Shinji Amano

Bystander effect in glioma suicide gene therapy using bone marrow stromal cells.

An established rat intracranial glioma was successfully treated through the tumoricidal bystander effect generated by intratumoral injection of rat bone marrow stromal cells (BMSCs) transduced with the herpes simplex virus-thymidine kinase gene (BMSCtk cells) followed by systemic ganciclovir administration. In the present study, we tested the bystander effect of this treatment strategy when using human BMSCs as the vector cells. Human BMSCtk cells were mixed with various kinds of brain tumor cell lines (human and rat glioma cells) and examined in vitro and in vivo tumoricidal bystander effects, by co-culture study and co-implantation study in the nude mouse, respectively. A significant in vitro bystander effect was observed between human BMSCtk cells and any of the tumor cells examined in the ganciclovir-containing medium. A potent in vivo bystander effect against human and rat glioma cells was also demonstrated when ganciclovir was administered. Migratory activity of the human BMSCs toward the tumor cells was enhanced by the conditioned media obtained from both human and rat glioma cells compared to the fresh media. The results of this study have demonstrated that the bystander effect generated by BMSCtk cells and ganciclovir is not cell type-specific, suggesting that the strategy would be quite feasible for clinical use.

Dissecting Aneurysm at the Proximal Segment of the Anterior Cerebral Artery Associated with Infraoptic Course Anterior Cerebral Artery

A 48-year-old man presented a subarachnoid hemorrhage caused by a rupture of a dissecting aneurysm at the proximal segment (A1 segment) of the right anterior cerebral artery (ACA). He also had an anomalous artery named infraoptic course ACA and an agenesis of the contralateral ACA A1 segment. Balloon occlusion test at the bifurcation of the right internal carotid artery demonstrated that the distal segments of the bilateral ACAs were perfused through the infraoptic course ACA. Therefore, we surgically trapped the A1 segment including the aneurysm. The patient got discharged without any neurological deficit. Natural course of ACA dissecting aneurysms is unclear because of rarity of the disease and treatment strategy is still controversial. Most of the dissecting aneurysms in the A1 segment are surgically treated, because they often present with massive hemorrhage and poor prognosis. In the present case, the contralateral A1 segment was absent but trapping of the dissecting aneurysm could be achieved without vascular reconstruction (e.g., bypass surgery) because of the presence of the infraoptic course ACA.