Development of molecular medicine for hepatocellular carcinoma targeting on hepatic stellate cells

• Project/Area Number: 19591599
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Iwate Medical University
• Principal Investigator: WAKABAYASHI Go Iwate Medical University, 医学部, 教授 (50175064)
• Co-Investigator(Kenkyū-buntansha): MASUDA Tomoyuki 岩手医科大学, 医学部, 教授 (10199698) ; MAESAWA Chihaya 岩手医科大学, 医学部, 教授 (10326647)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝癌 / 肝星細胞 / AgngII / EGFR / ADAM / Ang11 / クロストーク / 肝星細胞胞 / AngII / 浸潤 / 転移

Research Abstract

For the development of new strategy targeting on the interaction between hepatoceullar carcinoma (HCC) and hepatic stellate cells, we investigated the cross-talk ; namely angiotensin II (AngII)-a disintegrin and metalloprotease domain (ADAM)- epidermal growth factor receptor (EGFR). In both cell types (HCC and HSC), the increase of proliferation/invasion activities by the administration of Ang II was observed. The transactivation (AngII-ADAM-EGFR) was inhibited by angiotensin receptor blocker (ARB) and/or ADAM inhior (TAPI2). These results suggested ARB and/or ADAM inhibitor will be new drugs for the treatment in both HCC and liver fibrosis.

Research Products

• [Journal Article] Molecular analysis of single isolated glands in gastric cancers and their surrounding gastric intestinal metaplastic mucosa (2010)
  • Author(s): Sugai T, Habano W, Jiao YF, Toyota M, Suzuki H, Tsukahara M, Koizuka H, Akasaka R, Koeda K, Wakabayashi G, Suzuki K.
  • Journal Title: Oncol Rep 23 Pages: 25-33
• [Journal Article] Molecular analysis of gastric differentiated-type intramucosal and submucosal cancers (2010)
  • Author(s): Sugai T, Habano W, Endoh M, Konishi Y, Akasaka R, Toyota M, Yamano H, Koeda K, Wakabayashi G, Suzuki K.
  • Journal Title: Int J Cancer
• [Journal Article] Primary retroperitoneal spindle cell liposarcoma: pathological and immunohistochemical findings (2010)
  • Author(s): Shioi Y, Hasegawa T, Otsuka K, Fujisawa K, Itabashi T, Kimura T, Wakabayashi G, Mue Y, Uesugi N, Sugai T.
  • Journal Title: Pathol Int 60 Pages: 472-6
  • NAID: 10029332263
• [Journal Article] Human intestinal spirochetosis in northern Japan (2010)
  • Author(s): Sato H, Nakamura SI, Habano W, Wakabayashi G, Adachi Y.
  • Journal Title: J Med Microbiol
• [Journal Article] Evaluation of UICC-TNM and JSBS staging systems for surgical patients with extrahepatic cholangiocarcinoma (2010)
  • Author(s): Sasaki R, Murata S, Oda T, Ohkohchi N, Takeda Y, Wakabayashi G
  • Journal Title: Langenbecks Arch Surg
• [Journal Article] Laparoscopic excision of retroperitoneal tumors: report of three cases (2010)
  • Author(s): Sasaki A, Suto T, Nitta H, Shimooki O, Obuchi T, Wakabayashi G
  • Journal Title: Surg Today 40 Pages: 176-80
  • NAID: 10027394328
• [Journal Article] Laparoscopic liver resection (2010)
  • Author(s): Sasaki A, Nitta H, Takahara T, Fujita M, Nakajima J, Obuchi T, Baba S, Umemura A, Otsuka K, Wakabayashi G.
