177,853 results match your criteria resistance treatments

Modulation of Akt vs Stat3 activity by the focal adhesion kinase in non-neoplastic mouse fibroblasts.

Exp Cell Res 2021 May 3:112601. Epub 2021 May 3.

Department of Biomedical and Molecular Sciences and Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6.

Adhesion of cells to each other and to the extracellular matrix (ECM) are both required for cellular functions. Cell-to-cell adhesion is mediated by cadherins and their engagement triggers the activation of Stat3, which offers a potent survival signal. Adhesion to the ECM on the other hand, activates FAK which attracts and activates Src, as well as receptor tyrosine kinases (RTKs), the PI3k/Akt and Ras/Erk pathways. Read More

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Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer.

Biochem Pharmacol 2021 May 3:114588. Epub 2021 May 3.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China; Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shenzhen 518000, China; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China. Electronic address:

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Read More

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Comparative macrolide use in humans and animals: should macrolides be moved off the World Health Organisation's critically important antimicrobial list?

J Antimicrob Chemother 2021 May 6. Epub 2021 May 6.

Veterinary Medicine Research and Development, Zoetis, Inc, Kalamazoo, MI, USA.

Macrolide antibiotics are categorized by the WHO as Highest Priority, Critically Important Antimicrobials due to their recommendation as treatment for severe cases of campylobacteriosis in humans; a self-limiting, rarely life-threatening, zoonotic foodborne infection. Low rates of macrolide resistance in Campylobacter jejuni and the availability of alternative treatments have prompted some regulatory schemes to assign macrolides to a lower importance category. Apart from rare, specific infections, macrolides largely play a supportive role to other drug classes in human medicine. Read More

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Suppression of Pseudomonas syringae pv. tomato infection by rhizosphere fungi.

Pest Manag Sci 2021 May 6. Epub 2021 May 6.

Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu Pref. 501-1193, Japan.

Background: Induced resistance against several plant pathogens was reported using different beneficial plant growth promoting microorganisms. The potential of 5 fungal isolates, Trichoderma harzianum GT 3-2, Fusarium equiseti GF 18-3, Fusarium equiseti GF 19-1, Phoma sp. GS 10-1 and Phoma sp. Read More

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Genetic interaction analysis in microbial pathogens: unravelling networks of pathogenesis, antimicrobial susceptibility and host interactions.

FEMS Microbiol Rev 2021 May;45(3)

Department of Molecular and Cellular Biology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.

Genetic interaction (GI) analysis is a powerful genetic strategy that analyzes the fitness and phenotypes of single- and double-gene mutant cells in order to dissect the epistatic interactions between genes, categorize genes into biological pathways, and characterize genes of unknown function. GI analysis has been extensively employed in model organisms for foundational, systems-level assessment of the epistatic interactions between genes. More recently, GI analysis has been applied to microbial pathogens and has been instrumental for the study of clinically important infectious organisms. Read More

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Tetracycline, sulfadimethoxine, and antibiotic resistance gene dynamics during anaerobic digestion of dairy manure.

J Environ Qual 2021 Mar 2. Epub 2021 Mar 2.

Dep. of Chemistry, Univ. at Buffalo, The State Univ. of New York, 611 Natural Science Complex, Buffalo, NY, 14260, USA.

Antibiotic use in animal husbandry is a potential entryway for antibiotics and antibiotic resistance genes (ARGs) to enter the environment through manure fertilizer application. The potential of anaerobic digestion (AD) to remove antibiotics and ARGs was investigated through tetracycline (TC) and sulfadimethoxine (SDM) additions into dairy manure digested for 44 d. This was the first study to evaluate antibiotics at concentrations quantified on-farm and relevant to field applications of manure. Read More

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Pharmacological Inhibition of Insulin Growth Factor-1 Receptor (IGF-1R) Alone or in Combination With Ruxolitinib Shows Therapeutic Efficacy in Preclinical Myeloproliferative Neoplasm Models.

Hemasphere 2021 May 30;5(5):e565. Epub 2021 Apr 30.

Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Germany.

Even after development of the JAK1/JAK2 inhibitor ruxolitinib, myeloproliferative neoplasm (MPN) patients require novel therapeutic options. While ruxolitinib can considerably improve quality of life and prolong survival, it does not modify the natural disease course in most patients. Moreover, resistance develops with prolonged use. Read More

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Standard versus double dose dolutegravir in patients with HIV-associated tuberculosis: a phase 2 non-comparative randomised controlled (RADIANT-TB) trial.

Wellcome Open Res 2021 11;6. Epub 2021 Jan 11.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Dolutegravir, a second-generation integrase strand transfer inhibitor (InSTI), is replacing efavirenz as first-line antiretroviral therapy (ART) in low middle-income countries (LMICs). Tuberculosis remains the leading cause of HIV-related morbidity and mortality in LMICs. Rifampicin is a key agent in the treatment of tuberculosis but induces genes involved in dolutegravir metabolism and efflux. Read More

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January 2021

Comparison of Cell-Free Extracts from Three Newly Identified Strains on the Inhibitory Effect of Adipogenic Differentiation and Insulin Resistance in 3T3-L1 Adipocytes.

Biomed Res Int 2021 15;2021:6676502. Epub 2021 Apr 15.

Cellular Reprogramming and Embryo Biotechnology Laboratory, Dental Research Institute, Seoul National University School of Dentistry, Seoul 08826, Republic of Korea.

Obesity and associated metabolic disorders, including cardiovascular disease and diabetes, are rapidly becoming serious global health problems. It has been reported that () extracts have the beneficial activities of antiobesity and antidiabetes, although few studies have compared the beneficial effects among various extracts. In this study, three new (named LP, LS, and L14) strains were identified, and the antiobesogenic and diabetic effects of their extracts were investigated and compared using 3T3-L1 cells . Read More

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Surveillance of Resistance to New Antibiotics in an Era of Limited Treatment Options.

Front Med (Lausanne) 2021 19;8:652638. Epub 2021 Apr 19.

Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.

As with any health threat, our ability to respond to the emergence and spread of antimicrobial resistance depends on our ability to understand the scale of the problem, magnitude, geographical spread, and trends over time. This is especially true for resistance emergence to newer antibiotics coming to the market as last-resort treatments. Yet current antibiotic surveillance systems are limited to monitoring resistance to commonly prescribed drugs that have been on the market for a long time. Read More

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Nanomaterials for Tumor Hypoxia Relief to Improve the Efficacy of ROS-Generated Cancer Therapy.

Front Chem 2021 19;9:649158. Epub 2021 Mar 19.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China.

Given the fact that excessive levels of reactive oxygen species (ROS) induce damage to proteins, lipids, and DNA, various ROS-generating agents and strategies have been explored to induce cell death and tumor destruction by generating ROS above toxic threshold. Unfortunately, hypoxia in tumor microenvironment (TME) not only promotes tumor metastasis but also enhances tumor resistance to the ROS-generated cancer therapies, thus leading to ineffective therapeutic outcomes. A variety of nanotechnology-based approaches that generate or release O continuously to overcome hypoxia in TME have showed promising results to improve the efficacy of ROS-generated cancer therapy. Read More

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Overview and Update on Methods for Cargo Loading into Extracellular Vesicles.

Processes (Basel) 2021 Feb 15;9(2). Epub 2021 Feb 15.

Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.

The enormous library of pharmaceutical compounds presents endless research avenues. However, several factors limit the therapeutic potential of these drugs, such as drug resistance, stability, off-target toxicity, and inadequate delivery to the site of action. Extracellular vesicles (EVs) are lipid bilayer-delimited particles and are naturally released from cells. Read More

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February 2021

Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.

Nature 2021 May 5. Epub 2021 May 5.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape. Read More

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ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma.

Nature 2021 May 5. Epub 2021 May 5.

Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAF-mutant melanoma, they are ineffective in non-BRAF mutant cells. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAF- and NRAS-mutant melanomas. Read More

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Clearance of Clostridioides difficile Colonization Is Associated with Antibiotic-Specific Bacterial Changes.

mSphere 2021 May 5;6(3). Epub 2021 May 5.

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA

The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing colonization across different community perturbations. However, those bacteria alone have been unable to clear colonization. Read More

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IL-1R1-Dependent Signals Improve Control of Cytosolic Virulent Mycobacteria .

mSphere 2021 May 5;6(3). Epub 2021 May 5.

Electron Microscopy Centre Amsterdam, Amsterdam University Medical Centre AMC, Amsterdam, The Netherlands

infections claim more than a million lives each year, and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from phagolysosomes to the cytosol upon phagocytosis by macrophages. Translocation from the phagolysosome to the cytosol is an ESX-1-dependent process, as previously shown Here, we show that , mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. Read More

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Establishment of a Novel Temozolomide Resistant Subline of Glioblastoma Multiforme Cells and Comparative Transcriptome Analysis With Parental Cells.

Anticancer Res 2021 May;41(5):2333-2347

Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.;

Background/aim: Glioblastoma multiforme (GBM) is a lethal disease with a high rate of chemoresistance to temozolomide (TMZ). The aim of the study was to establish a TMZ-resistant subline from the GBM-8401 cell line to determine the mechanisms of resistance and identify novel effective therapeutics for TMZ-resistant GBM.

Materials And Methods: Comparative transcriptome analysis of GBM-8401/TMZR cells and the parental line was performed using Ion Torrent sequencing. Read More

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Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma.

Steven G Gray

BMC Pulm Med 2021 May 5;21(1):148. Epub 2021 May 5.

Thoracic Oncology Research Group, Central Pathology Laboratory, CPL 30, TCDSJ Cancer Institute, St James's Hospital, Dublin, D08 RX0X, Ireland.

Background: The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Read More

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Peptide-coated polyurethane material reduces wound infection and inflammation.

Acta Biomater 2021 May 2. Epub 2021 May 2.

Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE, 22184 Lund, Sweden. Electronic address:

There is an urgent need for treatments that not only reduce bacterial infection that occurs during wounding but that also target the accompanying excessive inflammatory response. TCP-25, a thrombin-derived antibacterial peptide, scavenges toll-like receptor agonists such as endotoxins and lipoteichoic acid and prevents toll-like receptor-4 dimerization to reduce infection-related inflammation in vivo. Using a combination of biophysical, cellular, and microbiological assays followed by experimental studies in mouse and pig models, we show that TCP-25, when delivered from a polyurethane (PU) material, exerts anti-infective and anti-inflammatory effects in vitro and in vivo. Read More

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The effects of secreted aspartyl proteinase inhibitor ritonavir on azoles-resistant strains of Candida albicans as well as regulatory role of SAP2 and ERG11.

Immun Inflamm Dis 2021 May 5. Epub 2021 May 5.

The Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Background: Candida albicans, the main human fungal pathogen, can cause fungal infection and seriously affect people's health and life. This study aimed to investigate the effects of ritonavir (RIT) on C. albicans and the correlation between SAP2 as well as ERG11 and drug resistance. Read More

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Luteolin and cancer metastasis suppression: focus on the role of epithelial to mesenchymal transition.

Med Oncol 2021 May 5;38(6):66. Epub 2021 May 5.

Research Unit, Induced Resistance and Plant Bioprotection, EA 4707, SFR Condorcet FR CNRS 3417, Faculty of Sciences, University of Reims Champagne-Ardenne, PO Box 1039, 51687, Reims Cedex 2, France.

Epithelial to mesenchymal transition (EMT) is a physiological process that assumes a primary role in the induction of cancer metastasis. This results in increased cell renewal, and resistance to cell death and therapies. EMT, therefore, represents an effective strategy for regulating cancerous cell activity. Read More

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Rosmarinus officinalis L. (rosemary) extract has antibiofilm effect similar to the antifungal nystatin on Candida samples.

An Acad Bras Cienc 2021 30;93(2):e20190366. Epub 2021 Apr 30.

