樹状細胞と新規ケモカイン製剤の併用により肝がんの二次発がんを制御する手法の開発

2013 年度 研究成果報告書

• 研究課題/領域番号: 23659396
• 研究種目: 挑戦的萌芽研究
• 配分区分: 基金
• 研究分野: 消化器内科学
• 研究機関: 福井大学
• 研究代表者: 中本 安成 福井大学, 医学部, 教授 (40293352)
• 研究期間 (年度): 2011 – 2013
• キーワード: 癌 / 免疫学 / ﾄﾗﾝｽﾚｰｼｮﾅﾙﾘｻｰﾁ / 動物 / 内科

研究概要

肝がん治療後の再発（二次発がん）を抗腫瘍免疫によって制御する目的で、樹状細胞と新規ケモカイン製剤を併用する手法を開発した。樹状細胞の誘導についてOK-432と亜鉛を用いる方法の有用性、ケモカイン製剤についてがん免疫の賦活化作用が示唆された。さらに、組換技術を用いて本製剤の生物学的安定性を向上した。これより、樹状細胞とケモカイン製剤の併用によって肝がんの二次発がんが抑制される可能性が示された。

研究成果

• [雑誌論文] Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma (2014)
  • 著者名/発表者名: Yamashita T, Kitao A, Matsui O, Hayashi T, Nio K, Kondo M, Ohno N, Miyati T, Okada H, Yamashita T, Mizukoshi E, Honda M, Nakanuma Y, Takamura H, Ohta T, Nakamoto Y, Yamamoto M, Takayama T, Arii S, Wang XW, Kaneko S
  • 雑誌名: Hepatology 巻: (in press)
  • DOI: 10.1002/hep.27093.
  • 査読あり
• [雑誌論文] Intractable Liver and Biliary Diseases Study Group of Japan : Multicenter validation study of anti-programmed cell death-1 antibody as a serological marker for type 1 autoimmune hepatitis (2014)
  • 著者名/発表者名: Miyake Y, Yamamoto K, Matsushita H, Abe M, Takahashi A, Umemura T, Tanaka A, Nakamuta M, Nakamoto Y, Ueno Y, Saibara T, Takikawa H, Yoshizawa K, Ohira H, Zeniya M, Onji M, Tsubouchi H
  • 雑誌名: Hepatol. Res 巻: (in press)
  • DOI: 10.1111/hepr.12305.
  • 査読あり
• [雑誌論文] In vivo immunological antitumoreffect of OK-432-stimulated dendritic cell transfer after radiofrequencyablation (2014)
  • 著者名/発表者名: Nakagawa H, Mizukoshi E, Iida N, Terashima T, Kitahara M, Marukawa Y, KitamuraK, Nakamoto Y, Hiroishi K, Imawari M, Kaneko S
  • 雑誌名: Cancer Immunol Immunother 巻: 63 ページ: 347-356
  • DOI: 10.1007/s00262-013-1514-7.
  • 査読あり
• [雑誌論文] Pathophysiological Decrease in the Regional Cerebral Blood Flow in Hashimoto's Encephalopathy : A Multiple-Case SPECT Study (2014)
  • 著者名/発表者名: Muramatsu T, Ikawa M, Yoneda M, Sugimoto K, Matsunaga A, Yamamura O, Hamano T, Okazawa H, Nakamoto Y
  • 雑誌名: Eur Neurol 巻: 72 ページ: 13-19
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24777056
  • 査読あり
• [雑誌論文] Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma (2013)
  • 著者名/発表者名: Yamashita T, Honda M, Nakamoto Y, Baba M, Nio K, Hara Y, Zeng SS, Hayashi T, Kondo M, Takatori H, Yamashita T, Mizukoshi E, Ikeda H, Zen Y, Takamura H, Wang XW, Kaneko S
  • 雑誌名: Hepatology 巻: 57 ページ: 1484-1497
  • DOI: 10.1002/hep.26168.
  • 査読あり
• [雑誌論文] Increase in CD14+HLA-DR -/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis (2013)
  • 著者名/発表者名: Arihara F, Mizukoshi E, Kitahara M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S
  • 雑誌名: Cancer Immunol. Immunother 巻: 62 ページ: 1421-1430
  • DOI: 10.1007/s00262-013-1447-1.
  • 査読あり
• [雑誌論文] Correction : TNF-α and Tumor Lysate Promote the Maturation of Dendritic Cells for Immunotherapy for Advanced Malignant Bone and Soft Tissue Tumors (2013)
  • 著者名/発表者名: Miwa S, Nishida H, Tanzawa Y, Takata M, Takeuchi A, Yamamoto N, Shirai T, Hayashi K, Kimura H, Igarashi K, Mizukoshi E, Nakamoto Y, Kaneko S, Tsuchiya H
  • 雑誌名: PLoS One (eCollection 2013.) 巻: 24 ページ: 8
