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https://www.readbyqxmd.com/read/27925355/epigenetic-analysis-of-the-ifn%C3%AE-3-gene-identifies-a-novel-marker-for-response-to-therapy-in-hcv-infected-subjects
#1
Jeffrey F Waring, J Wade Davis, Emily Dumas, Daniel Cohen, Kenneth Idler, Stephen Abel, Robert Georgantas, Thomas Podsadecki, Sandeep Dutta
Chronic hepatitis C virus (HCV) infection is characterized by high inter-individual variability in response to pegylated interferon and ribavirin. A genetic polymorphism on chromosome 19 (rs12979860) upstream of interferon-λ-3 (IFNλ3) is associated with a 2-fold change in sustained virologic response rate after 48 weeks of treatment with pegylated interferon/ribavirin in HCV genotype 1 (GT1) treatment-naïve patients. We conducted epigenetic analysis on the IFNλ3 promoter to investigate whether DNA methylation is associated with response to HCV therapy...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27923599/the-role-of-the-atm-chk-p53-pathway-in-mediating-dna-damage-in-hand-foot-syndrome-induced-by-pld
#2
Jie Yang, Long Qiao, Zhen Zeng, Junnai Wang, Tao Zhu, Juncheng Wei, Mingfu Wu, Shuangmei Ye, Xiaoyuan Huang, Ding Ma, Ronghua Liu, Qinglei Gao
Pegylated liposomal doxorubicin (PLD) has been approved to treat patients with various types of cancers because it rarely caused side effects, such as cardiotoxicity, in comparison to doxorubicin, but it frequently results in hand-foot syndrome (HFS). This may affect the quality of life and require a reduction in the PLD dose. The pathophysiology of HFS was not well understood. This study was aimed at exploring the mechanism of HFS induced by PLD. We compared the effects of different doses of PLD on the proliferation inhibition and apoptosis in vitro in HaCaT cells and analyzed the skin changes and skin cell DNA damage in vivo using a zebrafish model...
December 3, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27923186/influence-of-surface-passivation-of-2-methoxyestradiol-loaded-plga-nanoparticles-on-cellular-interactions-pharmacokinetics-and-tumour-accumulation
#3
Gopikrishna J Pillai, Bindhu Paul-Prasanth, Shantikumar V Nair, Deepthy Menon
In the present work, 2-Methoxyestradiol [2ME2] loaded PLGA nanoparticles [NPs] were stabilized with Casein or poly(ethylene glycol) [PEG] and evaluated for its cellular interactions, pharmacokinetics and tumour accumulation. Surface stabilized PLGA nanoparticles prepared through a modified emulsion route possessed similar size, surface charge, drug loading and release characteristics. Particle-cell interactions as well as the anti-angiogenesis activity were similar for both nanoformulations in vitro. However, in vivo pharmacokinetics and tumour accumulation of the drug were substantially improved for the PEGylated nanoformulation...
November 29, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27920523/pegylated-and-nanoparticle-conjugated-sulfonium-salt-photo-triggers-necrotic-cell-death
#4
Alaa A Fadhel, Xiling Yue, Ebrahim H Ghazvini Zadeh, Mykhailo V Bondar, Kevin D Belfield
Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919801/folic-acid-capped-pegylated-magnetic-nanoparticles-enter-cancer-cells-mostly-via-clathrin-dependent-endocytosis
#5
Emilie Allard-Vannier, Katel Hervé-Aubert, Karine Kaaki, Thibaut Blondy, Anastasia Shebanova, Konstantin V Shaitan, Anastasia A Ignatova, Marie-Louise Saboungi, Alexey V Feofanov, Igor Chourpa
BACKGROUND: This work is focused on mechanisms of uptake in cancer cells of rationally designed, covalently assembled nanoparticles, made of superparamagnetic iron oxide nanoparticles (SPIONs), fluorophores (doxorubicin or Nile Blue), polyethylene glycol (PEG) and folic acid (FA), referred hereinafter as SFP-FA. METHODS: SFP-FA were characterized by DLS, zetametry and fluorescence spectroscopy. The SFP-FA uptake in cancer cells was monitored using fluorescence-based methods like fluorescence-assisted cell sorting, LSCM with single-photon and two-photon excitation...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27917084/sofosbuvir-and-simeprevir-combination-therapy-for-hcv-genotype-1-infection-results-of-a-single-center-va-experience
#6
Seth N Sclair, Maria Del Pilar Hernandez, Evan Vance, Dani Gilinski, Helen Youtseff, Maribel Toro, Marie Antoine, Lennox J Jeffers, Adam Peyton
Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection...
