Chemotherapeutic Sensitization of Leptomycin B Resistant Lung Cancer Cells by Pretreatment with Doxorubicin

The development of novel targeted therapies has become an important research focus for lung cancer treatment. Our previous study has shown leptomycin B (LMB) significantly inhibited proliferation of lung cancer cells; however, p53 wild type lung cancer cells were resistant to LMB. Therefore, the objective of this study was to develop and evaluate a novel therapeutic strategy to sensitize LMB-resistant lung cancer cells by combining LMB and doxorubicin (DOX). Among the different treatment regimens, pretreatment with DOX (pre-DOX) and subsequent treatment with LMB to A549 cells significantly decreased the 50% inhibitory concentration (IC50) as compared to that of LMB alone (4.4 nM vs. 10.6 nM, P<0.05). Analysis of cell cycle and apoptosis by flow cytometry further confirmed the cytotoxic data. To investigate molecular mechanisms for this drug combination effects, p53 pathways were analyzed by Western blot, and nuclear proteome was evaluated by two dimensional-difference gel electrophoresis (2D-DIGE) and mass spectrometry. In comparison with control groups, the levels of p53, phospho-p53 (ser15), and p21 proteins were significantly increased while phospho-p53 (Thr55) and survivin were significantly decreased after treatments of pre-DOX and LMB (P<0.05). The 2D-DIGE/MS analysis identified that sequestosome 1 (SQSTM1/p62) had a significant increase in pre-DOX and LMB-treated cells (P<0.05). In conclusion, our results suggest that drug-resistant lung cancer cells with p53 wild type could be sensitized to cell death by scheduled combination treatment of DOX and LMB through activating and restoring p53 as well as potentially other signaling pathway(s) involving sequestosome 1

Mechanical and Physical Effects of Electroosmotic Dewatering of Clayey Soils

Electrokinetic (EK) treatment is studied for fine grained dredged soils as an innovative and cost-effective method to accelerate the dewatering and improve their mechanical behaviour. Owing to their high-water content, the dredged sediments take a very long time for the consolidation process, much more than those considered in the typical problems of geotechnical engineering. Some electroosmotic tests in oedometer conditions on a clayey soil have been carried out at the University of Napoli Federico II in a special apparatus (special oedometer), adopting a pore fluid with different salt concentration. The results show that the addition of soluble salts in small quantities (until 8 g/l) can improve the electroosmotic consolidation of soft clay. On the contrary, excessive salinity reduces the efficiency of electroosmotic dewatering. The optimal salinity content has been then determined. At the end of the EK tests, some triaxial tests have been performed on the treated specimens in order to analyse the effectiveness of the EK treatment in the improvement of the soil mechanical propertie

Influence of electroosmotic treatment on the hydro-mechanical behaviour of clayey silts: preliminary experimental results

Preliminary results of an investigation focused on the influence of electrokinetic treatment on the mechanical and hydraulic behaviour of clayey soils are presented. The experimental programme aims at providing a contribution to the sustainability of contaminant extraction or containment via electroosmosis. Changes in the hydraulic and mechanical properties of two illitic clayey soils, subjected to a DC electric field, were investigated. Samples of the two soils were subjected to electrokinetic filtration, for different periods of time, and under different constant loads. Afterwards, they were tested under onedimensional compression to detect changes in stiffness and hydraulic conductivity due to the electrical treatment. After the application of a DC field for a few hours, a small reversible increment in the average soil stiffness was observed, with respect to the untreated soil, while the hydraulic conductivity was not affected substantially. Dramatic changes of the mechanical and hydraulic soil properties, correlated to changes of the soil pH, were observed following non-conditioned electrokinetic treatment with duration of the order of days.Peer ReviewedPostprint (published version

Research Challenges Involving Coupled Flows in Geotechnical Engineering

Coupled fluid, chemical, heat, and electrical flows are common phenomena that arc relevant to a wide variety of applications in Geotechnical Engineering, including the use of engineered clay barriers for waste containment, electro-osmosis for soil consolidation, highly compacted bentonite buffers for high-level radioactive nuclear waste disposal, and electrokinetics for soil contaminant removal. among others. For all of these applications, a fundamental understanding of coupled flow phenomena is required, including the basis of the various phenomena. the potential effect of the phenomena on fundamental soil behavior, and the applicability of the phenomena in both natural and built environments. This chapter highlights some of the advances over the past approximate three decades, including the effects of osmotic phenomena (chemico-osmosis, electro-osmosis, and thermo-osmosis) on the mechanical behavior of clays, the formulations and measurement of coupled flow phenomena, the distinction between phenomenological and microscopic (physical-based) formalisms, and considerations with respect to both saturated and unsaturated soil conditions. Based on the description of these advances, research challenges pertaining lo the study of coupled flow phenomena for Geotechnical Engineering applications are identified