Abstract:
:Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) have an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti-angiogenic agents, such as bevacizumab. In this study we hypothesized that upregulation of MMP activity during anti-angiogenic therapy can improve CRAd-S-pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho=-0.38; **P=0.003), we show that VEGF-blocking antibody treatment followed by CRAd-S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***P<0.0001). Our data propose a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy.
journal_name
Gene Therjournal_title
Gene therapyauthors
Thaci B,Ulasov IV,Ahmed AU,Ferguson SD,Han Y,Lesniak MSdoi
10.1038/gt.2012.42subject
Has Abstractpub_date
2013-03-01 00:00:00pages
318-27issue
3eissn
0969-7128issn
1476-5462pii
gt201242journal_volume
20pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::VP22, a structural protein from herpes simplex virus type I, exhibits the unique property of intercellular trafficking. This protein is exported from primary expressing cells and subsequently imported into neighbouring cells. This property is conserved when VP22 is genetically fused to a protein, making it a promising...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301904
更新日期:2003-02-01 00:00:00
abstract::Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being introduced into clin...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3303067
更新日期:2008-01-01 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::Although systemic administration of neutralizing anti-TNF antibodies has been used successfully in treating rheumatoid arthritis, there is a potential for side effects. We transduced a collagen reactive T-cell hybridoma with tissue-specific homing properties to assess therapeutic effects of local delivery to inflamed ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301980
更新日期:2003-08-01 00:00:00
abstract::We have previously established a stable HIV-1 packaging cell line, psi 422, which yielded high titers of an HIV-1 vector capable of efficiently transducing CD4+ cells. In order to increase the safety of this gene delivery system, we have now replaced the HIV-1 vector with an HIV-2 vector to abolish any risk of homolog...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300563
更新日期:1998-01-01 00:00:00
abstract::Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the target...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.48
更新日期:2016-10-01 00:00:00
abstract::Both atherosclerosis and arterial interventions induce oxidative stress mediated in part by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases that have a pivotal role in the development of neointimal hyperplasia and restenosis. For small interfering RNA (siRNA) targeting of the NOX2 (Cybb) component of the ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.69
更新日期:2010-10-01 00:00:00
abstract::Radioiodide concentrating activity in the thyroid, mediated by human Na+/I- symporter (hNIS), provides a mechanism for effective radioiodide treatment for patients who have invasive, recurrent, and metastatic thyroid cancers after total thyroidectomy. In an attempt to develop hNIS gene transfer for radioiodide therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301170
更新日期:2000-05-01 00:00:00
abstract::Tissue-specific promoters for gene therapy are typically too big for adeno-associated virus (AAV) vectors; thus, the exploration of small effective non-viral regulatory elements is of particular interest. Wild-type AAV can specifically integrate into a region on human chromosome 19 termed AAVS1. Earlier work has deter...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.134
更新日期:2009-01-01 00:00:00
abstract::Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The poten...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300832
更新日期:1999-03-01 00:00:00
abstract::Cationic liposomes provide a means to introduce genes into cells both ex vivo and in vivo. In the past few years their use has been described in several tissues, e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially available poly-cationic liposome formulation in delivering a reporter gene i...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Numerous approaches in gene therapy of human cancers are focused on the establishment of cell type specific or inducible expression vectors allowing the targeted and regulated expression of therapeutic genes. Various conditionally active vectors have been created carrying promoters responding to certain factors or the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300451
更新日期:1997-06-01 00:00:00
abstract::The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this re...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301636
更新日期:2002-02-01 00:00:00
abstract::Adenovirus (Ad)-mediated delivery of anti-angiogenic molecules into tumors constitutes an appealing approach for growth inhibition. However, lack of expression on tumors of Ad receptors leads to weak tumor transduction. Therefore, to provide Ad with a new entry pathway into tumors, an NGR peptide was inserted into eit...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.97
更新日期:2009-12-01 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::We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor). We have recently reported that HIV-IT(V) administered intramuscularly to male mice localizes pr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Isolated limb perfusion (ILP) is a limb salvage surgical modality used to deliver chemotherapy and biologic agents to locally advanced and recurrent extremity soft tissue sarcoma (STS), and may be readily tailored for delivery of gene therapy. We set out to test the feasibility of delivering AdFLAGp53 (replication inc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302911
更新日期:2007-04-01 00:00:00
abstract::Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.183
更新日期:2012-05-01 00:00:00
abstract::Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) promotes soft tissue and bone healing, and is Food and Drug Administration-approved for treatment of diabetic ulcers and periodontal defects. The short half-life of topical rhPDGF-BB protein application necessitates bolus, high-dose delivery. Gene therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.73
更新日期:2017-01-01 00:00:00
abstract::We have constructed two recombinant adeno-associated virus (AAV) vectors (pJJ-3GC and pJJ-3ASA) which contained either the human glucocerebrosidase (GC) or arylsulfatase A (ASA) cDNA under the control of an SV40 promoter. These plasmids were co-transfected to 293 cells with a helper plasmid containing trans-acting AAV...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Integration site analysis was performed on six dogs with canine leukocyte adhesion deficiency (CLAD) that survived greater than 1 year after infusion of autologous CD34+ bone marrow cells transduced with a gammaretroviral vector expressing canine CD18. A total of 387 retroviral insertion sites (RIS) were identified in...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.52
更新日期:2008-07-01 00:00:00
abstract::To achieve high transgene expression in the liver, we have compared the reporter gene expression among various murine retroviral long terminal repeats (LTRs) or leader sequences in vitro. Transient reporter gene expression assays revealed the highest gene expression by the polycythemic strain of spleen focus-forming v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301655
更新日期:2002-02-01 00:00:00
abstract::The concept and application of ethical principles in the context of medical research is changing rapidly. This is especially true for fast moving fields such as gene therapy, a relatively new but rapidly maturing field offering opportunities to influence health at a fundamental level, which may become a cornerstone of...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302354
更新日期:2004-11-01 00:00:00
abstract::The clinical efficacy and safety as well as the application range of gene therapy will be broadened by developing systems capable of finely modulating the expression of therapeutic genes. Transgene regulation will be crucial for maintaining appropriate levels of a gene product within the therapeutic range, thus preven...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302251
更新日期:2004-04-01 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::Breast cancer is the leading cancer diagnosed in women and the second leading cause of cancer-related deaths in women. Current limitations to standard chemotherapy in the clinic are extensively researched, including problems arising from repeated treatments with the same drugs. The phenomenon that cancer cells become ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2016.67
更新日期:2016-12-01 00:00:00
abstract::Adenoviral gene transfer to hematopoietic stem cells (HSCs)/progenitors would provide a new approach to the treatment of hematopoietic diseases and study of the hematopoietic system. We have previously reported that an adenovirus (Ad) vector composed of whole Ad serotype 35 (Ad35), which belongs to subgroup B, shows e...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302562
更新日期:2005-10-01 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
abstract::Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of P...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.117
更新日期:2010-01-01 00:00:00