Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma

A member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene) is an increasingly important target in various cancer types, including glioblastoma (GBM). EGFR is among the most frequently altered oncogenes in GBM, and EGFR inhibition has been tested as an experimental therapy. Functional interactions between EGFR and TrkB have been demonstrated. In the present study, we investigated the role of TrkB and EGFR, and their interactions, in GBM. Analyses of NTRK2 and EGFR gene expression from The Cancer Genome Atlas (TCGA) datasets showed an increase in NTRK2 expression in the proneural subtype of GBM, and a strong correlation between NTRK2 and EGFR expression in glioma CpG island methylator phenotype (G-CIMP+) samples. We showed that when TrkB and EGFR inhibitors were combined, the inhibitory effect on A172 human GBM cells was more pronounced than when either inhibitor was given alone. When U87MG GBM cells were xenografted into the flank of nude mice, tumor growth was delayed by treatment with TrkB and EGFR inhibitors, given alone or combined, only at specific time points. Intracranial GBM growth in mice was not significantly affected by drug treatments. Our findings indicate that correlations between NTRK2 and EGFR expression occur in specific GBM subgroups. Also, our results using cultured cells suggest for the first time the potential of combining TrkB and EGFR inhibition for the treatment of GBM

Pb–Zn–Cd–As Pollution in Soils Affected 1 by Mining Activities in Central and Southern 2 Spain: a Scattered Legacy Posing Potential 3 Environmental and Health Concerns

In this chapter, published geochemical data for soils from several Pb–Zn mine sites and districts from Spain are reviewed. Although most of the mines have closed down, a legacy of highly polluted soils still remains throughout the sites constituting a potential hazard for the environment and human health. The fate of the studied metals and metalloids in these soils is mainly controlled by factors such as mining methods, concentration and metallurgical operations, mineralogy of the ore, gangue and host rock, fracturing of the host rocks, physiography, climate, and soil types (pedogenic evolution). It can be concluded that the most polluted soils (identified on the basis of an enrichment factor) are those of the Sierra Minera (La Unión District – SE Spain), at more than 488 (Pb), 163 (Zn), 99 (Cd), and 1698 (As) times the background values from non-contaminated soils. Pb is usually related to As, which in turn is bound to Fe oxides and oxyhydroxides.Metal bearing jarosite and other soluble phases also play a relevant role in the studied soil–water systems, because these minerals are dissolved during intense rainy events, thus resulting in high rates of metal leaching and mobilization by runoff