Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments.
Mahmoud S. Alghamri,Brandon L. McClellan,Margaret S. Hartlage,Santiago Haase,Syed M Faisal,Rohit Thalla,Ali Dabaja,Kaushik Banerjee,Stephen Carney,Anzar A. Mujeeb,Michael R. Olin,James J. Moon,Anna Schwendeman,Pedro R. Lowenstein,Maria G. Castro +14 more
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TLDR
Glioblastomas are one of the most lethal types of cancers accounting for ~80% of all central nervous system (CNS) primary malignancies [1, as discussed by the authors.Abstract:
Gliomas are one of the most lethal types of cancers accounting for ~80% of all central nervous system (CNS) primary malignancies [1; 2]. Amongst gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis [2]. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas.read more
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Cell-based and cell-free immunotherapies for glioblastoma: current status and future directions
None Robert Lu,Matthew McGiffen +1 more
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TSPO PET Imaging as a Potent Non-Invasive Biomarker for Diffuse Intrinsic Pontine Glioma in a Patient-Derived Orthotopic Rat Model
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Book ChapterDOI
Epigenetics and personalized medicine of brain cancer
TL;DR: In this paper , the second most frequent type of neoplasms in children and adults, the primary tumors of the CNS being the leading cause of death in these patients, and the plethora of epigenetic mechanisms makes it very difficult to be comprehended since it includes not only the methylation of DNA sequences, histone acetylation, and miRNA regulation but also G-quadruplex structures.
Posted ContentDOI
iPSC-derived astrocytes to model phenotype-specific differential neuroinflammatory and metabolic responses in X-linked adrenoleukodystrophy
TL;DR: In this paper , a miRNA sequencing in X-linked adrenoleukodystrophy (X-ALD) cells derived from induced pluripotent stem cells (iPSC) derived from healthy controls and patients with AMN or cALD was performed.
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