bims-malgli 2020-12-27 papers

Issue of 2020–12–27
six papers selected by
Oltea Sampetrean, Keio University

Cancers (Basel). 2020 Dec 17. pii: E3813. [Epub ahead of print]12(12):

MiR-181 Family Modulates Osteopontin in Glioblastoma Multiforme.

Anantha Marisetty, Jun Wei, Ling-Yuan Kong, Martina Ott, Dexing Fang, Aria Sabbagh, Amy B Heimberger.

MiRNAs can silence a wide range of genes, which may be an advantage for targeting heterogenous tumors like glioblastoma. Osteopontin (OPN) plays both an oncogenic role in a variety of cancers and can immune modulate macrophages. We conducted a genome wide profiling and bioinformatic analysis to identify miR-181a/b/c/d as potential miRNAs that target OPN. Luciferase assays confirmed the binding potential of miRNAs to OPN. Expression levels of miR-181a/b/c/d and OPN were evaluated by using quantitative real-time PCR and enzyme-linked immunosorbent assay in mouse and human glioblastomas and macrophages that showed these miRNAs were downregulated in Glioblastoma associated CD11b+ cells compared to their matched blood CD14b+ cells. miRNA mimicking and overexpression using lentiviruses showed that MiR-181a overexpression in glioblastoma cells led to decreased OPN production and proliferation and increased apoptosis in vitro. MiR-181a treatment of immune competent mice bearing intracranial glioblastoma demonstrated a 22% increase in median survival duration relative to that of control mice.

Keywords: cancer stem cells; glioblastoma; glioblastoma-infiltrating macrophages (GIMs); macrophages; miRNA, miR-181; microRNAs; osteopontin; osteopontin (OPN); reverse transcription polymerase chain reaction (RT-PCR)

DOI: https://doi.org/10.3390/cancers12123813

Carcinogenesis. 2020 Dec 21. pii: bgaa139. [Epub ahead of print]

NFIA and NFIB function as tumour suppressors in high-grade glioma in mice.

Kok-Siong Chen, Zorana Lynton, Jonathan W C Lim, Thomas Robertson, Richard M Gronostajski, Jens Bunt, Linda J Richards.

Nuclear factor one (NFI) transcription factors are implicated in both brain development and cancer in mice and humans and play an essential role in glial differentiation. NFI expression is reduced in human astrocytoma samples, particularly those of higher grade, whereas over-expression of NFI protein can induce the differentiation of glioblastoma cells within human tumour xenografts and in glioblastoma cell lines in vitro. These data indicate that NFI proteins may act as tumour suppressors in glioma. To test this hypothesis, we generated complex mouse genetic crosses involving six alleles to target gene deletion of known tumour suppressor genes that induce endogenous high-grade glioma in mice, and overlaid this with loss of function Nfi mutant alleles, Nfia and Nfib, a reporter transgene and an inducible Cre allele. Deletion of Nfi resulted in reduced survival time of the mice, increased tumour load and a more aggressive tumour phenotype than observed in glioma mice with normal expression of NFI. Together, these data indicate that NFI genes represent a credible target for both diagnostic analyses and therapeutic strategies to combat high-grade glioma.

DOI: https://doi.org/10.1093/carcin/bgaa139

Front Oncol. 2020 ;10 602378

The Epigenetics of Glioma Stem Cells: A Brief Overview.

Luis M Valor, Irati Hervás-Corpión.

Glioma stem cells (GSCs) are crucial in the formation, perpetuation and recurrence of glioblastomas (GBs) due to their self-renewal and proliferation properties. Although GSCs share cellular and molecular characteristics with neural stem cells (NSCs), GSCs show unique transcriptional and epigenetic features that may explain their relevant role in GB and may constitute druggable targets for novel therapeutic approaches. In this review, we will summarize the most important findings in GSCs concerning epigenetic-dependent mechanisms.

Keywords: DNA; H3.3; HDACi; Polycomb; acetylation; glioblastoma; histone; methylation

DOI: https://doi.org/10.3389/fonc.2020.602378

Cancer Treat Res Commun. 2020 Dec 02. pii: S2468-2942(20)30090-3. [Epub ahead of print]25 100255

Featuring how calcium channels and calmodulin affect glioblastoma behavior. A review article.

Mohammed A Azab, Abdulraheem Alomari, Ahmed Y Azzam.

