Abstract:
:Chronic inflammation in tibialis anterior muscles of mdx mice was produced by a single injection of a recombinant adenovirus vector (AV) expressing an immunogenic beta-galactosidase (beta-gal). In regions of intense beta-gal staining, mononuclear infiltrates abounded, and muscle fibers showed strong extrasynaptic utrophin immunostaining, restoration of dystrophin-associated protein complex, and a marked reduction of the prevalence of centronucleation. Immunoblot analysis confirmed an increase of endogenous utrophin without an increase of the mRNA of the major muscle isoform utrA. Significantly better maximal tetanic force values were demonstrated in the inflammatory versus control mdx muscles. The resistance to lengthening contraction- induced damage was also significantly increased in the former. In muscles of mice lacking TNF-alpha gene, AV vector did not induce inflammation and extrajunctional utrophin increase did not occur. In the inflammatory mdx muscles, proteolytic activity of calcium-activated calpain was reduced, and in mdx myotubes in vitro, incubation with NO donors also reduced calpain-mediated utrophin proteolysis. Since utrophin was shown to be a natural substrate of calpain and known inhibitors of calpain in cultured mdx myotubes increased utrophin levels, the above results were consistent with the following conclusions: (1) extrasynaptic utrophin increase is mainly responsible for the antidystrophic effect; (2) extrasynaptic utrophin increase is a result of posttranscriptional mechanism(s) related to proinflammatory factors; and (3) reduction of endogenous muscle calpain activity by inflammatory cytokines has an important role in the stabilization and increase of the extrasynaptic utrophin.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Waheed I,Gilbert R,Nalbantoglu J,Guibinga GH,Petrof BJ,Karpati Gdoi
10.1089/hum.2005.16.489keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
489-501issue
4eissn
1043-0342issn
1557-7422journal_volume
16pub_type
杂志文章abstract::The central nervous system (CNS) is a predominant site of involvement in several lysosomal storage diseases (LSDs); and for many patients, these diseases are diagnosed only after the onset of symptoms related to the progressive accumulation of macromolecules within lysosomes. The mucopolysaccharidosis type VII (MPS VI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015707
更新日期:2000-03-01 00:00:00
abstract::Foamy virus (FV) vectors are a promising gene delivery system for use in hematopoietic stem cell gene therapy. Previous FV vector marking studies in the NOD/SCID xenotransplantation model used umbilical cord blood (UCB)-derived SCID repopulating cells (SRCs) that were assayed 5-10 weeks posttransplantation. We now rep...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340460732481
更新日期:2004-01-01 00:00:00
abstract::Adeno-associated viral (AAV) vectors are becoming increasingly popular in basic research as well as in clinical gene therapy. Due to its exceptional resistance against physical and chemical stress, however, the increasing use of AAV in laboratories and clinics around the globe raises safety concerns. Proper decontamin...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.120
更新日期:2020-11-06 00:00:00
abstract::Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. In this study, we tried to illuminate the impact of WIF-1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.005
更新日期:2007-04-01 00:00:00
abstract::The in vitro genetic manipulation of dendritic cells (DCs) for the expression of foreign proteins or peptides will assist in the development of immunotherapeutic approaches to treat cancer, immunological disorders, and/or infectious diseases. Reports have shown the expansion and differentiation of CD34(+) progenitor c...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050207975
更新日期:2000-12-10 00:00:00
abstract::Adenoviral vectors used in gene therapy are predominantly derived from adenovirus serotype 5 (Ad5), which infects a broad range of cells. Ad5 cell entry involves interactions with the coxsackie-adenovirus receptor (CAR) and integrins. To assess these receptors in vivo, we mutated amino acid residues in fiber and pento...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403765255165
更新日期:2003-05-20 00:00:00
abstract::Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.5-621
更新日期:1998-03-20 00:00:00
abstract::We report on an antitumor treatment involving electrogene therapy (EGT), a newly developed in vivo gene transfer method using electroporation. We carried out in vivo EGT in a subcutaneous model of CT26 colon carcinoma cells, using plasmid DNAs encoding interleukin 12 (IL-12) subunits. For this purpose, we developed tw...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750270922
更新日期:2001-07-01 00:00:00
abstract::The use of nonionic polymeric micelles orally to protect and deliver plasmid DNA in vivo was investigated. Parathyroid hormone (PTH)(1-34) gene (179 bp) was inserted into a human cytomegalovirus promoter (PCMV) and E. coli competent cells were used to amplify the cDNA. Polymeric micelle formations (100 microl) formed ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.015
更新日期:2009-11-01 00:00:00
abstract::Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrogenesis. Transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are key profibrotic cytokines that regulate HSC activation and proliferation with functional convergence. Dual RNA interference against their ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.047
更新日期:2019-02-01 00:00:00
abstract::The inherited deficiency in adenosine deaminase (ADA), which results in severe combined immunodeficiency, is generally regarded as an optimal model for the development of human somatic gene therapy. The ideal target for the correction of ADA deficiency and other lympho-hematopoietic disorders would be the hematopoieti...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1991.2.3-203
更新日期:1991-10-01 00:00:00
abstract::C-C chemokine receptor type 5 (CCR5) is a major co-receptor for the entry of human immunodeficiency virus type-1 (HIV-1) into target cells. Human hematopoietic stem cells (hHSCs) with naturally occurring CCR5 deletions (Δ32) or artificially disrupted CCR5 have shown potential for curing acquired immunodeficiency syndr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.126
