Glioblastoma (GBM) consists of a heterogeneous collection of competing cellular clones which communicate with each other and with the tumor microenvironment (TME). MicroRNAs (miRNAs) present various exchange mechanisms: free miRNA, extracellular vesicles (EVs), or gap junctions (GJs). GBM cells transfer miR-4519 and miR-5096 to astrocytes through GJs. Oligodendrocytes located in the invasion front present high levels of miR-219-5p, miR-219-2-3p, and miR-338-3p, all related to their differentiation. There is a reciprocal exchange between GBM cells and endothelial cells (ECs) as miR-5096 promotes angiogenesis after being transferred into ECs, whereas miR-145-5p acts as a tumor suppressor. In glioma stem cells (GSCs), miR-1587 and miR-3620-5p increase the proliferation and miR-1587 inhibits the hormone receptor co-repressor-1 (NCOR1) after EVs transfers. GBM-derived EVs carry miR-21 and miR-451 that are up-taken by microglia and monocytes/macrophages, promoting their proliferation. Macrophages release EVs enriched in miR-21 that are transferred to glioma cells. This bidirectional miR-21 exchange increases STAT3 activity in GBM cells and macrophages, promoting invasion, proliferation, angiogenesis, and resistance to treatment. miR-1238 is upregulated in resistant GBM clones and their EVs, conferring resistance to adjacent cells via the CAV1/EGFR signaling pathway. Decrypting these mechanisms could lead to a better patient stratification and the development of novel target therapies.

Glioblastoma multiforme (GBM) is one of the deadliest brain tumors. Current standard therapy includes tumor resection surgery followed by radiotherapy and chemotherapy. Due to the tumors invasive nature, recurrences are almost a certainty, giving the patients after diagnosis only a 12–15 months average survival time. Therefore, there is a dire need of finding new therapies that could potentially improve patient outcomes. Ferroptosis is a newly described form of cell death with several implications in cancer, among which GBM. Agents that target different molecules involved in ferroptosis and that stimulate this process have been described as potentially adjuvant anti-cancer treatment options. In GBM, ferroptosis stimulation inhibits tumor growth, improves patient survival, and increases the efficacy of radiation and chemotherapy. This review provides an overview of the current knowledge regarding ferroptosis modulation in GBM.

IntroductionVentriculomegaly (VM) is a fetal brain malformation which may present independently (isolated form) or in association with different cerebral malformations, genetic syndromes or other pathologies (non-isolated form).MethodsThis paper aims to study the effect of ventriculomegaly on the internal tridimensional architecture of fetal brains by way of Klingler's dissection. Ventriculomegaly was diagnosed using fetal ultrasonography during pregnancy and subsequently confirmed by necropsy. Taking into consideration the diameter of the lateral ventricle (measured at the level of the atrium), the brains were divided into two groups: moderate ventriculomegaly (with atrial diameter between 13 and 15 mm) and severe ventriculomegaly (with atrial diameter above 15 mm).Results and discussionThe results of each dissection were described and illustrated, then compared with age-matched reference brains. In the pathological brains, fascicles in direct contact with the enlarged ventricles were found to be thinner and displaced inferiorly, the opening of the uncinate fasciculus was wider, the fornix was no longer in contact with the corpus callosum and the convexity of the corpus callosum was inverted. We have studied the prevalence of neurodevelopmental delay in children born with ventriculomegaly in the literature and discovered that a normal developmental outcome was found in over 90% of the mild VM cases, approximately 75% of the moderate and 60% in severe VM, with the correlated neurological impairments ranging from attention deficits to psychiatric disorders.