GFAP-Positive Neoplastic Astrocytes in Spontaneous Oligodendrogliomas and Mixed Gliomas of Rats

Nagatani, Mariko; Yamakawa, Seiki; Saito, Tsubasa; Andõ, Ryõ; Hoshiya, Toru; Tamura, Kazutoshi; Uchida, Katsuhisa

doi:10.1177/0192623312463987

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…GFAP is the principal intermediate filament of mature astrocytes and is expressed in normal as well as in neoplastic astrocytes. 10,23 Consistent with previous observations, a higher proportion of astrocytomas was positive for GFAP as compared with oligodendrogliomas in the present study. This is in overall concordance with numerous reports which describe a high GFAP expression in astrocytomas but infrequent expression in oligodendrogliomas.…”

Section: Discussionsupporting

confidence: 93%

Canine Central Nervous System Neoplasm Phenotyping Using Tissue Microarray Technique

et al. 2017

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Tissue microarrays (TMAs) represent a useful technique for the simultaneous phenotyping of large sample numbers and are particularly suitable for histopathologic tumor research. In this study, TMAs were used to evaluate semiquantitatively the expression of multiple antigens in various canine central nervous system (CNS) neoplasms and to identify markers with potential discriminative diagnostic relevance. Ninety-seven canine CNS neoplasms, previously diagnosed on hematoxylin and eosin sections according to the World Health Organization classification, were investigated on TMAs, with each tumor consisting of 2 cylindrical samples from the center and the periphery of the neoplasm. Tumor cells were phenotyped using a panel of 28 monoclonal and polyclonal antibodies, and hierarchical clustering analysis was applied to group neoplasms according to similarities in their expression profiles. Hierarchical clustering generally grouped cases with similar histologic diagnoses; however, gliomas especially exhibited a considerable heterogeneity in their positivity scores. Multiple tumor groups, such as astrocytomas and oligodendrogliomas, significantly differed in the proportion of positive immunoreaction for certain markers such as p75, AQP4, GFAP, and S100 protein. The study highlights AQP4 and p75 as novel markers, helping to discriminate between canine astrocytoma and oligodendroglioma. Furthermore, the results suggest that p75 and proteolipid protein may represent useful markers, whose expression inversely correlates with malignant transformation in canine astrocytomas and oligodendrogliomas, respectively. Tissue microarray was demonstrated to be a useful and time-saving tool for the simultaneous immunohistochemical characterization of multiple canine CNS neoplasms. The present study provides a detailed overview of the expression patterns of different types of canine CNS neoplasms.

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Section: Discussionsupporting

confidence: 93%

Canine Central Nervous System Neoplasm Phenotyping Using Tissue Microarray Technique

et al. 2017

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“…Reactive astrocytes create an inflammatory microenvironment in the areas surrounding the tumor and help in progression and spread of tumor by activating MMPs which degrade extracellular matrix and eventually help in the spread of tumor to adjacent healthy areas in case of brain tumors 27 . In accordance with previous reports, IHC with GFAP revealed a dense population of reactive astrocytes in the peri tumoral region and around the blood vessels in control tumor section 27,31 . Surprisingly, treatment with RSV and TMZ + RSV showed almost complete elimination of reactive astrocytes from peri-tumoral areas and blood vessels.…”

Section: Discussionsupporting

confidence: 92%

Roscovitine effectively enhances antitumor activity of temozolomide in vitro and in vivo mediated by increased autophagy and Caspase-3 dependent apoptosis

Pandey

Ranjan

Narne

et al. 2019

Sci Rep

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Gliomas are incurable solid tumors with extremely high relapse rate and definite mortality. As gliomas readily acquire resistance to only approved drug, temozolomide (TMZ), there is increasing need to overcome drug resistance by novel therapeutics or by repurposing the existing therapy. In the current study, we investigated antitumor efficacy of roscovitine, a Cdk inhibitor, in combination with TMZ in vitro (U87, U373, LN 18 and C6 cell lines) and in vivo (orthotopic glioma model in Wistar rats) glioma models. We observed that TMZ treatment following a pre-treatment with RSV significantly enhanced chemo-sensitivity and suppressed the growth of glioma cells by reducing Cdk-5 activity and simultaneous induction of autophagy and Caspase-3 mediated apoptosis. Additionally, reduced expression of Ki67, GFAP and markers of angiogenesis (CD31, VEGF) was observed in case of TMZ + RSV treatments. Also, presence of reactive astrocytes in peri-tumoral areas and in areas around blood vessels was completely diminished in TMZ + RSV treated brain sections. Taken together, results in the current study provide evidence that RSV in conjunction with TMZ restricts glioma growth, reduces angiogenesis and also eliminates reactive astrocytes thereby preventing the spread of glioma to adjacent healthy brain tissues and thus might be more potent therapeutic option for glioma.

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“…The markers included Olig-2, GFAP, and nestin. Their interpretation of results from these stains support the identification of GFAP+ spindle cells that are morphologically different from reactive astrocytes and postulated that these are the first reported GFAP+ neoplastic astrocytes (Nagatani et al, 2013). Figure 1 depicts morphologic and immunohistochemical characteristics of microglial cell tumors.…”

Section: Distinguishing Between Astrocytomas and Microglial Cell Tumomentioning

confidence: 73%

Central nervous system tumors in 2-year rat carcinogenicity studies: perspectives on human risk assessment

2019

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Rodent in vivo carcinogenicity bioassays are required for human risk assessment and have been utilized in this capacity for decades. Accordingly, there is an abundance of data that could be accessed and analyzed to better understand the translatability of xenobiotic-induced rodent tumors to human risk assessment. In the past decade, various groups have published assessments of the value garnered by these lifetime rodent studies. Results and recommendations from the International Council for Harmonization Expert Working Group (ICH-S1 EWG) on the predictability of the current testing paradigm and proposal for an integrated approach to human carcinogenicity risk assessment are pending. Central nervous system (CNS) tumors in rats are rare and translatability to human remains unknown. This review focuses on microglial cell tumors (MCT) of the CNS in rats including its classification, nomenclature, incidence and translatability to human risk assessment. Based on emerging immunohistochemistry (IHC) characterization, glial tumors previously thought of astrocytic origin are more likely MCTs. These may be considered rodent specific and glucose dysregulation may be one component contributing to their formation. Based on review of the literature, MCTs are rarely diagnosed in humans, thus this tumor type may be rat-specific. We propose to include MCTs as a tumor type in revised International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) classification and all glial tumors to be classified as MCTs unless proven otherwise by IHC.

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GFAP-Positive Neoplastic Astrocytes in Spontaneous Oligodendrogliomas and Mixed Gliomas of Rats

Cited by 9 publications

References 22 publications

Canine Central Nervous System Neoplasm Phenotyping Using Tissue Microarray Technique

Canine Central Nervous System Neoplasm Phenotyping Using Tissue Microarray Technique

Roscovitine effectively enhances antitumor activity of temozolomide in vitro and in vivo mediated by increased autophagy and Caspase-3 dependent apoptosis

Central nervous system tumors in 2-year rat carcinogenicity studies: perspectives on human risk assessment

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