Production of a Bioink Containing Decellularized Spinal Cord Tissue for 3D Bioprinting.

For the past few years, three-dimensional (3D) bioprinting has emerged as a promising approach in the field of regenerative medicine. This technique allows for the production of 3D scaffolds to support cell transplantation due to its ability to mimic the extracellular environment. One alternative to enhancing cell adhesion, survival, and proliferation is the use of decellularized extracellular matrix as a bioink component. The aim of this study was to produce a bioink using lyophilized rat decellularized spinal cord tissue (DSCT) for 3D bioprinting of nervous tissue. DNA quantification, hematoxylin and eosin and DAPI staining indicated that 1% sodium dodecyl sulfate and 9 h processing were effective in removing the cells from the spinal cord samples. The cell viability assay showed that the decellularized matrix is not cytotoxic for PC12 cells. The hydrogel containing DSCT, alginate, and gelatine used as the base for the bioink has a shear thinning behavior and low G″/G' ratio, allowing for good printability without compromising cell viability after 3D bioprinting. The bioink supported long-term PC12 cell survival, with 93% of live cells 4 weeks after printing, and stimulated the production of laminin-1 and neurofilament-M. This bioink, therefore, represents an easily available biomaterial for central nervous system tissue engineering.

In vitro evaluation of antitumoral efficacy of catalase in combination with traditional chemotherapeutic drugs against human lung adenocarcinoma cells.

Lung cancer is the most lethal cancer-related disease worldwide. Since survival rates remain poor, there is an urgent need for more effective therapies that could increase the overall survival of lung cancer patients. Lung tumors exhibit increased levels of oxidative markers with altered levels of antioxidant defenses, and previous studies demonstrated that the overexpression of the antioxidant enzyme catalase (CAT) might control tumor proliferation and aggressiveness. Herein, we evaluated the effect of CAT treatment on the sensitivity of A549 human lung adenocarcinoma cells toward various anticancer treatments, aiming to establish the best drug combination for further therapeutic management of this disease. Exponentially growing A549 cells were treated with CAT alone or in combination with chemotherapeutic drugs (cisplatin, 5-fluorouracil, paclitaxel, daunorubicin, and hydroxyurea). CalcuSyn(®) software was used to assess CAT/drug interactions (synergism or antagonism). Growth inhibition, NFκB activation status, and redox parameters were also evaluated in CAT-treated A549 cells. CAT treatment caused a cytostatic effect, decreased NFκB activation, and modulated the redox parameters evaluated. CAT treatment exhibited a synergistic effect among most of the anticancer drugs tested, which is significantly correlated with an increased H2O2 production. Moreover, CAT combination caused an antagonism in paclitaxel anticancer effect. These data suggest that combining CAT (or CAT analogs) with traditional chemotherapeutic drugs, especially cisplatin, is a promising therapeutic strategy for the treatment of lung cancer.

Potential crosstalk between cofilin-1 and EGFR pathways in cisplatin resistance of non-small-cell lung cancer.

Current challenge in oncology is to establish the concept of personalized medicine in clinical practice. In this context, non-small-cell lung cancer (NSCLC) presents clinical, histological and molecular heterogeneity, being one of the most genomically diverse of all cancers. Recent advances added Epidermal Growth Factor Receptor (EGFR) as a predictive biomarker for patients with advanced NSCLC. In tumors with activating EGFR mutations, tyrosine kinase inhibitors (TKI) are indicated as first-line treatment, although restricted to a very small target population. In this context, cofilin-1 (a cytosolic protein involved with actin dynamics) has been widely studied as a biomarker of an aggressive phenotype in tumors, and overexpression of cofilin-1 is associated with cisplatin resistance and poor prognosis in NSCLC. Here, we gather information about the predictive potential of cofilin-1 and reviewed the crosstalk between cofilin-1/EGFR pathways. We aimed to highlight new perspectives of how these interactions might affect cisplatin resistance in NSCLC. We propose that cofilin-1 quantification in clinical samples in combination with presence/absence of EGFR mutation could be used to select patients that would benefit from TKI's treatment. This information is of paramount importance and could result in a possibility of guiding more effective treatments to NSCLC patients.