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https://www.readbyqxmd.com/read/28343170/mirnas-single-nucleotide-polymorphisms-snps-and-age-related-macular-degeneration-amd
#1
John Paul SanGiovanni, Peter M SanGiovanni, Przemysław Sapieha, Vincent De Guire
Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD. The presence of certain single nucleotide polymorphisms (SNPs) may influence the explanatory value of these biomarkers. Here we present findings from an integrated approach used to determine whether AAMD-associated SNPs have the capacity to influence miRNA-mRNA pairing and, if so, to what extent such pairing may be manifested in a discrete AAMD transcriptome...
March 27, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28342789/enhanced-gastric-stability-of-esomeprazole-by-molecular-interaction-and-modulation-of-microenvironmental-ph-with-alkalizers-in-solid-dispersion
#2
Hien Van Nguyen, Namhyun Baek, Beom-Jin Lee
Due to the instability of esomeprazole magnesium dihydrate (EPM), a proton pump inhibitor, in gastric fluid, enteric-coated dosage form is commonly used for therapeutic application. In this study, we prepared new gastric fluid resistant solid dispersions (SDs) containing alkalizers. Then, new mechanistic evidence regarding the effects of pharmaceutical alkalizers on the aqueous stability of EPM in simulated gastric fluid was investigated. The alkalizer-loaded SD were prepared by dissolving or dispersing EPM, hydroxypropyl methylcellulose (HPMC) 6 cps, and an alkalizer, in ethanol 50% (v/v) followed by spray drying...
March 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28342435/-therapeutic-aggressiveness-and-liquid-oncology
#3
F J Barón Duarte, M S Rodríguez Calvo, J R Amor Pan
Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend...
January 2017: Cuadernos de Bioética: Revista Oficial de la Asociación Española de Bioética y Ética Médica
https://www.readbyqxmd.com/read/28340413/design-synthesis-and-biological-evaluation-of-novel-coumarin-based-benzamides-as-potent-histone-deacetylase-inhibitors-and-anticancer-agents
#4
Tooba Abdizadeh, Mohammad Reza Kalani, Khalil Abnous, Zahra Tayarani-Najaran, Bibi Zahra Khashyarmanesh, Rahman Abdizadeh, Razieh Ghodsi, Farzin Hadizadeh
Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec)...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339737/a-novel-chronic-opioid-monitoring-tool-to-assess-prescription-drug-steady-state-levels-in-oral-fluid
#5
Naum Shaparin, Neel Mehta, Frank Kunkel, Richard Stripp, Damon Borg, Elizabeth Kolb
Objective. : Interpretation limitations of urine drug testing and the invasiveness of blood toxicology have motivated the desire for the development of simpler methods to assess biologically active drug levels on an individualized patient basis. Oral fluid is a matrix well-suited for the challenge because collections are based on simple noninvasive procedures and drug concentrations better correlate to blood drug levels as oral fluid is a filtrate of the blood. Well-established pharmacokinetic models were utilized to generate oral fluid steady state concentration ranges to assess the interpretive value of the alternative matrix to monitor steady state plasma oxycodone levels...
February 23, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28339671/characteristics-of-donor-specific-anti-hla-antibodies-and-outcome-in-renal-transplant-patients-treated-with-a-standardized-induction-regimen
#6
Daniel Zecher, Christian Bach, Christoph Staudner, Carsten A Böger, Tobias Bergler, Bernhard Banas, Bernd M Spriewald
Background.: Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients. Methods.: Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology...
February 18, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339517/omics-studies-their-use-in-diagnosis-and-reclassification-of-sle-and-other-systemic-autoimmune-diseases
#7
Maria Teruel, Chris Chamberlain, Marta E Alarcón-Riquelme
Omics studies of systemic autoimmune diseases (SADs) in general, and SLE in particular, have delivered isolated information from transcriptome, epigenome, genome, cytokine and metabolome analyses. Such analyses have resulted in the identification of disease susceptibility genes and the description of IFN expression signatures, allowing extensive insight into the mechanisms of disease and the development of new therapies. Access to such technologies allows the recognition of patterns of disease at a pathway level, thereby, to reclassify SLE and other SADs and to develop new therapeutics from a personalized perspective...
October 19, 2016: Rheumatology
https://www.readbyqxmd.com/read/28339474/a-decrease-in-intact-parathyroid-hormone-ipth-levels-is-associated-with-higher-mortality-in-prevalent-hemodialysis-patients
#8
Ricardo Villa-Bellosta, Laura Rodriguez-Osorio, Sebastian Mas, Younes Abadi, Mercedes Rubert, Concepción de la Piedra, Carolina Gracia-Iguacel, Ignacio Mahillo, Alberto Ortiz, Jesús Egido, Emilio González-Parra
BACKGROUND: The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. METHODS: We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations...
