Novel strategies for cancer therapy targeting premetastatic niche

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390376
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: KONNO Hiroyuki 浜松医科大学, 医学部, 教授 (00138033)
• Co-Investigator(Kenkyū-buntansha): OHTA Manabu 浜松医科大学, 医学部附属病院, 講師 (40397394) ; KAMIYA Kinji 浜松医科大学, 医学部附属病院, 助教 (20324361) ; SETOU Mitsutoshi 浜松医科大学, 医学部, 教授 (20302664) ; SETOGUCHI Tomohiko 浜松医科大学, 医学部附属病院, 医員 (80436956) ; UEHARA Takashi 浜松医科大学, 医学部附属病院, 医員 (70464120)
• Project Period (FY): 2009 – 2011
• Keywords: 消化器悪性腫瘍 / 分子標的治療 / 転移機構 / 悪性化 / 網羅的解析

Research Abstract

1. Mechanisms of colorectal liver metastasis : We compared difference in miRNA expression between primary colorectal cancers and their liver metastases using microarray. We focused on miR-122 which was the most up-regulated in liver metastases compared with primary tumors and has been reported as a liver-specific miRNA. Immunohistochemical analysis revealed that expression level of cationic amino acid transporter 1(CAT1), a target gene of miR-122, was significantly lower in liver metastases compared with primary tumors. Furthermore, patients with CAT-1 low primary colorectal cancer had significantly shorter liver metastasis-free survival than the patients with CAT-1 high tumors.
2. Lipid alteration in gastric cancer : We compared the lipid content between gastric cancer and its adjacent non-neoplastic mucosa using imaging mass spectrometry and found that potassium-adducted phosphatidylcholine(PC)(16 : 0/18 : 1) was predominantly expressed in cancer lesions. Lysophosphatidylcholine(LPC) is known to be converted to PC in the presence of acyl-CoA by LPCAT1 in Lands' cycle. Immunohistochemical analysis revealed that LPCAT1 was highly expressed in cancer predominantly in differentiated adenocarcinoma. LPCAT1 protein and concomitant lipid alterations in gastric mucosa appear to be involved in the carcinogenic or developmental process of gastric cancer.

Research Products

• [Journal Article] Loss of lymphatic vessels and regional lipid accumulation is associated with great saphenous vein incompetence (2012)
  • Author(s): Tanaka H, Zaima N, Sasaki T, Yamamoto N, Sano M, Konno H, Setou M, Unno N
  • Journal Title: J Vasc Surg Volume: 55 Pages: 1440-8
• [Journal Article] Frequent fracture of TrapEase inferior vena cava filters : a long-term follow-up assessment (2012)
  • Author(s): Sano M, Unno N, Yamamoto N, Tanaka H, Konno H
  • Journal Title: Arch Intern Med Volume: 172 Pages: 189-91
• [Journal Article] Impact of cell cycle disruption on impaired hepatic regeneration in aged livers with ischemic insult (2012)
  • Author(s): Suzuki A, Sakaguchi T, Inaba K, Suzuki S, Konno H
  • Journal Title: J Surg Res Volume: 173 Pages: 267-77
• [Journal Article] Hepatectomy for metastatic liver tumors complicated with right umbilical portion (2011)
  • Author(s): Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Takehara Y, Baba S, Nakamura S, Konno H
  • Journal Title: Hepatogastroenterology Volume: 58 Pages: 984-7
• [Journal Article] Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer (2011)
