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https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#1
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27885607/mouse-models-for-campylobacter-jejuni-colonization-and-infection
#2
Martin Stahl, Franziska A Graef, Bruce A Vallance
Relevant animal models for Campylobacter jejuni infection have been difficult to establish due to C. jejuni's inability to cause disease in many common animal research models. Fortunately, recent work has proven successful in developing several new and relevant mouse models of C. jejuni infection, including the SIGIRR-deficient mouse strain that develops acute enterocolitis in response to C. jejuni. Here we describe how to properly infect mice with C. jejuni, as well as a number of accompanying histological techniques to aid in studying C...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27813447/fostering-innovative-product-development-for-neglected-tropical-diseases-through-partnerships
#3
Amy Starr, Katy M Graef, Jennifer Dent
Neglected tropical diseases are a group of infectious diseases that threaten and impact a significant portion of individuals living in low- and middle-income countries. Healthcare product R&D, which has been relatively limited for this group of infectious diseases, is timely and requires significant risk and resource investment by companies. Regardless of these costs, the global community has recognized the impact on human health that developing products for these diseases could have. Incentives, including 'push' and 'pull' funding, and platforms that support sharing of intellectual property through partnerships, such as The World Intellectual Property Organization Re:Search, are driving R&D...
September 2016: Pharmaceutical Patent Analyst
https://www.readbyqxmd.com/read/27811061/liver-p53-is-stabilized-upon-starvation-and-required-for-amino-acid-catabolism-and-gluconeogenesis
#4
Andreas Prokesch, Franziska A Graef, Tobias Madl, Jennifer Kahlhofer, Steffi Heidenreich, Anne Schumann, Elisabeth Moyschewitz, Petra Pristoynik, Astrid Blaschitz, Miriam Knauer, Matthias Muenzner, Juliane G Bogner-Strauss, Gottfried Dohr, Tim J Schulz, Michael Schupp
The ability to adapt cellular metabolism to nutrient availability is critical for survival. The liver plays a central role in the adaptation to starvation by switching from glucose-consuming processes and lipid synthesis to providing energy substrates like glucose to the organism. Here we report a previously unrecognized role of the tumor suppressor p53 in the physiologic adaptation to food withdrawal. We found that starvation robustly increases p53 protein in mouse liver. This induction was posttranscriptional and mediated by a hepatocyte-autonomous and AMP-activated protein kinase-dependent mechanism...
November 3, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27443210/antibiotic-use-and-resistance-in-animals-belgian-initiatives
#5
Els Daeseleire, Evelyne De Graef, Geertrui Rasschaert, Thijs De Mulder, Tina Van den Meersche, Els Van Coillie, Jeroen Dewulf, Marc Heyndrickx
The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed...
May 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27421251/sleep-and-pain-in-pediatric-illness-a-conceptual-review
#6
REVIEW
Jennifer M Allen, Danielle M Graef, Jennifer H Ehrentraut, Brooklee L Tynes, Valerie M Crabtree
BACKGROUND: Sleep disruption is a common comorbidity of pediatric pain. Consequences of pain and disrupted sleep, evidence for the pain-sleep relation, and how aspects of illness, treatment, and pharmacological pain management may contribute to or exacerbate these issues are presented. AIMS: This conceptual review explored the relation between pain and sleep in children diagnosed with chronic medical or developmental conditions. The goal of this review is to expand upon the literature by examining common themes in sleep disturbances associated with painful conditions across multiple pediatric illnesses...
November 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27245853/autophagy-regulation-depends-on-er-homeostasis-controlled-by-lipid-droplets
#7
Ariadna P Velázquez, Martin Graef
Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegeneration, metabolic diseases, cancer, and aging. A key feature of autophagy is the de novo formation of autophagosomes, double-membrane vesicular structures encapsulating cytoplasmic cargo for vacuolar turnover and recycling. The membrane rearrangements underlying nucleation, expansion, closure, and vacuolar fusion of autophagosomes are driven by multicomponent core autophagy machinery in cooperation with numerous factors involved in a variety of cellular processes...
