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

• 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
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• 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
  • NAID: 10025137871
  • 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] 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): 三田篤義, 宮川眞一, 他
  • Journal Title: Transplant Proc 41 Pages: 314-315
  • 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, 宮川償一, 他
  • Journal Title: 消化器外科 32 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
  • NAID: 10024305908
  • 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] Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma. (2008)
  • Author(s): 小林聡, 宮川眞一, 他
  • Journal Title: J Hepatobiliary Pancreat Surg 15 Pages: 515-521
  • NAID: 10024305908
  • Peer Reviewed
• [Journal Article] Clinical and pathological features of primary carcinoma of the cystic duct. (2008)
  • Author(s): 中田岳成, 小林聡, 宮川眞一, 他
  • Journal Title: J Hepatobiliary Pancreat Surg 16 Pages: 75-82
  • NAID: 10025137871
  • 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): 中田岳成, 小林聡, 宮川眞一, 他
  • Journal Title: Hepatogastroenterology 55 Pages: 865-872
  • Peer Reviewed
• [Journal Article] Identification of oligopeptide binding to colon cancer cells separated from patients using laser capture microdissection. (2008)
  • Author(s): 久保直樹, 清水明, 宮川眞一, 他
  • Journal Title: J Drug Target 16 Pages: 396-404
  • Peer Reviewed
• [Journal Article] Anti-proinflammatory effects of sirolimus on human islet preparations. (2008)
  • Author(s): 三田篤義, 宮川眞一, 他
  • Journal Title: Transplantation 86 Pages: 46-53
  • Peer Reviewed
• [Journal Article] Surgical treatment for anorectal malignant melanoma : report of five cases and review of 79 Japanese cases. (2008)
  • Author(s): 石曽根聡, 宮川眞一, 他
  • Journal Title: Int J Colorectal Dis 23 Pages: 1257-1262
  • Peer Reviewed
• [Journal Article] NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor eχpression. (2008)
  • Author(s): 小松大介, 宮川屏一, 他
  • Journal Title: Oncogene 27 Pages: 4724-4732
  • Peer Reviewed
• [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, 宮川波一, 清水明, 他
  • Journal Title: 消化器科 47 Pages: 81-84
  • 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, 宮川屏一, 他
  • Journal Title: 外科 70 Pages: 1319-1322
• [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] 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, 宮川眞一, 他
  • 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, 宮川屏一, 清水明, 他
  • Organizer: 第20回日本肝胆膠外科学会・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
• [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
  • Organizer: 第62回日本消化器外科学会定期学術総会
  • Place of Presentation: 東京 京王プラザ
  • 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
• [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
  • Organizer: 第107回日本外科学会定期学術集会
  • Place of Presentation: 大阪 大阪国際会議場リーガロイヤルホテル
  • Year and Date: 2007-04-11
• [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