Antitumor effect of gene transfection and DNA vacccine of beta-defensins

• Project/Area Number: 16591894
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: ABIKO Yoshihiro Health Sciences University of Hokkaido, Institute of Personalized Medical Science, Professor (90260819)
• Co-Investigator(Kenkyū-buntansha): KAKU Tohru Health Sciences University of Hokkaido, School of Dentistry, Professor (60133253) ; ARAKAWA Toshiya Health Sciences University of Hokkaido, School of Dentistry, Assistant Professor (40306254) ; NAGAYASU Hiroki Health Sciences University of Hokkaido, Institute of Personalized Medical Science, Associate Professor (90265075) ; OKUMURA Kazuhiko Health Sciences University of Hokkaido, School of Dentistry, Assistant Professor (60194510)
• Project Period (FY): 2004 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥150,000); Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: Beta-defensin / Antitumor / Gene therapy / DNA vaccine / Squamous cell carcinoma / Lymphoma / 樹状細胞 / 遺伝子導入 / CCR6

Research Abstract

The present study examined whether increased expression of beta-defensins by the gene transfection affected antitumor of squamous cell carcinoma (SCC), and whether DNA vaccine with beta-defensins affected antitumor of lymphoma. In order to observe the antitumor effect of increased expression of beta-defensins on SCC, adenovirus vectors with beta-defensin were transfected into SCC tissues in nude mice. The diameter of the tumor mass into which the gene was trandected was significantly smaller than that of the controls. The results indicate that beta-defensins themselves may posses a direct antitumor effect against SCC. In order to observe the antitumor effect of DNA vaccine with beta-defensins on lymphoma, the vaccine was injected into A20 lymphoma inBALB/c mice. The survival rate of the vaccination group was significantly longer than that of the control group. The results indicate that DNA vaccine with beta-defensins may be useful in the treatment of lymphoma.

