ◽  
Multidrug Resistance Proteins ◽  
Acquired Drug Resistance ◽  
Resistance Proteins

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

The role of microvesicles in cancer progression and drug resistance

2013 ◽  
Vol 41 (1) ◽  
pp. 293-298 ◽  
Author(s):  
Samireh Jorfi ◽  
Jameel M. Inal
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Progression ◽  
Chemotherapeutic Agents ◽  
Malignant Cells ◽  
Intercellular Transport ◽  
Wide Range ◽  
Anti Cancer ◽  
Mdr Multidrug Resistance

Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.

scholarly journals A role of ATP hydrolysis in the ribosomal elongation cycle of higher eukaryotes

1999 ◽  
Vol 15 (1) ◽  
pp. 10-11
Author(s):  
A. I. Serebryanik ◽  
A. V. El'skaya
Keyword(s):  
Atp Hydrolysis ◽  
Elongation Cycle ◽  
Higher Eukaryotes

scholarly journals Molecular surveillance of the Plasmodium vivax multidrug resistance 1 gene in Peru between 2006 and 2015

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Fredy E. Villena ◽  
Jorge L. Maguiña ◽  
Meddly L. Santolalla ◽  
Edwar Pozo ◽  
Carola J. Salas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Plasmodium Vivax ◽  
Amazon Basin ◽  
North Coast ◽  
Molecular Surveillance ◽  
Synonymous Mutations ◽  
The North ◽  
Multidrug Resistance 1 Gene

Abstract Background The high incidence of Plasmodium vivax infections associated with clinical severity and the emergence of chloroquine (CQ) resistance has posed a challenge to control efforts aimed at eliminating this disease. Despite conflicting evidence regarding the role of mutations of P. vivax multidrug resistance 1 gene (pvmdr1) in drug resistance, this gene can be a tool for molecular surveillance due to its variability and spatial patterns. Methods Blood samples were collected from studies conducted between 2006 and 2015 in the Northern and Southern Amazon Basin and the North Coast of Peru. Thick and thin blood smears were prepared for malaria diagnosis by microscopy and PCR was performed for detection of P. vivax monoinfections. The pvmdr1 gene was subsequently sequenced and the genetic data was used for haplotype and diversity analysis. Results A total of 550 positive P. vivax samples were sequenced; 445 from the Northern Amazon Basin, 48 from the Southern Amazon Basin and 57 from the North Coast. Eight non-synonymous mutations and three synonymous mutations were analysed in 4,395 bp of pvmdr1. Amino acid changes at positions 976F and 1076L were detected in the Northern Amazon Basin (12.8%) and the Southern Amazon Basin (4.2%) with fluctuations in the prevalence of both mutations in the Northern Amazon Basin during the course of the study that seemed to correspond with a malaria control programme implemented in the region. A total of 13 pvmdr1 haplotypes with non-synonymous mutations were estimated in Peru and an overall nucleotide diversity of π = 0.00054. The Northern Amazon Basin was the most diverse region (π = 0.00055) followed by the Southern Amazon and the North Coast (π = 0.00035 and π = 0.00014, respectively). Conclusion This study showed a high variability in the frequencies of the 976F and 1076L polymorphisms in the Northern Amazon Basin between 2006 and 2015. The low and heterogeneous diversity of pvmdr1 found in this study underscores the need for additional research that can elucidate the role of this gene on P. vivax drug resistance as well as in vitro and clinical data that can clarify the extend of CQ resistance in Peru.

scholarly journals Role of glycine-534 and glycine-1179 of human multidrug resistance protein (MDR1) in drug-mediated control of ATP hydrolysis

2001 ◽  
Vol 356 (1) ◽  
pp. 71 ◽  
Author(s):  
Gergely SZAKÁCS ◽  
Csilla ÖZVEGY ◽  
Éva BAKOS ◽  
Balázs SARKADI ◽  
András VÁRADI
Keyword(s):  
Multidrug Resistance ◽  
Atp Hydrolysis ◽  
Multidrug Resistance Protein ◽  
Resistance Protein

scholarly journals The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors

2022 ◽  
Vol 12 ◽  
Author(s):  
Huan Tong ◽  
He Wei ◽  
Alhaji Osman Smith ◽  
Juan Huang
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Epigenetic Modification ◽  
Advanced Malignancy ◽  
Tumor Drug Resistance ◽  
New Strategies

Tumor immunotherapy, one of the efficient therapies in cancers, has been called to the scientific community’s increasing attention lately. Among them, immune checkpoint inhibitors, providing entirely new modalities to treat cancer by leveraging the patient’s immune system. They are first-line treatments for varieties of advanced malignancy, such as melanoma, gastrointestinal tumor, esophageal cancer. Although immune checkpoint inhibitors (ICIs) treatment has been successful in different cancers, drug resistance and relapses are common, such as in colorectal cancer. Therefore, it is necessary to improve the efficacy of immune checkpoint therapy for cancer patients who do not respond or lowly response to current treatments. N6-methyladenosine (m6A), as a critical regulator of transcript expression, is the most frequently internal modification of mRNA in the human body. Recently, it has been proposed that m6A epigenetic modification is a potential driver of tumor drug resistance. In this report, we will briefly outline the relevant mechanisms, general treatment status of immune checkpoint inhibitors in colorectal cancer, how m6A epigenetic modifications regulate the response of ICIs in CRC and provide new strategies for overcoming the resistance of ICIs in CRC.

DEVELOPMENT OF PLATINUM(IV) COMPLEXES AS ANTICANCER PRODRUGS: THE STORY SO FAR

COSMOS ◽  
2012 ◽  
Vol 08 (01) ◽  
pp. 121-134 ◽  
Author(s):  
DANIEL YUAN QIANG WONG ◽  
WEE HAN ANG
Keyword(s):  
Heavy Metals ◽  
Drug Resistance ◽  
Paradigm Shift ◽  
Chemotherapeutic Agents ◽  
High Toxicity ◽  
Toxic Heavy Metals ◽  
Antitumor Properties ◽  
New Strategies ◽  
Unique Chemical

The serendipitous discovery of the antitumor properties of cisplatin by Barnett Rosenberg some forty years ago brought about a paradigm shift in the field of medicinal chemistry and challenged conventional thinking regarding the role of potentially toxic heavy metals in drugs. Platinum(II)-based anticancer drugs have since become some of the most effective and widely-used drugs in a clinician's arsenal and have saved countless lives. However, they are limited by high toxicity, severe side-effects and the incidence of drug resistance. In recent years, attention has shifted to stable platinum(IV) complexes as anticancer prodrugs. By exploiting the unique chemical and structural attributes of their scaffolds, these platinum(IV) prodrugs offer new strategies of targeting and killing cancer cells. This review summarizes the development of anticancer platinum(IV) prodrugs to date and some of the exciting strategies that utilise the platinum(IV) construct as targeted chemotherapeutic agents against cancer.

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