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https://www.readbyqxmd.com/read/29352745/negative-supercoiling-of-dna-by-gyrase-is-inhibited-in-salmonella-enterica-serovar-typhimurium-during-adaptation-to-acid-stress
#1
Aoife M Colgan, Heather J Quinn, Stefani C Kary, Lesley A Mitchenall, Anthony Maxwell, Andrew Ds Cameron, Charles J Dorman
DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4 to 5) macrophage vacuole and DNA relaxation correlates with upregulation of Salmonella genes involved in adaptation to the macrophage environment. Bacterial ATP levels did not increase during adaptation to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic-membrane-located inhibitor of proton-driven F1 F0 ATP synthase activity. Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation...
January 20, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29352737/bronchiolitis-obliterans-syndrome-is-associated-with-increased-p-glycoprotein-expression-and-loss-of-glucocorticoid-receptor-from-steroid-resistant-pro-inflammatory-cd8-t-cells
#2
Greg Hodge, Sandra Hodge, Phan Tien Nguyen, Aeneas Yeo, Parama Sarkar, Arash Badiei, C L Holmes-Liew, Paul N Reynolds, Mark Holmes
Immunosuppressive therapy fails to suppress the production of pro-inflammatory cytokines, particularly by CD8+T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant...
January 20, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29352734/resistance-to-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-the-role-of-cancer-stem-cells
#3
REVIEW
Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi
Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance...
January 20, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352713/clinical-variables-associated-with-overall-survival-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-sipuleucel-t-immunotherapy
#4
Xiao X Wei, Jaselle Perry, Emily Chang, Li Zhang, Robert A Hiatt, Charles J Ryan, Eric J Small, Lawrence Fong
BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its approval by the Food and Drug Administration was based on demonstration of an overall survival (OS) benefit in randomized placebo-controlled phase III trials. However, treatment was associated with a prostate-specific antigen (PSA) decline in only a small minority of patients. Understanding the clinical factors that are associated with OS could help guide treatment decisions, including patient selection and the timing of sipuleucel-T relative to other therapies...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352627/indications-and-limits-of-stereoelectroencephalography-seeg
#5
REVIEW
Lorella Minotti, Alexandra Montavont, Julia Scholly, Louise Tyvaert, Delphine Taussig
Epilepsy surgery is now an accepted treatment to achieve seizure control in carefully selected patients, both children and adults, suffering from drug-resistant focal epilepsy. Although surgical strategies can often be defined on the basis of non-invasive diagnostic procedures, and despite the recent advances in this field, an increasing number of more complex cases requires invasive EEG (iEEG) to provide precise information on the localization of the epileptogenic zone (EZ), its relationships with eloquent cortex (EC), and the feasibility of a tailored surgical resection...
January 15, 2018: Neurophysiologie Clinique, Clinical Neurophysiology
https://www.readbyqxmd.com/read/29352387/current-perspectives-on-erythema-multiforme
#6
REVIEW
Marianne Lerch, Carlo Mainetti, Benedetta Terziroli Beretta-Piccoli, Thomas Harr
Recognition and timely adequate treatment of erythema multiforme remain a major challenge. In this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. The diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings...
January 19, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29352386/glucose-homeostasis-in-major-depression-and-schizophrenia-a-comparison-among-drug-na%C3%A3-ve-first-episode-patients
#7
Johann Steiner, Brisa S Fernandes, Paul C Guest, Henrik Dobrowolny, Gabriela Meyer-Lotz, Sabine Westphal, Katrin Borucki, Kolja Schiltz, Zoltán Sarnyai, Hans-Gert Bernstein
There is evidence for insulin resistance in drug-naïve first-episode schizophrenia (Sz) patients. We have tested whether impaired insulin homeostasis is also present in first-episode patients with major depression (MD) and if this can be discerned from stress-related and medication effects. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined in a cross-sectional cohort study of acute first-episode drug-naïve patients with MD (n = 18) or Sz (n = 24), and healthy controls (C, n = 43)...
January 19, 2018: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#8
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#9
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352146/effects-of-renal-denervation-on-cardiac-structural-and-functional-abnormalities-in-patients-with-resistant-hypertension-or-diastolic-dysfunction
#10
Shiying Wang, Suxia Yang, Xinxin Zhao, Jun Shi
The aim of the present study is to systematically evaluate the impact of RDN on cardiac structure and function in patients with resistant hypertension (RH) or diastolic dysfunction. We retrieved Pubmed, Embase and Cocharane Library databases, from inception to April 1st, 2016. Studies reporting left ventricular mass (LVMI) or left ventricular (LV) diastolic function (reflected by the ratio of mitral inflow velocity to annular relaxation velocity [E/e']) responses to RDN were included. Two randomized controlled trials (RCTs), 3 controlled studies and 11 uncontrolled studies were finally identified...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352056/relationship-between-adverse-events-and-antiplatelet-drug-resistance-in-neurovascular-intervention-a-meta-analysis
#11
Eun Jung Shim, Chang-Woo Ryu, Soonchan Park, Han Na Lee, Hee Sup Shin, Sang-Beom Kim
BACKGROUND: This meta-analysis aimed to evaluate the association between antiplatelet resistance and the risk of procedure-related complications in neurovascular interventions. METHODS: We identified relevant articles by searching electronic databases and reviewed the reference lists of selected papers. The risk of adverse events between antiplatelet responders and hyporesponders during neurointervention was compared in eligible clinical studies. Risk ratios (RRs) and 95% CIs were pooled using a random-effects meta-analysis...
