Optimization of therapeutic strategy for esophageal squamous cell carcinoma based on modeling of intratumoral heterogeneity using omics data and genome editing

• Project/Area Number: 26293304
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokushima
• Principal Investigator: IMOTO Issei 徳島大学, 大学院医歯薬学研究部, 教授 (30258610)
• Co-Investigator(Kenkyū-buntansha): 丹黒 章 徳島大学, 大学院医歯薬学研究部, 教授 (10197593) ; 高山 哲治 徳島大学, 大学院医歯薬学研究部, 教授 (10284994)
• Co-Investigator(Renkei-kenkyūsha): YANAGAWA Hiroaki 徳島大学, 病院, 准教授 (50263827) ; OTSUJI Eigo 京都府立医科大学, 医学(系)研究科, 教授 (20244600) ; TAJIMA Atsushi 徳島大学, 大学院医歯薬学研究部, 准教授 (10396864) ; MASUDA Kiyoshi 徳島大学, 大学院医歯薬学研究部, 准教授 (00457318)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: ゲノム / オミックス / 分子プロファイリング / ゲノム編集 / 食道癌 / シミュレーション / 食道扁平上皮癌 / 癌 / 腫瘍内不均一性

Outline of Final Research Achievements

To optimize therapeutic strategy overcoming the therapy resistance, recurrence, and metastasis for realizing the personalized medicine in patients with ESCC, we have detected intratumoral heterogeneity and estimated the clonal structure and its association with functional features of tumor based on the simulation by omics data modeling using tumors and plasma DNAs and experimental validation using genome editing technology. Novel molecular targets for ESCC were identified using integrated data. In addition, we have developed highly efficient mutation-introducing methods into cell lines using Crispr/Cas9 system, selected mutated clones by various reagents including anti-cancer reagents, and determined the pattern of mutations necessary for the therapy resistance in ESCC.

Research Products

• [Int'l Joint Research] Thomas Jefferson University(米国)
• [Journal Article] Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with gastric cancer. (2017)
  • Author(s): Shoda K, Ichikawa D, Fujita Y, Masuda K, Hiramoto H, Hamada J, Arita T, Konishi H, Kosuga T, Komatsu S, Shiozaki A, Okamoto K, Imoto I, Otsuji E.
  • Journal Title: Oncotarget Volume: 17 Issue: 17 Pages: 28796-28804
  • DOI: 10.18632/oncotarget.15675
  • NAID: 120006306639
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome. (2017)
  • Author(s): Matsudate Y, Naruto T, Hayashi Y, Minami M, Tohyama M, Yokota K, Yamada D, Imoto I, Kubo Y.
  • Journal Title: J Dermatol Sc Volume: 印刷中 Issue: 3 Pages: 206-211
  • DOI: 10.1016/j.jdermsci.2017.02.282
  • Peer Reviewed
• [Journal Article] A 590 kb deletion caused by non-allelic homologous recombination between two LINE-1 elements in a patient with mesomelia-synostosis syndrome. (2017)
  • Author(s): Kohmoto T, Naruto T, Watanabe M, Fujita Y, Ujiro S, Okamoto N, Horikawa H, Masuda K, Imoto I.
  • Journal Title: Am J Med Genet A Volume: 173 Issue: 4 Pages: 1082-1086
  • DOI: 10.1002/ajmg.a.38122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection. (2017)
  • Author(s): Okamoto N, Watanabe M, Naruto T, Matsuda K, Kohmoto T, Saito M, Masuda K, Imoto I.
  • Journal Title: Hum Genome Var Volume: 4 Issue: 1 Pages: 16045-16045
  • DOI: 10.1038/hgv.2016.45
  • NAID: 120006955876
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma (2017)
  • Author(s): K.Kajiura, K.Masuda, T.Naruto, T.Kohmoto, M.Watanabe, M.Tsuboi, H.Takizawa, K.Kondo, A.Tangoku, I.Imoto
  • Journal Title: Oncotarget Volume: 8 Issue: 2 Pages: 2890-2905
  • DOI: 10.18632/oncotarget.13761
  • Peer Reviewed / Open Access
• [Journal Article] Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer. (2017)
  • Author(s): Shoda K, Ichikawa D, Fujita Y, Masuda K, Hiramoto H, Hamada J, Arita T, Konishi H, Komatsu S, Shiozaki A, Kakihara N, Okamoto K, Taniguchi H, Imoto I, Otsuji E.