August 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27025160/vantage-095-an-international-multicenter-open-label-study-of-vorinostat-mk-0683-in-combination-with-bortezomib-in-patients-with-relapsed-and-refractory-multiple-myeloma
#8
David S Siegel, Meletios Dimopoulos, Sundar Jagannath, Hartmut Goldschmidt, Simon Durrant, Jonathan L Kaufman, Xavier Leleu, Arnon Nagler, Fritz Offner, Thorsten Graef, Joseph E Eid, Jennifer Houp, Christine Gause, Scott Vuocolo, Kenneth C Anderson
BACKGROUND: The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. PATIENTS AND METHODS: Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen...
June 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/26953354/lipid-droplet-mediated-er-homeostasis-regulates-autophagy-and-cell-survival-during-starvation
#9
Ariadna P Velázquez, Takashi Tatsuta, Ruben Ghillebert, Ingmar Drescher, Martin Graef
Lipid droplets (LDs) are conserved organelles for intracellular neutral lipid storage. Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress response. Here, we demonstrate that LDs are dispensable as a membrane source for autophagy, but fulfill critical functions for endoplasmic reticulum (ER) homeostasis linked to autophagy regulation. In the absence of LDs, yeast cells display alterations in their phospholipid composition and fail to buffer de novo fatty acid (FA) synthesis causing chronic stress and morphologic changes in the ER...
March 14, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/26942419/anti-infectives-in-drug-delivery-overcoming-the-gram-negative-bacterial-cell-envelope
#10
Florian Graef, Sarah Gordon, Claus-Michael Lehr
Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide...
March 5, 2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/26068612/a-year-of-cornea-in-review-2013
#11
REVIEW
Juan G Arbelaez, Matthew T Feng, Tomas J Pena, Marianne O Price, Francis W Price
PURPOSE: The goal of this study was to provide an update of significant corneal literature published in 2013. DESIGN: This study is a systematic literature review. METHODS: We conducted a systematic review of the English-language literature published from January 1, 2013, to December 31, 2013, using the following PubMed search and Medical Subject Headings terms: cornea transplantation, keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, cross linking, pre-Descemet's layer, Rho-associated kinase, keratoprosthesis, infectious keratitis, corneal dystrophy, corneal astigmatism, and keratoconus...
January 2015: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/26037057/first-in-human-pet-quantification-study-of-cerebral-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-using-the-novel-specific-radioligand-18-f-flubatine
#12
Osama Sabri, Georg-Alexander Becker, Philipp M Meyer, Swen Hesse, Stephan Wilke, Susanne Graef, Marianne Patt, Julia Luthardt, Gudrun Wagenknecht, Alexander Hoepping, René Smits, Annegret Franke, Bernhard Sattler, Bernd Habermann, Petra Neuhaus, Steffen Fischer, Solveig Tiepolt, Winnie Deuther-Conrad, Henryk Barthel, Peter Schönknecht, Peter Brust
α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (-)-[(18)F]Flubatine, formerly known as (-)-[(18)F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification...
September 2015: NeuroImage
https://www.readbyqxmd.com/read/25996066/repurposing-pharma-assets-an-accelerated-mechanism-for-strengthening-the-schistosomiasis-drug-development-pipeline
#13
Roopa Ramamoorthi, Katy M Graef, Jennifer Dent
Schistosomiasis, one of 17 diseases deemed to be neglected by the World Health Organization, has received little attention from the biopharmaceutical industry. Due to this, only a handful of drugs have been developed to treat schistosomiasis, with only one, praziquantel, used in most endemic regions. Growing concern over resistance coupled with praziquantel's incomplete efficacy across all stages of the Schistosoma platyhelminth life cycle highlights the urgent need for new drugs. The WIPO Re:Search consortium is a platform whereupon biopharmaceutical company compounds are being repurposed to efficiently and cost-effectively develop new drugs for neglected diseases such as schistosomiasis...
