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Gene therapy for malignant brain tumor by infusion of antisense oligonucleotide

反义寡核苷酸输注治疗恶性脑肿瘤的基因治疗

基本信息

批准号：
08407043
负责人：
FUKUI Masashi
金额：
$ 25.54万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

1. Genetic characterization of malignant gliomasWe recognized the microsatellite instability in the chromosome 10 in 6 out of 31 humanﾟCgliomas. And rare apoptosis was recognized in malignant gliomas. These findingsﾟCsuggested that the genetic abnormality strongly associated with the malignantﾟCtransformation of the gliomas.2. Establishment of quantitative measurement of antisenseoligonucleotide in theﾟCorgans.After obtaining the organs, brain, liver, and kidney, DNA fractions was extracted using centrifugation and filters. The DNA fractions were electrophorated on the acrylamide gel and trasbiotted to the membrane. A quantitative measurement of antisenseoligonucleotide was performed using RI-labeled senseoligonucleotide.3. Selective delivery of antisenseoligonucleotide by intracarotid bradykinin infusion We injected antisenseoligonucleotide from internal carotid artery in tumor-bearing rat. The delivered oligonucleotide was measured by the methods described above. The antisenseoligonucleotide was selectively delivered into the brain tumor by 1.4 fold, compared with the control study.3. Effect of intracarotid bradykinin infusion on vital signs in dogs.Using 20 dogs, we examined the effect of intracarotid bradykinin infusion on vital signs. At the dose of 1 and 2.5 gamma, intracarotid bradykinin infusion did not change the vital signs significantly. On the other hand, at the dose of 5 and 10 gamma, it changed the vital signs including cerebral blood flow at the beginning of the infusion.

1. 恶性神经胶质瘤的遗传特征我们在 31 例人类神经胶质瘤中的 6 例中发现了 10 号染色体的微卫星不稳定性。在恶性神经胶质瘤中发现了罕见的细胞凋亡。这些发现表明遗传异常与胶质瘤的恶性转化密切相关。2．建立器官中反义寡核苷酸的定量测量。获得器官、脑、肝脏和肾脏后，通过离心和过滤提取DNA组分。 DNA 级分在丙烯酰胺凝胶上电泳并转至膜上。使用RI标记的正义寡核苷酸进行反义寡核苷酸的定量测量。 3．通过颈动脉内缓激肽输注选择性递送反义寡核苷酸我们从颈内动脉向荷瘤大鼠注射反义寡核苷酸。通过上述方法测量递送的寡核苷酸。与对照研究相比，反义寡核苷酸选择性地递送至脑肿瘤中1.4倍。3．颈动脉内缓激肽输注对狗生命体征的影响。我们使用 20 只狗，检查了颈动脉内缓激肽输注对生命体征的影响。在1和2.5γ剂量下，颈动脉内输注缓激肽没有显着改变生命体征。另一方面，在5和10γ剂量下，它改变了输注开始时包括脑血流在内的生命体征。