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図書 |
図書
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キケロー [著] ; 岡道男訳
目次情報:
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図書
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山下太郎 [著] . 山添文雄 [著] . 熊谷昌士 [著] . 真鍋勝 [著] . 戸谷哲也 [著]
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論文
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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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山下, 太郎 ; Yamashita, Taro
概要:
取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1425号，学位授与年月日：平成12年3月31日,学位授与年：2000
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石田, 晃介 ; 堀井, 里和 ; 山下, 竜也 ; 荒井, 邦明 ; 山下, 太郎 ; 加賀谷, 尚史 ; 酒井, 佳夫 ; 水腰, 英四郎 ; 本多, 政夫 ; 金子, 周一
概要:
症例は81歳女性．肝S7の腫瘍精査のため当院紹介となった．腹部超音波，腹部CT，腹部MRI，腹部血管造影にて肝adrenal rest tumor（HART）が疑われた．131I-アドステロールを用いた副腎皮質シンチグラフィで集積を認め，H
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ARTと診断した．切除標本ではHARTに合致した所見であった．HARTの診断に副腎皮質シンチグラフィが有用である可能性が示唆された． An 81-year-old female was referred to our hospital for the examination of an S7 liver tumor. The tumor was suspected to be a hepatic adrenal rest tumor (HART) based on ultrasonography, dynamic CT, Gd-EOB-DTPA-enhanced MRI, and CT during abdominal angiography. After various hormonal tests, the tumor was confirmed as hormonally non-functional. The diagnosis of HART was confirmed based on 131I-adosterol accumulation in the tumor by adrenocortical scintigraphy. The resected tumor was histologically compatible with HART, and it may have been able to produce cortisol based on the immunohistochemical findings of various adrenocortical hormone metabolic enzymes. Adrenocortical scintigraphy may thus be useful in diagnosing HART.
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論文
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高田, 佳子 ; 山下, 竜也 ; 島谷, 明義 ; 飯田, 宗穂 ; 荒井, 邦明 ; 北村, 和哉 ; 加賀谷, 尚史 ; 山下, 太郎 ; 酒井, 佳夫 ; 中本, 安成 ; 本多, 政夫 ; 金子, 周一 ; 小山, 有
概要:
金沢大学医学部附属病院内科（旧第一内科）<br />Case is 60 year-old-man who had been followed up about liver injury and diabetes mellitus in a
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nother clinic from 1990. He visited our hospital suffering from epigastralgia in October 2003, and admitted with the finding of hemobilia pointed out by upper GI examination. We diagnosed the illness as hepatocellular carcinoma with hemobilia, because of multiple tumors in the right lobe of the liver, portal vein thrombus, and the elevation of tumor markers such as alpha-fetoprotein (AFP), protein induced by vitamin-K absence (PIVKA-II) and AFP L3 fraction with alcoholic liver cirrhosis. He was treated with combination therapy consisting of hepatic arterial chemotherapy and injection of Interferon-ﾎｱ, and done as an outpatient after the first course treatment. The biliary infection was aggravated during the 4th course, and died 8 months after the initial diagnosis. It is said that hepatocellular carcinoma diagnosed incidentally with hemobilia is relatively rare and that prognosis is poor. In spite of the absence of decrease in tumor on imaging, this case can be considered as one in which this patient got the more prolongud life by interferon combined hepatic arterial chemotherapy.
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論文
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山田, 和俊 ; 北村, 和哉 ; 丹尾, 幸樹 ; 島上, 哲朗 ; 荒井, 邦明 ; 柿木, 嘉平太 ; 山下, 太郎 ; 酒井, 佳夫 ; 水腰, 英四郎 ; 金子, 周一
概要:
症例は57歳男性，食道静脈瘤に対し内視鏡的硬化療法（EIS）を施行したが，その際の止血に難渋した．凝固能の低下，プロトロンビン時間（PT），ヘパプラスチンテスト（HpT）の解離，第V因子の著明な低下，第V因子インヒビターの上昇などを認め，後
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天性第V因子欠損症と診断した．診断時には出血症状を認めておらず，慎重に経過観察をしたところ，自然経過にて凝固能は改善と第V因子インヒビター力価の低下を認めた．内視鏡治療により生じた後天性第V因子欠損症は非常に稀であり，報告する．We report a 57-year-old male with esophageal varices who had difficulty in hemostasis after endoscopic injection sclerotherapy (EIS). Laboratory data revealed a decrease in blood clotting, a dissociation in prothrombin activity with the hepaplastin test results, and a significant reduction in factor V (FV) activity. Therefore, we made the diagnosis of an acquired FV inhibitor. Since the patient had no unusual bleeding at the time of diagnosis, we provided careful observation with no particular treatment. Subsequently we confirmed that there was an improvement in blood clotting and a decrease in the FV inhibitor titer. We report a case of acquired FV deficiency caused by EIS, which is extremely rare.
