patho-physiologic role of HSP90 in the aseptic inflammatory process

• Project/Area Number: 22659075
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: SATO Noriyuki 札幌医科大学, 医学部, 教授 (50158937)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,090,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 分子病理 / HSP / 抗原提示細胞 / 自然免疫 / CTL / 癌ワクチン / endosome / IFNα

Research Abstract

This study was intended to analyze patho-physiologic role of heat shock protein 90(HSP90) in the aseptic inflammatory process. Specifically we tried to identify HSP90 receptor molecule that is considered to be expressed on inflammatory cells such as macrophages and dendritic cells. We successfully obtained such candidate molecules, and it may be possible to regulate the pathologic inflammatory process involving with these molecule.

Research Products

• [Journal Article] Establishment of a monoclonal anti-pan HLA class I antibody suitable for immunostaining of formalin-fixed tissue : Unusually high frequency of down-regulation in breast cancer tissues (2012)
  • Author(s): Torigoe, T., Asanuma, H., Nakazawa. E., Tamura, Y., Hirohashi, Y., Yamamoto, E., Kanaseki, T., Hasegawa, T., Sato, N.
  • Journal Title: Pathol Int Volume: 62 Issue: 5 Pages: 303-8
  • DOI: 10.1111/j.1440-1827.2012.02789.x
  • NAID: 10031185205
  • Peer Reviewed
• [Journal Article] Sorting Nexin 5 of a New Diagnostic Marker of Papillary Thyroid Carcinoma Regulates Caspase-2 (2012)
  • Author(s): Ara S,Kikuchi T,Matsumiya H,Kojima T,Kubo T, Ye RC, Sato A, Kon SI, Honma T,Asakura K, Hasegawa T, Himi T,Sato N, Ichimiya S.
  • Journal Title: Cancer Science Volume: 103 Issue: 7 Pages: 1356-62
  • DOI: 10.1111/j.1349-7006.2012.02296.x
  • Peer Reviewed
• [Journal Article] ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells (2012)
  • Author(s): Matsuzaki J,Torigoe T,Hirohashi Y, Kamiguchi K,Tamura Y, Tsukahara T,Kubo T, Takahashi A, Nakazawa E,Saka E, Yasuda K,Takahashi S,Sato N.
  • Journal Title: Carcinogenesis Volume: 33 Issue: 5 Pages: 996-1003
  • DOI: 10.1093/carcin/bgs118
  • Peer Reviewed
• [Journal Article] Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses (2012)
  • Author(s): Mizuuchi M, Hirohashi Y, Torigoe T, Takafumi K, Yasuda K, Saito T, Sato N.
  • Journal Title: Exp Mol Pathol Volume: 92 Pages: 185-190
  • URL: http://dx.doi.org/10.1016/j.yexmp.2011.10.002
  • Peer Reviewed
• [Journal Article] Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population (2012)
  • Author(s): Mori T, Nishizawa S, Hirohashi Y, Torigoe T, Tamura Y, Takahashi A, Kochin V, Fujii R, Toru K, Greene MI, Hara I, Sato N.
  • Journal Title: Exp Mol Pathol Volume: 92 Pages: 27-32
  • URL: http://dx.doi.org/10.1016/j.yexmp.2011.09.016
  • Peer Reviewed
• [Journal Article] SOX2 is expressed in stem-like cells of human lung adenocarcinoma and augments the tumor-initiating potential (2011)
  • Author(s): Nakatsugawa, M., Takahashi, A., Hirohashi, Y., Torigoe, T., Inoda, S., Asanuma, H., Tamura, Y., Hasegawa, T., Takahashi, H., and Sato, N.
  • Journal Title: Lab Invest. Volume: 91 Issue: 12 Pages: 1796-1804
  • DOI: 10.1038/labinvest.2011.140
  • Peer Reviewed
• [Journal Article] Tumor associated dendritic cells : molecular mechanisms to suppress anti-tumor immunity (2011)
  • Author(s): Hirohashi, Y. and Sato, N.
  • Journal Title: Immunotherapy Volume: 3 Issue: 8 Pages: 945-947
  • DOI: 10.2217/imt.11.94
  • Peer Reviewed
• [Journal Article] Tumor-Produced Secreted Form of Binding of Immunoglobulin Protein Elicits Antigen-Specific Tumor Immunity. (2011)
  • Author(s): Tamura Y, Hirohashi Y, Kutomi G, Nakanishi K, Kamiguchi K, Torigoe T, Sato N.
