Basic research to sonodynamic therapy for the brain tumor

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Fukuoka University
• Principal Investigator: FUKUSHIMA Takao Fukuoka University, Sch. of Med., Prof., 医学部, 教授 (10078735)
• Co-Investigator(Kenkyū-buntansha): OSHIRO Shinya Fukuoka University, Sch. of Med., Assistant, 医学部, 助手 (40309901) ; TSUGU Hitoshi Fukuoka University, Sch. of Med., Assistant, 医学部, 助手 (80279273) ; YAMAMOTO Masaaki Fukuoka University, Sch. of Med., Assistant Prof., 医学部, 助教授 (80240125)
• Project Period (FY): 2001 – 2002
• Keywords: human glioma cells / sonodynamic therapy / Photofrin / α 2MR / LRP / RAP / Rose Bengal / blood brain barrier / electron microscopic study

Research Abstract

We investigated two different kinds of glioma cells which were different in manifestation of α 2MR/LRP in order to make clear presence of tumor cells brain tumor resistant to sonodynamic therapy and to clarify the mechanism of tolerance to the ultrasound. Cytocidal effect by sonodynamic therapy was meaningful in the U251MG cell that α 2MR/LRP appeared, and there were a little reinforcement effects in an U105MG cell. Cytocidal effect in U251MG cells was restrained by interrupting the combination of α 2MR/LRP by RAP. The form change of a tumor cell was remarkable in the U251MG cell with manifestation of α 2MR/LRP and was poor in an U105MG cell without 2MR/LRP. We thought that these results showed that presence of α 2MR/LRP participated in treatment sensitivity of sonodynamic therapy.
We studied to clarify the influence to the blood brain barrier on sonodynamic therapy using an electron microscopy. In the rat brain, localized lesions were produced within the basal ganglia with peak focal intensity of 100 W/cm2 and sonic time of 3 minutes and Rose Bengal was administrated as a photosensitizer. Electron microscopic examination showed degenerated cells at the perivascular space, and swelling of dendrites and endothelial cells. In the cytoplasm of the endothelial cells, swelling of mitochondria, a large number of pinocytic vesicles and disruption of endothelial cell membranes were observed. These phenomena were more prominent at the central area rather than peripheral area, and were more intense with Rose Bengal administration. These findings suggest that the increase of permeability of blood brain barrier occurs due to disruption of endothelial cell membrane and the increase of pinocytic vesicles of the cytoplasm rather than the opening of tight junction.