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[使用阿糖胞苷和云芝多糖对恶性脑肿瘤进行术后局部化疗的研究]

[Study on postoperative local chemotherapy of malignant brain tumors using ACNU and PSK].

作者信息

Saito Y, Hori T, Takami M, Muraoka K, Hokama Y, Numata H

出版信息

Gan To Kagaku Ryoho. 1983 Sep;10(9):1963-71.

PMID:6577813
Abstract

There have been many attempts to treat patients with malignant brain tumors represented by glioblastomas using nitrosourea (NU) derivatives such as BCNU and CCNU but the clinical results are not so remarkable compared with previous reports concerning experimental studies. The reason for an efficacy of NU derivatives in brain tumors is considered to be its higher lipid solubility which makes the drug crossing the BBB easily. On the other hand, there is some evidence that higher lipid solubility did not guarantee NU to reach always to all portions of solid tumor after systemic administration. We have performed a chemotherapy of malignant brain tumors using ACNU for five years. This drug is not only lipid but also water-soluble in some grade; therefore, the drug is administrated intravascularly and locally with ease. Nine cases of malignant gliomas were treated with local chemotherapy employing ACNU and two cases of glioblastomas are surviving now over five years and about four years, respectively. From the anatomical standpoint of view, it is considered to be necessary for local chemotherapy of brain tumors to possess some pathognomonic characters such as cyst formations, central necrosis and localized cortico-meningeal adhesions, which are rather frequently found in malignant gliomas and are suspected also easily by CT examination preoperatively. A local chemotherapy in the present study has been performed using 10 to 50 mg of ACNU through an indwelling catheter inserted during operation. No general toxicity occurred in all patients except one, who experienced purulent meningitis after long-term drainage. In our study on concentration of ACNU, intracarotid injection resulted in higher concentration in brain tumor tissue than intravenous injection, but these concentration considered to be not high enough to suppress the tumor cell growth. On the other hand, the intracavitary concentration of ACNU at 24 hr after drug administration was high enough to suppress the tumor cell growth.

摘要

人们曾多次尝试使用亚硝基脲(NU)衍生物如卡莫司汀(BCNU)和洛莫司汀(CCNU)来治疗以胶质母细胞瘤为代表的恶性脑肿瘤患者,但与先前有关实验研究的报告相比,临床结果并不显著。NU衍生物对脑肿瘤有效的原因被认为是其较高的脂溶性,这使得药物易于穿过血脑屏障。另一方面,有证据表明,较高的脂溶性并不能保证NU在全身给药后总能到达实体瘤的所有部位。我们使用嘧啶亚硝脲(ACNU)对恶性脑肿瘤进行化疗已经五年了。这种药物在一定程度上不仅具有脂溶性,还具有水溶性;因此,可以轻松地进行血管内和局部给药。9例恶性胶质瘤患者接受了使用ACNU的局部化疗,2例胶质母细胞瘤患者目前分别存活了五年多和四年左右。从解剖学角度来看,脑肿瘤的局部化疗被认为有必要具备一些特征性表现,如囊肿形成、中央坏死和局限性皮质-脑膜粘连,这些在恶性胶质瘤中相当常见,术前通过CT检查也很容易被怀疑。本研究中的局部化疗是在手术期间通过留置导管注入10至50毫克的ACNU进行的。除了1例患者在长期引流后发生化脓性脑膜炎外,所有患者均未出现全身毒性。在我们关于ACNU浓度的研究中,颈内动脉注射导致脑肿瘤组织中的浓度高于静脉注射,但这些浓度被认为不足以抑制肿瘤细胞的生长。另一方面,给药后24小时ACNU的腔内浓度足以抑制肿瘤细胞的生长。

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