Epigenetic mechanisms of development of follicular helper-T like tumors

• Project/Area Number: 25461407
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: Sakata-Yanagimoto Mamiko 筑波大学, 医学医療系, 准教授 (80451805)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: lymphoma / RHOA / TET2 / AITL / follicular helper T cell / BCL6 / T細胞リンパ腫 / メチル化

Outline of Final Research Achievements

Angioimmunoblastic T-cell lymphoma (AITL) is a hematologic malignancy. AITL tumor cells have features of follicular helper T cells. Loss-of-function mutations in TET2, encoding an epigenetic regulator, are frequently found in AITL samples. We clarified mechanisms of AITL development using a lymphoma model in Tet2 gene-trap mice, and genomic analysis of human AITL. TET2 gene-trap mice developed lymphoma having features of follicular helper T cells, accompanying hypermehtylation of silencer of Bcl6. We also identified RHOA mutations as well as TET2 mutations in 70% of AITL samples.

Research Products

• [Journal Article] Variegated RHOA mutations in adult T-cell leukemia/lymphoma (2016)
  • Author(s): Nagata Y, Kontani K, Enami T, Kataoka K, Ishii R, Totoki Y, Kataoka TR, Hirata M, Aoki K, Nakano K, Kitanaka A, Sakata-Yanagimoto M, Egami S, Shiraishi Y, Chiba K, Tanaka H, Shiozawa Y, Yoshizato T, (9名), Miyano S, Nureki O, Shibata T, Haga H, Shimoda K, Katada T, Chiba S, Watanabe T, Ogawa S
  • Journal Title: Blood Volume: 127 Issue: 5 Pages: 596-604
  • DOI: 10.1182/blood-2015-06-644948
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A nationwide survey of co-occurrence of malignant lymphomas and myelodysplastic syndromes/myeloproliferative neoplasms. (2016)
  • Author(s): Sakata-Yanagimoto M, Yokoyama Y, Muto H, Obara N, Kurita N, Kato T, Hasegawa Y, Miyazaki Y, Kurokawa M, Chiba S
  • Journal Title: Annals of Hematology Volume: 98 Issue: 5 Pages: 829-830
  • DOI: 10.1007/s00277-016-2612-3
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of a fusion gene composed of a Hippo pathway gene MST2 and a common translocation partner ETV6 in a recurrent translocation t(8;12)(q22;p13) in acute myeloid leukemia. (2015)
  • Author(s): Ogawa S, Yokoyama Y, Suzukawa K, Nanmoku T, Kurita N, Seki M, Maie K, Suyama T, Takaiwa N, Sakata-Yanagimoto M, Obara N, Hasegawa Y, Chiba S
  • Journal Title: Annals of Hematology Volume: 94 Issue: 8 Pages: 1431-1433
  • DOI: 10.1007/s00277-015-2391-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] G17V RHOA: Genetic evidence of GTP-unbound RHOA playing a role in tumorigenesis in T cells. (2015)
  • Author(s): Chiba S, Enami T, Ogawa S, Sakata-Yanagimoto M.
  • Journal Title: Small GTPases Volume: 6 Issue: 2 Pages: 100-103
  • DOI: 10.4161/21541248.2014.988088
  • Peer Reviewed
• [Journal Article] Age-Dependent Decrease of DNA Hydroxymethylation in Human T Cells (2015)
  • Author(s): Truong TP, Sakata-Yanagimoto M, Yamada M, Nagae G, Enami T, Nakamoto-Matsubara R, Aburatani H, Chiba S.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 55 Issue: 1 Pages: 1-6
  • DOI: 10.3960/jslrt.55.1
  • NAID: 130005083797
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] Improvement of Renal Function by Long-Term Sustained Eculizumab Treatment in a Patient with Paroxysmal Nocturnal Hemoglobinuria. (2015)
  • Author(s): Ninomiya H, Obara N, Niiori-Onishi A, Yokoyama Y, Sakata-Yanagimoto M, Hasegawa Y, Chiba S
  • Journal Title: Case Reports in Hematology Volume: 673195 Pages: 1-4
  • DOI: 10.1155/2015/673195
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Complete Remission in Systemic Skin Interdigitating Dendritic Cell Sarcoma after ABVD Chemotherapy (2015)
  • Author(s): Kyogoku C, Seki M, Ogawa S, Miyamoto K, Ito Y, Kurita N, Yokoyama Y, Sakata-Yanagimoto M, Obara N, Hasegawa Y, Fujishima F, Ichinohasama R, Nakamura S, Chiba S.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 55 Issue: 1 Pages: 33-37
  • DOI: 10.3960/jslrt.55.33
  • NAID: 130005083796
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] Late occurrence of Epstein-Barr virus-associated lymphoproliferative disorder in a patient with follicular lymphoma treated with bendamustine and rituximab. (2015)
  • Author(s): Muroi K, Sakata-Yanagimoto M, Sato T, Yokoyama Y, Maie K, Kurita N, Obara N, Hasegawa Y, Noguchi M, Chiba S.