更新日期:2012-02-01 00:00:00
abstract::This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via wee...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2010.020
更新日期:2010-09-01 00:00:00
abstract::The purpose of this study was to determine the safety and antitumor activity of IFN-gamma retroviral vector in patients with advanced melanoma. Seventeen patients (9 single courses, 8 multiple courses) received a total of 363 intratumor injections of IFN-gamma retroviral vector (1 x 10(7) PFU/ml administered at 0.3, 0...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/10430349950017978
更新日期:1999-05-20 00:00:00
abstract::PhD-trained biomedical scientists are moving into an increasingly diverse variety of careers within the sciences. However, graduate and postdoctoral training programs have historically focused on academic career preparation, and have not sufficiently prepared trainees for transitioning into other scientific careers. A...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.154
更新日期:2016-11-01 00:00:00
abstract::Retrovirus-mediated gene transfer is currently the most common method for the application of genetic therapy to cancer and many inherited and acquired disorders. Here we report the generation of an amphotropic producer cell line (CA2) that synthesizes viral particles carrying a bicistronic cassette in which the select...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.17-2165
更新日期:1996-11-10 00:00:00
abstract::Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increas...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.7-989
更新日期:1998-05-01 00:00:00
abstract::The transfer of a drug resistance gene into hematopoietic cells is an approach being investigated to overcome the problem of myelosuppression produced by anticancer drugs. Chemotherapeutic agents are often given in combination in order to increase their effectiveness. Consequently, there is an advantage in designing v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.17-2537
更新日期:1998-11-20 00:00:00
abstract::Recombinant adeno-associated virus serotype 2 (rAAV2)-based human gene therapy for cystic fibrosis has progressed through a series of preclinical studies and phase I and II clinical trials. This agent has shown an encouraging safety profile, consistent levels of DNA transfer, and positive evidence of short-term clinic...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.2005.16.921
更新日期:2005-08-01 00:00:00
abstract::Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carryi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.036
更新日期:2008-08-01 00:00:00
abstract::At present, much more studies have focused on the role of microRNAs in osteoporosis, but the more specific role of microRNA-150-3p (miR-150-3p) in osteoporosis still needs full exploration. We aim at investigating the role of miR-150-3p in osteoporosis and at exploring the related mechanisms. Bone marrow mesenchymal s...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.005
更新日期:2021-01-22 00:00:00
abstract::Sphingosine kinase 1 (SPK1) has been identified as a central mediator of ischemia preconditioning and plays a protective role in ischemia/reperfusion (I/R)-induced cardiomyocyte death. In the present study, we investigated the protective effect of adenovirus-mediated SPK1 gene (Ad-SPK1) transfer on I/R-induced cardiac...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.036
更新日期:2007-11-01 00:00:00
abstract::Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.099
更新日期:2017-03-01 00:00:00
abstract::Virotherapy is a unique modality for the treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Various viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic prote...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.138
更新日期:2017-10-01 00:00:00
abstract::Restoration of correct splicing of βIVS2-654-globin pre-mRNA was previously accomplished in erythroid cells from β-thalassemia/HbE patients by an engineered U7 small nuclear RNA (snRNA) that carried a sequence targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP+623 snRNA. In this study, this ap...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.145
更新日期:2020-11-02 00:00:00
abstract::The influence of serum on the production of retroviral vectors by the HT1080 human fibrosarcoma-derived packaging cell line FLYRD18 was investigated. A fourfold increase in virus titer was observed under serum-free conditions, as compared with medium supplemented with 10% fetal calf serum. A similar improvement was al...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017329
更新日期:1999-08-10 00:00:00
abstract::Adenovirus type 5 (Ad5) is a commonly used vector for gene therapy, but its efficacy is limited by high seroprevalence and off-target hepatic and splenic sequestration. In order to circumvent these limitations, the use of vectors derived from rare species adenoviruses is appealing. The opportunity to retarget rare spe...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.016
更新日期:2014-04-01 00:00:00
abstract::Malignant mesothelioma is a tumor of the pleura for which there is no satisfactory treatment. It is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalitie...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.17-2641
更新日期:1998-11-20 00:00:00
abstract::Activation of T cells is necessary for efficient retroviral-mediated gene transfer. In addition, if the population of infused cells is to be limited to transduced cells, a means of positive selection is required. We describe a clinical scale procedure for activation of donor T cells with anti-CD3/CD28 beads followed b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252939087
更新日期:2002-05-20 00:00:00
abstract::Replication-deficient viral vectors are currently being used in gene transfer strategies to treat cancer cells. Unfortunately, viruses are limited in their ability to diffuse through tissue. This makes it virtually impossible to infect the majority of tumor cells in vivo and results in inadequate gene transfer. This p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.8-1209
更新日期:1998-05-20 00:00:00