Myeloid-derived suppressor cells (MDSCs) are a subgroup of immunosuppressive heterogeneous cells derived from bone marrow (BM) stem cells. They not only strongly inhibit T cell-mediated antitumor immune response but also directly induce tumorigenesis and promote tumor growth and metastasis. Besides, the nonresolving inflammation (NRI), a prime cause of tumor development, is present in the glioma microenvironment. However, the relationship between MDSCs and NRI, especially in the view of relevant molecular regulatory networks, has not been fully elucidated in gliomas. In the present study, the MDSC- and NRI-associated molecular regulatory network and key regulatory points are reviewed, and the targeted therapeutic strategies against gliomas are further discussed.

Gliomas are the most common primary brain tumors, the grading of which is associated with biological behavior and prognosis. With rapid advances in our understanding of glioma biology and a move toward personalized medicine, it is important to obtain a greater understanding of these tumors, beyond that provided by conventional neuroimaging. “Imaging genomics” is an emerging field which has an immense potential to greatly expand our understanding of glioma behavior. This article reviews the relationship between the radiologic and genomic features of gliomas, which may aid in personalizing patient treatment.

Background: Vasculogenic mimicry (VM) describes the functional plasticity of aggressive tumor cells to form newly recognized microcirculation, lined by tumor cells rather than endothelial cells, in solid tumors. The presence of VM in glioma is significantly associated with high tumor grade and poor prognosis. However, whether VM is a regular feature or only a temporary phenomenon during glioma growth is unknown. This study was designed to observe VM during the growth of subcutaneous and orthotopic xenograft glioma in Balb/c nude mice. Methods: The human glioblastoma cell line (U87) was used as xenografts in Balb/c nude mice models. The xenografts were obtained at different stages of tumor growth, and evaluated for VM and endothelium-dependent vessels by dual staining for endothelial marker CD34 and periodic acid-Schiff (PAS). Results: It was found that the PAS-positive patterns which were identified as VM were persistent during tumor growth of both subcutaneous and orthotropic xenografts. Further analysis showed that the microvessel density (MVD) of endothelium-dependent vessels was positively correlated with the tumor size of subcutaneous xenograft (r = 0.406, P = 0.009), while no significant correlation was found between VM density (VMD) and the tumor size (r = 0.107, P = 0.512). Furthermore, VMD was negatively correlated with MVD (r = −0.404, P = 0.010). Conclusion: The study results revealed that both VM and endothelium-dependent vessels coexist persistently during glioblastoma xenograft growth, indicating that VM may complement microcirculation in gliomas.

Background: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. Current treatment against this tumor consists of maximal surgical resection without threatening the patient's life, followed by a treatment with temozolomide, with or without combined radiotherapy. GBM is resistant to the conventional antitumor therapies, so in this research, we tried to inhibit tumor growth with the combination of three drugs: (1) panobinostat, an inhibitor of histone deacetylases, (2) 3-Dezaneplanocin-A (DZNep), an inhibitor of EZH2, a protein which belongs to the polycomb repressor complex 2, acting as a histone methylase, and (3) temozolomide, an alkylating agent. Methods: The T98G GBM commercial cell line was used. Cells were exposed to single treatments of the drugs and to the three possible combinations among them. Soon after, two-dimensional (2D) and 3D clonogenic assays were assessed for in vitro tumorigenicity testing. Real-time quantitative polymerase chain reaction of 2 proapoptotic genes (BAX and NOXA) and 2 antiapoptotic genes (BCL2 and BCL-XL) was also assessed. Results: The panobinostat and temozolomide combination produced a positive effect against T98G glioblastoma cells by reducing soft agar colony formation, by inducing high expression levels of NOXA, and by reducing BCL-XL expression. Equally, the panobinostat and DZNep combination produced a positive effect against T98G glioblastoma cells by reducing colony formation in adherent conditions and by inducing high expression levels of BAX. Finally, temozolomide alone was the most efficient drug for decreasing BCL2 expression. Conclusion: Panobinostat and temozolomide combination or panobinostat and DZNep combination might be more efficient against glioblastoma cells than just temozolomide.

Background: Glioblastomas with an oligodendroglioma component (GBMO) represents a pathology entity with indefinite diagnostic criterion and controversial prognosis, which prevents it from clinical application. The aim of this study is to disclose the clinical and genetic features of GBMO. Methods: A total of 169 glioblastoma multiforme (GBM) and 86 GBMO were reviewed. To reduce bias in patient selection, propensity score analysis was performed, and 68 pairs of GBMO-GBM were thereby generated. The survival time of the two groups was compared using the Kaplan–Meier method. Independent predictors of survival were identified using the Cox proportional-hazards model. Results: Compared to GBM, GBMO was correlated with younger age, higher frequencies of isocitrate dehydrogenase (IDH) mutation, and 1p19q co-deletion (P < 0.05). Among the propensity-score-matched pairs of patients, GBMO patients displayed both prolonged progression-free survival (12 months vs. 9 months, P = 0.005) and overall survival (18.5 months vs. 15 months, P = 0.007) than GBM patients. On top of IDH and 1p/19q, GBMO and GBM could be reclassified into subgroups with the distinct clinical outcome (P < 0.05). Conclusion: GBMO, a subgroup associated with younger age, high frequencies of IDH mutation f and 1p19q co-deletion, confers a favorable prognosis. It should be cautious to propose the deletion of GBMO in the new World Health Organization classification of tumors of the central nervous system.