Inhibition of Retinoblastoma In Vitro and In Vivo with Conditionally Replicating Oncolytic Adenovirus H101

Song, Xin; Zhou, Yixiong; Jia, Renbing; Xu, Xiaofang; Wang, Haibo; Hu, Ji-Fan; Ge, Shengfang

doi:10.1167/iovs.09-3516

Cited by 25 publications

(32 citation statements)

References 32 publications

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“…Nevertheless, the differences in action of DTIC may be due to different concentrations used (2 mM vs. 5 mg/ml). In addition, tumor cell lysis caused by oncolytic adenovirus has been previously shown to block the cell cycle at the G 2 /M phase, 10,23 which is consistent with our data and caused a distinct accumulation of cells in S and G 2 phases. The combination, however, did not lead to an obvious cell arrest in a certain phase.…”

Section: Discussionsupporting

confidence: 92%

“…The deletion of the 78.3-85.8 mm gene segment in the E3 region, which includes the adenovirus death protein, enhances the safety of the product. 10 It has been previously demonstrated that H101 exhibits potential antitumor activity with low toxicity and good tolerance in vitro and in vivo. 10,11 However, the therapeutic effect of H101 on UM has not been previously investigated.…”

Section: Introductionmentioning

confidence: 99%

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Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Cun¹,

Song²,

Jia³

et al. 2012

Cancer Biology & Therapy

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These authors contributed equally to this work.Keywords: uveal melanoma, oncolytic adenovirus, dacarbazine, combination therapy, cell cycle Uveal melanoma is the most common primary intraocular malignancy in adults; however, current therapeutic modalities, including chemotherapy, have not been successful. Oncolytic viruses serve as an emerging gene therapy tool for cancer treatment because they specifically kill tumor cells while sparing normal cells. The oncolytic virus H101 has been approved by the Chinese State Food and Drug Administration for the treatment of certain malignancies. Unfortunately, the monotherapy of adenovirus has demonstrated limited efficacy in a clinical setting. Thus, novel treatment strategies in which an oncolytic virus is combined with existing chemicals are advancing toward potential clinical use. In this study, we chose the combination of oncolytic virus H101 and the alkylating agent dacarbazine (DTIC) to treat uveal melanoma cells in vitro. Our results demonstrated that the combination exerted a synergistic antitumor effect without enhanced toxicity to normal cells via a type of cell cycle block other than the induction of apoptosis. Further investigation is warranted to elucidate the specific underlying mechanisms of this co-treatment therapy. Our study suggests the virochemo combination therapy is feasible and is a potentially promising approach for the treatment of uveal melanoma.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Cun¹,

Song²,

Jia³

et al. 2012

Cancer Biology & Therapy

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“…We then evaluated the cytopathic effect of Ad/SA infection in the cell panel. These viruses were as potent as wild-type (wt) adenovirus in NSCLC cell lines and far more potent than Oncorine, 21 the only CRAd used in clinic. Ad/SA had a significant lytic effect at a multiplicity of infection (MOI) as low as 0.5 in all NSCLC cell lines (Figure 3b).…”

Section: Resultsmentioning

confidence: 99%

“…For large A-431 tumor xenografts, a high dose of cisplatin (150 mg) was given twice (days 0 and 10), and the cetuximab treatment period was extended to 4 weeks, as per a previously published protocol. 21 Moribund mice were killed when the experimental end point (tumor size exceeding 2 cm) was reached.…”

Section: Immunoblot Analysismentioning

confidence: 99%

S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma

Lee

Yun²,

Yun

et al. 2011

Gene Ther

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“…Therefore, Ads-mediated p53 cancer gene therapy constitutes a promising treatment approach for patients with ESCC (34). H101 is a recombinant human type 5 Ads with a total deletion of the E1B 55 K gene, which is able to proliferate effectively in p53 mutant cells, but not in p53 wild-type cells (35). However, H101 has limited potential for the eradication of tumors when used as a monotherapy due to its low infection efficiency (10).…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitor trichostatin A enhances the antitumor effect of the oncolytic adenovirus H101 on esophageal squamous cell carcinoma in vitro and in vivo

Zhao

et al. 2017

Oncology Letters

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Abstract. Replication-selective oncolytic virotherapy provides a novel modality to treat cancer by inducing cell death in tumor cells but not in normal cells. However, the utilization of oncolytic viruses as a stand-alone treatment is problematic due to their poor transduction efficiency in vivo. H101 was the first oncolytic adenovirus (Ads) to be approved by the Chinese FDA, and exhibits modest antitumor effects when applied as a single agent. The multiple histone deacetylase inhibitor trichostatin A (TSA) has been demonstrated to potently enhance the spread and replication of oncolytic Ads in several infection-resistant types of cancer. The present study aimed to investigate the antitumor effects of H101 in combination with TSA on esophageal squamous cell carcinoma (ESCC) in vitro and in vivo, and determine the mechanisms underlying these effects. H101 and TSA in combination increased the survival of mice harboring human ESCC cell line-tumor xenografts, as compared with mice treated with these agents individually. Therefore, TSA may enhance the antitumor effects of H101 in ESCC.

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Inhibition of Retinoblastoma In Vitro and In Vivo with Conditionally Replicating Oncolytic Adenovirus H101

Abstract: These results suggest that H101 effectively inhibits the growth of retinoblastoma cells in vitro and in mice and may serve as a novel therapy for retinoblastoma.

Cited by 25 publications

References 32 publications

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

Combination of oncolytic adenovirus and dacarbazine enhances antitumor ability against uveal melanoma cells via cell cycle block

S100A2 promoter-driven conditionally replicative adenovirus targets non-small-cell lung carcinoma

Histone deacetylase inhibitor trichostatin A enhances the antitumor effect of the oncolytic adenovirus H101 on esophageal squamous cell carcinoma in vitro and in vivo

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