Role of Faascin protein in proliferation and invasion of hepatocellular carcinoma.

• Project/Area Number: 20591614
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: TAKETOMI Akinobu Kyushu University, 医学研究院・消化器・総合外科, 助教 (70363364)
• Co-Investigator(Kenkyū-buntansha): MAEHARA Yoshihiko 九州大学, 大学院・医学研究院, 教授 (80165662) ; SHIRABE Ken 九州大学, 大学院・医学研究院, 講師 (70264025) ; YAMASHITA Yoichi 九州大学, 大学院・医学研究院, 助教 (00404070) ; SUGIMACHI Keishi 九州大学, 大学院・医学研究院, 助教 (90452763)
• Co-Investigator(Renkei-kenkyūsha): AISHIMA Shinichi 九州大学, 大学院・医学研究院, 助教
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Fascin / 肝細胞癌 / 予後 / 無再発生存 / 浸潤 / 転移

Research Abstract

BACKGROUND : Fascin is an actin-bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry. METHODS : A total of 137 patients with HCC were stained with anti-fascin antibody. The tumor cells having unequivocal cytoplasmic and/or membranous fascin immunoreactivity were defined as fascin-positive. RESULTS : Immunohistochemically, 23 (16.8%) HCCs having unequivocal fascin immunoreactivity were found. Tumors showing fascin expression were larger and less differentiated than those showing no fascin expression (P=0.0239 and 0.0018, respectively). Portal venous invasion, bile duct invasion, and intrahepatic metastasis were detected significantly more frequently in fascin-positive group (P=0.0029, 0.0333, and 0.0403, respectively). In addition, high alpha-fetoprotein (AFP) levels were significantly associated with the fascin expression in HCC (P=0.0116). Fascin-positive group had significantly poorer outcomes than fascin-negative group and was an independent prognostic factor for disease-free survival. CONCLUSIONS : Fascin might become a novel marker of progression in HCC and a significant indicator of a poor prognosis for patients with HCC.

