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Hayashi, Tomoyuki ; Yamashita, Taro ; Terashima, Takeshi ; Suda, Tsuyoshi ; Okada, Hikari ; Asahina, Yoshiro ; Hayashi, Takehiro ; Hara, Yasumasa ; Nio, Kouki ; Sunagozaka, Hajime ; Takatori, Hajime ; Arai, Kuniaki ; Yamashita, Tatsuya ; Mizukoshi, Eishiro ; Honda, Masao ; Kaneko, Shuichi ; 林, 智之 ; 山下, 太郎 ; 寺島, 健志 ; 須田, 烈史 ; 岡田, 光 ; 朝日向, 良朗 ; 丹尾, 幸樹 ; 砂子阪, 肇 ; 鷹取, 元 ; 荒井, 邦明 ; 山下, 竜也 ; 水腰, 英四郎 ; 本多, 政夫 ; 金子, 周一
概要:
金沢大学先進予防医学研究科<br />Background: Sorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survi
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val in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug's survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that serum cytokines levels could predict the survival of advanced HCC patients, as sorafenib targets signaling pathways activated in the tumor stromal microenvironment and potentially affects serum cytokine profiles. Methods: Of 143 patients with advanced-stage HCC, 104 who were recruited between 2003 and 2007 received hepatic arterial infusion chemotherapy (HAIC) that mainly targets tumor epithelial cells at S-phase (cohort 1); additionally, 39 recruited between 2010 and 2012 received sorafenib, which primarily targets the stromal vascular endothelial cells. Serum samples were collected and aliquoted prior to the treatment. Serum EGF, bFGF, HGF, IFN-γ, IL-10, IL-12, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10, MIG, PDGF-BB, SCF, SDF1, TGF-β, TGF-α, TNF-α, and VEGF-A were measured via enzyme-linked immunosorbent assays. The Modified Response Evaluation Criteria in Solid Tumors were used to assess tumor responses. Results: The median survival time of HCC patients in cohorts 1 (HAIC-treated) and 2 (sorafenib-treated) were 12.0 and 12.4 months, respectively. Kaplan-Meier analysis revealed no significant survival differences between the 2 groups. Patients who survived more than 2 years after sorafenib treatment exhibited higher serum levels of IL-10, IL-12, TNF-a, IL-8, SDF-1, EGF, PDGF-BB, SCF, and TGF-α. Furthermore, cohort 2 patients with higher serum IL-5 (>12 pg/mL), IL-8 (>10 pg/mL), PDGF-BB (>300 pg/mL), and VEGF-A (>50 pg/mL) levels achieved longer survival; cohort 1 patients did not. Hierarchical cluster analysis of 6 cytokines robustly enriched for comparison analysis between cohorts 1 and 2 (IL-5, IL-8, TGF-α, PDGF-BB, CXCL9, and VEGF-A) revealed that elevation of these cytokines correlated with better survival when treated with sorafenib but not with HAIC. Conclusions: Patients who exhibited survival benefits owing to sorafenib treatment tended to present higher serum cytokines levels, potentially reflecting the activation of stromal signaling in the tumor microenvironment. Our study thus introduces novel biomarkers that may identify advanced HCC patients who may experience survival benefits with sorafenib treatment. © 2017 The Author(s).
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Sunagozaka, Hajime ; Honda, Masao ; Yamashita, Taro ; Nishino, Ryuhei ; Takatori, Hajime ; Arai, Kuniaki ; Yamashita, Tatsuya ; Sakai, Yoshio ; Kaneko, Shuichi
概要:
The identification of genes involved in tumor growth is crucial for the development of inventive anticancer treatments.
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Here, we have cloned a 17-kDa secretory protein encoded by c19orf10 from hepatocellular carcinoma (HCC) serial analysis of gene expression libraries. Gene expression analysis indicated that c19orf10 was overexpressed in approximately two-thirds of HCC tissues compared to the adjacent noncancerous liver tissues, and its expression was significantly positively correlated with that of alpha-fetoprotein (AFP). Overexpression of c19orf10 enhanced cell proliferation of AFP-negative HLE cells, whereas knockdown of c19orf10 inhibited cell proliferation of AFP-positive Hep3B and HuH7 cells along with G1 cell cycle arrest. Supplementation of recombinant c19orf10 protein in culture media enhanced cell proliferation in HLE cells, and this effect was abolished by the addition of antibodies developed against c19orf10. Intriguingly, c19orf10 could regulate cell proliferation through the activation of Akt/mitogen-activated protein kinase pathways. Taken together, these data suggest that c19orf10 might be one of the growth factors and potential molecular targets activated in HCC. Copyright © 2010 UICC.
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| 3.
