The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Telomerase-Specific Replication-Selective Virotherapy for Human Cancer
Abstract
Purpose: Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on human cancer cells. Experimental Design: We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in human cancer cells in vitro and in vivo. Results: TRAD induced selective E1A and E1B expression in human cancer cells, but not in normal cells such as human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Conclusions: Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in human cancer cells, an outcome that has important implications for the treatment of human cancers.
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“We developed a novel telomerase-dependent replicative adenovirus type 5 vector (Telomelysin, OBP-301) in which E1A and E1B genes, required for adenoviral replication, were transcribed under the hTERT promoter.(106)”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [106]
In the citing paper
“Indeed, Telomelysin could efficiently kill head and neck, lung, esophageal, pancreatic, hepatic, prostate, and cervical cancers, as well as melanoma, sarcoma, and mesothelioma cells.(106,110)”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [106]
Citations
Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 2×
“Many studies have demonstrated that the majority of malignant tumors express telomerase activity (4), whereas most normal cells do not (5).”
BackgroundStructure and function of telomeres
Blackburn, E. H. (1991) · Nature · doi:10.1038/350569a0 · Cited by 3,596
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
The RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227
Meyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784
An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells
Bischoff, J. R., Kirn, D. H., Williams, A., Heise, C. C., Horn, S. T., Muna, M., Ng, L., Nye, J. A., Sampson-Johannes, A., Fattaey, A., et al. (1996) · Science · doi:10.1126/science.274.5286.373 · Cited by 1,769
A Mammalian Telomerase-Associated Protein
Harrington, L. A., McPhail, T., Mar, V. L., Zhou, W., Oulton, R., Program, A. E., Bass, M. B., Arruda, I., & Robinson, M. O. (1997) · Science · doi:10.1126/science.275.5302.973 · Cited by 661
Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas
Nakayama, J., Tahara, H., 栄治, 田., Saito, M., Ito, K., Nakamura, H., Nakanishi, T., Nakanishi, E., Ide, T., & Ishikawa, F. (1998) · Nature Genetics · doi:10.1038/ng0198-65 · Cited by 605
Rodríguez, R., Schuur, E. R., Lim, H. Y., Henderson, G. A., Simons, J. W., & Henderson, D. (1997) · PubMed · Cited by 584
Kirn, D. H., Martuza, R. L., & Zwiebel, J. A. (2001) · Nature Medicine · doi:10.1038/89901 · Cited by 505
Adenovirus-Mediated p53 Gene Transfer in Advanced Non-Small-Cell Lung Cancer
Swisher, S. G., Roth, J. A., Nemunaitis, J. J., Lawrence, D. D., Kemp, B. L., Carrasco, C. H., Connors, D. G., El‐Naggar, A. K., Fossella, F. V., Glisson, B. S., et al. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.9.763 · Cited by 495
高倉, 正. (2002) · Medical Entomology and Zoology · Cited by 475
Telomerase activity in human cancer
Shay, J. W., & Wright, W. E. (1996) · Current Opinion in Oncology · doi:10.1097/00001622-199601000-00012 · Cited by 404
Rothmann, T., Hengstermann, A., Whitaker, N. J., Scheffner, M., & Hausen, H. Z. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9470-9478.1998 · Cited by 349
Reconstitution of human telomerase activity in vitro
Beattie, T. L., Zhou, W., Robinson, M. O., & Harrington, L. A. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70067-3 · Cited by 345
Kurihara, T., Brough, D. E., Kovesdi, I., & Kufe, D. W. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9180 · Cited by 237
Gu, J. H., Kagawa, S., Takakura, M., Kyo, S., Inoue, M., Roth, J. A., & Fang, B. (2000) · PubMed · Cited by 186
Self-citationA telomerase-dependent conditionally replicating adenovirus for selective treatment of cancer.
