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https://www.readbyqxmd.com/read/28228084/the-development-of-oncoltyic-adenovirus-therapy-in-the-past-and-future-for-the-case-of-pancreatic-cancer
#1
Mizuho Sato-Dahlman, Masato Yamamoto
Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy strategies may provide new options for treatment of various cancers including pancreatic cancer. Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers and it has been employed for the development of potent oncolytic virotherapy agents for pancreatic cancer...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28228083/oncolytic-virus-regulatory-aspects-from-quality-control-to-clinical-studies
#2
Teruhide Yamaguchi, Eriko Uchida
Oncolytic viruses, which include both naturally occurring wild-type viruses/attenuated viruses and genetically modified viruses, have recently been developed for use in innovative cancer therapies. Genetically modified oncolytic viruses possess the unique ability to replicate conditionally as a unique gene therapy product. Since oncolytic viruses exhibit prolonged persistence in patients, viral shedding and transmission to third parties should be major concerns for clinical trials, along with the clinical safety and efficacy...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28228073/principal-physicochemical-methods-used-to-characterize-dendrimer-molecule-complexes-used-as-genetic-therapy-agents-nanovaccines-or-drug-carriers
#3
Rodríguez Fonseca Rolando Alberto, Rodrigues Joao, Muñoz-Fernández María de Los Angeles, Martínez Muñoz Alberto, Fragoso Vázquez Manuel Jonathan, Correa Basurto José
Nanomedicine is the application of nanotechnology to medicine. This field is related to the study of nanodevices and nanomaterials applied to various medical uses, such as in improving the pharmacological properties of different molecules. Dendrimers are synthetic nanoparticles whose physicochemical properties vary according to their chemical structure. These molecules have been extensively investigated as drug nanocarriers to improve drug solubility and as sustained-release systems. New therapies such as gene therapy and the development of nanovaccines can be improved by the use of dendrimers...
February 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28223920/therapeutic-potential-of-secreted-amyloid-precursor-protein-apps%C3%AE
#4
REVIEW
Bruce G Mockett, Max Richter, Wickliffe C Abraham, Ulrike C Müller
Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28223542/the-in-vitro-and-vivo-effects-of-nuclear-and-cytosolic-parafibromin-expression-on-the-aggressive-phenotypes-of-colorectal-cancer-cells-a-search-of-potential-gene-therapy-target
#5
Hua-Chuan Zheng, Jia-Jie Liu, Jing Li, Ji-Cheng Wu, Lei Yang, Gui-Feng Zhao, Xin Zhao, Hua-Mao Jiang, Ke-Qiang Huang, Zhi-Jie Li
Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223472/overexpression-of-sarcoendoplasmic-reticulum-calcium-atpase-2a-promotes-cardiac-sympathetic-neurotransmission-via-abnormal-endoplasmic-reticulum-and-mitochondria-ca-2-regulation
#6
Julia Shanks, Neil Herring, Errin Johnson, Kun Liu, Dan Li, David J Paterson
Reduced cardiomyocyte excitation-contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague-Dawley, Wistar Kyoto, and spontaneously hypertensive rats...
February 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28223236/effect-of-hyaluronic-acid-binding-to-lipoplexes-on-intravitreal-drug-delivery-for-retinal-gene-therapy
#7
Thomas F Martens, Karen Peynshaert, Thaís Leite Nascimento, Elias Fattal, Marcus Karlstetter, Thomas Langmann, Serge Picaud, Jo Demeester, Stefaan C De Smedt, Katrien Remaut, Kevin Braeckmans
Intravitreal administration of nanomedicines could be valuable for retinal gene therapy, if their mobility in the vitreous and therapeutic efficacy in the target cells can be guaranteed. Hyaluronic acid (HA) as an electrostatic coating of polymeric gene nanomedicines has proven to be beneficial on both accounts. While electrostatic coating provides an easy way of coating cationic nanoparticles, the stability of electrostatic complexes in vivo is uncertain. In this study, therefore, we compare electrostatic with covalent coating of gene nanocarriers with HA for retinal gene therapy via intravitreal administration...