January 19, 2018: Journal of Neurointerventional Surgery
https://www.readbyqxmd.com/read/29351990/saa3-is-a-key-mediator-of-the-protumorigenic-properties-of-cancer-associated-fibroblasts-in-pancreatic-tumors
#12
Magdolna Djurec, Osvaldo Graña, Albert Lee, Kevin Troulé, Elisa Espinet, Lavinia Cabras, Carolina Navas, María Teresa Blasco, Laura Martín-Díaz, Miranda Burdiel, Jing Li, Zhaoqi Liu, Mireia Vallespinós, Francisco Sanchez-Bueno, Martin R Sprick, Andreas Trumpp, Bruno Sainz, Fátima Al-Shahrour, Raul Rabadan, Carmen Guerra, Mariano Barbacid
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351800/drug-resistance-genes-pvcrt-o-and-pvmdr-1-polymorphism-in-patients-from-malaria-endemic-south-western-coastal-region-of-india
#13
Shiny Joy, Benudhar Mukhi, Susanta K Ghosh, Rajeshwara N Achur, D Channe Gowda, Namita Surolia
BACKGROUND: Malaria is highly prevalent in many parts of India and is mostly caused by the parasite species Plasmodium vivax followed by Plasmodium falciparum. Chloroquine (CQ) is the first-line treatment for blood stage P. vivax parasites, but cases of drug resistance to CQ have been reported from India. One of the surveillance strategies which is used to monitor CQ drug resistance, is the analysis of single nucleotide polymorphisms (SNPs) of the associated gene markers. Susceptibility to CQ can also be determined by copy number assessment of multidrug resistant gene (mdr-1)...
January 19, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29351487/contribution-of-parasympathetic-muscarinic-augmentation-of-insulin-secretion-to-olanzapine-induced-hyperinsulinemia
#14
Michael R Rickels, Elys M Perez, Amy J Peleckis, Erica Alshehabi, Huong-Lan Nguyen, Darko Stefanovski, Karl Rickels, Karen L Teff
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized fifteen healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet and activity controlled inpatient conditions...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351227/differential-association-of-cx37-and-cx40-genetic-variants-in-atrial-fibrillation-with-and-without-underlying-structural-heart-disease
#15
Sebastian Carballo, Anna Pfenniger, David Carballo, Nicolas Garin, Richard W James, François Mach, Dipen Shah, Brenda R Kwak
Atrial fibrillation (AF) appears in the presence or absence of structural heart disease. The majority of foci causing AF are located near the ostia of pulmonary veins (PVs), where cardiomyocytes and vascular smooth muscle cells interdigitate. Connexins (Cx) form gap junction channels and participate in action potential propagation. Genetic variants in genes encoding Cx40 and Cx37 affect their expression or function and may contribute to PV arrhythmogenicity. DNA was obtained from 196 patients with drug-resistant, symptomatic AF with and without structural heart disease, who were referred for percutaneous catheter ablation...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#16
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
https://www.readbyqxmd.com/read/29351202/antimicrobial-peptides-diversity-mechanism-of-action-and-strategies-to-improve-the-activity-and-biocompatibility-in-vivo
#17
REVIEW
Prashant Kumar, Jayachandran N Kizhakkedathu, Suzana K Straus
Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life...
January 19, 2018: Biomolecules
https://www.readbyqxmd.com/read/29350909/dual-drug-delivery-system-based-on-biodegradable-organosilica-core-shell-architectures
#18
Jiang-Lan Li, Ying-Jia Cheng, Chi Zhang, Han Cheng, Jun Feng, Ren-Xi Zhuo, Xuan Zeng, Xian-Zheng Zhang
To overcome drug resistance, efficient cancer therapeutic strategies using combination of small-molecule drugs and macromolecule drugs are highly desired. However, due to their significant differences in molecular weight and size, it is difficult to load them simultaneously in one vector and to release them individually. Here, a biodegradable organosilica based core/shell-structured nanocapsule was designed and used as a dual stimuli-responsive drug vector to solve this problem. Biodegradable organosilica shell coated outside the macromolecule model drug "core" would be disrupted by high glutathione (GSH) levels inside tumor cells, resulting in the escape of the entrapped drugs...
January 19, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29350902/hierarchically-self-assembled-supramolecular-host-guest-delivery-system-for-delivery-of-chemotherapeutics-to-drug-resistant-cancer-tumours
#19
Hongwei Cheng, Xiaoshan Fan, Xiaoyuan Wang, Enyi Ye, Xian Jun Loh, Zibiao Li, Yun-Long Wu
In this report, a new star-like copolymer -CD-g-(PNIPAAm-b-POEGA)x consisting of a -CD core, grafted with temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer tumours. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host-guest inclusion complexation between the -cyclodextrin cavity and the anti-cancer drug...
January 19, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29350549/abiraterone-acetate-and-its-use-in-the-treatment-of-metastatic-prostate-cancer-a-review
#20
Orazio Caffo, Antonello Veccia, Stefania Kinspergher, Francesca Maines
Abiraterone acetate, which targets enzymatic complexes playing a central role in steroidogenesis, demonstrated to increase survival significantly in both chemo-naive and docetaxel pretreated, becoming one of the drugs of choice for metastatic castration-resistant prostate cancer. More recently, this agent in combination to androgen deprivation therapy demonstrated to be efficacious also in metastatic castration-sensitive prostate cancer. The present review is aimed to outline the clinical development of abiraterone acetate, the pivotal trials which led to its approval for the clinical practice, new evidence about its efficacy in metastatic castration-sensitive prostate cancer, its place in the therapeutic landscape of prostate cancer and future directions of development...
January 19, 2018: Future Oncology
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