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口腔扁平上皮癌における新規遠隔転移抑制治療の開発

Research Project

Project/Area Number 23K20333
Project/Area Number (Other) 20H03888 (2020-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2020-2023)
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionOkayama University

Principal Investigator

長塚 仁  岡山大学, 医歯薬学域, 教授 (70237535)

Co-Investigator(Kenkyū-buntansha) 山近 英樹  独立行政法人国立病院機構岡山医療センター(臨床研究部), 独立行政法人国立病院機構 岡山医療センター(臨床研究部), 歯科医師 (10294422)
中野 敬介  岡山大学, 医歯薬学域, 准教授 (10325095)
河合 穂高  岡山大学, 医歯薬学域, 研究准教授 (10803687)
江口 傑徳  岡山大学, 医歯薬学域, 講師 (20457229)
高畠 清文  岡山大学, 医歯薬学域, 助教 (70736537)
辻極 秀次  岡山理科大学, 理学部, 教授 (70335628)
Project Period (FY) 2020-04-01 – 2025-03-31
Project Status Declined (Fiscal Year 2024)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2024: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords前転移niche / 口腔扁平上皮癌 / 頭頸部癌 / 骨髄由来細胞 / 骨髄移植 / 転移niche / 転移
Outline of Research at the Start

口腔扁平上皮癌は発生初期段階からリンパ節転移を起こすことが知られており、転移の成立した症例は予後が著しく悪く、転移を早期に察知、抑制することは患者のQOLの向上に繋がる。近年、腫瘍が遠隔臓器に転移する際に形成される「前転移niche」の重要性が指摘されており、骨髄由来細胞がその形成に大きな役割を果たすことが報告されている。しかし、口腔癌における前転移nicheと骨髄由来細胞の関係は未だ明らかとなっていない。本研究は、口腔癌の前転移niche形成に関わる骨髄由来細胞に着目し、そのメカニズムを解明することで、前転移niche形成抑制に着目した、新規腫瘍転移抑制治療の開発を目的としている。

Outline of Annual Research Achievements

口腔扁平上皮癌は発生初期段階からリンパ節転移を起こすことが知られており、転移の成立した症例は予後が著しく悪く、転移を早期に察知、抑制することは 患者のQOLの向上に繋がる。近年、腫瘍が遠隔臓器に転移する際に形成される「前転移niche」の重要性が指摘されており、骨髄由来細胞がその形成に大きな役割 を果たすことが報告されている。しかし、口腔癌における前転移nicheと骨髄由来細胞の関係は未だ明らかとなっていない。本研究は、口腔癌の前転移niche形成 に関わる骨髄由来細胞に着目し、そのメカニズムを解明することで、前転移niche形成抑制に着目した、新規腫瘍転移抑制治療の開発を目的としている。本年は昨年、転移や腫瘍の生存に重要な役割を果たすことが明らかとなった、CCR2陽性BMDCのプロファイルを明らかとするためOPALを用いた多重染色を再度実施し、同細胞がGr1, CD11b陽性の骨髄由来免疫抑制細胞であることが明らかとなった。

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

Report

(4 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (35 results)

All 2024 2023 2022 2021 2020

All Journal Article (22 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 22 results,  Open Access: 22 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Rab11 suppresses head and neck carcinoma by regulating EGFR and EpCAM exosome secretion2024

    • Author(s)
      Yoshida Kunihiro、Htike Kaung、Eguchi Takanori、Kawai Hotaka、Eain Htoo Shwe、Tran Manh Tien、Sogawa Chiharu、Umemori Koki、Ogawa Tatsuo、Kanemoto Hideka、Ono Kisho、Nagatsuka Hitoshi、Sasaki Akira、Ibaragi Soichiro、Okamoto Kuniaki
    • Journal Title

      Journal of Oral Biosciences

      Volume: 66 Issue: 1 Pages: 205-216

    • DOI

      10.1016/j.job.2023.11.007

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polymeric Materials, Advances and Applications in Tissue Engineering: A Review2023

    • Author(s)
      Socci Maria Cecilia、Rodriguez Gabriela、Oliva Emilia、Fushimi Shigeko、Takabatake Kiyofumi、Nagatsuka Hitoshi、Felice Carmelo Jose、Rodriguez Andrea Paola
    • Journal Title

      Bioengineering

      Volume: 10 Issue: 2 Pages: 218-218

    • DOI

      10.3390/bioengineering10020218

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel Artificial Scaffold for Bone Marrow Regeneration: Honeycomb Tricalcium Phosphate2023

