Abstract:
:Patients frequently experience a loss of salivary function following irradiation (IR) for the treatment of an oral cavity and oropharyngeal cancer. Herein, we tested if transfer of fibroblast growth factor-2 (FGF2) cDNA could limit salivary dysfunction after fractionated IR (7.5 or 9 Gy for 5 consecutive days to one parotid gland) in the miniature pig (minipig). Parotid salivary flow rates steadily decreased by 16 weeks post-IR, whereas blood flow in the targeted parotid gland began to decrease ~3 days after beginning IR. By 2 weeks, post-IR salivary blood flow was reduced by 50%, at which point it remained stable for the remainder of the study. The single preadministration of a hybrid serotype 5 adenoviral vector encoding FGF2 (AdLTR2EF1a-FGF2) resulted in the protection of parotid microvascular endothelial cells from IR damage and significantly limited the decline of parotid salivary flow. Our results suggest that a local treatment directed at protecting salivary gland endothelial cells may be beneficial for patients undergoing IR for oral cavity and oropharyngeal cancer.
journal_name
Gene Therjournal_title
Gene therapyauthors
Guo L,Gao R,Xu J,Jin L,Cotrim AP,Yan X,Zheng C,Goldsmith CM,Shan Z,Hai B,Zhou J,Zhang C,Baum BJ,Wang Sdoi
10.1038/gt.2014.63subject
Has Abstractpub_date
2014-10-01 00:00:00pages
866-73issue
10eissn
0969-7128issn
1476-5462pii
gt201463journal_volume
21pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Human pluripotent stem cell-derived neural progenitor (hNP) cells are an excellent resource for understanding early neural development and neurodegenerative disorders. Given that many neurodegenerative disorders can be correlated with defects in the mitochondrial genome, optimal utilization of hNP cells requires an ab...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.134
更新日期:2012-05-01 00:00:00
abstract::Hypoxia initiates an adaptive physiological response in all organisms and plays a role in the pathogenesis of several human diseases. The hypoxia/HIF-inducible factor-1 (HIF-1) transcription factor mediates transcriptional responses to hypoxia by binding to a cis-acting hypoxia-responsive element (HRE) present within ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301605
更新日期:2001-12-01 00:00:00
abstract::Confinement of transgene expression to target cells is highly desirable in gene therapy. Current strategies of transcriptional targeting to tumors usually rely on tissue-specific promoters to control gene expression. However, such promoters generally have much lower activity than the constitutive viral promoters. We h...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302029
更新日期:2003-08-01 00:00:00
abstract::Gene delivery of angiogenic growth factors is a promising approach for the treatment of ischemic cardiovascular diseases. However, success of this new therapeutic principle is hindered by the lack of critical understanding as to how disease pathology affects the efficiency of gene delivery and/or the downstream signal...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302781
更新日期:2006-09-01 00:00:00
abstract::Intraperitoneal (i.p.) recurrence of cisplatin-refractory and p53 mutant ovarian cancer is a major clinical problem, despite surgery and chemotherapy. dl1520 (ONYX-015) is an E1B-55 kDa gene-deleted adenovirus engineered selectively to replicate in and destroy cancer cells lacking functional p53. However, a correlatio...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301319
更新日期:2000-11-01 00:00:00
abstract::The bystander effect (BSE) is an interesting and important property of the herpes thymidine kinase/ganciclovir (hTK/GCV) system of gene therapy for cancer. With the BSE, not only are the hTK expressing cells killed upon ganciclovir (GCV) exposure but also neighboring wild-type tumor cells. On testing a large number of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300784
更新日期:1998-12-01 00:00:00
abstract::Lentiviral vectors pseudotyped with the baculovirus envelope protein GP64 transduce primary cultures of human airway epithelia (HAE) at their apical surface. Our goal in this study was to harness a directed evolution approach to develop a novel envelope glycoprotein with increased transduction properties for HAE. Usin...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2017.78
更新日期:2017-10-01 00:00:00
abstract::Current tools for the inhibition of microRNA (miR) function are limited to modified antisense oligonucleotides, sponges and decoy RNA molecules and none have been used to understand miR function during development. CRISPR/Cas-mediated deletion of miR sequences within the genome requires multiple chromosomal deletions ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.22
更新日期:2016-06-01 00:00:00
abstract::Direct gene transfer for the treatment of human diseases requires a vector which can be administered efficiently, safely and repeatedly. Cationic liposomes represent one of the few examples that can meet these requirements. Currently, more than a dozen cationic liposome formulations have been reported. These liposomes...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:
更新日期:1995-12-01 00:00:00
abstract::For certain gene therapy applications, the simultaneous delivery of multiple genes would allow for novel therapies. In the case of adeno-associated virus (AAV) vectors, the limited packaging capacity greatly restricts current methods of carrying multiple transgene cassettes. To address this issue, a recombinant AAV (r...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.106
更新日期:2009-11-01 00:00:00
abstract::RNAi represents a powerful technology to specifically downregulate the expression of target genes. For cancer research and therapy, an efficient in vivo delivery system is supposed to distribute RNAi to all tumour cells upon systemic administration. We present replication-competent murine leukaemia virus (MLV) vectors...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.48
更新日期:2011-10-01 00:00:00
abstract::Cationic lipid-based delivery systems such as lipoplexes or stabilized plasmid-lipid particles (SPLP) represent a safer alternative to viral systems for gene therapy applications. We studied the impact of cell cycle status on the efficiency of transfection of human ovarian carcinoma tumor cells using two cationic-lipi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300837
