AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, Krakow 30-059, Poland.
Jagiellonian University, Institute of Zoology and Biomedical Research, Krakow 31-007, Poland.
ACS Chem Neurosci. 2020 Dec 16;11(24):4447-4459. doi: 10.1021/acschemneuro.0c00648. Epub 2020 Nov 18.
Glioblastoma multiforme (GBM) is a primary brain tumor with a very high degree of malignancy and is classified by WHO as a glioma IV. At present, the treatment of patients suffering from GBM is based on surgical resection of the tumor with maximal protection of surrounding tissues followed by radio- and pharmacological therapy using temozolomide as the most frequently recommended drug. This strategy, however, does not guarantee success and has devastating consequences. Testing of new substances or therapies having potential in the treatment of GBM as well as detection of their side effects cannot be done on humans. Animal models of the disease are usually used for these purposes, and one possibility is the implantation of human tumor cells into rodent brains. Such a solution was used in the present study the purpose of which was comparison of elemental anomalies appearing in the brain as a result of implantation of different glioblastoma cell lines. These were two commercially available cell lines (U87MG and T98G), as well as tumor cells taken directly from a patient diagnosed with GBM. Using total reflection X-ray fluorescence we determined the contents of P, S, K, Ca, Fe, Cu, Zn, and Se in implanted-left and intact-right brain hemispheres. The number of elemental anomalies registered for both hemispheres was positively correlated with the invasiveness of GBM cells and was the highest for animals subjected to U87MG cell implantation, which presented significant decrease of P, K, and Cu levels and an increase of Se concentration within the left hemisphere. The abnormality common for all three groups of animals subjected to glioma cell implantation was increased Fe level in the brain, which may result from higher blood supply or the presence of hemorrhaging regions. In the case of the intact hemisphere, elevated Fe concentration may also indicate higher neuronal activity caused by taking over some functions of the left hemisphere impaired as a result of tumor growth.
多形性胶质母细胞瘤(GBM)是一种高度恶性的原发性脑肿瘤,被世界卫生组织(WHO)归类为 IV 级胶质瘤。目前,GBM 患者的治疗基于最大限度地保护周围组织的肿瘤切除术,然后进行放射和药物治疗,其中替莫唑胺是最常推荐的药物。然而,这种策略并不能保证成功,而且会带来毁灭性的后果。为了检测治疗 GBM 的新物质或疗法的潜在作用及其副作用,不能在人体上进行测试。通常使用疾病的动物模型来进行这些测试,其中一种可能性是将人类肿瘤细胞植入啮齿动物的大脑中。本研究就采用了这种解决方案,其目的是比较植入不同胶质母细胞瘤细胞系后大脑中出现的元素异常。这些细胞系是两种市售的细胞系(U87MG 和 T98G),以及直接从诊断为 GBM 的患者中取出的肿瘤细胞。使用全反射 X 射线荧光法,我们确定了植入左脑半球和完整右脑半球中的 P、S、K、Ca、Fe、Cu、Zn 和 Se 的含量。两个脑半球记录到的元素异常数量与 GBM 细胞的侵袭性呈正相关,并且对于接受 U87MG 细胞植入的动物最高,这些动物的 P、K 和 Cu 水平显著降低,而 Se 浓度升高,左半球。所有三组接受神经胶质瘤细胞植入的动物共有的异常是大脑中铁水平升高,这可能是由于更高的血液供应或出血区域的存在。对于完整的脑半球,铁浓度升高也可能表明由于肿瘤生长导致左半球受损而接管了一些功能,神经元活动增加。