雑誌文献を検索します。書籍を検索する際には「書籍検索」を選択してください。

Brain and Nerve No to Shinkei Volume 38, Issue 11 （November 1986）

Brain and Nerve 脳と神経 38巻11号（1986年11月発行）

Japanese English

原著

ACNU髄腔内投与による悪性leptomeningeal tumorの治療—毒性および治療効果に関する実験的研究 INTRATHECAL ACNU AGAINST MALIGNANT LEPTOMENINGEAL TUMORS:TOXICITY AND THERAPEUTIC EFFECT IN EXPERIMENTAL ANIMALS 永谷雅昭 ¹ , 有田憲生 ¹ , 生塩之敬 ¹ , 早川徹 ¹ , 黄祖源 ¹ , 吉峰俊樹 ¹ , 森信太郎 ¹ , 最上平太郎 ¹ Masaaki Nagatani ¹ , Norio Arita ¹ , Yukitaka Ushio ¹ , Toru Hayakawa ¹ , Huang Tzuu-Yuan ¹ , Toshiki Yoshimine ¹ , Shintaro Mori ¹ , Heitaro Mogami ¹ ¹大阪大学脳神経外科 ¹Department of Neurosurgery, Osaka University Medical School pp.1071-1075

発行日 1986年11月1日 Published Date 1986/11/1

DOI https://doi.org/10.11477/mf.1406205808

PDF(3346KB)

有料閲覧

Abstract 文献概要
1ページ目 Look Inside

　抄録　悪性leptomeningeal tumorに対する治療としては，従来放射線照射および化学療法，特にmetho—trexateやcytosine arabinosideの髄腔内投与が行われてきたが，効果は極めて限られたものであり，治療成績向上のため新たな治療法の導入が望まれる。そこで，ACNU （Nimustine hydrochloride）髄腔内投与による悪性leptomeningeal tumor治療の妥当性に関し検討を行った。毒性は，ACNUを正常ラット大槽内に投与し観察した。その結果，ACNU3.0mg／kg以上の髄腔内投与では体重が減少し，6.0mg／kgで死亡など全身に対する急性毒性が生じ，また脳底部などに脳血管透過性の亢進や同部に髄鞘の脱落およびneuronの消失が認められた。1.5mg／kg以下では以上の変化は認められなかった。治療効果は，Walker256 carcinosarcoma cell大槽内移植により作成したmeningeal carcinomatosisラットを用いて観察した。その結果，腫瘍移植2日あるいは5日目にACNU1.5mg／kg髄腔内に投与した群は無治療対照群と比し，有意に生存日数が延長した（55％より145％）。以上より，ACNU髄腔内投与は悪性leptomeningealtumorに対し有効な治療法となりうることが示唆された。

Leptomeningeal dissemination is one of the ma-jor causes which increase the morbidity and morta-lity of the patients with malignant brain tumors. The incidence of this complication is increasing, however, no sufficient treatment is available at present. Therefore, in an attempt to establish a new treatment, we studied toxicity and therapeu-tic effect of intrathecal ACNU (nimustine hydro-chloride) using experimental animals. Systemic and local toxicity was tested in normal rats that received ACNU intracisternally. The animals given ACNU more than 3.0 mg/kg progressively lost their body weight, and ACNU 6.0 mg/kg was fatal in 80% of animals. Animals given ACNU less than 1.5 mg/kg gained weight in the same rate as in control animals. Increased capillary permeability to intravenous Evans blue was ob-served in the subpial region of the brain in the rats given ACNU 6.0 mg/kg intracisternally. The increase of capillary permeability was dominant along the ambient cistern, hypocampal fissure, and at the base of the brain. Demyelinization and loss of neurons were seen in the same areas as well. These changes were not observed in the animal given ACNU less than 1.5 mg/kg. Thera-peutic effect of intrathecal ACNU against the leptomeningeal tumor was studied in rats with meningeal carcinomatosis which was induced byintracisternal inoculation of 1×10⁴ cells of Walker 256 carcinosarcoma. The median survival times of the animal given ACNU 1.5 mg/kg intrathecally on day 2 or 5 after tumor inoculation were pro-longed by 55 to 64%, and 64 to 145%, respecti-vely, as compared to those of untreated control animals (p<0.01). These findings suggest that intrathecal ACNU is one of the promising ap-proaches in the treatment of malignant leptome-ningeal tumor.