  • Author(s): Shinmura K, Goto M, Suzuki M, Tao H, Yamada H, Igarashi H, Matsuura S, Maeda M, Konno H, Matsuda T, Sugimura H
  • Journal Title: J Pathol Volume: 225 Pages: 414-23
• [Journal Article] Near-infrared multichannel Raman spectroscopy with a 1064 nm excitation wavelength for ex vivo diagnosis of gastric cancer (2011)
  • Author(s): Kawabata T, Kikuchi H, Okazaki S, Yamamoto M, Hiramatsu Y, Yang J, Baba M, Ohta M, Kamiya K, Tanaka T, Konno H
  • Journal Title: J Surg Res Volume: 169 Pages: e137-43
• [Journal Article] Postoperative bile leakage managed by interventional intrabiliary ethanol ablation (2011)
  • Author(s): Sakaguchi T, Shibasaki Y, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Ota M, Miyazaki S, Takehara Y, Yamashita S, Kamiya M, Ushio T, Kawamura K, Suzuki S, Konno H
  • Journal Title: Hepatogastroenterology Volume: 58 Pages: 157-60
• [Journal Article] Distribution of phospholipid molecular species in autogenous access grafts for hemodialysis analyzed using imaging mass spectrometry (2011)
  • Author(s): Tanaka H, Zaima N, Yamamoto N, Suzuki M, Mano Y, Konno H, Unno N, Setou M
  • Journal Title: Anal Bioanal Chem Volume: 400 Pages: 1873-80
• [Journal Article] Surgical intervention for imatinib and sunitinib-resistant GISTs (2011)
  • Author(s): Kikuchi H, Setoguchi T, Miyazaki S, Yamamoto M, Ohta M, Kamiya K, Sakaguchi T, Konno H
  • Journal Title: Int J Clin Oncol Volume: 16 Pages: 741-5
• [Journal Article] Microarray analysis identifies versican and CD9 as potent prognostic markers in gastric GISTs (2011)
  • Author(s): Setoguchi T, Kikuchi H, Yamamoto M, Baba M, Ohta M, Kamiya K, Tanaka T, Baba S, Goto-Inoue N, Setou M, Sasaki T, Mori H, Sugimura H, Konno H
  • Journal Title: Microarray analysis identifies versican and CD9 as potent prognostic markers in gastric GISTs Volume: 102 Pages: 883-9
• [Journal Article] EPH-EPHRIN in human gastrointestinal cancers (2010)
  • Author(s): Sugimura H, Wang JD, Mori H, Tsuboi M, Nagura K, Igarashi H, Tao H, Nakamura R, Natsume H, Kahyo T, Shinmura K, Konno H, Hamaya Y, Kanaoka S, Kataoka H, Zhou XJ
  • Journal Title: World J Gastrointest Oncol Volume: 2 Pages: 421-8
• [Journal Article] Pancreatic neuroendocrine cell tumor secreting parathyroid hormone-related protein and gastrin (2010)
  • Author(s): Morita Y, Suzuki S, Sakaguchi T, Oishi K, Suzuki A, Fukumoto K, Inaba K, Baba S, Takehara Y, Konno H
  • Journal Title: Surg Today Volume: 40 Pages: 1192-6
• [Journal Article] Assessment of pelvic hemodynamics during an open repair of an infrarenal abdominal aortic aneurysm (2010)
  • Author(s): Inuzuka K, Unno N, Yamamoto N, Sagara D, Suzuki M, Nishiyama M, Tanaka H, Mano Y, Konno H
  • Journal Title: Surg Today Volume: 40 Pages: 738-44
• [Journal Article] Bile leak test by ICG fluorescence images after hepatectomy (2010)
  • Author(s): Sakaguchi T, Suzuki A, Unno N, Morita Y, Oishi K, Fukumoto K, Inaba K, Suzuki M, Tanaka H, Sagara D, Suzuki S, Nakamura S, Konno H
  • Journal Title: Am J Surg Volume: 200 Pages: e19-23
