Development of anti-cancer drug modified by the peptide binding to Hepatocellular carcinoma

2008 Fiscal Year Final Research Report

• Project/Area Number: 19591581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shinshu University
• Principal Investigator: KOBAYASHI Akira Shinshu University, 医学部・附属病院, 講師 (90334903)
• Co-Investigator(Kenkyū-buntansha): MIYAGAWA Shinichi 信州大学, 医学部, 教授 (80229806) ; SHIMIZU Akira 信州大学, 医学部・附属病院, 助教(特定雇用) (00447773)
• Project Period (FY): 2007 – 2008
• Keywords: バイオパンニング法 / 肝細胞癌 / ペプチド / 消化器癌標的治療

Research Abstract

癌細胞に特異的に結合するペプチドが同定できれば、そのペプチドで抗癌剤を修飾し、癌組織により高濃度に、また非癌部組織により低濃度に抗癌剤を分布させ、効果を高めつつ副作用の低減を図ることが可能となる。当研究では、ファージライブラリーを用いたバイオパンニング法という方法で、肝細胞癌に特異的に結合するペプチドを同定した。同ペプチドを提示したファージ、ならびにビオチン修飾した同合成ペプチドを用いて、各種悪性腫瘍由来細胞株ならびに肝細胞癌手術切除標本において、その肝細胞癌結合性を確認した。

