Abstract:
:In order to determine the potential of alternative splicing as a means of targeting the expression of therapeutic genes to tumor cells in vivo, a series of episomal plasmid-based "splice-activated gene expression" (pSAGE) vectors was generated, which contain minigene cassettes composed of various combinations of the three alternatively spliced exons present in the differentially expressed adhesion protein CD44R1 (v8, v9, and v10) with or without their corresponding intronic sequences, positioned in-frame between the CD44 leader sequence and a "leaderless" human liver/bone/kidney alkaline phosphatase (ALP) cDNA. Because both the v8-v9 and v9-v10 introns contain multiple in-frame stop codons, the expression and enzymatic activity of ALP are dependent upon the accurate removal of intronic sequences from the pre-mRNA transcripts encoded by these constructs. The various pSAGE constructs were introduced into CD44H-positive (T24) and CD44R1-positive (PC3) target cells by electroporation and transfectants selected in hygromycin B. ALP expression was determined by staining with the ALP substrate, BCIP/INT, and the transfected cells tested for their sensitivity to the inactive prodrug, etoposide phosphate. ALP-mediated dephosphorylation of etoposide phosphate generates the potent topoisomerase II inhibitor etoposide. The data obtained indicate that whereas the v8-v9 intron is spliced in both CD44H- and CD44R1-positive cells, the v9-v10 intron is efficiently and accurately removed only in CD44R1-positive cells. Furthermore, only CD44R1-positive cells were sensitized to etoposide phosphate when transfected with the v9-v10.ALP construct. These data emphasize the potential usefulness of alternative splicing as a novel means of targeting gene expression to tumor cells in vivo.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Hayes GM,Carpenito C,Davis PD,Dougherty ST,Dirks JF,Dougherty GJdoi
10.1038/sj.cgt.7700427subject
Has Abstractpub_date
2002-02-01 00:00:00pages
133-41issue
2eissn
0929-1903issn
1476-5500journal_volume
9pub_type
杂志文章abstract::Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700237
更新日期:2000-10-01 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::Interferon-gamma (IFN-γ) exhibits biological activities that are considered to have important roles in tumor suppression. Therefore, the IFN-γ gene is a potential candidate for in vivo cytokine gene therapy against skin cancer. The present study evaluated the efficacy of a hydrodynamics-based IFN-γ gene transfection f...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.36
更新日期:2011-09-01 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::Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted to overcome tumor-induced T-cell anergy by the direct injection of vectors carrying the genes encoding one of a variety of cytokines. We hypothesised that the polyclonal stimulation o...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700461
更新日期:2002-05-01 00:00:00
abstract::Replication-selective oncolytic viruses are being developed for human cancer therapy. We previously developed an attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site. OBP-301...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.57
更新日期:2012-11-01 00:00:00
abstract::Histological grading (HG) is an important prognostic factor of colorectal adenocarcinoma (CRAC): the high-grade CRAC patients have poorer prognosis after tumor resection. Especially, the high-grade stage II CRAC patients are recommended to receive adjuvant chemotherapy. Due to the subjective nature of HG assessment, i...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0139-1
更新日期:2020-09-01 00:00:00
abstract::Despite the fact that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells, TRAIL resistance in cancer cells has challenged the use of TRAIL as a therapeutic agent. First, prostate carcinoma cell lines (DU145, LNCaP and PC3) were screened for sensitivity to a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700877
更新日期:2006-01-01 00:00:00
abstract::At the Eleventh International Conference on Gene Therapy of Cancer (December 12-14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.cgt.7700602
更新日期:2003-07-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.7
更新日期:2016-06-01 00:00:00
abstract::Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modula...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.29
更新日期:2014-07-01 00:00:00
abstract::In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700776
更新日期:2005-02-01 00:00:00
abstract::The antitumor activity of a recombinant canarypox virus expressing wild type murine p53 (ALVAC-p53) was investigated in two murine syngeneic tumors harboring an endogenous p53 mutation (CMS4 and TS/A). Direct intratumor injections of ALVAC-p53 in CMS4 pre-established subcutaneous tumors induced total tumor regression ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700279
