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Wen-Rui Hao, Michael Chen, Yi-Jou Chen, Yu-Cheng Su, Chiu-Min Cheng, Hsiang-Yin Hsueh, An-Pei Kao, Yuan-Chin Hsieh, Johny Chang, Ming-Yang Tseng, Kuo-Hsiang Chuang
The sensitivities of solid-phase immunoassays are limited by the quantity of detection antibodies bound to their antigens on the solid phase. Here, we developed a poly-protein G-expressing bacterium as an antibody-trapping microparticle to enhance the signals of immunoassays by increasing the accumulation of detection antibodies on the given antigen. Eight tandemly repeated fragment crystallisable (Fc) binding domains of protein G were stably expressed on the surface of Escherichia coli BL21 cells (termed BL21/8G)...
April 20, 2017: Scientific Reports
Derek J Hodgson, Yves Aubin
A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor [Met-GCSF] used to boost the immune system in chemotherapy treated cancer patients), and interferon alpha-2 (used for the treatment of various viral infections), have been chemically modified with the addition of a polyethylene glycol (PEG) chain. This modification prolongs residency of the drug in the body and reduces metabolic degradation, which allows less frequent administration of the products...
February 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
Wen-Wei Lin, Yuan-Chin Hsieh, Yi-An Cheng, Kuo-Hsiang Chuang, Chien-Chiao Huang, Chih-Hung Chuang, I-Ju Chen, Kai-Wen Cheng, Yun-Chi Lu, Ta-Chun Cheng, Yeng-Tseng Wang, Steve R Roffler, Tian-Lu Cheng
Sensitive determination of the pharmacokinetics of PEGylated molecules can accelerate the process of drug development. Here, we combined different anti-PEG Fab expressing 293T cells as capture cells (293T/3.3, 293T/6.3, and 293T/15-2b cells) with four detective anti-PEG antibodies (3.3, 6.3, 7A4, or 15-2b) to optimize an anti-PEG cell-based sandwich ELISA. Then, we quantified free PEG (mPEG2K-NH2 and mPEG5K-NH2) or PEG-conjugated small molecules (mPEG5K-biotin and mPEG5K-NIR797), proteins (PegIntron and Pegasys), and nanoparticles (Liposomal-Doxorubicin and quantum-dots)...
December 20, 2016: Analytical Chemistry
Yan-Hua Ding, Bin Liu, Xin Zhang, Li Sun, Hong Zhang, Hua Luo, Yan-Fu Sun, Cheng-Jiao Liu, Qi Zhang, Yu-Chen Cao, Hong Chen, Jun-Qi Niu
This study aimed to explore and evaluate the tolerability and antiviral activity of pegylated recombinant human consensus interferon-α (PEG-CIFN) in adults with hepatitis C virus (HCV) infection. A total of 48 adult subjects chronically infected with HCV were divided into five groups, which were treated separately with PEG-CIFN 1.0 µg/kg (n=10), 1.5 µg/kg (n=10), 2.0 µg/kg (n=9) or 3.0 µg/kg (n=10), or pegylated IFN α-2a (Pegasys) 180 µg (n=9) as controls. Symptoms were observed and laboratory results collected to monitor adverse reactions, adjust drug dosage and evaluate tolerability...
January 2017: Experimental and Therapeutic Medicine
Simon D Baugh
Chronic Hepatitis B is a major global health issue, and has no known cure. Currently there are over 240 million people infected with the disease, and it leads to the death of over 686,000 people each year. A total of seven treatments which help to control the disease are currently available: interferon-based treatments (pegasys, and interferon alpha), and nucleoside and nucleotide analogs (Viread, Baraclude, Tyzeka, Hepsera, Epivir-HBV), but all require continuing treatment to maintain control of the disease...
January 4, 2017: Infectious Disorders Drug Targets
Yuan-Chin Hsieh, Ta-Chun Cheng, Hsin-Ell Wang, Jia-Je Li, Wen-Wei Lin, Chien-Chiao Huang, Chih-Hung Chuang, Yeng-Tseng Wang, Jaw-Yuan Wang, Steve R Roffler, Kuo-Hsiang Chuang, Tian-Lu Cheng
Attachment of polyethylene glycol (PEG) molecules to nanoparticles (PEGylation) is a widely-used method to improve the stability, biocompatibility and half-life of nanomedicines. However, the evaluation of the PEGylated nanomedicine pharmacokinetics (PK) requires the decomposition of particles and purification of lead compounds before analysis by high performance liquid chromatography (HPLC), mass spectrometry, etc. Therefore, a method to directly quantify un-decomposed PEGylated nanoparticles is needed. In this study, we developed anti-PEG bioparticles and combined them with anti-PEG antibodies to generate a quantitative enzyme-linked immunosorbent assay (ELISA) for direct measurement of PEGylated nanoparticles without compound purification...
