Abstract:
:Specificity is a prerequisite for systemic gene therapy of hepatocarcinoma. In vitro, the tumor-specific viral death effector Apoptin selectively induces apoptosis in malignant hepatic cells. Intratumoral treatment of xenografted subcutaneous hepatomas with Apoptin results in tumor regression. Here, we report a systemic delivery vehicle containing the Apoptin gene linked to asialoglycoprotein (Asor), which targets asialoglycoprotein receptor (ASGPR) present only on the surface of hepatocytes. In vitro, the protein-DNA complex Asor-Apoptin induced apoptosis in HepG2 hepatocarcinoma cells but not in normal L-02 hepatocytes. Non-hepatocyte-derived tumorigenic human A549 cells lacking the membrane ASGPR were not affected by Asor-Apoptin. In vivo systemic delivery of Asor-Apoptin via the tail vein into mice bearing in situ hepatocarcinoma resulted in specific and efficient distribution of Apoptin in both hepatocarcinoma cells and normal hepatocytes. Five days after injection of Asor-Apoptin, the in situ hepatocarcinomas showed significant signs of regression, whereas the surrounding normal hepatocytes did not. Systemically delivered Asor-LacZ expressing non-apoptotic LacZ gene did not inhibit tumor growth. Our data reveal that systemic delivery of Asor-Apoptin specifically induces apoptosis in malignant hepatocytes and thus constitutes a powerful and safe therapeutics against hepatocarcinomas.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Peng DJ,Sun J,Wang YZ,Tian J,Zhang YH,Noteborn MH,Qu Sdoi
10.1038/sj.cgt.7700985subject
Has Abstractpub_date
2007-01-01 00:00:00pages
66-73issue
1eissn
0929-1903issn
1476-5500pii
7700985journal_volume
14pub_type
杂志文章abstract::Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene gamma(1)34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700890
更新日期:2006-03-01 00:00:00
abstract::Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700938
更新日期:2006-06-01 00:00:00
abstract::Chemotherapy remains the main tool for the treatment of cancers, but is often hampered by tumor cell resistance. In this context, the transfer of genes able to accentuate the effect of anticancer drugs may constitute a useful approach, as exemplified by inactivation of nuclear factor (NF)-kappa B via direct transfer o...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700467
更新日期:2002-06-01 00:00:00
abstract::NPS-2143 is a calcium-sensing receptor (CaSR) antagonist that has been demonstrated to possess anticancer activity. To date, the effects of NPS-2143 on gastric cancer (GC) cell growth, motility, and apoptosis have not been investigated. In the present study, we firstly investigated the expression of CaSR in GC tissues...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0128-4
更新日期:2020-08-01 00:00:00
abstract::B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) h...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.35
更新日期:2013-07-01 00:00:00
abstract::Chimeric antigen receptor (CAR) therapy has shown promise against B cell malignancies in the clinic. However, limited success in patients with solid tumors has prompted the development of new CAR strategies. In this study, a B7H6-specific CAR was combined with different variants of T-bet, a transcription factor that a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-018-0012-7
更新日期:2018-06-01 00:00:00
abstract::To improve the expression levels of transgenes in malignant hematopoietic cells, we developed a novel adenoviral-alphavirus hybrid vector Ad5/F11p-SFV-GFP that contains a Semliki Forest Virus (SFV) replicon and chimeric fibers of Ad5 and Ad11p. Ad5/F11p-SFV-GFP infected >95% of K562, U937 or Jurkat cells and 23.65% of...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.37
更新日期:2013-08-01 00:00:00
abstract::Salmonella typhimurium (hereafter S. typhimurium), as Gram-negative facultative anaerobic bacteria, are good candidates for cancer therapy and delivering therapeutic antitumor agents. However, it is necessary to reduce the virulence of such bacteria and enhance their tumor-targeting ability, and their immunostimulator...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-018-0021-6
更新日期:2018-08-01 00:00:00
abstract::We aimed to analyze the association between the distribution of dendritic cells (DC) with expression of tumor-infiltrating T lymphocytes and clinicopathologic parameters with prognosis in epithelial ovarian cancer (EOC). Thirty-three EOC patient samples were surgically resected, and pathology was examined for clinicop...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.7
更新日期:2015-03-01 00:00:00
abstract::The growth of new blood vessels is an essential condition for the development of tumors with a diameter greater than 1-2 mm and also for their metastatic dissemination. RNasin, the placental ribonuclease inhibitor, is known to have antiangiogenic activity through the inhibition of angiogenin and basic fibroblast growt...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700302
更新日期:2001-04-01 00:00:00
abstract::The success of cancer gene therapies requiring in vivo gene transfer is severely hampered by the low efficacy of gene transfer, which has been difficult to improve. We therefore established a novel strategy to increase the share of transduced cells post gene transfer. We hypothesized that in vivo selection of tumor ce...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700995
更新日期:2007-01-01 00:00:00
abstract::Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 f...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700957
更新日期:2006-08-01 00:00:00
