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In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors.

Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse.

SummaryConnexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients. Consequently, TAT-Cx43266-283 reduced GSC motility, as analyzed by time-lapse microscopy, and strongly reduced their invasive ability. Interestingly, we investigated the effects of TAT-Cx43266-283 on freshly removed surgical specimens as undissociated glioblastoma blocks, which revealed a dramatic reduction in the growth, migration, and survival of these cells. In conclusion, a region of CX43 (amino acids 266–283) exerts an important anti-tumor effect in patient-derived glioblastoma models that includes impairment of GSC migration and invasion.

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Five-year-old 'Spring' navel (Citrus sinensis (L.) Osbeck) orange trees were completely defruited, 50% defruited or left fully laden to study effects of fruit load on concentrations of nitrogen (N) and carbohydrate, net assimilation of CO2 (Ac) and stomatal conductance (gs) of mature leaves on clear winter days just before fruit harvest. Leaves on defruited trees were larger, had higher starch concentrations and greater leaf dry mass per area (LDMa) than leaves on fruited trees. Both Ac and gs were more than 40% lower in sunlit leaves on defruited trees than in sunlit leaves on trees with fruit. Leaves immediately adjacent to fruit were smaller, had lower leaf nitrogen and carbohydrate concentrations, lower LDMa and lower Ac than leaves on non-fruiting branches of the same trees. Removing half the crop increased individual fruit mass, but reduced fruit color development. Half the trees were shaded with 50% shade cloth for 4 months before harvest to determine the effects of lower leaf temperature (Tl) and leaf-to-air vapor pressure difference on leaf responses. On relatively warm days when sunlit Tl > 25 degrees C, shade increased Ac and gs, but had no effect on the ratio of internal to ambient CO2 (Ci/Ca) concentration in leaves, implying that high mesophyll temperatures in sunlit leaves were more important than gs in limiting Ac. Sunlit leaves were more photoinhibited than shaded leaves on cooler days when Tl < 25 degrees C. Shade decreased total soluble sugar concentrations in leaves, but had no effect on leaf starch concentrations. Shading had no effects on canopy volume, yield or fruit size, but shaded fruit developed better external color than sun-exposed fruit. Overall, the presence of a normal fruit crop resulted in lower foliar carbohydrate concentrations and higher Ac compared with defruited trees, except on warm days when Ac was reduced by high leaf temperatures.

Meningiomas are usually considered to be benign central nervous system tumors; however, they show heterogenous clinical, histolopathological and cytogenetic features associated with a variable outcome. In recent years important advances have been achieved in the identification of the genetic/molecular alterations of meningiomas and the signaling pathways involved. Thus, monosomy 22, which is often associated with mutations of the NF2 gene, has emerged as the most frequent alteration of meningiomas; in addition, several other genes (e.g. AKT1, KLF4, TRAF7, SMO) and chromosomes have been found to be recurrently altered often in association with more complex karyotypes and involvement of multiple signaling pathways. Here we review the current knowledge about the most relevant genes involved and the signaling pathways targeted by such alterations. In addition, we summarize those proposals that have been made so far for classification and prognostic stratification of meningiomas based on their genetic/genomic features.

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