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https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#1
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28069963/pathogen-boosted-adoptive-cell-transfer-immunotherapy-to-treat-solid-tumors
#2
Gang Xin, David M Schauder, Weiqing Jing, Aimin Jiang, Nikhil S Joshi, Bryon Johnson, Weiguo Cui
Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28059794/oxidative-stress-synaptic-dysfunction-and%C3%A2-alzheimer-s-disease
#3
Eric Tönnies, Eugenia Trushina
Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28028417/a-twofold-comparison-between-dual-cure-resin-modified-cement-and-glass-ionomer-cement-for-orthodontic-band-cementation
#4
Hanaa El Attar, Omnia Elhiny, Ghada Salem, Ahmed Abdelrahman, Mazen Attia
AIM: To test the solubility of dual cure resin modified resin cement in a food simulating solution and the shear bond strength compared to conventional Glass ionomer cement. MATERIALS AND METHOD: The materials tested were self-adhesive dual cure resin modified cement and Glass Ionomer (GIC). Twenty Teflon moulds were divided into two groups of tens. The first group was injected and packed with the modified resin cement, the second group was packed with GIC. To test the solubility, each mould was weighed before and after being placed in an analytical reagent for 30 days...
December 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28000531/cytokines-and-metabolic-factors-regulate-tumoricidal-t-cell-function-during-cancer-immunotherapy
#5
Adam J Adler, Payal Mittal, Joseph M Ryan, Beiyan Zhou, Jeffrey S Wasser, Anthony T Vella
Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL. Conversely, immunotherapies can mitigate specific metabolic stressors...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27997540/il-7-receptor-mutations-and-steroid-resistance-in-pediatric-t-cell-acute-lymphoblastic-leukemia-a-genome-sequencing-study
#6
Yunlei Li, Jessica G C A M Buijs-Gladdines, Kirsten Canté-Barrett, Andrew P Stubbs, Eric M Vroegindeweij, Willem K Smits, Ronald van Marion, Winand N M Dinjens, Martin Horstmann, Roland P Kuiper, Rogier C Buijsman, Guido J R Zaman, Peter J van der Spek, Rob Pieters, Jules P P Meijerink
BACKGROUND: Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27986884/beyond-rchop-a-blueprint-for-diffuse-large-b-cell-lymphoma-research
#7
REVIEW
Grzegorz S Nowakowski, Kristie A Blum, Brad S Kahl, Jonathan W Friedberg, Lawrence Baizer, Richard F Little, David G Maloney, Laurie H Sehn, Michael E Williams, Wyndham H Wilson, John P Leonard, Sonali M Smith
Diffuse large B cell lymphoma (DLBCL) comprises multiple molecular and biological subtypes, resulting in a broad range of clinical outcomes. With standard chemoimmunotherapy, there remains an unacceptably high treatment failure rate in certain DLBCL subsets: activated B cell (ABC) DLBCL, double-hit lymphoma defined by the dual translocation of MYC and BCL2, dual protein-expressing lymphomas defined by the overexpression of MYC and BCL2, and older patients and those with central nervous system involvement. The main research challenges for DLBCL are to accurately identify molecular subsets and to determine if specific chemotherapy platforms and targeted agents offer differential benefit...
December 2016: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27986363/efficacy-of-folfoxiri-plus-bevacizumab-in-liver-limited-metastatic-colorectal-cancer-a-pooled-analysis-of-clinical-studies-by-gruppo-oncologico-del-nord-ovest
#8
Chiara Cremolini, Mariaelena Casagrande, Fotios Loupakis, Giuseppe Aprile, Francesca Bergamo, Gianluca Masi, Roberto Moretto R, Filippo Pietrantonio, Federica Marmorino, Gemma Zucchelli, Gianluca Tomasello, Giuseppe Tonini, Giacomo Allegrini, Cristina Granetto, Laura Ferrari, Lucio Urbani, Umberto Cillo, Pierluigi Pilati, Elisa Sensi, Alessio Pellegrinelli, Massimo Milione, Gabriella Fontanini, Alfredo Falcone
Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest...
December 13, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27982188/tensile-strength-of-resin-cements-used-with-base-metals-in-a-simulating-passive-cementation-technique-for-implant-supported-prostheses
#9
Hilmo Barreto Leite Falcão, Ricardo Faria Ribeiro, Raphael Freitas de Souza, Ana Paula Macedo, Rossana Pereira de Almeida
The aim of this study was to analyze the tensile strength of two different resin cements used in passive cementation technique for implant-supported prosthesis. Ninety-six plastic cylinders were waxed in standardized forms, cast in commercially pure titanium, nickel-chromium and nickel-chromium-titanium alloys. Specimens were cemented on titanium cylinders using self-adhesive resin cement or conventional dual-cured resin cement. Specimens were divided in 12 groups (n=8) in accordance to metal, cement and ageing process...