    • Author(s)
      Inada Yasunori、Takabatake Kiyofumi、Tsujigiwa Hidetsugu、Nakano Keisuke、Shan Qiusheng、Piao Tianyan、Chang Anqi、Kawai Hotaka、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 16 Issue: 4 Pages: 1393-1393

    • DOI

      10.3390/ma16041393

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Role of Hedgehog Signaling in the Melanoma Tumor Bone Microenvironment2023

    • Author(s)
      Shamsoon Karnoon、Hiraki Daichi、Yoshida Koki、Takabatake Kiyofumi、Takebe Hiroaki、Yokozeki Kenji、Horie Naohiro、Fujita Naomasa、Nasrun Nisrina Ekayani、Okui Tatsuo、Nagatsuka Hitoshi、Abiko Yoshihiro、Hosoya Akihiro、Saito Takashi、Shimo Tsuyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 10 Pages: 8862-8862

    • DOI

      10.3390/ijms24108862

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of deep learning classifiers in histopathological diagnosis of oral squamous cell carcinoma by pathologists2023

    • Author(s)
      Sukegawa Shintaro、Ono Sawako、Tanaka Futa、Inoue Yuta、Hara Takeshi、Yoshii Kazumasa、Nakano Keisuke、Takabatake Kiyofumi、Kawai Hotaka、Katsumitsu Shimada、Nakai Fumi、Nakai Yasuhiro、Miyazaki Ryo、Murakami Satoshi、Nagatsuka Hitoshi、Miyake Minoru
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1

    • DOI

      10.1038/s41598-023-38343-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enzyme‐Cleaved Bone Marrow Transplantation Improves the Engraftment of Bone Marrow Mesenchymal Stem Cells2023

    • Author(s)
      Kawai Hotaka、Oo May Wathone、Takabatake Kiyofumi、Tosa Ikue、Soe Yamin、Eain Htoo Shwe、Sanou Sho、Fushimi Shigeko、Sukegawa Shintaro、Nakano Keisuke、Takeshi Takarada、Nagatsuka Hitoshi
    • Journal Title

      JBMR Plus

      Volume: 7 Issue: 3 Pages: 1-10

    • DOI

      10.1002/jbm4.10722

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] EpEX, the soluble extracellular domain of EpCAM, resists cetuximab treatment of EGFR-high head and neck squamous cell carcinoma2023

    • Author(s)
      Umemori Koki、Ono Kisho、Eguchi Takanori、Kawai Hotaka、Nakamura Tomoya、Ogawa Tatsuo、Yoshida Kunihiro、Kanemoto Hideka、Sato Kohei、Obata Kyoichi、Ryumon Shoji、Yutori Hirokazu、Katase Naoki、Okui Tatsuo、Nagatsuka Hitoshi、Ibaragi Soichiro
    • Journal Title

      Oral Oncology

      Volume: 142 Pages: 106433-106433

    • DOI

      10.1016/j.oraloncology.2023.106433

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ligneous periodontitis exacerbated by Beh?et’s disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C?>?T: a case report2023

    • Author(s)
      Shinoda-Ito Yuki、Hirai Anna、Omori Kazuhiro、Ideguchi Hidetaka、Yamamoto Hideki、Kato Fumino、Obata Kyoichi、Ogawa Tatsuo、Nakano Keisuke、Nakadoi Takato、Katsuyama Eri、Ibaragi Soichiro、Yamamoto Tadashi、Nagatsuka Hitoshi、Hirasawa Akira、Takashiba Shogo
    • Journal Title

      BMC Oral Health

      Volume: 23 Issue: 1 Pages: 843-843

    • DOI

      10.1186/s12903-023-03586-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment2022

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Takabatake Kiyofumi、Tomida Shuta、Eguchi Takanori、Ono Kisho、Shan Qiusheng、Ohara Toshiaki、Yoshida Saori、Omori Haruka、Sukegawa Shintaro、Nakano Keisuke、Okamoto Kuniaki、Sasaki Akira、Nagatsuka Hitoshi
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1172/jci.insight.148960

    • NAID

      120007186650

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SOD3 Expression in Tumor Stroma Provides the Tumor Vessel Maturity in Oral Squamous Cell Carcinoma2022

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Eain Htoo Shwe、Soe Yamin、Takabatake Kiyofumi、Sanou Sho、Shan Qiusheng、Inada Yasunori、Fujii Masae、Fukuhara Yoko、Wang Ziyi、Sukegawa Shintaro、Ono Mitsuaki、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 11 Pages: 2729-2729