Universidade Estadual Paulista(UNESP), Instituto de Ciência e Tecnologia, Departamento de Biociências e Diagnóstico Bucal, Av. Engenheiro Francisco José Longo, 777, 12245-000 São José dos Campos, SP, Brazil.

Candida spp. are naturally opportunistic and can promote infections. These yeasts can form biofilm, after penetration and adhesion to the biotic or abiotic surfaces. Read More

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Treatment for diabetic peripheral neuropathy: What have we learned from animal models?

Mark Yorek

Curr Diabetes Rev 2021 May 3. Epub 2021 May 3.

Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242 . United States.

Introduction: Animal models have been widely used to investigate the etiology and potential treatments for diabetic peripheral neuropathy. What we have learned from these studies and the extent that this information has been adaptable to the human condition will be the subject of this review article.

Methods: A comprehensive search of the PubMed database was performed, and relevant articles on the topic were included in this review. Read More

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Various strategies applied for the removal of emerging micropollutant sulfamethazine: a systematic review.

Environ Sci Pollut Res Int 2021 May 4. Epub 2021 May 4.

Department of Biotechnology, GM Institute of Technology, Davangere, KA, 577006, India.

Pharmaceutical active drug(s) especially sulfamethazine (SMZ) is considered as one of the major emerging microcontaminants due its long-term existence in the environmental system and that can influence on the developmental of antibacterial resistance genes. Because of this region it has a great concern in the aquatic system. Moreover, the vast utilization of SMZ, excretion of undigested portion by animals and also through dumping or mishandling, SMZ is frequently detected in various samples (including water) of different places and its surroundings. Read More

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Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1.

Am J Cancer Res 2021 15;11(4):1428-1445. Epub 2021 Apr 15.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University Shanghai 200062, China.

The overexpression of ATP-binding cassette transporters subfamily B member 1 (ABCB1) is known to be the primary trigger of multidrug resistance (MDR) in colorectal cancer (CRC), leading to chemotherapy failure. However, factors that regulate chemoresistance in CRC cells are largely unknown. To identify proteins involved in MDR in CRC, we used proteomics and transcriptomics approaches to analyze HCT8/T cells and parental HCT8 cells. Read More

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Ripretinib for the treatment of advanced gastrointestinal stromal tumor.

John R Zalcberg

Therap Adv Gastroenterol 2021 15;14:17562848211008177. Epub 2021 Apr 15.

Department of Medical Oncology, Alfred Health and the School of Public Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract yet represent the most common GI sarcomas. Most GISTs are driven by activating mutations of the and/or genes. Prior to the development of tyrosine kinase inhibitors (TKIs), GISTs were associated with a poor prognosis because conventional cytotoxic chemotherapy was relatively ineffective. Read More

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ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.

Oncogene 2021 May 4. Epub 2021 May 4.

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance. Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation. However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive. Read More

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High-Throughput Approaches for the Identification of Antivirulents.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Department of Biosciences, Rice University, Houston, Texas, USA

Antimicrobial resistance is a serious medical threat, particularly given the decreasing rate of discovery of new treatments. Although attempts to find new treatments continue, it has become clear that merely discovering new antimicrobials, even if they are new classes, will be insufficient. It is essential that new strategies be aggressively pursued. Read More

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A Quorum Sensing System Enables Suppression of Innate Immunity.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA

Some bacterial pathogens utilize cell-cell communication systems, such as quorum sensing (QS), to coordinate genetic programs during host colonization and infection. The human-restricted pathosymbiont (group A streptococcus [GAS]) uses the Rgg2/Rgg3 QS system to modify the bacterial surface, enabling biofilm formation and lysozyme resistance. Here, we demonstrate that innate immune cell responses to GAS are substantially altered by the QS status of the bacteria. Read More

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Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Center for Microbial Dynamics & Infection, School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA

Bacteriocins are proteinaceous antimicrobials produced by bacteria that are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Due to their antipseudomonal activity, R-pyocins have potential as therapeutics in infection. is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF). Read More

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