更新日期:2001-02-01 00:00:00
abstract::Apatinib, a selective vascular endothelial growth factor receptor 2-tyrosine kinase inhibitor, has demonstrated activity against a wide range of solid tumors, including advanced hepatocellular carcinoma (HCC). Preclinical and preliminary clinical results have confirmed the synergistic antitumor effects of apatinib in ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-0186-7
更新日期:2020-06-12 00:00:00
abstract::The prognosis of glioblastoma remains poor despite intensive research efforts. Glioblastoma stem cells (GSCs) contribute to tumorigenesis, invasive capacity, and therapy resistance. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a stem cell marker, is involved in the maintenance of GSCs, although ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00282-5
更新日期:2021-01-07 00:00:00
abstract::Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701093
更新日期:2008-01-01 00:00:00
abstract::All animal experiments were approved by the Animal Care and Use Committee (ACUC), Louisiana State University Health Science Center and not The People's Hospital of Liaoning Province as indicated in the original version of the Article. The PDF and HTML versions of the Article have been modified accordingly. ...
journal_title:Cancer gene therapy
pub_type: 已发布勘误
doi:10.1038/s41417-019-0082-1
更新日期:2019-07-01 00:00:00
abstract::Various therapeutic approaches toward killing glioma cells by inducing apoptosis have been developed, but these approaches are often hampered by anti-apoptotic mechanisms. In this study, we attempted to develop a technique that overrides the resistance toward apoptosis in glioma cells. To date, p53- and Fas-mediated a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700160
更新日期:2000-05-01 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::Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the d...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.75
更新日期:2013-01-01 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::Transforming growth factor-beta (TGF-beta) is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-beta by malignant cells may therefore be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In order to evaluate the role of tumor-derived TGF-beta on tumor...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Multicomponent lipoplexes have recently emerged as especially promising transfection candidates, as they are from 10 to 100 times more efficient than binary complexes usually employed for gene delivery purposes. Previously, we investigated a number of chemical-physical properties of DNA-lipid complexes that were propo...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.12
更新日期:2011-08-01 00:00:00
abstract::ING4 as a member of inhibitor of growth (ING) tumor suppressor family has potent inhibitory effects on a variety of tumors. Interleukin-24 (IL-24), a cytokine-tumor suppressor, also shows broad-spectrum and tumor-specific antitumor activities. In this report, we constructed an ING4/IL-24 bicistronic adenovirus (Ad-ING...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.31
更新日期:2011-09-01 00:00:00
abstract::Most cancer vaccines to date have made use of common tumor antigens or allogenic cancer cell lines. The majority of tumor antigens may, however, be unique patient-specific antigens. Dendritic cells (DCs) are the most potent antigen-presenting cells known. The present report is a full-scale preclinical evaluation of au...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700837
更新日期:2005-06-01 00:00:00
abstract::Delivery of the full-length tumor antigen might be more successful in immunotherapy than single peptides and has the advantage that patients no longer need to be selected for their HLA type. In this study, we tested the in vitro induction of CAMEL/NY-ESO-ORF2-specific T cells by dendritic cells infected with an adenov...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700674
更新日期:2004-03-01 00:00:00
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 system...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700985
更新日期:2007-01-01 00:00:00
abstract::Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transc...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700846
更新日期:2005-12-01 00:00:00
abstract::Suicide gene therapy using herpes simplex virus type-1 (HSV-1) thymidine kinase (TK) is a widely exploited approach for gene therapy of cancer and other hyperproliferative disorders. Despite its popularity, clinical success has been so far hampered mostly by the relative inefficiency of TK gene transfer and its limite...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700526
更新日期:2003-01-01 00:00:00
abstract::The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancer...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700226
更新日期:2000-09-01 00:00:00