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https://www.readbyqxmd.com/read/30343550/the-pharmacological-inhibition-of-erk5-enhances-apoptosis-in-acute-myeloid-leukemia-cells
#1
Changhee Kang, Jong Soo Kim, C-Yoon Kim, Eun-Young Kim, Hyung-Min Chung
Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Extracellular signal-regulated kinase 5 (ERK5) plays a novel role in chemoresistance in some cancer cells and this pathway is a central mediator of cell survival and apoptotic regulation. The aim of this study was to investigate the effect of ERK5 inhibitor, XMD8-92, on proliferation and apoptosis in AML cell lines. Findings showed that XMD8-92 inhibited the activation of ERK5 by G-CSF and decreased the expression of c-Myc and Cyclin D1...
October 31, 2018: International Journal of Stem Cells
https://www.readbyqxmd.com/read/30343548/-achalasia-updates-on-diagnosis-and-management-from-the-last-decade
#2
REVIEW
Amir Mari, Fadi Abu Backer, Hana Amara, Mahmud Mahamid
Achalasia is a rare idiopathic disease, associated with significant morbidity and negative impact on life quality. The disorder is characterized by impairments in the esophageal motility and loss of the lower esophageal sphincter (LES) relaxation. Achalasia symptoms include dysphagia, regurgitations, chest pain, vomiting and weight loss. Diagnosis of achalasia is based on an appropriate clinical presentation and typical findings on complementary tests. These tests include endoscopy showing a dilated esophageal lumen containing fluid or food, High-resolution manometry (HRM) shows evidence of obstruction at the gastro-esophageal junction and motility failure, and barium swallow shows esophageal dilation and distal narrowing...
October 2018: Harefuah
https://www.readbyqxmd.com/read/30343540/-pr-emptive-treatment-for-hyperemesis-gravidarum
#3
Rana Cohen, Gideon Koren
BACKGROUND: Hyperemesis gravidarum (HG) affects around 1% of pregnant women. The experience is traumatic, and many women hesitate to start a subsequent pregnancy in view of the tendency of HG to re-occur. OBJECTIVES: A 25 year old woman who experienced HG in her previous pregnancy was very afraid to start a second pregnancy, as she considered the termination of the first, traumatic pregnancy. She was advised to use pre- emptive antiemetic therapy with an anti emetic drug before any symptom appeared...
October 2018: Harefuah
https://www.readbyqxmd.com/read/30343537/-quantifying-patients-drug-adherence-by-electronic-records-of-drug-purchasing
#4
Dalia Weitzman, Gideon Koren
INTRODUCTION: One of the most widely used methods for estimating patient adherence to drug therapy is the use of proportion of days covered (PDC), which is based on the assumption that patients who chronically purchase a drug do actually consume it. OBJECTIVES: To investigate whether PDC reflect adherence based on steady state levels of lithium. METHODS: Using data on over 2000 patients on lithium in steady state, we correlated PDC with lithium steady state serum concentrations...
October 2018: Harefuah
https://www.readbyqxmd.com/read/30343529/high-throughput-screening-in-colorectal-cancer-tissue-originated-spheroids
#5
Jumpei Kondo, Tomoya Ekawa, Hiroko Endo, Kanami Yamazaki, Norio Tanaka, Yoji Kukita, Hiroaki Okuyama, Jiro Okami, Fumio Imamura, Masayuki Ohue, Kikuya Kato, Taisei Nomura, Arihiro Kohara, Seiichi Mori, Shingo Dan, Masahiro Inoue
Patient-derived cancer organoid culture is an important live material that reflects clinical heterogeneity. However, the limited amount of organoids available for each case as well as the considerable amount of time and cost to expand in vitro makes it impractical to perform high-throughput drug screening using organoid cultures from multiple patients. Here, we report an advanced system for the high-throughput screening of 2427 drugs using the cancer tissue-originated spheroid (CTOS) method. In this system, we apply the CTOS method in an ex vivo platform from xenograft tumors, using machines to handle CTOSs and reagents, and testing a CTOS reference panel of multiple CTOS lines for the hit drugs...