Glioblastoma (GBM) is considered to be the most aggressive primary brain tumor with an extremely bad prognosis. Recurrence after treatment is a major problem with a survival rate for one year ranging about 39.7%. Ideal outcomes are still difficult to be achieved despite the recent treatment combinations. The ultimate capacity to regrow after resection is considered to be related to the availability of self-regenerating populations of stem cells. We made a literature review interpreting how calcium channels and calcium-regulated proteins mechanistically elaborate glioblastoma virulence in different ways. Calcium channels, and calcium-regulated proteins have shown diverse interconnected roles in shaping different aspects of GBM biology as indicated in some experimental studies. The beneficial prospective of those roles granting GBM different aggressive potentials pose variable applications in targeted therapy whether it is experimental or clinical trials.

Keywords: CNS; Calcium; Calmodulin; Glioblastoma; Stem cells

DOI: https://doi.org/10.1016/j.ctarc.2020.100255

J Cancer Res Ther. 2020 Oct-Dec;16(6):16(6): 1476-1481

Yet another utility for isocitrate dehydrogenase.1: Can it serve as an immunomarker to assess tumor margins in gliomas?

Shaline Rao, Aarthi Rajkumar, Sandhya Sundaram, Mintu Elizabeth Joyce, Prathiba Duvuru.

Background: Isocitrate dehydrogenase-1 (IDH1) mutation is now an established early event in gliomagenesis. The ability to detect this mutation by several techniques including immunohistochemistry makes it a significant marker for diagnosing and prognosticating gliomas. This study was done to assess the expression of mutant IDH1 in different grades of gliomas and evaluate its utility in differentiating reactive gliosis from glioma and defining surgical margins of these tumors in the operative specimens.
Materials and Methods: A total of fifty cases including equal number of Grade I, II, III, and IV gliomas and gliosis were included in the study. Formalin-fixed, paraffin-embedded tissue sections from these lesions were immunostained with IDH1 and Ki-67 antibody, and percentage of tumor cells that stained positive with these markers was assessed.
Results: Grades II, III, and IV showed consistent immunopositivity for IDH1. No immunostaining was noted in Grade I glioma and gliosis. Mean Ki-67 labeling index correlated with grades of gliomas with low activity in Grade I and high activity in Grade IV. Individual tumor cells infiltrating into adjacent normal brain parenchyma also stained positive with IDH1 antibody.
Conclusion: Immunostaining for IDH1 mutation can be utilized as a reliable marker in the precise diagnosis of diffuse gliomas and also in objective assessment of surgical margins to differentiate gliomas from gliosis.

Keywords: Glioma; infiltration; isocitrate dehydrogenase-1; surgical margin

DOI: https://doi.org/10.4103/jcrt.JCRT_22_17

Neuro Oncol. 2020 Dec 21. pii: noaa295. [Epub ahead of print]

Epidemiology of Brainstem High-Grade Gliomas in Children and Adolescents in the United States, 2000-2017.

Nirav Patil, Michael E Kelly, Debra Nana Yeboa, Robin A Buerki, Gino Cioffi, Sweta Balaji, Quinn T Ostrom, Carol Kruchko, Jill Barnholtz-Sloan.

BACKGROUND: Limited population-based data exists for the brainstem gliomas for children ages ≤19 years, which includes high-grade aggressively-growing tumors such as diffuse intrinsic pontine glioma (DIPG). We examined the overall incidence and survival patterns in children with brainstem High-Grade glioma (HGG) by age, sex, and race and ethnicity.
METHODS: We used data from Central Brain Tumor Registry of the United States (CBTRUS), obtained through data use agreements with the Centers for Disease Control (CDC) and the National Cancer Institute (NCI) from 2000 - 2017, and survival data from the CDC's National Program of Cancer Registries (NPCR), from 2001 - 2016 for malignant brainstem HGG for ages ≤19 years (per WHO ICD-O-3 codes). HGG was determined by established histologic and/or imaging criteria. Age-adjusted incidence rates and survival data were used to assess differences overall and by age, sex race, and ethnicity.
RESULTS: The incidence of brainstem HGG was higher among the female and Non-Hispanic population. Majority (69.8%) of these tumors were diagnosed radiographically. Incidence was higher in children aged 01-09 years compared to older children. Whites had a higher incidence compared to Blacks. However, the risk of death was higher among Blacks and Other race compared to Whites. There was no difference in survival by sex.
CONCLUSIONS: We report the most comprehensive incidence and survival data on these lethal brainstem HGGs. Incidence and survival among patients with brainstem HGGs differed significantly by race, ethnicity, age-groups and grade.

Keywords: Brainstem; CBTRUS; DIPG; Glioma; High-Grade Glioma

DOI: https://doi.org/10.1093/neuonc/noaa295