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https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#1
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936165/enzymatically-modified-starch-favorably-modulated-intestinal-transit-time-and-hindgut-fermentation-in-growing-pigs
#2
M A Newman, Q Zebeli, K Velde, D Grüll, T Molnar, W Kandler, B U Metzler-Zebeli
Aside from being used as stabilizing agents in many processed foods, chemically modified starches may act as functional dietary ingredients. Therefore, development of chemically modified starches that are less digestible in the upper intestinal segments and promote fermentation in the hindgut receives considerable attention. This study aimed to investigate the impact of an enzymatically modified starch (EMS) on nutrient flow, passage rate, and bacterial activity at ileal and post-ileal level. Eight ileal-cannulated growing pigs were fed 2 diets containing 72% purified starch (EMS or waxy cornstarch as control) in a cross-over design for 10 d, followed by a 4-d collection of feces and 2-d collection of ileal digesta...
2016: PloS One
https://www.readbyqxmd.com/read/27936162/discovery-of-a-novel-isothiazolonaphthoquinone-based-small-molecule-activator-of-foxo-nuclear-cytoplasmic-shuttling
#3
Bastien Cautain, Francisco Castillo, Loana Musso, Bibiana I Ferreira, Nuria de Pedro, Lorena Rodriguez Quesada, Susana Machado, Francisca Vicente, Sabrina Dallavalle, Wolfgang Link
FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology...
2016: PloS One
https://www.readbyqxmd.com/read/27936027/two-photon-microscopy-analysis-of-gold-nanoparticle-uptake-in-3d-cell-spheroids
#4
Tushar D Rane, Andrea M Armani
Nanomaterials can be synthesized from a wide range of material systems in numerous morphologies, creating an extremely diverse portfolio. As result of this tunability, these materials are emerging as a new class of nanotherapeutics and imaging agents. One particularly interesting nanomaterial is the gold nanoparticle. Due to its inherent biocompatibility and tunable photothermal behavior, it has made a rapid transition from the lab setting to in vivo testing. In most nanotherapeutic applications, the efficacy of the agent is directly related to the target of interest...
2016: PloS One
https://www.readbyqxmd.com/read/27936016/a-tool-for-investigating-asthma-and-copd-exacerbations-a-newly-manufactured-and-well-characterised-gmp-wild-type-human-rhinovirus-for-use-in-the-human-viral-challenge-model
#5
Daniel J Fullen, Bryan Murray, Julie Mori, Andrew Catchpole, Daryl W Borley, Edward J Murray, Ganesh Balaratnam, Anthony Gilbert, Alex Mann, Fiona Hughes, Rob Lambkin-Williams
BACKGROUND: Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. METHODS AND STOCK DEVELOPMENT: A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA) was obtained with appropriate medical history and consent...
2016: PloS One
https://www.readbyqxmd.com/read/27935882/-puncture-treatment-of-pseudoaneurysms-of-femoral-arteries-with-the-use-of-human-thrombin
#6
D S Panfilov, B N Kozlov, S D Panfilov, M S Kuznetsov, G G Nasrashvili, V M Shipulin
The authors analysed both immediate and remote results of puncture treatment with the use of human thrombin under ultrasound control in patients with iatrogenic false aneurysms of femoral arteries. The study included a total of 32 patients presenting with post-puncture pseudoaneurysms of femoral arteries after previous endovascular manipulations. The clinical diagnosis was verified by means of ultrasound duplex scanning. Puncture treatment was carried out using lyophilisate of human thrombin at a concentration of 500 IU according to the patented technique...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#7
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935783/the-role-of-pharmacogenomics-in-anesthesia-pharmacology
#8
Brett Morgan, Edwin N Aroke, Jennifer Dungan
The field of pharmacogenomics seeks to identify the impact of genetic variants on drug dosing, response, metabolism, and safety outcomes. The narrow therapeutic indices for anesthesia drugs, variability of patient responses to anesthesia, and the risks associated with surgery make anesthetics and the perioperative period prime targets for pharmacogenetic research. Anesthesia providers strive to optimize anesthesia delivery and patient outcomes and to specifically reduce anesthesia-related risks and negative outcomes...
