Extraneural Metastasis of Primary Glioma Occurring in a Setting of Occupational Ionizing Radiation Exposure

Prabhakaran, Nitya; Miller, Douglas C.; Litofsky, N. Scott; Frazier, Shellaine R.

doi:10.1155/2019/1748739

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…In this brief report, we compared the rate of BEC (bEnd.3 cells) division over 96 h, with those which have been exposed to selected concentrations of conditioned media, which was derived from cultured cancer cells grown under either normoxic (21% O 2 ) or hypoxic (5% O 2 ) conditions of incubation. We chose two types of cancers: breast cancer, which has a preference for metastically relocating to the CNS, and the aggressive glioblastoma cancer, which tends to have a preference for neural tissue with less than 2% metastasis occurring [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

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The Paracrine Effect of Hypoxic and Normoxic Cancer Secretion on the Proliferation of Brain Endothelial Cells (bEnd.3)

Rado

Fisher

2022

Cells

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Background: This study aimed to investigate the disruption of cell cycle phases of bEnd.3 cells exposed to cancer paracrine secretion. Cancer cells have been reported to use the secretion of paracrine factors to compromise the endothelial barrier to prepare for their passage into the parenchyma. As cancer cells are known to act differently under conditions of hypoxia, we investigated how conditional media (CM) derived from breast and glioblastoma cells incubated under conditions of normoxia and hypoxia would affect proliferation of brain endothelial cells (bEnd.3). Methods: Brain endothelial cells (bEnd.3) were cultivated with normoxic and hypoxic CM generated from breast cancer MCF7 cells and glioblastoma U-87 cells. Cell proliferation was evaluated using the trypan blue exclusion assay and phases of the cell cycle were evaluated using flow cytometry. Results: bEnd.3 proliferations was suppressed more aggressively with hypoxic CM after 72 and 96 h; cell cycle analysis showed that paracrine treatment tended to prevent BECs from entering the G2 phase, thus suppressing cell division. Conclusions: MCF7 and U-87 cells induce suppressed proliferation of BECs deferentially under hypoxia by blocking cell cycle progression to the G2 phase.

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Section: Discussionmentioning

confidence: 99%

“…These GBM cells arise from the brain’s glial tissue [ 2 ]. However, as opposed to breast cancer, which is well known to metastically enter into the central nervous system (CNS), GBM has a very low rate (<2%) of metastasis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

The Paracrine Effect of Hypoxic and Normoxic Cancer Secretion on the Proliferation of Brain Endothelial Cells (bEnd.3)

Rado

Fisher

2022

Cells

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“…Analysis of the abstract/full-text of these 165 articles was performed, including collection of the molecular testing information. To investigate the molecular characterization of GBM with extraneural metastasis, 35 full-text articles32,36,38–70 reporting a total of 42 cases that had data from molecular genetic testing or IHC analysis for IDH1 R132H/p53 were analyzed. Pertinent clinical information, including age, sex, timeline of disease course, follow-up, and molecular/immunophenotypic profiling were extracted from the 35 publications.…”

Section: Methodsmentioning

confidence: 99%

“…32,38,39,61,66 EGFR amplification was analyzed in 15 studies and MGMT promoter methylation status was evaluated in 19 studies. Of the 35 studies, 9 did not have documented data of molecular genetic testing, 40,42,44,45,55,58,67 but these were included because the status of TP53 and/or IDH were evaluated by IHC, which has been found to be highly concordant with the molecular assays for these genes performed in other studies. 73,74 A subset of the cases were studied before IDH1/2 was understood, and mutational status for these genes is not known in all cases.…”

Section: Literature Reviewmentioning

confidence: 99%

TP53 Mutation and Extraneural Metastasis of Glioblastoma

Zhang¹,

Katsakhyan²,

LiVolsi³

et al. 2021

American Journal of Surgical Pathology

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Extraneural metastases of glioblastoma (GBM), although rare, are becoming an increasingly recognized occurrence. Currently, the biological mechanism underlying this rare occurrence is not understood. To explore the potential genomic drivers of extraneural metastasis in GBM, we present the molecular features of 4 extraneural metastatic GBMs, along with a comprehensive review and analysis of previously reported cases that had available molecular characterization. In addition to our 4 cases, 42 patients from 35 publications are reviewed. To compare the molecular profiles between GBM cases with extraneural metastasis and the general GBM population, genomic data from GBM samples in The Cancer Genome Atlas (TCGA) database were also analyzed. We found that 64.5% (20/31) of the cases with extraneural metastasis that were tested for TP53 changes had at least 1 TP53 pathogenic variant detected in either 1 or both primary and metastatic tumors. In contrast, TP53 mutation was significantly less frequent in the unselected GBM from TCGA (22.6%, 56/248) (P=0.000). In addition, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was more common in unselected TCGA GBM cases (48.6%, 170/350) than in cases with extraneural metastasis (31.8%, 7/22), although not statistically significant. Although isocitrate dehydrogenase (IDH) mutation is a rare occurrence in high-grade astrocytomas, IDH-mutant grade 4 astrocytomas are at least as likely to metastasize as IDH wild-type GBMs; 3 metastatic cases definitively harbored an IDH1 (p.R132H) mutation in our analysis. Our findings not only provide potential biomarkers for earlier screening of extraneural metastasis, but could also suggest clues to understanding biological mechanisms underlying GBM metastasis, and for the development of therapeutic modalities.

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“…The most common types of malignant brain tumors (MBTs) are gliomas, comprising approximately 80% of all primary brain neoplasms [12][13][14] . Glioblastomas are the most frequent and the most aggressive intraparenchymal MBTs in the adult population 15 .…”

mentioning

confidence: 99%

Assessment of trace metal alterations in the blood, cerebrospinal fluid and tissue samples of patients with malignant brain tumors

Stojsavljević

Vujotić

Rovčanin

et al. 2020

Sci Rep

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The pathogenesis of malignant brain tumors (MBTs) should be better understood due to the evident association between prolonged exposure to metals and increased risk of MBTs. The present research aimed to find trace metals that could contribute to the pathogenesis of MBTs. Essential trace elements (Mn, Co, Zn, Cu, Se) and relevant toxic metals (Al, Ni, As, Sr, Cd, Ce, Pt, Pb, U) in the serum, cell fraction (CF), cerebrospinal fluid (CSF) and cancerous tissue (CT) samples of MBT patients were analyzed. The results were compared with sex-and age-matched control groups. For the first time, this research showed that elemental profiles of serum, CF, CSF and CT samples in MBT patients were significantly altered compared to the appropriate controls, as well as that higher contents of trace elements (particularly Mn, Se, and Pb) could be involved in the pathogenesis of MBTs. However, the most noticeable change found was the elevated U content, indicating its considerable role as a major cerebral discriminator of the presence/absence of MBTs. The U/Se ratio could be considered as an appropriate blood marker in diagnostic MBT evaluation. The reported results could contribute to better understanding of the poorly understood pathogenesis of MBTs. Furthermore, the reported results could highlight a molecular basis for the pathophysiological changes caused by the hazardous effects of trace metals on brain homeostasis. The importance of trace metals in the neurosciences has become more compelling during the first decade of the 21 st century 1 , as there is considerable interest in finding the relationships between trace metals and various neurological diseases, including central nervous system (CNS) malignancies. Metals show their harmful effects at the first stage of cancerogenesis (initiation) 2. Initiation can affect normal biochemical reactions, leading to alterations in metal profiles. Considering that trace metals play a significant role in neoplastic processes, the metal contents in neoplastic samples can differ from the composition in control ones 3. Homeostasis of metals within tight physiological limits is maintained through the mechanisms of uptake, distribution, accumulation, and secretion. Each breakdown has deleterious effects on metal-regulated metabolic pathways and can be a crucial step in the pathogenesis of various diseases. The most important pathway in metal-induced cancerogenesis is the ability of a metal to modulate gene expression by interfering with signal transduction pathways, leading to the deregulation of cell proliferation, activation of numerous transcription factors, disruption of cell cycle course, and apoptosis 4. Metal homeostasis is critical for the proper functioning of the brain 5. The brain is a target organ for toxic environmental pollutants 6. The balance of metals within the brain is regulated through the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier. In physiological conditions, these barriers regulate CNS homeostasis

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Extraneural Metastasis of Primary Glioma Occurring in a Setting of Occupational Ionizing Radiation Exposure

Cited by 7 publications

References 36 publications

The Paracrine Effect of Hypoxic and Normoxic Cancer Secretion on the Proliferation of Brain Endothelial Cells (bEnd.3)

The Paracrine Effect of Hypoxic and Normoxic Cancer Secretion on the Proliferation of Brain Endothelial Cells (bEnd.3)

TP53 Mutation and Extraneural Metastasis of Glioblastoma

Assessment of trace metal alterations in the blood, cerebrospinal fluid and tissue samples of patients with malignant brain tumors

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