〔調査報告〕1923 年の『大阪朝日新聞 神戸附録』その１

We, the Society for the Research of Modern Culture of Kobe, have been studying the cultural formation of the port city of Kobe from various aspects. In this paper（ which will form the first part of our whole research） we deliver a report on the trend of movies, theater, performing arts, fine arts and photography in the city, by scrutinizing a series of articles, Zassô-en, written by the Kobe correspondents, in the newspaper Kobe Furoku, Osaka Asahi Shimbun, issued in 1923. Through the Zassô-en articles we can see not only various incidents reported by the correspondents but also their love for their hometown, which encouraged them to plan and carry out diverse cultural and artistic events in the town. We can also find the trend of the picture houses and moviegoers in Shinkaichi, Kobe, in those days, especially the way the entrepreneurs attracted people. Concerning the theater, the articles tell us that the things gladly accepted then were comedy and Shinkokugeki

Acetylation Unleashes Protein Demons of Dementia

Aberrant posttranslational modifications of proteins can impair synaptic plasticity and may render neurons vulnerable to degeneration during aging. In this issue of Neuron, Min et al. show that acetylation of the amino acid lysine in the microtubule-associated protein tau prevents its ubiquitin-mediated degradation, resulting in “tau tangles” similar to those of dementias. Other recent studies suggest that lysine hyperacetylation contributes to the accumulation of amyloid β-peptide in Alzheimer's disease and to impaired cognitive function resulting from a trophic factor deficit

VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers

Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC

MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I.

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8+ T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients

乳化剤無添加のジアシルグリセロールで調製した油中水滴型エマルションの乳化特性に及ぼす塩類の影響

The effect of various types of salt on the properties of water-in-oil emulsions prepared with diacylglycerol (DAG) without the addition of an emulsifier was examined. Aqueous salt solutions containing 0, 0.025, 0.05, 0.1, 0.25M and 0.5M concentrations of NaCl, KCl, CaCl_2, MgCl_2, Na_2S0_4, K_2 SO_4 and MgSO_4 were each separately used as aqueous phase. The same volume of DAG and each salt solution was emulsified at 10,000 rpm for 5 min. The emulsion stability, the particle-size distribution and the flow behavior of each emulsion were measured. The emulsion stability was markedly increased by the addition of all types of salt tested, the stability depended on salt concentration up to 0.1M. In spite of the combination of different anion, this effect was stronger for those salts having a divalent cation than a monovalent cation. On the other hand, the particle-size distribution of the all of the emulsions was similar, regardless of the type of salt or its concentration. A high salt concentration had a greater effect and increased for those salts having a divalent cation than a monovalent cation on flow behavior. From these results, we thought that divalent cations in the emulsions would have strengthened the film of the oil-water interface