Research Products

• [Journal Article] Increased expression of beta-defensin-2 and -3 during the development of autoimmune sialoadenitis in MRL/lpr mice (2007)
  • Author(s): Saitoh M, Kurashige Y, Yamaza ki M, Nishimura M, Nakamura S, Noro D, TakeshimaM, Araka wa T, Takuma T, Igarashi S, Ka ku T, Inoue T, Abiko Y
  • Journal Title: Med Mol Morph 40 Pages: 157-162
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Salivary defensins and their importance in oral health and disease(Review) (2007)
  • Author(s): Abiko Y, Saitoh M
  • Journal Title: Curr Pharm Design 13 Pages: 3065-3072
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Role of beta-defensin in oral epithelial health and disease(Award review) (2007)
  • Author(s): Abiko Y, Satoh M, Nishimura M, Yamazaki M, Sawamura D, Kaku T
  • Journal Title: Med Mol Morph 40 Pages: 179-184
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Increased expression of beta-defensin-2 and -3 during the development of autoimmune sialoadenitis in MRL/lpr mice. Med Mol Morph (2007)
  • Author(s): Saitoh, M., Kurashige, Y., Yamazaki, M., Nishimura, M., Nakamura, S., Noro, D., Takeshima, M., Arakawa, T., Takuma, T., Igarashi, S., Kaku, T., Inoue, T., Abiko, Y
  • Journal Title: Med Mol Morph 40 Pages: 157-162
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Salivary defensins and their importance in oral health and disease(Review) (2007)
  • Author(s): Abiko, Y., Saitoh, M
  • Journal Title: Curr Pharm Design 13 Pages: 3065-3072
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of beta-defensin in oral epithelial health and disease(Award review) (2007)
  • Author(s): Abiko, Y., Satoh, M., Nishimura, M., Yamazaki, M., Sawamura, D., Kaku, T
  • Journal Title: Med Mol Morph 40 Pages: 179-184
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of beta-defensin in oral epithelial health and disease (2007)
  • Author(s): Abiko Y., et. al.
  • Journal Title: Med.Mol.Morphol. 40 Pages: 179-184
  • Peer Reviewed
• [Journal Article] Salivary defensins and their importance in oral health and disease (2007)
  • Author(s): Abiko Y.and Saitoh M.
  • Journal Title: Curr.Pharm.Des. 18 Pages: 3065-3072
  • Peer Reviewed
• [Journal Article] Increased expression of beta-defensin-2 and -3 during the development of autoimmune sialoadenitis in MRL/lpr mice (2007)
  • Author(s): Saitoh M., et. al.
  • Journal Title: Med.Mo1.Morphol. 40 Pages: 157-162
  • Peer Reviewed
• [Journal Article] Ameloblastic carcinoma ex ameloblastoma : report of a case-possible involvement of CpG island hypermethylation of the p16 gene in malignant transformation. (2007)
  • Author(s): Abiko Y, Nagayasu H, Takeshima M, Yamazaki M, Nishimura M, Kusano K, Kitajo H, Saitoh M, Kawakami T, Chiba I, Kaku T
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103 Pages: 72-76
• [Journal Article] Morphology of Malassez's epithelial rest-like cells in the cementum : transmission electron microscopy, immunohistochemical, and TdT-mediated dUTP-biotin nick end labeling studies. (2006)
  • Author(s): Suzuki M, Matsuzaka K, Yamada S, Shimono M, Abiko Y, Inoue T
  • Journal Title: J Periodontal Res 41 Pages: 280-287
• [Journal Article] Connexin 43 transfection in basaloid squamous cell carcinoma cells (2006)
  • Author(s): Shima K, Muramatsu T, Abiko Y, Yamaoka Y, Sasaki H, Shimono M
  • Journal Title: Oncol Rep 16 Pages: 285-288
• [Journal Article] Single-nucleotide Polymorphism(SNP) in B-Defensin 2 in a Japanese Population and an Effect of - 1029 SNP on Promoter Activity (2005)
  • Author(s): Kusano k, Abiko Y, Nishimura M, Arakawa T, Takeshima M, Fujimoto A, Takuma T, Kaku T
  • Journal Title: Oral Science International 2 Pages: 80-84
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection (2005)
  • Author(s): Sawamura D, Goto M, Shibaki A, Akiyama M, McMillan JR, A biko Y, Shimizu H
  • Journal Title: Gene Ther 12 Pages: 857-861
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Single-nucleotide Polymorphism(SNP) in 6-Defensin 2 in a Japanese Population and an Effect of - 1029 SNP on Promoter Activity (2005)
  • Author(s): Kusano, k., Abiko, Y., Nishimura, M., Arakawa, T., Takeshima, M., Fujimoto, A., Takuma, T., Kaku, T
  • Journal Title: Oral Science International 2 Pages: 80-84
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection (2005)
  • Author(s): Sawamura, D., Goto, M., Shibaki, A., Akiyama, M., McMillan, JR., Abiko, Y., Shimizu, H
  • Journal Title: Gene Ther 12 Pages: 857-61
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of osteopontin expression and fenction in oral cancer cell lines by antisense oligonucleotides (2005)
  • Author(s): Muramatsu T., Shima K., Ohta K., Kizaki H., Abiko Y., Shimono M.
  • Journal Title: Cancer Letter 217 Pages: 87-95
• [Journal Article] Single-nucleotide polymorphism(SNP) in beta-difensin 2 in a Japanese population and an effect of -1029 SNP on promoter activity (2005)
  • Author(s): Kusano K, Abiko Y, Nishimura M, Arakawa T, Takeshima M, Fujimoto A, Takuma T.Kaku T.
  • Journal Title: Oral Science International 2(2) Pages: 80-84
