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Cytotoxic Effects of Arsenite in Combination With Gamabufotalin Against Human Glioblastoma Cell Lines
Get PDFGlioblastoma is a fatal primary malignant brain tumor, and the 5-year survival rate of treated glioblastoma patients still remains <5%. Considering the sustained development of metastasis, tumor recurrence, and drug resistance, there is an urgent need for the novel therapeutic approaches to combat glioblastoma. Trivalent arsenic derivative (arsenite, AsIII) with remarkable clinical efficacy in leukemia has been shown to exert cytocidal effect against glioblastoma cells. Gamabufotalin, an active bufadienolide compound, also shows selective cytocidal effect against glioblastoma cells, and has been suggested to serve as a promising adjuvant therapeutic agent to potentiate therapeutic effect of conventional anticancer drugs. In order to gain novel insight into therapeutic approaches against glioblastoma, the cytotoxicity of AsIII and gamabufotalin was explored in the human glioblastoma cell lines U-87 and U-251. In comparison with U-251 cells, U-87 cells were highly susceptible to the two drugs, alone or in combination. More importantly, clinically achieved concentrations of AsIII combined with gamabufotalin exhibited synergistic cytotoxicity against U-87 cells, whereas showed much less cytotoxicity to human normal peripheral blood mononuclear cells. G2/M cell cycle arrest was induced by each single drug, and further augmented by their combination in U-87 cells. Downregulation of the expression levels of cdc25C, Cyclin B1, cdc2, and survivin was observed in U-87 cells treated with the combined regimen and occurred in parallel with G2/M arrest. Concomitantly, lactate dehydrogenase leakage was also observed. Intriguingly, SB203580, a specific inhibitor of p38 MAPK, intensified the cytotoxicity of the combined regimen in U-87 cells, whereas wortmannin, a potent autophagy inhibitor, significantly rescued the cells. Collectively, G2/M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of AsIII and gamabufotalin. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a possible strategy composed of AsIII, gamabufotalin, and a p38 MAPK inhibitor may provide novel insight into approaches designed to combat glioblastoma.Article 628914, This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Use of 13 C-NMR Chemical Shifts; Application of Principal Component Analysis for Categorizing Structurally Similar Methoxyflavones and Correlation Analysis between Chemical Shifts and Cytotoxicity
Get PDFThe 13C-NMR spectral data for the 15-carbon flavonoid skeleton in eleven methoxyflavones isolated from Kaempferia parviflora (Zingiberaceae) were processed by principal component analysis (PCA). Based on the PCA score plots, the methoxyflavones were categorized into three groups according to their structural features. The cytotoxicities of the methoxyflavones toward 3T3-L1 murine preadipocyte cells were evaluated by 3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and found to differ according to structure. The relationship between the 13C-NMR chemical shifts of the methoxyflavones and their cytotoxicities was investigated using Pearson's correlation analysis. The 13C-NMR signal at C-10, a quaternary carbon, was correlated with cytotoxicity. Based on these results, a structural design which lowers the 13C-NMR chemical shift at C-10 would be important for the development of cytotoxic compounds. Although quantitative structure-activity and structure-property relationships are well established paradigms for predicting trends among a series of compounds, quantitative property-activity relationships have been relatively unstudied. This approach offers a new strategy for directing structure-activity relationship research
Autocrine secretion of insulin-like growth factor-I mediates growth hormone-stimulated DNA synthesis and proliferation in primary cultures of adult rat hepatocytes