• [Journal Article] A novel method of measuring human lymphatic pumping using indocyanine green fluorescence lymphography (2010)
  • Author(s): Unno N, Nishiyama M, Suzuki M, Tanaka H, Yamamoto N, Sagara D, Mano Y, Konno H
  • Journal Title: J Vasc Surg Volume: 52 Pages: 946-52
• [Journal Article] Long-term survival after a repetitive surgical approach in a patient with acinar cell carcinoma of the pancreas and recurrent liver metastases (2010)
  • Author(s): Suzuki A, Sakaguchi T, Morita Y, Oishi K, Fukumoto K, Inaba K, Takehara Y, Baba S, Suzuki S, Konno H
  • Journal Title: Surg Today Volume: 40 Pages: 679-83
• [Journal Article] Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for H meeting the Milan criteria (2010)
  • Author(s): Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Nakamura S, Konno H
  • Journal Title: Surg Today Volume: 40 Pages: 638-45
• [Journal Article] Recent concepts of antiangiogenic therapy (2010)
  • Author(s): Konno H, Yamamoto M, Ohta M
  • Journal Title: Surg Today Volume: 40 Pages: 494-500
• [Journal Article] Analysis of intrahepatic venovenous shunt by hepatic venography (2010)
  • Author(s): Sakaguchi T, Suzuki S, Inaba K, Fukumoto K, Takehara Y, Nasu H, Kamiya M, Yamashita S, Ushio T, Nakamura S, Konno H
  • Journal Title: Surgery Volume: 147 Pages: 805-10
• [Journal Article] Analysis of anatomic variants of mesenteric veins by 3D portography using multidetector-row computed tomography (2010)
  • Author(s): Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Kamiya K, Ota M, Setoguchi T, Takehara Y, Nasu H, Nakamura S, Konno H
  • Journal Title: Am J Surg Volume: 200 Pages: 15-22
• [Journal Article] Imaging mass spectrometry of gastric carcinoma in formalin-fixed paraffin-embedded tissue microarray (2010)
  • Author(s): Morita Y, Ikegami K, Goto-Inoue N, Hayasaka T, Zaima N, Tanaka H, Uehara T, Setoguchi T, Sakaguchi T, Igarashi H, Sugimura H, Setou M, Konno H
  • Journal Title: Cancer Sci Volume: 101 Pages: 267-73
• [Journal Article] TSU68, an antiangiogenic receptor tyrosine kinase inhibitor, induces tumor vascular normalization in a human cancer xenograft nude mouse model (2009)
  • Author(s): Ohta M, Kawabata T, Yamamoto M, Tanaka T, Kikuchi H, Hiramatsu Y, Kamiya K, Baba M, Konno H
  • Journal Title: Surg Today Volume: 39 Pages: 1046-53
• [Journal Article] Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients (2009)
  • Author(s): Yamada H, Shinmura K, Goto M, Iwaizumi M, Konno H, Kataoka H, Yamada M, Ozawa T, Tsuneyoshi T, Tanioka F, Sugimura H
  • Journal Title: Mol Cancer Volume: 8 Pages: 63
• [Journal Article] Impaired lymphatic function recovered after great saphenous vein stripping in patients with varicose vein : venodynamic and lymphodynamic results (2009)
  • Author(s): Suzuki M, Unno N, Yamamoto N, Nishiyama M, Sagara D, Tanaka H, Mano Y, Konno H
  • Journal Title: J Vasc Surg Volume: 50 Pages: 1085-91
• [Journal Article] Altered expression of the human base excision repair gene NTH1 in gastric cancer (2009)
  • Author(s): Goto M, Shinmura K, Igarashi H, Kobayashi M, Konno H, Yamada H, Iwaizumi M, Kageyama S, Tsuneyoshi T, Tsugane S, Sugimura H