August 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27916398/ruxolitinib-for-the-treatment-of-inadequately-controlled-polycythaemia-vera-without-splenomegaly-response-2-a-randomised-open-label-phase-3b-study
#7
Francesco Passamonti, Martin Griesshammer, Francesca Palandri, Miklos Egyed, Giulia Benevolo, Timothy Devos, Jeannie Callum, Alessandro M Vannucchi, Serdar Sivgin, Caroline Bensasson, Mahmudul Khan, Nadjat Mounedji, Guray Saydam
BACKGROUND: In the pivotal RESPONSE study, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy at controlling haematocrit and improving splenomegaly and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea. In this study, we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy. METHODS: RESPONSE-2 is a randomised, open-label, phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia, Australia, Europe, and North America...
December 1, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27916078/-effects-of-ifosfamide-in-combination-with-pegylated-liposomal-doxorubicin-and-dexamethasone-in-the-treatment-of-relapsed-refractory-multiple-myeloma
#8
N An, M Shen, X Li, Z X Huang, S L Chen
Objective: To investigate the efficacy and adverse effects of ifosfamide in combination with pegylated liposomal doxorubicin and dexamethasone (CDD) in treating patients with relapsed/refractory multiple myeloma (MM). Methods: The clinical data of 30 relapsed/refractory MM patients treated with CDD regimen in Department of Hematology and Oncology of Beijing Chaoyang Hospital from November 2012 to November 2015 were retrospectively analyzed. The CDD treatment included ifosfamide 0.5-1.0 g/d on d1-4, pegylated liposomal doxorubicin 40-60 mg/d on d1, and dexamethasone 10-20 mg/d on d1-4...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27915019/the-impact-of-cell-surface-pegylation-and-short-course-immunotherapy-on-islet-graft-survival-in-an-allogeneic-murine-model
#9
Jaime A Giraldo, R Damaris Molano, Hernán R Rengifo, Carmen Fotino, Kerim M Gattás-Asfura, Antonello Pileggi, Cherie L Stabler
: Islet transplantation is a promising therapy for Type 1 diabetes mellitus; however, host inflammatory and immune responses lead to islet dysfunction and destruction, despite potent systemic immunosuppression. Grafting of poly(ethylene glycol) (PEG) to the periphery of cells or tissues can mitigate inflammation and immune recognition via generation of a steric barrier. Herein, we sought to evaluate the complementary impact of islet PEGylation with a short-course immunotherapy on the survival of fully-MHC mismatched islet allografts (DBA/2 islets into diabetic C57BL/6J recipients)...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27914267/intein-mediated-site-specific-synthesis-of-tumor-targeting-protein-delivery-system-turning-peg-dilemma-into-prodrug-like-feature
#10
Yingzhi Chen, Meng Zhang, Hongyue Jin, Yisi Tang, Huiyuan Wang, Qin Xu, Yaping Li, Feng Li, Yongzhuo Huang
Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature...
November 27, 2016: Biomaterials
https://www.readbyqxmd.com/read/27914241/engot-ov-6-trinova-2-randomised-double-blind-phase-3-study-of-pegylated-liposomal-doxorubicin-plus-trebananib-or-placebo-in-women-with-recurrent-partially-platinum-sensitive-or-resistant-ovarian-cancer
#11
Christian Marth, Ignace Vergote, Giovanni Scambia, Willi Oberaigner, Andrew Clamp, Regina Berger, Christian Kurzeder, Nicoletta Colombo, Peter Vuylsteke, Domenica Lorusso, Marcia Hall, Vincent Renard, Sandro Pignata, Rebecca Kristeleit, Sevilay Altintas, Gordon Rustin, Robert M Wenham, Mansoor Raza Mirza, Peter C Fong, Amit Oza, Bradley J Monk, Haijun Ma, Florian D Vogl, Bruce A Bach
AIMS: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. METHODS: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m(2) once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo...
