論文 - 詳細
| RRC ID | 39768 |
|---|---|
| 著者 | Braiden V, Ohtsuru A, Kawashita Y, Miki F, Sawada T, Ito M, Cao Y, Kaneda Y, Koji T, Yamashita S. |
| タイトル | Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter. |
| ジャーナル | Hum Gene Ther |
| Abstract |
To investigate the usefulness of heat shock protein (HSP) promoter for breast cancer gene therapy, hyperthermia and HSV thymidine kinase (tk) suicide gene combination therapy was examined with mouse mammary cancer cell line FM3A. HSP promoter activity was markedly increased after heat shock (41-45 degrees C), with maximum activation (about 400-fold) at 3 hr. An in vitro cytotoxic assay showed that HSP-tk-transduced FM3A cells became more sensitive (more than 50,000 times) to ganciclovir (GCV) with heat shock, but untreated cells showed no increased cytotoxic sensitivity to GCV compared with control FM3A cells. In addition to promoter-oriented selective cell killing, a "chemosensitization effect" as a bystander effect was demonstrated by hyperthermia and suicide gene combination therapy, using a non-heat-inducible promoter. Immunohistochemical analysis revealed that this synergistic killing effect was dependent on apoptotic cell death with upregulation of both Fas and FasL (Fas ligand) expression. We also examined the efficacy of HSP-tk gene therapy in vivo by implanting breast cancer in subcutaneous and intraperitoneal models of BALB/c nude mice targeted by the HVJ-anionic liposome method. Significant tumor regression was observed in HSP-tk-transduced tumors followed by hyperthermia therapy, but no such inhibition was noted in either the mock vector transfection or hyperthermia group compared with control tumor-bearing mice. Our results demonstrate that this combination system is synergistically effective in mediating Fas-dependent apoptosis for a specific gene therapy targeting HSP-expressing mammary carcinomas, even in advanced and heat-resistant breast cancer. |
| 巻・号 | 11(18) |
| ページ | 2453-63 |
| 公開日 | 2000-12-10 |
| DOI | 10.1089/10430340050207948 |
| PMID | 11119417 |
| MeSH | Animals Antiviral Agents / pharmacology Apoptosis Breast Neoplasms / genetics* Breast Neoplasms / therapy* Dose-Response Relationship, Drug Fas Ligand Protein Female Ganciclovir / pharmacology Genetic Therapy / methods* Heat-Shock Proteins / genetics* Hot Temperature Immunohistochemistry In Situ Nick-End Labeling Liposomes / metabolism Mammary Neoplasms, Animal / metabolism Membrane Glycoproteins / metabolism Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Plasmids / metabolism Promoter Regions, Genetic* Retroviridae / metabolism Temperature Thymidine Kinase / metabolism Time Factors Tissue Distribution Transduction, Genetic Transfection Tumor Cells, Cultured Up-Regulation fas Receptor / metabolism |
| IF | 4.51 |
| 引用数 | 45 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | FM3A(RCB0086) FM3A FT-101(RCB0032) |