October 21, 2018: Cancer Science
https://www.readbyqxmd.com/read/30343517/in-vitro-metabolism-of-magnolol-and-honokiol-in-rat-liver-microsomes-and-their-interactions-withs-seven-cyp-substrates
#6
Yu Huang, Chunming Liu, Shu Liu, Zhiqiang Liu, Sainan Li, Yueqi Wang
RATIONALE: Magnolol and honokiol are the main active components of Magnolia officinalis Rehd. et Wils. The study of their interactions with liver microsomes is very important for the clinical safety of M. officinalis Rehd. et Wils. METHODS: The main metabolites of magnolol and honokiol in RLMs (rat liver microsomes) were investigated by UHPLC-Q Exactive and their possible structures were identified. In addition, CYP450 isoenzymes of the major rat metabolites of magnolol and honokiol were identified using a specific inhibitor...
October 21, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/30343514/combination-immunotherapy-with-il-2-surface-modified-tumor-cell-vaccine-and-pd-1-blockade-against-renal-cell-carcinoma
#7
Xinji Zhang, Xiaojun Shi, Jinlong Li, Zhiming Hu, Jimin Gao, Shihao Wu, Zhaolin Long
Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin-interleukin-2 (SA-IL-2) surface-modified tumor cell vaccine developed through our protein-anchor technology could induce specific anti-tumor T-cell response, but this immunotherapy can not completely eradicate the tumor. These effector T-cells highly expressed program death receptor-1 (PD-1), and the expression of program death ligand-1 (PD-L1) in tumor environment also was up-regulated after the SA-IL-2-modified vaccine therapy...
October 21, 2018: Cancer Science
https://www.readbyqxmd.com/read/30343511/dual-inhibition-of-ezh1-2-over-activates-wnt-signaling-to-deplete-cancer-stem-cells-in-multiple-myeloma
#8
Makoto Nakagawa, Shuhei Fujita, Takuo Katsumoto, Kazutsune Yamagata, Yoko Ogawara, Ayuna Hattori, Yuki Kagiyama, Daisuke Honma, Kazushi Araki, Tatsuya Inoue, Ayako Kato, Koichiro Inaki, Chisa Wada, Yoshimasa Ono, Masahide Yamamoto, Osamu Miura, Yasuharu Nakashima, Issay Kitabayashi
Multiple myeloma (MM) is an incurable hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development of novel therapies, relapse of MM eventually occurs due to a remaining population of drug-resistant myeloma stem cells. Side population (SP) cells exhibit cancer stem cell-like characteristics in MM; thus targeting these cells is a promising strategy to completely cure this malignancy. Here, we showed that SP cells expressed higher levels of enhancer of zeste homolog (EZH) 1 and EZH2, which encode the catalytic subunits of Polycomb repressive complex 2 (PRC2), than non-SP cells, suggesting that EZH1 as well as EZH2 contributes to the stemness maintenance of the MM cells and that targeting both EZH1/2 is potentially a significant therapeutic approach for eradicating myeloma stem cells...
October 21, 2018: Cancer Science
https://www.readbyqxmd.com/read/30343509/cost-effectiveness-of-immune-checkpoint-inhibitors-for-microsatellite-instability-high-mismatch-repair-deficient-metastatic-colorectal-cancer
#9
Jacqueline N Chu, Jin Choi, Sassan Ostvar, James A Torchia, Kerry Lynn Reynolds, Angela Tramontano, Justin F Gainor, Daniel C Chung, Jeffrey W Clark, Chin Hur
BACKGROUND: Patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI-H/dMMR mCRC treatment. METHODS: The treatment of hypothetical patients with MSI-H/dMMR mCRC was simulated in 2 treatment scenarios: a third-line treatment and an exploratory first-line treatment...
