Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: A tissue microarray-based study

Saggioro, Fabiano Pinto; Neder, Luciano; Stávale, João Norberto; Paixão-Becker, Aline Nazareth Paiva de; Malheiros, Suzana Mária Fleury; Soares, Fernando Augusto; Pittella, José Eymard Homem; Matias, Caio César Marconato Simões; Colli, Benedicto Oscar; Carlotti, Carlos Gilberto; Franco, Marcello

doi:10.1016/j.prp.2013.12.012

Cited by 39 publications

(31 citation statements)

References 42 publications

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“…Activated NK cells may express CD95 and provide direct immune control by recognizing malignant cells with low or negative expression of MHC antigens [42]. Moreover, glioblastoma cells express the CD95 ligand [43] and may be susceptible to CD95 ligand-initiated cell killing and therapy [44]. Moreover, CD95-positive cytotoxic cells may trigger several pathways of caspase activation in glioblastoma cell lines [45].…”

Section: Discussionmentioning

confidence: 99%

Immune phenotypes predict survival in patients with glioblastoma multiforme

Mostafa

Paľa

Högel³

et al. 2016

J Hematol Oncol

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BackgroundGlioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM.MethodsImmune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively.ResultsUsing descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival.ConclusionsDefined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0272-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Immune phenotypes predict survival in patients with glioblastoma multiforme

Mostafa

Paľa

Högel³

et al. 2016

J Hematol Oncol

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“…The response maps calculated with the source methodology did not correlate well with Caspase 3 staining or necrosis quantification performed in either the training or test set cases. In the first case, this could be due to the fact that untreated GBs have been reported to inherently express activated Caspase 3 as part of their intrinsic process of cell death (35,36) or even related to migration and invasiveness (37). The responding source profile shows an increase in PUFAs, which seem to be related to cumulative apoptosis (38), whereas Caspase 3 content correlates with early stage apoptosis (39), indicating that a different staining, such as TUNEL (40), may be needed to better correlate cumulative apoptosis with the changes detected in the nosologic maps.…”

Section: Correlation Between Calculated Nosologic Maps and Histopathomentioning

confidence: 99%

MRSI-based molecular imaging of therapy response to temozolomide in preclinical glioblastoma using source analysis

et al. 2016

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Characterization of glioblastoma (GB) response to treatment is a key factor for improving patients' survival and prognosis. MRI and magnetic resonance spectroscopic imaging (MRSI) provide morphologic and metabolic profiles of GB but usually fail to produce unequivocal biomarkers of response. The purpose of this work is to provide proof of concept of the ability of a semi‐supervised signal source extraction methodology to produce images with robust recognition of response to temozolomide (TMZ) in a preclinical GB model. A total of 38 female C57BL/6 mice were used in this study. The semi‐supervised methodology extracted the required sources from a training set consisting of MRSI grids from eight GL261 GBs treated with TMZ, and six control untreated GBs. Three different sources (normal brain parenchyma, actively proliferating GB and GB responding to treatment) were extracted and used for calculating nosologic maps representing the spatial response to treatment. These results were validated with an independent test set (7 control and 17 treated cases) and correlated with histopathology. Major differences between the responder and non‐responder sources were mainly related to the resonances of mobile lipids (MLs) and polyunsaturated fatty acids in MLs (0.9, 1.3 and 2.8 ppm). Responding tumors showed significantly lower mitotic (3.3 ± 2.9 versus 14.1 ± 4.2 mitoses/field) and proliferation rates (29.8 ± 10.3 versus 57.8 ± 5.4%) than control untreated cases. The methodology described in this work is able to produce nosological images of response to TMZ in GL261 preclinical GBs and suitably correlates with the histopathological analysis of tumors. A similar strategy could be devised for monitoring response to treatment in patients. Copyright © 2016 John Wiley & Sons, Ltd.

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“…GBM is one of the most intractable types of refractory tumor. Surgery and radiotherapy have been the predominant forms of therapy for GBM, however, the curative effect is poor (4). Gene treatment offers possible approaches in the treatment of GBM, however, it retains shortcomings, including the lack of special target genes and high-efficiency carriers (5).…”

Section: Introductionmentioning

confidence: 99%

Screening of differentially expressed genes associated with human glioblastoma and functional analysis using a DNA microarray

Wang

Wei

et al. 2015

Molecular Medicine Reports

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Abstract. Glioblastoma multiforme (GBM) is the most malignant type of human glioma, and has a poor prognosis. Screening differentially expressed genes (DEGs) in brain tumor samples and normal brain samples is of importance for identifying GBM and to design specific-targeting drugs. The transcriptional profile of GSE30563, containing three genechips of brain tumor samples and three genechips of normal brain samples, was downloaded from Gene Expression Omnibus to identify the DEGs. The differences in the expression of the DEGs in the two different samples were compared through hierarchical biclustering. The co-expression coefficient of the DEGs was calculated using the information from COXPRESdb, the network of the DEGs was constructed and functional enrichment and pathway analysis were performed. Finally, the transcription factors of important DEGs were predicted. A total of 1,006 DEGs, including 368 upregulated and 638 downregulated DEGs, were identified. A close correlation was demonstrated between six important genes, associated with immune response, HLA-DQB1, HLA-DRB1, HLA-DPA1, HLA-B, HLA-DMA and HLA-DRA, and the immune response. Allograft rejection was selected as the most significant pathway. A total of 17 transcription factors, including nuclear factor (NF)-κB and NF-κB1, and their binding sites containing these six DEGs, were also identified. The DEGs, including major histocompatibility complex (MHC) class II, DQβ1, MHC class II, DRβ1, MHC class IB, MHC class II, DMα, MHC class II, DPα1, MHC class II, DRα, may provide novel targets for the diagnosis and treatment of GBM. The transcription factors of these six genes and their binding sites may also provide evidence and direction for identifying target-specific drugs.

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Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: A tissue microarray-based study

Cited by 39 publications

References 42 publications

Immune phenotypes predict survival in patients with glioblastoma multiforme

Immune phenotypes predict survival in patients with glioblastoma multiforme

MRSI-based molecular imaging of therapy response to temozolomide in preclinical glioblastoma using source analysis

Screening of differentially expressed genes associated with human glioblastoma and functional analysis using a DNA microarray

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