  • Journal Title: Gastric Cancer Volume: 1 Issue: 1 Pages: 126-135
  • DOI: 10.1007/s10120-016-0599-z
  • NAID: 40021062596
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Detection of 1p36 deletion by clinical exome-first diagnostic approach. (2016)
  • Author(s): Watanabe M, Horikawa H, et al.
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1
  • DOI: 10.1038/hgv.2016.6
  • Description: in press
  • Peer Reviewed / Open Access
• [Journal Article] Novel human mutation and CRISPR/Cas genome-edited mice reveal importance of C-terminal domain of MSX1 in tooth and palate development (2016)
  • Author(s): S.N.Mitsui, A.Yasue, K.Masuda, T.Naruto, Y.Minegishi, S.Oyadomari, S.Noji, I.Imoto, E.Tanaka
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 38398-38398
  • DOI: 10.1038/srep38398
  • Peer Reviewed / Open Access
• [Journal Article] Exome-first approach identified a novel gloss deletion associated with Lowe syndrome. (2016)
  • Author(s): Watanabe M, Nakagawa R, Kohmoto T, Naruto T, Suga K, Goji A, Horikawa H, Masuda K, Kagami S, Imoto I.
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1 Pages: 16037-16037
  • DOI: 10.1038/hgv.2016.37
  • NAID: 120006955875
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome. (2016)
  • Author(s): Kohmoto T, Shono M, Naruto T, Watanabe M, Suga K, Nakagawa R, Kagami S, Masuda K, Imoto I.
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1
  • DOI: 10.1038/hgv.2016.4
  • NAID: 120006955871
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel COL11A1 missense mutation in siblings with non-ocular Stickler syndrome (2016)
  • Author(s): Kohmoto T, Tsuji A, Morita K, Naruto T, Masuda K, Kashimada K, Enomoto K, Morio T, Harada H, Imoto I
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1 Pages: 16003-16003
  • DOI: 10.1038/hgv.2016.3
  • Peer Reviewed / Open Access
• [Journal Article] A novel missense mutation of COL5A2 in a patient with Ehlers-Danlos syndrome. (2016)
  • Author(s): Watanabe M, Nakagawa R, Naruto T, Kohmoto T, Suga K, Goji A, Kagami S, Masuda K, Imoto I.
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1 Pages: 16030-16030
  • DOI: 10.1038/hgv.2016.30
  • NAID: 120006955874
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-203 Suppresses Invasion and Epithelial-mesenchymal Transition Induction via Targeting NUAK1 and SNAI2 in Head and Neck Cancer (2016)
  • Author(s): Obayashi, M., Yoshida, M., Tsunematsu, T., Ogawa, I., Sasahira, T., Kuniyasu, H., Imoto, I., Abiko, Y., Xu, D., Fukunaga, S., Tahara, H., Kudo, Y., Nagao, T., Takata, T.
  • Journal Title: Oncotarget Volume: 6972 Issue: 7 Pages: 8223-39
  • DOI: 10.18632/oncotarget.6972
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma (2015)
  • Author(s): Hamada J, Shoda K, Masuda K, Fujita Y, Naruto T, Kohmoto T, Miyakami Y, Watanabe M, Kudo Y, Fujiwara H, Ichikawa D, Otsuji E, Imoto I
  • Journal Title: Oncotarget Volume: - Issue: 13 Pages: 17111-17128
  • DOI: 10.18632/oncotarget.7937
  • NAID: 120006240043
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel COL11A1 mutation affecting splicing in a apatient with Stickler syndrome (2015)
  • Author(s): Tomohiko Kohmoto,Takuya Naruto, Haruka Kobayashi, Miki Watanabe, Nana Okamoto, Kiyoshi Masuda, Issei Imoto, Nobuhiko Okamoto
  • Journal Title: Human Genome Variation Volume: 2 Issue: 1 Pages: 15043-15043
  • DOI: 10.1038/hgv.2015.43
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Simultaneous detection of both single nucleotide variations and copy number alterations by next-generation sequencing in Gorlin syndrome (2015)
  • Author(s): Morita K, Naruto T, Tanimoto K, Yasukawa C, Oikawa Y, Masuda K, Imoto I, Inazawa J, Omura K, Harada H.