  • DOI: 10.1371/annotation/7c0f14e6-cfba-4f5fb93d-1a149eaeec96
  • 査読あり
• [雑誌論文] Detection of preclinically latent hyperperfusion due to stroke-like episodes by arterial spin-labeling perfusion MRI in MELAS patients (2013)
  • 著者名/発表者名: Ikawa M1, Yoneda M, Muramatsu T, Matsunaga A, Tsujikawa T, Yamamoto T, Kosaka N, Kinoshita K, Yamamura O, Hamano T, Nakamoto Y, Kimura H
  • 雑誌名: Mitochondrion 巻: 13 ページ: 676-680
  • DOI: 10.1016/j.mito.2013.09.007.
  • 査読あり
• [雑誌論文] Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking spinocerebellar degeneration (2013)
  • 著者名/発表者名: Matsunaga A, Ikawa M, Fujii A, Nakamoto Y, Kuriyama M, Yoneda M
  • 雑誌名: Eur. Neurol 巻: 69 ページ: 14-20
  • DOI: 10.1159/000342217.
  • 査読あり
• [雑誌論文] TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors (2013)
  • 著者名/発表者名: Miwa S1, Nishida H, Tanzawa Y, Takata M, Takeuchi A, Yamamoto N, Shirai T, Hayashi K, Kimura H, Igarashi K, Mizukoshi E, Nakamoto Y, Kaneko S, Tsuchiya H
  • 雑誌名: PLoS One 巻: 7 ページ: e52926
  • DOI: 10.1371/journal.pone.0052926.
  • 査読あり
• [雑誌論文] Clinical relevance and sequence analysis of the Helicobacter pylori dupA region from two areas in Japan with different gastric cancer risks (2012)
  • 著者名/発表者名: Matsuda H, Ito Y, Suto H, Yamakawa A, Satomi S, Ohtani M Yamazaki Y, Kusaka Y, Shimabukuro Y, Kikuchi K, Keida Y, Azuma T, Nakamoto Y
  • 雑誌名: Immuno-Gatroenterology 巻: 1:2 ページ: 127-135
  • URL: http://www.stmconnect.com/ig
  • 査読あり
• [雑誌論文] Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma (2012)
  • 著者名/発表者名: Marukawa Y, Nakamoto Y, Kakinoki K, Tsuchiyama T, Iida N, Kagaya T, Sakai Y, Naito M, Mukaida N, Kaneko S
  • 雑誌名: Cancer Gene Ther 巻: 19 ページ: 312-319
  • DOI: 10.1038/cgt.2012.3.
  • 査読あり
• [雑誌論文] Nucleostemin in Injury-Induced Liver Regeneration (2012)
  • 著者名/発表者名: Shugo H, Ooshio T, Naito M, Naka K, Hoshii T, Tadokoro Y, Muraguchi T, Tamase A, Uema N, Yamashita T, Nakamoto Y, Suda T, Kaneko S, Hirao A
  • 雑誌名: Stem Cells Dev 巻: 21 ページ: 3044-3054
  • DOI: 10.1089/scd.2011.0725.
  • 査読あり
• [雑誌論文] Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update (2012)
  • 著者名/発表者名: Kaneko S, Furuse J, Kudo M, Ikeda K, Honda M, Nakamoto Y, Onchi M, Shiota G, Yokosuka O, Sakaida I, Takehara T, Ueno Y, Hiroishi K, Nishiguchi S, Moriwaki H, Yamamoto K, Sata M, Obi S, Miyayama S, Imai Y
  • 雑誌名: Hepatol. Res 巻: 42 ページ: 523-542
  • DOI: 10.1111/j.1872-034X.2012.00981.x.
  • 査読あり
• [雑誌論文] Evaluation of systemic redox states in patients carrying the MELAS A3243G mutation in mitochondrial DNA (2012)
  • 著者名/発表者名: Ikawa M, Arakawa K, Hamano T, Nagata M, Nakamoto Y, Kuriyama M, Koga Y, Yoneda M
  • 雑誌名: Eur. Neurol 巻: 67 ページ: 232-237
  • DOI: 10.1159/000336568.
  • 査読あり
• [雑誌論文] Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization (2011)
  • 著者名/発表者名: Nakamoto Y, Mizukoshi E, Kitahara M, Arihara F, Sakai Y, Kakinoki K, Fujita Y, Marukawa Y, Arai K, Yamashita T, Mukaida N, Matsushima K, Matsui O, Kaneko S
  • 雑誌名: Clin. Exp.Immunol 巻: 163 ページ: 165-177
  • DOI: 10.1111/j.1365-2249.2010.04246.x.
  • 査読あり
• [雑誌論文] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma (2011)
