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https://www.readbyqxmd.com/read/29782948/dendritic-peg-outer-shells-enhance-serum-stability-of-polymeric-micelles
#1
Hao-Jui Hsu, Yanxiao Han, Michael Cheong, Petr Král, Seungpyo Hong
A higher surface density of poly(ethylene glycol) (PEG) on polymeric micelles enhances their stability in serum, leading to improved plasma circulation. To obtain fundamental, mechanistic understanding of the PEG effect associated with polymeric architecture/configuration, we have synthesized PEGylated dendron-based copolymers (PDCs) and linear block copolymers (LBCs) with similar molecular weights. These copolymers formed dendron (hyperbranched) and linear micelles, respectively, which were compared in terms of their stabilities in serum, micelle-serum protein interactions, and in vivo biodistributions...
May 18, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29780549/a-thioether-directed-palladium-cleavable-linker-for-targeted-bioorthogonal-drug-decaging
#2
Benjamin J Stenton, Bruno L Oliveira, Maria J Matos, Laura Sinatra, Gonçalo J L Bernardes
We describe the development of a bifunctional linker that simultaneously allows site-specific protein modification and palladium-mediated bioorthogonal decaging. This was enabled by a thioether binding motif in the propargyl carbamate linker and a readily available palladium complex. We demonstrate the efficiency of this reaction by controlled drug release from a PEGylated doxorubicin prodrug in cancer cells. The linker can be easily installed into cysteine bearing proteins which we demonstrated for the construction of an anti-HER2 nanobody-drug conjugate...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29779479/optimizing-antitumor-efficacy-and-adverse-effects-of-pegylated-liposomal-doxorubicin-by-scheduled-plasmapheresis-impact-of-timing-and-dosing
#3
Romeo Ngoune, Christine Contini, Michael Marcus Hoffmann, Dominik Elverfeldt, Karl Winkler, Gerhard Putz
BACKGROUND: Nanoscale drug delivery systems accumulate in solid tumors preferentially by the enhanced permeation and retention effect (EPR-effect). Nevertheless, only a miniscule fraction of a given dosage reaches the tumor, while >90% of the given drug ends up in otherwise healthy tissues, leading to the severe toxic reactions observed during chemotherapy. Once accumulation in tumor has reached its maximum, extracorporeal elimination of circulating nanoparticles by plasmapheresis can diminish toxicities...
May 18, 2018: Current Drug Delivery
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#4
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29773440/case-report-identification-of-recombinant-hcv-genotype-1b-2b-by-viral-sequencing-in-two-patients-with-treatment-failure-who-responded-to-re-treatment-with-sofosbuvir-and-daclatasvir
#5
Luis Antonio Uribe-Noguez, Alicia Ocaña-Mondragón, José Antonio Mata-Marín, Allison Cázares-Cortázar, Rosa María Ribas-Aparicio, María Elena Gómez-Torres, Jesus Gaytán-Martínez, María de la Luz Martínez-Rodríguez
Hepatitis C virus (HCV) infection is a global health problem. HCV has been classified into seven genotypes and >67 subtypes. Genotyping is necessary to enable selection of appropriate treatments. The commercial molecular techniques currently used do not identify some HCV subtypes, mixed infections and recombinant forms. In this study, the core-E1 and NS5B regions were sequenced and phylogenetically analysed to identify infections by HCV recombinant genotype 1b-2b in two patients who had initially been diagnosed with HCV genotype 2 infection by reverse hybridization with a Versant HCV Genotype 2...
May 15, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29768546/first-wave-protease-inhibitors-for-hepatitis-c-genotype-1-treatment-a-real-life-experience-in-brazilian-patients
#6
Silvana Gama Florencio Chachá, João Paulo Vilela Rodrigues, Roberta Chaves Araújo, Leonardo Régis Leira Pereira, Márcia Guimarães Villanova, Fernanda Fernandes Souza, Rodrigo de Carvalho Santana, Ana de Lourdes Candolo Martinelli
INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center...
March 2018: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29768009/use-of-dual-ligand-modification-in-kupffer-cell-targeted-liposomes-to-examine-the-contribution-of-kupffer-cells-to-accelerated-blood-clearance-abc-phenomenon
#7
Chaoyang Lai, Cong Li, Xiang Luo, Mengyang Liu, Xinrong Liu, Ling Hu, Le Kang, Qiujun Qiu, Yihui Deng, Yanzhi Song
The "accelerated blood clearance (ABC) phenomenon" is known to be involved in the adaptive immune system. Regretfully, the relationship between the ABC phenomenon and innate immune system, especially with respect to Kupffer cells (KCs) has been largely unexplored. In this study, the contribution of KCs to ABC was examined using the 4-aminophenyl-α-D-mannopyranoside (APM) lipid derivative DSPE-PEG2000-APM (DPM) and the 4-aminophenyl-β-L-fucopyranoside (APF) lipid derivative DSPE-PEG2000-APF (DPF) as ligands for mannose/fucose receptors on KCs, which were synthesized and modified on the surface of liposomes...
