Functional Analysis of Heparanase-Development of Therapeutic Modalities for Antiangiogenesis and Defferentiation-

• Project/Area Number: 18591464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: NAOMOTO Yoshio Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor (00237190)
• Co-Investigator(Kenkyū-buntansha): MATSUOKA Yoshio Okayama University, Medical and Dental Hospital, Assistant Professor (30332795) ; TANAKA Noriaki Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor (10127566)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,930,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: invasion / metastasis / angiogenesis / differentiation / ペパラナーゼ / 血管新生 / ヘパラナーゼ / 乳癌 / 胃癌

Research Abstract

The precise mechanism of cancer development has been revealed by the investigators in the world. We have studied about the role of heparanase in cancer invasion, angiogenesis and differentiation. Our studies indicated that 1) Heparanase expression correlated with cancers of esophagus, stomach, colon and breast., 2) Heparanse contribute to the angiogenesis in cancer tissues through Cox-2 induction., and 3) Heparanase induce cell differentiation via nuclear translocation combined with HSP90. These results may contribute to know the mechanism of cancer progression and to develop rational cancer treatments.

Research Products

• [Journal Article] Heparanase and vascular endothelial growth factor expression in the progression of oral mucosal melanoma. (2008)
  • Author(s): Rivera RS, Nagatsuka H, Siar CH, Gunduz M, Tsujigiwa H, Han PP, Katase N, Tamamura R, Ng KH, Naomoto Y, Nakajima M, Nagai N.
  • Journal Title: Oncol Rep. 19 Pages: 657-661
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Heparanase and vascular endothelial growth factor expression in the progression of oral mucosal melanoma (2008)
  • Author(s): Rivera, RS., Nagatsuka, H., Siar, CH., Gunduz, M., Tsujigiwa, H., Han, PP., Katase, N., Tamamura, R., Ng., KH., Naomoto, Y., Nakajima, M., Nagai, N
  • Journal Title: Oncol Rep 19 (3) Pages: 657-661
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heparanase and vascular endothelial growth factor expression in the progression of oral mucosal melanoma (2008)
  • Author(s): Rivera RS, Nagatsuka H, Siar CH, Gunduz M, Tsujigiwa H, Han PP, Katase N, Tamamura R, Ng KH, Naomoto Y, Nakajima M, Nagai N.
  • Journal Title: Oncol Rep 19 Pages: 657-61
  • Peer Reviewed
• [Journal Article] Heparanase promotes angiogenesis through Cox-2 and HIFlalpha (2007)
  • Author(s): Naomoto Y, Gunduz M, Takaoka M, Okawa T, Gunduz E, Nobuhisa T, Kobayashi M, Shirakawa Y, Yamatsuji T, Sonoda R, Matsuoka J, Tanaka N
  • Journal Title: Med Hypotheses 68 Pages: 162-165
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa (2007)
  • Author(s): Ishii T, Murakami J, Notohara K, Cullings HM, Sasamoto H, Kambara T, Shirakawa Y, Naomoto Y, Ouchida M, Shimizu K, Tanaka N, Jass JR, Matsubara N.
  • Journal Title: Gut 56 Pages: 13-19
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Translocation of heparanase into nucleus results in cell differentiation (2007)
  • Author(s): Nobuhisa T, Naomoto Y, Okawa T, Takaoka M, Gunduz M, Motoki T, Nagatsuka H, Tsujigiwa H, Shirakawa Y, Yamatsuji T, Haisa M, Matsuoka J, Kurebayashi J, Nakajima M, Taniguchi S, Sagara J, Dong J, Tanaka N
  • Journal Title: Cancer Sci 98 Pages: 535-540
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Heparanase promotes angiogenesis through Cox-2 and HIFlalpha (2007)
