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https://www.readbyqxmd.com/read/28441474/dendrimer-modified-mos2-nanoflakes-as-a-platform-for-combinational-gene-silencing-and-photothermal-therapy-of-tumors
#1
Lingdan Kong, Lingxi Xing, Benqing Zhou, Lianfang Du, Xiangyang Shi
Exploitation of novel hybrid nanomaterials for combinational tumor therapy is challenging. In this work, we synthesized dendrimer-modified MoS2 nanoflakes for combinational gene silencing and photothermal therapy (PTT) of cancer cells. Hydrothermally synthesized MoS2 nanoflakes were modified with generation 5 (G5) poly(amidoamine) dendrimers partially functionalized with lipoic acid via disulfide bond. The formed G5-MoS2 nanoflakes display good colloidal stability and superior photothermal conversion efficiency and photothermal stability...
April 25, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28440798/improved-gene-delivery-to-adult-mouse-spinal-cord-through-the-use-of-engineered-hybrid-adeno-associated-viral-serotypes
#2
J J Siu, N J Queen, W Huang, F Q Yin, X Liu, C Wang, D M McTigue, L Cao
Adeno-associated viral (AAV) vectors are often used in gene therapy for neurological disorders because of its safety profile and promising results in clinical trials. One challenge to AAV gene therapy is effective transduction of large numbers of the appropriate cell type, which can be overcome by modulating the viral capsid through DNA shuffling. Our previous study demonstrates that Rec2, among a family of novel engineered hybrid capsid serotypes (Rec1~4) transduces adipose tissue with far superior efficiency than naturally occurring AAV serotypes...
April 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28440797/potential-mechanisms-of-microrna-141-3p-to-alleviate-chronic-inflammatory-pain-by-down-regulation-of-downstream-target-gene-hmgb1-in-vitro-and-in-vivo-studies
#3
W-S Shen, X-Q Xu, N-N Zhai, Z-S Zhou, J Shao, Y-H Yu
The present study aimed to investigate the potential role of microRNA-141-3p (miR-141-3p) in chronic inflammatory pain (CIP) by targeting HMGB1 gene. In the in vitro study, BV2 microglial cells were selected and assigned into blank, lipopolysaccharide (LPS), miR-141-3p mimics, mimics control, miR-141-3p inhibitor, inhibitor control, miR-141-3p mimics+LPS, mimics control+ LPS, miR-141-3p inhibitor+LPS, and inhibitor control+LPS groups. Ninety-six rats were randomly divided into 8 groups (12 rats in each group): blank control, model control, negative control (NC), miR-141-3p mimics+CFA, mimics control+CFA, HMGB1 shRNA+CFA, HMGB1 NC+CFA, and miR-141-3p mimics+HMGB1 shRNA+CFA groups...
April 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28440796/the-importance-of-international-collaboration-for-rare-diseases-research-a-european-perspective
#4
REVIEW
D Julkowska, C P Austin, C M Cutillo, D Gancberg, C Hager, J Halftermeyer, A H Jonker, L P L Lau, I Norstedt, A Rath, R Schuster, E Simelyte, S van Weely
Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare programme, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA...
April 25, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28440486/synergistic-antitumor-effects-of-cdk-inhibitor-sns%C3%A2-032-and-an-oncolytic-adenovirus-co%C3%A2-expressing-trail-and-smac-in-pancreatic-cancer
#5
Yun Ge, Wen Lei, Yingyu Ma, Yigang Wang, Buyun Wei, Xiaoyi Chen, Guoqing Ru, Xianglei He, Xiaozhou Mou, Shibing Wang
Gene therapy using oncolytic adenoviruses is a novel approach for human cancer therapeutics. The current study aimed to investigate whether the combined use of an adenovirus expressing tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) and second mitochondria‑derived activator of caspase (Smac) upon caspase activation (ZD55‑TRAIL‑IETD‑Smac) and cyclin‑dependent kinase (CDK) inhibitor SNS‑032 will synergistically reinforce their anti‑pancreatic cancer activities. The experiments in vitro demonstrated that SNS‑032 enhances ZD55‑TRAIL‑IETD‑Smac‑induced apoptosis and causes marked pancreatic cancer cell death...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28438704/folic-acid-decorated-polyamidoamine-dendrimer-exhibits-high-tumor-uptake-and-sustained-highly-localized-retention-in-solid-tumors-its-utility-for-local-sirna-delivery
#6
Leyuan Xu, W Andrew Yeudall, Hu Yang
The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic green fluorescent protein siRNA [siGFP]), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies...
