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https://www.readbyqxmd.com/read/29341833/immune-modified-response-evaluation-criteria-in-solid-tumors-imrecist-refining-guidelines-to-assess-the-clinical-benefit-of-cancer-immunotherapy
#1
F Stephen Hodi, Marcus Ballinger, Benjamin Lyons, Jean-Charles Soria, Mizuki Nishino, Josep Tabernero, Thomas Powles, David Smith, Axel Hoos, Chris McKenna, Ulrich Beyer, Ina Rhee, Gregg Fine, Nathan Winslow, Daniel S Chen, Jedd D Wolchok
Purpose Treating solid tumors with cancer immunotherapy (CIT) can result in unconventional responses and overall survival (OS) benefits that are not adequately captured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. We describe immune-modified RECIST (imRECIST) criteria, designed to better capture CIT responses. Patients and Methods Atezolizumab data from clinical trials in non-small-cell lung cancer, metastatic urothelial carcinoma, renal cell carcinoma, and melanoma were evaluated. Modifications to imRECIST versus RECIST v1...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29341369/structural-factors-affecting-binding-of-platinum-anticancer-agents-with-phospholipids-influence-of-charge-and-phosphate-clamp-formation
#2
Anil Kumar Gorle, Junyong Zhang, Qin Liu, Susan J Berners-Price, Nicholas P Farrell
We report a detailed NMR and DFT study of the interaction of polynuclear platinum anticancer agents (PPCs) with negatively charged phospholipids as a mechanism for their cellular uptake. The reactions of fully 15N-labelled [{trans-PtCl(NH3)2}2(-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (15N-1, 1,0,1/t,t,t) and the dinuclear [{trans-PtCl(NH3)2}2{-H2N(CH2)6NH2}]2+ (15N-2, 1,1/t,t) with the sodium salt of 1,2-dihexanoyl-sn-glycero-3-phosphate (DHPA) were studied at 298 K, pH ~5.4, by [1H,15N] HSQC 2D NMR spectroscopy...
January 17, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29340974/inhibiting-6-phosphogluconate-dehydrogenase-selectively-targets-breast-cancer-through-ampk-activation
#3
Xiaoyu Yang, Xiaochun Peng, Jiangrong Huang
PURPOSE: 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative pentose phosphate pathway, is involved in tumor growth and metabolism. Although high 6PGD activity has been shown to be associated with poor prognosis, its role and therapeutic value in breast cancer remain unknown. METHODS: The levels and roles of 6PGD were analyzed in breast cancer cells and their normal counterparts. The underlying mechanisms of 6PGD's roles are also analyzed. RESULTS: We found that 6PGD is aberrantly activated in breast cancer as shown by its increased transcriptional and translational levels as well as enzyme activity in breast cancer tissues and cell lines compared to normal counterparts...
January 16, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29340044/cepharanthine-hydrochloride-reverses-the-mdr1-p-glycoprotein-mediated-esophageal-squamous-cell-carcinoma-cell-cisplatin-resistance-through-jnk-and-p53-signals
#4
Pengjun Zhou, Rong Zhang, Ying Wang, Dandan Xu, Li Zhang, Jinhong Qin, Guifeng Su, Yue Feng, Hongce Chen, Siyuan You, Wen Rui, Huizhong Liu, Suhong Chen, Hongyuan Chen, Yifei Wang
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339643/effect-of-remote-ischemic-preconditioning-on-systemic-toxicity-and-ototoxicity-induced-by-cisplatin-in-rats-role-of-tnf-%C3%AE-and-nitric-oxide
#5
Marcos Jullian Barreto Martins, Avner Marcos Alves Batista, Yuri Neyson Ferreira Brito, Pedro Marcos Gomes Soares, Conceição da Silva Martins, Ronaldo de Albuquerque Ribeiro, Gerly Anne de Castro Brito, Marcos Rabelo de Freitas
BACKGROUND/AIMS: Cisplatin is a chemotherapeutic agent. The use of remote ischemic preconditioning (RIPC) was proposed after the observation that ischemic preconditioning of a cardiac vascular area could protect another completely distinctly. METHODS: This is an experimental study. Male Wistar rats were anesthetized, and they underwent a hearing evaluation via measurement of the brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group 1, whereas saline solution was administered IP to group 2...
