Accelerated production of multiple cytokines and chemokines by Epstein-Barr virus-infected natural killer cells and T cells

金沢大学医薬保健研究域保健学系[Originals][原著]平成22年10月28日受付, 平成22年12月3日受理

Michiko Kon : Still Lives

After a preface by Kline that comments on the fetishistic aspect of Kon's staged photographic tableaux, Kasahara addresses the artist's concerns as a photographer opposed to prevailing trends in contemporary Japanese photography. Biographical notes

Studies on the cutaneous innervation of lizards

Volume: 34Start Page: 549End Page: 56

Observations on the structure of the cochlear duct limbus of reptiles

Volume: 35Start Page: 37End Page: 5

Role of JAK-STAT signaling in the pathogenic behavior of fibroblast-like synoviocytes in rheumatoid arthritis: Effect of the novel JAK inhibitor peficitinib

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) play a crucial role in the pathogenesis of RA. RA-FLS display passive pro-inflammatory responses and self-directed aggressive responses, such as pro-inflammatory mediator production, reduced apoptosis and formation of a thickened synovial lining. Evidence suggests a role for Janus kinase (JAK)-signal transducer and transcriptional activator (STAT) signaling in the passive response but the aggressive behavior of RA-FLS is poorly understood. The pharmacologic effects of the novel JAK inhibitor, peficitinib, on cytokine-induced intracellular signaling and self-directed aggressive behavior of RA-FLS (e.g., increased expression of apoptosis-resistant genes and sodium nitroprusside-induced apoptosis) were investigated and compared with approved JAK inhibitors. RA-FLS assembly to form a lining-like structure and pro-inflammatory mediator production was investigated in three-dimensional (3D)-micromass culture. Peficitinib inhibited STAT3 phosphorylation in RA-FLS following induction by interferon (IFN)-α2b, IFN-γ, interleukin (IL)-6, oncostatin M, and leukemia inhibitory factor in a concentration-related manner, and was comparable to approved JAK inhibitors, tofacitinib and baricitinib. Peficitinib and tofacitinib suppressed autocrine phosphorylation of STAT3 and expression of apoptosis-resistant genes, and promoted cell death. In 3D-micromass culture, peficitinib reduced multi-layered RA-FLS cells to a thin monolayer, an effect less pronounced with tofacitinib. Both compounds attenuated production of vascular endothelial growth factor-A, matrix metalloproteinases, IL-6 and tumor necrosis factor superfamily-11. This study confirmed the pathogenic role of uncontrolled JAK-STAT signaling in the aggressive and passive responses of RA-FLS that are critical for RA progression. The novel JAK inhibitor peficitinib suppressed the pro-inflammatory behavior of RA-FLS, accelerated cell death and abrogated thickening of the synovium

Treatment preferences among Japanese patients and physicians for epidermal growth factor receptor‐mutant non‐small cell lung cancer

Abstract Introduction Evidence is limited on preferences of Japanese patients and physicians in treatment for epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC). Several oral or intravenous novel agents for EGFR exon 20 insertions are under development. The aim of our study was to investigate which attributes of novel treatments influenced selection of oral or intravenous agents among treated patients and treating physicians in Japan. Methods The study was designed by board‐certified oncologists, patient representatives, and analytics specialists. Eligible participants completed an online survey with a discrete choice experiment presenting two treatment profiles described by attributes: mode of administration (oral or intravenous); frequency of administration; overall response rate (ORR); average progression‐free survival (PFS); chance of experiencing severe side effects (SEs); mild–moderate gastrointestinal SEs; mild–moderate skin‐related SEs; and patient out‐of‐pocket costs. Results Fifty‐four patients (all self‐reported EGFR‐mutant) and 74 physicians participated from December 2021 to August 2022. All attributes being equal, there was greater preference for oral administration. However, there was greater preference for intravenous over oral, when ORR and PFS improved by 10% and 1 month, and severe SEs reduced by 10%. Physicians exhibited greater preference for PFS compared to patients (p < 0.01). Ranked order of attribute importance was as follows: (1) PFS; (2) ORR; (3) severe SEs, expressed by patients and physicians alike. Conclusions Our study revealed Japanese physician and patient preferences in treatment options for EGFR‐mutant NSCLC. Compared to the strong preference for a more efficacious drug, the preference of oral versus intravenous revealed a smaller impact

Comparison of Physicians’ Compliance, Clinical Efficacy, and Drug Cost before and after Introduction of Asthma Prevention and Management Guidelines in Japan (JGL2003)

Background: This study investigated the variations in the clinical efficacy and drug cost following the introduction of the Asthma Prevention and Management Guidelines in Japan (JGL2003). Methods: The medical charts of fifty outpatients treated continuously for asthma, aged 16-50 years, from October 2002 to October 2004 at Showa University Hospital were analyzed for physicians’ compliance with asthma guidelines, symptom severity, episodes in various occasions, prescriptions and drug costs. Results: Physicians’ compliance with the guidelines, which were defined as the number of patient visits treated in conformity with the JGL over the total number of patient visits, was found to be high before (89.4%) and after (90.3%) the introduction of JGL2003, without a statistical difference. On the other hand, the distribution of asthma symptom severity varied significantly (P < 0.0001). Fewer patients were recognized as having more severe asthma symptoms after the introduction of JGL2003. Significantly more patients with severe asthma symptoms were detected in the physicians’ noncompliant group than in the compliant group (P < 0.0001). The number of patients prescribed with oral corticosteroids, long-acting β2-agonists containing patches, long-acting oral β2-agonists, short-acting inhaled β2-agonists, sustained-released theophylline and leukotriene receptor antagonists decreased after the introduction of JGL2003. Furthermore, the total annual drug cost per patient decreased significantly by an average of 16,259 yen (P = 0.006). Conclusions: The JGL2003 was judged to have improved criteria, which thus resulted in the high compliance of physicians with the guidelines, in the remission of asthma symptoms and in the reduction in the total annual drug cost per patient