February 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28222949/rare-bleeding-disorders-old-diseases-in-the-era-of-novel-options-for-therapy
#8
Tami Livnat, Assaf Arie Barg, Sarina Levy-Mendelovich, Gili Kenet
Rare diseases are defined as life-threatening or chronically debilitating diseases with a prevalence of less than one per 2000 according to the European Union or one per 1250 according to the USA. Congenital rare bleeding disorders RBD are reported in most populations, with incidence varying from 1 in 5000 (Hemophilia A), 1:30,000 (Hemophilia B) to much rarer (1:500,000 for FVII deficiency, 1-3 million for Prothrombin or FXIII deficiency). Acquired Hemophilia A is also a rare bleeding disorder with estimated frequency of 1 in million...
February 14, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28221337/modulation-of-digital-flexor-tendon-healing-by-vascular-endothelial-growth-factor-gene-transfection-in-a-chicken-model
#9
W F Mao, Y F Wu, Q Q Yang, Y L Zhou, J B Tang
A major challenge in tendon injury is the weak intrinsic healing capacity of tendon, which may cause re-rupture after surgery. Growth factors are believed to be critical during tendon healing. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. One hundred and twenty eight deep flexor tendons in the long toes of chickens were completely transected and injected with 2 × 10(9) particles of AAV2-VEGF or saline before surgically repaired...
February 21, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28219841/experimental-and-computational-surface-hydrophobicity-analysis-of-a-non-enveloped-virus-and-proteins
#10
Caryn L Heldt, Amna Zahid, K Saagar Vijayaragavan, Xue Mi
The physical characteristics of viruses needs to be understood in order to manipulate the interaction of viruses with host cells, as well as to create specific molecular recognition techniques to detect, purify, and remove viruses. Viruses are generally believed to be positively charged at physiological pH, but there are few other defining characteristics. Here, we have experimentally and computationally demonstrated that a non-enveloped virus is more hydrophobic than a panel of model proteins. Reverse-phase and hydrophobic interaction chromatography and ANS fluorescence determined the experimental hydrophobic strength of each entity...
February 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28219395/efficient-precise-knockin-with-a-double-cut-hdr-donor-after-crispr-cas9-mediated-double-stranded-dna-cleavage
#11
Jian-Ping Zhang, Xiao-Lan Li, Guo-Hua Li, Wanqiu Chen, Cameron Arakaki, Gary D Botimer, David Baylink, Lu Zhang, Wei Wen, Ya-Wen Fu, Jing Xu, Noah Chun, Weiping Yuan, Tao Cheng, Xiao-Bing Zhang
BACKGROUND: Precise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy. However, HDR efficiency remains low in some cell types, including some of great research and clinical interest, such as human induced pluripotent stem cells (iPSCs). RESULTS: Here, we show that a double cut HDR donor, which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage, increases HDR efficiency by twofold to fivefold relative to circular plasmid donors at one genomic locus in 293 T cells and two distinct genomic loci in iPSCs...
February 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28218744/live-cell-imaging-to-compare-the-transfection-and-gene-silencing-efficiency-of-calcium-phosphate-nanoparticles-and-a-liposomal-transfection-agent
#12
S Chernousova, M Epple
The processing of DNA (for transfection) and siRNA (for gene silencing), introduced into HeLa cells by triple-shell calcium phosphate nanoparticles, was followed by live-cell imaging. For comparison, the commercial liposomal transfection agent Lipofectamine(TM) was used. The cells were incubated with these delivery systems, carrying either eGFP-encoding DNA or siRNA against eGFP. In the latter case, HeLa cells which stably expressed eGFP were used. The expression of eGFP started after 5 h in the case of nanoparticles and after 4 h in the case of Lipofectamine...
February 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28218692/early-insights-from-commercialization-of-gene-therapies-in-europe
#13
Nicolas Touchot, Mathias Flume
After years of research and development, gene therapies are now becoming a commercial reality with several products approved by European regulatory authorities [...].