  • Journal Title: Annals of Hematology Volume: 94 Issue: 12 Pages: 2061-2062
  • DOI: 10.1007/s00277-015-2463-3
  • NAID: 120007134139
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Molecular mechanisms of angioimmunoblastic T-cell lymphoma (2015)
  • Author(s): Sakata-Yanagimoto M.
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 3 Pages: 246-252
  • DOI: 10.11406/rinketsu.56.246
  • NAID: 130005065344
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Acute painful crisis in a female Nigerian patient with sickle cell disease (2015)
  • Author(s): Nin S, Seki M, Maie K, Kuroda A, Miyamoto K, Ogawa S, Ito Y, Kurita N, Yokoyama Y, Sakata Yanagimoto M, Obara N, Hasegawa Y, Ogino Y, Ito T, Chiba S.
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 1 Pages: 30-34
  • DOI: 10.11406/rinketsu.56.30
  • NAID: 130004920690
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed / Open Access
• [Journal Article] Double somatic mosaic mutations in TET2 and DNMT3A-origin of peripheral T cell lymphoma in a case. (2015)
  • Author(s): Nguyen TB, Sakata-Yanagimoto M, Nakamoto-Matsubara R, Enami T, Ito Y, Kobayashi T, Obara N, Hasegawa Y, Chiba S.
  • Journal Title: Ann Hematol. Volume: inpress
  • Peer Reviewed
• [Journal Article] Multistep tumorigenesis in peripheral T cell lymphoma. (2015)
  • Author(s): Sakata-Yanagimoto M.
  • Journal Title: Int J Hematol. Volume: inpress
  • Peer Reviewed
• [Journal Article] Notch2 signaling in mast cell development and distribution in the intestine. (2015)
  • Author(s): Sakata-Yanagimoto M, Chiba S.
  • Journal Title: Methods Mol Biol. Volume: 1220 Pages: 79-89
  • DOI: 10.1007/978-1-4939-1568-2_6
  • ISBN: 9781493915675, 9781493915682
  • Peer Reviewed
• [Journal Article] Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice. (2014)
  • Author(s): Muto H, Sakata-Yanagimoto M, Nagae G, Shiozawa Y, Miyake Y, Yoshida K, Enami T, Kamada Y, Kato T, Uchida K, Nanmoku T, Obara N, Suzukawa K, Sanada M, Nakamura N, Aburatani H, Ogawa S, Chiba S
  • Journal Title: Blood Cancer J. Volume: 12 Issue: 12 Pages: e264-e264
  • DOI: 10.1038/bcj.2014.83
  • Peer Reviewed / Open Access
• [Journal Article] Detection of the G17V RHOA mutation in angioimmunoblastic T-cell lymphoma and related lymphomas using quantitative allele-specific PCR (2014)
  • Author(s): Nakamoto-Matsubara R, Sakata-Yanagimoto M, Enami T, Yoshida K, Yanagimoto S, Shiozawa Y, Nanmoku T, Satomi K, Muto H, Obara N, Kato T, Kurita N, Yokoyama Y, Izutsu K, Ota Y, Sanada M, Shimizu S, Komeno T, Sato Y, Ito T, Kitabayashi I, Takeuchi K, Nakamura N, Ogawa S, Chiba S.
