Neocarzinostatinによるmeningea gliomatosis modelの治療

TREATMENT OF A RAT MENINGEAL GLIOMATOSIS MODEL WITH NEOCARZINOSTATIN

　抄録　これまでの知見により，neocarzinostatin （NCS）がglioma細胞に対して特異的に殺細胞姓を示し，正常のglia細胞に対しては腫瘍細胞に対する有効濃度では障害を及ぼさないことが判明しており，meningeal gliomatosis （MG）に対するその髄腔内投与療法の可能性が示唆されている。そこで我々は，NCSの髄腔内投与によるMGの治療の妥当性に関する検討を行うためにC6 glioma細胞を用いてMGモデルを作成し，NCSによる化学療法実験を行い，この薬剤の抗腫瘍効果を調べた。その結果，腫瘍細胞移植後1日目にNCSの髄腔内治療を行った群では，1μg／kgという低濃度でMGモデルラットに対する延命効果（％ILS＝52.1）が出現し，10μg／kg投与群ではその効果はさらに著明となった（％ILS＝108.5）。一方，NCSによる治療を腫瘍移植後3日目に行った群では，治療効果が減少し，5日目の治療群では，NCS 100μg／kgという高濃度にもかかわらず延命効果は全く認められなかった。これよりNCSはMGの初期に対しては低濃度によっても著明な延命効果を現すことが示され，MGに対するNCSの髄腔内投与療法の有用性が証明された。

Meningeal gliomatosis (MG), pathologically, is caused by the diffuse dissemination or infiltration of glioma cells in the subarachnoid space, for which an effective, systematic treatment has not been contrived. Although, in the case of malignant ieptomengeal tumor, in general, intrathecal che-motherapy with such anticancer drugs as metho-trexate and cytosine arabinoside (Ara-C) has been applied, the effect of this kind of treatment is limited, especially on MG. Therefore, the develop-ment of a new type of treatment is urgently needed. According to recent reports, neocarzi-nostatin (NCS) has been disclosed to have a strong cytocidal effect on glioma cells instead of injur-ing normal glia cells, and the intrathecal injection of NCS is suggested to be effective on MG.

In order to evaluate the efficacy of intrathecal treatment with NCS on MG, a rat MG model using C6 glioma cells has been produced and intrathecal chemotherapy with NCS was performed on this MG model. In MG rats which were treated intrathecally with NCS (1 μg/kg) 1 day after tumor inoculation, the survival time was significantly prolonged by this treatment, where % ILS was 52.1%. Furthermore, it was more significantly prolonged with 10 μg/kg NCS, where 108.5% of % ILS was obtained. Contrary to these effects, this prolongation of the survival time of MG rats by the treatment with NCS showed a tendency to decrease in MG rats treated with NCS 3 days after tumor inoculation. No chemotherapeutic effect was observed in MG rats treated with even 100 μg/kg NCS 5 days after tumor inoculation. In conclusion, intrathecal chemotherapy with a low dose of NCS was proved to be effective in the early stages of MG.