Degree Of Malignancy In Gliomas Research Articles

Abstract 4392: Neuropeptide Y system in glioblastoma

Abstract Gliomas constitute the most common primary cerebral tumors of the central nervous system (CNS), with glioblastoma (GBM) representing the most aggressive subtype. Neurotransmitters are important players in maintaining physiological processes in CNS and abnormal levels of their expression is pathogenic, leading to different processes, including neoplasia. Neuropeptide Y (NPY) is one of the neurotransmitters that is found to play a pivotal role in several malignancies. NPY, acting via its cognate receptors Y1, Y2 and Y5 (Y1R, Y2R and Y5R), has been shown to stimulate cancer cell proliferation, migration, invasiveness and dissemination, as well as tumor vascularization in various malignancies including neuroblastoma, Ewing sarcoma, colon, breast, prostate and liver cancers. Thus, the goal of this study was to determine if the NPY system is involved in glioma biology. Our immunohistochemistry staining of NPY, Y1R, Y2R, and Y5R in human GBM tissues revealed positive staining for NPY and Y2R in GBM cells. No expression of Y1R and Y5R was detected in GBM neoplastic population. To further elucidate the association between NPY and its receptors with GBM tumor stage and patients' survival, we used the available clinical data from the Cancer Genome Atlas Program (TCGA) database to analyze the gene expression of the NPY system. Y2R expression was increased in high-grade gliomas, while mRNA levels of NPY, Y1R and Y5R inversely correlated with the degree of glioma malignancy. Moreover, high Y2R expression was associated with worse survival in GBM patients. Importantly, endothelial Y2R is also responsible for angiogenic effects of NPY, suggesting its role in GBM vascularization. Altogether, these data suggest the involvement of NPY/Y2R axis in glioma progression toward more aggressive phenotype. Further functional studies are required to determine the role of the Y2R axis in this process. Citation Format: Nouran Abualsaud, Jason Tilan, Bahauddeen M. Alrfaei, Harrison Glor, Taylor Polk, Ewa Izycka-Swieszewska, Joanna Kitlinska. Neuropeptide Y system in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4392.

Signal-transducing adaptor protein 1 (STAP1) in microglia promotes the malignant progression of glioma.

Glioma is the most malignant primary brain tumor with a poor survival time. The tumour microenvironment, especially glioma-associated microglia/macrophages (GAMs), plays an important role in the pathogenesis of glioma. Currently, microglia (CD11b+/CD45Low) and macrophages (CD11b+/CD45High) are distinguished as distinct cell types due to their different origins. Moreover, signal-transducing adaptor protein 1 (STAP1) plays a role in tumourigenesis and immune responses. However, to date, no studies have been reported on STAP1 in GAMs. The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases were used to investigate the association between STAP1 mRNA levels and clinical parameters (grades, mutations in isocitrate dehydrogenase, and overall survival). RNA-sequencing, qRT-PCR, Western blotting, immunohistochemistry and immunofluorescence analyses were performed to detect the expression level of STAP1 and related proteins. BV-2 cells were used to construct a STAP1-overexpressing cell line. Phagocytosis of BV-2 cells was assessed by flow cytometry and fluorescence microscopy. C57BL/6 mice were used to establish orthotopic and subcutaneous glioma mouse models. Glioma growth was monitored by bioluminescence imaging. STAP1 expression in glioma-associated microglia is positively correlated with the degree of malignancy and poor prognosis of glioma. Moreover, STAP1 may promote M2-like polarisation by increasing ARG1 expression and inhibiting microglial phagocytosis of microglia. Increased ARG1 may be associated with the IL-6/STAT3 pathway. Impaired phagocytosis may be associated with decreased cofilin and filopodia. STAP1 is positively associated with the degree of glioma malignancy and may represent a potential novel therapeutic target for glioma.

Knocking down of Polo-like kinase 2 inhibits cell proliferation and induced cell apoptosis in human glioma cells

AimsPolo-like kinase 2 (PLK2) belongs to a family of serine/threonine kinases, and it is involved in tumorigenesis. The present study aimed to explore the potential clinical significance of PLK2 in the development of gliomas. Main methodsImmunohistochemistry (IHC) was performed to detect the expression of PLK2 in glioma tissues. Cell proliferation and apoptosis were determined by Cell Counting Kit 8 (CCK8) and flow cytometry analysis, respectively. Key findingsPLK2 expression gradually increased with the degree of glioma malignancy. High PLK2 expression was associated with a poor prognosis in glioma. Short hairpin RNAs targeting PLK2 (shPLK2) inhibited the viability and induced apoptosis of glioma cells, both in vitro and in vivo. Ring finger protein 180 (RNF180), an E3 ubiquitin ligase, interacted with PLK2 and induced the ubiquitination of PLK2. Overexpression of PLK2 in glioma cells significantly inhibited RNF180 upregulation-induced cell apoptosis. The expression level of RNF180 gradually decreased with the degree of glioma malignancy. SignificanceKnocking down of PLK2 may suppress the glioma development through cancer cell proliferation inhibition and cell apoptosis promotion. Furthermore, RNF180 may mediate the ubiquitination of PLK2. The present findings may help improve the clinical management of glioma in the future.

