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-3, can improve the efficacy for gallbladder cancers (GBCs) of the replication-deficient adenovirus-based herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) therapy directed by the carcinoembryonic antigen (CEA) promoter. Cytopathic effects of AxdAdB-3 plus AxCEAprTK (an adenovirus expressing HSVtk directed by CEA promoter) or AxCAHSVtk (an adenovirus expressing HSVtk directed by a nonspecific CAG promoter) with GCV administration were examined in several GBC lines and normal cells. Efficacy in vivo was tested in severe combined immunodeficiency disease mice with GBC xenografts. Addition of AxdAdB-3 (1 multiplicity of infection, MOI) significantly enhanced the cytopathic effects of AxCEAprTK (10 MOI)/GCV on GBC cells. The augmented effect was attributable to the replication of the AxCEAprTK and also to the enhanced CEA promoter activity, which was presumably transactivated by E1A. In normal cells, AxdAdB-3 (20 MOI) plus AxCEAprTK (200 MOI)/GCV was not cytopathic, whereas AxdAdB-3 (1 MOI) plus AxCAHSVtk (10 MOI)/GCV was significantly toxic. Low-dose AxdAdB-3 (2 x 10(7) PFU, plaque-forming unit) plus AxCEAprTK (2 x 10(8) PFU)/GCV significantly suppressed the growth of GBC xenografts as compared with either AxdAdB-3 (2 x 10(7) PFU)/GCV or AxCEAprTK (2 x 10(9) PFU)/GCV alone. E1A, E1B double-restricted replicating adenovirus at low dose significantly augmented the efficacy of CEA promoter-directed HSVtk/GCV therapy without obvious toxicity to normal cells, suggesting a potential use of this combination for treating GBC and other CEA-producing malignancies.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Fukuda K,Abei M,Ugai H,Kawashima R,Seo E,Wakayama M,Murata T,Endo S,Hamada H,Hyodo I,Yokoyama KKdoi
10.1038/cgt.2008.67subject
Has Abstractpub_date
2009-02-01 00:00:00pages
126-36issue
2eissn
0929-1903issn
1476-5500pii
cgt200867journal_volume
16pub_type
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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doi:10.1038/sj.cgt.7700873
更新日期:2006-02-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章,撤回出版物
doi:10.1038/s41417-019-0158-y
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abstract::Expression of costimulatory molecules by recombinant poxviruses is a promising strategy for enhancing therapeutic vaccines. CD40-CD40L interactions are critical for conditioning dendritic cells (DC) and priming T- and B-cell immunity. We constructed a vaccinia virus expressing murine CD40L (rV-CD40L) and studied its i...
journal_title:Cancer gene therapy
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doi:10.1038/sj.cgt.7700762
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章,多中心研究
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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
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential r...
journal_title:Cancer gene therapy
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更新日期:2020-11-30 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700707
更新日期:2004-05-01 00:00:00
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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abstract::A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 ce...
journal_title:Cancer gene therapy
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更新日期:1997-03-01 00:00:00
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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更新日期:2006-08-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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更新日期:2012-01-01 00:00:00
abstract::Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-017-0001-2
更新日期:2018-02-01 00:00:00
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journal_title:Cancer gene therapy
pub_type: 杂志文章
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更新日期:2011-10-01 00:00:00
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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::Adenoviral vectors are widely used in cancer gene therapy. After systemic administration however, the majority of the virus homes to the liver and the expressed transgene may cause hepatotoxicity. To restrict transgene expression to tumor cells, tumor- or tissue-specific promoters are utilized. The tumor antigen epith...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700882
更新日期:2006-02-01 00:00:00