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抄録 Leptomeningeal tumorに対する治療法の一つとして,私達はACNU髄腔内投与法の検討を重ねてきた。しかしながら,ACNU投与後の腫瘍増殖能におよぼす影響はin vivoにおける細胞動態の面からは未だ明らかにされていなかった。今回,Walker 256腫瘍大槽内移植により作成したラット髄膜癌腫症モデルにACNU静脈内または髄腔内投与を行い,両投与法の腫瘍細胞増殖能におよぼす影響を抗BrdU抗休を用いた合成期細胞核標識率(labeling index:L.I.)より検討した。ACNU 15mg/kg静脈内投与後の合成期細胞核のL.I.は12時間後まで40%台と商値のままであったが,24時間後以降10%台に低下し,その後腫瘍細胞は減少する傾向にあった。ACNU1.5mg/kg髄腔内投与後のL.I.は4時間後の早期より20%台に低下し,48時間後までは10%台を示したが,96時間後上昇し,増殖能の回復が認められた。すなわち,本実験脳腫瘍モデルにおいて,ACNUの静脈内および髄腔内投与は腫瘍増殖能に対し,異なった影響を示した。これらの結果は制癌剤の至適投与法や多剤併用療法の開発に有用な情報になると考えられる。
We have studied the effecacy of intrathecal ACNU against experimental leptomeningeal tu-mors. In the present report, the effect of ACNU on the growth kinetics of the tumor was evaluated by the immunohistochemical technique using anti-BrdU monoclonal antibody. The experimentalleptomeningeal tumor was developed by inocula-tion of Walker 256 carcinosarcoma cells into the cisterna magna of rats. Seven days after the in-oculation of tumor cells, the animals were treated either by intravenous (15 mg/kg) or intrathecal (1. 5 mg/kg) ACNU. Four, 12, 24, 48, 96 or 144 hours after treatment, the animals received intra-venous BrdU (200 mg/kg). Thirty minutes there-after, they were sacrificed and the brain was removed. L. I. was calculated by counting the immunoreactive tumor cells. L. I. of the tumor without treatment on the seventh day after ino-culation was over 40%. L. I. began to decrease 24 hours after intravenous ACNU, and remained 11% up to 96 hours. On the other hand, L. I. already decreased to 20% 4 hours after intrathecal ACNU and remained to be low (17%) up to 48 hours. However, L. I. increased to 38% at 96 hours. Thus, the effect on the growth kinetics of the tumor differs between intravenous and intra-thecal ACNU. These results are considered to be useful informations for determining the optimal dosage of the antineoplatsic agent against the brain tumor and developing the effective combina-tion chemotherapy.
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