Expression of Neuronal Markers, NFP and GFAP, in Malignant Astrocytoma

Hashemi, Farhad B.; Naderian, Majid; Kadivar, Maryam; Nilipour, Yalda; Gheytanchi, Elmira

doi:10.7314/apjcp.2014.15.15.6315

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…Local variability of GFAP immunostaining was highlighted in many studies (Cras et al, 1988;Cruz-Sanchez et al, 1992;Gullotta et al, 1985;Herpers et al, 1986;Royds et al, 1986;Sharpe & Baskin, 2016;Tascos et al, 1982;van der Meulen et al, 1978;Velasco et al, 1980). Thus, as was already noted in 1985 (Gullotta et al, 1985) and many times thereafter (Hashemi et al, 2014;Sembritzki et al, 2002) analysis of different areas of the same tumor is necessary to determine GFAP expression levels of a tumor. This is emphasized by two studies that specifically analyzed regional differences within astrocytoma grade IV.…”

Section: Nomentioning

confidence: 93%

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Importance of GFAP isoform‐specific analyses in astrocytoma

Bodegraven

Asperen

Robe

et al. 2019

Glia

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Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and treatment strategies. Although recent developments in the molecular biology of glioma have improved diagnosis, classical histological methods and biomarkers are still being used. The glial fibrillary acidic protein (GFAP) is a classical marker of astrocytoma, both in clinical and experimental settings. GFAP is used to determine glial differentiation, which is associated with a less malignant tumor. However, since GFAP is not only expressed by mature astrocytes but also by radial glia during development and neural stem cells in the adult brain, we hypothesized that GFAP expression in astrocytoma might not be a direct indication of glial differentiation and a less malignant phenotype. Therefore, we here review all existing literature from 1972 up to 2018 on GFAP expression in astrocytoma patient material to revisit GFAP as a marker of lower grade, more differentiated astrocytoma. We conclude that GFAP is heterogeneously expressed in astrocytoma, which most likely masks a consistent correlation of GFAP expression to astrocytoma malignancy grade. The GFAP positive cell population contains cells with differences in morphology, function, and differentiation state showing that GFAP is not merely a marker of less malignant and more differentiated astrocytoma. We suggest that discriminating between the GFAP isoforms GFAPδ and GFAPα will improve the accuracy of assessing the differentiation state of astrocytoma in clinical and experimental settings and will benefit glioma classification.

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Section: Nomentioning

confidence: 93%

“…Zamecnik, Vargova, Homola, Kodet, & Sykova, 2004 Grade III (n = 5) and grade IV (n = 74) GFAP reactivity in all tumors. Hashemi, Naderian, Kadivar, Nilipour, & Gheytanchi, 2014 Grade I, II, and III (n = 15), Grade IV (n = 10)…”

Section: Inconsistent Correlation Of Gfap Expression Levels To Astrmentioning

confidence: 99%

Importance of GFAP isoform‐specific analyses in astrocytoma

Bodegraven

Asperen

Robe

et al. 2019

Glia

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“…In GBM there are low levels of these filaments, suggesting reduced neural differentiation. Thus, independent studies illustrated that the induction of NF proteins in GBM cells causes a reduction in the progression and malignance of the disease [13]. Finally, fatty acid synthase (FASN) protein, a multifunctional enzyme that plays a central role in lipid synthesis, is particularly noteworthy in regard to glioma.…”

Section: Introductionmentioning

confidence: 99%

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

Colapietro

Mancini

Vitale

et al. 2020

IJMS

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Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression of βIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analyses of Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan–Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin’s effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.

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“…Hypoxia-inducible factor 1 (HIF-1α) initiates the transcription of a number of hypoxia-inducible genes, including those encoding vascular endothelial growth factor and its receptors. High levels of nuclear localized HIF-1α are observed in the majority of glioblastomas and anaplastic astrocytomas, particularly surrounding areas of necrosis in glioblastomas [ 15 ], and expression levels correlated with gliomal tumor grade [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Monoamine oxidase B levels are highly expressed in human gliomas and are correlated with the expression of HiF-1α and with transcription factors Sp1 and Sp3

Sharpe

Baskin

2015

Oncotarget

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Monoamine oxidases A and B (MAOA and MAOB) are highly expressed in many cancers. Here we investigated the level of MAOB in gliomas and confirmed its high expression. We found that MAOB levels correlated with tumor grade and hypoxia-inducible factor 1-alpha (HiF-1α) expression. HiF-1α was localized to the nuclei in high-grade gliomas, but it was primarily cytosolic in low-grade gliomas and normal human astrocytes. Expression of both glial fibrillary acidic protein (GFAP) and MAOB are correlated to HiF-1α expression levels. Levels of MAOB are correlated by the levels of transcription factor Sp3 in the majority of GBM examined, but this control of MAOB expression by Sp3 in low grade astrocytic gliomas is significantly different from control in the in the majority of glioblastomas. The current findings support previous suggestions that MAOB can be exploited for the killing of cancer cells. Selective cell toxicity can be achieved by designing non-toxic prodrugs that require MAOB for their catalytic conversion into mature cytotoxic chemotherapeutics.

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Expression of Neuronal Markers, NFP and GFAP, in Malignant Astrocytoma

Cited by 7 publications

References 30 publications

Importance of GFAP isoform‐specific analyses in astrocytoma

Importance of GFAP isoform‐specific analyses in astrocytoma

Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma

Monoamine oxidase B levels are highly expressed in human gliomas and are correlated with the expression of HiF-1α and with transcription factors Sp1 and Sp3

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