Search

Non‐small cell lung cancer (NSCLC) with wild‐type epidermal growth factor receptor (EGFR) is intrinsic resistance to EGFR‐tyrosine kinase inhibitors (TKIs), such as afatinib. Celastrol, a natural compound with antitumor activity, was reported to induce paraptosis in cancer cells. In this study, intrinsic EGFR‐TKI‐resistant NSCLC cell lines H23 (EGFR wild‐type and KRAS mutation) and H292 (EGFR wild‐type and overexpression) were used to test whether celastrol could overcome primary afatinib resistance through paraptosis induction. The synergistic effect of celastrol and afatinib on survival inhibition of the NSCLC cells was evaluated by CCK‐8 assay and isobologram analysis. The paraptosis and its modulation were assessed by light and electron microscopy, Western blot analysis, and immunofluorescence. Xenografts models were established to investigate the inhibitory effect of celastrol plus afatinib on the growth of the NSCLC tumors in vivo. Results showed that celastrol acted synergistically with afatinib to suppress the survival of H23 and H292 cells by inducing paraptosis characterized by extensive cytoplasmic vacuolation. This process was independent of apoptosis and not associated with autophagy induction. Afatinib plus celastrol‐induced cytoplasmic vacuolation was preceded by endoplasmic reticulum stress and unfolded protein response. Accumulation of intracellular reactive oxygen species and mitochondrial Ca2+ overload may be initiating factors of celastrol/afatinib‐induced paraptosis and subsequent cell death. Furthermore, Celastrol and afatinib synergistically suppressed the growth of H23 cell xenograft tumors in vivo. The data indicate that a combination of afatinib and celastrol may be a promising therapeutic strategy to surmount intrinsic afatinib resistance in NSCLC cells. [ABSTRACT FROM AUTHOR]

In this paper, the existence and multiplicity results for semilinear elliptic equations at resonance are obtained by the minimax methods and Morse theory. [ABSTRACT FROM AUTHOR]

The TiO 2 /bentonite composite was synthesized by modifying calcium-based bentonite with Nano-TiO 2 . The products before and after modification were characterized via the approach of X-ray power diffraction(XRD) and scanning electron microscope(SEM).The effect of TiO 2 /bentonite composite on mercury removal from aqueous solutions of HgCl 2 was studied at different dosage, pH, adsorption time and the initial concentration of Hg 2+ was investigated and compared with the bentonite by indoor simulation experiment, as well as the orthogonal experiments to determine the optimal condition of Hg 2+ adsorption. The experimental results showed:after modified by TiO 2 , TiO 2 /bentonite composite particles were apparently smaller, the basal spacing was increased and with a loose and porous structure. The adsorption rates of TiO 2 /bentonite composite on Hg 2+ were increased compared with bentonite. The Hg 2+ adsorption rates were increased with the increasing dosages, pH and adsorption time. The adsorption rates were higher than 98.0% when the dosage was 1.5 g·L -1 , pH 7.0, and the adsorption time was 120 min. The adsorption rates became smaller with increasing initial concentration of Hg 2+ . False secondary dynamic equation could describe the adsorption of TiO 2 /bentonite composite on Hg 2+ , and the chemical adsorption was dominant. The adsorption isotherm of Hg 2+ conformed to Langmuir equation, indicating that the adsorption of Hg 2+ was typical monolayer adsorption. The optimal experimental condition was:dosage of 2.0 g·L -1 , pH 8.0, adsorption time of 16 h and the initial Hg 2+ concentration of 45 mg·L -1 . Under this condition, the adsorption rate was 99.9%, and the equilibrium concentration of Hg 2+ was 0.034 mg·L -1 .