  • Author(s): Naomoto, Y., Gunduz, M., Takaoka, M., Okawa, T., Gunduz, E., Nobuhisa, T., Kobayashi, M.,Shirakawa, Y., Yamatsuji, T., Sonoda, R., Matsuoka, J., Tanaka, N
  • Journal Title: Med Hypotheses 68 (1) Pages: 162-165
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa (2007)
  • Author(s): Ishii, T., Murakami, J., Notohara, K., Cullings, HM., Sasamoto, H., Kambara, T., Shirakawa, Y., Naomoto, Y., Ouchida, M., Shimizu, K., Tanaka, N., Jass, JR., Matsubara, N
  • Journal Title: Gut 56 (1) Pages: 13-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Translocation of heparanase into nucleus results in cell differentiation (2007)
  • Author(s): Nobuhisa, T., Naomoto, Y., Okawa, T., Takaoka, M., Gunduz, M., Motoki, T., Nagatsuka, H.,Tsujigiwa, H., Shirakawa, Y., Yamatsuji, T., Haisa, M., Matsuoka, J., Kurebayashi, J.,Nakajima, M., Taniguchi, S., Sagara, J., Dong, J., Tanaka, N
  • Journal Title: Cancer Sci 98 (4) Pages: 535-540
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Heparanase promotes angiogenesis through Cox-2 and HIF1alpha (2007)
  • Author(s): Naomoto Y, Gunduz M, Takaoka M, Okawa T, Gunduz E, Nobuhisa T, Kobayashi M, Shirakawa Y, Yamatsuji T, Sonoda R, Matsuoka J, Tanaka N
  • Journal Title: Med Hypotheses 68 Pages: 162-5
  • Peer Reviewed
• [Journal Article] Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa (2007)
  • Author(s): Ishii T, Murakami J, Notohara K, Cullings HM, Sasamoto H, Kambara T, ShirakawaY, Naomoto Y, Ouchida M, Shimizu K, Tanaka N, Jass JR, Matsubara N.
  • Journal Title: Gut 56 Pages: 13-9
  • Peer Reviewed
• [Journal Article] Translocation of heparanase into nucleus results in cell differentiation. (2007)
  • Author(s): Nobuhisa T, Naomoto Y, et al.
  • Journal Title: Cancer Science 98・4 Pages: 535-540
• [Journal Article] The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach. (2006)
  • Author(s): Ohtawa Y, Naomoto Y, Shirakawa Y, Takaoka M, Murata T, Sonoda R, Sakurama K, Yamatsuji T, Gunduz M, Tsujigiwa H, Nagatsuka H, Terada N, Itano S, Horiki S, Yanagihara K, Nakajima M, Tanaka N.
  • Journal Title: Hum Pathol. 37 Pages: 1145-1152
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach (2006)
  • Author(s): Ohtawa, Y., Naomoto, Y., Shirakawa, Y., Takaoka, M., Murata, T., Sonoda, R., Sakurama, K., Yamatsuji, T., Gunduz, M., Tsujigiwa, H., Nagatsuka, H., Terada, N., Itano, S., Horiki, S., Yanagihara, K., Nakajima, M., Tanaka, N
  • Journal Title: Hum Pathol 37 (9) Pages: 1145-1152
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] COX-2 induction by heparanase in the progression of breast cancer. (2006)
  • Author(s): Imada T, Naomoto Y, et al.
  • Journal Title: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 17・2 Pages: 221-228
• [Journal Article] Heparanase promotes angiogenesis through Cox-2 and HIF1 alpha. (2006)
  • Author(s): Nomoto Y, et al.
  • Journal Title: Medical Hypothesis 68・1 Pages: 162-165
• [Presentation] Malignant pleural mesothelioma-targeted gene therapy (2007)
  • Author(s): Takuya Fukazawa, Junji Matsuoka, Yoshio Naomoto, Yuataka Maeda, Mary L. Durbin, Noriaki Tanaka.
  • Organizer: 2007 AACR Annual Meeting
  • Place of Presentation: Los Angeles, CA
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Molecular analysis of ING4 and its splicing variants in oral cancer (2007)
  • Author(s): Esra Gunduz, Mehmet Gunduz, Hitoshi Nagatsuka, Beyhan Cengiz, Levent Beder, Kadir Demircan, Naila Mahmut, Phuu P. Han, Kunihiro Fukushima, Yoshio Naomoto, Kenji Shimizu, Noriyuki Nagai.
  • Organizer: 2007 AACR Annual Meeting
  • Place of Presentation: Los Angeles, CA
  • Description: 「研究成果報告書概要(和文)」より