Research Products

• [Journal Article] Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation. (2010)
  • Author(s): Taketomi A, Fukuhara T, Morita K, Kayashima H, Ninomiya M, Yamashita Y, Ikegami T, Uchiyama H, Yoshizumi T, Soejima Y, Shirabe K, Maehara Y.
  • Journal Title: Ann Surg Oncol. 17(9) Pages: 2283-2289
• [Journal Article] Predictors of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. (2010)
  • Author(s): Taketomi A, Toshima T, Kitagawa D, Motomura T, Takeishi K, Mano Y, Kayashima H, Sugimachi K, Aishima S, Yamashita Y, Ikegami T, Gion T, Uchiyama H, Soejima Y, Maeda T, Shirabe K, Maehara Y.
  • Journal Title: Ann Surg Oncol. 17(10) Pages: 2740-2746
• [Journal Article] Living donor hepatectomies with procedures to prevent biliary complications. (2010)
  • Author(s): Taketomi A, Morita K, Toshima T, Takeishi K, Kayashima H, Ninomiya M, Uchiyama H, Soejima Y, Shirabe K, Maehara Y.
  • Journal Title: J Am Coll Surg. 211(4) Pages: 456-464
• [Journal Article] Evaluation of ERCC1 Expression for Cisplatin Sensitivity in Human Hepatocellular Carcinoma. (2010)
  • Author(s): Ueda S, Shirabe K, Morita K, Umeda K, Kayashima H, Uchiyama H, Soejima Y, Taketomi A, Maehara Y.
  • Journal Title: Ann Surg Oncol.
• [Journal Article] The significance of fibroblast growth factor receptor 2 expression in differentiation of hepatocellular carcinoma. (2010)
  • Author(s): Harimoto N, Taguchi K, Shirabe K, Adachi E, Sakaguchi Y, Toh Y, Okamura T, Kayashima H, Taketomi A, Maehara Y.
  • Journal Title: Oncology. 78(5-6) Pages: 361-368
• [Journal Article] p62+ Hyaline inclusions in intrahepatic cholangiocarcinoma associated with viral hepatitis or alcoholic liver disease. (2010)
  • Author(s): Aishima S, Fujita N, Mano Y, Iguchi T, Taketomi A, Maehara Y, Oda Y, Tsuneyoshi M.
  • Journal Title: Am J Clin Pathol. 134(3) Pages: 457-465
  • NAID: 120005227181
• [Journal Article] Deceleration of regenerative response improves the outcome of rat with massive hepatectomy. (2010)
  • Author(s): Ninomiya M, Shirabe K, Terashi T, Ijichi H, Yonemura Y, Harada N, Soejima Y, Taketomi A, Shimada M, Maehara Y.
  • Journal Title: Am J Transplant. 10(7) Pages: 1580-1587
• [Journal Article] CX3CL1 (fractalkine) : a signpost for biliary inflammation in primary biliary cirrhosis. (2010)
  • Author(s): Shimoda S, Harada K, Niiro H, Taketomi A, Maehara Y, Tsuneyama K, Kikuchi K, Nakanuma Y, Mackay IR, Gershwin ME, Akashi K.
  • Journal Title: Hepatology. 51(2) Pages: 567-575
• [Journal Article] Intratumoral neoadjuvant immunotherapy using IL-12 and dendritic cells is an effective strategy to control recurrence of murine hepatocellular carcinoma in immunosuppressed mice. (2010)
  • Author(s): Kayashima H, Toshima T, Okano S, Taketomi A, Harada N, Yamashita Y, Tomita Y, Shirabe K, Maehara Y.
  • Journal Title: J Immunol. 185(1) Pages: 698-708
• [Journal Article] Mutations in hepatitis C virus genotype 1b and the sensitivity of interferon-ribavirin therapy after liver transplantation. (2010)
  • Author(s): Fukuhara T, Taketomi A, Okano S, Ikegami T, Soejima Y, Shirabe K, Maehara Y.
  • Journal Title: J Hepatol. 52(5) Pages: 672-680
• [Journal Article] Variants in IL28B in Liver Recipients and Donors Correlate With Response to Peg-Interferon and Ribavirin Therapy for Recurrent Hepatitis C. (2010)
  • Author(s): Fukuhara T, Taketomi A, Motomura T, Okano S, Ninomiya A, Abe T, Uchiyama H, Soejima Y, Shirabe K, Matsuura Y, Maehara Y
  • Journal Title: Gastroenterology. 139(5) Pages: 1577-1585
• [Journal Article] The impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation. (2009)
