Sanders Lundqvist (cloudenemy4)

On presentation to our clinic in 2019, the lesion demonstrated significant progression. The patient's tumor was identified as RGNT, WHO grade I. One hundred thirty patients were identified across 80 studies. RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors. RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors. The overexpression of (basic)helix-loop-helix ((b)HLH) transcription factors (TFs) is frequent in malignant glioma. We investigated molecular effects upon disruption of the (b)HLH network by a dominant-negative variant of the E47 protein (dnE47). Our goal was to identify novel molecular subgroup-specific therapeutic strategies. Glioma cell lines LN229, LNZ308, and GS-2/GS-9 were lentivirally transduced. Functional characterization included immunocytochemistry, immunoblots, cytotoxic, and clonogenic survival assays in vitro, and latency until neurological symptoms in vivo. Results of cap analysis gene expression and RNA-sequencing were further validated by immunoblot, flow cytometry, and functional assays in vitro. The induction of dnE47-RFP led to cytoplasmic sequestration of (b)HLH TFs and antiglioma activity in vitro and in vivo. Downstream molecular events, ie, alterations in transcription start site usage and in the transcriptome revealed enrichment of cancer-relevant pathways, particularly of the DNA damage response (DDR) pathway. Pharmacologic validation of this result using ataxia telangiectasia and Rad3 related (ATR) inhibition led to a significantly enhanced early and late apoptotic effect compared with temozolomide alone. Gliomas overexpressing (b)HLH TFs are sensitive toward inhibition of the ATR kinase. The combination of ATR inhibition plus temozolomide or radiation therapy in this molecular subgroup are warranted. Gliomas overexpressing (b)HLH TFs are sensitive toward inhibition of the ATR kinase. The combination of ATR inhibition plus temozolomide or radiation therapy in this molecular subgroup are warranted. Although mutations in the promoter region of the telomerase reverse transcriptase ( p) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of p status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up. We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 ( ) or gene mutations were excluded from this study. Among the 147 cases of wild-type GBM, 92 (62.6%) had the p mutation. Clinical, immunohistochemical, and genetic factors ( , gene mutation, CD133, ATRX expression, -methylguanine-DNA methyltransferase [ ] promoter methylation) and copy number alterations (CNAs) were investigated. GBM patients with the p mutation were older at first diagnosis versus those with p wild type (66.0 vs. 60.0 years, respectively, = .034), and had shorter progression-free survival (7 vs. 10 months, respectively, = .015) and overall survival (16 vs. 24 months, respectively, = .017). Notably, magnetic resonance imaging performed showed that p-mutant GBM was strongly associated with multifocal/distant lesions ( = .004). According to the CNA analysis, p mutations were positively correlated with amp/gain, deletion, and deletion; however, these mutations were negatively correlated with amp/gain, gain, and deletion. p mutations were strongly correla