January 2017: Annual Review of Nursing Research
https://www.readbyqxmd.com/read/27934884/rapid-affordable-and-portable-medium-throughput-molecular-device-for-zika-virus
#9
Kamfai Chan, Scott C Weaver, Pui-Yan Wong, Sherly Lie, Eryu Wang, Mathilde Guerbois, Siva Praneeth Vayugundla, Season Wong
Zika virus (ZIKV) has gained global attention as an etiologic agent of fetal microcephaly and Guillain-Barré syndrome. Existing immuno-based rapid tests often fail to distinguish between Zika and related flaviviruses that are common in affected regions of Central and South Americas and the Caribbean. The US CDC and qualified state health department laboratories can perform the reverse transcription polymerase chain reaction (RT-PCR) ZIKV test using highly sophisticated instruments with long turnaround times...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934635/metabolism-of-the-mek1-2-inhibitor-pimasertib-involves-a-novel-conjugation-with-phospho-ethanolamine-in-patients-with-solid-tumors
#10
Holger Scheible, Friedrich Kraetzer, Andreas Marx, Andreas Johne, Elmar Wimmer
Pimasertib (AS703026 or MSC1936369B) is a selective inhibitor of MEK1/2, the mitogen-activated protein kinase (MAPK) signaling pathway, which is often dysregulated in cancer cells. Pimasertib has shown potent preclinical anti tumor activity and its clinical activity is being investigated in various tumor types. In this phase I study, the disposition and biotransformation of (14)C-radiolabeled pimasertib was investigated in six patients with locally advanced or metastatic solid tumors (NCT 01713036). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and radiodetection techniques were used to investigate the profiles and structures of metabolites in plasma, urine and feces after a single oral dose of (14)C-pimasertib...
December 1, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27933959/novel-tetrahydropyrido-4-3-d-pyrimidines-as-potent-inhibitors-of-chaperone-heat-shock-protein-90
#11
Fen Jiang, Hui-Jie Wang, Yu-Hui Jin, Qiong Zhang, Zhi-Hui Wang, Jian-Min Jia, Fang Liu, Lei Wang, Qi-Chao Bao, Dong-Dong Li, Qi-Dong You, Xiao-Li Xu
Heat shock protein 90 (Hsp90) is a potential target for oncology therapeutics. Some inhibitors have shown antitumor effects in clinical trials, spurring the discovery of small molecule Hsp90 inhibitors. Here, we describe the structural optimization studies of a hit compound, tetrahydropyrido[4,3-d]pyrimidine-based Hsp90 inhibitor 15, which exhibits inhibitory activity against Hsp90. A series of analogues were synthesized, and their structure-activity and structure-property relationships were analyzed. These explorations led to the discovery of compound 73, which exhibited potent in vitro activities, good physicochemical properties, favorable ADME properties, and a potent antitumor effect in an HCT116 xenograft model...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27933614/antiviral-agents-for-infectious-mononucleosis-glandular-fever
#12
REVIEW
Muireann De Paor, Kirsty O'Brien, Tom Fahey, Susan M Smith
BACKGROUND: Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial...
December 8, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27933456/penicillin-v-acylases-from-gram-negative-bacteria-degrade-n-acylhomoserine-lactones-and-attenuate-virulence-in-pseudomonas-aeruginosa
#13
Avinash Vellore Sunder, Putri Dwi Utari, Sureshkumar Ramasamy, Ronald van Merkerk, Wim Quax, Archana Pundle
Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood...
December 8, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27933367/antipsychotic-inductors-of-brain-hypothermia-and-torpor-like-states-perspectives-of-application
#14
REVIEW
Yury S Tarahovsky, Irina S Fadeeva, Natalia P Komelina, Maxim O Khrenov, Nadezhda M Zakharova
Hypothermia and hypometabolism (hypometabothermia) normally observed during natural hibernation and torpor, allow animals to protect their body and brain against the damaging effects of adverse environment. A similar state of hypothermia can be achieved under artificial conditions through physical cooling or pharmacological effects directed at suppression of metabolism and the processes of thermoregulation. In these conditions called torpor-like states, the mammalian ability to recover from stroke, heart attack, and traumatic injuries greatly increases...