abstract::Combination therapy with replicative oncolytic viruses is a recent topic in innovative cancer therapy, but few studies have examined the efficacy of oncolytic adenovirus plus replication-deficient adenovirus carrying a suicide gene. We aim to evaluate whether an E1A, E1B double-restricted oncolytic adenovirus, AxdAdB-...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.67
更新日期:2009-02-01 00:00:00
abstract::A novel gene, HA117, was discovered in our previous work. Using the pSOS-HUS vector method which we designed at previous study, we screened for small interfering RNAs (siRNAs) that targeted HA117. The pSOS-HUS siRNA screening results were verified and a delivery system was developed that contained a recombinant adenov...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.32
更新日期:2011-09-01 00:00:00
abstract::Engineered retroviruses are widely used vectors for cancer gene therapy approaches. However, the ability to target cells of therapeutic interest while controlling the expression of the transferred genes would improve both the efficiency and the safety of viral vectors. In this study, we investigated the ability of a r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700640
更新日期:2003-11-01 00:00:00
abstract::The aim of the present study is to identify the optimal anticancer agents for use in combination with gene therapy using wild-type (wt) p53 gene transfer. We used adenoviral vectors expressing human wt p53 (AdCAp53) and investigated the effects of wt p53 gene transfer in combination with 12 anticancer agents on a huma...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700096
更新日期:2000-02-01 00:00:00
abstract::MicroRNAs (miRNAs) were discovered more than a decade ago as noncoding, single-stranded small RNAs (approximately 22 nucleotides) that control the timed gene expression pattern in Caenorhabditis elegans life cycle. A number of these evolutionarily conserved, endogenous miRNAs have been shown to regulate mammalian cell...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2008.8
更新日期:2008-06-01 00:00:00
abstract::MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. In this study, we investigate whether let-7b acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. We analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and adjacent ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.75
更新日期:2015-04-01 00:00:00
abstract::Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2/neu-expressing tumors in mice by delivering an interleukin-2 fusion ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700786
更新日期:2005-04-01 00:00:00
abstract::Circular RNAs (circRNAs) are involved in the regulation of many pathophysiological processes as non-coding RNAs. This study focuses on the role of circRACGAP1 in the development of non-small cell lung cancer (NSCLC). Expression patterns of circRACGAP1 and miR-144-5p in NSCLC tissues and cell lines were quantified by q...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00209-0
更新日期:2020-08-11 00:00:00
abstract::Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00274-5
更新日期:2020-12-14 00:00:00
abstract::Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700967
更新日期:2006-10-01 00:00:00
abstract::We report that radiation enhances the antitumor efficacy of the oncolytic adenovirus vector VRX-007 in Syrian hamster tumors. We used tumor-specific irradiation of subcutaneous tumors and compared treatment options of radiation alone or combined with VRX-007 and cyclophosphamide (CP). Radiation therapy further augment...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.50
更新日期:2013-09-01 00:00:00
abstract::We recently described a novel nonviral/viral vector for gene transfer, the plasmovirus (Noguiez-Hellin P, Robert-le Meur M, Laune S, et al. C R Acad Sci Paris, Sciences de la Vie. 1996;319:45-50; Noguiez-Hellin P, Robert-le Meur M, Salzmann J-L, et al. Proc Natl Acad Sci USA. 1996;93:4175-4180). Plasmoviruses are plas...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Enginee...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2012.59
更新日期:2012-11-01 00:00:00
abstract::E6AP was originally identified as the ubiquitin-protein ligase involved in human papillomavirus (HPV) E6-mediated p53 degradation and has since been shown to act as an E3 ubiquitin-protein ligase in the ubiquitination of several other protein substrates. To further define E6AP function at the molecular and cellular le...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700623
更新日期:2003-09-01 00:00:00
abstract::Tumor-endothelial interaction contributes to local prostate tumor growth and distant metastasis. In this communication, we designed a novel approach to target both cancer cells and their "crosstalk" with surrounding microvascular endothelium in an experimental hormone refractory human prostate cancer model. We evaluat...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700790
更新日期:2005-03-01 00:00:00
abstract::A nonviral gene delivery vector has been developed in our laboratory based on the cationic polymer, poly(2-(dimethylethylamino)ethyl methacrylate) (p(DMAEMA)). p(DMAEMA)-based polyplexes have been successfully used for the transfection of OVCAR-3 cells in vitro. However, these polyplexes were unable to transfect OVCAR...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700311
更新日期:2001-06-01 00:00:00
abstract::T cells can be reprogrammed to redirect specificity to tumor-associated antigens (TAAs) through the enforced expression of chimeric antigen receptors (CARs). The prototypical CAR is a single-chain molecule that docks with TAA expressed on the cell surface and, in contrast to the T-cell receptor complex, recognizes tar...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2014.69
更新日期:2015-03-01 00:00:00
abstract::The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integr...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.64
更新日期:2016-12-01 00:00:00