January 17, 2018: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/29339439/idh1-2-mutations-sensitize-acute-myeloid-leukemia-to-parp-inhibition-and-this-is-reversed-by-idh1-2-mutant-inhibitors
#6
Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Mohammed Khurshed, Bartlomiej Przychodzen, Hideki Makishima, Mingjiang Xu, Fonnet E Bleeker, Johanna W Wilmink, Hetty Carraway, Sudipto Mukherjee, Mikkael A Sekeres, Cornelis J F Van Noorden, Jaroslaw P Maciejewski
PURPOSE: Somatic mutations in IDH1/2 occur in ~20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increases in DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known. EXPERIMENTAL DESIGN: Well-characterized primary IDH1MUT, IDH2MUT and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation and PARP inhibitors...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29339403/a-phase-1-study-of-azacitidine-combined-with-chemotherapy-in-childhood-leukemia-a-report-from-tacl-consortium
#7
Weili Sun, Timothy Triche, Jemily Malvar, Paul Gaynon, Richard Sposto, Xiaojing Yang, Henrique Bittencourt, Andrew E Place, Yoav Messinger, Chris Fraser, Luciano Dalla-Pozza, Bodour Salhia, Peter Jones, Alan S Wayne, Lia Gore, Todd M Cooper, Gangning Liang
Growing evidence indicates that aberrant DNA hypermethylation is associated with leukemogenesis, chemotherapy resistance, and relapse. DNA methyltransferase inhibitors such as azacitidine and decitabine have been shown to reverse drug resistance and prime leukemia cells to cytotoxic agents in vitro. Here we report the first pediatric phase 1 study using azacitidine in sequence with chemotherapy in patients with relapsed/refractory leukemia. Fourteen patients were enrolled, twelve with acute myeloid leukemia (AML) and two with acute lymphoblastic leukemia (ALL)...
January 16, 2018: Blood
https://www.readbyqxmd.com/read/29338543/lucidone-suppresses-dengue-viral-replication-through-the-induction-of-heme-oxygenase-1
#8
Wei-Chun Chen, Chin-Kai Tseng, Chun-Kuang Lin, Shen-Nien Wang, Wen-Hung Wang, Shih-Hsien Hsu, Yu-Hsuan Wu, Ling-Chien Hung, Yen-Hsu Chen, Jin-Ching Lee
Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29336885/structural-basis-for-activity-and-specificity-of-an-anticoagulant-anti-fxia-monoclonal-antibody-and-a-reversal-agent
#9
Lauren K Ely, Marco Lolicato, Tovo David, Kate Lowe, Yun Cheol Kim, Dharmaraj Samuel, Paul Bessette, Jorge L Garcia, Thomas Mikita, Daniel L Minor, Shaun R Coughlin
Coagulation factor XIa is a candidate target for anticoagulants that better separate antithrombotic efficacy from bleeding risk. We report a co-crystal structure of the FXIa protease domain with DEF, a human monoclonal antibody that blocks FXIa function and prevents thrombosis in animal models without detectable increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and active site, while the heavy chain provides electrostatic interactions with the surface of FXIa. The structure accounts for the specificity of DEF for FXIa over its zymogen and related proteases, its active-site-dependent binding, and its ability to inhibit substrate cleavage...
January 2, 2018: Structure
https://www.readbyqxmd.com/read/29336655/reversible-cicatricial-ectropion-associated-with-egfr-inhibitors
#10
Stacy Scofield-Kaplan, James Todaro, Bryan J Winn
The management of cicatricial ectropion resulting from epidermal growth factor receptor (EGFR) inhibitors is unclear. We describe two cases of bilateral cicatricial ectropion following the use of an EGFR inhibitor who were treated with oral doxycycline, topical ophthalmic steroid and antibiotic ointment to the eyelids, and topical facial steroid cream with lubrication. The first case resolved with discontinuation of panitumumab infusions along with institution of the aforementioned regimen. However, it is unclear whether the resolution was from discontinuation of the infusions or from the instituted regimen...
