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Human osteosarcoma cells MG-63 were cultured on anodically etched titania nanotubes (TiO2 NT), with diameters ranging from 40-100 nm, to study the correlations between cell proliferation and adhesion on the 2.5 dimensional (2.5D) extracellular matrix (ECM). Unlike other reports, mostly based on mouse stem cells, and 2D cell culture, our studies indicate that the 2.5D NT promote higher proliferation and activity, but less 2D adhesion. Proliferation of the MG-63 cells was significantly higher in the NTs, the best being the 70 nm diameter sample, compared to planar titania (control). This is consistent with previous studies. However, cellular adhesion was stronger on TiO2 NT with increasing diameter, and highest on the control as obtained from shear stress measurement, paxilin imaging, and western blot measurements probing focal adhesion kinase, p130 CAS, and extracellular-regulated kinase, in addition to cell morphology imaging by fluorescence microscopy. We provide direct videography of cell migration, and cell speed data indicating faster filopodial activity on the TiO2 NT surfaces having lower adhesion. This evidence was not available previously. The NT matrices promote cells with smaller surface area, because of less 2D stretching. In contrast, on comparatively planar 2D-like surfaces uniaxial stretching of the cell body with strong anchoring of the filopodia, resulted in larger cell surface area, and demonstrated stronger adhesion. The difference in the results, with those previously published, may be generally attributed to, among others, the use of mouse stem cells (human osteosarcoma used here), and unannealed as-grown TiO2 NTs used previously (annealed ECMs used here). © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 842-852, 2016. [ABSTRACT FROM AUTHOR]

Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti–lung cancer and anti–lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs. [ABSTRACT FROM AUTHOR]

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)