  • Journal Title: J. Immunol Volume: 186 Issue: 7 Pages: 4325-4330
  • DOI: 10.4049/jimmunol.1004048
  • Peer Reviewed
• [Journal Article] Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells. (2011)
  • Author(s): Oura, J., Tamura, Y., Kamiguchi, K., Kutomi, G., Sahara, H., Torigoe, T., Himi, T., and Sato, N.
  • Journal Title: Int. Immunol Volume: 23 Issue: 4 Pages: 223-237
  • DOI: 10.1093/intimm/dxq475
  • Peer Reviewed
• [Journal Article] Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma (2011)
  • Author(s): Kano, M., Tsukahara, T., Emori, M., Murase, M., Torigoe, T., Kawaguchi, S., Wada, T., Yamashita, T., Sato, N.
  • Journal Title: Cancer Sci Volume: 102 Issue: 8 Pages: 1443-1137
  • DOI: 10.1111/j.1349-7006.2011.01962.x
  • NAID: 10030241866
  • Peer Reviewed
• [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients (2011)
  • Author(s): Kameshima, H., Tsuruma, T., Torigoe, T., Takahashi, A., Hirohashi, Y., Tamura, Y., Tsukahara, T., Ichimiya, S., Kanaseki, T., Iwayama, Y., Sato, N., Hirata, K.
  • Journal Title: Cancer Sci Volume: 102 Issue: 6 Pages: 1181-1187
  • DOI: 10.1111/j.1349-7006.2011.01918.x
  • NAID: 10029294487
  • Peer Reviewed
• [Journal Article] Comparison of speedy PCR-ssp method and serological typing of hla-a24 for Japanese cancer patients. (2011)
  • Author(s): Nakatsugawa M, Hirohashi Y, Torigoe T, Inoda S, Kiriyama K, Tamura Y, Sato E, Takahashi H, Sato N.
  • Journal Title: J Immunoassay Immunochem Volume: 32 Issue: 2 Pages: 93-102
  • DOI: 10.1080/15321819.2010.543219
  • Peer Reviewed
• [Journal Article] Cytotixic T lymphocytes efficiently recognize human colon cancer stem-like cells (2011)
  • Author(s): Inoda, S., Hirohashi, Y., Torigoe, T., Takahashi, A., Morita, R., Nakatsugawa, M., Nishizawa, S., Tamura, Y., Tsuruma, T., Terui, T., Ishitani, K., Hirata, K. and Sato, N.
  • Journal Title: Am. J. Pathol. Volume: 178 Pages: 1805-1813
  • URL: http://dx.doi.org/10.1016/j.ajpath.2011.01.004
  • Peer Reviewed
• [Journal Article] Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer (2011)
  • Author(s): Miyazaki A, Kobayashi J, Torigoe T, Hirohashi Y, Yamamoto T, Yamaguchi A, Asanuma H, Takahashi A, Michifuri Y, Nakamori K, Nagai I, Sato N, Hiratsuka H.
  • Journal Title: Cancer Sci Volume: 102 Issue: 2 Pages: 324-329
  • DOI: 10.1111/j.1349-7006.2010.01789.x
  • NAID: 10029289826
  • Peer Reviewed
• [Journal Article] The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma (2011)
  • Author(s): Inoda S, Morita R, Hirohashi Y, Torigoe T, Asanuma H, Nakazawa E, Nakatsugawa M, Tamura Y, Kamiguchi K, Tsuruma T, Terui T, Ishitani K, Hashino S, Wang Q, Greene MI, Hasegawa T, Hirata K, Asaka M, Sato N
  • Journal Title: Exp. Mol. Pathol Volume: 90 Pages: 55-60
  • URL: http://dx.doi.org/10.1016/j.yexmp.2010.10.001
  • Peer Reviewed
• [Journal Article] Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlong primary B cells and their cognate T cell help (2011)
  • Author(s): Nagashima, T., Ichimiya, S., Kikuchi, T., Saito, Y., Matsumiya, H., Ara, S., Koshiba, S., Zhang, J., Hatate, S., Tonooka, A., Kubo, T., Hirose, B., Shirasaki, H., Izumi, T., Takami, T., Himi, T. and Sato, N.
  • Journal Title: Am. J. Pathol Volume: 171 Issue: 1 Pages: 222-232
  • DOI: 10.1016/j.ajpath.2010.11.033
  • Peer Reviewed
• [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma (2011)
  • Author(s): Tanaka, T., Kitamura, H., Torigoe, T., Hirohashi, Y., Masumori, N., Sato, N. and Tsukamoto, T.
