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S Miyatake

Publications and source records attributed to S Miyatake.

113 records · Page 7Linked to original sources
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Experimental gene therapy against subcutaneously implanted glioma with a herpes simplex virus-defective vector expressing interferon-gamma.

We investigated the feasibility of local treatment or tumor vaccination with a herpes simplex virus (HSV) type 1-defective vector. The vector was engineered to express murine interferon-gamma (IFN-gamma) for experimental gene therapy against mouse glioma Rous sarcoma virus (RSV). The murine IFN-gamma gene was driven by the cytomegalovirus promoter. The helper virus (tsk) was thermosensitive; consequently, this vector could only proliferate at 31 degrees C. A high level of murine IFN-gamma expression was confirmed in vitro and in vivo by immunohistochemistry using anti-mouse IFN-gamma monoclonal antibody. This engineered vector (dvHSV/MulFN-gamma) inhibited the proliferation of mouse glioma RSV cells in vitro, and an intratumoral (i.t.) local injection of the vector caused i.t. necrosis in vivo. The immunological effect of dvHSV/MulFN-gamma was also examined in a mouse glioma RSV cell implantation model. A subcutaneous (s.c.) implant of 1 x 10(6) mouse glioma RSV cells after treatment with dvHSV/MulFN-gamma was rejected. However, the implant after treatment with an engineered HSV-defective vector containing an antisense nucleotide sequence of the murine IFN-gamma gene was not rejected. In addition, in another group of mice in which RSV cells treated with dvHSV/MulFN-gamma were implanted into a femoral (s.c.) region and nontreated RSV cells were implanted into a contralateral femoral (s.c.) region, the implanted RSV cells were rejected. The rejection of the implanted mouse glioma RSV was blocked by anti-asialo GM1, which was known to inhibit natural killer cell activity. These results revealed that the HSV-defective vector could realize a high efficiency of transfection to glioma cells through short-time treatment, and that the IFN-gamma gene transferred to the cells had the effect of tumor vaccination, which was suggested be related to natural killer cells. In conclusion, dvHSV/MulFN-gamma may be useful for the gene therapy of malignant glioma through either i.t. local injection or a practical tumor vaccination with ex vivo gene transfer.

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Enhanced detection of brain tumors by [18F]fluorodeoxyglucose PET with glucose loading.

OBJECTIVE: We applied glucose loading during PET studies with [18F]2-fluoro-2-deoxy-D-glucose (FDG) to enhance detection of brain tumors by diminution of FDG uptake in normal gray matter. MATERIALS AND METHODS: This study involved three patients with glioblastomas. Two PET scans were performed in all cases within 1 week in control and with glucose loading state. RESULTS: In all patients, tumor was depicted more clearly with glucose loading than in the control study. The FDG uptake ratio of tumor to normal cortical gray matter showed a mean increase of 27% with glucose loading. CONCLUSION: This technique might be useful for detection of recurrent or residual tumors.

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Defective herpes simplex virus vectors expressing thymidine kinase for the treatment of malignant glioma.

Viral vectors used for cancer gene therapy have usually been either replication-incompetent vectors expressing a gene product that leads to the destruction of the tumor or replication-competent vectors that are inherently cytotoxic to the tumor cells. We have sought to combine the attributes of these different approaches using a defective herpes simplex virus (HSV) vector that consists of a defective particle, containing tandem repeats of the HSV thymidine kinase (TK) gene, and a replication-competent, non-neurovirulent HSV mutant as a helper virus. HSV-TK activity in defective vector-infected cells was significantly greater than that in helper virus-infected cells which contained a single copy of HSV-TK. Infection of cells with this defective vector renders them, as well as surrounding uninfected cells, sensitive to killing by ganciclovir. Ganciclovir treatment of C57BL/6 mice bearing TK-defective vector/helper virus-infected subcutaneous GL261 gliomas resulted in significantly decreased tumor size.

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