  • Journal Title: Carcinogenesis Volume: 30 Pages: 1345-52
• [Journal Article] Intraoperative indocyanine green fluorescence lymphography, a novel imaging technique to detect a chyle fistula after an esophagectomy (2009)
  • Author(s): Kamiya K, Unno N, Konno H
  • Journal Title: Surg Today Volume: 39 Pages: 421-4
• [Journal Article] Detection of hepatocellular carcinomas with near-infrared fluorescence imaging using indocyanine green : its usefulness and limitation
  • Author(s): Morita Y, Sakaguchi T, Unno N, Shibasaki Y, Suzuki A, Fukumoto K, Inaba K, Baba S, Takehara Y, Suzuki S, Konno H
  • Journal Title: Int J Clin Oncol Volume: (in press)
• [Journal Article] Peripancreatic Arterial Anatomy Analyzed by 3-D Multidetector-Row CT
  • Author(s): Sakaguchi T, Suzuki S, Inaba K, Takehara Y, Nasu H, Konno H
  • Journal Title: Hepatogastroenterology Volume: (in press)
• [Presentation] 胃癌集学的治療における審査腹腔鏡の有用性 (2011)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、藤田剛、瀬戸口智彦、菊池寛利、平松良浩、神谷欣志、馬場恵、田中達郎、今野弘之
  • Organizer: 第49回日本癌治療学会学術集会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20111000
• [Presentation] 胃癌における胃幹細胞マーカーLgr5発現の免疫組織学的検討 (2011)
  • Author(s): 瀬戸口智彦、菊池寛利、藤田剛、宮崎真一郎、飯野一郎太、平松良浩、太田学、神谷欣志、坂口孝宣、馬場恵、田中達郎、今野弘之
  • Organizer: JDDW2011
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 20111000
• [Presentation] cT4胸部食道癌に対する外科的切除の位置づけ (2011)
  • Author(s): 神谷欣志、太田学、藤田剛、宮崎真一郎、飯野一郎太、瀬戸口智彦、菊池寛利、平松良浩、今野弘之
  • Organizer: 第65回日本食道学会学術集会
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 20110900
• [Presentation] 食道再建術・吻合法の工夫食道再建術における術中ICG蛍光血管造影の有用性 (2011)
  • Author(s): 神谷欣志、宮崎真一郎、太田学、藤田剛、菊池寛利、平松良浩、飯野一郎太、瀬戸口智彦、坂口孝宣、今野弘之
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20110700
• [Presentation] NAC及び外科的介入を考慮した化学療法の検討 (2011)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、瀬戸口智彦、菊池寛利、平松良浩、神谷欣志、田中達郎、坂口孝宣、今野弘之
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20110700
• [Presentation] GIST悪性化関連遺伝子群の機能解析 (2011)
  • Author(s): 瀬戸口智彦、菊池寛利、宮崎真一郎、飯野一郎太、平松良浩、太田学、神谷欣志、坂口孝宣、田中達郎、今野弘之
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20110700
• [Presentation] 胃体上部早期胃癌における噴門側胃切除の有用性 (2011)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、瀬戸口智彦、菊池寛利、平松良浩、神谷欣志、馬場恵、田中達郎、今野弘之
  • Year and Date: 20110500
• [Presentation] 質量顕微鏡法を用いた肝細胞癌の脂質解析 (2011)
  • Author(s): 森田剛文、坂口孝宣、柴崎泰、大石康介、鈴木淳司、本和彦、稲葉圭介、鈴木昌八、瀬藤光利、今野弘之
  • Organizer: 第111回日本外科学会定期学術集会
  • Year and Date: 20110500
• [Presentation] 胃癌術後化学療法治療患者のQOL評価 (2011)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、瀬戸口智彦、菊池寛利、平松良浩、神谷欣志、馬場恵、田中達郎、今野弘之
  • Organizer: 第83回日本胃癌学会総会
  • Place of Presentation: 青森県三沢市
  • Year and Date: 20110300
• [Presentation] GIST予後予測因子Versican、CD9の臨床病理学的検討 (2011)
  • Author(s): 瀬戸口智彦、菊池寛利、平松良浩、太田学、神谷欣志、坂口孝宣、田中達郎、高橋剛、柳本喜智、西田俊朗、今野弘之
  • Organizer: 第83回日本胃癌学会総会
  • Place of Presentation: 青森県三沢市
  • Year and Date: 20110300
• [Presentation] 外科医が行う胃癌化学療法外科的アプローチを考慮した胃癌化学療法 (2010)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、瀬戸口智彦、菊池寛利、平松良浩、神谷欣志、坂口孝宣、今野弘之
  • Organizer: 第72回日本臨床外科学会総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 20101100
