Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown.Methods: WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were silenced or overexpressed in GBM cells to assess functional effects in vitro and in vivo. Phospho-kinase arrays and TCF/LEF reporter assays were used to identify WNT6-signaling pathways, and significant associations with stem cell features and cancer-related pathways were validated in patients. Survival analyses were performed with Cox regression and Log-rank tests. Meta-analyses were used to calculate the estimated pooled effect.Results: We show that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and normal brain, at mRNA and protein levels. Functionally, WNT6 increases typical oncogenic activities in GBM cells, including viability, proliferation, glioma stem cell capacity, invasion, migration, and resistance to temozolomide chemotherapy. Concordantly, in in vivo orthotopic GBM mice models, using both overexpressing and silencing models, WNT6 expression was associated with shorter overall survival, and increased features of tumor aggressiveness. Mechanistically, WNT6 contributes to activate typical oncogenic pathways, including Src and STAT, which intertwined with the WNT pathway may be critical effectors of WNT6-associated aggressiveness in GBM. Clinically, we establish WNT6 as an independent prognostic biomarker of shorter survival in GBM patients from several independent cohorts.Conclusion: Our findings establish WNT6 as a novel oncogene in GBM, opening opportunities to develop more rational therapies to treat this highly aggressive tumor.

In this work, polymer nanocomposite films based on poly(L-lactic acid) (PLLA) were reinforced with mesoporous silica nanoparticles, mesoporous cellular foam (MCF) and Santa Barbara amorphous-15 (SBA). PLLA is a biobased aliphatic polyester, that possesses excellent thermomechanical properties, and has already been commercialized for packaging applications. The aim was to utilize nanoparticles that have already been established as nanocarriers to enhance the mechanical and thermal properties of PLLA. Since the introduction of antibacterial properties has become an emerging trend in packaging applications, to achieve an effective antimicrobial activity, micro/nano 3D micropillars decorated with cone- and needle-shaped nanostructures were implemented on the surface of the films by means of thermal nanoimprint lithography (t-NIL), a novel and feasible fabrication technique with multiple industrial applications. The materials were characterized regarding their composition and crystallinity using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD), respectively, and their thermal properties using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Their mechanical properties were examined by the nanoindentation technique, while the films’ antimicrobial activity against the bacteria Escherichia coli and Staphylococcus aureus strains was tested in vitro. The results demonstrated the successful production of nanocomposite PLLA films, which exhibited improved mechanical and thermal properties compared to the pristine material, as well as notable antibacterial activity, setting new groundwork for the potential development of biobased smart packaging materials.

Glioblastoma (GBM) is the most common and most deadly primary malignant brain tumor. Current therapies are not effective, the average survival of GBM patients after diagnosis being limited to few months. Therefore, the discovery of new treatments for this highly aggressive brain cancer is urgently needed. Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, three chalcone derivatives were tested regarding their inhibitory activity and selectivity towards GBM cell lines (human and mouse) and a non-cancerous mouse brain cell line. The chalcone 1 showed the most potent and selective cytotoxic effects in the GBM cell lines, being further investigated regarding its ability to reduce critical hallmark features of GBM and to induce apoptosis and cell cycle arrest. This derivative showed to successfully reduce the invasion and proliferation capacity of tumor cells, both key targets for cancer treatment. Moreover, to overcome potential systemic side effects and its poor water solubility, this compound was encapsulated into liposomes. Therapeutic concentrations were incorporated retaining the potent in vitro growth inhibitory effect of the selected compound. In conclusion, our results demonstrated that this new formulation can be a promising starting point for the discovery of new and more effective drug treatments for GBM.

The non-tumour ductal epithelium adjacent to invasive ductal carcinoma shows a higher COX-2 expression than does the invasive ductal carcinoma. However, the different localisation of the immunohistochemically-detected protein suggests a possible post-translational regulation of the protein.