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林, 智之 ; 鷹取, 元 ; 土山, 寿志 ; 上山本, 伸治 ; 太田, 肇 ; 稲邑, 克久 ; 辻, 宏和 ; 宮森, 弘年 ; 松田, 充 ; 蓑内, 慶次 ; 朝日向, 良朗 ; 北村, 和哉 ; 加賀谷, 尚史 ; 金子, 周一 ; Hayashi, Tomoyuki ; Takatori, Hajime ; Doyama, Hisashi ; Kamiyamamoto, Shinji ; Ohta, Hajime ; Inamura, Katsuhisa ; Tsuji, Hirokazu ; Miyamori, Hirotoshi ; Matsuda, Mitsuru ; Minouchi, Keiji ; Asahina, Yoshiro ; Kitamura, Kazuya ; Kagaya, Takashi ; Kaneko, Shuichi
概要:
[背景・目的] 現在, スクリーニング上部消化管内視鏡検査における咽頭領域の観察が十分に浸透しているとはいい難い状況である. 北陸地区における上部消化管内視鏡での咽頭観察の現状について調査した. [方法] 日本消化器内視鏡学会専門医114名
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にアンケートを送付し, 回答のあった73名を対象とし調査した. [結果] 咽頭観察を全例に行っている医師は79.5%, スクリーニングに画像強調観察(image-enhanced endoscopy:IEE)を用いた(I群)のは61.6%であった. 観察時間はI群が白色光(W群)と比べ有意に長く(p<0.001), 1年以内の癌の発見率はI群がW群と比べ有意に高かった(p=0.007). 問題点として, 観察の困難さ, 苦痛増強の可能性などの意見が多かった. [結論] スクリーニングにおける咽頭観察において, 癌の発見にはIEEにて時間をかけて観察することが重要である可能性が示唆された. 今後, さらなる咽頭観察の啓蒙活動が重要と考えられる.<br />出版者照会後に全文公開
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| 4.
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Hayashi, Tomoyuki ; Miura, Miyabi ; Takatori, Hajime ; Kitamura, Kazuya ; Yamashita, Tatsuya ; Kaneko, Shuichi
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Sunagozaka, Hajime ; Honda, Masao ; Yamashita, Taro ; Nishino, Ryuhei ; Takatori, Hajime ; Arai, Kuniaki ; Yamashita, Tatsuya ; Sakai, Yoshio ; Kaneko, Shuichi
概要:
金沢大学医薬保健研究域医学系<br />The identification of genes involved in tumor growth is crucial for the development of inventive ant
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icancer treatments. Here, we have cloned a 17-kDa secretory protein encoded by c19orf10 from hepatocellular carcinoma (HCC) serial analysis of gene expression libraries. Gene expression analysis indicated that c19orf10 was overexpressed in approximately two-thirds of HCC tissues compared to the adjacent noncancerous liver tissues, and its expression was significantly positively correlated with that of alpha-fetoprotein (AFP). Overexpression of c19orf10 enhanced cell proliferation of AFP-negative HLE cells, whereas knockdown of c19orf10 inhibited cell proliferation of AFP-positive Hep3B and HuH7 cells along with G1 cell cycle arrest. Supplementation of recombinant c19orf10 protein in culture media enhanced cell proliferation in HLE cells, and this effect was abolished by the addition of antibodies developed against c19orf10. Intriguingly, c19orf10 could regulate cell proliferation through the activation of Akt/mitogen-activated protein kinase pathways. Taken together, these data suggest that c19orf10 might be one of the growth factors and potential molecular targets activated in HCC. © 2010 UICC.
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Wada, Taizo ; Maeba, Hideaki ; Ikawa, Yasuhiro ; Hashida, Yoko ; Okumura, Akiko ; Shibata, Fumie ; Tone, Yumi ; Inoue, Masayuki ; Koizumi, Shoichi ; Takatori, Hajime ; Sakai, Yoshio ; Kaneko, Shuichi ; Yachie, Akihiro
概要:
金沢大学附属病院小児科<br />Reactive plasmacytosis is a transient expansion of plasma cell progenitors and precursors. This rare co
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ndition has been reported to occur mainly in infections and tumors. We describe a case of acute hepatitis A presenting with marked peripheral blood plasmacytosis. Plasma cells made up 27.5% of the mononuclear cells and had the immunophenotype CD10-CD19 +CD20-CD21-CD23-CD34 -CD38++HLA-DR+. Although the level of interleukin 6 was not increased, the presence of activated T-cells with an inverted CD4/CD8 ratio and high levels of soluble interleukin 2 receptor and neopterin indicated a marked immune response to acute hepatitis A. The patient's plasma cells had almost disappeared from the blood by hospital day 16. This report may represent the first described case of reactive peripheral blood plasmacytosis in acute hepatitis A. © 2007 The Japanese Society of Hematology.
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