論文 - 詳細
| RRC ID | 37633 |
|---|---|
| 著者 | Kurihara Y, Watanabe Y, Onimatsu H, Kojima T, Shirota T, Hatori M, Liu D, Kyo S, Mizuguchi H, Urata Y, Shintani S, Fujiwara T. |
| タイトル | Telomerase-specific virotheranostics for human head and neck cancer. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:Long-term outcomes of patients with squamous cell carcinoma of the head and neck (SCCHN) remain unsatisfactory despite advances in combination of treatment modalities. SCCHN is characterized by locoregional spread and it is clinically accessible, making it an attractive target for intratumoral biological therapies. EXPERIMENTAL DESIGN:OBP-301 is a type 5 adenovirus that contains the replication cassette in which the human telomerase reverse transcriptase promoter drives expression of the E1 genes. OBP-401 contained the replication cassette and the green fluorescent protein (GFP) gene. The antitumor effects of OBP-301 were evaluated in vitro by the sodium 30-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate assay and in vivo in an orthotopic xenograft model. Virus spread into the lymphatics was also orthotopically assessed by using OBP-401. RESULTS:Intratumoral injection of OBP-301 resulted in the shrinkage of human SCCHN tumors orthotopically implanted into the tongues of BALB/c nu/nu mice and significantly recovered weight loss by enabling oral ingestion. The levels of GFP expression following ex vivo infection of OBP-401 may be of value as a positive predictive marker for the outcome of telomerase-specific virotherapy. Moreover, whole-body fluorescent imaging revealed that intratumorally injected OBP-401 could visualize the metastatic lymph nodes, indicating the ability of the virus to traffic to the regional lymphatic area and to selectively replicate in neoplastic lesions, resulting in GFP expression and cell death in metastatic lymph nodes. CONCLUSIONS:These results illustrate the potential of telomerase-specific oncolytic viruses for a novel therapeutic and diagnostic approach, termed theranostics, for human SCCHN. |
| 巻・号 | 15(7) |
| ページ | 2335-43 |
| 公開日 | 2009-4-1 |
| DOI | 10.1158/1078-0432.CCR-08-2690 |
| PII | 1078-0432.CCR-08-2690 |
| PMID | 19318473 |
| MeSH | Adenoviridae / genetics* Animals Carcinoma, Squamous Cell / diagnosis Carcinoma, Squamous Cell / pathology Carcinoma, Squamous Cell / therapy* Cell Line, Tumor Head and Neck Neoplasms / diagnosis Head and Neck Neoplasms / pathology Head and Neck Neoplasms / therapy* Humans Mice Mice, Nude Oncolytic Virotherapy* Oncolytic Viruses / genetics* Promoter Regions, Genetic Survival Analysis Telomerase / genetics* Xenograft Model Antitumor Assays |
| IF | 10.107 |
| 引用数 | 21 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MRC-5 |