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https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#1
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29346387/inferring-the-risk-factors-behind-the-geographical-spread-and-transmission-of-zika-in-the-americas
#2
Lauren M Gardner, András Bóta, Karthik Gangavarapu, Moritz U G Kraemer, Nathan D Grubaugh
BACKGROUND: An unprecedented Zika virus epidemic occurred in the Americas during 2015-2016. The size of the epidemic in conjunction with newly recognized health risks associated with the virus attracted significant attention across the research community. Our study complements several recent studies which have mapped epidemiological elements of Zika, by introducing a newly proposed methodology to simultaneously estimate the contribution of various risk factors for geographic spread resulting in local transmission and to compute the risk of spread (or re-introductions) between each pair of regions...
January 18, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29344362/development-of-biomarker-combinations-for-postoperative-acute-kidney-injury-via-bayesian-model-selection-in-a-multicenter-cohort-study
#3
Allison Meisner, Kathleen F Kerr, Heather Thiessen-Philbrook, Francis Perry Wilson, Amit X Garg, Michael G Shlipak, Peter Kavsak, Richard P Whitlock, Steven G Coca, Chirag R Parikh
Background: Acute kidney injury (AKI) is a frequent complication of cardiac surgery. We sought prognostic combinations of postoperative biomarkers measured within 6 h of surgery, potentially in combination with cardiopulmonary bypass time (to account for the degree of insult to the kidney). We used data from a large cohort of patients and adapted methods for developing biomarker combinations to account for the multicenter design of the study. Methods: The primary endpoint was sustained mild AKI, defined as an increase of 50% or more in serum creatinine over preoperative levels lasting at least 2 days during the hospital stay...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29344310/drug-repurposing-screening-identifies-tioconazole-as-an-atg4-inhibitor-that-suppresses-autophagy-and-sensitizes-cancer-cells-to-chemotherapy
#4
Pei-Feng Liu, Kun-Lin Tsai, Chien-Jen Hsu, Wei-Lun Tsai, Jin-Shiung Cheng, Hsueh-Wei Chang, Chung-Wai Shiau, Yih-Gang Goan, Ho-Hsing Tseng, Chih-Hsuan Wu, John C Reed, Lee-Wei Yang, Chih-Wen Shu
Background: Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clinical cancer research remains controversial due to the limited number of drugs that specifically inhibit autophagy-related (ATG) proteins. Methods: We screened FDA-approved drugs using a novel platform that integrates computational docking and simulations as well as biochemical and cellular reporter assays to identify potential drugs that inhibit autophagy-required cysteine proteases of the ATG4 family...
2018: Theranostics
https://www.readbyqxmd.com/read/29344305/a-tumor-activatable-theranostic-nanomedicine-platform-for-nir-fluorescence-guided-surgery-and-combinatorial-phototherapy
#5
Xiaoning Li, Canan Schumann, Hassan A Albarqi, Christopher J Lee, Adam W G Alani, Shay Bracha, Milan Milovancev, Olena Taratula, Oleh Taratula
Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29343959/antitumor-effect-of-a-new-nano-vector-with-mirna-135a-on-malignant-glioma
#6
Chaofeng Liang, Weitong Sun, Haiyong He, Baoyu Zhang, Cong Ling, Bocheng Wang, Tengchao Huang, Bo Hou, Ying Guo
Introduction: MiR-135a is found to selectively induce apoptosis in glioma cell but not in normal neurons and glial cells. However, low transfection efficacy limits its application in vivo as other miRNAs. We prepared a new kind of nano-vector based on polyethylene glycol methyl ether (mPEG) and hyper-branched polyethylenimine (hy-PEI) in order to improve the miRNA delivery system into the glioma cells. Methods: The mPEG-g-PEI/miR-135a was constructed and detected by 1H NMR and FTIR analyses...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29343578/a-new-quinoline-brd4-inhibitor-targets-a-distinct-latent-hiv-1-reservoir-for-re-activation-from-other-shock-drugs
#7
Erik Abner, Mateusz Stoszko, Lei Zeng, Heng-Chang Chen, Andrea Izquierdo-Bouldstridge, Tsuyoshi Konuma, Eduard Zorita, Elisa Fanunza, Qiang Zhang, Tokameh Mahmoudi, Ming-Ming Zhou, Guillaume J Filion, Albert Jordan
Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents the eradication of the virus from patients. To achieve complete depletion, the existing virus-suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. We previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol) that is able to reactivate viral transcription in several models of HIV latency including J-Lat cells through an unknown mechanism. MMQO potentiates the activity of known latency-reversing agents (LRAs) or 'shock' drugs such as PKC agonists or HDAC inhibitors...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#8
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29342279/incidence-and-predictors-of-post-transplant-lymphoproliferative-disease-after-kidney-transplantation-during-adulthood-and-childhood-a-registry-study
#9
Anna Francis, David W Johnson, Armando Teixeira-Pinto, Jonathan C Craig, Germaine Wong
Background: Differences in the epidemiology of post-transplant lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant recipients remain unclear. Methods: Using the Australian and New Zealand Dialysis and Transplant Registry (1963-2015), the cumulative incidences of PTLD in children (age <20 years) and adults were calculated using a competing risk of death model and compared with age-matched population-based data using standardized incidence ratios (SIRs)...
January 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29342009/how-academic-health-systems-can-achieve-population-health-in-vulnerable-populations-through-value-based-care-the-critical-importance-of-establishing-trusted-agency
#10
Donald E Wesson, Heather E Kitzman
Improving population health may require health systems to proactively engage patient populations as partners in the implementation of healthy behaviors as a shared value using strategies that incentivize healthy outcomes for the population as a whole. The current reactive health care model, which focuses on restoring the health of individuals after it has been lost, will not achieve the goal of improved population health. To achieve this goal, health systems must proactively engage in partnerships with the populations they serve...
January 16, 2018: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#11
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29341021/assessment-of-blood-brain-barrier-leakage-with-gadolinium-enhanced-mri
#12
Min-Chi Ku, Sonia Waiczies, Thoralf Niendorf, Andreas Pohlmann
The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs) containing gadolinium are used in association with MRI in routine clinical practice to detect and quantify BBB leakage. Under normal circumstances CAs do not cross the intact BBB. However due to their small size they extravasate from the blood into the brain tissue even when the BBB is partially compromised. Here we describe an MR method based on T1-weighted images taken prior to and after CA injection...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29341020/mri-in-the-study-of-animal-models-of-stroke
#13
Pedro Ramos-Cabrer, Daniel Padro
Stroke consists of the loss of cerebral functions resulting from the interruption of blood supply to a region of the brain, and represents the second cause of death and the leading cause of major disability in adults in Europe. Stroke is a very active field of research at preclinical and clinical levels, and Magnetic Resonance Imaging (MRI) is one of the most powerful tools that scientist and clinicians have for the study of the onset, evolution and consequences of this devastating disease, as well as for the monitoring of the success of available treatments, or for the development of novel therapeutic strategies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29340526/simulating-the-behavior-of-patients-who-leave-a-public-hospital-emergency-department-without-being-seen-by-a-physician-a-cellular-automaton-and-agent-based-framework
#14
Milad Yousefi, Moslem Yousefi, F S Fogliatto, R P M Ferreira, J H Kim
The objective of this study was to develop an agent based modeling (ABM) framework to simulate the behavior of patients who leave a public hospital emergency department (ED) without being seen (LWBS). In doing so, the study complements computer modeling and cellular automata (CA) techniques to simulate the behavior of patients in an ED. After verifying and validating the model by comparing it with data from a real case study, the significance of four preventive policies including increasing number of triage nurses, fast-track treatment, increasing the waiting room capacity and reducing treatment time were investigated by utilizing ordinary least squares regression...
