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https://www.readbyqxmd.com/read/28212575/upregulation-of-mucin-glycoprotein-muc1-in-the-progression-to-esophageal-adenocarcinoma-and-therapeutic-potential-with-a-targeted-photoactive-antibody-drug-conjugate
#1
Mohammed Adil Butt, Hayley Pye, Rehan J Haidry, Dahmane Oukrif, Saif-U-Rehman Khan, Ignazio Puccio, Michael Gandy, Halla W Reinert, Ellie Bloom, Mohammed Rashid, Gokhan Yahioglu, Mahendra P Deonarain, Rifat Hamoudi, Manuel Rodriguez-Justo, Marco R Novelli, Laurence B Lovat
BACKGROUND: Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS: MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212547/resveratrol-induces-cell-cycle-arrest-and-apoptosis-with-docetaxel-in-prostate-cancer-cells-via-a-p53-p21waf1-cip1-and-p27kip1-pathway
#2
Santosh Kumar Singh, Saswati Banerjee, Edward P Acosta, James W Lillard, Rajesh Singh
Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#3
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212507/higher-severity-of-cocaine-addiction-is-associated-with-tactile-and-somatic-hallucinations
#4
C Roncero, L Grau-López, R F Palma-Álvarez, L Rodriguez-Cintas, E Ros-Cucurull, A Esojo, C Daigre
BACKGROUND: The aim of this study is to describe the features of cocaine-dependent patients who have had cocaine-induced tactile/somatic hallucinations (CITSH), and to analyze the association with addiction-related variables and psychiatric comorbidity, comparing patients with CITSH, patients with cocaine psychotic symptoms (CIP) and no CITSH, and patients without any psychotic symptom. METHOD: A cross-sectional study was conducted in 767 cocaine-dependent patients in an outpatient treatment center for addictions...
December 1, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28212464/oxytocin-reduces-ethanol-self-administration-in-mice
#5
Courtney E King, William C Griffin, Lauryn N Luderman, Malcolm M Kates, Jacqueline F McGinty, Howard C Becker
BACKGROUND: Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. METHODS: Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking ("drinking-in-the-dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage...
February 17, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28212385/the-effect-of-tumour-size-on-drug-transport-and-uptake-in-3-d-tumour-models-reconstructed-from-magnetic-resonance-images
#6
Wenbo Zhan, Wladyslaw Gedroyc, Xiao Yun Xu
Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size...
2017: PloS One
https://www.readbyqxmd.com/read/28212219/drug-infusion-systems-technologies-performance-and-pitfalls
#7
Uoo R Kim, Robert A Peterfreund, Mark A Lovich
This review aims to broadly describe drug infusion technologies and raise subtle but important issues arising from infusion therapy that can potentially lead to patient instability and morbidity. Advantages and disadvantages of gravity-dependent drug infusion are described and compared with electromechanical approaches for precise control of medication infusion, including large-volume peristaltic and syringe pumps. This review discusses how drugs and inert carriers interact within infusion systems and outlines several complexities and potential sources of drug error...
February 16, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28211594/substance-dependence-among-those-without-symptoms-of-substance-abuse-in-the-world-mental-health-survey
#8
Luise Lago, Meyer D Glantz, Ronald C Kessler, Nancy A Sampson, Ali Al-Hamzawi, Silvia Florescu, Jacek Moskalewicz, Sam Murphy, Fernando Navarro-Mateu, Yolanda Torres de Galvis, Maria Carmen Viana, Miguel Xavier, Louisa Degenhardt
The World Health Organization (WHO) World Mental Health (WMH) Survey Initiative uses the Composite International Diagnostic Interview (CIDI). The first 13 surveys only assessed substance dependence among respondents with a history of substance abuse; later surveys also assessed substance dependence without symptoms of abuse. We compared results across the two sets of surveys to assess implications of the revised logic and develop an imputation model for missing values of lifetime dependence in the earlier surveys...
February 17, 2017: International Journal of Methods in Psychiatric Research
https://www.readbyqxmd.com/read/28210989/net-clinical-benefit-of-dabigatran-vs-warfarin-in-venous-thromboembolism-analyses-from-re-cover-%C3%A2-re-cover%C3%A2-ii-and-re-medy%C3%A2
#9
Martin Feuring, Sam Schulman, Henry Eriksson, Ajay J Kakkar, Sebastian Schellong, Stefan Hantel, Elke Schueler, Jörg Kreuzer, Samuel Z Goldhaber
The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2...
February 16, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28210927/efficacy-and-safety-of-daclatasvir-plus-pegylated-interferon-alfa-2a-and-ribavirin-in-previously-untreated-hcv-subjects-coinfected-with-hiv-and-hcv-genotype-1-a-phase-iii-open-label-study
#10
Mark S Sulkowski, Walford J Fessel, Adriano Lazzarin, Juan Berenguer, Natalia Zakharova, Hugo Cheinquer, Pierre Côté, Douglas Dieterich, Adrian Gadano, Gail Matthews, Jean-Michel Molina, Christophe Moreno, Juan Antonio Pineda, Federico Pulido, Antonio Rivero, Jurgen Rockstroh, Dennis Hernandez, Fiona McPhee, Timothy Eley, Zhaohui Liu, Patricia Mendez, Eric Hughes, Stephanie Noviello, Peter Ackerman
BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks...