  • 著者名/発表者名: Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Sakai A, Sakai Y, Kagaya T, Yamashita T, Honda M, Kaneko S
  • 雑誌名: HEPATOLOGY 巻: 53 ページ: 1206-1216
  • DOI: 10.1002/hep.24149.
  • 査読あり
• [雑誌論文] Frequency of CD45RO+ subset in CD4+CD25(high) regulatory T cells associated with progression of hepatocellular carcinoma (2011)
  • 著者名/発表者名: Takata Y, Nakamoto Y, Nakada A, Terashima T, Arihara F, Kitahara M, Kakinoki K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S
  • 雑誌名: Cancer Lett 巻: 307 ページ: 165-173
  • DOI: 10.1016/j.canlet.2011.03.029.
  • 査読あり
• [雑誌論文] Hokuriku Liver Study Group : Malnutrition impairs interferon signaling through mTOR and FoxO pathways in patients with chronic hepatitis C (2011)
  • 著者名/発表者名: Honda M, Takehana K, Sakai A, Tagata Y, Shirasaki T, Nishitani S, Muramatsu T, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, Yamashita T, Nakamura M, Shimakami T, Yi M, Lemon SM, Suzuki T, Wakita T, Kaneko S
  • 雑誌名: GASTROENTEROLOGY 巻: 141 ページ: 128-140
  • DOI: 10.1053/j.gastro.2011.03.051.
  • 査読あり
• [雑誌論文] Randomized, phase II study comparing interferon combined with hepatic arterial infusion of fluorouracil plus cisplatin and fluorouracil alone in patients with advanced hepatocellular carcinoma (2011)
  • 著者名/発表者名: Yamashita T, Arai K, Sunagozaka H, Ueda T, Terashima T, Yamashita T, Mizukoshi E, Sakai A, Nakamoto Y, Honda M, Kaneko S
  • 雑誌名: Oncology 巻: 81 ページ: 281-290
  • DOI: 10.1159/000334439.
  • 査読あり
• [学会発表] Clinical evaluation of patency capsule system in high risk patients for video capsule endoscopy (2013)
  • 著者名/発表者名: Ohtani M, Suto H, Nakamoto Y
  • 学会等名: Japan Digestive DiseaseWeek 2013
  • 発表場所: Tokyo
  • 年月日: 2013-10-12
• [学会発表] MicroRNA Dynamics in Precancerous Lesions in a Mouse Model of Chronic Hepatitis B (2012)
  • 著者名/発表者名: Nakamoto Y, Yamashita T, Kaneko S
  • 学会等名: 第63回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • 発表場所: Boston, Massachusetts, Hepatology 56 (4,Suppl.) 315A
  • 年月日: 2012-11-13
• [学会発表] High Incidence of HBV Reactivation after R-CHOP and CHOP Regimens among Patients Treated with Six Immunosuppressive Chemotherapies (2012)
  • 著者名/発表者名: Naito T, Nemoto T, Matsuda H, Ohtani M, Suto H Nakamoto Y
  • 学会等名: 第63回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • 発表場所: Boston, Massachusetts, Hepatology 56 (4,Suppl.) 643A
  • 年月日: 2012-11-11
• [学会発表] Differential Dynamics of the NF-kappaB subunits RELA and RELB in a Mouse Model of Chronic Hepatitis B (2011)
  • 著者名/発表者名: Nakamoto Y, Yamashita T, Kaneko S
  • 学会等名: 第62回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • 発表場所: San Francisco, California, Hepatology 54 (4,Suppl.) 1300A
  • 年月日: 2011-11-08
• [学会発表] Increase of CD14+HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma and its impact for prognosis of patients (2011)
  • 著者名/発表者名: Arihara F, Mizukoshi E, Kitahara M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S
  • 学会等名: 第62回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • 発表場所: San Francisco, California, Hepatology 54 (4,Suppl.) 1400A
  • 年月日: 2011-11-08