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https://www.readbyqxmd.com/read/28549238/risk-factors-and-mechanisms-contributing-to-tki-induced-vascular-events-in-patients-with-cml
#1
REVIEW
Peter Valent, Emir Hadzijusufovic, Gregor Hoermann, Wolfgang Füreder, Gerit-Holger Schernthaner, Wolfgang R Sperr, Rudolf Kirchmair, Dominik Wolf
Vascular adverse events (VAE) are an emerging problem in patients with chronic myeloid leukemia (CML) receiving second-generation BCR-ABL1 tyrosine kinase inhibitors (TKI). Relevant VAE comprise peripheral, cerebral, and coronary artery changes in patients receiving nilotinib, venous and arterial occlusive events during ponatinib therapy, and pulmonary hypertension in patients receiving dasatinib. Although each TKI binds to a unique profile of molecular targets in leukemic cells and vascular cells, the exact etiology of drug-induced vasculopathies remains uncertain...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28549219/design-synthesis-and-properties-of-a-potent-inhibitor-of-pseudomonas-aeruginosa-deacetylase-lpxc
#2
Grazia Piizzi, David T Parker, Yunshan Peng, Markus Rolf Dobler, Anup Patnaik, Som Wattanasin, Eugene Liu, Francois Lenoir, Jill Nunez, John Kerrigan, David McKenney, Colin S Osborne, Donghui Yu, Leanne Lanieri, Jade Bojkovic, JoAnne Dzink-Fox, Maria-Dawn Lilly, Elizabeth R Sprague, Yipin Lu, Hongming Wang, Srijan Ranjitkar, Bing Wang, Meir Glick, Lawrence G Hamann, Ruben Tommasi, Xia Yang, Charles R Dean
Over the past several decades the frequency of antibacterial resistance in hospitals, including multi-drug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28549173/incidental-mosquitocidal-effect-of-an-ivermectin-mass-drug-administration-on-anopheles-farauti-conducted-for-scabies-control-in-the-solomon-islands
#3
Christian Kositz, Jeptah Talina, Jason Diau, Rowena Asugeni, Cheryl Whitehorn, David Mabey, Carlos Chaccour, Michael Marks
Background: The Solomon Islands is targeting elimination of malaria by 2030. The dominant vector is the predominantly exophagic, exophilic Anopheles farauti sensu strictu. This biting behaviour limits the efficacy of conventional vector control tools and highlights the need for new strategies. When administered to humans ivermectin has been shown to have a mosquitocidal effect. Mass drug administration (MDA) with ivermectin is an emerging strategy in the control of scabies. In this study we explored any incidental effect of ivermectin MDA conducted for scabies control on mosquitoes...
May 26, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28547936/fragment-based-drug-discovery-as-alternative-strategy-to-the-drug-development-for-neglected-diseases
#4
REVIEW
Juliana da Fonseca Rezende E Mello, Renan Augusto Gomes, Drielli Gomes Vital-Fujii, Glaucio Monteiro Ferreira, Gustavo Henrique Goulart Trossini
Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery (FBDD) emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area...
May 26, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28547896/assembly-of-breast-cancer-heterotypic-spheroids-on-hyaluronic-acid-coated-surfaces
#5
Marco P Carvalho, Elisabete C Costa, Ilídio J Correia
Drug screening is currently demanding for realistic models that are able to reproduce the structural features of solid tumors. 3D cell culture systems, namely spheroids, emerged as a promising approach to provide reliable results during drug development. So far, Liquid Overlay Technique (LOT) is one of the most used methods for spheroids assembly. It comprises cellular aggregation due to their limited adhesion to certain biomaterials, like agarose. However, researchers are currently improving this technique in order to obtain spheroids on surfaces that mimic cancer extracellular matrix (ECM), since cell-ECM interactions modulate cells behavior and their drug resistance profile...
May 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28547702/emerging-treatments-in-eating-disorders
#6
REVIEW
Michael Lutter
Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments...
May 25, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28547654/potential-teratogenic-effects-of-clomiphene-citrate
#7
REVIEW
Alessandra Scaparrotta, Francesco Chiarelli, Alberto Verrotti
Clomiphene citrate (CC) is the oldest drug used to regulate the process of ovulation. Considering the great use of CC over the last 40 years, it is important to understand the possible risks associated with its use. The aim of this review was to evaluate the possible teratogenic effects of CC, analyzing results obtained from animal and human studies. The pharmacokinetics of CC and possible mechanisms involved in teratogenesis are examined. Fetal exposure to CC is possible due to the long half-life of CC and its metabolites...