February 16, 2017: Hepatology International
https://www.readbyqxmd.com/read/28210867/management-and-outcome-of-gastrointestinal-bleeding-in-patients-taking-oral-anticoagulants-or-antiplatelet-drugs
#11
Sven Pannach, Julia Goetze, Sandra Marten, Thomas Schreier, Luise Tittl, Jan Beyer-Westendorf
BACKGROUND: Non-vitamin K dependent oral anticoagulants (NOACs) significantly decrease overall major bleeding rates compared with vitamin K antagonists (VKAs) but there is conflicting evidence regarding the relative risk of gastrointestinal bleeding. Since data regarding the types, the management, and the outcome of NOAC-associated gastrointestinal bleeding are scarce, we aimed to fill this gap by comparing cases of gastrointestinal bleeding associated with NOAC, VKA, or antiplatelet therapy...
February 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28210512/porphyria-cutanea-tarda-in-a-patient-with-end-stage-renal-disease-a-case-of-successful-treatment-with-deferoxamine-and-ferric-carboxymaltose
#12
Natacha Rodrigues, Fernando Caeiro, Alice Santana, Teresa Mendes, Leonor Lopes
Porphyria cutanea tarda (PCT) is a rare disease, with a strong association with hepatitis C virus. PCT is particularly problematic in end-stage renal disease patients as they have no renal excretion of porphyrins and these are poorly dialyzed. Also, conventional treatment of PCT is compromised in these patients as hydroxychloroquine is contraindicated, phlebotomies with the stipulated frequency are poorly tolerated in already anaemia-prone patients, and iron-chelating agents are less efficient in removing iron and contribute to worsening anaemia...
2017: Case Reports in Nephrology
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#13
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
: Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#14
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209683/evaluation-of-6-remote-first-nations-community-based-buprenorphine-programs-in-northwestern-ontario-retrospective-study
#15
Solomon Mamakwa, Meldon Kahan, Dinah Kanate, Mike Kirlew, David Folk, Sharon Cirone, Sara Rea, Pierre Parsons, Craig Edwards, Janet Gordon, Fiona Main, Len Kelly
OBJECTIVE: To evaluate established opioid addiction treatment programs that use traditional healing in combination with buprenorphine-naloxone maintenance treatment in 6 First Nations communities in the Sioux Lookout region of northwestern Ontario. DESIGN: Retrospective cohort study. SETTING: Six First Nations communities in northwestern Ontario. PARTICIPANTS: A total of 526 First Nations participants in opioid-dependence treatment programs...
February 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28209540/in-vitro-characterization-of-ph-sensitive-azithromycin-loaded-methoxy-poly-ethylene-glycol-block-poly-aspartic-acid-graft-imidazole-micelles
#16
Fangfang Teng, Peizong Deng, Zhimei Song, Feilong Zhou, Runliang Feng, Na Liu
In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5...
February 9, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28209527/exploring-deformable-particles-in-vascular-targeted-drug-delivery-softer-is-only-sometimes-better
#17
Margaret B Fish, Catherine A Fromen, Genesis Lopez-Cazares, Alexander W Golinski, Timothy F Scott, Reheman Adili, Michael Holinstat, Omolola Eniola-Adefeso
The ability of vascular-targeted drug carriers (VTCs) to localize and bind to a targeted, diseased endothelium determines their overall clinical utility. Here, we investigate how particle modulus and size determine adhesion of VTCs to the vascular wall under physiological blood flow conditions. In general, deformable microparticles (MPs) outperformed nanoparticles (NPs) in all experimental conditions tested. Our results indicate that MP modulus enhances particle adhesion in a shear-dependent manner. In low shear human blood flow profiles in vitro, low modulus particles showed favorable adhesion, while at high shear, rigid particles showed superior adhesion...
February 4, 2017: Biomaterials
https://www.readbyqxmd.com/read/28209155/intranasal-oxytocin-reduces-provoked-symptoms-in-female-patients-with-posttraumatic-stress-disorder-despite-exerting-sympathomimetic-and-positive-chronotropic-effects-in-a-randomized-controlled-trial
#18
M Sack, D Spieler, L Wizelman, G Epple, J Stich, M Zaba, U Schmidt
BACKGROUND: Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans...
February 17, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28208750/the-consequences-of-chromosome-segregation-errors-in-mitosis-and-meiosis
#19
REVIEW
Tamara Potapova, Gary J Gorbsky
Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28208698/advances-in-molecular-imaging-of-locally-delivered-targeted-therapeutics-for-central-nervous-system-tumors
#20
REVIEW
Umberto Tosi, Christopher S Marnell, Raymond Chang, William C Cho, Richard Ting, Uday B Maachani, Mark M Souweidane
Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB...
February 8, 2017: International Journal of Molecular Sciences
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