  • Author(s): Taketomi A, Sanefuji K, Soejima Y, Yoshizumi T, Uhciyama H, Ikegami T, Harada N, Yamashita Y, Sugimachi K, Kayashima H, Iguchi T, Maehara Y.
  • Journal Title: Transplantation 87(4) Pages: 531-537
• [Journal Article] Donor risk in adult-to-adult living donor liver transplantation : Impact of left lobe graft. (2009)
  • Author(s): Taketomi A, Kayashima H, Soejima Y, Yoshizumi T, Uhciyama H, Ikegami T, Yamashita Y, Harada N, Shimada M, Maehara Y.
  • Journal Title: Transplantation 87(3) Pages: 445-450
• [Journal Article] Fascin expression in progression and prognosis of hepatocellular carcinoma. (2009)
  • Author(s): Iguchi T, Aishima S, Umeda K, Sanefuji K, Fujita N, Sugimachi K, Gion T, Taketomi A, Maehara Y, Tsuneyoshi M.
  • Journal Title: J Surg Oncol 100(7) Pages: 575-579
• [Journal Article] A comprehensive analysis of immunohistochemical studies in intrahepatic cholangiocarcinoma using the survival tree model. (2009)
  • Author(s): Iguchi T, Yamashita N, Aishima S, Kuroda Y, Terashi T, Sugimachi K, Taguchi K, Taketomi A, Maehara Y, Tsuneyoshi M.
  • Journal Title: Oncology 76(4) Pages: 293-300
• [Journal Article] Fascin overexpression is involved in carcinogenesis and prognosis of human intrahepatic cholangiocarcinoma : immunohistochemical and molecular analysis. (2009)
  • Author(s): Iguchi T, Aishima S, Taketomi A, Nishihara Y, Fujita N, Sanefuji K, Sugimachi K, Yamashita YI, Maehara Y, Tsuneyoshi M.:
  • Journal Title: Hum Pathol 40(2) Pages: 174-180
• [Journal Article] Fascin expression in progression and prognosis of hepatocellular carcinoma (2009)
  • Author(s): Iguchi T, et al.
  • Journal Title: Journal of Surgical Oncology 100 Pages: 575-579
  • Peer Reviewed
• [Presentation] ウイルスおよび宿主の遺伝子解析による肝移植後再発C型肝炎に対する高精度なIFN治療効果予測 (2010)
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  • Organizer: 第28回日本肝移植研究会
  • Place of Presentation: 広島、シンポジウム
• [Presentation] 再発肝細胞癌に対する生体肝移植の役割と治療成績 (2010)
  • Author(s): 武冨紹信、調憲、前原喜彦
  • Organizer: 第8回日本消化器外科学会大会(DDW2010)
  • Place of Presentation: 横浜、シンポジウム
• [Presentation] 肝左葉グラフトを第一選択とする生体肝移植ドナー選択基準の意義 (2010)
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  • Organizer: 第46回日本移植学会総会
  • Place of Presentation: 京都、ワークショップ
• [Presentation] 再発肝細胞癌に対する生体肝移植の治療成績 (2010)
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  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都、優秀演題講演
• [Presentation] 胆道合併症ゼロを目指した生体肝移植ドナー肝切除の工夫 (2010)
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  • Organizer: 第72回日本臨床外科学会総会
  • Place of Presentation: 横浜、主題関連口演
• [Presentation] 肝細胞癌に対する肝切除後10年生存例の検討 (2009)
  • Author(s): 武冨紹信、調憲、本村貴志、間野洋平、戸島剛男、武石一樹、森田和豊、萱島寛人、二宮瑞樹、内山秀昭、副島雄二、相島慎一、前原喜彦
  • Organizer: 第45回日本肝癌研究会
  • Place of Presentation: 福岡、シンポジウム
• [Presentation] HCV遺伝子変異を指標とした肝移植後C型肝炎再発に対するIFN・リバビリン療法の効果予測 (2009)
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  • Organizer: 第27回日本肝移植研究会
  • Place of Presentation: 三島、シンポジウム
• [Presentation] Stage IV肝細胞癌に対する治療戦略決定のための予後予測システムの構築 (2009)
  • Author(s): 武冨紹信、森田和豊、梅田健二、永田茂行、杉町圭史、池上徹、祇園智信、副島雄二、調憲、前原喜彦
  • Organizer: 第64回日本消化器外科学会
  • Place of Presentation: 大阪、企画口演
• [Presentation] HCV遺伝子変異を指標とした肝移植後C型肝炎再発に対するIFN・リバビリン療法の効果予測 (2009)
  • Author(s): 武冨紹信、副島雄二、前原喜彦
  • Organizer: 第13回日本肝臓学会大会(JDDW2009)
  • Place of Presentation: 京都、ワークショップ
• [Presentation] 生体肝移植後の肝細胞癌再発に対する外科治療の意義 (2009)
  • Author(s): 武冨紹信、本村貴志、間野洋平、戸島剛男、武石一樹、森田和豊、梅田健二、萱島寛人、二宮瑞樹、内山秀昭、副島雄二、調憲、前原喜彦
  • Organizer: 第47回日本癌治療学会総会
  • Place of Presentation: 横浜、シンポジウム
• [Presentation] 小型肝細胞癌に対する系統的肝切除の妥当性の検討 (2008)
  • Author(s): 武冨紹信、杉町圭史、武石一樹、戸島剛男、森田和豊、池上徹、山下洋市、祇園智信、副島雄二、前原喜彦
  • Organizer: 第34回日本外科系連合学会学術集会
  • Place of Presentation: 東京、シンポジウム