Altered Elemental Distribution in Male Rat Brain Tissue as a Predictor of Glioblastoma Multiforme Growth—Studies Using SR-XRF Microscopy

Abstract

Glioblastoma multiforme (GBM) is a particularly malignant primary brain tumor. Despite enormous advances in the surgical treatment of cancer, radio- and chemotherapy, the average survival of patients suffering from this cancer does not usually exceed several months. For obvious ethical reasons, the search and testing of the new drugs and therapies of GBM cannot be carried out on humans, and for this purpose, animal models of the disease are most often used. However, to assess the efficacy and safety of the therapy basing on these models, a deep knowledge of the pathological changes associated with tumor development in the animal brain is necessary. Therefore, as part of our study, the synchrotron radiation-based X-ray fluorescence microscopy was applied for multi-elemental micro-imaging of the rat brain in which glioblastoma develops. Elemental changes occurring in animals after the implantation of two human glioma cell lines as well as the cells taken directly from a patient suffering from GBM were compared. Both the extent and intensity of elemental changes strongly correlated with the regions of glioma growth. The obtained results showed that the observation of elemental anomalies accompanying tumor development within an animal’s brain might facilitate our understanding of the pathogenesis and progress of GBM and also determine potential biomarkers of its extension. The tumors appearing in a rat’s brain were characterized by an increased accumulation of Fe and Se, whilst the tissue directly surrounding the tumor presented a higher accumulation of Cu. Furthermore, the results of the study allow us to consider Se as a potential elemental marker of GBM progression.

Glioblastoma multiforme influence on the elemental homeostasis of the distant organs: the results of inter-comparison study carried out with TXRF method

“…noticed that the level of the element is higher within in the region of brain tumor comparing to the healthy tissue 98 . Similar observations were done during our previous study, analyzing brain samples taken from the area of glioma cells implantation 35 . The increased demand and accumulation of selenium in GBM tissue may be the cause of its low serum level.…”

“…As it was shown in our earlier work 35 and one can see in the Figures S1 - S3 from the Appendix, after the implantation of T98G cells in the rat brain, no neoplastic tumor had developed. Despite this fact, in this study the animals from group T showed a number of elemental anomalies in the examined organs.…”

“…shown that cancerous GBM tissue is characterized by diminished concentration of this element, which is probably related to the decrease of phospholipids (i.e. lecithin, sphingomyelin) level within tumor 35 , 46 , 47 . The present study showed decreased concentration of P in most of the examined organs.…”

Advancements in Image-Based Models for High-Grade Gliomas Might Be Accelerated

“…Planeta and colleagues applied X-ray fluorescence microscopy based on synchrotron radiation to study the micro changes of the rat brain in which HGG develops [103] (Figure 10A) (Table 2). The changes in the animal brain implanted with two different stabilized lines of human HGG and with an HGG (GB) taken directly from a patient were compared.…”

“…Orthotopic rat models of GB. [103] LAT1 as a new marker for GICs. LAT1+ and LAT1-glioma cells sorted by flow cytometry.…”