  • Journal Title: PLoS ONE Volume: 9 Issue: 10 Pages: e109714-e109714
  • DOI: 10.1371/journal.pone.0109714
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disease-Specific Mutations in Mature Lymphoid Neoplasms-Recent Advances (2014)
  • Author(s): Sakata-Yanagimoto M, Enami T, Yokoyama Y, Chiba S
  • Journal Title: Cancer Science Volume: 105 Issue: 6 Pages: 623-629
  • DOI: 10.1111/cas.12408
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M, Yoshida K
  • Journal Title: Nature Genet. Volume: 46 Issue: 2 Pages: 171-175
  • DOI: 10.1038/ng.2872
  • Peer Reviewed
• [Presentation] Clonal evolution in T-cell lymphoma: Tumor cells and beyond (2016)
  • Author(s): Mamiko Sakata-Yangimoto, Shigeru Chiba
  • Organizer: 10th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: from Biology to Therapeutics
  • Place of Presentation: Hawaii、USA
  • Year and Date: 2016-02-10
  • Invited
• [Presentation] ゲノム解析に基づいた個別化治療-血管免疫芽球性T細胞リンパ腫 (2015)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2015-10-29
  • Invited
• [Presentation] Molecular mechanisms of the development of peripheral T-cell lymphoma (2015)
  • Author(s): Mamiko Sakata-Yanagimoto, Shigeru Chiba
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 金沢、石川県立音楽堂
  • Year and Date: 2015-10-16
  • Invited
• [Presentation] Pathogenic mechanisms in angioimmunoblastic T-cell lymphoma (2015)
  • Author(s): Mamiko Sakata-Yanagimoto
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] T細胞リンパ腫におけるRHＯA変異 (2015)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第9回北海道病理医会共催プログラム
  • Place of Presentation: 札幌、北海道大学
  • Year and Date: 2015-08-22
  • Invited
• [Presentation] 血液がんの薬物療法-内服薬の進歩と課題 (2015)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 文部科学省がんプロフェッショナル養成基盤推進プラン採択事業 市民公開シンポジウム がんの薬物治療，現在と未来
  • Place of Presentation: 野田、東京理科大学野田キャンパス
  • Year and Date: 2015-06-27
  • Invited
• [Presentation] 末梢性T細胞リンパ腫のクローン進化 (2015)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第19回日本がん分子標的治療学会学術集会
  • Place of Presentation: 松山、松山全日空ホテル
  • Year and Date: 2015-06-10
  • Invited
• [Presentation] A Nation-wide Survey of Co-occurrence of Malignant Lymphoma and Myelodysplastic Syndromes/Myeloproliferative Neoplasms (2015)
  • Author(s): Mamiko Sakata-Yanagimoto
  • Organizer: The 6th JSH International Symposium 2015 in KARUIZAWA
  • Place of Presentation: 軽井沢、軽井沢プリンスホテルウエスト
  • Year and Date: 2015-05-22
  • Int'l Joint Research
• [Presentation] 血管免疫芽球性T細胞リンパ腫におけるRHOA変異 (2015)
  • Author(s): 坂田(柳元）麻実子
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-05-01
  • Invited
• [Presentation] T細胞リンパ腫におけるRHOA変異. (2015)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第5回 臨床血液病理研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-02-27
  • Invited
• [Presentation] Somatic RHOA Mutation in Angioimmunoblastic T Cell Lymphoma. (2015)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: The 30th Nagoya International Cancer Treatment Symposium
  • Place of Presentation: 名古屋
  • Year and Date: 2015-02-14 – 2015-02-15
  • Invited
• [Presentation] Discrimination of mutations arising in premalignant cells and those in lymphoma cells in AITL. (2015)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 7th Annual T-Cell Lymphoma Forum
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2015-01-29 – 2015-01-31
  • Invited
• [Presentation] 教育講演「造血器腫瘍におけるTET2異常」 (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第76回 日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] Mutations in epigenetic and metabolic regulators in peripheral T-cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第76回 日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] Multistep tumorigenesis in peripheral T-cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第76回 日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] Multistep tumorigenesis in peripheral T-cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 2014 Lymphoma Symposium ZENYAKU
  • Place of Presentation: 東京
  • Year and Date: 2014-10-11
  • Invited
• [Presentation] Premalignant and disease-specific mutations in age-related hematologic malignancies. (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第5回 つくばグローバルサイエンスウィーク 2014 (Tsukuba Global Science Week 2014)
  • Place of Presentation: つくば
  • Year and Date: 2014-09-28 – 2014-09-30
• [Presentation] Multistep tumorigenesis in peripheral T-cell lymphoma (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] Identification of multistep genetic abnormalities in angioimmunoblastic T-cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] T 細胞リンパ腫におけるクローン進化のメカニズム (2014)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第2回 ブリストル血液学アカデミー
  • Place of Presentation: 京都
  • Year and Date: 2014-09-20
  • Invited
• [Presentation] 末梢性T細胞リンパ腫における多段階発がん (2014)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第32回 日本ヒト細胞学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-08-30 – 2014-08-31
  • Invited
• [Presentation] Somatic RHOA mutation in angioimmunoblastic T cell lymphoma (2014)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第10回 麒麟塾
  • Place of Presentation: 東京
  • Year and Date: 2014-07-12
• [Presentation] T細胞リンパ腫におけるエピゲノム経路異常 (2014)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第2回 がんと代謝研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-10 – 2014-07-11
  • Invited
• [Presentation] Discrimination of Mutations Arising in Pre-malignant Cells and Those in Lymphoma Cells in Angioimmunoblasitc T-cell Lymphoma (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 第54回 日本リンパ網内系学会総会
  • Place of Presentation: 山形
  • Year and Date: 2014-06-19 – 2014-06-21
• [Presentation] Multi-step tumorigenesis in peripheral T-cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: Malignant Lymphoma Academy 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-06-14 – 2014-06-15
  • Invited
• [Presentation] Impaired RHOA Function Leads to Development of Angioimmunoblastic T-Cell Lymphoma (2014)
  • Author(s): Terukazu Enami
  • Organizer: 19th Congress of the EHA 2014
  • Place of Presentation: ミラノ
  • Year and Date: 2014-06-12 – 2014-06-15
• [Presentation] 末梢性T細胞リンパ腫における多段階発がん (2014)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第12回先端血液学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2014-06-07
  • Invited
• [Presentation] Discrimination of mutations arising in pre-malignant cells and those in lymphoma cells in angioimmunoblasitc t-cell lymphoma. (2014)
  • Author(s): Sakata-Yanagimoto M, Chiba S.