    • DOI

      10.3390/biomedicines10112729

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer2022

    • Author(s)
      Ono Kisho、Sato Kohei、Nakamura Tomoya、Yoshida Yume、Murata Shogo、Yoshida Kunihiro、Kanemoto Hideka、Umemori Koki、Kawai Hotaka、Obata Kyoichi、Ryumon Shoji、Hasegawa Kazuaki、Kunisada Yuki、Okui Tatsuo、Ibaragi Soichiro、Nagatsuka Hitoshi、Sasaki Akira
    • Journal Title

      International Journal of Medical Sciences

      Volume: 19 Issue: 8 Pages: 1320-1333

    • DOI

      10.7150/ijms.74109

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line derived xenograft model2022

    • Author(s)
      Shan Qiusheng、Takabatake Kiyofumi、Omori Haruka、Kawai Hotaka、Oo May、Sukegawa Shintaro、Fujii Masae、Inada Yasunori、Sano Sho、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Oncology Letters

      Volume: 24 Issue: 5 Pages: 382-382

    • DOI

      10.3892/ol.2022.13502

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes2022

    • Author(s)
      Shan Qiusheng、Takabatake Kiyofumi、Kawai Hotaka、Oo May、Inada Yasunori、Sukegawa Shintaro、Fushimi Shigeko、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Oncology Reports

      Volume: 47 Issue: 4 Pages: 1-10

    • DOI

      10.3892/or.2022.8292

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Crosstalk between cancer and different cancer stroma subtypes promotes the infiltration of tumor associated macrophages into the tumor microenvironment of oral squamous cell carcinoma2022

    • Author(s)
      Shan Qiusheng、Takabatake Kiyofumi、Kawai Hotaka、Oo May、Sukegawa Shintaro、Fujii Masae、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Oncology

      Volume: 60 Issue: 6 Pages: 1-10

    • DOI

      10.3892/ijo.2022.5368

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.2021

    • Author(s)
      Kayo Yoshida, Kaya Yoshida, Natsumi Fujiwara, Mariko Seyama, Kisho Ono, Hotaka Kawai, Jiajie Guo, Ziyi Wang, Yao Weng, Yaqiong Yu, Yoko Uchida-Fukuhara, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Hiroshi Kamioka, Hirohiko Okamura, Kazumi Ozaki
    • Journal Title

      Biochim Biophys Acta - Molecular Basis of Disease

      Volume: 1867 Issue: 11 Pages: 166236-166236

    • DOI

      10.1016/j.bbadis.2021.166236

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endoscopic-assisted resection of pleomorphic adenoma in the accessory parotid gland2021

    • Author(s)
      Hasegawa Kazuaki、Sukegawa Shintaro、Ono Sawako、Ando Midori、Shibata Akane、Sukegawa-Takahashi Yuka、Fujimura Ai、Matsuyama Tamamo、Ibaragi Soichiro、Nagatsuka Hitoshi、Mizobuchi Koichi、Sasaki Akira、Furuki Yoshihiko
    • Journal Title

      The Journal of Medical Investigation

      Volume: 68 Issue: 3.4 Pages: 376-380

    • DOI

      10.2152/jmi.68.376

    • NAID

      130008115663

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma2021

    • Author(s)
      Omori Haruka、Shan Qiusheng、Takabatake Kiyofumi、Nakano Keisuke、Kawai Hotaka、Sukegawa Shintaro、Tsujigiwa Hidetsugu、Nagatsuka Hitoshi
    • Journal Title

      Cancers

      Volume: 13 Issue: 14 Pages: 3491-3491

    • DOI

      10.3390/cancers13143491

    • NAID

      120007126502

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation of Absorption-Resistant Hard Tissue Using Dental Pulp-Derived Cells and Honeycomb Tricalcium Phosphate2021

    • Author(s)
      Takabatake Kiyofumi、Nakano Keisuke、Kawai Hotaka、Inada Yasunori、Sukegawa Shintaro、Qiusheng Shan、Fushimi Shigeko、Tsujigiwa Hidetsugu、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 14 Issue: 12 Pages: 3409-3409

    • DOI

      10.3390/ma14123409

    • NAID

      120007099350

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer-Associated Stromal Cells Promote the Contribution of MMP2-Positive Bone Marrow-Derived Cells to Oral Squamous Cell Carcinoma Invasion2021

    • Author(s)
      Oo May Wathone、Kawai Hotaka、Takabatake Kiyofumi、Shan Qiusheng、Eain Htoo Shwe、Sukegawa Shintaro、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Cancers