Research Products

• [Journal Article] Clinical and pathological features of primary carcinoma of the cystic duct (2009)
  • Author(s): Nakata T, Kobayashi A, Miwa S, Soeda J, Uehara T, Miyagawa S
  • Journal Title: J Hepatobiliary Pancreat Surg 16(1) Pages: 75-82
  • Peer Reviewed
• [Journal Article] Purification method using iodixanol(OptiPrep)-based density gradient significantly reduces cytokine chemokine production from human islet preparations, leading to prolonged beta-cell survival during pretransplantation culture (2009)
  • Author(s): Mita A, Ricordi C, Miki A, Barker S, Khan A, Alvarez A, Hashikura Y, Miyagawa S, Ichii H
  • Journal Title: Transplant Proc 41(1) Pages: 314-5
  • Peer Reviewed
• [Journal Article] 【腫瘍占居部位からみた肝切除の手技と工夫】右肝静脈合併肝切除における後区域静脈還流温存のための工夫 (2009)
  • Author(s): 清水明, 小林聡, 内川裕司, 三輪史郎, 宮川眞一
  • Journal Title: 消化器外科 32巻2号 Pages: 173-181
• [Journal Article] Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma (2008)
  • Author(s): Kobayashi A, Miyagawa S, Miwa S, Nakata T
  • Journal Title: J Hepatobiliary Pancreat Surg 15(5) Pages: 515-21
  • Peer Reviewed
• [Journal Article] Arterial reconstruction in a case of subintimal dissection of celiac arterial tributaries in living donor liver transplantation : a case report (2008)
  • Author(s): Ikegami T, Masuda Y, Ohno Y, Urata K, Nakazawa Y, Miwa S, Hashikura Y, Miyagawa S
  • Journal Title: Transplant Proc 40(10) Pages: 3794-6
  • Peer Reviewed
• [Journal Article] Surgical treatment for anorectal malignant melanoma : report of five cases and review of 79 Japanese cases (2008)
  • Author(s): Ishizone S, Koide N, Karasawa F, Akita N, Muranaka F, Uhara H, Miyagawa S
  • Journal Title: Int J Colorectal Dis 23(12) Pages: 1257-62
  • Peer Reviewed
• [Journal Article] Primary liver carcinoma exhibiting dual hepatocellular-biliary epithelial differentiations associated with citrin deficiency : a case report (2008)
  • Author(s): Soeda J, Yazaki M, Nakata T, Miwa S, Ikeda S, Hosoda W, Iijima M, Kobayashi K, Saheki T, Kojiro M, Miyagawa S
  • Journal Title: J Clin Gastroenterol 42(7) Pages: 855-60
  • Peer Reviewed
• [Journal Article] NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression (2008)
  • Author(s): Komatsu D, Kato M, Nakayama J, Miyagawa S, Kamata T
  • Journal Title: Oncogene 7 ; 27(34) Pages: 4724-32
  • Peer Reviewed
• [Journal Article] Anti-proinflammatory effects of sirolimus on human islet preparations (2008)
  • Author(s): Mita A, Ricordi C, Miki A, Barker S, Haertter R, Hashikura Y, Miyagawa S, Burke GW 3rd, Inverardi L, Ichii H
  • Journal Title: Transplantation 15 ; 86(1) Pages: 46-53
  • Peer Reviewed
• [Journal Article] Identification of oligopeptide binding to colon cancer cells separated from patients using laser capture microdissection (2008)
  • Author(s): Kubo N, Akita N, Shimizu A, Kitahara H, Parker AL, Miyagawa S
  • Journal Title: J Drug Target 16(5) Pages: 396-404
  • Peer Reviewed
• [Journal Article] Identification of genes associated with multiple nodules in hepatocellular carcinoma using cDNA microarray : multicentric occurrence or intrahepatic metastasis? (2008)
  • Author(s): Nakata T, Seki N, Miwa S, Kobayashi A, Soeda J, Nimura Y, Kawasaki S, Miyagawa S
  • Journal Title: Hepatogastroenterology 55(84) Pages: 865-72
  • Peer Reviewed
• [Journal Article] Reduction of Calponin h1 expression in human colon cancer blood vessels (2008)
  • Author(s): Yanagisawa Y, Takeoka M, Ehara T, Itano N, Miyagawa S, Taniguchi S
  • Journal Title: Eur J Surg Oncol 34(5) Pages: 531-7
  • Peer Reviewed
• [Journal Article] Nonsurgical policy for treatment of bilioenteric anastomotic stricture after living donor liver transplantation (2008)
  • Author(s): Mita A, Hashikura Y, Masuda Y, Ohno Y, Urata K, Nakazawa Y, Ikegami T, Terada M, Yamamoto H, Miyagawa S
  • Journal Title: Transpl Int 21(4) Pages: 320-7
  • Peer Reviewed
• [Journal Article] Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer (2008)
  • Author(s): Noike T, Miwa S, Soeda J, Kobayashi A, Miyagawa S
  • Journal Title: Hum Pathol 39(2) Pages: 201-8
  • Peer Reviewed
• [Journal Article] Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model (2008)
  • Author(s): Kubota K, Soeda J, Misawa R, Mihara M, Miwa S, Ise H, Takahashi M, Miyagawa S
  • Journal Title: Carcinogenesis 29(2) Pages: 448-54
  • Peer Reviewed
• [Journal Article] 【処置と小手術のコツと合併症】基本手技総論腹腔穿刺 (2008)
  • Author(s): 小林聡, 代田智樹, 宮川眞一
  • Journal Title: 外科 70巻12号 Pages: 1319-1322
• [Journal Article] 【再発肝癌診療におけるコンセンサスと個別化】再発時期の観点からみた再肝切除の成績 (2008)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎, 横山隆秀, 中田岳成, 三原基弘, 宮川雄輔, 大野康成, 清水明, 添田純平, 鈴木史恭, 秋田眞吾, 古澤徳彦, 増田雄一, 荒居琢磨
  • Journal Title: 消化器科 47巻1号 Pages: 81-84
  • Peer Reviewed
• [Journal Article] Is major hepatectomy with pancreatoduodenectomy justified for advanced biliary malignancy? (2007)
  • Author(s): Miwa S, Kobayashi A, Akahane Y, Nakata T, Mihara M, Kusama K, Ogawa S, Soeda J, Miyagawa S
