Visualization of Intrathoracically Disseminated Solid Tumors in Mice with Optical Imaging by Telomerase-Specific Amplification of a Transferred Green Fluorescent Protein Gene
Open accessAbstract
Currently available methods for detection of tumors in vivo such as X-ray, computed tomography, and ultrasonography are noninvasive and have been well studied; the images, however, are not specific for tumors. Direct optical imaging of tumor cells in vivo that can clearly distinguish them from surrounding normal tissues may be clinically useful. Here, we describe a new approach to visualizing tumors whose fluorescence can be detected using tumor-specific replication-competent adenovirus (OBP-301, Telomelysin) in combination with Ad-GFP, a replication-deficient adenovirus expressing green fluorescent protein (GFP). Human telomerase reverse transcriptase is the catalytic subunit of telomerase, which is highly active in cancer cells but quiescent in most normal somatic cells. We constructed an adenovirus 5 vector in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site and showed that OBP-301 replicated efficiently in human cancer cells, but not in normal cells such as human fibroblasts. When the human lung and colon cancer cell lines were infected with Ad-GFP at a low multiplicity of infection, GFP expression could not be detected under a fluorescence microscope; in the presence of OBP-301, however, Ad-GFP replicated in these tumor cells and showed strong green signals. In contrast, coinfection with OBP-301 and Ad-GFP did not show any signals in normal cells such as fibroblasts and vascular endothelial cells. We also found that established subcutaneous tumors could be visualized after intratumoral injection of OBP-301 and Ad-GFP. A549 human lung tumors and SW620 human colon tumors transplanted into BALB/c nu/nu mice were intratumorally injected with 8 × 105 plaque-forming units of Ad-GFP in combination with 8 × 106 plaque-forming units of OBP-301. Within 3 days of treatment, the fluorescence of the expressed GFP became visible by a three-chip color cooled charged-coupled device camera in these tumors, whereas intratumoral injection of Ad-GFP alone could not induce GFP fluorescence. Moreover, intrathoracic administration of Ad-GFP and OBP-301 could visualize disseminated A549 tumor nodules in mice after intrathoracic implantation. Our results indicate that intratumoral or intrathoracic injection of Ad-GFP in combination with OBP-301 might be a useful diagnostic method that provides a foundation for future clinical application.
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A novel approach has been developed to visualize cancer cells using a cancer-specific replication-competent adenovirus expressing GFP.
“A novel approach has been developed to visualize cancer cells using cancer-specific replication-competent adenovirus expressing the green fluorescent protein (GFP).”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [115]
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Kuroda, S., Fujiwara, T., Shirakawa, Y., Yamasaki, Y., Yano, S., Uno, F., Tazawa, H., Hashimoto, Y., Watanabe, Y., Noma, K., et al. (2011) · Okayama Igakkai Zasshi (Journal of Okayama Medical Association) · doi:10.4044/joma.123.103
Self-citationIn Vivo Imaging of Human Cancer with Telomerase-Specific Replication-Selective Adenovirus
Fujiwara, T. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-797-2_9
Self-citationŠtagljar, I., & Snider, J. D. (2009) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1164525.626290
Sugio, K., Sakurai, F., Katayama, K., Tashiro, K., Matsui, H., Kawabata, K., Kawase, A., Iwaki, M., Hayakawa, T., Fujiwara, T., et al. (2023) · doi:10.1158/1078-0432.c.6519299.v1
Self-citationSugio, K., Sakurai, F., Katayama, K., Tashiro, K., Matsui, H., Kawabata, K., Kawase, A., Iwaki, M., Hayakawa, T., Fujiwara, T., et al. (2023) · doi:10.1158/1078-0432.c.6519299
Self-citationData from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer
Sakai, R., Kagawa, S., Yamasaki, Y., Kojima, T., Uno, F., Hashimoto, Y., Watanabe, Y., Urata, Y., Tanaka, N., & Fujiwara, T. (2023) · doi:10.1158/1535-7163.c.6531678
Self-citationData from Preclinical Evaluation of Differentially Targeting Dual Virotherapy for Human Solid Cancer
Sakai, R., Kagawa, S., Yamasaki, Y., Kojima, T., Uno, F., Hashimoto, Y., Watanabe, Y., Urata, Y., Tanaka, N., & Fujiwara, T. (2023) · doi:10.1158/1535-7163.c.6531678.v1
Self-citationアポトーシス誘導replication competent adenovirus 作製とそのがん治療への応用
充宏, 中., 公文, 裕., 川嶋, 健., 紀章, 田., & 井上, 正. (2005) · doi:10.18947/cytometryresearch.15.2_15
- Authors
- Umeoka, T., Kawashima, T., Kagawa, S., Teraishi, F., Taki, M., Nishizaki, M., Kyo, S., Nagai, K., Urata, Y., Tanaka, N., & Fujiwara, T.
- Affiliations
- Okayama University (JP)
- Kanazawa University (JP)
- Oncolys BioPharma (Japan) (JP)
- Venue
- Cancer Research
- Published
- 2004-09-01
- Volume
- 64
- Issue
- 17
- Pages
- 6259-6265
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2160107647
- Cited by
- 72
- References
- 23
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 1 · 2019: 1 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 6
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Okayama University Scientific Achievement Repository (Okayama University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- tumor imaging, human telomerase reverse transcriptase, adenoviral vector, OBP-301, green fluorescent protein, lung cancer, colon cancer, tumor-specific gene expression, tumor nodules, fluorescence imaging, nude mice, A549 cells, SW620
- MeSH terms
- Adenoviridae, Animals, Carcinoma, Non-Small-Cell Lung, DNA-Binding Proteins, Female, Gene Amplification, Humans, Luminescent Proteins, Lung Neoplasms, Mice, Inbred BALB C, Mice, Nude, Microscopy, Fluorescence, Neoplasm Transplantation, Transplantation, Heterologous, Gene Transfer Techniques, Transgenes, Telomerase, Green Fluorescent Proteins, Mice
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