January 11, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29340053/indomethacin-based-stimuli-responsive-micelles-combined-with-paclitaxel-to-overcome-multidrug-resistance
#15
Shuanghu Wang, Xueying Tan, Shujuan Li, Yunfang Zhou, Peiwu Geng, Ailian Hua, Aiping Deng, Zhihong Yu
Development of multidrug resistance against antitumor agents is a major limiting factor for the successful chemotherapy. Currently, both amphiphilic polymeric micelles and chemosensitizers have been proposed to overcome MDR during chemotherapy. Herein, the redox-responsive polymeric micelles composed of dextran and indomethacin (as chemosensitizer) using a disulfide bond as the linker are prepared (DEX-SS-IND) for delivery of antitumor agent paclitaxel (PTX). The high level of glutathione in tumor cells selectively breaks the disulfide bond, leading to the rapid breakdown and deformation of redox-responsive polymeric micelles...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340047/inhibition-of-polo-like-kinase-4-plk4-a-new-therapeutic-option-for-rhabdoid-tumors-and-pediatric-medulloblastoma
#16
Simone Treiger Sredni, Anders W Bailey, Amreena Suri, Rintaro Hashizume, Xingyao He, Nundia Louis, Tufan Gokirmak, David R Piper, Daniel M Watterson, Tadanori Tomita
Rhabdoid tumors (RT) are highly aggressive and vastly unresponsive embryonal tumors. They are the most common malignant CNS tumors in infants below 6 months of age. Medulloblastomas (MB) are embryonal tumors that arise in the cerebellum and are the most frequent pediatric malignant brain tumors. Despite the advances in recent years, especially for the most favorable molecular subtypes of MB, the prognosis of patients with embryonal tumors remains modest with treatment related toxicity dreadfully high. Therefore, new targeted therapies are needed...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339972/evaluation-of-green-tea-extract-as-a-safe-personal-hygiene-against-viral-infections
#17
Yun Ha Lee, Yo Han Jang, Young-Seok Kim, Jinku Kim, Baik Lin Seong
Background: Viral infections often pose tremendous public health concerns as well as economic burdens. Despite the availability of vaccines or antiviral drugs, personal hygiene is considered as effective means as the first-hand measure against viral infections. The green tea catechins, in particular, epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity. In this study, we evaluated the green tea extract as a safe personal hygiene against viral infections. Results: Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29339551/inhibition-of-flt3-and-pim-kinases-by-ec-70124-exerts-potent-activity-in-preclinical-models-of-acute-myeloid-leukemia
#18
Noelia Puente-Moncada, Paula Costales, Isaac Antolín, Luz Elena Núñez, Patricia Oro, Maria Ana Hermosilla, Jhudit Perez-Escuredo, Nicolas Rios-Lombardia, Ana M Sanchez-Sanchez, Elisa Luño, Carmen Rodriguez, Vanesa Martin, Francisco Moris
Internal tandem duplication (ITD) or tyrosine kinase domain mutations of FLT3 is the most frequent genetic alteration in acute myeloid leukemia (AML) and are associated with poor disease outcome. Despite considerable efforts to develop single-target FLT3 drugs, so far, the most promising clinical response has been achieved using the multikinase inhibitor midostaurin. Here we explore the activity of the indolocarbazole EC-70124, from the same chemical space as midostaurin, in preclinical models of AML, focusing on those bearing FLT3-ITD mutations...
January 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29339392/a-novel-piperazine-based-drug-lead-for-cryptosporidiosis-from-the-medicines-for-malaria-venture-open-access-malaria-box
#19
R S Jumani, K Bessoff, M S Love, P Miller, E E Stebbins, J E Teixeira, M A Campbell, M J Meyers, J A Zambriski, V Nunez, A K Woods, C W McNamara, C D Huston
Cryptosporidiosis causes life-threatening diarrhea in children under age five, and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to a need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#20
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
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