Development of a TET-ON system for expression of chemokine (BRAK) and the killing of cancer cells

• Project/Area Number: 19791355
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Morphological basic dentistry
• Research Institution: Kanagawa Dental College
• Principal Investigator: BHAWAL Ujjal Kanagawa Dental College, 歯学部, 特別研究員 (50433339)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,570,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: ケモカイン / BRAK / CXCL14 / Tet-On / 口腔扁平上皮癌細胞 / 進展 / メチル化 / Tet-ON / 口腔扁平上皮癌細胞株 / 口腔扁平上皮癌

Research Abstract

BRAK/CXCL14はどの正常細胞でも発現しているケモカインであり、種の異なるマウスとヒトのBRAK/CXCL14のアミノ酸配列が非常に高い相同性を示すことから、非常に普遍的かつ重要な機能を持つ分子と考えられる。BRAK/CXCL14のin vivoにおける腫瘍抑制機構を明らかにすることは、口腔癌ばかりでなく、種々の癌の進展機構の解明と、将来における癌のドーマント療法開発の分子標的として有望であり、また、全ての正常細胞で発現していることから将来における遺伝子導入等における治療において副作用の少ない新しい標的分子と考えられる。

Research Products

• [Journal Article] Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates the expression of vascular endothelial growth factor (2008)
  • Author(s): Sato F, Bhawal UK, Kawamoto T, Fujimoto K, Imanaka T, Imaizumi T, Kondo J, Noshiro M, Kusumi T, Kato Y, Kijima H
  • Journal Title: Genes Cells 13(2) Pages: 131-144
  • Peer Reviewed
• [Journal Article] mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma (2008)
  • Author(s): Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, Ohmori H, Yasui W, Bosserhoff AK, Kuniyasu H. High
  • Journal Title: Cancer Science 99(9) Pages: 1806-1812
  • Peer Reviewed
• [Journal Article] Loss of 14-3-3 Sigma Expression and Presence of Human Papillomavirus Type 16 E6 in Oral Squamous Cell Carcinoma (2008)
  • Author(s): Bhawal UK, Sugiyama M, Nomura Y, Kuniyasu H, Tsukinoki K
  • Journal Title: Archives of Otolaryngology Head & Neck Surgery 134(10) Pages: 1055-1059
  • Peer Reviewed
• [Journal Article] Reg IV expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland (2008)
  • Author(s): Sasahira T, Oue N, Kirita T, Luo Y, Bhawal UK, Fujii K, Yasui W, Kuniyasu H
  • Journal Title: Histopathology 53(6) Pages: 667-675
  • Peer Reviewed
• [Journal Article] Effects of oral disinfectants on the cell cycle and viability of primary human gingival fibroblasts in vitro (2008)
  • Author(s): Nomura Y, Bhawal UK, Nishikiori R, Sawajiri M, Hirata I, Okazaki M
  • Journal Title: Dent Mater J (In Press)
  • Peer Reviewed
• [Journal Article] Basic-helix-loop-helix(bHLH)transcription factor DEC2 negative ly regulates the expression of vascular endothelial growth factor (2008)
  • Author(s): Sato F, Bhawal UK, et.al.
  • Journal Title: Genes Cells 13(2) Pages: 131-144
  • Peer Reviewed
• [Journal Article] High mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral sauamous cell carcinoma (2008)
  • Author(s): Sasahira T, Kirita T, Oue N, Bhawal UK, et.al.
  • Journal Title: Cancer Science 99(9) Pages: 1806-1812
  • Peer Reviewed
• [Journal Article] Transcriptional repression by the basic helix-loop-helix protein Dec2 : multiple mechanisms through E-box elements (2007)
  • Author(s): Fujimoto K, Hamaguchi H, Hashiba T, Nakamura T, Kawamoto T, Sato F, Noshiro M, Bhawal UK, Suardita K, Kato Y
  • Journal Title: Int J Mol Med 19(6) Pages: 925-32
  • Peer Reviewed
• [Journal Article] Receptor for advanced glycation end products(RAGE) is important in the prediction of recurrence in human oral squamous cell carcinoma (2007)
  • Author(s): Sasahira T, Kirita T, Bhawal UK, Yamamoto K, Ohmori H, Fujii K, Kuniyasu H
  • Journal Title: Histopathology 51(2) Pages: 166-72
  • Peer Reviewed
• [Journal Article] Methylation and intratumoural heterogeneity of 14-3-3 sigma in oral cancer (2007)
  • Author(s): Bhawal UK, Tsukinoki K, Sasahira T, Sato F, Mori Y, Muto N, Sugiyama M, Kuniyasu H
  • Journal Title: Oncol Rep 18(4) Pages: 817-24
  • Peer Reviewed
• [Journal Article] High-risk human papillomavirus type 16E7 oncogene associates with Cdc25A over-expression in oral squamous cell carcinomas (2007)
  • Author(s): Bhawal UK, Sugiyama M, Tsukinoki K, Ikeda MA, Kuniyasu H
  • Journal Title: Virchows Arch 450(1) Pages: 65-71
  • Peer Reviewed
• [Journal Article] UCN-01(7-hydroxystaurosporine) induces apoptosis and G1 arrest of both primary and metastatic oral cancer cell lines in vitro (2007)
  • Author(s): Otsubo A, Bhawal UK (co-first author), Nomura Y, Mitani Y, Ozawa K, Kuniyasu H, Sugiyama M