April 21, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28438067/gene-therapy-for-patients-with-advanced-solid-tumors-a-phase-i-study-using-gene-electrotransfer-to-muscle-with-the-integrin-inhibitor-plasmid-amep
#7
Iben Spanggaard, Karin Dahlstroem, Line Laessoee, Rasmus Hvass Hansen, Helle Hjorth Johannesen, Helle Westergren Hendel, Céline Bouquet, Pierre Attali, Julie Gehl
BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. MATERIAL AND METHODS: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle...
April 25, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28436941/insr-gene-polymorphisms-correlate-with-sensitivity-to-platinum-based-chemotherapy-and-prognosis-in-patients-with-epithelial-ovarian-cancer
#8
J-L Hu, X-L Hu, Q Han, A-Y Guo, C-J Wang, Y-Y Wen, S-D Cang
This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single nucleotide polymorphism (tag SNP) of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (OR=0...
April 24, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28436446/opioid-self-administration-is-attenuated-by-early-life-experience-and-gene-therapy-for-anti-inflammatory-il-10-in-the-nucleus-accumbens-of-male-rats
#9
Michael J Lacagnina, Ashley M Kopec, Stewart S Cox, Richa Hanamsagar, Corinne Wells, Susan Slade, Peter M Grace, Linda R Watkins, Edward D Levin, Staci D Bilbo
Early-life conditions can contribute to the propensity for developing neuropsychiatric disease, including substance abuse disorders. However, the long-lasting mechanisms that shape risk or resilience for drug addiction remain unclear. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation, and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10)...
April 24, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28435453/sirna-delivery-with-pegylated-graphene-oxide-nanosheets-for-combined-photothermal-and-genetherapy-for-pancreatic-cancer
#10
Feng Yin, Kuan Hu, Yangzi Chen, Mengying Yu, Dongyuan Wang, Qianqian Wang, Ken-Tye Yong, Fei Lu, Yongye Liang, Zigang Li
Since the successful exfoliation of graphene from graphite in 2004, graphene and graphene oxide (GO) have been considered the most promising two-dimensional (2D) nanomaterials with distinguished physical and chemical characteristics and have attracted great attention in many different fields. Graphene oxide is well-known for its distinct physiochemical properties and shows only minimal cytotoxicity compared to carbon nanotubes. Until now, only limited efforts have been invested in utilizing GO for gene therapy in pancreatic cancer treatments...
2017: Theranostics
https://www.readbyqxmd.com/read/28434868/hif-1%C3%AE-dependent-wound-healing-angiogenesis-in%C3%A2-vivo-can-be-controlled-by-site-specific-lentiviral-magnetic-targeting-of-shp-2
#11
Yvonn Heun, Kristin Pogoda, Martina Anton, Joachim Pircher, Alexander Pfeifer, Markus Woernle, Andrea Ribeiro, Petra Kameritsch, Olga Mykhaylyk, Christian Plank, Florian Kroetz, Ulrich Pohl, Hanna Mannell
Hypoxia promotes vascularization by stabilization and activation of the hypoxia inducible factor 1α (HIF-1α), which constitutes a target for angiogenic gene therapy. However, gene therapy is hampered by low gene delivery efficiency and non-specific side effects. Here, we developed a gene transfer technique based on magnetic targeting of magnetic nanoparticle-lentivirus (MNP-LV) complexes allowing site-directed gene delivery to individual wounds in the dorsal skin of mice. Using this technique, we were able to control HIF-1α dependent wound healing angiogenesis in vivo via site-specific modulation of the tyrosine phosphatase activity of SHP-2...