October 2016: Brazilian Dental Journal
https://www.readbyqxmd.com/read/27976854/polymeric-quaternary-ammonium-containing-coatings-with-potential-dual-contact-based-and-release-based-antimicrobial-activity
#10
Denisa Druvari, Nikos D Koromilas, Georgia Ch Lainioti, Georgios Bokias, Gavriil Vasilopoulos, Apostolos Vantarakis, Ilias Baras, Nancy Dourala, Joannis K Kallitsis
In the present work, reactive blending of copolymers with complementary functional groups was applied to control their antimicrobial activity and antifouling action in real conditions. For this purpose, two series of copolymers, poly(4-vinylbenzyl chloride-co-acrylic acid), P(VBC-co-AAx), and poly(sodium 4-styrenesulfonate-co-glycidyl methacrylate), P(SSNa-co-GMAx), were synthesized via free radical copolymerization and further modified by the incorporation of biocidal units either covalently (4-vinyl benzyl dimethylhexadecylammonium chloride, VBCHAM) or electrostatically bound (cetyltrimethylammonium 4-styrenesulfonate, SSAmC16)...
December 28, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27974196/a-combinatorial-crispr-cas9-attack-on-hiv-1-dna-extinguishes-all-infectious-provirus-in-infected-t-cell-cultures
#11
Gang Wang, Na Zhao, Ben Berkhout, Atze T Das
Current drug therapies effectively suppress HIV-1 replication but do not inactivate the provirus that persists in latent reservoirs. Recent studies have found that the guide RNA (gRNA)-directed CRISPR/Cas9 system can be used for sequence-specific attack on this proviral DNA. Although potent inhibition of virus replication was reported, HIV-1 can escape from a single antiviral gRNA by mutation of the target sequence. Here, we demonstrate that combinations of two antiviral gRNAs delay viral escape, and identify two gRNA combinations that durably block virus replication...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27967320/effect-of-steam-autoclaving-on-the-tensile-strength-of-resin-cements-used-for-bonding-two-piece-zirconia-abutments
#12
Marcos Alexandre Fadanelli, Flà  Via Lucisano Botelho Amaral, Roberta Tarkany Basting, Cecilia Pedroso Turssi, Bruno Salles Sotto-Maior, Fabiana Mantovani Gomes Franà  A
PURPOSE: this study evaluated the effects of steam autoclave sterilization on the tensile strength of two types of resin cements used to bond customized CAD/CAM zirconia abutments onto titanium bases. METHODS: forty sets of zirconia abutments cemented to screwed titanium bases of implants analogs were divided into four groups (n = 10). Two groups were treated with a conventional chemically activated resin cement (ML - Multilink Ivoclar Vivadent) and the other two groups with a self-adhesive dual resin cement (U200 - U200 RelyX 3M ESPE)...
December 14, 2016: Journal of Oral Implantology
https://www.readbyqxmd.com/read/27917405/efficacy-and-safety-of-3-week-response-guided-triple-direct-acting-antiviral-therapy-for-chronic-hepatitis-c-infection-a-phase-2-open-label-proof-of-concept-study
#13
George Lau, Yves Benhamou, Guofeng Chen, Jin Li, Qing Shao, Dong Ji, Fan Li, Bing Li, Jialiang Liu, Jinlin Hou, Jian Sun, Cheng Wang, Jing Chen, Vanessa Wu, April Wong, Chris L P Wong, Stella T Y Tsang, Yudong Wang, Leda Bassit, Sijia Tao, Yong Jiang, Hui-Mien Hsiao, Ruian Ke, Alan S Perelson, Raymond F Schinazi
BACKGROUND: To shorten the course of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, we examined the antiviral efficacy and safety of 3 weeks of response-guided therapy with an NS3 protease inhibitor and dual NS5A inhibitor-NS5B nucleotide analogue. METHODS: In this open-label, phase 2a, single centre study, Chinese patients with chronic HCV genotype 1b infection without cirrhosis were randomly allocated by a computer program to one of three treatment groups (sofosbuvir, ledipasvir, and asunaprevir; sofosbuvir, daclatasvir, and simeprevir; or sofosbuvir, daclatasvir, and asunaprevir) until six patients in each group (1:1:1) achieved an ultrarapid virological response (plasma HCV RNA <500 IU/mL by day 2, measured by COBAS TaqMan HCV test, version 2...
October 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27898590/reactivation-of-simian-immunodeficiency-virus-reservoirs-in-the-brain-of-virally-suppressed-macaques
#14
Lucio Gama, Celina M Abreu, Erin N Shirk, Sarah L Price, Ming Li, Greg M Laird, Kelly A Metcalf Pate, Stephen W Wietgrefe, Shelby L O'Connor, Luiz Pianowski, Ashley T Haase, Carine Van Lint, Robert F Siliciano, Janice E Clements
OBJECTIVE: Resting CD4 T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation. DESIGN: Pigtailed macaques were dual inoculated with SIVDeltaB670 and SIV17E-Fr and treated with an efficacious central nervous system-penetrant ART...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27882021/compressive-strength-and-the-effect-of-duration-after-photo-activation-among-dual-cure-bulk-fill-composite-core-materials
#15
Fahad Alkhudhairy, Fahim Vohra
OBJECTIVES: To assess compressive strength and effect of duration after photoactivation on the compressive strength of different dual cure bulk fill composites. METHODS: Seventy-two disc shaped (4x10mm) specimens were prepared from three dual cure bulk fill materials, ZirconCore (ZC) (n=24), MulticCore Flow (MC) (n=24) and Luxacore Dual (LC) (n=24). Half of the specimens in each material were tested for failure loads after one hour [MC1 (n=12), LC1 (n=12) & ZC1 (n=12)] and the other half in 7 days [MC7 (n=12), LC7 (n=12), ZC7 (n=12)] from photo-polymerization using the universal testing machine at a cross-head speed of 0...