January 16, 2018: Orbit
https://www.readbyqxmd.com/read/29335895/pharmacokinetics-antiviral-activity-and-safety-of-rilpivirine-in-pregnant-women-with-hiv-1-infection-results-of-a-phase-3b-multicenter-open-label-study
#11
Olayemi Osiyemi, Salih Yasin, Carmen Zorrilla, Ceyhun Bicer, Vera Hillewaert, Kimberley Brown, Herta M Crauwels
INTRODUCTION: Physiologic changes during pregnancy may impact the pharmacokinetics of drugs. In addition, efficacy and safety/tolerability concerns have been identified for some antiretroviral agents. METHODS: Human immunodeficiency virus (HIV)-1-infected pregnant women (18-26 weeks gestation) receiving the non-nucleoside reverse transcriptase inhibitor rilpivirine 25 mg once daily were enrolled in this phase 3b, open-label study examining the impact of pregnancy on the pharmacokinetics of rilpivirine when it is given in combination with other antiretroviral agents...
January 15, 2018: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/29335220/adeno-associated-virus-vector-mediated-expression-of-dj-1-attenuates-learning-and-memory-deficits-in-2-2%C3%A2-4-4%C3%A2-tetrabromodiphenyl-ether-bde-47-treated-mice
#12
Juan Zhuang, Shan Wang, Qun Shan, Zi-Feng Zhang, Meng-Qiu Li, Gui-Hong Zheng, Shao-Hua Fan, Dong-Mei Wu, Bin Hu, Jun Lu, Yuan-Lin Zheng
Evidence indicates that oxidative stress is the central pathological feature of 2, 2´, 4, 4´-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity. Protein kinase C delta (PKCδ), an oxidative stress-sensitive kinase, can be proteolytically cleaved to yield a catalytically active fragment (PKCδ-CF) that is involved in various neurodegenerative disorders. Here, we showed that BDE-47 treatment increased ROS, malondialdehyde, and protein carbonyl levels in the mouse hippocampus. In turn, excessive ROS induced caspase-3-dependent PKCδ activation and stimulated NF-κB p65 nuclear translocation, resulting in inflammation in the mouse hippocampus...
January 8, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29335204/synthesis-and-biological-evaluation-of-bifendate-derivatives-bearing-6-7-dihydro-dibenzo-c-e-azepine-scaffold-as-potential-p-glycoprotein-and-tumor-metastasis-inhibitors
#13
Xiaoke Gu, Yanfei Jiang, Yingying Qu, Jing Chen, Dingding Feng, Chenglin Li, Xiaoxing Yin
As a continuation of previous research, fifteen bifendate derivatives bearing 6,7-dihydro-dibenzo [c,e]azepine scaffold were synthesized and evaluated as P-gp-medicated multidrug resistance (MDR) reversal agents. Biological evaluation indicated that compounds 6k and 9c more potently reversed P-gp-mediated MDR than bifendate and verapamil (VRP) by blocking P-gp mediated drug efflux function and not by decreasing P-gp expression in K562/A02 MDR cells. Interestingly, wound-healing and chamber migration assay showed that 6k and 9c could significantly attenuate the migration of MDA-MB-231 cells...
January 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29334822/vibsanol-a-induces-differentiation-of-acute-myeloid-leukemia-cells-via-activation-of-the-pkc-signaling-pathway-and-induction-of-ros
#14
Meng Yang, Shuang Xing, Hong-Ling Ou, Lu Zhang, Xing Shen, Guo-Lin Xiong, Fang-Min Wang, He Xiao, Yan-Hong Tu, Yu-Wen Cong, Xin-Ru Wang, Zu-Yin Yu
Identifying novel differentiating agents to promote leukemia-cell differentiation is a pressing need. Here, we demonstrated that vibsanol A, a vibsane-type diterpenoid, inhibited the growth of acute myeloid leukemia (AML) cells via induction of cell differentiation, which was characterized by G1 cell cycle arrest. The differentiation-inducing effects of vibsanol A were dependent upon protein kinase C (PKC) activation, and subsequent activation of the extracellular signal-regulated kinase (ERK) pathway. Furthermore, vibsanol A treatment increased reactive oxygen species (ROS) levels, and the ROS scavenger NAC reversed the vibsanol A-induced cell differentiation, indicating an important role for ROS in the action of vibsanol A...