  • Journal Title: Gan To Kagaku Ryoho 37 Pages: 396-8
• [Journal Article] Concomitant laparoscopic splenectomy and cholecystectomy (2010)
  • Author(s): Sasaki A, Nitta H, Otuska K, Kimura Y, Obuchi T, Wakabayashi G
  • Journal Title: Surg Laparosc Endosc Percutan Tech 20 Pages: 66-8
• [Journal Article] Tailored laparoscopic resection for suspected gastric gastrointestinal stromal tumors (2010)
  • Author(s): Sasaki A, Koeda K, Obuchi T, Nakajima J, Nishizuka S, Terashima M, Wakabayashi G
  • Journal Title: Surgery 147 Pages: 516-20
• [Journal Article] Minimally invasive surgical enucleation for esophageal leiomyoma: report of seven cases (2010)
  • Author(s): Obuchi T, Sasaki A, Nitta H, Koeda K, Ikeda K, Wakabayashi G
  • Journal Title: Dis Esophagus 23
• [Journal Article] Laparoscopy-assisted major liver resections employing a hanging technique: the original procedure (2010)
  • Author(s): Nitta H, Sasaki A, Fujita T, Itabashi H, Hoshikawa K, Takahara T, Takahashi M, Nishizuka S, Wakabayashi G
  • Journal Title: Ann Surg 251 Pages: 450-3
• [Journal Article] Risk factors for early postoperative small bowel obstruction after colectomy for colorectal cancer (2010)
  • Author(s): Nakajima J, Sasaki A, Otsuka K, Obuchi T, Nishizuka S, Wakabayashi G
  • Journal Title: World J Surg 34 Pages: 1086-90
• [Journal Article] Laparoscopy-assisted major liver resections employing a hanging technique : the original procedure. (2010)
  • Author(s): Nitta H, Sasaki A, Fujita T, Itabashi H, Hoshikawa K, Takahara T, Takahashi M, Nishizuka S, Wakabayashi G.
  • Journal Title: Ann Surg 251(3) : Pages: 450-453
  • Peer Reviewed
• [Journal Article] Molecular analysis of single isolated glands in gastric cancers and their surrounding gastric intestinal metaplastic mucosa. (2010)
  • Author(s): Sugai T, Habano W, Endoh M, Konishi Y, Akasaka R, Toyota M, Yamano H, Koeda K, Wakabayashi G, Suzuki K.
  • Journal Title: Int J Cancer (Epub ahead of print)(印刷中)
  • Peer Reviewed
• [Journal Article] Standardization of basic skills for laparoscopic liver surgery towards laparoscopic donor hepatectomy (2009)
  • Author(s): Wakabayashi G, Nitta H, Takahara T, Shimazu M, Kitajima M, Sasaki A
  • Journal Title: J Hepatobiliary Pancreat Surg 16 Pages: 439-44
  • NAID: 10025139665
• [Journal Article] Laparoscopic liver resection: how far can we go? (2009)
  • Author(s): Wakabayashi G
  • Journal Title: J Hepatobiliary Pancreat Surg 16 Pages: 403-4
  • NAID: 10025139482
• [Journal Article] Status of endoscopic liver surgery in Japan: a questionnaire survey conducted by the Japanese Endoscopic Liver Surgery Study Group (2009)
  • Author(s): Tsuchiya M, Otsuka Y, Tamura A, Nitta H, Sasaki A, Wakabayashi G, Kaneko H
  • Journal Title: J Hepatobiliary Pancreat Surg 16 Pages: 405-9
  • NAID: 10025139490
• [Journal Article] Mohs chemosurgery for local control of giant recurrent papillary thyroid cancer (2009)
  • Author(s): Tomisawa Y, Ogasawara S, Kashiwaba M, Inaba T, Takeda Y, Sugimura Y, Hatakeyama G, Asahi H, Wakabayashi G
  • Journal Title: Thyroid 19 Pages: 657-9
• [Journal Article] Ghrelin and leptin levels in cachectic patients with cancer of the digestive organs (2009)
  • Author(s): Takahashi M, Terashima M, Takagane A, Oyama K, Fujiwara H, Wakabayashi G
  • Journal Title: Int J Clin Oncol 14 Pages: 315-20