2017: PloS One
https://www.readbyqxmd.com/read/28339196/discovery-of-a-small-molecule-degrader-of-bromodomain-and-extra-terminal-bet-proteins-with-picomolar-cellular-potencies-and-capable-of-achieving-tumor-regression
#9
Bing Zhou, Jiantao Hu, Fuming Xu, Zhuo Chen, Longchuan Bai, Ester Fernandez-Salas, Mei Lin, Liu Liu, Chao-Yie Yang, Yujun Zhao, Donna McEachern, Sally Przybranowski, Bo Wen, Duxin Sun, Shaomeng Wang
The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic "readers" and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation. Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28338008/noninvasive-measurement-of-transdermal-drug-delivery-by-impedance-spectroscopy
#10
Pasquale Arpaia, Umberto Cesaro, Nicola Moccaldi
The effectiveness in transdermal delivery of skin permeation strategies (e.g., chemical enhancers, vesicular carrier systems, sonophoresis, iontophoresis, and electroporation) is poorly investigated outside of laboratory. In therapeutic application, the lack of recognized techniques for measuring the actually-released drug affects the scientific concept itself of dosage for topically- and transdermally-delivered drugs. Here we prove the suitability of impedance measurement for assessing the amount of drug penetrated into the skin after transdermal delivery...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337826/diagnostic-outcome-of-contrast-videofluoroscopic-swallowing-studies-in-216-dysphagic-dogs
#11
Rachel E Pollard, Stanley L Marks, Diane M Cheney, Cecily M Bonadio
Determining the anatomic and functional origin for dysphagia is critical for development of an appropriate therapeutic plan and determination of the prognosis. The purpose of this retrospective study was to report the quantitative and qualitative outcome of contrast videofluoroscopic swallowing studies in a large cohort of dysphagic dogs presenting to a tertiary veterinary care hospital. The videofluoroscopic swallowing studies were reviewed to generate values for pharyngeal constriction ratio, timing of swallowing events (maximum pharyngeal contraction, opening of upper esophageal sphincter, closing of upper esophageal sphincter, and reopening of epiglottis), type of esophageal peristalsis generated, and esophageal transit time...
March 23, 2017: Veterinary Radiology & Ultrasound
https://www.readbyqxmd.com/read/28337701/ct-guided-drainage-of-pericardial-effusion-after-open-cardiac-surgery
#12
Nour-Eldin Abdelrehim Nour-Eldin, Mohammed Alsubhi, Tatjana Gruber-Rouh, Thomas J Vogl, Benjamin Kaltenbach, Hazem Hamed Soliman, Wael Eman Hassan, Sherif Maher Abolyazid, Nagy N Naguib
PURPOSE: This study was designed to evaluate the safety and efficacy of CT-guided drainage of the pericardial effusion in patients after cardiac surgery. MATERIALS AND METHODS: The study included 128 consecutive patients (82 males, 46 females; mean age 66.6 years, SD: 4.2) complicated by pericardial effusion or hemopericardium after cardiac surgeries between June 2008 and June 2016. The medical indication for therapeutic pericardiocentesis in all patients was hemodynamic instability caused by pericardial effusion...
March 23, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28337529/the-impact-of-repeated-cycles-of-radioligand-therapy-using-177-lu-lu-psma-617-on-renal-function-in-patients-with-hormone-refractory-metastatic-prostate-cancer
#13
Anna Yordanova, Anja Becker, Elisabeth Eppard, Stefan Kürpig, Christian Fisang, Georg Feldmann, Markus Essler, Hojjat Ahmadzadehfar
BACKGROUND: [(177)Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. METHODS: Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA-617 were investigated...
March 23, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28337289/overexpression-of-trim24-is-correlated-with-the-progression-of-human-cervical-cancer
#14
Li Lin, Weihua Zhao, Bo Sun, Xinyu Wang, Qiao Liu
TRIM24, originally known as intermediary factor 1-alpha, is involved in the development of several cancers. This study aimed to evaluate the expression level and prognostic value of TRIM24 in cervical cancer. In the present study, we showed that the expression of TRIM24 was markedly upregulated in cervical cancer cell lines and cancerous specimens at both transcriptional and translational levels. TRIM24 expression was analyzed in 147 archived cervical cancer specimens using immunohistochemistry, and the correlation between TRIM24 expression and clinicopathological parameters was evaluated...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337015/natural-tooth-preservation-versus-extraction-and-implant-placement-patient-preferences-and-analysis-of-the-willingness-to-pay
#15
D Re, C Ceci, F Cerutti, M Del Fabbro, S Corbella, S Taschieri
Objectives The aim of this study was to evaluate the patients' willingness to pay (WTP) values and preference for the treatment of a tooth with very poor prognosis, among two options: root canal therapy and crown positioning or tooth extraction, implant insertion and crown positioning.Methods A total of 103 patients were recruited from a private dental clinic and interviewed. A questionnaire measured individuals' preferences among the two alternative treatments for a tooth with poor prognosis and the maximum amount of money they would be willing to pay for their choice with a starting bid of [euro]2,000 in [euro]100 increment/decrement...
March 24, 2017: British Dental Journal
https://www.readbyqxmd.com/read/28336967/the-gene-expression-profiles-in-response-to-102-traditional-chinese-medicine-tcm-components-a-general-template-for-research-on-tcms
#16
Chao Lv, Xueting Wu, Xia Wang, Juan Su, Huawu Zeng, Jing Zhao, Shan Lin, Runhui Liu, Honglin Li, Xuan Li, Weidong Zhang
Traditional Chinese medicines (TCMs) have important therapeutic value in long-term clinical practice. However, because TCMs contain diverse ingredients and have complex effects on the human body, the molecular mechanisms of TCMs are poorly understood. In this work, we determined the gene expression profiles of cells in response to TCM components to investigate TCM activities at the molecular and cellular levels. MCF7 cells were separately treated with 102 different molecules from TCMs, and their gene expression profiles were compared with the Connectivity Map (CMAP)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336906/identification-and-evaluation-of-new-immunoregulatory-genes-in-mesenchymal-stromal-cells-of-different-origins-comparison-of-normal-and-inflammatory-conditions
#17
Mohammad Fayyad-Kazan, Mehdi Najar, Hussein Fayyad-Kazan, Gordana Raicevic, Laurence Lagneaux
BACKGROUND Mesenchymal stromal cells (MSCs) possess potent immunomodulatory properties that increase their value as a cell-based therapeutic tool for managing various immune-based disorders. Over the past years, accumulated results from trials using MSCs-based therapy have shown substantial contradictions. Although the reasons underlying these discrepancies are still not completely understood, it is well known that the immunomodulatory activities mediated by distinct MSCs differ in a manner dependent on their tissue origin and adequate response to inflammation priming...
March 24, 2017: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/28336808/potent-dual-bet-bromodomain-kinase-inhibitors-as-value-added-multi-targeted-chemical-probes-and-cancer-therapeutics
#18
Stuart W Ember, Que T Lambert, Norbert Berndt, Steven Gunawan, Muhammad Ayaz, Marilena Tauro, Jin-Yi Zhu, Paula J Cranfill, Patricia Greninger, Conor C Lynch, Cyril H Benes, Harshani R Lawrence, Gary W Reuther, Nicholas J Lawrence, Ernst Schonbrunn
Synergistic action of kinase and BET bromodomain inhibitors in cell killing has been reported for a variety of cancers. Using the chemical scaffold of the JAK2 inhibitor TG101348 we developed and characterized single agents which potently and simultaneously inhibit BRD4 and a specific set of oncogenic tyrosine kinases including JAK2, FLT3, RET, and ROS1. Lead compounds showed on-target inhibition in several blood cancer cell lines and were highly efficacious at inhibiting the growth of hematopoietic progenitor cells from myeloproliferative neoplasm (MPN) patients...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28336564/identification-of-a-novel-syk-c-myc-malat1-signaling-pathway-and-its-potential-therapeutic-value-in-ewing-sarcoma
#19
Haibo Sun, De-Chen Lin, Qi Cao, Brendan Pang, David D Gae, Victor Km Lee, Huey Jin Lim, Ngan Doan, Jonathan W Said, Sigal Gery, Marilynn Chow, Anand Mayakonda, Charles Forscher, Jeffrey W Tyner, H Phillip Koeffler
PURPOSE: Ewing Sarcoma (EWS) is a devastating soft tissue sarcoma affecting predominantly young individuals. Tyrosine kinases (TKs) and associated pathways are continuously activated in many malignancies including EWS; these enzymes provide candidate therapeutic targets. EXPERIMENTAL DESIGN: Two high-throughput screens (a siRNA library and a small-molecule inhibitor library) were performed in EWS cells to establish candidate targets. Spleen tyrosine kinase (SYK) phosphorylation was assessed in EWS patients and cell lines...
March 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28336087/dermatopontin-augments-angiogenesis-and-modulates-the-expression-of-transforming-growth-factor-beta-1-and-integrin-alpha-3-beta-1-in-endothelial-cells
#20
Venkat Raghavan Krishnaswamy, Uma Maheshwari Balaguru, Suvro Chatterjee, Purna Sai Korrapati
Dermatopontin (DPT) is a matricellular protein with cardinal roles in cutaneous wound healing. The protein is also reported to be altered in various anomalies including cancer. The present study is aimed to unravel the role of DPT in angiogenesis which is imperative in many physiological and pathological processes. DPT's capabilities on promoting angiogenesis were assessed using various in vitro and ex vivo systems. The results indicated that DPT enhances cell motility and induces lamellipodia formation in endothelial cells...
March 11, 2017: European Journal of Cell Biology
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