Study on the practical application of chemo-radiotherapy for malignant brain tumor

恶性脑肿瘤放化疗的实际应用研究

• 批准号: 11671393
• 负责人: NAGASHIMA Tadashi
• 金额: $ 1.98万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671393/
• 关键词: Malignant brain tumor; Cisplatin; Low-dose; Antisense oligodeoxynucleotide; MAP-1A mRNA; MAP-1A; アンチセンス; 遺伝子治療; 悪性グリオーマ; 化学療法; CDDP; NK活性; 殺細胞効果

Ten days after subcutaneous inoculation of human glioma cells, GL9, in the rear flank of nude mice, they were assesed for growth suppression by CDDP.Totally, 20mg/Kg of CDDP was administeredto each mouse ; in one group (high dose CDDP group), 10mg/Kg of CDDP on every tenth day, and in the other (low dose CDDP group), 2mg/Kg on every day. Measurement of the tumor volume in each group revealed no significant difference between the tow groups in terms of the efficiency of tumor growth suppresion. Twenty-one days after inoculation, we measure the splenic natural killer (NK) cell activity in eachi mouse. The results showed that the low-dose cisplatin group, and significantly decreased in the high-dase cisplatin group, as compared to the control group.C6 glioma cells with a concentration of 10^6 are implanted stereotactically within rat brain tissue. After 7 days, an angled cannula connected to a miniosmotic pump contained 1 mM antisense, sennse, or scramble phosphorothiorate oligodeoxynucleotide in 100 ul sterile saline is inserted into the established tumor of C6 glioma cells in each rat brain tissue. The effectiveness of antisense phosphorothionate oligodeoxynucleotide for MAP-1A mRNA was determined by comparing the tumor volume 10days after treatment. Tumor volume revealed to be significantly smaller in the antisense oligonucleotide group, as compared to the sense and scramble oligonuleotide group.The results of our studies suggest that the separate administration of low- dose CDDP and the antisense therapy for MAP-1A mRNA are useful treatment strategies for malignant brain tumors.

将人胶质瘤细胞GL 9接种于裸鼠后腹皮下10天后，观察顺铂（CDDP）对裸鼠生长的抑制作用，CDDP剂量为20 mg/Kg，高剂量组（10 mg/Kg），每10天1次，低剂量组（2 mg/Kg），每天1次。各组肿瘤体积的测量显示，两组之间的肿瘤生长抑制效率无显著差异。接种后21天，我们检测了每只小鼠脾脏自然杀伤（NK）细胞活性。结果显示，低剂量顺铂组与对照组相比，高剂量顺铂组明显降低。将浓度为10^6的C6胶质瘤细胞立体定向植入大鼠脑组织内。7天后，将连接到微渗透泵的成角度的套管插入每个大鼠脑组织中已建立的C6神经胶质瘤细胞的肿瘤中，所述微渗透泵在100 μ l无菌盐水中含有1 mM反义、有义或乱序硫代磷酸寡脱氧核苷酸。通过比较治疗后10天肿瘤体积来确定MAP-1A mRNA反义硫代磷酸寡核苷酸的有效性。反义寡核苷酸组的肿瘤体积明显小于正义和乱序寡核苷酸组，我们的研究结果表明，小剂量CDDP的单独给药和MAP-1A mRNA的反义治疗是恶性脑肿瘤的有效治疗策略。

项目成果

松野彰他: "GH産生下垂体腺腫におけるGHRHの発現に関する免疫組織化学による検討"ホルモンと臨床99. 47. 89-91 (1999)

Akira Matsuno 等人：“产生 GH 的垂体腺瘤中 GHRH 表达的免疫组织化学研究”激素和临床科学 99. 47. 89-91 (1999)

Tanaka S, Kamitani H, Amin MR, Watanabe T, Oka, H, Fujii K, Nagashima T, Hori T: "Preliminary individual adjubant therapy for gliomas based on the results of molecular biological analyses for drug-resistant genes"J Neuro-Oncology. 46. 157-171 (2000)

Tanaka S，Kamitani H，Amin MR，Watanabe T，Oka，H，Fujii K，Nagashima T，Hori T：“基于耐药基因分子生物学分析结果的神经胶质瘤的初步个体辅助治疗”J Neuro-Oncology

Matsuno, A, Nagashima, T, Ohtsugi Y, Utsunomiya H, Takekoshi S, Munakata S, Nagao K, Osamura RY, Watanabe K: "Elektron microscopic observation of intracellular expression of mRNA and its protein product : Technical review on ultrastuctual in situ hybridiz

Matsuno, A, Nagashima, T, Ohtsugi Y, Utsunomiya H, Takekoshi S, Munakata S, Nagao K, Osamura RY, Watanabe K：“Elektron 显微镜观察 mRNA 及其蛋白产物的细胞内表达：超结构原位杂交技术综述

長島 正他: "中枢神経原発悪性リンパ腫"Annual Review 神経. 2001. 186-194 (2001)

Masaru Nagashima 等：“原发性中枢神经系统恶性淋巴瘤”年度评论神经病学。 186-194 (2001)

Matsuno A他: "Drolleration index and prophylactic radiosurgery"J Neurosurg. 91. 898 (1999)

Matsuno A 等人：“Drolleration 指数和预防性放射外科”J Neurosurg。91. 898 (1999)