Get PDFThe intracellular signaling pathway of growth hormone (GH)-stimulated DNA synthesis and proliferation was investigated in primary cultures of adult rat hepatocytes. DNA synthesis and cell proliferation were detected in hepatocyte parenchymal cells grown in serum-free, defined medium containing GH (100 ng/ml). GH-stimulated hepatocyte DNA synthesis and proliferation were almost completely blocked by TG101209 (10−6 M), a selective Janus kinase (JAK)2 inhibitor, U-73122 (10−6 M), a selective phospholipase C (PLC) inhibitor, and a monoclonal antibody to insulin-like growth factor-I (IGF-I) receptor (100 ng/ml) or anti-secretion agents such as somatostatin (10−6 M) and BAPTA/AM (10−7 M). In addition, blocking monoclonal antibodies to IGF-I, but not transforming growth factor-α, completely inhibited GH-induced hepatocyte DNA synthesis and proliferation. IGF-I levels in the culture medium increased rapidly versus baseline levels within 5 min in response to GH (100 ng/ml), and the maximum IGF-I level (100 pg/ml) was reached 20 min after GH stimulation. Autocrine secretion of IGF-I into the culture medium was inhibited by a growth-inhibitory dose of TG101209, U-73122, somatostatin, or BAPTA/AM. These data indicate that the proliferative mechanism of action of GH is mediated mainly through a GH receptor/JAK2/PLC-stimulated increase in the autocrine secretion of IGF-I by primary cultured hepatocytes, followed by stimulation of the 95 kDa IGF-I receptor tyrosine kinase signaling pathway.Article No.17375
To Measure Economic Values of Personal Information
Get PDF本研究では，仮想的な状況を想定し，コンジョイント分析を行うことにより，個人情報（氏名・住所・性別・生年月日）ならびに SNS のアカウント情報（SNS の ID やパスワードなど）の価値の測定を試みた。その際，2019 年 3 月に実施した「労働者の情報セキュリティ意識および行動に関する調査 2019」の結果（個票データ）を用いた。その結果，属性として用いた「慰謝料」「精神的被害」「実被害」および企業の対応（「金券」「詫び状」「HP」）の係数は概ね統計的に有意となり，それぞれのコンジョイントカードで設定されている選択肢の効用に影響を与えていることがわかった。この結果を用いて個人情報と SNS のアカウント情報の限界支払意思額をそれぞれ計算したところ，精神的被害を貨幣価値で測ると前者が約 11,084 円（後者が 3,516 円），実被害については前者が約 38,593 円（後者が 44,014 円）になった。また，企業の対応について見てみると，500 円の金券を送るよりも，詫び状を送ったりする方が個人にとって高い評価をしていることなども明らかになった。In this article, under the hypothetical situation we assumed, we measure economic value of personal information such as personal information and their account information of SNS. For the purpose, we conduct conjoint analysis by using the micro data collected from the Web-based survey at March 2019. As a result, it is found that the estimated coefficients of “consolation money,” “mental damage,” “real damage” and “firm’s correspondence” （“cash voucher,” “apologetic letter,” and “HP”） are statistically significant. Subsequently, by using the results, we calculate the amount of willing to pay （WTP） of personal information and account information of SNS, respectively. Then, we can find that the amount of mental damage of the former is ¥11,084 JP （the latter is ¥3,516 JP） and the amount of real damage of the former is ¥38,593 JP （the latter is ¥44,014 JP）. In addition, about firm’s correspondence, it is found that sending apologetic letter would be estimated higher rather than sending cash voucher of ¥500 JP.通巻第44号, 論文 / Article
Management Issues Faced by Kokusai-Tsuuun and Designated Companies in the Tokyo Region in the Japanese Transportation Industry during the Interwar Period
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Establishing a Curator Course at Josai University and the Role of Museums as Centers for Cultural Policy
Get PDF本稿は、地域活性化やまちづくりとしての役割が課せられつつあるミュージアムの今日的状況を検証しつつ、そこで働く学芸員の新たな役割について検討した。その上で、政策学を基軸とした現代政策学部を中心に学芸員養成課程を設置した場合の有効性について検討した。その結果、実際に学芸員職として博物館で働く機会は限定されているものの、官民を問わず、文化政策の担い手が必要とされる中で、学芸員資格は有効であることが明らかとなった。そして、城西大学の学芸員養成課程における学びは、履修者のキャリアの幅を広げる可能性があることが結論づけられた。This paper explores the role of museums, which are recently being assigned as centers for regional revitalization and community development, and examines the new roles of curators working in them. The author also looks at the effectiveness of establishing a curator course in the Faculty of Contemporary Policy at Josai University, based in based on policy studies. The results show it is clear that a curator qualification is effective in meeting a need for cultural policy leaders, both public and private, although the opportunities to actually work in a museum as a curator are limited. It concluded that the curator course at Josai University could broaden students’ career opportunities in other fields.論文 / Article