  • NAID: 10025864071
• [Journal Article] A novel formulation of cisplatin (CDDP) (2009)
  • Author(s): Sugitachi A, Kimura Y, Itabashi T, Noda H, Ishida K, Nishizuka S, Otsuka K, Kashiwaba M, Nitta H, Koeda K, Mizuno M, Sasaki A, Ikeda K, Takamori Y, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 36 Pages: 2294-6
• [Journal Article] Laparoscopic Heller myotomy with Dor fundoplication for achalasia: long-term outcomes and effect on chest pain (2009)
  • Author(s): Sasaki A, Obuchi T, Nakajima J, Kimura Y, Koeda K, Wakabayashi G
  • Journal Title: Dis Esophagus
• [Journal Article] Ten-year experience of totally laparoscopic liver resection in a single institution (2009)
  • Author(s): Sasaki A, Nitta H, Otsuka K, Takahara T, Nishizuka S, Wakabayashi G
  • Journal Title: Br J Surg 96 Pages: 274-9
• [Journal Article] Endoscopic subtotal thyroidectomy: the procedure of choice for Graves' disease? (2009)
  • Author(s): Sasaki A, Nitta H, Otsuka K, Obuchi T, Kurihara H, Wakabayashi G
  • Journal Title: World J Surg 33 Pages: 67-71
• [Journal Article] Local recurrence after surgical resection of pancreatic cancer effectively treated with combined chemoradiotherapy (2009)
  • Author(s): Obuchi T, Sasaki A, Shimooki O, Minakawa Y, Abe T, Nitta H, Otsuka K, Koeda K, Ikeda K, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 36 Pages: 991-4
• [Journal Article] Laparoscopic surgery for splenic artery aneurysm (2009)
  • Author(s): Obuchi T, Sasaki A, Nakajima J, Nitta H, Otsuka K, Wakabayashi G.
  • Journal Title: Surg Laparosc Endosc Percutan Tech 19 Pages: 338-40
• [Journal Article] Laparoscopic subtotal cholecystectomy for severe cholecystitis (2009)
  • Author(s): Nakajima J, Sasaki A, Obuchi T, Baba S, Nitta H, Wakabayashi G
  • Journal Title: Surg Today 39 Pages: 870-5
  • NAID: 10025555209
• [Journal Article] DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer (2009)
  • Author(s): Kato K, Maesawa C, Itabashi T, Fujisawa K, Otsuka K, Kanno S, Tada H, Tatemichi Y, Kotani K, Oikawa H, Sugai T, Wakabayashi G, Masuda T
  • Journal Title: Int J Oncol 35 Pages: 467-76
• [Journal Article] The ideal follow-up after breast cancer operation (2009)
  • Author(s): Kashiwaba M, Inaba T, Takeda Y, Komatsu H, Kawagishi R, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 36 Pages: 1423-7
• [Journal Article] Palliative chemotherapy for metastatic breast cancer with capecitabine (2009)
  • Author(s): Inaba T, Kashiwaba M, Takeda Y, Komatsu H, Tomisawa Y, Takiyama I, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 36 Pages: 769-72
• [Journal Article] CYP1B1, but not CYP1A1, is downregulated by promoter methylation in colorectal cancers (2009)
  • Author(s): Habano W, Gamo T, Sugai T, Otsuka K, Wakabayashi G, Ozawa S
  • Journal Title: Int J Oncol 34 Pages: 1085-91
• [Journal Article] Assessment of gastric motor function by cine magnetic resonance imaging (2009)
  • Author(s): Baba S, Sasaki A, Nakajima J, Obuchi T, Koeda K, Wakabayashi G
  • Journal Title: J Gastroenterol Hepatol 24 Pages: 1401-6
• [Journal Article] DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer. (2009)
  • Author(s): Kato K, Maesawa C, Itabashi T, Fujisawa K, Otsuka K, Kanno S, Tada H, Tatemichi Y, Kotani K, Oikawa H, Sugai T, Wakabayashi G.Masuda T.