January 16, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29334406/dasatinib-induced-pulmonary-arterial-hypertension
#15
REVIEW
Nurgül Özgür Yurttaş, Ahmet Emre Eşkazan
Drug-induced (Group 1) pulmonary hypertension (PH) is an important subgroup of PH involving dasatinib as a likely related agent, which is a second-generation tyrosine kinase inhibitor (TKI), that is used in the treatment of chronic myeloid leukemia (CML). The mechanism of dasatinib-induced pulmonary arterial hypertension (PAH) is unclear. However, the occurence of PAH at a late onset in CML patients suggests a chronic pathological mechanism with an insidious onset rather than an acute inflammatory or cardiac etiology...
January 15, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29333750/hydroperoxide-traces-in-common-cyclic-ethers-as-initiators-for-controlled-raft-polymerizations
#16
Steffen Eggers, Volker Abetz
Herein, a reversible addition-fragmentation chain transfer (RAFT) polymerization is introduced for reactive monomers like N-acryloylpyrrolidine or N,N-dimethylacrylamide working without a conventional radical initiator. As a very straightforward proof of principle, the method takes advantage of the usually inconvenient radical-generating hydroperoxide contaminations in cyclic ethers like tetrahydrofuran or 1,4-dioxane, which are very common solvents in polymer sciences. The polymerizations are surprisingly well controlled and the polymers can be extended with a second block, indicating their high livingness...
January 15, 2018: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29333572/possible-protective-effect-of-the-algae-spirulina-against-nephrotoxicity-induced-by-cyclosporine-a-and-or-gamma-radiation-in-rats
#17
Maha M Aziz, Nihad I Eid, Ahmed S Nada, Nour El-Din Amin, Afaf A Ain-Shoka
The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity...
January 15, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29332571/role-of-heart-rate-reduction-in-the-management-of-myocarditis
#18
Chen Guang-Yi, Ge Li-Sha, Li Yue-Chun
The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease...
January 10, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29331612/arterial-spin-labeling-cerebral-perfusion-magnetic-resonance-imaging-in-migraine-aura-an-observational-study
#19
Marc E Wolf, Shuhei Okazaki, Philipp Eisele, Christina Rossmanith, Johannes Gregori, Martin Griebe, Matthias Günther, Achim Gass, Michael G Hennerici, Kristina Szabo, Rolf Kern
BACKGROUND: Changes in cerebral perfusion during migraine with aura (MA) have been assessed mainly using dynamic susceptibility contrast (DSC) magnetic resonance perfusion imaging. A contrast agent-free method to assess these changes would be desirable. We assessed changes in cerebral perfusion during MA using arterial spin labeling (ASL) perfusion magnetic resonance imaging. METHODS: We investigated 4 patients with a standardized protocol including ASL perfusion imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow-up...
January 10, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29331588/antagonism-of-cysteinyl-leukotriene-receptor-1-cysltr1-by-montelukast-suppresses-cell-senescence-of-chondrocytes
#20
Wei Song, Yumin Zhang, Jun Wang, Tao Ma, Linjie Hao, Kunzheng Wang
Aging is closely associated with osteoarthritis (OA). Although its underlying mechanisms remain unknown, cellular senescence in chondrocytes has become an important therapeutic target for the treatment of OA. Cysteinyl leukotriene receptors (cysLTRs) mediate the pathobiological function of cysteinyl leukotrienes (cysLTs). However, the roles of cysLTRs in the pathogenesis of OA have not been reported before. In the current study, we found that cysLTR1 but not cysLTR2 is expressed in human primary chondrocytes...
January 10, 2018: Cytokine
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