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(3) Pages: 391-7
  • Peer Reviewed
• [Journal Article] Apoptotic and necrotic influence of dental resin polymerization initiators in human gingival fibroblast cultures (2007)
  • Author(s): Masuki K, Nomura Y, Bhawal UK, Sawajiri M, Hirata I, Nahara Y, Okazaki M
  • Journal Title: Dent Mater J 26(6) Pages: 861-9
  • Peer Reviewed
• [Journal Article] The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma (2007)
  • Author(s): Sasahira T, Kirita T, Bhawal UK, Ikeda M, Nagasawa A, Yamamoto K, Kuniyasu H
  • Journal Title: Virchows Arch 450(3) Pages: 287-95
  • Peer Reviewed
• [Journal Article] Human papillomavirus-16 in oral squamous cell carcinoma : clinical correlates and 5-year survival (2007)
  • Author(s): Sugiyama M, Bhawal UK (co-first author), Kawamura M, Ishioka Y, Shigeishi H, Kamata N
  • Journal Title: Br J Oral Maxillofac Surg 45(2) Pages: 116-22
  • Peer Reviewed
• [Presentation] 口腔扁平上皮癌におけるBRAKとEGFRの発現 (2009)
  • Author(s): バワールウジャール、生駒丈晴、小澤重幸、松本剛一、畑隆一郎、久保田英朗
  • Organizer: 口腔難治疾患研究センター報告会
  • Place of Presentation: 神奈川歯科大学
  • Year and Date: 2009-03-21
• [Presentation] ケモカイン(BRAK)のTet-On発現ベクターを用いた癌進展抑制機構の解析・口腔扁平上皮癌におけるBRAKとEGFRの発現 (2009)
  • Author(s): バワールウジャール、生駒丈晴、小澤重幸、松本剛一、畑隆一郎、久保田英朗
  • Organizer: 神奈川歯科大学学会例会
  • Place of Presentation: 神奈川歯科大学
  • Year and Date: 2009-01-15
• [Presentation] IL-1β mediated up-regulation of DEC in human gingival epithelium in a NF-kB and Cox-2 independent pathway (2009)
  • Author(s): Bhawal UK, Sato F, Ikoma T, Dohi M, Honma Y, Kijima H, Kubota E
  • Organizer: The 11th Meeting of Hirosaki International Forum of Medical Science
  • Place of Presentation: Hirosaki
• [Presentation] Basic-helix-loop-helix (bHLH) transcription factor DEC1 regulates CyclinD1 expression through E-box elements (2008)
  • Author(s): バワールウジャール、生駒丈晴、土肥雅彦、小林優、久保田英朗
  • Organizer: 神奈川歯科大学学会総会
  • Place of Presentation: 神奈川歯科大学
  • Year and Date: 2008-12-06
• [Presentation] 低酸素下におけるbHLH 型転写因子DEC2とVascular endothelial growth factor(VEGF)発現の制御機構 (2008)
  • Author(s): バワールウジャール、生駒丈晴、松本剛一、小林優、久保田英朗
  • Organizer: 神奈川歯科大学学会総会
  • Place of Presentation: 神奈川歯科大学
  • Year and Date: 2008-12-06
• [Presentation] DEC2 negatively regulates VEGF expression in oral squamous cell carcinoma (2008)
  • Author(s): Bhawal UK, Sato F, Ikoma T, Kijima H, Kubota E
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] TrkB and TrkC are associated with tumor progression, and poor prognosis in oral squamous cell carcinoma (2008)
  • Author(s): Luo Y, Sasahira T, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] HMGB1-inducible MIA is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma (2008)
  • Author(s): Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, Ohmori H, Luo Y, Yasui W, Bosserhoff AK, Kuniyasu H
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Angiotensin activation system in HT29 colon cancer cells enhances liver metastasis (2008)
  • Author(s): Kuniyasu H, Sasahira T, Luo Y, Bhawal UK, Morikawa Y, Shimomoto T, Ohmori H
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] IL-1β mediated up-regulation of HIF-1α and DEC transcription factor in human gingival cell (2008)
  • Author(s): バワールウジャール、生駒丈晴、土肥雅彦、小林優、久保田英朗
  • Organizer: 第18回日本口腔粘膜学会総会
  • Place of Presentation: 東京
• [Presentation] 口腔粘膜上皮細胞の炎症性サイトカイン発現におけるHMGB1とHMGB1レセプターとの関連 (2008)
  • Author(s): 生駒丈晴、バワールウジャール、土肥雅彦、小林優、久保田英朗
  • Organizer: 第18回日本口腔粘膜学会総会
  • Place of Presentation: 東京
• [Presentation] DEC2 negatively regulates VEGF expression in oral squamous cell carcinoma (2008)
  • Author(s): Bhawal UK, Sato F, Ikoma T, Kijima H, Kubota E
  • Organizer: 14th World Congress on Advances in Oncology
  • Place of Presentation: Greece
• [Presentation] DEC2 negatively regulates VEGF expression in oral squamous cell carcinoma (2008)
  • Author(s): Bhawal UK, Sato F, Kijima H, Kubota E
  • Organizer: 86th General Session & Exhibition of the IADR
  • Place of Presentation: Canada
• [Presentation] DEC2 negatively regulates VEGF expression in oral SCC (2008)
  • Author(s): Bhawal UK, Ikoma T, et.al.
  • Organizer: 14th World Congress on Advances in Oncology
  • Place of Presentation: Heraklion, Athens, Greece
• [Presentation] DEC2 negatively regulates VEGF expression in oral SCC (2008)
  • Author(s): Bhawal UK, Sato F, et.al.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