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Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Emily Wonder, Lorena Simón-Gracia, Pablo Scodeller, Ramsey N Majzoub, Venkata Ramana Kotamraju, Kai K Ewert, Tambet Teesalu, Cyrus R Safinya
Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells...
March 2, 2018: Biomaterials
Muyang Yang, Lixia Yu, Ruiwei Guo, Anjie Dong, Cunguo Lin, Jianhua Zhang
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell...
March 15, 2018: Nanomaterials
Rohan Parikh, Samantha K Kurosky, Margarita Udall, Jane Chang, Joseph C Cappelleri, Jim P Doherty, James A Kaye
OBJECTIVE: The objective of this article is to describe real-world treatment patterns and outcomes in patients with platinum-refractory/resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (PRROC) in the United States, United Kingdom, and Canada. METHODS/MATERIALS: Physicians retrospectively reviewed medical records of women aged 18 years or older who were diagnosed with PRROC between January 2010 and June 2014. Patient characteristics, initial PRROC therapy, and health care utilization were assessed; progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier and Cox proportional hazards methods...
March 14, 2018: International Journal of Gynecological Cancer
Midori Kjellin, Terése Wesslén, Erik Löfblad, Johan Lennerstrand, Anders Lannergård
BACKGROUND: The clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome. METHOD: Thirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011-2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated...
March 14, 2018: Upsala Journal of Medical Sciences
Ting Zhang, Songlei Zhou, Ling Hu, Bo Peng, Yang Liu, Xiang Luo, Xinrong Liu, Yanzhi Song, Yihui Deng
Polysialic acid (PSA) is a nonimmunogenic and biodegradable polysaccharide. In recent years, PSA has shown its potential applications to cancer treatment. In this study, PSA-polyethylene glycol (PEG) conjugate was synthesized for the decoration of epirubicin (EPI)-loaded liposomes. The study aimed to evaluate the PSA-PEG conjugated modified liposomes (EPI-PSL) in vitro and in vivo to investigate the role of PSA on physicochemical characteristics and antitumor activity in PEGylated liposomes. EPI-PSL showed a particle size of 116...
March 13, 2018: Drug Delivery and Translational Research
Marta Vilalta, Jourdan Brune, Marjan Rafat, Luis Soto, Edward E Graves
Recently it has been observed in preclinical models that that radiation enhances the recruitment of circulating tumor cells to primary tumors, and results in tumor regrowth after treatment. This process may have implications for clinical radiotherapy, which improves control of a number of tumor types but which, despite continued dose escalation and aggressive fractionation, is unable to fully prevent local recurrences. By irradiating a single tumor within an animal bearing multiple lesions, we observed an increase in tumor cell migration to irradiated and unirradiated sites, suggesting a systemic component to this process...
March 13, 2018: Clinical & Experimental Metastasis
Biki Gupta, Bijay Kumar Poudel, Shobha Regmi, Shiva Pathak, Hima Bindu Ruttala, Milan Gautam, Gyeong Jin An, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
PURPOSE: Lung cancer is the leading cause of cancer-related deaths. The aim of this study was to design solid lipid core nanocapsules (SLCN) comprising a solid lipid core and a PEGylated polymeric corona for paclitaxel (PTX) and erlotinib (ERL) co-delivery to non-small cell lung cancer (NSCLC), and evaluate their physicochemical characteristics and in vitro activity in NCI-H23 cells. METHODS: PTX/ERL-SLCN were prepared by nanoprecipitation and sonication and physicochemically characterized by dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy...
March 13, 2018: Pharmaceutical Research
Claudia Conte, Francesca Mastrotto, Vincenzo Taresco, Aleksandra Tchoryk, Fabiana Quaglia, Snjezana Stolnik, Cameron Alexander
In the treatment of lung cancer, there is an urgent need of innovative medicines to optimize pharmacological responses of conventional chemotherapeutics while attenuating side effects. Here, we have exploited some relatively unexplored subtle differences in reduction potential, associated with cancer cell microenvironments in addition to the well-known changes in intracellular redox environment. We report the synthesis and application of novel redox-responsive PLGA (poly(lactic-co-glycolic acid)) -PEG (polyethylene glycol) nanoparticles (RR-NPs) programmed to change surface properties when entering tumor microenvironments, thus enhance cell internalization of the particles and their drug cargo...
March 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Daria Tretiakova, Natalia Onishchenko, Ivan Boldyrev, Ilya Mikhalyov, Alexander Tuzikov, Nicolai Bovin, Evgeniy Evtushenko, Elena Vodovozova
Previously, we proposed a liposomal formulation of melphalan (Mlph)-a chemotherapeutic alkylating agent-incorporated in a fluid lipid bilayer in the form of dioleoylglyceride ester. In this work, we compared the stabilizing effect of different amphiphiles included in the Mlph-liposomes, such as phosphatidylinositol (PI), ganglioside GM1 , a conjugate of N-carboxymethyl-modified oligoglycine with dioleoylphosphatidylethanolamine (acidic lipopeptide), and polyethylene glycol (2000 Da) conjugated with dipalmitoylphosphatidylethanolamine (PEG-lipid), upon incubation in human serum...
March 1, 2018: Colloids and Surfaces. B, Biointerfaces
Boshra Amiri, Hasan Ahmadvand, Ali Farhadi, Aazam Najmafshar, Mohsen Chiani, Dariush Norouzian
Vinblastine (VB), as a chemotherapeutic agent, is widely used in treatment of different types of cancer. However, its clinical application is limited due to its low water solubility, side effects and multidrug resistance. The aim of this study was to increase the therapeutic efficacy of VB using drug delivery systems. For this purpose, a PEGylated niosomal formulation of vinblastine (Pn-VB) was prepared by thin film hydration method and physicochemically characterized. Drug release pattern was performed by dialysis diffusion method...