December 8, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27933277/lectins-from-synadenium-carinatum-scll-and-artocarpus-heterophyllus-artinm-are-able-to-induce-beneficial-immunomodulatory-effects-in-a-murine-model-for-treatment-of-toxoplasma-gondii-infection
#15
Eliézer L P Ramos, Silas S Santana, Murilo V Silva, Fernanda M Santiago, Tiago W P Mineo, José R Mineo
Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27933141/emergence-of-serotype-k1-klebsiella-pneumoniae-st23-strains-co-producing-the-plasmid-mediated-ampc-beta-lactamase-dha-1-and-an-extended-spectrum-beta-lactamase-in-korea
#16
Hae Suk Cheong, Doo Ryeon Chung, Chaeyoeng Lee, So Hyun Kim, Cheol-In Kang, Kyong Ran Peck, Jae-Hoon Song
BACKGROUND: Serotype K1 Klebsiella pneumoniae has emerged as an important community pathogen causing various infections, including liver abscesses. Although serotype K1 K. pneumoniae community isolates have been reported as susceptible to most classes of antimicrobial agents, a few cases of infection caused by extended-spectrum beta-lactamase (ESBL)-producing serotype K1 K. pneumoniae have recently been reported in Asian countries. We identified three ESBL-producing strains of serotype K1 K...
2016: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/27932943/vacuolar-protein-sorting-genes-in-parkinson-s-disease-a-re-appraisal-of-mutations-detection-rate-and-neurobiology-of-disease
#17
REVIEW
Stefano Gambardella, Francesca Biagioni, Rosangela Ferese, Carla L Busceti, Alessandro Frati, Giuseppe Novelli, Stefano Ruggieri, Francesco Fornai
Mammalian retromers play a critical role in protein trans-membrane sorting from endosome to the trans-Golgi network (TGN). Recently, retromer alterations have been related to the onset of Parkinson's Disease (PD) since the variant p.Asp620Asn in VPS35 (Vacuolar Protein Sorting 35) was identified as a cause of late onset PD. This variant causes a primary defect in endosomal trafficking and retromers formation. Other mutations in VPS genes have been reported in both sporadic and familial PD. These mutations are less defined...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932568/targeting-hif2-in-clear-cell-renal-cell-carcinoma
#18
Hyejin Cho, William G Kaelin
Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1...
December 8, 2016: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/27932229/regorafenib-for-patients-with-hepatocellular-carcinoma-who-progressed-on-sorafenib-treatment-resorce-a-randomised-double-blind-placebo-controlled-phase-3-trial
#19
Jordi Bruix, Shukui Qin, Philippe Merle, Alessandro Granito, Yi-Hsiang Huang, György Bodoky, Marc Pracht, Osamu Yokosuka, Olivier Rosmorduc, Valeriy Breder, René Gerolami, Gianluca Masi, Paul J Ross, Tianqiang Song, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Masatoshi Kudo, Ann-Lii Cheng, Josep M Llovet, Richard S Finn, Marie-Aude LeBerre, Annette Baumhauer, Gerold Meinhardt, Guohong Han
BACKGROUND: There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment. METHODS: In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled...
December 5, 2016: Lancet
https://www.readbyqxmd.com/read/27932068/rovalpituzumab-tesirine-a-dll3-targeted-antibody-drug-conjugate-in-recurrent-small-cell-lung-cancer-a-first-in-human-first-in-class-open-label-phase-1-study
#20
Charles M Rudin, M Catherine Pietanza, Todd M Bauer, Neal Ready, Daniel Morgensztern, Bonnie S Glisson, Lauren A Byers, Melissa L Johnson, Howard A Burris, Francisco Robert, Tae H Han, Sheila Bheddah, Noah Theiss, Sky Watson, Deepan Mathur, Bharathi Vennapusa, Hany Zayed, Satwant Lally, Donald K Strickland, Ramaswamy Govindan, Scott J Dylla, Stanford L Peng, David R Spigel
BACKGROUND: Rovalpituzumab tesirine is a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), a novel target identified in tumour-initiating cells and expressed in more than 80% of patients with small-cell lung cancer. We aimed to assess the safety and activity of rovalpituzumab tesirine in patients who progressed after one or more previous regimen. METHODS: We conducted a phase 1 open-label study at ten cancer centres in the USA...
December 2, 2016: Lancet Oncology
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