  • Organizer: 第12回幹細胞シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-30 – 2014-05-31
• [Presentation] Multistep tumorigenesis in peripheral T-cell lymphoma (2014)
  • Author(s): Sakata-Yanagimoto M.
  • Organizer: 6th T-cell Lymphoma Forum
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Reduced Tet2 function contributes to development of T-cell Lymphoma with follicular helper T-cell like features through epigenetic dysregulation (2014)
  • Author(s): Muto H, Sakata-Yanagimoto M, et al.
  • Organizer: 6th T-cell Lymphoma Forum
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Somatic G17V Rhoa Mutation Specifies Angioimmunoblastic T-Cell Lymphoma (2013)
  • Author(s): Sakata-Yanagimoto M, et al.
  • Organizer: The American Society of Hematology 55th Annual Meeting and Exposition
  • Place of Presentation: New Orleans, LA,USA
• [Presentation] A Novel Diagnostic Method For AITL By Detecting RHOA G17V Hotspot Mutation Using Allele-Specific Real-Time PCR (2013)
  • Author(s): Nakamoto-Matsubara R, Sakata-Yanagimoto M, et al.
  • Organizer: The American Society of Hematology 55th Annual Meeting and Exposition
  • Place of Presentation: New Orleans, LA,USA
• [Presentation] Hypermethylation of Bcl6 Is a Potential Cause of Development of Lymphoma with Tfh Features in Tet2 Knockdown Mice (2013)
  • Author(s): Muto H, Sakata-Yanagimoto M, et al.
  • Organizer: The American Society of Hematology 55th Annual Meeting and Exposition
  • Place of Presentation: New Orleans, LA,USA
• [Presentation] Age-dependent decrease of hydroxymethylcytosine in T cells (2013)
  • Author(s): Phu Truong, Sakata-Yanagimoto M, et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Distinct gene mutation profils in angioimmunoblastic T-cell lympoma (2013)
  • Author(s): Sakata-Yanagimoto M et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Novel diagnostic method using specific mutations for AITL (2013)
  • Author(s): Nakamoto-Matsubara R, Sakata-Yanagimoto M, et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] TET2 binds and regulates O-linked N-acetylglucosamine transferase (2013)
  • Author(s): Enami T, Sakata-Yanagimoto M, et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Bcl6 is hypermethylated in lymphomas developed in Tet2 knockdown mice (2013)
  • Author(s): Muto H, Sakata-Yanagimoto M, et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Specific mutation profiles in angioimmunoblastic T-cell lymphoma (2013)
  • Author(s): Sakata-Yanagimoto M, et al.
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] TET2 as a gate keeper for lymphoid malignancies (2013)
  • Author(s): Muto H, et al.
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] TET2 binds and regulates O-linked N-acetylblucosamine transferase (2013)
  • Author(s): Enami T, Sakata-Yanagimoto M, et al.
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Novel diagnostic method using specific mutations for AITL (2013)
  • Author(s): Matsubara-Nakamoto R, Sakata-Yanagimoto M, et al.
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Patent(Industrial Property Rights)] Detection technology for T cell lymphoma (2014)
  • Inventor(s): 千葉滋、柳元麻実子、小川誠司
  • Industrial Property Rights Holder: 千葉滋、柳元麻実子、小川誠司
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-05-01
  • Overseas
• [Patent(Industrial Property Rights)] T細胞リンパ腫の検出方法 (2013)
  • Inventor(s): 千葉滋、坂田（柳元）麻実子、小川誠司
  • Industrial Property Rights Holder: 千葉滋、坂田（柳元）麻実子、小川誠司
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-05-01