1999 Fiscal Year Final Research Report Summary
Clinicopathological study in the relationship among sensitivity, clonality, and growth potential after treatment in human gliomas
| Project/Area Number |
09671407
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | UNIVERSITY OF THE RYUKYUS |
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Principal Investigator |
YOSHII Yoshihiko University of the Ryukyus, Neurosurgery, Professor, 医学部, 教授 (50110507)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Etsuo University of the Ryukyus, Pathology(I), Professor, 医学部, 教授 (40031968)
SAITO Atsushi University of the Ryukyus, Neurosurgery, Associate Professor, 医学部・附属病院, 講師 (40305199)
TSURUSHIMA Hideo University of the Ryukyus, Neurosurgery, Assistant Professor, 医学部, 助手 (50315470)
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| Project Period (FY) |
1997 – 1999
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| Keywords | gliomas / clonality / resistant factor / immunohistochemical study / Vitamin K2 / apoptsis / oxidative stress |
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| Research Abstract |
In 30 well-studied patients with gliomas, immunoreactivity for Cu/Zn SOD, GST-pi, metallothionein, bcl-2, p53 and cytometric evidence of DNA ploidy in the G2M cell cycle phase were evaluated from routinely prepared tissue blocks. Hypertetraploid gliomas with high SOD immunoreactivity showed a significantly short time to progression (p<0.05) (1 to 5 months after radiotherapy and chemotherapy) compared with hypertetraploid, low-SOD immunoreactivity gliomas or tetraploid, low-SOD immunoreactivity gliomas. The tumor cells with high SOD activity also tended to be resistant for radiotherapy and anticancer drugs.
On the other hand, in 12 well-studied pairs who had the malignant brain tumors and received the first removal of the tumor at onset and the second operation at recurrence after the initial operation combined with radiotherapy and chemotherapy, those immunoreactivity was also evaluated. On conclusion, it suggests that the oncogene of bcl-2 in the malignant brain tumors may show more important factor for the resistance to adjuvant therapy than an antioxidant enzyme such as GST-pi and that the intrinsic factors like Cu/Zn SOD, GST-pi, and bcl-2 is also induced by radiation and anti-cancer drugs.
The antitumor effects of vitamin K2 were studied using three glioma cell lines. As the results, vitamin K2 showed growth inhibition in a dose-dependent manner and resulted in oligonucleosomal DNA fragmentation. Furthermore, the vitamin K2 significantly accumulated in the G0G1 phase of the cell cycle. Those results suggested that the vitamin K2 can inhibit the proliferation of the cells through the induction of cell cycle arrest and apoptosis for the tumor cells.
The combined treatment of vitamin K2 with ACNU, 5-FU and INF-b enhanced the growth inhibition significantly.
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