October 21, 2018: Cancer
https://www.readbyqxmd.com/read/30343508/phosphodiesterase-type-5-inhibitors-improve-microvascular-dysfunction-markers-in-pulmonary-arterial-hypertension-associated-with-congenital-heart-disease
#10
Mariana M Clavé, Nair Y Maeda, Ana M Thomaz, Sergio P Bydlowski, Antonio A Lopes
BACKGROUND: Ideally, vasodilator therapies for pulmonary arterial hypertension (PAH) should have a favorable impact on markers of vascular dysfunction, in addition to their known effects on hemodynamics, cardiac function, and patient's physical capacity. METHODS: We analyzed circulating (plasma) markers of endothelial and platelet activation/dysfunction (enzyme-linked immunoassays) in the specific setting of advanced PAH associated with congenital heart disease, during the course of sildenafil and tadalafil therapies...
October 20, 2018: Congenital Heart Disease
https://www.readbyqxmd.com/read/30343500/hemostatic-profile-under-fluid-resuscitation-during-rivaroxaban-anticoagulation-an-in-vitro-survey
#11
Tuukka A Helin, Marleen Zuurveld, Mikko Manninen, Joost C M Meijers, Riitta Lassila, Herm Jan M Brinkman
BACKGROUND: Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown. STUDY DESIGN AND METHODS: In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma...
October 21, 2018: Transfusion
https://www.readbyqxmd.com/read/30343499/thiazole-substituted-benzoylpiperazine-derivatives-as-acetylcholinesterase-inhibitors
#12
Zafer Sahin, Merve Ertas, Ceysu Bender, Emre F Bülbül, Barkin Berk, Sevde N Biltekin, Leyla Yurttaş, Şeref Demirayak
Hit, Lead & Candidate Discovery After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid-20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic-framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified...
October 21, 2018: Drug Development Research
https://www.readbyqxmd.com/read/30343496/dose-translation-between-laboratory-animals-and-human-in-preclinical-and-clinical-phases-of-drug-development
#13
Anroop Nair, Mohamed Aly Morsy, Shery Jacob
Preclinical Research & Development Appropriate translation and determination of the maximum recommended starting dose in human is a vital task in new drug development and research. Allometric scaling is the most frequently used approach for dose extrapolation based on normalization of dose-to-body surface area. Misinterpretation of allometric dose conversion and safety factor application can lead to major problems in calculating maximum recommended safe starting dose in first-in-human clinical trials. Therefore, dose translation always necessitates careful consideration of body surface area, pharmacological, physiological and anatomical factors, pharmacokinetic parameters, metabolic function, receptor, and life span...
October 21, 2018: Drug Development Research
https://www.readbyqxmd.com/read/30343494/the-treasure-of-now-and-an-uncertain-future-delay-discounting-and-health-behaviors-among-cancer-survivors
#14
Christine E Sheffer, Austin Miller, Warren K Bickel, Julia A Devonish, Richard J O'Connor, Chong Wang, Cheryl Rivard, Elizabeth A Gage-Bouchard
BACKGROUND: The identification of new therapeutic targets to improve health behaviors among cancer survivors (CS) is likely to improve cancer treatment outcomes. Delay discounting (DD) rate is the degree to which one devalues rewards as a function of time to receipt. Lower DD rates (ie, prioritizing long-term over immediate rewards) are associated with healthier behaviors. CS often experience distress and thoughts of early mortality that can potentially shift priorities to the present and negatively impact DD rates, especially when newly diagnosed...
October 21, 2018: Cancer
https://www.readbyqxmd.com/read/30343489/automated-symptom-and-treatment-side-effect-monitoring-for-improved-quality-of-life-among-adults-with-diabetic-peripheral-neuropathy-in-primary-care-a-pragmatic-cluster-randomized-controlled-trial
#15
A S Adams, J A Schmittdiel, A Altschuler, E A Bayliss, R Neugebauer, L Ma, W Dyer, J Clark, B Cook, D Willyoung, M Jaffe, J D Young, E Kim, J M Boggs, L Prosser, E Wittenberg, B Callaghan, M Shainline, R M Hippler, R W Grant
AIMS: To evaluate the effectiveness of automated symptom and side effect monitoring on quality of life among individuals with symptomatic diabetic peripheral neuropathy. METHODS: We conducted a pragmatic, cluster randomized controlled trial (July 2014 to July 2016) within a large healthcare system. We randomized 1834 primary care physicians and prospectively recruited from their lists 1270 individuals with neuropathy who were newly prescribed medications for their symptoms...