April 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28433106/novel-perspectives-on-wilson-disease-treatment
#12
Christian Rupp, Wolfgang Stremmel, Karl-Heinz Weiss
Wilson disease is an autosomal-recessive copper overload disorder causing hepatic and neurologic symptoms. Commonly used medical therapy shows satisfactory results with regard to hepatic disease but only limited effects in neurologically affected patients. In recent years several new therapy options have been developed, showing promising results that might improve the management of Wilson disease in the near future. Optimization of treatment regimens depending on biochemical response pattern seems worthwhile, especially in the decoppering phase of therapy...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28432001/in-vivo-and-in-vitro-study-of-osteogenic-potency-of-endothelin-1-on-bone-marrow-derived-mesenchymal-stem-cells
#13
Long-Wei Hu, Xiao Wang, Xin-Qun Jiang, Li-Qun Xu, Hong-Ya Pan
Bone marrow-derived mesenchymal stem cells (BMSCs) are a major source of osteoblasts and are crucial for bone remolding and repair and thus they are widely used for tissue engineering applications. Tissue engineering in combination with gene therapy is considered as a promising approach in new bone regeneration. Endothelin-1(EDN-1)is produced by vascular endothelial cells which plays an important role during bone development. However, its role in BMSCs remains largely unknown. We established EDN-1 overexpressed BMSCs, proliferation ability and osteogenesis differentiation were detected respectively...
April 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28429752/lncrna-hit-promotes-cell-proliferation-of-non-small-cell-lung-cancer-by-association-with-e2f1
#14
L Yu, F Fang, S Lu, X Li, Y Yang, Z Wang
Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively...
April 21, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28429751/preclinical-study-of-raav2-strail-pharmaceutical-efficacy-biodistribution-and-safety-in-animals
#15
Q Ru, W Li, X Wang, S Zhang, L Chen, Y Zhang, Y Ge, Y Zu, Y Liu, D Zheng
The recombinant sTRAIL has been in clinical trial for various human malignancies. However, the half-life time of sTRAIL is very short, which might be an important factor influencing its clinical efficacy for cancer therapy. We previously reported the recombinant adeno-associated virus (AAV)-encoding sTRAIL95-281-mediated sTRAIL expression in vivo up to 8 months and suppressed tumor growth markedly in mouse xenografts. In the present study, we further evaluated the clinical potency for cancer gene therapy and the safety in mouse and non-human primates...
April 21, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28429750/correlations-of-tnf-%C3%AE-gene-promoter-polymorphisms-with-the-risk-of-thymoma-associated-myasthenia-gravis-in-a-northern-chinese-han-population
#16
H-W Yang, P Lei, Y-C Xie, Z-L Han, D Li, S-H Wang, Z-L Sun
This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group)...
April 21, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28428056/recent-development-of-synthetic-nonviral-systems-for-sustained-gene-delivery
#17
REVIEW
Yonggang Xiang, Nwe Nwe Linn Oo, Jin Ping Lee, Zibiao Li, Xian Jun Loh
Sustained gene delivery is of particular importance today because it circumvents the need for repeated therapeutic administration and provides spatial and temporal control of the release profile. Better understanding of the genetic basis of diseases and advances in gene therapy have propelled significant research on biocompatible gene carriers for therapeutic purposes. Varied biodegradable polymer-based architectures have been used to create new compositions with unique properties suitable for sustained gene delivery...
April 18, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28427886/identification-of-excipients-for-stabilizing-fiberless-adenovirus-as-biopharmaceuticals
#18
Grit Kupgan, Shyamal P Choudhari, Nicholas H Flynn, Adane Nigatu, Sravanthi Vupputuri, William D Picking, Wendy L Picking, Joshua D Ramsey
Reducing the promiscuous tropism of native adenovirus by using fiberless adenovirus is advantageous towards its use as a gene therapy vector or vaccine component. The removal of the fiber protein on native adenovirus abrogates several undesirable interactions; however, this approach decreases the particle's physical stability. In order to create stable fiberless adenovirus for pharmaceutical use, the effects of temperature and pH on the particle's stability profile must be addressed. Our results indicate that the stability of fiberless adenovirus is increased when it is stored in mildly acidic conditions around pH 6...
April 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28427583/improving-atrial-fibrillation-therapy-is-there-a-gene-for-that
#19
REVIEW
William J Hucker, Alan Hanley, Patrick T Ellinor
Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment...
April 25, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#20
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
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