  • Journal Title: Int J Oncol 35 Pages: 467-476
  • Peer Reviewed
• [Journal Article] Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. (2009)
  • Author(s): Kato K, Maesawa C, Wakabayashi G, Masuda T., et al
  • Journal Title: Int J Oncol 33(In press)
  • Peer Reviewed
• [Journal Article] Kitajima M. Correlation of motility and neuronal integrity with a focus on the grade of intestinal allograft rejection (2008)
  • Author(s): Watanabe T, Hoshino K, Tanabe M, Morikawa Y, Kawachi S, Wakabayashi G, Shimazu M
  • Journal Title: Am J Transplant 8 Pages: 529-36
• [Journal Article] A case of complete response in supraclavicular lymph node involvement from cancer of the sigmoid colon to FOLFOX4 therapy after laparoscopy-assisted colectomy (2008)
  • Author(s): Suto T, Ito N, Obuchi T, Uesugi N, Sugai T, Nakamura SI, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 35 Pages: 669-72
• [Journal Article] Chitin/cisplatin-an adhesive anticancer drug (2008)
  • Author(s): Sugitachi A, Otsuka K, Itabashi T, Chiba T, Kimura Y, Sasaki A, Ikeda K, Uesugi N, Takamori Y, Kurozumi S, Mori T, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 35 Pages: 2021-3
• [Journal Article] Protein and lysate array technologies in cancer research (2008)
  • Author(s): Spurrier B, Honkanen P, Holway A, Kumamoto K, Terashima M, Takenoshita S, Wakabayashi G, Austin J, Nishizuka S
  • Journal Title: Biotechnol Adv 26 Pages: 361-9
• [Journal Article] Laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein: report of three cases (2008)
  • Author(s): Sasaki A, Nitta H, Nakajima J, Obuchi T, Baba S, Wakabayashi G
  • Journal Title: Surg Today 38 Pages: 955-8
  • NAID: 10022612689
• [Journal Article] Laparoscopic cholecystectomy in patients with a history of gastrectomy. (2008)
  • Author(s): Sasaki A, Nakajima J, Nitta H, Obuchi T, Baba S, Wakabayashi G
  • Journal Title: Surg Today 38 Pages: 790-4
  • NAID: 10022611958
• [Journal Article] Endoscopic thyroidectomy by the breast approach: a single institution's 9-year experience (2008)
  • Author(s): Sasaki A, Nakajima J, Ikeda K, Otsuka K, Koeda K, Wakabayashi G
  • Journal Title: World J Surg 32 Pages: 381-5
• [Journal Article] Application of quantitative proteomic analysis for cancer therapy using "reverse-phase" protein lysate microarrays (2008)
  • Author(s): Nishizuka S, Spurrier B, Honkanen P, Austin J, Wakabayashi G
  • Journal Title: Gan To Kagaku Ryoho 35 Pages: 200-5
• [Journal Article] High density 'reverse-phase' protein lysate microarray (2008)
  • Author(s): Nishizuka S, Ishida K, Noda H, Takahashi M, Wakabayashi G
  • Journal Title: Seikagaku 80 Pages: 1047-54
  • NAID: 10024455069
• [Journal Article] Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines (2008)
  • Author(s): Mitomo S, Maesawa C, Ogasawara S, Iwaya T, Shibazaki M, Yashima-Abo A, Kotani K, Oikawa H, Sakurai E, Izutsu N, Kato K, Komatsu H, Ikeda K, Wakabayashi G, Masuda T
  • Journal Title: Cancer Sci 99 Pages: 280-6
  • NAID: 10024002213
• [Journal Article] Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines (2008)
  • Author(s): Itabashi H, Maesawa C, Oikawa H, Kotani K, Sakurai E, Kato K, Komatsu H, Nitta H, Kawamura H, Wakabayashi G, Masuda T
  • Journal Title: Hepatol Res 38 Pages: 601-13
  • NAID: 10024148920
• [Journal Article] Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines. (2008)
  • Author(s): Itabashi H, Maesawa C, Wakawayashi G, Masuda T.
  • Journal Title: Hepatol Res 38 Pages: 601-613
  • NAID: 10024148920
  • Peer Reviewed
• [Journal Article] Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines
  • Author(s): Itabashi H, Maesawa C, Oikawa H, Kotani K, Sakurai E, Kato K, Komatsu H, Nitta H, Kawamura H, Wakabayashi G, Masuda T
  • Journal Title: Hep Res (In press)
  • NAID: 10024148920
  • Peer Reviewed