Comparison of Elemental Anomalies Following Implantation of Different Cell Lines of Glioblastoma Multiforme in the Rat Brain: A Total Reflection X-ray Fluorescence Spectroscopy Study.

Karolina Planeta,Agnieszka Drozdz,Joanna Chwiej,Katarzyna Matusiak,Krzysztof Janeczko,Beata Ostachowicz,Zuzanna Setkowicz,Natalia Janik-Olchawa,Damian Ryszawy

doi:10.1021/acschemneuro.0c00648

Karolina Planeta, Agnieszka Drozdz + Show 7 more

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https://doi.org/10.1021/acschemneuro.0c00648

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Abstract

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.

Highlights

One of the most common primary brain tumors are gliomas, which usually develop from glial cells, non-neuronal cells supporting the functions of neurons
Results of our experiment revealed a decrease of potassium level in both left and right brain hemispheres taken from rats subjected to implantation of U87MG cells
The largest number of elemental anomalies, both within implanted and intact hemispheres, was observed in rats subjected to implantation of U87MG cells

Summary

Introduction

One of the most common primary brain tumors are gliomas, which usually develop from glial cells, non-neuronal cells supporting the functions of neurons. As different types of glial cells exist, various types of gliomas are distinguished, but the most aggressive is glioblastoma multiforme (GBM), which accounts for about 54% of all glioma cases and represents about 16% of all brain tumors. Median survival of patients suffering from GBM is 14−16 months and only 9.8% of them survive 5 years.. The high aggressiveness of GBM results from its complex nature, which includes the presence of necrotic and hemorrhagic regions or cellular atypia within the same tumor mass. Standard glioblastoma treatment includes surgical resection of the tumor, radiotherapy, and chemotherapy, usually based on temozolomide (TMZ). Despite such radical therapy, there is no significant improvement in the patient survival rate. The location and infiltrating nature of the tumor prevent its total resection and make precise radio-

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