• [Journal Article] 成長期ラット顎関飾円板におけるversican isoform mRNAの発現-TaqMan probeを用いたreal-time quantitative PCRによる分析- (2005)
  • Author(s): 鳥谷奈保子, 荒川陵哉, 田隈泰信, 安彦善裕, 溝口 到
  • Journal Title: 北海道医療大学歯学会雑誌 24(1) Pages: 31-39
• [Journal Article] Beta defensin-s engineered epidermis shows highly protective effect fro bacterial infection (2005)
  • Author(s): Sawamura D, Goto M, Shibaki A, Akiyama M, McMillan JR, Abiko Y, Shimizu H.
  • Journal Title: Gene Therapy 12 Pages: 857-861
• [Journal Article] Cell proliferation, apoptosis and apoptosis-related factors in odontogenic keratocysts and in dentigerous cysts (2005)
  • Author(s): Kichii E, Enokiya Y, Muramatsu T, Hashimoto S, Inoue T, Abiko Y, Shimono M.
  • Journal Title: J Oral Pathol Med 36 Pages: 280-286
• [Journal Article] Current dental implant research (2005)
  • Author(s): Inoue T, Matsuzaka K, Yoshinari M, Tanaka T, Abiko Y., Shimono M
  • Journal Title: Dentistry in Japan 41 Pages: 196-213
• [Journal Article] Beta defensinn-3 engineered epidermis shows highly protective effect for bacterial infection (2005)
  • Author(s): Sawamura D, Goto M, Shibaki A, Akiyama M, McMillan JR, Abiko Y, et al.
  • Journal Title: Gene Ther 24
• [Journal Article] Inhibition of osteopontin expression and function in oral cancer lines by antisense oligonucleotides. (2005)
  • Author(s): Muramatsu T, Shima K, Ohta K, Kizaki H, Ro Y, Kohno Y, Abiko Y, et al.
  • Journal Title: Cancer Lett 217(1) Pages: 87-95
• [Journal Article] C-terminal domain of human CAP18 antimicrobial peptide induces apotosis in oral squamous cell (2004)
  • Author(s): Okumura K, Itoh A, Isogai E, Hirose K, Hosokawa Y, Abiko Y, Shibata T, Hirata M, Isogai H
  • Journal Title: Cancer Lett 212 Pages: 185-194
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Correlated expression of human beta defensin-1,-2 and -3 mRNAs in gingival tissues of young children (2004)
  • Author(s): Saitoh M, Abiko Y, Shimabukuro S, Kusano K, Nishimura M, Arakawa T, Nakashima K, Takuma T, Kaku T, Igarashi S
  • Journal Title: Arch Oral Biol 49 Pages: 799-803
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Effect of defensin peptides on eukaryotic cells primary epithelial cells,flibroblasts and squamous cell carcinoma cell lines (2004)
  • Author(s): Nishimura M, Abiko Y, Kurashi ge Y, Takeshima M, Yamazaki M, Kusano K, Saitoh M, Nakas hima K, Inoue T, Kaku T
  • Journal Title: J Dermatol Sci 36 Pages: 87-95
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 小児歯肉におけるヒトβディフェンシン1-2-3mRNAの発現及び局在 (2004)
  • Author(s): 斉藤 正人、島袋 鎮太郎、坂口 也子、桜井 有子、野呂 大輔、菅谷 裕行、五十嵐 清治、西村 学子、安彦 善裕
  • Journal Title: 小児歯科学雑誌 42 Pages: 69-74
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] 口腔扁平苔癬におけるβディフェンシン2の発現と臨床病理学的所見との関連についての検討 (2004)
  • Author(s): 野口 忠秀, 神部 芳則, 草間 幹夫, 安彦 善裕, 賀来 亨
  • Journal Title: 日本口腔粘膜学会雑誌 10 Pages: 6-10
  • NAID: 10013391951
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] C-terminal domain of human CAP18 antimicrobial peptide induces apotosis in oral squamous cell (2004)
  • Author(s): Okumura, K., Itoh, A., Isogai, E., Hirose, K., Hosokawa, Y., Abiko, Y., Shibata, T., Hirata, M., Isogai, H
  • Journal Title: Cancer Lett 212 Pages: 185-94
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Correlated expression of human beta defensin-1, -2 and -3 mRNAs in gingival tissues of young children (2004)
  • Author(s): Saitoh, M., Abiko, Y., Shimabukuro, S., Kusano, K., Nishimura, M., Arakawa, T., Nakashima, K., Takuma, T., Kaku, T., Igarashi, S
  • Journal Title: Arch Oral Biol 49 Pages: 799-803
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effect of defensin peptides on eukaryotic cells : primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines (2004)
  • Author(s): Nishimura, M., Abiko, Y., Kurashige, Y., Takeshima, M., Yamazaki, M., Kusano, K., Saitoh, M., Nakashima, K., Inoue, T., Kaku, T
  • Journal Title: J Dermatol Sci 36 Pages: 87-95
  • NAID: 10016185292
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An immunohistochemical study of the localization of induviblee nitric oxide synthase(iNOS) and heat shock protein(HSP) in pleomorphic adenoma (2004)
  • Author(s): Yamaguchi M, Abiko Y, Nishimura M, et al.
  • Journal Title: Acta Histochem.Cytochem. 37(4) Pages: 267-271
• [Journal Article] Effect of defensin peptides on eukaryotic cells : primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines (2004)
  • Author(s): Nishimura M, Abiko Y, et al.
  • Journal Title: J.Dermatol Sci. 36(2) Pages: 87-95
  • NAID: 10016185292
• [Journal Article] Correlated expression of human beta defensin-1,-2 and -3 mRNAs in gingival tissues of young children (2004)
  • Author(s): Saitoh M, Abiko Y, Shimabukuro S, Kusano K, Nishimura M, et al.
  • Journal Title: Arch Oral Biol 49 Pages: 499-803
• [Journal Article] Atypical carcinoid (neuroendocrine carcinoma) of the gingival : Couterpart of a laryngeal tumor (2004)
  • Author(s): Abiko Y, Ogawa I, Hattori Y, Kusano K, Nishimura M, et al.
  • Journal Title: Pathol.International 54(2) Pages: 97-100