May 25, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28547273/case-distribution-and-complications-of-mid-urethral-sling-surgery-in-a-canadian-city-before-and-after-the-health-canada-advisory-on-pelvic-floor-mesh
#8
Kevin Carlson, Richard Baverstock, Andrea Civitarese, R Trafford Crump
INTRODUCTION AND HYPOTHESIS: Increased incidences of complications related to the use of mid-urethral slings (MUS) for the treatment of stress urinary incontinence resulted in both the Food and Drug Administration (FDA) and Health Canada issuing advisories in 2008 and 2010 respectively. The purpose of this study was to assess the effect these advisories had on the number of surgeons performing MUS surgery and post-surgical complications in Calgary, Canada. METHODS: In this study, we conducted a retrospective analysis of administrative data between 2006 and 2011...
May 25, 2017: International Urogynecology Journal
https://www.readbyqxmd.com/read/28546901/macrophages-as-effectors-of-acute-and-chronic-allograft-injury
#9
Yianzhu Liu, Malgorzata Kloc, Xian C Li
Organ transplants give a second chance of life to patients with end-stage organ failure. However, the immuno-logical barriers prove to be very challenging to overcome and graft rejection remains a major hurdle to long-term transplant survival. For decades, adaptive immunity has been the focus of studies, primarily based on the belief that T cells are necessary and sufficient for rejection. With better-developed immunosuppressive drugs and protocols that effectively control adaptive cells, innate immune cells have emerged as key effector cells in triggering graft injury and have therefore attracted much recent attention...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28546853/caveolin-1-an-oxidative-stress-related-target-for-cancer-prevention
#10
REVIEW
Shengqi Wang, Neng Wang, Yifeng Zheng, Jin Zhang, Fengxue Zhang, Zhiyu Wang
Aberrant oxidative metabolism is one of the hallmarks of cancer. Reactive species overproduction could promote carcinogenesis via inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy was considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, has been shown to mediate tumorigenesis and progression through oxidative stress modulation recently. Reactive species could modulate the expression, degradation, posttranslational modifications, and membrane trafficking of Cav-1, while Cav-1-targeted treatments could scavenge the reactive species...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28546515/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#11
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28546460/common-toxidromes-in-movement-disorder-neurology
#12
N Malek, M R Baker
BACKGROUND: Physicians can come across patients who are exposed to certain prescription drugs or toxins that can result in adverse effects and complications which have high rates of morbidity and mortality. OBJECTIVE: To summarise the key clinical features and management of the common movement disorder toxidromes relevant to physicians (with an interest in neurology). METHODS: We searched PUBMED from 1946 to 2016 for papers relating to movement toxidromes and their treatment...
June 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28546082/targeting-gpnmb-with-glembatumumab-vedotin-current-developments-and-future-opportunities-for-the-treatment-of-cancer
#13
REVIEW
April A N Rose, Marco Biondini, Rafael Curiel, Peter M Siegel
GPNMB has emerged as an immunomodulator and an important positive mediator of tumor progression and metastasis in numerous solid cancers. Tumor intrinsic GPNMB-mediated effects on cellular signaling, coupled with the ability of GPNMB to influence the primary tumor and metastatic microenvironments in a non-cell autonomous fashion, combine to augment malignant cancer phenotypes. In addition, GPNMB is often overexpressed in a variety of cancers, making it an attractive therapeutic target. In this regard, glembatumumab vedotin, an antibody-drug conjugate (ADC) that targets GPNMB, is currently in clinical trials as a single agent in multiple cancers...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28546075/antimicrobial-storage-and-antibiotic-knowledge-in-the-community-a-cross-sectional-pilot-study-in-north-western-angola
#14
Joana Cortez, Edite Rosário, João E Pires, João Taborda Lopes, Moisés Francisco, Erika Vlieghe, Miguel Brito
BACKGROUND: Antimicrobials are drugs that were once lifesavers and mainly curative. Nowadays their value is increasingly under pressure because of the fast and worldwide emergence of antimicrobial resistance, which, in low resources settings, frequently occurs in microorganisms that are likely to be transmitted in the community. METHODS: A cross-sectional pilot study including 102 households within the 10th HDSS round in Dande, Bengo Province, Angola. RESULTS: From the total 102 households piloted, 77...
May 22, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28546001/mito-methyl-coumarin-a-novel-mitochondria-targeted-drug-with-great-antitumor-potential-was-synthesized
#15
Huanan Wang, Wenqing Xu
Due to higher transmembrane potential of tumor cells, enhanced accumulation of cationic drugs in tumor mitochondria has been attributed to a higher (more negative inside) mitochondrial transmembrane potential compared with normal cells, emerging researchers are focus on developing mitochondria-targeted antitumor drugs. Coumarins showed great potential on antitumor, but mitochondria-targeted coumarin derivatives have not been reported. In the present study, we synthesized mitochondria-targeted-methyl coumarin (mito-methyl coumarin) through coupling 6-methyl coumarin to TPP...