March 13, 2018: Drug Development and Industrial Pharmacy
Christopher J White, Jeffrey W Bode
The covalent conjugation of large, functionalized molecules remains a frontier in synthetic chemistry, as it requires rapid, chemoselective reactions. The potassium acyltrifluoroborate (KAT)-hydroxylamine amide-forming ligation shows promise for conjugations of biomolecules under aqueous, acidic conditions, but the variants reported to date are not suited to ligations at micromolar concentrations. We now report that 2-pyridyl KATs display significantly enhanced ligation kinetics over their aryl counterparts...
February 28, 2018: ACS Central Science
Steffen Großhans, Matthias Rüdt, Adrian Sanden, Nina Brestrich, Josefine Morgenstern, Stefan Heissler, Jürgen Hubbuch
Fourier-transform infrared spectroscopy (FTIR) is a well-established spectroscopic method in the analysis of small molecules and protein secondary structure. However, FTIR is not commonly applied for in-line monitoring of protein chromatography. Here, the potential of in-line FTIR as a process analytical technology (PAT) in downstream processing was investigated in three case studies addressing the limits of currently applied spectroscopic PAT methods. A first case study exploited the secondary structural differences of monoclonal antibodies (mAbs) and lysozyme to selectively quantify the two proteins with partial least squares regression (PLS) giving root mean square errors of cross validation (RMSECV) of 2...
March 5, 2018: Journal of Chromatography. A
Baek Gyu Jun, Eui Ju Park, Woong Cheul Lee, Jae Young Jang, Soung Won Jeong, Young Don Kim, Gab Jin Cheon, Young Sin Cho, Sae Hwan Lee, Hong Soo Kim, Yun Nah Lee, Sang Gyune Kim, Young Seok Kim, Boo Sung Kim
Background/Aims: This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. Methods: This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype...
March 14, 2018: Korean Journal of Internal Medicine
Sandra P Amaral, Maun H Tawara, Marcos Fernandez-Villamarin, Erea Borrajo, José Martínez-Costas, Anxo Vidal, Ricardo Riguera, Eduardo Fernandez-Megia
Herein we describe that the generation of dendrimers represents a powerful tool in the control of the size and biodistribution of polyion complexes (PIC). Using a combinatorial screening of six dendrimers (18-243 terminal groups) and five oppositely charged PEGylated copolymers, a dendrimer to PIC hierarchical transfer of structural information was revealed with PIC diameters that increased from 80 to 500 nm on decreasing the dendrimer generation. This rise in size, also accompanied by a micelle to vesicle transition, is interpreted according to a cone- to rod-shaped progression in the architecture of the unit PIC (uPIC)...
March 12, 2018: Angewandte Chemie
Ghaly M F, Fadia M Attia, Rania M Saleh, Heba M, Maha Anani
IL-22 plays a vital role in improving hepatic damage by targeting hepatocytes that express high levels of IL-22 receptor1. IP-10 is a chemokine that recruit mononuclear cells to liver parenchyma and improves the host immune response against hepatitis C virus. The study targeted 27 patients with chronic HCV who received pegylated Interferon and Ribavirin. IL-22 and IP-10 serum levels were measured by Elisa. The level of the serum IL-22 is higher in HCV patients groups receiving the antiviral treatment compared to control group and its levels significantly increased with response to treatment...
June 2017: Egyptian Journal of Immunology
Victoria P Strouvelle, Dominique L Braun, Valentina Vongrad, Alexandra U Scherrer, Yik Lim Kok, Roger D Kouyos, Marcel Stöckle, Andri Rauch, Katharine Darling, Matthias Hoffmann, Karin J Metzner, Huldrych F Günthard
Pegylated interferon-alpha (pIFN-α) is suggested to lower HIV-1 DNA load in antiretroviral therapy (ART) treated patients. We studied the kinetics of total HIV-1 DNA levels in 40 HIV-1/hepatitis C (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into three groups according to start of ART: Chronic HIV-1 infection (n=22), acute HIV-1 infection (n=8), no-ART (n=10). Total HIV-1 DNA levels were quantified in 247 PBMC samples and remained stable before, during, and after pIFN-α treatment in all three groups...
March 8, 2018: Journal of Infectious Diseases
Qing Hu, Qing Chen, Xiuyun Yan, Bomei Ding, Dawei Chen, Lifang Cheng
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS: CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes...
March 12, 2018: Nanomedicine
Giovanni Damiani, Chiara Franchi, Paolo Pigatto, Andrea Altomare, Alessia Pacifico, Stephen Petrou, Sebastiano Leone, Maria Caterina Pace, Marco Fiore
AIM: To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy. METHODS: This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017...
February 27, 2018: World Journal of Hepatology
Tomas Majtan, Erez M Bublil, Insun Park, Erland Arning, Teodoro Bottiglieri, Frank Glavin, Jan P Kraus
AIMS: PEGylated human truncated cystathionine beta-synthase, lacking the C-terminal regulatory domain (PEG-CBS), is a promising preclinical candidate for enzyme replacement therapy in homocystinuria (HCU). It was designed to function as a metabolic sink to decrease the severely elevated plasma and tissue homocysteine concentrations. Here we evaluated pharmacokinetics (PK), pharmacodynamics (PD) and sub-chronic toxicity of PEG-CBS in homocystinuric mice and wild type rats and monkeys to estimate the minimum human efficacious dose for clinical trials...
March 8, 2018: Life Sciences
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