Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer

Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings

Incumbent/Opposition Dynamics and Ideological Similitude on Emotions in Political Manifestos

The study involved the analysis of emotion-associated language in the UK Conservative and Labour party general election manifestos between 2000 to 2019. While previous research have shown a general correlation between ideological positioning and overlap of public policies, there are still conflicting results in matters of sentiments in such manifestos. Using new data, we present how valence level can be swayed by party status within government with incumbent parties presenting a higher frequency in positive emotion-associated words while negative emotion-associated words are more prevalent in opposition parties. We also demonstrate that parties with ideological similitude use positive language prominently further adding to the literature on the relationship between sentiments and party status.Comment: 14 pages, 3 figures, 1 appendi

The Impact of Incumbent/Opposition Status and Ideological Similitude on Emotions in Political Manifestos

The study involved the analysis of emotion-associated language in the UKConservative and Labour party general election manifestos between 2000 to 2019.While previous research have shown a general correlation between ideologicalpositioning and overlap of public policies, there are still conflicting resultsin matters of sentiments in such manifestos. Using new data, we present howvalence level can be swayed by party status within government with incumbentparties presenting a higher frequency in positive emotion-associated wordswhile negative emotion-associated words are more prevalent in oppositionparties. We also demonstrate that parties with ideological similitude usepositive language prominently further adding to the literature on therelationship between sentiments and party status.Comment: 14 pages, 3 figures, 1 appendi