  • Journal Title: PLoS One Volume: 10 Issue: 11 Pages: e0140480-e0140480
  • DOI: 10.1371/journal.pone.0140480
  • NAID: 120006871193
  • Peer Reviewed / Open Access
• [Journal Article] A unique TBX5 microdeletion with microinsertion detected in patient with Holt-Oram syndrome. (2015)
  • Author(s): Morine M, et al.
  • Journal Title: Am J Med Genet A Volume: 167 Issue: 12 Pages: 3192-3196
  • DOI: 10.1002/ajmg.a.37359
  • Peer Reviewed
• [Journal Article] HER2 amplification detected in the circulating DNA of patients with gastric cancer: a retrospective pilot study. (2015)
  • Author(s): Shoda K, Masuda K, Ichikawa D, Arita T, Miyagami Y, Watanabe M, Konishi H, Imoto I, Otsuji E.
  • Journal Title: Gastric Cancer Volume: 18 Issue: 4 Pages: 698-710
  • DOI: 10.1007/s10120-014-0432-5
  • NAID: 40020631406
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers (2015)
  • Author(s): S.Honda, P.Loher, M.Shigematsu, JP.Palazzo, R.Suzuki, I.Imoto, I.Rigoutsos, Y.Kirino
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 112 Issue: 29 Pages: 3816-3825
  • DOI: 10.1073/pnas.1510077112
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Deep intronic GPR143 mutation in a Japanese family with ocular albinism. (2015)
  • Author(s): Naruto T, Okamoto N, Masuda K, Endo T, Hatsukawa Y, Kohmoto T, Imoto I.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 11334-11334
  • DOI: 10.1038/srep11334
  • NAID: 120006875681
  • Peer Reviewed / Open Access
• [Journal Article] A FRMD7 variant in a Japanese family causes congenital nystagmus. (2015)
  • Author(s): Kohmoto T, Okamoto N, Satomura S, Naruto T, Komori T, Hashimoto T, Imoto I.
  • Journal Title: Hum Genome Variation Volume: 2 Issue: 1 Pages: 15002-15002
  • DOI: 10.1038/hgv.2015.2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P (2015)
  • Author(s): Inoue A, Okamoto K, Fujino Y, Nakagawa T, Muguruma N, Sannomiya K, Mitsui Y, Takaoka T, Kitamura S, Miyamoto H, Okahisa T, Fujimori T, Imoto I, Takayama T
  • Journal Title: Br J Cancer Volume: 112 Issue: 2 Pages: 403-412
  • DOI: 10.1038/bjc.2014.545
  • Peer Reviewed
• [Journal Article] Overexpression of SMYD2 contributes to malignant outcome in gastric cancer (2014)
  • Author(s): Komatsu S, Ichikawa D, Hirajima S, Nagata H, Nishimura Y, Kawaguchi T, Miyamae M, Okajima W, Ohashi T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Tsuda H, Imoto I, Inazawa J, Otsuji E
  • Journal Title: Br J Cancer Volume: 112 Issue: 2 Pages: 357-64
  • DOI: 10.1038/bjc.2014.543
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer. (2014)
  • Author(s): Hosoda F, Inazawa J, et al.
