TMIC-19. NEURODEVELOPMENTAL SUBTYPES SHAPE LIPID METABOLIC REPROGRAMMING IN GLIOMAS

alexandrossfakianakis shared this article with you from Inoreader TMIC-19. NEURODEVELOPMENTAL SUBTYPES SHAPE LIPID METABOLIC REPROGRAMMING IN GLIOMAS via # Neuro-Oncology Current Issue Abstract Gliomas have been classified into molecular (proneural, classical, mesenchymal) and neurodevelopmental (astrocyte, mesenchymal, neural progenitor cell (NPC), oligodendrocyte progenitor cell (OPC)) subtypes describing inter- and intra-tumoral heterogeneity; however, the functional outcomes and therapeutic implications of these subtypes has yet to be fully described. Metabolic reprogramming is a hallmark of cancer, and malignant cells, including gliomas, acquire metabolic adaptations in response to a multitude of intrinsic (oncogenotype, mutations) and extrinsic (tumor microenvironment) factors to fuel neoplastic progression. Altered metabolism in glioma is of particular interest given the extensive molecular heterogeneity of tumors, while also developing in the brain microenvironment, a tissue known for its unique metabolic milieu. It is unknown whether neurodevelopmental subtypes influence metabolism in gliomas. Preliminary comprehensive lipidomi c and transcriptomic analysis of over 200 patient-derived glioma samples revealed that distinct lipid signatures were linked to neurodevelopmental subtypes. Specifically, proneural-like gliomas (OPC, NPC, Neuron) had a lipid metabolic profile enriched in ether lipids. Conversely, mesenchymal-like gliomas (radial glia, MES.progenitor, vascular) have a lipid metabolic profile enriched in triacylglycerides (TAGs). Intriguingly, these differences in lipid metabolic programs between subtypes were associated with environmental dependencies; in contrast to more mesenchymal like gliomas, which could grow irrespective of tumor microenvironment (brain or in vitro cell culture), the proneural-like gliomas required features of the brain microenvironment to accumulate complex fatty acids and grow. Collectively, these data emphasize the metabolic heterogeneity within gliomas, and reveal a subset of gliomas that lack metabolic plasticity in fatty acid biosynthetic programs, indicating a potential brain-microenvironment specific metabolic dependency linked to transcriptional identity that may be targeted for therapy. View on Web

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CSIG-19. THE PI3K/AKT/MTOR SIGNALING CASCADE MAY CONTRIBUTE TO SEX DIFFERENCES IN GLIOBLASTOMA

alexandrossfakianakis shared this article with you from Inoreader CSIG-19. THE PI3K/AKT/MTOR SIGNALING CASCADE MAY CONTRIBUTE TO SEX DIFFERENCES IN GLIOBLASTOMA via # Neuro-Oncology Current Issue Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. It is more prevalent in males and female patients exhibit a survival advantage. Understanding the molecular mechanisms that underlie those sex differences could support novel treatment strategies. The PI3K/Akt/mTOR signaling cascade plays a crucial role in GBM development and progression as it is involved in the regulation of cellular growth, survival, nutrient sensing, and metabolic activity. To investigate whether the PI3K/Akt/mTOR signaling cascade may differ in male and female GBM patients, we first assessed survival data of male and female GBM patients using the TCGA RPPA phosphoproteome data set and found that changes in protein phosphorylation of components of the PI3K/Akt/mTOR pathway, including mTOR phosphorylation, worsen the outcome of male but not female GBM patients in a dose-dependent fashion. This was supported by in vitro experiments of murine tran sformed astrocytes where pathway stimulation via treatment with insulin, IGF-1, or EGF significantly increased pathway activity in male but not female cells. Furthermore, pathway inhibition via serum deprivation resulted in a significant decrease in pathway activity in male but not female cells, indicating that male transformed astrocytes exhibit higher sensitivity to inhibitory conditions (serum deprivation) and stimulatory conditions (insulin, IGF-1, or EGF treatment). Together, these data suggest that (i) the PI3K/Akt/mTOR pathway activity may affect male and female GBM outcome differently, and (ii) there are sex differences in the regulation of the PI3K/Akt/mTOR signaling cascade in GBM which may contribute to the sex disparity in GBM. Our data add to the growing body of literature regarding the presence of sex differences in PI3K/Akt/mTOR signaling in health and disease and provide important insight for the development of translatable approaches to treatment for male and female GBM patients. View on Web

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Varicella Zoster Virus Reactivation Following COVID‐19 Vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross‐sectional Chinese study of 318 cases

alexandrossfakianakis shared this article with you from Inoreader Varicella Zoster Virus Reactivation Following COVID‐19 Vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross‐sectional Chinese study of 318 cases via Journal of Medical Virology Abstract Recently, varicella-zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID-19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against SARS-CoV-2 in a Chinese cohort of AIIRD patients. A cross-sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex-matched HCs who got COVID-19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to H Cs, patients had higher rates of rash (p=0.001), arthralgia (p<0.001) and insomnia (p=0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID-19 vaccination (p=0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (OR, 20.69; 95%CI, 1.08-396.79; p=0.044), chronic hepatitis B virus infection (OR, 24.34; 95%CI, 1.27-466.74; p=0.034), and mycophenolate mofetil (OR, 40.61; 95%CI, 3.33-496.15; p=0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID-19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation. This article is protected by copyright. All rights reserved. View on Web

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Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1

alexandrossfakianakis shared this article with you from Inoreader Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1 via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 14 November 2022; doi:10.1038/s41368-022-00207-y Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1 View on Web

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