May 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28545838/strategies-for-targeted-drug-delivery-in-treatment-of-colon-cancer-current-trends-and-future-perspectives
#16
REVIEW
Antara Banerjee, Surajit Pathak, Vimala Devi S, Dharani Vasan, Ramachandran Murugesan, Rama S Verma
Despite advances in treatment modalities, colon cancer (CC) is the third most common cause of cancer-related death worldwide. Subsequent unfavorable effects owing to toxicity of conventional drugs are a challenging problem associated with chemotherapy. There is noticeable concern toward site-specific/targeted delivery of chemotherapeutic drugs specifically to the affected site of the colon in a predictable and reproducible manner. However, the biggest challenge in successful drug targeting for the colon is avoidance of drug absorption and/or degradation in the upper gastrointestinal tract before the drug reaches the colon...
May 22, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28545837/emerging-technologies-for-prediction-of-drug-candidate-efficacy-in-the-preclinical-pipeline
#17
Denis Menshykau
The pharmaceutical industry is tackling increasingly complex multifactorial diseases, resulting in increases in research & development (R&D) costs and reductions in the success rates for drug candidates during Phase 2 and 3 clinical trials, with a lack of efficacy being the primary reason for drug candidate failure. This implies that the predictive power of current preclinical assays for drug candidate efficacy is suboptimal and, therefore, that alternatives should be developed. Here, I review emerging in vitro, imaging, and in silico technologies and discuss their potential contribution to drug efficacy assessment...
May 22, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28545541/mal-gene-overexpression-as-a-marker-of-high-grade-serous-ovarian-carcinoma-stem-like-cells-that-predicts-chemoresistance-and-poor-prognosis
#18
Laura Zanotti, Chiara Romani, Laura Tassone, Paola Todeschini, Renata Alessandra Tassi, Elisabetta Bandiera, Giovanna Damia, Francesca Ricci, Laura Ardighieri, Stefano Calza, Sergio Marchini, Luca Beltrame, Germana Tognon, Maurizio D'Incalci, Sergio Pecorelli, Enrico Sartori, Franco Odicino, Antonella Ravaggi, Eliana Bignotti
BACKGROUND: The existence of cancer stem cells (CSCs) within a tumor bulk has been demonstrated for many solid tumors including epithelial ovarian carcinoma (EOC). CSCs have been associated to tumor invasion, metastasis and development of chemoresistant recurrences. In this context, we aim to characterize EOC CSCs from the molecular point of view in order to identify potential biomarkers associated with chemoresistance. METHODS: We isolated a population of cells with stem-like characteristics (OVA-BS4 spheroids) from a primary human EOC cell line under selective conditions...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28545389/structural-insight-into-the-inactivation-of-mycobacterium-tuberculosis-non-classical-transpeptidase-ldtmt2-by-biapenem-and-tebipenem
#19
Mario A Bianchet, Ying H Pan, Leighanne A Brammer Basta, Harry Saavedra, Evan P Lloyd, Pankaj Kumar, Rohini Mattoo, Craig A Townsend, Gyanu Lamichhane
BACKGROUND: The carbapenem subclass of β-lactams is among the most potent antibiotics available today. Emerging evidence shows that, unlike other subclasses of β-lactams, carbapenems bind to and inhibit non-classical transpeptidases (L,D-transpeptidases) that generate 3 → 3 linkages in bacterial peptidoglycan. The carbapenems biapenem and tebipenem exhibit therapeutically valuable potencies against Mycobacterium tuberculosis (Mtb). RESULTS: Here, we report the X-ray crystal structures of Mtb L,D-transpeptidase-2 (LdtMt2) complexed with biapenem or tebipenem...
May 25, 2017: BMC Biochemistry
https://www.readbyqxmd.com/read/28545372/lectin-carbohydrate-interactions-implications-for-the-development-of-new-anticancer-agents
#20
Evellyne de Oliveira Figueirôa, Cassia Regina Albuquerque da Cunha, Priscilla B S Albuquerque, Raiana Apolinário de Paula, Mary Ângela Aranda-Souza, Matheus Alves da Silva, Adrielle Zagmignan, Maria G Carneiro-da-Cunha, Luís Cláudio Nascimento da Silva, Maria Tereza Dos Santos Correia
Lectins are a large group of proteins found in animals, plants, fungi, and bacteria that recognize specific carbohydrate targets and play an important role in cell recognition and communication, host-pathogen interactions, embryogenesis, and tissue development. Recently, lectins have emerged as important biomedical tools that have been used in the development of immunomodulatory, antipathogenic, and anticancer agents. Several lectins have been shown to have the ability to discriminate between normal cells and tumor cells as a result of their different glycosylation patterns...
May 22, 2017: Current Medicinal Chemistry
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