September 2016: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/27881659/glycosylphosphatidylinositol-anchored-anti-hiv-scfv-efficiently-protects-cd4-t-cells-from-hiv-1-infection-and-deletion-in-hu-pbl-mice
#16
Chaobaihui Ye, Weiming Wang, Liang Cheng, Guangming Li, Michael Wen, Qi Wang, Qing Zhang, Dan Li, Paul Zhou, Lishan Su
: Despite success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of the HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from a homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance in permissive cells...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27879042/high-antibiotic-resistance-of-helicobacter-pylori-and-its-effect-on-tailored-and-empiric-eradication-of-the-organism-in-lower-silesia-poland
#17
Stanisław Ferenc, Jan Gnus, Magdalena Kościelna, Małgorzata Kinda, Andriy Yarka, Luke Stewart, Wojciech Witkiewicz
BACKGROUND: At present, the resistance to antibiotics is considered the most important reason for Helicobacter pylori (HP) eradication failure. The aim of this study was to estimate the prevalence of antimicrobial resistance of HP strains and to evaluate tailored and empiric therapeutic regimens in patients with peptic ulcer disease associated with infection of this microorganism. MATERIALS AND METHODS: Between May 2011 and February 2013, 185 consecutive Polish patients with at least one positive Helicobacter pylori test (urease test, histopathologic examination, and/or culture) underwent eradication therapy...
November 23, 2016: Helicobacter
https://www.readbyqxmd.com/read/27871482/push-out-bond-strength-of-fiber-posts-to-intraradicular-dentin-using-multimode-adhesive-system
#18
Siavash Savadi Oskoee, Mahmoud Bahari, Soodabeh Kimyai, Saeed Asgary, Katayoun Katebi
INTRODUCTION: Because there is little information about bond strength of fiber posts cemented with a universal adhesive system (UAS) with different resin cements, the aim of this study was to compare the effect of different bonding strategies in the application of UASs on push-out bond strength of fiber posts to intraradicular dentin. METHODS: Seventy-two single-rooted teeth were randomly divided into 6 groups: self-adhesive resin cement (SAC), dual-cure resin cement (DCC), UAS in the etch-and-rinse (E&R) mode and SAC (E&R + SAC), UAS in the self-etch (SE) mode and SAC (SE + SAC), UAS in the E&R mode and DCC (E&R + DCC), and UAS in the SE mode and DCC (SE + DCC)...
December 2016: Journal of Endodontics
https://www.readbyqxmd.com/read/27847748/effects-of-radiant-exposure-and-wavelength-spectrum-of-light-curing-units-on-chemical-and-physical-properties-of-resin-cements
#19
Adriano Fonseca Lima, Stephanie Ellen Ferreira Formaggio, Lígia França Aires Zambelli, Alan Rodrigo Muniz Palialol, Giselle Maria Marchi, Cintia Helena Coury Saraceni, Marcelo Tavares de Oliveira
OBJECTIVES: In this study, we evaluated the influence of different radiant exposures provided by single-peak and polywave light-curing units (LCUs) on the degree of conversion (DC) and the mechanical properties of resin cements. MATERIALS AND METHODS: Six experimental groups were established for each cement (RelyX ARC, 3M ESPE; LuxaCore Dual, Ivoclar Vivadent; Variolink, DMG), according to the different radiant exposures (5, 10, and 20 J/cm(2)) and two LCUs (single-peak and polywave)...
November 2016: Restorative Dentistry & Endodontics
https://www.readbyqxmd.com/read/27843249/in-vitro-evaluation-of-stainless-steel-crowns-cemented-with-resin-modified-glass-ionomer-and-two-new-self-adhesive-resin-cements
#20
REVIEW
Sidhant Pathak, K K Shashibhushan, P Poornima, Vv Subba Reddy
AIMS: To assess and compare the retentive strength of two dual-polymerized self-adhesive resin cements (RelyX U200, 3M ESPE & SmartCem2, Dentsply Caulk) and a resin-modified glass ionomer cement (RMGIC; RelyX Luting 2, 3M ESPE) on stainless steel crown (SSC). MATERIALS AND METHODS: Thirty extracted teeth were mounted on cold cured acrylic resin blocks exposing the crown till the cemento-enamel junction. Pretrimmed, precontoured SSC was selected for a particular tooth...
July 2016: International Journal of Clinical Pediatric Dentistry
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