May 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29766002/influence-of-vitamin-d-receptor-gene-polymorphisms-on-response-to-pegylated-interferon-in-chronic-hepatitis-b-egyptian-patients
#8
Gomaa Mostafa-Hedeab, Dina Sabry, Ghada Mostafa Abdelaziz, Manal Ewaiss, Nagla Adli, Wael Fathy
Background: We explored the effect of vitamin D receptor gene ( VDR ) polymorphisms in response to PEG-IFN treatment in Egyptian chronic hepatitis B (CHB) patients. Methods: Two hundred hepatitis B virus (HBV) patients (42.3±10.7 years) on PEG-IFN α-2a (180 µg /kg for 48 weeks) and one hundred control subjects (37.3 ±12 years) were enrolled in the study. Vitamin D levels and hepatitis B surface antigen (HBsAg) expression were assessed by ELISA. VDR polymorphisms FokI T>C (rs 10735810), BsmI A>G (rs 1544410), ApaI (rs7975253), and TaqI C>T (rs 731236), were genotyped using real-time PCR...
April 2018: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29765290/extended-half-life-factor-viii-and-factor-ix-preparations
#9
REVIEW
Lukas Graf
In the last couple of years, several extended half-life factor VIII and factor IX preparations were intensively studied and gained approval. In order to extend half-lives, techniques like fusion to protein conjugates (Fc part of IgG1 or albumin), chemical modification (PEGylation), and protein sequence modification are implemented. With these techniques, it is possible to extend half-lives of factor IX products 4- to 6- fold, while half-life extension of factor VIII products is limited to 1.5- to 2-fold due to their interaction with von Willebrand factor...
April 2018: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/29765257/spotlight-on-certolizumab-pegol-in-the-treatment-of-axial-spondyloarthritis-efficacy-safety-and-place-in-therapy
#10
REVIEW
Josefina Marin, María Laura Acosta Felquer, Enrique R Soriano
Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204...
2018: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/29765256/grazoprevir-elbasvir-for-the-treatment-of-adults-with-chronic-hepatitis-c-a-short-review-on-the-clinical-evidence-and-place-in-therapy
#11
REVIEW
Nimisha Sulejmani, Syed-Mohammed Jafri
Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection...
2018: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29765238/higher-baseline-viral-diversity-correlates-with-lower-hbsag-decline-following-pegylated-interferon-alpha-therapy-in-patients-with-hbeag-positive-chronic-hepatitis-b
#12
Hu Li, Li Zhang, Hong Ren, Peng Hu
Background: Viral diversity seems to predict treatment outcomes in certain viral infections. The aim of this study was to evaluate the association between baseline intra-patient viral diversity and hepatitis B surface antigen (HBsAg) decline following PEGylated interferon-alpha (Peg-IFN-α) therapy. Patients and methods: Twenty-six HBeAg-positive patients who were treated with Peg-IFN-α were enrolled. Nested polymerase chain reaction (PCR), cloning, and sequencing of the hepatitis B virus S gene were performed on baseline samples, and normalized Shannon entropy (Sn) was calculated as a measure of small hepatitis B surface protein (SHBs) diversity...
2018: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29762255/ombitasvir-paritaprevir-ritonavir-dasabuvir-ribavirin-for-chronic-hepatitis-c-virus-genotype-1b-infected-cirrhotics-turquoise-iv
#13
Vasily Isakov, Dzmitry Paduta, Rolando M Viani, Jeffrey V Enejosa, Viktor Pasechnikov, Olga Znoyko, Pavel Ogurtsov, Pavel O Bogomolov, Marina V Maevskaya, Xiaotian Chen, Nancy S Shulman
OBJECTIVE: An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. PATIENTS AND METHODS: In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks...
May 14, 2018: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29761292/-chronic-hepatitis-b-and-d-delta-current-and-future-treatments
#14
REVIEW
N Wortmann, C Höner Zu Siederdissen, M Cornberg
BACKGROUND: Worldwide, hepatitis B virus (HBV) infection is among the 30 leading causes of death, despite effective vaccination and therapeutic options. Chronic hepatitis delta (coinfection with hepatitis D virus) leads to a rapid disease progression. AIMS: Based on current international guidelines and studies, an overview about present and future therapeutic options for chronic hepatitis B and delta is provided. RESULTS: Therapy with nucleoside or nucleotide analogues leads to nearly complete HBV DNA suppression, which is associated with regression of liver fibrosis and a lower risk for the development of hepatocellular carcinoma...
May 14, 2018: Der Internist
https://www.readbyqxmd.com/read/29757876/a-randomized-trial-of-prophylactic-extended-carboplatin-infusion-to-reduce-hypersensitivity-reactions-in-recurrent-ovarian-cancer
#15
Katherine LaVigne, David M Hyman, Qin C Zhou, Alexia Iasonos, William P Tew, Carol Aghajanian, Vicky Makker, Martee L Hensley, Jason Konner, Rachel N Grisham, Nicholas Cangemi, Krysten Soldan, David R Spriggs, Paul J Sabbatini, Roisin E OʼCearbhaill
OBJECTIVE: Hypersensitivity with repeated exposure to platinum agents is common and can preclude continued treatment, even in patients with disease that remains platinum sensitive. We sought to compare the effects of prophylactic, extended carboplatin infusion versus standard infusion on the rate of carboplatin hypersensitivity reactions (HSRs) in women with recurrent ovarian cancer. METHODS: This was a single-institution, randomized, nonblinded trial comparing a graded, 3-hour extended infusion of carboplatin with a standard 30-minute infusion in patients with recurrent ovarian cancer who were enrolled from January 2011 to April 2015...
