ArticleScientific reports2018
Hepatocellular carcinoma-targeting oncolytic adenovirus overcomes hypoxic tumor microenvironment and effectively disperses through both central and peripheral tumor regions.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Advancements on the synergistic application of oncolytic viruses and molecularly targeted therapies for the treatment of solid tumors (Review).International journal of oncology · 2026Review
- Adenoviruses Encapsulated in PEGylated DOTAP-Folate Liposomes Are Protected from the Pre-Existing Humoral Immune Response.Pharmaceutics · 2025Article
- p53-Bad* Fusion Gene Therapy Induces Apoptosis In Vitro and Reduces Zebrafish Tumor Burden in Hepatocellular Carcinoma.Molecular pharmaceutics · 2023Article
- Immunotherapy by mesenchymal stromal cell delivery of oncolytic viruses for treating metastatic tumors.Molecular therapy oncolytics · 2022Review
- Tumor-targeted fluorescence labeling systems for cancer diagnosis and treatment.Cancer science · 2022Review
- Oncolytic virus: A catalyst for the treatment of gastric cancer.Frontiers in oncology · 2022Review
- Polymer Coated Oncolytic Adenovirus to Selectively Target Hepatocellular Carcinoma Cells.Pharmaceutics · 2021Article
- CRISPR-Cas12a with an oAd Induces Precise and Cancer-Specific Genomic Reprogramming of EGFR and Efficient Tumor Regression.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Strategies for Targeting Gene Therapy in Cancer Cells With Tumor-Specific Promoters.Frontiers in oncology · 2020Review
- Analysis of endogenous and exogenous tumor upregulated promoter expression in canine tumors.PloS one · 2020Article
- Overcoming the limitations of locally administered oncolytic virotherapy.BMC biomedical engineering · 2019Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-specific promoter driven replication of oncolytic adenovirus (Ad) is cancer-specific, but shows low transcriptional activity. Thus, we generated several chimeric α-fetoprotein (AFP) promoter variants, containing reconstituted enhancer and silencer regions, to preferentially drive Ad replication in hepatocellular carcinoma (HCC). Modified AFP promoter, containing 2 enhancer A regions and a single enhancer B region (a2bm), showed strong and HCC-specific transcription. In AFP-positive HCCs, gene expression was 43- to 456-fold higher than those of control AFP promoter lacking enhancers. a2bm promoter was further modified by inserting multiple hypoxia-responsive elements (HRE) to generate Ha2bm promoter, which showed stronger transcriptional activity than a2bm promoter under hypoxic conditions. Ha2bm promoter-regulated oncolytic Ad (Ha2bm-d19) showed a stronger antitumor and proapoptotic effect than did a2bm promoter-regulated oncolytic Ad (a2bm-d19) in HCC xenograft tumors. Systemically administered Ha2bm-d19 caused no observable hepatotoxicity, whereas control replication-competent Ad, lacking cancer specificity (d19), induced significant hepatic damage. Ha2bm-d19 caused significantly lower expression of interleukin-6 than d19, showing that HCC-targeted delivery of Ad attenuates induction of the innate immune response against Ad. This chimeric AFP promoter enabled Ad to overcome the hypoxic tumor microenvironment and target HCC with high specificity, rendering it a promising candidate for the treatment of aggressive HCCs.
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