Wirth, T. C., Zender, L., Schulte, B., Mundt, B., Plentz, R. R., Rudolph, K. L., Manns, M. P., Kubicka, S., & Kühnel, F. (2003) · PubMed · Cited by 171
Matsubara, S., Wada, Y., Gardner, T. A., Egawa, M., Park, M. S., Hsieh, C., Zhau, H. E., Kao, C. H., Kamidono, S., Gillenwater, J. Y., et al. (2001) · PubMed · Cited by 149
Li, Y., Yu, D., Chen, Y., Amin, P. R., Zhang, H., Nguyen, N., & Henderson, D. (2001) · PubMed · Cited by 147
Komata, T., Kondo, Y., Kanzawa, T., Hirohata, S., Koga, S., Sumiyoshi, H., Srinivasula, S. M., Barna, B. P., Germano, I. M., Takakura, M., et al. (2001) · PubMed · Cited by 130
Self-citationGeoerger, B., Grill, J., Opolon, P., Morizet, J., Aubert, G., Terrier‐Lacombe, M., Paillerets, B. B., Barrois, M., Feunteun, J., Kirn, D. H., et al. (2002) · PubMed · Cited by 117
Adachi, Y., Reynolds, P. N., Yamamoto, M., Wang, M., Takayama, K., Matsubara, S., Muramatsu, T., & Curiel, D. T. (2001) · PubMed · Cited by 97
Abdul‐Ghani, R., Ohana, P., Matouk, I., Ayesh, S. K., Ayesh, B. M., Laster, M., Bibi, O., Giladi, H., Molnar-Kimber, K. L., Sughayer, M. A., et al. (2000) · Molecular Therapy · doi:10.1006/mthe.2000.0196 · Cited by 89
Tsukuda, K., Wiewrodt, R. G., Molnar-Kimber, K. L., Jovanovic, V. P., & Amin, K. M. (2002) · PubMed · Cited by 89
Peng, X., Won, J.-H., Rutherford, T., Fujii, T., Zelterman, D. A., Pizzorno, G., Sapi, E., Leavitt, J. C., Kacinski, B. M., Crystal, R. G., et al. (2001) · PubMed · Cited by 65
Komata, T., Kondo, Y., Kanzawa, T., Ito, H., Hirohata, S., Koga, S., Sumiyoshi, H., Takakura, M., Inoue, M., Barna, B. P., et al. (2002) · Human Gene Therapy · doi:10.1089/104303402753812421 · Cited by 62
Self-citationKomata, T., Koga, S., Hirohata, S., Takakura, M., Germano, I. M., Inoue, M., Kyo, S., Kondo, S., & Kondo, Y. (2001) · International Journal of Oncology · doi:10.3892/ijo.19.5.1015 · Cited by 35
Self-citationDeng, J., Kloosterbooer, F., Xia, W., & Hung, M. (2002) · PubMed · Cited by 26
Wirth, T. C., Zender, L., Schulte, B., Mundt, B., Plentz, R. R., Rudolph, K. L., Manns, M. P., Kuehnel, F., & Kubicka, S. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)80118-6 · Cited by 5
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Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers
Kyo, S., Takakura, M., Fujiwara, T., & Inoue, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00878.x · Cited by 347
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Ruden, M., & Puri, N. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.06.007 · Cited by 324
Nemunaitis, J. J., Tong, A. W., Nemunaitis, M., Senzer, N. N., Phadke, A. P., Bedell, C., Adams, N., Zhang, Y.-A., Maples, P. B., Chen, S., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.262 · Cited by 266
Self-citationTargeting telomerase for cancer therapy
Guterres, A. N., & Villanueva, J. (2020) · Oncogene · doi:10.1038/s41388-020-01405-w · Cited by 265
Metadata
- Authors
- Kawashima, T., Kagawa, S., Kobayashi, N., Shirakiya, Y., Umeoka, T., Teraishi, F., Taki, M., Kyo, S., Tanaka, N., & Fujiwara, T.
- Affiliations
- Okayama University (JP)
- Kanazawa University (JP)
- Venue
- Clinical Cancer Research
- Published
- 2004-01-01
- Volume
- 10
- Issue
- 1
- Pages
- 285-292
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2128023051
- Cited by
- 262
- References
- 30
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 10 · 2023: 19 · 2022: 9 · 2021: 16 · 2020: 15 · 2019: 3 · 2018: 10 · 2017: 7 · 2016: 13 · 2015: 7 · 2014: 5 · 2013: 12 · 2012: 15
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Keywords
- telomerase, human telomerase reverse transcriptase, replication-competent adenovirus, virotherapy, hTERT promoter, internal ribosome entry site, anticancer activity, intratumoral injection, tumor growth inhibition
- MeSH terms
- Adenoviridae, Adenoviridae Infections, Animals, Carcinoma, Non-Small-Cell Lung, Colonic Neoplasms, Cytopathogenic Effect, Viral, Female, Fibroblasts, Genetic Vectors, Humans, Lung Neoplasms, Mice, Inbred BALB C, Mice, Nude, Promoter Regions, Genetic, Virus Replication, Gene Expression Regulation, Viral, Gene Expression Regulation, Neoplastic, Apoptosis, Adenovirus E1 Proteins, Telomerase, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, In Vitro Techniques
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