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Sci Rep: 白血病药物砒霜显示出治疗小儿脑癌的希望!

2020-07-27 Cathy 转化医学网

髓母细胞瘤(medulloblastoma)是一种儿童常见的颅内恶性肿瘤,其生长极其迅速;手术不易全部切除;肿瘤细胞有沿脑脊液产生播散性种植的倾向。而近日,巴西科学家发现一种治疗白血病的药物三氧化二砷

髓母细胞瘤(medulloblastoma)是一种儿童常见的颅内恶性肿瘤,其生长极其迅速;手术不易全部切除;肿瘤细胞有沿脑脊液产生播散性种植的倾向。而近日,巴西科学家发现一种治疗白血病的药物三氧化二砷具有治疗髓母细胞瘤的潜力。

巴西圣保罗大学里贝雷普雷托医学院(FMRP-USP)的研究人员证实,白血病药物三氧化二砷具有治疗髓母细胞瘤的潜力,髓母细胞瘤是儿童最常见的一种脑癌。当他们在从这类肿瘤中最具攻击性的亚组提取的细胞上测试三氧化二砷时,他们成功杀死了肿瘤细胞。该药物还使肿瘤细胞对放射治疗更加敏感。

该研究发表在《科学报告》上。题为“Arsenic Trioxide exerts cytotoxic and radiosensitizing effects in pediatric Medulloblastoma cell lines of SHH Subgroup”

该文章的第一作者Paulo Henrique dos Santos Klinger说:“目前根据分子特征识别了12个髓母细胞瘤亚组,这些亚组也与预后有关。其中SHH是预后最差的亚组之一。该肿瘤的 TP53基因具有体细胞突变,目前通过化学和放射疗法治疗。 ”这也是他在FMRP-USP硕士研究的一部分,并得到了巴西国家科学技术发展委员会(CNPq)的奖学金资助。

这项研究是由FMRP-USP教授Luiz Gonzaga Tone领导的“新兴治疗目标与肿瘤发生相关的发育途径之间的相互作用:关注儿童恶性肿瘤”项目的一部分。

Tone说:“该项目致力于深入研究控制正常胚胎发育的信号通路失调及其与儿童癌症的发病和进展的联系。”

放射疗法可能会对孩子的大脑造成严重的不良影响,从而引起认知,内分泌和运动方面的问题。因此,制定减少或消除放射治疗需求的治疗策略非常重要。

在这项研究中,研究人员选择了不同的SHH肿瘤细胞系,并测试了不同剂量的三氧化二砷(一种用于治疗急性髓性白血病的药物)。他们还测试了不同剂量的放疗与给药的关系。

事实证明,三氧化二砷能够杀死肿瘤细胞并阻止新的肿瘤细胞集落的形成。当药物与放射疗法结合时,效果增强。并且这种药物对健康细胞没有明显毒性。

此外,三氧化二砷可单独用于治疗3岁以下儿童的髓母细胞瘤,也可与化疗药物结合使用。这个年龄段的脑癌儿童不能接受放射治疗,因为它可能对中枢神经系统造成不可逆转的损害。

突变

之所以选择三氧化二砷,是因为它是白血病中著名的SHH信号通路阻断剂。SHH途径对人类胚胎发育至关重要,当胚胎发育完成时,SHH途径被关闭。但如果由于某种原因重新激活该途径,那么癌症就会发展,包括皮肤癌以及白血病和髓母细胞瘤。

该论文的通讯作者,Elvis Terci Valera教授说:“三氧化二砷的另一个优点是它具有穿过血脑屏障的能力,可以保护中枢神经系统免受循环毒素或病原体的侵害。先前的研究表明这种渗透在髓母细胞瘤中是可行的。”

SHH型髓母细胞瘤的预后一般为中等,其中50%的患者对治疗反应良好。但是,当TP53基因发生体细胞突变时,预后会变差,因为该基因在细胞分裂控制中起着关键作用,并且能够抵消可能导致癌症的改变。

Klinger说:“该基因的种系突变与李-佛美尼综合症(LFS)有关,通常涉及TP53功能的丧失,并增加了各类肿瘤的易感性。”

李-佛美尼综合症与一系列癌症的遗传易感性有关,并会增加儿童患髓母细胞瘤的风险,尤其是SHH型髓母细胞瘤。

目前,研究人员正计划在动物模型中测试该药物,以确定结果是否与细胞实验的结果相同。如果它们相同,则可以随后在人体进行测试。

原始出处:Paulo Henrique dos Santos Klinger,Lara Elis Alberici Delsin, Gustavo Alencastro Veiga Cruzeiro, et al. Arsenic Trioxide exerts cytotoxic and radiosensitizing effects in pediatric Medulloblastoma cell lines of SHH Subgroup. Scientific Reports (2020). 

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    2020-07-28 hittouch
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