Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to possess some anti-cancer and anti-inflammation capabilities. In this study, fisetin has exhibited inhibitory effects on the adhesion, migration, and invasion ability of a highly metastatic PC-3 cells under non-cytotoxic concentrations. Gelatin zymography assay showed that fisetin inhibited the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. Our result also showed that fisetin could inhibit the phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2) and Akt. Moreover, fisetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun, and the binding abilities of NF-kappaB and activator protein-1 (AP-1). Also, the results showed that the protein and mRNA levels of MMP-2 and MMP-9 were significantly reduced by Western blot and semi-quantitative RT-PCR. Further, treating specific inhibitors for PI3K (Wortmannin) or JNK (SP600125) to PC-3 cells could reduce the protein expressions of MMP-2 and MMP-9. These results showed fisetin could inhibit the metastatic ability of PC-3 by reducing MMP-2 and MMP-9 expressions through suppressing phosphoinositide 3-kinase/Akt (PI3K/Akt) and JNK signaling pathways. This suggested fisetin can serve as a potential candidate for treating cancer metastasis.

α-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring steroidal glycoalkaloid in immature green tomatoes. Some reports demonstrated that α-tomatine had various anticarcinogenic properties. The purpose of this study is to investigate the anti-metastatic effect of α-tomatine in NCI-H460 human non-small cell lung cancer cells. First, the results showed that α-tomatine significantly suppressed the abilities of the adhesion, invasion, and migration of NCI-H460 cells under non-cytotoxic concentrations. Molecular data also showed α-tomatine could inhibit the activation of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt signal involve in the downregulation the enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-7 (MMP-7). Next, α-tomatine also strongly inhibited the degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding ability of NF-κB by α-tomatine treatment was further observed. Furthermore, α-tomatine significantly decreased the levels of phospho-Akt and MMP-7 in Akt1-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Presented results indicated α-tomatine might be further application for treating cancer metastasis.

This study investigated the outcomes and the prognostic factors among the very elderly (patients ≥80 years old) requiring prolonged mechanical ventilation (PMV).Between 2006 and 2014, all of the very elderly patients of age 80 or more transferred to respiratory care center (RCC) of a tertiary medical center were retrospectively identified, and only patients who used mechanical ventilation (MV) for >3 weeks were included in this study.A total of 510 very elderly patients undergoing PMV were identified. The mean age of the patients was 84.3 ± 3.3 years, and it ranged from 80 to 96 years. Male comprised most of the patients (n = 269, 52.7%), and most of the patients were transferred to RCC from medical ICU (n = 357, 70.0%). The APACHE II scores on RCC admission was 17.6 ± 6.0. At least 1 comorbidity was found in 419 (82.2%) patients. No significant differences of gender, disease severity, diagnosis, dialysis, laboratory examinations, comorbidities, and outcome were found between octogenarians (aged 80–89) and nonagenarians (aged ≥ 90). The overall in-hospital mortality rate was 21.8%. In the multivariate analysis, patients who had APACHE II score ≥ 15(odds ratio [OR], 2.30, 95% confidence interval [CI], 1.36–3.90), or albumin ≤ 2 g/dL (OR, 3.92, 95% CI, 2.17–7.01) were more likely to have significant in-hospital mortality (P < 0.05).The in-hospital mortality rate of the very elderly PMV patients in our RCC is 21.8%, and poor outcomes in this specific population were found to be associated with a higher APACHE II score and lower albumin level.