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Background: Anaplastic lymphoma kinase (ALK) is a validated molecular target in non-small-cell lung cancer (NSCLC). However, the clinical benefits of ALK inhibitors are almost universally limited by the emergence of drug resistance. Methods: We monitored the plasma circulating tumor DNA (ctDNA) using captured-based ultra-deep sequencing analysis of one patient with metastatic ALK-positive NSCLC who had received therapies including first-, second- and third-generation ALK inhibitors. Functional in vitro studies were further undertaken to elucidate the mechanism of resistance. Results: ALK T1151Sins mutation was detected when the patient developed resistance to ceritinib, and undetectable when she responded to lorlatinib. MET amplification was present when the tumor developed resistance to lorlatinib, and reduced when the patient received combination therapy of lorlatinib with crizotinib, which corresponded to clinical radiologic responses. In addition, further functional in vitro studies demonstrated that ALK harboring the T1151Sins mutation, while conferring resistance to ceritinib, was inhibited by lorlatinib. Conclusions: Clinical evidence and in vitro validation revealed the clinical usefulness of captured-base ultra-deep sequencing on longitudinal plasma ctDNA in revealing the underlying resistance mechanism and guiding the precise administration of ALK inhibitors in patients with advanced ALK-positive NSCLC. [ABSTRACT FROM AUTHOR]

In this text, the new crystal forms of geffitinib were explored through evaporation solution crystallization experiment. The formation of salts was confirmed by the single crystal X-ray diffraction, powder X-ray diffraction, thermo gravimetric analysis and differential scanning calorimetry, Raman spectroscopy, hot-stage microscopy and Hirshfeld surface analysis. Furthermore, Hirshfeld surface analysis confirmed that the driving force and supporting force for the formation of crystals were C-C, C-H, N-H, H-H, O-H and Cl-H interactions. The dissolution rate of the new salts of gefitinib in phosphate buffer of pH 6.8 was evaluated, and the results showed a significant increase in solubility. [ABSTRACT FROM AUTHOR]

Cinnamomum zelanicum is one of the popular medicinal plants. The plant has many pharmaceutical uses in traditional medicine. In this study, copper nanoparticles were synthesized using the aqueous extract of Cinnamomum zelanicum. The CuNPs were characterized using different techniques such as EDX, FE-SEM, XRD, and FT-IR. The FE-SEM results confirm spherical morphology for the nanoparticles with size of 19.55 to 69.70 nm. For investigating the antioxidant property of CuNPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-human lung carcinoma effects of CuNPs, MTT assay was used on the NCI-H2126, NCI-H1437, NCI-H1573, and NCI-H661 cell lines. DPPH test revealed similar antioxidant potentials for Cinnamomum zelanicum aqueous extract, CuNPs, and butylated hydroxytoluene. Copper nanoparticles had very low cell viability and anti-lung carcinoma properties dose-dependently against NCI-H2126, NCI-H1437, NCI-H1573, and NCI-H66 cell lines without any cytotoxicity on the normal cell line. The best result of anti-lung carcinoma properties of CuNPs against the above cell lines was seen in the case of the NCI-H2126 cell line. According to the above findings, the copper nanoparticles containing Cinnamomum zelanicum can be administrated in humans for the treatment of several types of lung carcinoma. [ABSTRACT FROM AUTHOR]

Direct exposure to Ultraviolet (UV) radiation causes progressive damages in retinal cells, which is one of the hypothetical mechanisms underlying age-related retinopathy or macular degeneration. The protective effects of Apocynin against UV damages were firstly tested in retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs). Subsequently the beneficial effect of Apocynin on mouse retinas against light damage were examined. Next, microarray profiling was used to identify the genes regulated by Apocynin in both RPEs and RGCs. A candidate gene was isolated for functional characterisation by knock-down study. Apocynin was shown to inhibit cell death, reduce oxidative stress and deoxyribonucleic acid damages in both RPEs and RGCs challenged with UV. Intravitreal application of Apocynin also improved retinal dysfunction caused by light damage. Sirtuin 1 (SIRT1) was identified as induced by Apocynin by microarray study. The induction was confirmed by realtime-PCR and western blotting. Knocking down SIRT1 antagonised the protective effect of Apocynin against UV damages in both RPEs and RGCs. Apocynin is a novel agent that shows both in vitro and in vivo efficacies against UV radiation induced retina damages. SIRT1 pathway is implicated in UV radiation protection of Apocynin in retinal cells. [ABSTRACT FROM AUTHOR]