What Does Reduced FDG Uptake Mean in High-Grade Gliomas?

As well as in many others cancers, FDG uptake is correlated with the degree of malignancy in gliomas, that is, commonly high FDG uptake in high-grade gliomas. However, in clinical practice, it is not uncommon to observe high-grade gliomas with low FDG uptake. Our aim was to explore the tumor metabolism in 2 populations of high-grade gliomas presenting high or low FDG uptake. High-resolution magic-angle spinning nuclear magnetic resonance spectroscopy was realized on tissue samples from 7 high-grade glioma patients with high FDG uptake and 5 high-grade glioma patients with low FDG uptake. Tumor metabolomics was evaluated from 42 quantified metabolites and compared by network analysis. Whether originating from astrocytes or oligodendrocytes, the high-grade gliomas with low FDG avidity represent a subgroup of high-grade gliomas presenting common characteristics: low aspartate, glutamate, and creatine levels, which are probably related to the impaired electron transport chain in mitochondria; high serine/glycine metabolism and so one-carbon metabolism; low glycerophosphocholine-phosphocholine ratio in membrane metabolism, which is associated with tumor aggressiveness; and finally negative MGMT methylation status. It seems imperative to identify this subgroup of high-grade gliomas with low FDG avidity, which is especially aggressive. Their identification could be important for early detection for a possible personalized treatment, such as antifolate treatment.

Some features controlling the blood D-dimer level after resection of malignant brain glioma

The study included 50 patients. Three to four weeks after resection of malignant brain glioma (MBG), the blood D-dimer level was determined in patients immediately before the onset of ART. An increase in the blood D-dimer level more than by 0.25 μg/mL was detected in 78% of patients. More often, a high D-dimer level was detected in patients aged 60 years or more. In the same age group, an increase in the D-dimer level was significantly larger (p<0.05) than in younger patients (1.2 and 0.6 μg/mL, respectively). The degree of brain tumor malignancy did not affect the rate and value of an increase in the blood D-dimer level. Our findings indicate that an increased blood D-dimer level in patients without symptoms of venous thrombosis after craniotomy for MBG is more pronounced in patients aged 60 years and over. The degree of glioma malignancy has no significant effect on this indicator.

Modern tactics of treatment of malignant glyom of the brain and the case of the complete answer of the tumor on the background of the long-term reception of bevacizumab

Gliomas are common primary brain tumors in adults. This high degree of glioma malignancy is characterized by a disappointing outlook, despite the modern approaches to treatment. Therefore cases of prolonged relapse-free period of the disease, as well as treatment regimen and control regimen concerning gliomas with high degree of anaplasia are of exceptional interest. Even more exceptionally interesting is the drug bevacizumab, which in our clinical practice allowed to provide the patient with the diseasefree high-grade glioma from 2012 year to the present.

Correlation between Deregulated Expression of PER2 Gene and Degree of Glioma Malignancy

Correlation between Deregulated Expression of PER2 Gene and Degree of Glioma Malignancy

Expression of Rb2/p130 protein correlates with the degree of malignancy in gliomas

It has been reported that there is an inverse correlation between the immunohistochemical expression of Rb2/p130, a member of the retinoblastoma gene family, and the degree of malignancy in at least some histological types. In order to investigate the expression of this protein in gliomas, we evaluated 58 samples from patients with resected gliomas. We focused on the relationship between the degree of malignancy of the glioma and the immunohistochemical detection of Rb2/p130. Expression of Rb2/p130 was observed in 38 glioma specimens (65.5%), including a high expression level in low-grade glioma specimens (> 30% positive cells in 84% of tumors) and a low expression level in high-grade glioma specimens (> 30% positive cells in 12% of tumors). The most aggressive of the gliomas exhibited very low to undetectable levels of Rb2/p130. Moreover, we observed an inverse correlation between Rb2/p130 expression and the degree of malignancy. These findings suggest that the differentiation of gliomas might be partially mediated by the Rb2/p130 gene, and that Rb2/ p130 expression can additionally be an indicator of a better prognosis in patients with gliomas.

Expression of matrix metalloproteinase-2 in glial and neuronal tumor cell lines: inverse correlation with proliferation rate

The expression of matrix metalloproteinases (MMPs) has been found to be positively correlated to the degree of malignancy in gliomas, indicating that poorly differentiated brain tumor cells produce more MMPs than differentiated ones. We determined the production of active MMP-2 in five glial (U138MG, U373MG, A172, C6, GOS-3), two neuronal (SK-N-SH, SK-N-MC), and two pluripotent cell lines with facultative neuronal and glial differentiation (P19 and NT2) by gelatin zymography. The MMP-2 activity profiles were compared to the proliferative activities of the cell lines. MMP-2 expression varied from barely existent (P19 cells) to strong (U138MG and SK-N-SH). Interestingly, for the cell lines with high MMP-2 expression levels, low proliferative activities were recorded, and vice versa. Retinoic acid induced neuronal differentiation and a reduction of proliferation of P19 cells; the differentiated cells produced significantly more MMP-2 than untreated cells. Upon confluency, GOS-3 cells showed reduced proliferation, but increased MMP expression. Thus, proliferative activity was inversely correlated to MMP-2 expression in the tumor cell lines analyzed.