Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.
Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.
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发表时间：
2001-10
期刊：
影响因子：
11.2
通讯作者：
L. Bello;G. Carrabba;C. Giussani;V. Lucini;F. Cerutti;F. Scaglione;J. Landré;M. Pluderi;G. Tomei;R. Villani;R. Carroll;P. Black;A. Bikfalvi
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作者：
L. Bello;G. Carrabba;C. Giussani;V. Lucini;F. Cerutti;F. Scaglione;J. Landré;M. Pluderi;G. Tomei;R. Villani;R. Carroll;P. Black;A. Bikfalvi
这项研究评估了抗血管生成药物和常规化疗药物联合治疗实验性人类神经胶质瘤的疗效。作为抗血管生成药物，我们使用了重组人 PEX，这是基质金属蛋白酶 2 的一个片段，我们之前已证明它在体外和体内对人胶质母细胞瘤具有显着的抗有丝分裂、抗侵袭和抗血管生成特性。我们使用卡铂和依托泊苷作为我们机构（Ospedale Maggiore de Milano）常规用于治疗恶性胶质瘤的两种化疗药物。传统的化疗药物以高剂量或低剂量和半连续方案给药。与单独化疗相比，大剂量化疗和 PEX 联合治疗并没有提高生存率，但与肿瘤体积、血管分布和增殖指数的减少以及细胞凋亡的增加有关。所有这些动物都经历了严重的副作用。据记录，接受低度和半连续化疗和抗血管生成治疗的动物存活时间最长。该方案没有副作用，肿瘤体积、血管分布和增殖指数显着减少，细胞凋亡增加。我们的数据表明，低剂量化疗联合 PEX 可成功用于体内对抗人类恶性胶质瘤。
This study evaluates the efficacy of the combination of an antiangiogenic drug and conventional chemotherapeutics for the treatment of experimental human gliomas. As an antiangiogenic, we used recombinant human PEX, a fragment of matrix metalloproteinase-2 that we have previously shown to have a significant antimitotic, anti-invasive, and antiangiogenic properties against human glioblastoma in vitro and in vivo. We used carboplatin and etoposide as the two chemotherapeutic drugs routinely used in our institution (Ospedale Maggiore de Milano) for the treatment of malignant gliomas. Conventional chemotherapeutic drugs were administered at high dose or at a low and semicontinuous regimen. Combined treatment of high-dose chemotherapy and PEX did not produce an improvement of survival in comparison with chemotherapy alone, but it was associated with a decrease in tumor volume, vascularity, and proliferative index and an increased apoptosis. All of these animals experienced severe side effects. The longest survival was documented in animals submitted to low and semicontinuous chemotherapy and antiangiogenic treatment. This regimen was associated with no side effects, marked decrease in tumor volume, vascularity, and proliferative index, and an increased apoptosis. Our data suggest that low-dose chemotherapy in combination with PEX can be successfully used against human malignant glioma in vivo.