  • Journal Title: Oncogene. Volume: in press Issue: 9 Pages: 1196-206
  • DOI: 10.1038/onc.2014.57
  • Peer Reviewed
• [Journal Article] A novel PTCH1 mutation in a patient with Gorlin syndrome. (2014)
  • Author(s): Okamoto N, Naruto T, Kohmoto T, Komori T, Imoto I
  • Journal Title: Hum Genome Variation Volume: 1 Issue: 1
  • DOI: 10.1038/hgv.2014.22
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hypomethylation of long interspersed nuclear element-1 (LINE-1) is associated with poor prognosis via activation of c-MET in hepatocellular carcinoma (2014)
  • Author(s): C. Zhu, T. Utsunomiya, T. Ikemoto, S. Yamada, Y. Morine, S. Imura, Y. Arakawa, C. Takasu, D. Ishikawa, I. Imoto, and M. Shimada
  • Journal Title: Ann Surg Onco Volume: 21 Issue: S4 Pages: 729-735
  • DOI: 10.1245/s10434-014-3874-4
  • Peer Reviewed
• [Journal Article] HuR regulates alternative splicing of the TRA2 β gene in human colon cancer cells under oxidative stress. (2014)
  • Author(s): Akaike Y, Masuda K, Kuwano Y, Nishida K, Kajita K, Kurokawa K, Satake Y, Shoda K, Imoto I, Rokutan K.
  • Journal Title: Mol Cell Biol Volume: 34 Issue: 15 Pages: 2857-73
  • DOI: 10.1128/mcb.00333-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific molecular signatures of non-tumor liver tissues may predict a risk for development of hepatocellular carcinoma (2014)
  • Author(s): Utsunomiya T, Shimada M, Morine Y, Tajima A, Imoto I
  • Journal Title: Cancer Sci Volume: 印刷中 Issue: 7 Pages: 749-754
  • DOI: 10.1111/cas.12431
  • Peer Reviewed
• [Journal Article] The expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer. (2014)
  • Author(s): Kikuchi R, Kikuchi Y, Tsuda H, Maekawa H, Kozaki KI, Imoto I, Tamai S, Shiotani A, Iwaya K, Sakamoto M, Sekiya T, Matsubara O
  • Journal Title: Human Cell Volume: 印刷中 Issue: 3 Pages: 121-128
  • DOI: 10.1007/s13577-014-0092-0
  • Peer Reviewed
• [Presentation] Frequent silencing of the candidate tumor suppressor TSLAC1 by promoter methylation in early stage lung adenocarcinoma. (2016)
  • Author(s): Kohmoto T, Kajiura K, Naruto T,Masuda K、Kondo K, Tangoku A, Imoto I.
  • Organizer: The 66th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-10-21
  • Int'l Joint Research
• [Presentation] Long interspersed nuclear element-1 (LINE1)-mediated 8q13 microdeletion detected in a Japanese case with mesomelia-synostoses syndrome. (2016)
  • Author(s): Imoto I, Naruto T, Kohmoto T, Watanabe M, Ujiro S, Masuda K.
  • Organizer: The 66th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-10-20
  • Int'l Joint Research
• [Presentation] がん体細胞変異検出の特性からみた検査の考え方 (2016)
  • Author(s): 井本逸勢
  • Organizer: 第23回日本遺伝子診療学会大会
  • Place of Presentation: イイノホール＆カンファレンスセンター（東京都・千代田区）
  • Year and Date: 2016-10-08
  • Invited
• [Presentation] 肺腺癌の早期からDNAメチル化により高頻度に発現抑制を受ける新規癌抑制遺伝子候補TSLAC1の同定 (2016)
  • Author(s): 成戸卓也、梶浦耕一郎、増田清士、近藤和也、丹黒章、井本逸勢
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-08
• [Presentation] EBV関連胃癌患者における遊離DNAの有用性の検討 (2016)
  • Author(s): 庄田勝俊、市川大輔、藤田悠司、増田清士、濵田隼一、有田智洋、小西博貴、小松周平、塩崎敦、岡本和真、井本逸勢、大辻英吾
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-07
• [Presentation] RNA結合蛋白質TIA1による食道癌進展機構の解明 (2016)
  • Author(s): 増田清士、濵田隼一、庄田勝俊、藤田悠司、井本逸勢
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-07
• [Presentation] 新規RNA結合蛋白質MRF1は癌関連microRNA発現以上を誘導し食道癌の進展を促進する (2016)
  • Author(s): 藤田悠司、増田清士、井本逸勢
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-07
• [Presentation] 8q13 microdeletion in a Japanese case with mesomelia-synostoses syndrome. (2016)
  • Author(s): Imoto I, Naruto T, Kohmoto T, Horikawa H, Masuda K.
