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

スキー実習におけるグループ・ローテーション指導の効果について(2) : 中級グループでの試み

The purpose of this study was to make clear the effect of the Group Rotation Teaching in the medium grade class of Ski Intensive Course. Results are summarized as follows: 1) Through the Group Rotation Teaching, students have received more various helpful advice than the beginner\u27s class. Students are content with the Group Rotation Teaching, because they meet many teaching methods and teachers in this class. But their skill of skiing isn\u27t superior to the beginner. 2) For teachers, the Group Rotation Teaching is valuable to exchange their views and information about teaching skiing. Through the meeting about Group Rotation Teaching, They talk about not only teaching skiing, but about themselves

Can Persistent Homology Features Capture More Intrinsic Information about Tumors from ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Images of Head and Neck Cancer Patients?

This study hypothesized that persistent homology (PH) features could capture more intrinsic information about the metabolism and morphology of tumors from 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images of patients with head and neck (HN) cancer than other conventional features. PET/CT images and clinical variables of 207 patients were selected from the publicly available dataset of the Cancer Imaging Archive. PH images were generated from persistent diagrams obtained from PET/CT images. The PH features were derived from the PH PET/CT images. The signatures were constructed in a training cohort from features from CT, PET, PH-CT, and PH-PET images; clinical variables; and the combination of features and clinical variables. Signatures were evaluated using statistically significant differences (p-value, log-rank test) between survival curves for low- and high-risk groups and the C-index. In an independent test cohort, the signature consisting of PH-PET features and clinical variables exhibited the lowest log-rank p-value of 3.30 × 10−5 and C-index of 0.80, compared with log-rank p-values from 3.52 × 10−2 to 1.15 × 10−4 and C-indices from 0.34 to 0.79 for other signatures. This result suggests that PH features can capture the intrinsic information of tumors and predict prognosis in patients with HN cancer

Expression of tricellulin in epithelial cells and non-epithelial cells

Tricellulin is the first molecular component of tricellular tight junctions at tricellular contacts where three epithelial cells meet, and it is required for the their formation and maintenance of the epithelial barrier. Tricellulin binds other tight junction proteins, and its expression and distribution are affected by the bicellular tight junction protein occludin and lipolysis-stimulated lipoprotein receptor (LSR) which is expressed at tricellular contacts. Tricellulin is also detected in endothelial cells, neurons, microglia and astrocytes. Here, we focused tricellulin expression in various types of epithelial cells, nasal epithelial cells, pancreatic duct epithelial cells cells and hepatocytes, and non-epithelial cells, dendritic cells and Schwann cells, compared to expression of the bicellular tight junction protein occludin and LSR, and discuss the regulation and the role of tricellulin in cellular specificity

The Verification of Engine Analysis Model Accuracy by Measuring Oil Film Pressure in the Main Bearings of a Motorcycle High-Speed Engine Using a Thin-Film Sensor

To improve the accuracy of the calculation analysis of crank journal bearings in motorcycle engines and accurately understand lubrication conditions, the oil film conditions of actual crankshafts and journal bearings should be measured. This research study focuses on the oil film pressure generated in the main bearing, and by using an original thin-film pressure sensor with improved durability achieved through the use of DLC (Diamond-like Carbon), it was possible to perform experiments at a maximum of 13,000 rpm and full load, which was not possible before. This established a method for measuring the oil film pressure generated in the main bearing of a high-speed motorcycle engine during operation without changing the surrounding environment. The maximum oil film pressure was 140 MPa, and the oil film pressure generated by each main bearing was successfully measured under different experimental conditions. The timing of pressure onset agreed well between the calculation and experiment stages, but the peak oil film pressure values were different. By varying the temperature of the engine in the calculation model, the calculated values approached the measured values. In the future, we plan to investigate ways to improve the accuracy of the current analytical model