2015: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/25853747/ibrutinib-in-previously-treated-waldenstr%C3%A3-m-s-macroglobulinemia
#14
MULTICENTER STUDY
Steven P Treon, Christina K Tripsas, Kirsten Meid, Diane Warren, Gaurav Varma, Rebecca Green, Kimon V Argyropoulos, Guang Yang, Yang Cao, Lian Xu, Christopher J Patterson, Scott Rodig, James L Zehnder, Jon C Aster, Nancy Lee Harris, Sandra Kanan, Irene Ghobrial, Jorge J Castillo, Jacob P Laubach, Zachary R Hunter, Zeena Salman, Jianling Li, Mei Cheng, Fong Clow, Thorsten Graef, M Lia Palomba, Ranjana H Advani
BACKGROUND: MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenström's macroglobulinemia. MYD88(L265P) triggers tumor-cell growth through Bruton's tyrosine kinase, a target of ibrutinib. CXCR4(WHIM) mutations confer in vitro resistance to ibrutinib. METHODS: We performed a prospective study of ibrutinib in 63 symptomatic patients with Waldenström's macroglobulinemia who had received at least one previous treatment, and we investigated the effect of MYD88 and CXCR4 mutations on outcomes...
April 9, 2015: New England Journal of Medicine
https://www.readbyqxmd.com/read/25755291/the-bruton-tyrosine-kinase-inhibitor-ibrutinib-with-chemoimmunotherapy-in-patients-with-chronic-lymphocytic-leukemia
#15
MULTICENTER STUDY
Jennifer R Brown, Jacqueline C Barrientos, Paul M Barr, Ian W Flinn, Jan A Burger, Anh Tran, Fong Clow, Danelle F James, Thorsten Graef, Jonathan W Friedberg, Kanti Rai, Susan O'Brien
The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients...
May 7, 2015: Blood
https://www.readbyqxmd.com/read/25564807/health-related-quality-of-life-in-youth-with-crohn-disease-role-of-disease-activity-and-parenting-stress
#16
Wendy N Gray, Shana L Boyle, Danielle M Graef, David M Janicke, Christopher D Jolley, Lee A Denson, Robert N Baldassano, Kevin A Hommel
OBJECTIVES: Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric inflammatory bowel disease. Family level predictors of HRQOL have been understudied as are the mechanisms through which disease activity affects HRQOL. The present study examines the relation between a family level factor (parenting stress) and HRQOL in youth with Crohn disease. Parenting stress is examined as a mechanism through which disease activity affects HRQOL. METHODS: A total of 99 adolescents with Crohn disease and their parents were recruited across 3 sites...
June 2015: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/25516832/wipo-re-search-accelerating-anthelmintic-development-through-cross-sector-partnerships
#17
REVIEW
Roopa Ramamoorthi, Katy M Graef, Jennifer Dent
Neglected tropical diseases (NTDs), malaria, and tuberculosis have a devastating effect on an estimated 1.6 billion people worldwide. The World Intellectual Property Organization (WIPO) Re:Search consortium accelerates the development of new drugs, vaccines, and diagnostics for these diseases by connecting the assets and resources of pharmaceutical companies, such as compound libraries and expertise, to academic or nonprofit researchers with novel product discovery or development ideas. As the WIPO Re:Search Partnership Hub Administrator, BIO Ventures for Global Health (BVGH) fields requests from researchers, identifies Member organizations able to fulfill these requests, and helps forge mutually beneficial collaborations...
December 2014: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/25229276/wipo-re-search-catalyzing-collaborations-to-accelerate-product-development-for-diseases-of-poverty
#18
REVIEW
Roopa Ramamoorthi, Katy M Graef, Anatole Krattiger, Jennifer C Dent
No abstract text is available yet for this article.
November 26, 2014: Chemical Reviews
https://www.readbyqxmd.com/read/25112808/identification-of-drug-resistant-subpopulations-in-canine-hemangiosarcoma
#19
A Khammanivong, B H Gorden, A M Frantz, A J Graef, E B Dickerson
Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression...
September 2016: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/25035565/functional-convergence-spasm
#20
Abhishek Ghosh, Susanta K Padhy, Gourav Gupta, Manoj K Goyal
Convergence spasm (CS) means intermittent episodes of convergence, miosis and accommodation with disconjugate gaze mimicking abducens palsy. The organic causes range from metabolic to host of neurological and ophthalmic diseases that we describe. It was first described as a presentation of psychogenic disorders by von Graefe as early as in 1856. Nonetheless, patients exhibiting this sign are often subjected to plethora of unnecessary, sophisticated and invasive diagnostic procedures. Such functional cases were treated with either cycloplegic/placebo eye drop or amytal abreaction...
July 2014: Indian Journal of Psychological Medicine
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