      Volume: 14 Issue: 1 Pages: 137-137

    • DOI

      10.3390/cancers14010137

    • NAID

      120007185107

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP2021

    • Author(s)
      Takabatake Kiyofumi、Tsujigiwa Hidetsugu、Yoshida Aki、Furumatsu Takayuki、Kawai Hotaka、Oo May Wathone、Nakano Keisuke、Nagatsuka Hitoshi
    • Journal Title

      Materials

      Volume: 14 Issue: 23 Pages: 7225-7225

    • DOI

      10.3390/ma14237225

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process2021

    • Author(s)
      Kawai Hotaka、Oo May Wathone、Tsujigiwa Hidetsugu、Nakano Keisuke、Takabatake Kiyofumi、Sukegawa Shintaro、Nagatsuka Hitoshi
    • Journal Title

      International Journal of Medical Sciences

      Volume: 18 Issue: 8 Pages: 1824-1830

    • DOI

      10.7150/ijms.51946

    • NAID

      120007019114

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of intramandibular neurofibroma resembling a radicular cyst in a neurofibromatosis type 1 patient2021

    • Author(s)
      Kunisada Yuki、Yoshioka Norie、Ibaragi Soichiro、Okui Tatsuo、Nagatsuka Hitoshi、Sasaki Akira
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 82 Pages: 105883-105883

    • DOI

      10.1016/j.ijscr.2021.105883

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 2022年度頭頸部腫瘍エキスパート育成講習会(3.口腔)2023

    • Author(s)
      長塚仁
    • Organizer
      2022年度エキスパート講習会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 骨髄由来間葉系幹細胞の新規採取技術および骨髄由来間葉系幹細胞移植法の確立2023

    • Author(s)
      河合 穂高,メイ ワト ウ,高畠 清文,佐能 彰,中野 敬介,宝田 剛,長塚 仁
    • Organizer
      第77回NPO法人日本口腔科学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 頭頸部領域(口腔・咽頭/喉頭・食道)における上皮内癌-病態と診断基準- 口腔の上皮内癌 病態の組織学的評価と診断2023

    • Author(s)
      長塚 仁
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 口腔癌間質由来のCCL2はCCR2陽性骨髄由来免疫抑制細胞の腫瘍間質への動員に関与する2023

    • Author(s)
      河合 穂高, メイ・ワトウ , 高畠 清文, 冨田 秀太, 小野 喜章, 江口 傑徳, 大原 利章, 中野 敬介, 長塚 仁
    • Organizer
      第26回日本がん免疫学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔癌間質細胞由来CCL2による骨髄由来細胞動員への関与2023

    • Author(s)
      河合 穂高、冨田 秀太、江口 傑徳、大原 利章、小野 喜章、長塚 仁
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] CCL2-CCR2 axisを介した癌関連線維芽細胞による骨髄由来細胞の動員2021

    • Author(s)
      河合 穂高,、メイワトウ、高畠 清文、大森 悠加、中野 敬介、長塚 仁
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 根治的頸部郭清術後に後頭リンパ節転移をきたした舌癌の一例2021

    • Author(s)
      小野 喜章, 吉岡 徳枝, 小畑 協一, 増井 正典, 岸本 晃治, 伊原木 聰一郎, 長塚 仁, 佐々木 朗
    • Organizer
      第45回日本頭頸部癌学会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 希少がん病理診断「頭頸部腫瘍・口腔」2021

    • Author(s)
      長塚 仁
    • Organizer
      厚生労働省国庫補助金事業 希少がん診断のための病理医育成事業 2021年度第2回希少がん病理診断講習会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 希少がん病理診断「頭頸部腫瘍・口腔」2021

    • Author(s)
      長塚 仁
    • Organizer
      厚生労働省国庫補助金事業 希少がん診断のための病理医育成事業 2021年度第2回希少がん病理診断エキスパート育成講習会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Diagnosis criteria for oral epithelial dysplasia and carcinoma in situ according to general rules for clinical and pathological studies on oral cancer2021

    • Author(s)
      Hitoshi Nagatsuka
    • Organizer
      The 12th Asia Pacific International Academy of Pathology Congress IPIAP
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口腔扁平上皮癌におけるCXCR4の腫瘍血管での役割2020

    • Author(s)
      大森 悠加, 河合 穂高, 吉田 沙織, 藤井 昌江, 単 秋生, 髙畠 清文, 中野 敬介, 長塚 仁
    • Organizer
      第31回日本臨床口腔病理学会 学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 口腔癌間質細胞が骨髄由来細胞の動員に与える影響2020

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Published: 2020-04-28   Modified: 2024-12-25  

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