模拟微重力和肿瘤病毒治疗相结合改善多形性胶质母细胞瘤研究
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多形性胶质母细胞瘤是最常见的侵袭性恶性原发性脑肿瘤,在美国每10万人中约有3.19人发病,男性发病率是女性的1.6倍。这是恶性脑肿瘤中发病率最高的。美国东北部发病率最高,中南部地区发病率最低,白人GBM的发病率最高。与女性相比,男性GBM更常见(3.97比2.53)。(1)GBM通常起源于称为星形胶质细胞的胶质细胞,通常位于幕上区(皮质叶),通常影响额叶。它是多种多样的。
显微镜下大体横断面显示出血和坏死、多形性细胞核和细胞、假性栅栏坏死和微血管增殖的区域(2)这种肿瘤的一个独特特征是其快速的局部生长和扩散,导致预后非常差,5年生存率低于5%。(1)
多种风险因素与GBM有关,如暴露于辐射、免疫系统较弱和年龄增长。诊断的中位年龄为64岁。这在儿童中并不常见,仅占0至19岁人群中报告的所有脑和中枢神经系统肿瘤的约3%。其他风险因素包括较高的社会经济地位。过敏易感性的降低和抗炎药物的使用与GBM风险的增加有关。(1)
已经确定了几种遗传和分子机制在GBM的发展中发挥作用。没有证据表明恶性程度较低的前体的原发性新发GBM与表皮生长因子受体(EGFR)过表达、多效性蛋白突变和10号染色体丢失有关。由低级星形细胞瘤或间变性星形细胞瘤引起的继发性GBM与IDH1突变有关,TP53突变导致α-合胞蛋白过表达;与帕金森病和19q染色体缺失有关的相同蛋白质(3)、(4)、(5)、(6)
方法假设:
1、假设,通过模拟微重力和溶瘤病毒治疗的结合,恶性胶质瘤细胞的生长将被中止。
2、恶性胶质瘤细胞(武田,2009年)在Dulbecco改良培养基中,补充青霉素(100单位/ml)、链霉素(100微克/ml)、10%胎牛血清、白细胞、粒细胞单核细胞集落刺激因子(GMSCF)和细小病毒H1,在37℃下,在加湿的5%二氧化碳气氛中,将使用基于回转台的三维(3D)培养系统置于模拟微重力环境中。通过倒置对比相位和量子显微镜、流式细胞术线粒体膜电位验证恶性胶质细胞坏死。经过两周的干预,所有恶性胶质瘤细胞都将死亡。
结果讨论:
模拟微重力对多形胶质母细胞瘤的影响:肯塔基州立大学Gliolabat进行了多项研究,以检查太空飞行期间微重力对包括GBM在内的不同肿瘤细胞的影响,结果表明微重力导致细胞增殖减少、分泌活性降低和凋亡诱导(10)。模拟微重力可以在地球上通过漂浮或使用一种设备产生三维引力波来产生,从而形成一个平均10−3G的环境,称为3D回转器(11)

DARC-G通用重力模拟系统|图文无关
在日本进行了一项研究,研究使用3D回转器模拟微重力对多形胶质母细胞瘤细胞增殖、线粒体活性和肿瘤细胞对顺铂敏感性的影响;化疗药物。本研究中使用了各种细胞系,包括D54MG(人脑胶质瘤;野生型p53)、U251MG(人脑胶质癌;突变型p53)和T98G(人脑胶质肿瘤;突变型p53)细胞系。样本分为2组;C组;100G力下细胞和CL组;在3D回转器产生的1G力下孵育的细胞。倒置相差显微镜用于检查肿瘤细胞的形态变化。荧光染料罗丹明123用于测量线粒体膜电位。A第一台FACS口径流式细胞仪用于测量细胞周期分布。该实验的结果表明,3天后,模拟微重力通过恶化线粒体活性诱导细胞生长抑制,并增加肿瘤细胞对顺铂的敏感性,12)
对甲状腺癌症细胞的模拟微重力效应:欧空局的不同地面设施,包括RPM和2D和3D倾斜仪S-g,已被用于暴露甲状腺癌症细胞。这些暴露导致暴露的TCC发生了各种变化,包括细胞骨架、ECM、局灶性粘附分子、增殖、凋亡率、迁移率和生长的早期变化([13,14,15,16,17,18)MCS的发展是主要发现。在不同的暴露时间后,受检的TCC和其他癌症(如乳腺癌和前列腺癌)的细胞以3D MCS的形式在r和s-g中发展(19,20,21,22,23,24,25,26)。
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