• [Presentation] 胃癌腹膜播種に対する審査腹腔鏡NBI画像診断を用いた新たな治療戦略 (2010)
  • Author(s): 神谷欣志、太田学、宮崎真一郎、飯野一郎太、上原隆志、瀬戸口智彦、菊池寛利、平松良浩、中村利夫、今野弘之
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20101000
• [Presentation] SF36による胃癌術後化学療法患者のQOL評価 (2010)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、上原隆志、瀬戸口智彦、菊池寛利、平松良浩、神谷欣志、馬場恵、田中達郎、今野弘之
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20101000
• [Presentation] NBI観察による胃癌腹膜播種診断胃癌腹膜播種結節の形態的特徴 (2010)
  • Author(s): 神谷欣志、山本真義、太田学、菊池寛利、川端俊貴、瀬戸口智彦、上原隆志、飯野一郎太、中村利夫、今野弘之
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 山口県下関市
  • Year and Date: 20100700
• [Presentation] QOLからみた胃癌手術術式のコンセンサス胃全摘術と噴門側胃切除術の術後QOL評価について (2010)
  • Author(s): 太田学、金井俊和、松本圭五、山本真義、神谷欣志、馬場恵、田中達郎、坂口孝宣、中村利夫、今野弘之
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 山口県下関市
  • Year and Date: 20100700
• [Presentation] 消化管間質腫瘍悪性度診断の新たなバイオマーカー(Versican、CD9)の同定 (2010)
  • Author(s): 瀬戸口智彦、菊池寛利、川端俊貴、山本真義、太田学、神谷欣志、坂口孝宣、田中達郎、椙村春彦、今野弘之
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 山口県下関市
  • Year and Date: 20100700
• [Presentation] 食道癌に対する外科治療の限界cStage II、III食道癌に対する外科治療成績 (2010)
  • Author(s): 神谷欣志、飯野一郎太、宮崎真一郎、上原隆志、瀬戸口智彦、川端俊貴、菊池寛利、山本真義、太田学、中村利夫、今野弘之
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20100400
• [Presentation] 胃癌術後QOL向上に役立つ手技・再建法とその機能的評価胃全摘と噴門側胃切除におけるGSRSを用いたQOL評価 (2010)
  • Author(s): 太田学、宮崎真一郎、飯野一郎太、上原隆志、瀬戸口智彦、川端俊貴、菊池寛利、山本真義、神谷欣志、馬場恵、田中達郎、今野弘之
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20100400
• [Presentation] 消化管間質腫瘍(GIST)転移能に関する遺伝子群の同定 (2010)
  • Author(s): 瀬戸口智彦、菊池寛利、飯野一郎太、上原隆志、川端俊貴、山本真義、太田学、神谷欣志、坂口孝宣、馬場恵、今野弘之
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20100400
• [Presentation] 質量顕微鏡による胃癌凍結標本の解析 (2010)
  • Author(s): 上原隆志、宮崎真一郎、飯野一郎太、瀬戸口智彦、川端俊貴、菊池寛利、山本真義、太田学、神谷欣志、馬場恵、田中達郎、今野弘之、瀬藤光利、馬場聡
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20100400
• [Presentation] 質量顕微鏡法を用いた肝細胞癌の脂質解析 (2010)
  • Author(s): 森田剛文、坂口孝宣、大石康介、鈴木淳司、福本和彦、稲葉圭介、鈴木昌八、瀬藤光利、今野弘之
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 20100400
• [Presentation] 消化管間質腫瘍(GIST)肝転移に関連する遺伝子群の検討 (2010)
  • Author(s): 瀬戸口智彦、菊池寛利、飯野一郎太、上原隆志、川端俊貴、山本真義、太田学、神谷欣志、坂口宣孝、馬場恵、田中達郎、今野弘之
  • Organizer: 第82回日本胃癌学会総会記事
  • Place of Presentation: 新潟県新潟市
  • Year and Date: 20100300
• [Presentation] 消化管間質腫瘍(GIST)転移制御のための新たな標的蛋白の同定 (2010)
  • Author(s): 瀬戸口智彦、菊池寛利、飯野一郎太、川端俊貴、山本真義、太田学、神谷欣志、坂口孝宣、馬場恵、田中達郎、今野弘之
  • Organizer: 第96回日本消化器病学会総会
  • Place of Presentation: 新潟県新潟市
  • Year and Date: 20100300
• [Presentation] 進行再発胃癌に対する積極的外科的アプローチを加えた化学療法 (2009)
  • Author(s): 太田学、飯野一郎太、上原隆志、瀬戸口智彦、川端俊貴、山本真義、神谷欣志、馬場恵、田中達郎、中村利夫、今野弘之
  • Organizer: 第71回日本臨床外科学会総会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20091100
• [Presentation] 腹腔鏡下NBI観察による胃癌腹膜播種診断 (2009)
  • Author(s): 神谷欣志,太田学,上原隆志,飯野一郎太,瀬戸口智彦,川端俊貴,山本真義,田中達郎,中村利夫,今野弘之
  • Organizer: 第64回日本消化器外科学会総会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 20090700
• [Presentation] 頭頸部癌患者に対する上部消化管スクリーニングにおけるNBIの位置づけ (2009)
  • Author(s): 神谷欣志、飯野一郎太、太田学、山本真義、川端俊貴、瀬戸口智彦、上原隆志、田中達郎、今野弘之
  • Organizer: 第63回日本食道学会学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 20090600