更新日期:1999-03-01 00:00:00
abstract::Inadequate antiprotease activity in the lungs due to alpha-1-antitrypsin (A1AT) deficiency is a factor of early-onset emphysema. We propose a new approach to gene therapy that involves the intratracheal delivery of macrophages expressing human A1AT (hA1AT). Recombinant adeno-associated virus (rAAV) plasmids encoding t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302121
更新日期:2003-12-01 00:00:00
abstract::In-stent restenosis results exclusively from neointimal hyperplasia due to mechanical injury and a foreign body response to the prosthesis. Inflammation mediated by monocyte chemoattractant protein-1 (MCP-1) might therefore underlie in-stent restenosis. We recently devised a new strategy for anti-MCP-1 gene therapy by...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302288
更新日期:2004-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Gene therapy
pub_type: 已发布勘误
doi:10.1038/s41434-020-00186-x
更新日期:2020-08-01 00:00:00
abstract::The production of high-titer recombinant adeno-associated virus (rAAV) vector is essential for treatment of genetic diseases affecting the retina and choroid, where anatomical constraints may limit injectable volumes. Problematically, cytotoxicity arising from overexpression of the transgene during vector production f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2017.50
更新日期:2017-08-01 00:00:00
abstract::Over the last years, RNA interference (RNAi) has become a widely used technique that permits the knock-down, and hence functional analysis, of individual genes in vertebrate cells. However, the high failure rate of the RNA molecules used in RNAi experiments continues to be a problem. In this paper, I describe a set of...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302656
更新日期:2006-03-01 00:00:00
abstract::We have developed a retroviral vector coexpressing the multidrug-resistance 1 (MDR1) cDNA for inducing cancer drug resistance and the truncated version of the low-affinity nerve growth factor receptor (DeltaLNGFR) for cell-surface marking of transduced cells. The vector is based on the FMEV backbone which mediates hig...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300942
更新日期:1999-07-01 00:00:00
abstract::The oncotropic phenotypes of several viruses correlate with tumor-associated deficiencies within interferon (IFN) signaling pathways. This observation formed the conceptual basis for developing oncolytic viruses deleted for viral proteins that inhibit the host IFN-dependent antiviral response, such as herpes simplex v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.68
更新日期:2009-09-01 00:00:00
abstract::A number of genetic disorders are manifested in cutaneous epithelium and gene therapy approaches for treatment of such diseases are being considered. A successful gene therapy protocol requires durable and correctly targeted gene expression within the tissue. The continuous renewal and high levels of compartmentalizat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301800
更新日期:2002-10-01 00:00:00
abstract::Prenatal gene therapy has been considered for Herlitz junctional epidermolysis bullosa (H-JEB), a lethal genodermatosis caused by the absence of any of the three subunits of laminin-5, resulting from birth in widespread blistering and erosions of skin and mucosae. To investigate this strategy in an animal model, adeno...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302832
更新日期:2006-12-01 00:00:00
abstract::Replication defective viral vectors provide a potentially useful means of gene transfer to oligodendrocytes and thus for studying the pathogenesis of white matter disease. In this study we have examined the expression pattern of E1/E3 deleted adenoviral vectors expressing the reporter gene LacZ (AdlacZ) as a means of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300971
更新日期:1999-08-01 00:00:00
abstract::To confer adenovirus vectors (AdV), the feature of integration into the host cell genome hybrid vectors were characterized in vitro, which express vectors derived from the prototypic foamy virus (FV) in the backbone of a high-capacity AdV. FVs constitute a subfamily of retroviruses with a distinct replication pathway ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302216
更新日期:2004-04-01 00:00:00
abstract::Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by progressive heterotopic bone formation. Currently, no definitive treatment exists for FOP. The activin receptor type IA / activin-like kinase 2 (ACVR1/ALK2) gene has been identified as the responsible gene for FOP...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.193
更新日期:2012-07-01 00:00:00
abstract::To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse....
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.29
更新日期:2010-07-01 00:00:00
abstract::Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits, including similar differentiation potential and cell surface markers, with their bone marrow counterparts. Owing to their general availability, higher abundance and ease of isolation AMSCs may be convenient autologous delivery vehicles for loc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.176
更新日期:2009-04-01 00:00:00
abstract::RNA interference (RNAi) is an evolutionarily conserved process by which plants and animals protect their genomes utilizing small, double-stranded RNAs to degrade target RNAs in a sequence-specific manner. Post-transcriptional gene silencing by these moieties can lead to degradation of both cellular and viral RNAs. It ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302339
更新日期:2004-12-01 00:00:00
abstract::The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful interve...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302755
更新日期:2006-07-01 00:00:00
abstract::This report examines the commercialization of gene therapy in the context of innovation theories that posit a relationship between the maturation of a technology through its life cycle and prospects for successful product development. We show that the field of gene therapy has matured steadily since the 1980s, with th...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.72
更新日期:2014-02-01 00:00:00
abstract::Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.158
更新日期:2011-05-01 00:00:00