Volumetric-modulated arc therapy as an alternative to intensity-modulated radiotherapy for primary tumors of advanced non–small-cell lung cancer: A multicenter retrospective analysis based on propensity score matching

Purpose: To investigate the effect of volumetric-modulated arc therapy (VMAT) versus intensity-modulated radiotherapy (IMRT) for advanced non–small-cell lung cancer (NSCLC). Methods: Cases in which the primary tumors were treated with IMRT or VMAT as initial intervention in stages III and IV NSCLC patients from September 2008 to March 2020 were retrospectively analyzed. Propensity Score Matching (PSM) was used to assess the efficacy and toxicity of the two radiotherapy techniques. Results: A total of 637 patients were included, out of which 483 cases were treated with IMRT, while 154 received VMAT. A total of 308 patients were selected after PSM. Patients who were having acute radiation esophagitis and pneumonia treated with VMAT had a lower percentage than those treated with IMRT (p < 0.05) before PSM. However, there was no significant difference in grades 3 - 4 toxicity (χ2 = 2.77, p = 0.096). There were also no significant differences in the primary endpoints between the two groups after PSM (p > 0.05), while for secondary endpoints, all lung V5, and V20, mean lung dose and heart V30, heart V40, mean heart dose in all patients and stage N2 patients in VMAT after PSM were significantly lower than those of IMRT (p < 0.05). Conclusion: Radiation therapy of A-NSCLC primary tumors using VMAT and IMRT seem to produce similar efficacy. The volume parameters of normal tissues and organs is significantly lower in VMAT, especially in patients with stage N2. Therefore, VMAT may be more beneficial for reducing radiation damage in normal tissues and organs

Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.

Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-β bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements