Urokinase antisense oligodeoxynucleotides as a novel therapeutic agent for malignant glioma: in vitro and in vivo studies of uptake, effects and toxicity.
Urokinase antisense oligodeoxynucleotides as a novel therapeutic agent for malignant glioma: in vitro and in vivo studies of uptake, effects and toxicity.
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尿激酶反义寡脱氧核苷酸作为恶性神经胶质瘤的新型治疗剂：摄取、作用和毒性的体外和体内研究。
DOI：
10.1006/bbrc.1996.1519
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Duncan,H
中科院分区：
文献类型：
--
作者：
Engelhard,H;Narang,C;Homer,R;Duncan,H
反义治疗可能为恶性胶质瘤患者提供一种更好的治疗方法。我们研究了尿激酶反义寡核苷酸对体外培养的大鼠和人脑胶质瘤细胞的摄取和作用，以及这些核苷酸在大鼠癌病和脑肿瘤模型中的摄取和毒性。培养的神经胶质瘤细胞很容易纳入荧光素异硫氰酸酯共轭寡核苷酸，所示的免疫荧光显微镜和流式细胞术。通过免疫荧光显微镜评估对尿激酶表达的影响因细胞系而异。北方印迹分析显示寡脱氧核苷酸处理后尿激酶表达降低。在体内也证明了肿瘤细胞的摄取，在超过预期治疗水平的浓度下没有可检测到的毒性。这些结果为进一步研究反义寡核苷酸作为一种新的治疗恶性胶质瘤的方法提供了依据。
Antisense therapy might offer an improved treatment for patients with malignant glioma. We studied the uptake and effects of urokinase antisense oligodeoxynucleotides on rat and human glioma cellsin vitroand the uptake and toxicity of these nucleotides in rat carcinomatosis and brain tumor models. Cultured glioma cells readily incorporated fluorescein isothiocyanate-conjugated oligonucleotides, as demonstrated by immunofluorescence microscopy and flow cytometry. Effects on urokinase expression as assessed by immunofluorescence microscopy varied according to cell line. Northern blot analysis showed decreases in urokinase expression with oligodeoxynucleotide treatment. Uptake into tumor cells was also demonstratedin vivo,with no detectable toxicity at concentrations exceeding expected therapeutic levels. These data are encouraging for the further study of antisense oligodeoxynucleotides as a new therapeutic modality for malignant glioma.