HOXD-AS2-STAT3 feedback loop attenuates sensitivity to temozolomide in glioblastoma.

AIMS: Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non-coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD-AS2-affected temozolomide sensitivity in glioblastoma. METHODS: We analyzed and validated the aberrant HOXD-AS2 expression in glioma specimens. Then we explored the function of HOXD-AS2 in vivo and in vitro and a clinical case was also reviewed to examine our findings. We further performed mechanistic experiments to investigate the mechanism of HOXD-AS2 in regulating TMZ sensitivity. RESULTS: Elevated HOXD-AS2 expression promoted progression and negatively correlated with prognosis of glioma; HOXD-AS2 attenuated temozolomide sensitivity in vitro and in vivo; The clinical case also showed that lower HOXD-AS2 sensitized glioblastoma to temozolomide; STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to form a complex and sequentially upregulate STAT3 signaling, thus forming a positive feedback loop regulating TMZ sensitivity in glioblastoma. CONCLUSION: Our study elucidated the crucial role of the HOXD-AS2-STAT3 positive feedback loop in regulating TMZ sensitivity, suggesting that this could be provided as a potential therapeutic candidate of glioblastoma.

Case Report: An Intracranial Aspergillus Infection with Cyst Formation.

Intracranial fungal infection is a rare condition that often requires surgical intervention. In this study, we present a case of intracranial fungal infection with a space-occupying effect and a long medical history of five years. We comprehensively evaluated the medical history, symptoms, imaging manifestations, and pathological examinations of the patient to confirm this rare case of fungal infection with cyst formation. Moreover, we reviewed the literature on intracranial fungal infection, hoping to draw awareness and attention to this rare disease.

A systematic review of multifocal and multicentric glioblastoma.

Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is more genetically heterogeneous, aggressive and resistant to chemoradiotherapy than unifocal GBM, and has a worse prognosis. There is no international consensus on the treatment of multiple GBM. This review discusses some paradigms of multiple GBM and focuses on the heterogeneity spread pathway, imaging diagnosis, pathology, molecular characterization and prognosis of multifocal and multicentric GBM. Several promising therapeutic methods of multiple GBM are also recommended.

Integrative transcriptome analysis identified a BMP signaling pathway-regulated lncRNA AC068643.1 in IDH mutant and wild-type glioblastomas.

Glioblastomas (GBMs) are classified into isocitrate dehydrogenase (IDH) mutant (IDH MT) and wild-type (IDH WT) subtypes, and each is associated with distinct tumor behavior and prognosis. The present study aimed to investigate differentially expressed long non-coding (lnc)RNAs and mRNAs between IDH MT and IDH WT GBMs, as well as to explore the interaction and potential functions of these RNAs. A total of 132 GBM samples with RNA profiling data (10 IDH MT and 122 IDH WT cases) were obtained from The Cancer Genome Atlas, and 62/78 and 142/219 up/downregulated lncRNAs and mRNAs between IDH MT and IDH WT GBMs were identified, respectively. Multivariate Cox analysis of the dysregulated lncRNAs/mRNAs identified three-lncRNA and fifteen-mRNA signatures with independent prognostic value, indicating that these RNAs may serve roles in determining distinct tumor behaviors and prognosis of patients with IDH MT/WT GBMs. Functional analysis of the three lncRNAs revealed that they were primarily associated with cell stemness or differentiation. Pearson's correlation analysis revealed that the protective lncRNA AC068643.1 was significantly positively correlated with two key bone morphogenetic protein (BMP) signaling-associated mRNAs, Bone morphogenetic protein 2 (BMP2) and Myostatin (MSTN), from the 15 mRNAs. Further in vitro studies demonstrated that BMP2 and MSTN directly stimulated AC068643.1 expression. In conclusion, the present study identified a BMP signaling pathway-regulated lncRNA AC068643.1, which may contribute to the different tumor behaviors observed between IDH MT and IDH WT GBMs.

Embryonal tumor with multilayered rosettes, C19MC-altered (ETMR): a newly defined pediatric brain tumor.

Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered, is a newly defined and rare pediatric malignant tumor of the central nervous system (CNS) in the 2016 WHO Classification of Tumors of the Central Nervous System. Here we present two cases of ETMR with amplification of the C19MC locus at chromosome 19q13.42. Case 1 is a fifteen-year-old boy, who underwent gamma knife surgery two times three years ago, after presenting with seizures. Magnetic resonance imaging (MRI) identified a large mass in the left frontotemporal lobe. Case 2 is a three-year-old boy who underwent surgery for a right frontal lobe tumor followed by chemotherapy. Eight months later, MRI identified a recurrent tumor in the bilateral frontal lobe. Histologically, cases 1 and 2 exhibited a typical papillary/trabecular and a multilayered rosette pattern resembling medulloepithelioma (ME) and ependymoblastoma (EBL), respectively. Immunohistochemically, CD99, synaptophysin, vimentin, and LIN28A were positive in both cases. Most importantly, both cases displayed amplification in the C19MC locus at 19q13.42 in a fluorescence in situ hybridization (FISH) analysis.

Morphological characteristics associated with rupture risk of multiple intracranial aneurysms.

OBJECTIVE: To identify the morphological parameters that are related to intracranial aneurysms (IAs) rupture using a case-control model. METHODS: A total of 107 patients with multiple IAs and aneurysmal subarachnoid hemorrhage between August 2011 and February 2017 were enrolled in this study. Characteristics of IAs location, shape, neck width, perpendicular height, depth, maximum size, flow angle, parent vessel diameter (PVD), aspect ratio (AR) and size ratio (SR) were evaluated using CT angiography. Multiple logistic regression analysis was used to identify the independent risk factors associated with IAs rupture. Receiver operating characteristic curve analysis was performed on the final model, and the optimal thresholds were obtained. RESULTS: IAs located in the internal carotid artery (ICA) was associated with a negative risk of rupture, whereas AR, SR1 (height/PVD) and SR2 (depth/PVD) were associated with increased risk of rupture. When SR was calculated differently, the odds ratio values of these factors were also different. The receiver operating characteristic curve showed that AR, SR1 and SR2 had cut-off values of 1.01, 1.48 and 1.40, respectively. SR3 (maximum size/PVD) was not associated with IAs rupture. CONCLUSIONS: IAs located in the ICA are associated with a negative risk of rupture, while high AR (>1.01), SR1 (>1.48) or SR2 (>1.40) are risk factors for multiple IAs rupture.