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2016-04-04
  • Int'l Joint Research
• [Presentation] ゲノム構造解析を基盤とするがん研究 (2015)
  • Author(s): 井本逸勢
  • Organizer: 第52回日本口腔組織培養学会大会
  • Place of Presentation: 徳島大学長井記念ホール(徳島県徳島市)
  • Year and Date: 2015-11-21
  • Invited
• [Presentation] エクソーム解析で潜在性エクソンを活性化させるGPR143 の深部イントロン変異を検出した眼白子症の家族例 (2015)
  • Author(s): 井本逸勢、成戸卓也、増田清士、河本知大、遠藤高生、初川嘉一、岡本伸彦.
  • Organizer: 第60回日本人類遺伝学会大会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-14
• [Presentation] アレイ法による網羅的DNAメチル化解析・ゲノム構造解析 (2015)
  • Author(s): 井本逸勢
  • Organizer: 第33回日本染色体遺伝子検査学会学術集会
  • Place of Presentation: かがわ国際会議場（香川県高松市）
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] Identification of a RNA binding protein, SSP1, inducing cell growth in esophageal squamous cell carcinoma (ESCC)through posttranscriptional regulation of target genes. (2015)
  • Author(s): Imoto I, Masuda K, Shoda K, Hamada J.
  • Organizer: American Association for Cancer Research Annual Meeting 2015
  • Place of Presentation: Philadelphia PA, USA
  • Year and Date: 2015-04-18
• [Presentation] Overexpression of SMYD2 contributes to malignant outcome in gastric cancer. (2014)
  • Author(s): Hirajima S, Komatsu S, Ichikawa D, Nagata H, Nishimura Y, Konishi H, Shiozaki A, Okamoto K, Tsuda H, Imoto I, Inazawa J, Otsuji E.
  • Organizer: 第７３回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-27
• [Presentation] A novel RNA binding protein, SSP1, induced cell growth in squamous cell carcinoma through posttranscriptional regulation. (2014)
  • Author(s): Masuda K, Shoda K, Hamada J, Imoto I.
  • Organizer: 第７３回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25
• [Presentation] HER2 amplification detected in the circulating DNA of patients with gastric cancer: a retrospective pilot study. (2014)
  • Author(s): Shoda K, Masuda K, Ichikawa D, Arita T, Konishi H, Imoto I, Otsuji E.
  • Organizer: 第７３回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25
• [Presentation] Identification of a novel tumor-suppressor gene through methylome analysis in smoking-associated lung adenocarcinoma. (2014)
  • Author(s): Imoto I.
  • Organizer: American Association for Cancer Reseach (AACR) Annual Meeting 2014
  • Place of Presentation: 米国・San Diego
  • Year and Date: 2014-04-06
• [Remarks] 徳島大学医学部人類遺伝学分野
  • URL: http://www.tokushima-u.ac.jp/med/culture/jinruiiden/
• [Remarks] 徳島大学医学部人類遺伝学分野
  • URL: http://jiniden.ait231.tokushima-u.ac.jp/web/
• [Remarks] 徳島大学医学部・人類遺伝学分野
  • URL: http://www.tokushima-u.ac.jp/med/culture/jinruiiden/
• [Remarks] 徳島大学医歯薬学研究部・人類遺伝学分野
  • URL: http://jiniden.ait231.tokushima-u.ac.jp/web/
• [Remarks] 教室ホームページ
  • URL: http://www.tokushima-u.ac.jp/med/culture/jinruiiden/