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28216148/epigenetic-modification-of-the-ccl5-ccr1-erk-axis-enhances-glioma-targeting-in-dedifferentiation-reprogrammed-bmscs
#14
Rui Chen, Wayne Yuk-Wai Lee, Xiao Hu Zhang, Jie Ting Zhang, Sien Lin, Liang Liang Xu, Biao Huang, Fu Yuan Yang, Hai Long Liu, Bin Wang, Lai Ling Tsang, Sandrine Willaime-Morawek, Gang Li, Hsiao Chang Chan, Xiaohua Jiang
The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis...
February 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28215303/neurotrophic-factors-used-to-treat-spinal-cord-injury
#15
S I Hodgetts, A R Harvey
The application of neurotrophic factors as a therapy to improve morphological and behavioral outcomes after experimental spinal cord injury (SCI) has been the focus of many studies. These studies vary markedly in the type of neurotrophic factor that is delivered, the mode of administration, and the location, timing, and duration of the treatment. Generally, the majority of studies have had significant success if neurotrophic factors are applied in or close to the lesion site during the acute or the subacute phase after SCI...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28215147/approaches-to-optimize-gene-therapy-for-the-treatment-of-hematologic-malignancies-overcoming-the-obstacles
#16
Yingzhe Jiang, Bing Xia, Yizhuo Zhang, Wen Xu
Gene transfer and oncolytic viruses provide new therapeutic approaches for the treatment of hematologic malignancies. However, it is still too early to introduce gene delivery or oncolytic viruses into standard clinical protocol. It is very important to discuss the obstacles that gene transfer and oncolytic virotherapy face for the further clinical application for treatment of hematologic malignancies, and updating the advances made to overcome them. The major concerns in this review include the approaches of the development of immuno-stimulatory gene transfer mediated-vaccination for leukemia therapy, RNAi-based therapy for leukemia and enhancement of sensitivity of target malignant cells to virotherapy and alteration of host immune response to favor oncolytic viruses...
February 15, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28213069/a-pilot-study-of-cell-mediated-gene-therapy-for-spinal-cord-injury-in-mini-pigs
#17
Islamov Rustem Robertovich, Sokolov Mikhail Evgenyevich, Bashirov Farid Vagizovich, Fadeev Filip Olegovich, Shmarov Maxim Michaylovich, Naroditskiy Boris Savelyevich, Povysheva Tatyana Vyacheslavovna, Shaymardanova Gulnara Ferdinantovna, Yakupov Radik Albertovich, Chelyshev Yuri Aleksandrovich, Lavrov Igor Aleksandrovich
Currently, in clinical practice there is no efficient way to overcome the sequences of neurodegeneration after spinal cord traumatic injury. Using a new experimental model of spinal cord contusion injury on miniature pigs, we proposed to deliver therapeutic genes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) to the damaged area, using umbilical cord blood mononuclear cells (UCBC). In this study, genetically engineered UCBC (2×10(6) cells in 200 ml of saline) were injected intrathecally to mini-pigs 10days after SCI...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212271/carbon-nanotubes-as-an-effective-opportunity-for-cancer-diagnosis-and-treatment
#18
REVIEW
Alessandro Sanginario, Beatrice Miccoli, Danilo Demarchi
Despite the current progresses of modern medicine, the resistance of malignant tumors to present medical treatments points to the necessity of developing new therapeutic approaches. In recent years, numerous studies have focused their attention on the promising use of nanomaterials, like iron oxide nanowires, zinc oxide or mesoporous silica nanoparticles, for cancer and metastasis treatment with the advantage of operating directly at the bio-molecular scale. Among them, carbon nanotubes emerged as valid candidates not only for drug delivery, but also as a valuable tool in cancer imaging and physical ablation...
February 15, 2017: Biosensors
https://www.readbyqxmd.com/read/28209901/vitamin-b3-modulates-mitochondrial-vulnerability-and-prevents-glaucoma-in-aged-mice
#19
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Kelly E Cochran, Vivek M Philip, Vittorio Porciatti, Oliver Smithies, Simon W M John
Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD(+), a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#20
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
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