  • Journal Title: J Hepatobiliary Pancreat Surg 14(2) Pages: 136-41
  • Peer Reviewed
• [Journal Article] Gastric small cell carcinoma successfully treated by surgery and postoperative chemotherapy consisting of cisplatin and S-1 : report of a case (2007)
  • Author(s): Koide N, Suzuki A, Saito H, Sato T, Murakami M, Ota H, Miyagawa S
  • Journal Title: Surg Today 37(11) Pages: 989-94
  • Peer Reviewed
• [Journal Article] Clinicopathologic features and istochemical analyses of proliferative ctivity and angiogenesis in small cell arcinoma of the esophagus (2007)
  • Author(s): Koide N, Saito H, Suzuki A, Sato T, Koiwai K, Nakamura N, Miyagawa S
  • Journal Title: J astroenterol 42(12) Pages: 932-8
  • Peer Reviewed
• [Journal Article] Detection of hepatic metastases from colorectal carcinoma : comparison of histopathologic features of anatomically resected liver with results of preoperative imaging (2007)
  • Author(s): Nomura K, Kadoya M, Ueda K, Fujinaga Y, Miwa S, Miyagawa S
  • Journal Title: J Clin Gastroenterol 41(8) Pages: 789-95
  • Peer Reviewed
• [Journal Article] In vivo bactericidal activities of Japanese rice-fluid against H. pylori in a Mongolian gerbil model (2007)
  • Author(s): Ishizone S, Maruta F, Suzuki K, Miyagawa S, Takeuchi M, Kanaya K, Oana K, Hayama M, Kawakami Y, Ota H
  • Journal Title: Int J Med Sci 10 ; 4(4) Pages: 203-8
  • Peer Reviewed
• [Journal Article] A clinical study of docetaxel with or without 5'DFUR as a second-line chemotherapy for advanced gastric cancer (2007)
  • Author(s): Maruta F, Ishizone S, Hiraguri M, Fujimori Y, Shimizu F, Kumeda S, Miyagawa S
  • Journal Title: Med Oncol 24(1) Pages: 71-5
  • Peer Reviewed
• [Journal Article] Modified Irinotecan / 5FU / Leucovorin therapy in advanced colorectal cancer and predicting therapeutic efficacy by expression of tumor-related enzymes (2007)
  • Author(s): Yanagisawa Y, Maruta F, Iinuma N, Ishizone S, Koide N, Nakayama J, Miyagawa S
  • Journal Title: Scand J Gastroenterol 42(4) Pages: 477-84
  • Peer Reviewed
• [Journal Article] 【肝細胞癌切除後の長期成績向上を目指して】初発病巣の治療系統的切除その適応と成績 (2007)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎
  • Journal Title: 外科 69巻5号 Pages: 511-514
  • Peer Reviewed
• [Presentation] バイオパンニング法による胆管癌特異的結合ペプチドの同定 (2008)
  • Author(s): 北原弘恵, 丸田福門, 久保直樹, 清水明, 秋田倫幸, 三輪史郎, 宮川眞一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 20081028-30
• [Presentation] 再発肝細胞癌に対する再肝切除の適応に関する検討 (2008)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎, 横山隆秀, 中田岳成, 三原基弘, 大野康成, 清水明, 鈴木史恭, 古澤徳彦
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 札幌・ロイトン札幌
  • Year and Date: 2008-07-18
• [Presentation] 肝腫瘍占拠部位別の肝切除術の工夫と理論. 右肝静脈合併肝切除における後区域静脈還流温存のための工夫 (2008)
  • Author(s): 清水明, 小林聡, 古澤徳彦, 鈴木史恭, 大野康成, 中田岳成, 三原基弘, 横山隆秀, 三輪史郎, 宮川眞一
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 札幌・北海道厚生年金会館
  • Year and Date: 2008-07-18
• [Presentation] 肝門部胆管癌治癒切除後の再発部位と再発危険因子に関する検討 (2008)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎, 横山隆秀, 中田岳成, 三原基弘, 大野康成, 清水明, 添田純平, 鈴木史恭, 秋田眞吾, 古沢徳彦, 増田雄一, 北川敬之, 野竹剛, 横井謙太
  • Organizer: 第20回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 山形・山形国際ホテル
  • Year and Date: 2008-05-29
• [Presentation] 進行胆嚢癌における予後因子と合併切除に関する検討 (2008)
  • Author(s): 清水明, 小林聡, 中田岳成, 横井謙太, 野竹剛, 北川敬之, 秋田眞吾, 古澤徳彦, 鈴木史恭, 添田純平, 大野康成, 三原基弘, 横山隆秀, 三輪史郎, 宮川眞一
  • Organizer: 第20回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 山形・山形国際ホテル
  • Year and Date: 2008-05-29
• [Presentation] 肝硬変合併肝細胞癌に対する系統的亜区域切除術の実際 (2008)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎, 横山隆秀, 中田岳成, 三原基弘, 大野康成, 清水明, 添田純平, 鈴木史恭, 古沢徳彦,北川敬之, 野竹剛, 横井謙太
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎・NCC&スタジオ
  • Year and Date: 2008-05-17
• [Presentation] 進行胆嚢癌に対する至適術式の検討 (2008)
  • Author(s): 清水明, 小林聡, 中田岳成, 竹内大輔, 野竹剛, 北川敬之, 横井謙太, 古澤徳彦, 秋田眞吾, 鈴木史恭, 添田純平, 大野康成, 三原基弘, 横山隆秀, 三輪史郎, 宮川眞一
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎・長崎新聞文化ホール
  • Year and Date: 2008-05-15
• [Presentation] バイオパンニング法を用いた肝細胞癌特異的結合ペプチドの同定 (2007)
  • Author(s): 清水明, 丸田福門, 秋田倫幸, 三輪史郎, 宮川眞一
  • Organizer: 第107回日本外科学会定期学術集会
  • Place of Presentation: 日大阪・大阪国際会議場
  • Year and Date: 20070411-13
• [Presentation] 再発肝癌診療におけるコンセンサスと個別化. 肝癌再発の危険因子と再肝切除の意義 (2007)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎
  • Organizer: 2007年度日本消化器関連学会週間
  • Place of Presentation: 神戸・神戸国際展示場
  • Year and Date: 2007-10-18
• [Presentation] 消化器癌の発生機序から見た治療戦略肝胆膵癌. 肝細胞癌標的治療へのバイオパンニング法の応用 (2007)
  • Author(s): 清水明, 丸田福門, 秋田倫幸, 添田純平, 小川真一郎, 三原基弘, 三輪史郎, 宮川眞一
  • Organizer: 第62回日本消化器外科学会定期学術総会
  • Place of Presentation: 新宿・京王プラザホテル
  • Year and Date: 2007-07-19
• [Presentation] 肝異時性多発癌に対する治療戦略 (2007)
  • Author(s): 小林聡, 宮川眞一, 三輪史郎, 中田岳成, 三原基弘, 宮川雄輔, 小川真一郎, 清水明, 添田純平, 名取恵子
  • Organizer: 第62回日本消化器外科学会定期学術総会
  • Place of Presentation: 新宿・京王プラザホテル
  • Year and Date: 2007-07-18
• [Presentation] 臓器移植. C型肝炎ウイルス関連肝疾患に対する肝移植の成績と問題点 (2007)
  • Author(s): 宮川眞一
  • Organizer: 第32回日本外科系連合学会総会
  • Place of Presentation: 新宿・京王プラザホテル
  • Year and Date: 2007-06-23