Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.     

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.     

Structural and thermal behavior of 45S5 Bioglass®-based compositions containing alumina and strontium

The present research exposes the influence of 2 mol% of Al₂O₃ and 2 mol% SrO in 45S5 Bioglass^®-based compositions. Four compositions were produced to elucidate the difference in how both oxides influence structure and thermal behavior separately and their synergy when together. Thermal properties, crystallization tendency, and sintering behavior was evaluated by differential scanning calorimetry, hot stage microscopy, and dilatometry. Changes of medium-range structures were characterized by Qⁿ distribution of Raman spectroscopy and evaluation of ³¹P, ²⁷Al, ²³Na, and ²⁹Si environment obtained by magic angle spinning nuclear magnetic resonance. Despite Qⁿ distribution was predominantly Q² in all samples, the composition criteria used enabled improved processing and stabilibity characteristics. The addition of Al₂O₃ and SrO promoted larger sinterability parameter (S_c) which indicates better sintering behavior, the glass stability against crystallization doubled (K_H) compared to 45S5 and the processing window enlarged from 106 to 171.     

Densification of 8Y‐Tetragonal‐Stabilized Zirconia Optoceramics with Improved Optical Properties by Y Segregation

8% Yttria‐stabilized zironcia (8YSZ) transparent ceramics have a wide technological applications. Segregation of the Y around the grain boundaries is favored by slow heating rate. The optimized sintering parameters helped in obtaining transparent ceramics of 8YSZ with a high percentage of cubic phase in addition to the presence of tetragonal phase. HRTEM was used to verify the grain growth suppression and to observe the presence of the cubic phase. The presence of cubic phase has suppressed the grain growth, which increased the transparency in the visible and infrared region without the addition of dopants or by utilizing high pressure.     

Reactions between Strontium-Substituted Lanthanum Manganite and Yttria-Stabilized Zirconia: II, Diffusion Couples

Formation of secondary phases and diffusion of cations in diffusion couples of yttria-stabilized zirconia and lanthanum manganite substituted with 0 to 60 mol% strontium have been studied by scanning electron microscopy and energy dispersive X-ray spectroscopy. Only the primary phases were observed after 120 h at 1200°C, while formation of secondary phases was identified already after 1 h heat treatment at 1350°C. The phase composition of the reaction layer altered from La₂Zr₂O₇ to SrZrO₃ at increasing Sr content in La _x Sr_{1- x} MnO₃. The thickness of the reaction layer was increasing with heat treatment time. In diffusion couples of La_0.4Sr_0.6MnO₃ formation of manganese oxide was observed in the perovskite layer after 1 h heat treatment at 1350°C, while isolated grains of SrZrO₃ relatively deep inside the zirconia were observed after longer heat treatment time. Diffusion of Mn into zirconia was observed preferenced along grain boundaries in the early stage of the interface reaction.     

The Devil Is in the Definitions

Problem: Traditional American zoning separates land uses, yet many urbanists and contemporary planners argue that bringing mixed use back to the American city is the key to restoring its vibrancy.

Purpose: This article compares the American and the German approaches to regulating land use.

Methods: I derive my conclusions from a review of German federal and local regulatory documents, and interviews I conducted in the German city of Stuttgart.

Results and conclusions: The U.S. zoning approach assumes that each land use district is suitable for only a single type of human activity, such as residential, commercial, or industrial use; whereas in Germany the prevailing principle is that each land use district is suitable for multiple types of activity, and most districts end up in mixed uses. Thus, despite some nominal similarities in the land use categories employed in both countries, the zoning methods are in fact starkly different.

Takeaway for practice: The German zoning system, which commonly mixes the land uses, challenges deeply engrained assumptions that underlie standard U.S. zoning, and it may offer useful alternatives for zoning reform.     

The effect of the absence of Ni,Co, and Ni–Co catalyst pretreatment on catalytic activity for hydrogen production via oxidative steam reforming of ethanol

This article presents a study of the catalytic performance of Ni, Co, and Ni–Co–Mg–Al mixed oxides obtained from hydrotalcite precursors for the oxidative steam reforming of ethanol (OSRE) when no pretreatment (pre-reduction) is accomplished. Two catalysts (a Ni-based monometallic and an equimolar Ni–Co-based catalyst) achieve in situ reduction over shorter time periods compared with the other bimetallic catalysts and also, exhibit the best catalytic activity. On the contrary, the monometallic Co catalyst did not exhibit good catalytic performance, likely because of the existence of resistant spinel phases to soft reduction processes and/or to the re-oxidation of Co. The equimolar presence of Ni and Co generates a synergistic effect evidenced by the increase in the reducibility, basicity, and mobility of electrophilic oxygen species of the solid. The results yield important information for better understanding the catalytic system under study.     

Studies on blends of natural rubber and ethylene propylene diene rubber modified with phosphorylated cardanol prepolymer: Processability,physico‐mechanical properties,and morphology

The melt processability and physico‐mechanical properties of blends of natural rubber (NR) and ethylene propylene diene rubber (EPDM) containing different dosages (0–10 phr) of phosphorylated cardanol prepolymer (PCP) were studied in unfilled and china‐clay‐filled mixes. The plasticizing effect of PCP in the blends was evidenced by progressive reduction in power consumption of the mixing and activation energy for melt flow with an increase in the dosage of PCP. The PCP‐modified blend vulcanizates showed higher tensile properties and tear strength despite a decrease in the chemical crosslink density (CLD) index. This is presumably due to the formation of a crosslinked network structure of PCP with the rubbers and improved dispersion of the filler particles in the rubber matrix, as evidenced by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Thermogravimetric analysis showed an increase in thermal stability of the blend vulcanizate in presence of 5 phr of PCP. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5123–5130, 2006     

Voltammetric stability of anodic films on the Ti6Al4V alloy in chloride medium

The biocompatibility and mechanical integrity of Ti and Ti6Al4V alloy can be affected by corrosion processes. This paper presents studies on the stability of anodic oxide films on Ti6Al4V and Ti in chloride medium. The oxides were grown potentiodynamically up to 8.0 V in the phosphate buffer saline (PBS) solution (pH 6.8) at 25 and 37 °C. The morphology of the obtained anodic oxides and the type of corrosion that occurred were analyzed by SEM–EDS. The Ti6Al4V alloy presented less corrosion resistance than pure Ti. Elemental analyses showed that the decrease of the alloy corrosion resistance is due mainly to the corrosion of Al.