November 30, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27912846/new-insights-and-evolving-role-of-pegylated-liposomal-doxorubicin-in-cancer-therapy
#12
REVIEW
Alberto A Gabizon, Yogita Patil, Ninh M La-Beck
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in important advantages over conventional chemotherapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912770/endometriosis-associated-clear-cell-carcinoma-arising-in-caesarean-section-scar-a-case-report-and-review-of-the-literature
#13
Gabriella Ferrandina, Eleonora Palluzzi, Francesco Fanfani, Stefano Gentileschi, Anna Lia Valentini, Maria Vittoria Mattoli, Ilaria Pennacchia, Giovanni Scambia, Gianfranco Zannoni
BACKGROUND: Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar. CASE PRESENTATION: In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10...
December 3, 2016: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27911829/supramolecular-pegylation-of-biopharmaceuticals
#14
Matthew J Webber, Eric A Appel, Brittany Vinciguerra, Abel B Cortinas, Lavanya S Thapa, Siddharth Jhunjhunwala, Lyle Isaacs, Robert Langer, Daniel G Anderson
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910975/heterogeneous-pegylation-of-diamond-nanoparticles
#15
Amanda S Barnard
Coating the surfaces of inorganic nanoparticles with polyethylene glycol (PEG) is an important step in the development of many nanoparticle-based drug delivery systems. The efficiency with which drug molecules can be loaded on to nanoparticle surfaces is contingent on the concentration, distribution and stability of the PEG coating. In this study the distribution and relative stability of PEG on diamond nanoparticles is predicted, for clean and passivated surface structures, in 3D. This is an ideal exemplar, since PEGylated diamond nanoparticles are already being trialed as carriers for doxorubicin (DOX)...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910741/topotecan-liposomes-a-visit-from-a-molecular-to-a-therapeutic-platform
#16
Shivani Saraf, Ankit Jain, Pooja Hurkat, Sanjay Kumar Jain
Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27909711/effect-of-partial-pegylation-on-particle-uptake-by-macrophages
#17
Lucero Sanchez, Yi Yi, Yan Yu
Controlling the internalization of synthetic particles by immune cells remains a grand challenge for developing successful drug carrier systems. Polyethylene glycol (PEG) is frequently used as a protective coating on particles to evade immune clearance, but it also hinders the interactions of particles with their intended target cells. In this study, we investigate a spatial decoupling strategy, in which PEGs are coated on only one hemisphere of particles, so that the other hemisphere is available for functionalization of cell-targeting ligands without the hindrance effect from the PEGs...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27906753/noninvasive-markers-of-liver-fibrosis-on-treatment-changes-of-serum-markers-predict-the-outcome-of-antifibrotic-therapy
#18
Sudeep Tanwar, Paul M Trembling, Brian J Hogan, Ankur Srivastava, Julie Parkes, Scott Harris, Paul Grant, Eleni Nastouli, Mathias Ocker, Klaus Wehr, Christoph Herold, Daniel Neureiter, Detlef Schuppan, William M Rosenberg
AIM: The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established. METHODS: A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study...
November 30, 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27905669/secondary-prophylaxis-of-hepatocellular-carcinoma-the-comparison-of-direct-acting-antivirals-with-pegylated-interferon-and-untreated-cohort
#19
R Vukotic, R Di Donato, F Conti, A Scuteri, C Serra, P Andreone
During the past two decades, several studies showed reduced rates of hepatocellular carcinoma recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies respect to untreated controls, even without reaching viral clearance. The recent development of new all-oral regimens with direct-acting antivirals has radically improved the therapeutic management of hepatitis C. Nevertheless, paradoxical, or at least unexpected, high rates of both occurrence and recurrence of hepatocellular carcinoma after a treatment with direct-acting antivirals, have been reported in the recent literature...
December 1, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27905173/hepatitis-c-virus-genotype-4-genotype-1-s-little-brother
#20
REVIEW
J Llaneras, M Riveiro-Barciela, M Buti, R Esteban
Treatment for hepatitis C virus genotype 4 infection has undergone a major advance over the past 5 years with the emergence of direct-acting antiviral agents. Previously, genotype 4 treatment had been limited to the combination of pegylated interferon and ribavirin, with low rates of sustained virological response. The combinations of new direct-acting agents have resulted in a radical improvement in hepatitis C therapy. Much of the currently available efficacy and safety information in the treatment of genotype 4 has been extrapolated through the results of genotype 1...
December 1, 2016: Journal of Viral Hepatitis
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