  • Journal Title: J. Cancer Res. Clin. Oncol Volume: 137 Issue: 5 Pages: 789-794
  • DOI: 10.1007/s00432-010-0940-6
  • Peer Reviewed
• [Journal Article] Heat shock protein 40 family, DNAJB8 is expressed in renal cancer stem-like cell, controls the tumor-initiating ability and can be a potent target of immunotherapy (2011)
  • Author(s): Nishizawa, S., Sato, N., et al
  • Journal Title: Cancer Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cytotixic T lymphocytes efficiently recognize human colon cancer stem-like cells (2011)
  • Author(s): Inoda, S., Sato, N., et al
  • Journal Title: Am.J.Pathol. Volume: 178 Pages: 1805-1813
  • Peer Reviewed
• [Journal Article] Tumor-Produced Secreted Form of Binding of Immunoglobulin Protein Elicits Antigen-Specific Tumor Immunity. Selected paper in "In this issue" of the Journal (2011)
  • Author(s): Tamura Y., Sato, N., et al.
  • Journal Title: J.Immunol. Volume: 186 Pages: 4325-4330
  • Peer Reviewed
• [Journal Article] Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells. Selected paper in "In this issue" of the Journal (2011)
  • Author(s): Oura, J., Sato, N., et al.
  • Journal Title: Int.Immunol. Volume: 23 Pages: 223-237
  • Peer Reviewed
• [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients. (2011)
  • Author(s): Kameshima, H., Sato, N., et al.
  • Journal Title: Cancer Sci. Volume: (in press)
  • NAID: 10029294487
  • Peer Reviewed
• [Journal Article] Comparison of speedy PCR-ssp method and serological typing of hla-a24 for Japanese cancer patients. (2011)
  • Author(s): Nakatsugawa M, Sato, N., et al.
  • Journal Title: J Immunoassay Immunochem. Volume: 32 Pages: 93-102
  • Peer Reviewed
• [Journal Article] SOX2 is expressed in stem-like cells of human lung adenocarcinoma and augments the tumor-initiating potential. (2011)
  • Author(s): Nakatsugawa, M., Sato, N., et al.
  • Journal Title: Lab Invest. Volume: (in press)
  • Peer Reviewed
• [Journal Article] DNA methyltransferase 1 is essential for maintenance of human colon cancer Stem-like cells. (2011)
  • Author(s): Morita, R., Sato, N., et al.
  • Journal Title: Am J.Pathol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cytotixic T lymphocytes efficiently recognize human colon cancer stem-like cells. (2011)
  • Author(s): Inoda, S., Sato, N., et al.
  • Journal Title: Am.J.Pathol. Volume: 178 Pages: 1805-1813
  • Peer Reviewed
• [Journal Article] Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer. (2011)
  • Author(s): Miyazaki A, Sato, N., et al.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 324-329
  • NAID: 10029289826
  • Peer Reviewed
• [Journal Article] The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma. (2011)
  • Author(s): Inoda S, Sato, N., et al.
  • Journal Title: Exp.Mol.Pathol. Volume: 90 Pages: 55-60
  • Peer Reviewed
• [Journal Article] Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlong primary_ B cells and their cognate T cell help. (2011)
  • Author(s): Nagashima, T., Sato, N., et al.
  • Journal Title: Am.J.Pathol. Volume: 171 Pages: 222-232
  • Peer Reviewed
• [Journal Article] Spatiotemporal regulation of heat shock protein 90-chaperoned self-DNA and CpG-oligodeoxynucleotide for type I IFN induction via targeting to static early endosome (2010)
  • Author(s): Okuya, K., Tamura, Y., Saito, K., Kutomi, G., Torigoe, T., Hirata, K., Sato, N.
  • Journal Title: J. Immunol. Volume: 184 Pages: 7092-7099
  • Peer Reviewed
• [Journal Article] Melanoma-targeted chemo-thermo-immuno(CTI)-therapy using N-propionyl-4-S-cysteaminylphenol-m agnetite nanoparticles elicits CTL response via heat shock protein-peptide complex release (2010)
  • Author(s): Sato A, Tamura Y, Sato N, Yamashita T, Takada T, Sato M, Osai Y, Okura M, Ono I, Ito A, Honda H, Wakamatsu K, Ito S, Jimbow K.