May 4, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29753376/effectiveness-of-sofosbuvir-ribavirin-and-peg-ifn%C3%AE-2a-in-the-treatment-of-na%C3%A3-ve-egyptian-patients-with-chronic-hepatitis-c-virus-genotype-4
#16
Fatma Abdallah, Gehad Mohamed, Mohsen Ibrahim, Mokhtar El Tarabily
BACKGROUND: Egypt is one of the largest epidemic areas of hepatitis C virus (HCV) in the world. Its prevalent genotype is 4 with a majority of subtype 4a. In 2013, the Food and Drug Administration approved a new direct-acting antiviral drug (sofosbuvir) to treat patients with chronic HCV infection. In Egypt, the patients are already being treated with sofosbuvir in conjunction with ribavirin and pegylated interferon alfa-2a (PEG-IFNα-2a) for 12 weeks since 2015. The present study was planned to explain the efficacy of this treatment regimen against the HCV genotype 4a in Egyptian patients and its pretreatment predictive factors of virological response...
May 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29750504/c1q-mediated-complement-activation-and-c3-opsonization-trigger-recognition-of-stealth-poly-2-methyl-2-oxazoline-coated-silica-nanoparticles-by-human-phagocytes
#17
Regina Tavano, Luca Gabrielli, Elisa Lubian, Chiara Fedeli, Silvia Visentin, Patrizia Polverino de Laureto, Giorgio Arrigoni, Alessandra Geffner-Smith, Fangfang Chen, Dmitri Simberg, Giulia Morgese, Edmondo Maria Benetti, Linping Wu, Seyed Moein Moghimi, Fabrizio Mancin, Emanuele Papini
Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol), (PEG), for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA engineered NPs have shown comparable pharmacokinetics, and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyl-triethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes and macrophages, and compared their performance with PEGylated and uncoated NP counterparts...
May 11, 2018: ACS Nano
https://www.readbyqxmd.com/read/29750037/simple-score-to-predict-risk-of-hepatocellular-carcinoma-in-chronic-hepatitis-c-patients-with-advanced-fibrosis-after-pegylated-interferon-and-ribavirin-therapy
#18
Ching-Chih Hu, Cheng-Hao Weng, Liang-Che Chang, Chih-Lang Lin, Yen-Ting Chen, Ching-Fang Hu, Man-Chin Hua, Li-Wei Chen, Rong-Nan Chien
Purpose: Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. Patients and methods: We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29746998/urokinase-injection-triggered-clearance-enhancement-of-a-4-arm-peg-conjugated-64-cu-bombesin-analog-tetramer-a-novel-approach-for-the-improvement-of-pet-imaging-contrast
#19
Kazushi Matsumura, Maki Zouda, Yasuhiro Wada, Fumiyoshi Yamashita, Mitsuru Hashida, Yasuyoshi Watanabe, Hidefumi Mukai
Radiolabeled antibodies, polyethylene glycol-conjugated (PEGylated) peptides, liposomes, and other materials were investigated as positron-emission tomography (PET) probes. These substances accumulate in tumors but often remain too long in circulation. We investigated the combination of intravenous urokinase injection and its substrate linker as a triggered radioisotope clearance enhancement system to improve imaging contrast. To this end, we synthesized a four-arm PEGylated 64 Cu-bombesin analog tetramer with a urokinase substrate linker...
May 7, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29746956/liposomal-delivery-of-a-pin1-inhibitor-complexed-with-cyclodextrins-as-new-therapy-for-high-grade-serous-ovarian-cancer
#20
Concetta Russo Spena, Lucia De Stefano, Stefano Palazzolo, Barbara Salis, Carlotta Granchi, Filippo Minutolo, Tiziano Tuccinardi, Roberto Fratamico, Sara Crotti, Sara D'Aronco, Marco Agostini, Giuseppe Corona, Isabella Caligiuri, Vincenzo Canzonieri, Flavio Rizzolio
Pin1, a prolyl isomerase that sustains tumor progression, is overexpressed in different types of malignancies. Functional inactivation of Pin1 restrains tumor growth and leaves normal cells unaffected making it an ideal pharmaceutical target. Although many studies on Pin1 have focused on malignancies that are influenced by sex hormones, studies in ovarian cancer have lagged behind. Here, we show that Pin1 is an important therapeutic target in high-grade serous epithelial ovarian cancer. Knock down of Pin1 in ovarian cancer cell lines induces apoptosis and restrains tumor growth in a syngeneic mouse model...
May 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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