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論文
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Ho, Tuyen Thuy Bich ; Nasti, Alessandro ; Seki, Akihiro ; Komura, Takuya ; Inui, Hiiro ; Kozaka, Takashi ; Kitamura, Yoji ; Shiba, Kazuhiro ; Yamashita, Taro ; Yamashita, Tatsuya ; Mizukoshi, Eishiro ; Kawaguchi, Kazunori ; Wada, Takashi ; Honda, Masao ; Kaneko, Shuichi ; Sakai, Yoshio ; 関, 晃裕 ; 小村, 卓也 ; 小阪, 孝史 ; 北村, 暘二 ; 柴, 和弘 ; 山下, 太郎 ; 水腰, 英四郎 ; 川口, 和紀 ; 和田, 隆志 ; 本多, 政夫 ; 金子, 周一 ; 酒井, 佳夫
概要:
金沢大学疾患モデル総合研究センター<br />Background Pancreatic ductular adenocarcinoma (PDAC) is among the most dreadful of malignancies,
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in part due to the lack of efficacious chemotherapy. Immune checkpoint inhibitors, including anti-programmed cell death 1 (anti-PD-1) antibodies, are novel promising forms of systemic immunotherapy. In the current study, we assessed whether gemcitabine (GEM) combined with anti-PD-1 antibody treatment was efficacious as immunochemotherapy for advanced PDAC using a murine model of liver metastasis. Methods The murine model of PDAC liver metastasis was established by intrasplenically injecting the murine pancreatic cancer cell line PAN02 into immunocompetent C57BL/6J mice. The mice were treated with an anti-PD-1 antibody, GEM, or a combination of GEM plus anti-PD-1 antibody, and compared with no treatment (control); liver metastases, immune cell infiltration, gene expression, immune cell response phenotypes, and overall survival were investigated. Results In the metastatic tumor tissues of mice treated with GEM plus anti-PD-1 antibody, we observed the increased infiltration of Th1 lymphocytes and M1 macrophages. Gene expression profile analysis of peripheral blood cells obtained from mice treated with GEM plus anti-PD-1 antibody clearly highlighted T cell and innate immune signaling pathways. Survival of PDAC liver metastasis mice was significantly prolonged by the combination therapy (median survival, 66 days) when compared with that of GEM alone treatment (median survival, 56 days). Expanded lymphocytes, which were isolated from the splenocytes of PDAC liver metastasis mice treated with GEM plus anti-PD-1 antibody, had an increased number of M1 macrophages. Conclusion The combination of anti-PD-1 antibody immunotherapy with GEM was beneficial to treat a murine model of PDAC liver metastasis by enhancing the immune response mediated by Th1 lymphocytes and M1 macrophages and was associated with CD8+ T cells. ©
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山下, 太郎 ; Yamashita, Taro
概要:
金沢大学附属病院総合診療部<br />肝細胞癌の再発、転移など、難治性に関わる重要な細胞集団として癌幹細胞が知られている。本研究ではEpCAM陽性癌幹細胞における可塑性について、特にがん幹細胞の維持制御機構と微小環境を構成する細胞との関連に
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ついて検討を行った。線維芽細胞はTGF-betaを分泌しEpCAM陽性癌幹細胞を増加させ、そのメカニズムとしてKDM2Bの発現誘導によるH3K36メチル基のエピジェネティックメモリー制御が考えられた。また癌微小環境を反映すると考えられる６種の血清サイトカインを同定、分子標的薬ソラフェニブの感受性、予後延長効果に関わる可能性を見出した。<br />Recent evidences suggest that hepatocellular carcinoma possesses cancer stem cells that play a pivotal role on local recurrence and distant organ metastasis after radical treatment. In this study, we found that fibroblasts secrets TGF-beta and induce the stemness in EpCAM+ hepatocellular carcinoma. This effect was mediated at least in part through the activation of H3K36 demethylase KDM2B to modify epigenetic memories and induce the population of EpCAM+ cancer stem cells. We further identified the six cytokines, potentially reflecting the activation of microenvironment of hepatocellular carcinoma, to predict the survival outcome of hepatocellular carcinoma patients who received sorafenib treatment.<br />研究課題/領域番号:26460994, 研究期間(年度):2014-04-01 - 2017-03-31
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山下, 太郎 ; Yamashita, Taro
概要:
金沢大学附属病院<br />肝細胞癌の再発、転移など、難治性に関わる重要な細胞集団として癌幹細胞が知られている。本研究ではEpCAM陽性癌幹細胞における遺伝子変異を全エクソンレベルで網羅的に解析した。EpCAM陽性癌幹細胞を有する肝癌では癌
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抑制遺伝子であるTP53の変異が認められ、さらに個体特異的にARIDやCDKNなど癌の未分化性、細胞周期に関わる遺伝子に変異が認められ、肝癌の難治性を克服する上で重要な分子標的と考えられた。<br />Recent evidences suggest that hepatocellular carcinoma possesses cancer stem cells that play a pivotal role on local recurrence and distant organ metastasis after radical treatment. In this study, we evaluated the genetic mutations observed in hepatocellular carcinoma containing EpCAM-positive cancer stem cells at whole exome level. We identified TP53, ARID, and CDKN mutations in EpCAM-positive hepatocellular carcinoma cells. These mutations may be responsible for the maintenance of EpCAM-positive cancer stem cells and therefore may be good targets for eradication of hepatocellular carcinoma.<br />研究課題/領域番号:23590967, 研究期間(年度):2011–2013
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