Radiosensitization of human glioma cells in vitro and in vivo with acyclovir and mutant HSV-TK75 expressed from adenovirus
| Autor: | Matthew Holmes, Rupert Schmidt-Ullrich, Peck Sun Lin, William T. Hawkins, Cyrus Amir, Elizabeth Rosenberg, Kristoffer Valerie |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
viruses Genetic enhancement Transplantation Heterologous Acyclovir Mice Nude Antiviral Agents Radiation Tolerance Thymidine Kinase Adenoviridae Mice Gentamicin protection assay Transduction Genetic In vivo Glioma Tumor Cells Cultured Animals Humans Medicine Radiology Nuclear Medicine and imaging Herpesviridae Tumor Stem Cell Assay Radiation business.industry Radiobiology medicine.disease Combined Modality Therapy Virology In vitro Transplantation Oncology Thymidine kinase Cell culture Mutation Cancer research business |
| Zdroj: | International Journal of Radiation Oncology*Biology*Physics. 52:831-836 |
| ISSN: | 0360-3016 |
| Popis: | Purpose : We recently reported that an adenovirus-expressing mutant HSV-TK75 (AdCMV-TK75) radiosensitized rat syngeneic gliomas in combination with low concentrations of acyclovir (ACV) much more effectively than a virus expressing wild-type herpes simplex virus thymidine kinase (HSV-TK). In this report we have examined whether similar radiosensitizing effects are also seen with human glioma cells in vitro and in vivo. Methods and Materials : Human U87 MG glioma cells were transduced with AdCMV-TK75 and exposed to ACV followed by single-dose irradiation and colony-forming survival assays. Similarly, U87 MG xenografts were infused with AdCMV-TK75 or Adβgal control virus, followed by ACV administration and fractionated irradiation. Therapeutic efficacy was monitored by tumor growth. Results : U87 MG cells transduced with AdCMV-TK75 were significantly more sensitive to ACV (3 μM) than cells transduced with either wild-type HSV-TK or control virus. To determine whether human cells also demonstrate improved radiosensitization similar to that seen with rat glioma cells and tumors, we transduced U87 MG cells with either AdCMV-TK75, AdCMV-TK, expressing wild-type HSV-TK, or Adβgal and then treated the cells with 3 μM of ACV. Cells transduced with AdCMV-TK75 were significantly more radiosensitive (dose enhancement ratio [D37]: 2.6) by colony-forming survival assay than cells transduced with either AdCMV-TK or Adβgal. Furthermore, we found that U87 MG xenografts infused with AdCMV-TK75 by slow positive pressure infusion were more radiosensitive after administration of ACV than tumors infused with Adβgal. A more dramatic result was achieved when fractionated irradiation was carried out concurrently with ACV administration, in which case AdCMV-TK75-treated tumors did not grow at all. Conclusions : These results demonstrate that transduction of human glioma cells in vitro and infusion of xenografts in vivo with AdCMV-TK75 and treatment with concentrations of ACV that can be achieved in vivo produce similar radiosensitization, as previously reported with rat glioma cells and intracerebral syngeneic tumors. In addition, concurrent treatment with ACV and radiation therapy is more efficient than when ACV is administered before radiation therapy. |
| Databáze: | OpenAIRE |
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