October 21, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/30343487/inhibiting-conjugation-as-a-tool-in-the-fight-against-antibiotic-resistance
#16
Fabrice E Graf, Martin Palm, Jonas Warringer, Anne Farewell
Hit, Lead & Candidate Discovery Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Most resistance genes are found on mobile genetic elements and primarily spread by conjugation...
October 21, 2018: Drug Development Research
https://www.readbyqxmd.com/read/30343445/a-review-of-data-of-findings-on-night-shift-work-and-the-development-of-dm-and-cvd-events-a-synthesis-of-the-proposed-molecular-mechanisms
#17
REVIEW
S Strohmaier, E E Devore, Y Zhang, E S Schernhammer
PURPOSE OF REVIEW: Night shift work has become highly prevalent in our 24/7 societies, with up to 18% of the US work force working alternate shift schedules. However, studies indicate that there may be adverse health effects of chronic night work across diverse populations. These effects are likely due to misalignment of the circadian system with work schedules, mediated by the system's primary marker melatonin as well as other downstream molecules. RECENT FINDINGS: Melatonin has multiple biologic actions that are relevant to cardiometabolic disease, including modulation of oxidative stress, inflammation, and (via the melatonin receptor) vasoconstriction...
October 20, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/30343434/role-of-fdg-pet-ct-in-monitoring-treatment-response-in-patients-with-invasive-fungal-infections
#18
Alfred O Ankrah, Lambert F R Span, Hans C Klein, Pim A de Jong, Rudi A J O Dierckx, Thomas C Kwee, Mike M Sathekge, Andor W J M Glaudemans
INTRODUCTION: Invasive fungal infections (IFIs) occur mostly in immunosuppressed patients and can be life-threatening. Inadequate treatment is associated with high morbidity and mortality. We examined the role of 2-fluorodeoxyglucose positron emission tomography integrated with CT (FDG-PET/CT) in monitoring IFIs and therapy decision-making, and evaluated the role of baseline metabolic parameters in predicting the metabolic response. METHODS: All patients between October 2009 and March 2018, diagnosed with IFIs, treated with antifungal drugs, and who underwent FDG-PET/CT at baseline and at one or more timepoints during treatment were retrospectively included...
October 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/30343418/drug-induced-liver-injury-highlights-of-the-recent-literature
#19
REVIEW
Mark Real, Michele S Barnhill, Cory Higley, Jessica Rosenberg, James H Lewis
Drug-induced liver injury (DILI), herbal-induced liver injury, and herbal and dietary supplement (HDS)-induced liver injury are an important aspect of drug safety. Knowledge regarding responsible drugs, mechanisms, risk factors, and the diagnostic tools to detect liver injury have continued to grow in the past year. This review highlights what we considered the most significant publications from among more than 1800 articles relating to liver injury from medications, herbal products, and dietary supplements in 2017 and 2018...
October 20, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/30343417/artificial-intelligence-and-the-future-of-the-drug-safety-professional
#20
Karolina Danysz, Salvatore Cicirello, Edward Mingle, Bruno Assuncao, Niki Tetarenko, Ruta Mockute, Danielle Abatemarco, Mark Widdowson, Sameen Desai
The healthcare industry, and specifically the pharmacovigilance industry, recognizes the need to support the increasing amount of data received from individual case safety reports (ICSRs). To cope with this increase, more healthcare and qualified professionals are required to capture and evaluate the data. To address the evolving landscape, it will be necessary to embrace assistive technologies such as artificial intelligence (AI) at scale. AI in the field of pharmacovigilance will possibly result in the transformation of the drug safety (DS) professional's daily work life and their career development...
October 20, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
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