December 19, 2016: Scientific Reports
Thibault Bahougne, Alessio Imperiale, Gerlinde Averous, Gerard Chabrier, Nelly Burnichon, Anne-Paule Gimenez-Roqueplo, Nassim Dali-Youcef, Rossella Libé, Eric Baudin, Catherine Roy, Herve Lang, Laurence Kessler
INTRODUCTION: Early and accurate identification of recurrences in patients with aggressive paraganglioma (PGL) poses significant challenges. Moreover, the most appropriate therapeutic strategy for recurrent PGL remains to be established. RESULTS: We report the case of 52-year-old man with a history of recurrent, sporadic, left retroperitoneal PGL that relapsed twice (at eight and nine years after the first surgical intervention). At the time of the second recurrence, 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) demonstrated a pathologically increased tracer uptake in multiple nodular lesions (10-15 mm in size) located close to the remnant of the left renal pedicle and in the left lombar paravertebral region...
November 28, 2016: Endocrine-related Cancer
Sojan Abraham, Jang-Gi Choi, Nora M Ortega, Junli Zhang, Premlata Shankar, N Manjunath Swamy
Because endogenous interferon type I (IFN-I) produced by HIV-1 infection might complicate the analysis of therapeutically administered IFN-I, we tested different humanized mouse models for induction of IFN-I during HIV-1 infection. While HIV-1 induced high levels of IFN-α in BLT mice, IFN-I was undetectable following infection in the Hu-PBL mouse model, in which only T cells expand. We therefore tested the effect of treatment with Pegylated IFN-2 (pegasys), in Hu-PBL mice. Pegasys prevented CD4 T cell depletion and reduced the viral load for 10 days, but the effect waned thereafter...
November 29, 2016: Oncotarget
Jin Hu, Guilin Wang, Wenguo Zhao, Weiping Gao
Conjugating therapeutic proteins and peptides to poly(ethylene glycol) (PEG) can improve their pharmacokinetics and therapeutic potential. However, PEGylation suffers from non-specific conjugation, low yield and immunogenicity. Herein we report a new and general methodology to synthesize a protein-polymer conjugate with site-specificity, high yield and activity, long circulation half-life and excellent therapeutic efficacy. A phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), was grown solely from the C-terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) PMPC conjugate of interferon-alpha in high yield...
September 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jin Hu, Guilin Wang, Wenguo Zhao, Xinyu Liu, Libin Zhang, Weiping Gao
Conjugating poly(ethylene glycol) (PEG), PEGylation, to therapeutic proteins is widely used as a means to improve their pharmacokinetics and therapeutic potential. One prime example is PEGylated interferon-alpha (PEGASYS). However, PEGylation usually leads to a heterogeneous mixture of positional isomers with reduced bioactivity and low yield. Herein, we report site-specific in situ growth (SIG) of a PEG-like polymer, poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), from the C-terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) POEGMA conjugate of interferon-alpha in high yield...
July 2016: Biomaterials
Young Eun Chon, Dong Joon Kim, Sang Gyune Kim, In Hee Kim, Si Hyun Bae, Seong Gyu Hwang, Jeong Heo, Jeong Won Jang, Byung Seok Lee, Hyung Joon Kim, Dae Won Jun, Kang Mo Kim, Woo Jin Chung, Moon Seok Choi, Jae Young Jang, Hyung Joon Yim, Won Young Tak, Ki Tae Yoon, Jun Yong Park, Kwang-Hyub Han, Ki Tae Suk, Hyun Woong Lee, Byoung Kuk Jang, Sang Hoon Ahn
Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type.We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated...
April 2016: Medicine (Baltimore)
J H C Martins, N C Santos, P Figueira, C Melo
The direct detection of reflected light from exoplanets is an excellent probe for the characterization of their atmospheres. The greatest challenge for this task is the low planet-to-star flux ratio, which even in the most favourable case is of the order of 10(-4) in the optical. This ratio decreases even more for planets in their host's habitable zone, typically lower than 10(-7). To reach the signal-to-noise level required for such detections, we propose to unleash the power of the Cross Correlation Function in combination with the collecting power of next generation observing facilities...
November 2016: Origins of Life and Evolution of the Biosphere
Edouard Alphandéry, Pierre Grand-Dewyse, Raphael Lefèvre, Chalani Mandawala, Mickael Durand-Dubief
Several nanoformulated anti-cancer substances are currently commercialized or under development. Pre-clinical and clinical results have revealed better properties, that is, larger efficacy and lower toxicity for these substances than for conventional anti-cancer treatments. Here, we review the development of several of these substances such as Marqibo, Myocet, Doxil, DaunoXome, MM398, MM302, Mepact, Versamune, Thermodox, Depocyt, Livatag, Abraxane, Eligard, Opaxio, Zinostatin Stimalamer (SMANCS), Pegasys and PegIntron, BIND-014, CRLX-101, Oncaspar, Neulasta, Aurimmune, Auroshell, AuNPs, Nanotherm, NanoXray, Magnetosome chains, Kadcyla (T-DM1), Ontak (DAB/IL2), Gendicine and Curcumin...