  • Journal Title: Cancer Sci Volume: 101 Issue: 9 Pages: 1939-1946
  • DOI: 10.1111/j.1349-7006.2010.01623.x
  • NAID: 10027831209
  • Peer Reviewed
• [Journal Article] Immune response against tumor antigens expressed on human cancer stem-like cells/tumor-initiating cells (2010)
  • Author(s): Hirohashi, Y., Torigoe, T., Inoda, S., Takahashi, A., Morita, R., Nishizawa, S., Tamura, Y., Suzuki, H., Yoyota, M. Sato, N.
  • Journal Title: Immunotherapy Volume: 2 Pages: 201-211
  • Peer Reviewed
• [Journal Article] Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model (2010)
  • Author(s): Ohno, K., Nishimori, H., Yasoshima, T., Kamiguchi, K., Hata, F., Fukui, R., Okuya, K., Kimura, Y., Denno, R., Kon, S., Uede, T., Sato, N. Hirata, K.
  • Journal Title: Surg. Today Volume: 40 Pages: 347-356
  • NAID: 10027395148
  • Peer Reviewed
• [Journal Article] Spatiotemporal regulation of heat shock protein 90-chaperoned self-DNA and CpG-oligodeoxynucleotide for type I IFN induction via targeting to static early endosome. (2010)
  • Author(s): Okuya, K., Sato, N., et al.
  • Journal Title: J.Immunol. Volume: 184 Pages: 7092-7099
  • Peer Reviewed
• [Journal Article] Melanoma-targeted chemo-thermo-immuno(CTI)-therapy using N-propionyl-4-S-cysteaminylphenol-magmetite nanoparticles elicits CTL response via heat shock protein-peptide complex release. (2010)
  • Author(s): Sato A, Sato, N., et al.
  • Journal Title: Cancer Sci. Volume: 101 Pages: 1939-1946
  • Peer Reviewed
• [Journal Article] Immune response against tumor antigens expressed on human cancer stem-like cells/tumor-initiating cells. (2010)
  • Author(s): Hirohashi, Y., Sato, N., et al.
  • Journal Title: Immunotherapy Volume: 2 Pages: 201-211
  • Peer Reviewed
• [Journal Article] Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model. (2010)
  • Author(s): Ohno, K., Sato, N., et al.
  • Journal Title: Surg.Today Volume: 40 Pages: 347-356
  • NAID: 10027395148
  • Peer Reviewed
• [Journal Article] Heat shock protein 40 family, DNAJB8 is expressed in renal cancer stem-like cell, controls the tumor-initiating ability and can be a potent target of immunotherapy.
  • Author(s): Nishizawa, S., Mori, T., Hirohashi, Y., Torigoe, T., Tamura, Y., Kamiguchi, K., Takahashi, A., Kanaseki, T., Nakazawa, E., Asanuma, H., Sokolovskaya, A., Morita, R., Yamada, R., Fujii, R., Kondo, T., Hasegawa, T., Hara, I. and Sato, N.
  • Journal Title: Cancer Res Volume: (in press) Pages: 11-3062
  • Peer Reviewed
• [Journal Article] DNA methyltransferase 1 is essential for maintenance of human colon cancer stem-like cells
  • Author(s): Morita, R., Hirohashi, Y., Torigoe, T., Takahashi, A., Saka, E., Asanuma, H., Suzuki, H., Tamura, H., Nakazawa, E., Ito-Inoda, S., Hashino, S., Hasegawa, T., Tokino, T., Toyota, M., Asaka, M. and Sato, N.
  • Journal Title: Am J. Pathol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Heat shock protein 90 governs self-nucleic acid recognition by Toll-like receptors
  • Author(s): Saito, K., Tamura, Y., Kukita, K., Kutomi, G., Okuya, K., Asanuma, H., Torigoe, T., Hirata, K., Sato, N.
  • Journal Title: Nature
  • Peer Reviewed
• [Presentation] がん幹細胞を標的とする免疫療法 (2011)
  • Author(s): 廣橋良彦、佐藤昇志, 他
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Stress Response Genes Expressed in Cancer Stem Cells-potent molecular targets for cancer therapy- (2011)
  • Author(s): Toshihiko Torigoe, Hirohashi Yoshihiko, Yasuaki Tamura, Noriyuki Sato
  • Organizer: The 5^<th> International Congress on Stress Responses in Biology and Medicine
  • Place of Presentation: Quebec City, Canada
• [Presentation] Stress Response Genes Expressed in Cancer Stem Cells -potent molecular targets for cancer therapy- (2011)
  • Author(s): Toshihiko Torigoe, Noriyuki Sato, 他
  • Organizer: The 5^<th> CSSI International Meeting
  • Place of Presentation: Quebec, Canada
• [Presentation] Immune responses against cancer stem cells (2010)
  • Author(s): Toshihiko Torigoe, Yoshihiko Hirohashi, Noriyuki Sato
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Progress of cancer immunotherapy. Immunotherapeutic clinical trial of surviving-based tumor antigens and manipulation of antigenicity enhancement by HSP90. Special Clinical Seminar. (2010)
  • Author(s): Noriyuki Sato.
