Adenovirus-mediated delivery of human IFNγ gene inhibits prostate cancer growth

Zhao, Peng; Zhu, Ying; Wu, Jiang; Liu, Ran Yi; Zhu, Xiu Yun; Xiao, Xia; Li, Hong Li; Huang, Bi; Xie, Fa Jun; Chen, Jiemin; Ke, Miao La; Huang, Wenlin

doi:10.1016/j.lfs.2007.05.028

Cited by 24 publications

(22 citation statements)

References 24 publications

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“…For the TUNEL assay, 48 NPC cells transiently transfected with siRNAs or stably overexpressing BST2 were incubated with cisplatin for 24 h in glass-bottom cell culture dishes (NEST Biotechnology, Wuxi, China). The cells were then subjected to a TUNEL assay using DeadEnd Fluorometric TUNEL System (Promega).…”

Section: Methodsmentioning

confidence: 99%

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

Kuang

Hua

et al. 2017

Cell Death Dis

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Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients. We previously generated a cisplatin-sensitive NPC cell line, S16, from CNE2 cells and found that eIF3a, ASNS and MMP19 are upregulated in S16 cells, which contributes to their cisplatin sensitivity. In this study, we found that BST2 is downregulated in cisplatin-sensitive S16 cells compared with CNE2 cells. Knockdown of BST2 in NPC cells sensitized their response to cisplatin and promoted cisplatin-induced apoptosis, whereas exogenous overexpression of BST2 increased their cisplatin resistance and inhibited cisplatin-induced apoptosis. Further investigation demonstrated that BST2-mediated cisplatin resistance depended on the activation of the NF-κB signaling pathway and consequent upregulation of anti-apoptotic genes, such as Bcl-XL and livin. Moreover, an analysis of clinical data revealed that a high BST2 level might serve as an independent indicator of poor prognosis in patients with locally advanced NPC treated with platinum-based chemoradiotherapy. These findings suggest that BST2 likely mediates platinum resistance in NPC, offering guidance for personalized and precise treatment strategies for patients with NPC.

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Section: Methodsmentioning

confidence: 99%

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

Kuang

Hua

et al. 2017

Cell Death Dis

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“…Ad/hIFN-␥ is a replication-incompetent recombinant adenovirus in which human IFN-␥ was inserted into an Ad5-based vector. Preclinical work in our laboratory established that sustained expression of human IFN-␥ in several different cell lines (including prostate carcinoma DU-145, PC-3, and human leukemia cell line K562) could inhibit tumor cell proliferation and hepatic fibrosis in vitro and in vivo (L. Li et al, 2006;Zhao et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Long-Term Toxicity of Ad/hIFN-γ, an Adenoviral Vector Encoding the Human Interferon-γGene, in Nonhuman Primates

Shao²,

Liu³

et al. 2008

Human Gene Therapy

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Interferon-gamma(IFN-gamma) plays an important role in the immunomodulation and growth inhibition of many tumor cells, but its clinical application is limited by its systemic toxicity. Ad/hIFN-gamma, a nonreplicating adenoviral vector encoding human IFN-gamma, has been reported to inhibit tumor growth in vitro and in a xenograft model. In this study, the long-term toxicity of Ad/hIFN-gamma was assessed in cynomolgus macaques (Macaca fascicularis). Thirty animals were enrolled into 5 groups, and administered intramuscularly, respectively, Ad/hIFN-gamma (3.3 x 10(10), 3.3 x 10(11), or 3.3 x 10(12) VP/kg), Ad/LacZ (vector control, 3.3 x 10(11) VP/kg), or excipient 3 times per week for 8 weeks, followed by a 4-week recovery period. At 12 weeks all experimental animals appeared generally healthy, and there were no statistically significant differences in body weight, urinalysis, hemogram, blood biochemistry, and electrocardiogram results between the treatment and control groups. No significant toxic effects were noted on macroscopic and microscopic examinations of organs and tissues. Preliminary investigation of the immunotoxicity of Ad/IFN-gamma indicated that anti-adenoviral and anti-hIFN-gamma antibodies were generated. These data demonstrate that long-term, high-dose intramuscular administration of Ad/IFN-gamma was not notably toxic and might be safe for clinical therapeutic use.

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“…Therefore, instead of IFN-γ molecule, IFN-γ-encoding gene has been used for the local production of IFN-γ by introducing the gene into immune cells or cancerous cells of diseased tissues [28][29][30][31][32].…”

Section: A N U S C R I P Tmentioning

confidence: 99%

“…To date, viral vectors of various kinds based on adenovirus, adeno-associated virus, and retrovirus have been used to deliver IFN-γ-encoding gene in vivo [28][29][30][31][32]. However, non-viral vectors with low immunogenicity and no pathogenicity might be preferred for gene delivery considering that virus-based gene vectors might entail risks of unexpected immune responses derived from viral components [33,34].…”

Section: A N U S C R I P Tmentioning

confidence: 99%