2015: Expert Review of Anticancer Therapy
Jan Jacques Michiels
Prospective studies indicate that the risk of microvascular and major thrombosis in untreated thrombocythemia in various myeloproliferative neoplasms (MPN-T) is not age dependent and causally related to platelet-mediated thrombosis in early, intermediate and advanced stages of thrombocythemia in MPN-T. If left untreated both microvascular and major thrombosis frequently do occur in MPN-T, but can easily be cured and prevented by low dose aspirin as platelet counts are above 350 × 10(9)/L. The thrombotic risk stratification in the retrospective Bergamo study has been performed in 100 essential thrombocythemia (ET) patients not treated with aspirin thereby overlooking the discovery in 1985 of aspirin responsive platelet-mediated arteriolar and arterial thrombotic tendency in MPN-T disease of ET and polycythemia vera (PV) patients...
August 4, 2015: World Journal of Critical Care Medicine
Dalia El Sabaawy, Sahar El-Haggar, Hoda El-Bahrawy, Imam Waked, Hala El-Said
HCV infection presents a vast burden in the regions of high prevalence such as Egypt, where most HCV isolates are genotype 4b. Combined treatment of three variants of pegylated interferon and ribavirin is still the standard of care in Egypt. However, no conclusive data confirming their efficacy are available. Here, 60 chronic HCV patients were randomized for ribavirin plus Peg Intron (PEG-IFNα-2b), Pegasys (PEG-IFNα-2a) or Reiveron Retard (PEG-IFNα-2a). Serum interferon and antibody (Ab) levels were measured, and responses and costs were compared...
June 2015: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Nadeem Javaid, Mohsin Raza Jafri, Zahoor Ali Khan, Nabil Alrajeh, Muhammad Imran, Athanasios Vasilakos
Appropriate network design is very significant for Underwater Wireless Sensor Networks (UWSNs). Application-oriented UWSNs are planned to achieve certain objectives. Therefore, there is always a demand for efficient data routing schemes, which can fulfill certain requirements of application-oriented UWSNs. These networks can be of any shape, i.e., rectangular, cylindrical or square. In this paper, we propose chain-based routing schemes for application-oriented cylindrical networks and also formulate mathematical models to find a global optimum path for data transmission...
2015: Sensors
B Podobnik, B Helk, V Smilović, Š Škrajnar, K Fidler, S Jevševar, A Godwin, P Williams
The covalent attachment of poly(ethylene glycol) (PEG) to therapeutic proteins is a commonly used approach for extending in vivo half-lives. A potential limitation of this PEGylation strategy is the adverse effect of PEG on conjugate viscosity. Interferon-alpha (IFN) was conjugated via its N-terminal amino group by reductive amination to α-aldehyde functional comb-shaped PolyPEG polymers (50 and 70 kDa) and to linear PEG (30 kDa). In vitro potencies of the purified PEGylated IFN conjugates were measured by reporter gene assay using a HEK293P/ISRE-SEAP cell line...
March 18, 2015: Bioconjugate Chemistry
Olga Khokhlova, Ara Reizis, Lidya Serebrovskaya, Natalia Gerasimova, Vadim Pokrovskiy
INTRODUCTION: Depletion of cellular pool and constant activation of plasmacytoid dendritic cells (pDCs) in HIV-infected persons (HIV+) are associated with disease progression and manifestation of opportunistic infections. The influence of highly-active antiretroviral treatment (HAART) and suppressed HCV-co-infection (HIV+/HCV+) on the extent of these changes remains unknown. OBJECTIVE: To study parameters of pDCs in peripheral blood of HIV+ and HIV+/HCV+ patients on HAART...
2014: Journal of the International AIDS Society
Debbie Hartwell, Keith Cooper, Geoff K Frampton, Louise Baxter, Emma Loveman
BACKGROUND: Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years...
October 2014: Health Technology Assessment: HTA
Bo Zhang, Mintao Hu, Lihua Huang, Yunchuan Pu, Hao Pei, Zhong Hua, Shangzhi Yao
The aim of the present study was to observe the effects of Fuzheng Huayu capsule combined with Pegasys (peginterferon α-2a) on hepatic fibrosis in rats and in the treatment of patients with genotype 1 hepatitis C and hepatic cirrhosis. A dimethylnitrosamine (DMN)-induced rat model of liver injury was established. Fuzheng Huayu capsule combined with Pegasys was administered to the rats and the DMN-induced hepatocyte apoptosis was observed. In addition, a total of 100 patients with genotype 1 hepatitis C and hepatic cirrhosis were treated by oral administration of Fuzheng Huayu capsule combined with Pegasys or with Pegasys alone...
October 2014: Experimental and Therapeutic Medicine
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