  • Organizer: 14^<th> International Congress on Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-24
• [Presentation] Progress of cancer immunotherapy. Immunotherapeutic clinical trial of surviving-based tumor antigens and manipulation of antigenicity enhancement by HSP90 Special Clinical Seminar (2010)
  • Author(s): Noriyuki Sato
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
• [Presentation] A novel DNAJ family protein is a cancer initiating cell antigen.-A potent molecular target for cancer immunotherapy- (2010)
  • Author(s): Toshihiko Torigoe, Yoshihiko Hirohashi, Satoshi Nishizawa, Akari Takahashi, Hiroko Asanuma, Munehide Nakatsugawa, Kenjiro Kamiguchi, Alisa A. Sokolovskaya, Noriyuki Sato
  • Organizer: The 8^<th> International Workshop on the Molecular Biology of Stress Responses
  • Place of Presentation: Seorak Mt., Korea
• [Book] Cancer, Immunology and Photonics Science, Optical Devices and Systems, Biomedical and Green Technologies (2010)
  • Author(s): Noriyuki Sato, Yoshihiko Hirohashi, Tomohide Tsukahara, Shingo Ichimiya, Yasuaki Tamura and Toshihiko Torigoe
• [Book] がん免疫療法の標的抗原、がん免疫療法-実用化へのチャレンジ- (2010)
  • Author(s): 守田玲菜、廣橋良彦、鳥越俊彦、佐藤昇志
  • Publisher: シーエムシー出版
• [Book] がん免疫療法の標的抗原、がん免疫療法-実用化へのチャレンジ- (2010)
  • Author(s): 守田玲菜、鳥越俊彦, et al.
  • Publisher: シーエムシー出版
• [Remarks]
  • URL: http://web.sapmed.ac.jp/patho1/index.html
• [Patent(Industrial Property Rights)] 改良された糖被覆リポソーム組成物 (2011)
  • Inventor(s): 梶原敏充、柿崎麻希、佐藤昇志(他4名)
  • Industrial Property Rights Holder: 梶原敏充、柿崎麻希、佐藤昇志(他4名)
  • Industrial Property Number: 2011-102962
  • Filing Date: 2011-05-02
• [Patent(Industrial Property Rights)] 改良された糖被覆リポソーム組成物 (2011)
  • Inventor(s): 梶原敏充、沼崎麻希、佐藤昇志, 他
  • Industrial Property Rights Holder: 梶原敏充、沼崎麻希、佐藤昇志, 他
  • Industrial Property Number: 2011-102962
  • Filing Date: 2011-05-02
• [Patent(Industrial Property Rights)] 抗原特異的T細胞誘導脳測定法 (2010)
  • Inventor(s): 鳥越俊彦、廣橋良彦、水内将人、佐藤昇志、鈴木哲、清水佳隆、佐藤雄一郎
  • Industrial Property Rights Holder: 鳥越俊彦、廣橋良彦、水内将人、佐藤昇志、鈴木哲、清水佳隆、佐藤雄一郎
  • Filing Date: 2010-08-30
  • Overseas
• [Patent(Industrial Property Rights)] インターフェロンα産生阻害剤 (2010)
  • Inventor(s): 田村保明、佐藤昇志、鳥越俊彦、齋藤慶太
  • Industrial Property Rights Holder: 田村保明、佐藤昇志、鳥越俊彦、齋藤慶太
  • Industrial Property Number: 2010-219422
  • Filing Date: 2010-09-29
• [Patent(Industrial Property Rights)] サバイビン由来のHLA-A24結合性癌抗原ペプチド (2010)
  • Inventor(s): 佐藤昇志、鳥越俊彦、廣橋良彦、井手之上里美、小林淳一
  • Industrial Property Rights Holder: 佐藤昇志、鳥越俊彦、廣橋良彦、井手之上里美、小林淳一
  • Industrial Property Number: 2004-191478
  • Filing Date: 2010-10-08