Establishment of early diagnosis method and elucidation of developing mechanism for invasive moles with serum cell-free microRNA profile

• Project/Area Number: 15K10703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Chiba University
• Principal Investigator: Usui Hirokazu 千葉大学, 大学院医学研究院, 講師 (90375634)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 胞状奇胎 / セルフリー核酸 / 侵入奇胎 / 腫瘍マーカー / 絨毛性疾患 / 血清マーカー / miRNA

Outline of Final Research Achievements

The difference between invasive moles and hydatidiform moles has been unveiled. We cannot resect the focus of invasive moles because the patient would need her uterus for fertility preservation. We tried to detect the serum cell-free miRNA to profile the invasive moles. The miRNAs of has-miR-520b and has-517a-3p which are known to be highly expressed in hydatidiform moles were identified in serum cell-free RNA fraction of almost all pre-evacuated patients with hydatidiform moles. On the other hand, these miRNAs were detected in only 30% of invasive moles patients. To identify the specific miRNA of invasive moles, we need the further analysis of the large volume focus of invasive moles.

Research Products

• [Journal Article] Presence of the methylenetetrahydrofolate reductase gene polymorphism MTHFR C677T in molar tissue but not maternal blood predicts failure of methotrexate treatment for low-risk gestational trophoblastic neoplasia. (2017)
  • Author(s): Qu J, Usui H, Kaku H, Shozu M.
  • Journal Title: Eur J Pharmacol. Volume: 794 Pages: 85-91
  • DOI: 10.1016/j.ejphar.2016.11.010
  • Peer Reviewed
• [Journal Article] Complete hydatidiform moles are composed of paternal chromosomes and maternal mitochondria (2017)
  • Author(s): Pan Zijun、Usui Hirokazu、Sato Asuka、Shozu Makio
  • Journal Title: Mitochondrial DNA A DNA Mapp Seq Anal Volume: - Issue: 6 Pages: 1-8
  • DOI: 10.1080/24701394.2017.1389916
  • Peer Reviewed
• [Journal Article] The Efficacy of Palonosetron Plus Dexamethasone in Preventing Chemoradiotherapy-induced Nausea and Emesis in Patients Receiving Daily Low-dose Cisplatin-based Concurrent Chemoradiotherapy for Uterine Cervical Cancer: A Phase II Study (2017)
  • Author(s): Mitsuhashi A, Usui H, Nishikimi K, Yamamoto N, Hanawa S, Tate S, Watanabe-Nemoto M, Uno T, Shozu M
  • Journal Title: American journal of clinical oncology Volume: 40 Issue: 2 Pages: 118-21
  • DOI: 10.1097/coc.0000000000000117
  • Peer Reviewed
• [Journal Article] Comparison Between Pathological Diagnosis and Cytogenetic Diagnosis by Short Tandem Repeat Polymorphism Analysis of Suspected Molar Pregnancies (2016)
  • Author(s): Usui, H., Kiyokawa, T., Qu, J., Nishikimi, K., Tate, S., Mitsuhashi, A., Nakatani, Y., and Shozu, M
  • Journal Title: J Reprod Med Volume: 61 Pages: 219-23
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ovarian nongestational choriocarcinoma and associated adenocarcinoma with the same germ cell origin determined by a molecular genetic approach: A case report. (2016)
  • Author(s): Koyanagi T, Fujiwara H, Usui H, Ariga H, Machida S, Takei Y, Saga Y, Shozu M, Fukushima N, Niki T, Matsubara S, Suzuki M.
  • Journal Title: Pathol Int. Volume: 66 Issue: 9 Pages: 529-534
  • DOI: 10.1111/pin.12445
  • Peer Reviewed
• [Journal Article] Efficacy of palonosetron plus aprepitant in preventing chemoradiotherapy-induced nausea and emesis in patients receiving daily low-dose cisplatin-based concurrent chemoradiotherapy for uterine cervical cancer: a phase II study. (2016)
  • Author(s): Hanawa S, Mitsuhashi A, Matsuoka A, Nishikimi K, Tate S, Usui H, Uno T, Shozu M
  • Journal Title: Support Care Cancer Volume: 24(11) Issue: 11 Pages: 4633-8
  • DOI: 10.1007/s00520-016-3306-z
  • Peer Reviewed
• [Journal Article] Mature cystic teratomas arise from meiotic oocytes, but not from pre-meiotic oogonia. (2016)
  • Author(s): Kaku H, Usui H, Qu J, Shozu M.
  • Journal Title: Genes Chromosomes Cancer. Volume: 55(4) Issue: 4 Pages: 355-64
  • DOI: 10.1002/gcc.22339
  • Peer Reviewed
• [Journal Article] The tumor-suppressive microRNA-1/133a cluster targets PDE7A and inhibits cancer cell migration and invasion in endometrial cancer (2015)
  • Author(s): Yamamoto N, Nishikawa R, Chiyomaru T, Goto Y, Fukumoto I, Usui H, Mitsuhashi A, Enokida H, Nakagawa M, Shozu M, and Seki N
  • Journal Title: Int J Oncol Volume: 47 Issue: 1 Pages: 325-334
  • DOI: 10.3892/ijo.2015.2986
  • Peer Reviewed
• [Journal Article] Early pregnancy-associated cardiomyopathy complicated with a complete hydatidiform mole coexistent with a live fetus and exacerbated by induced abortion (2015)
  • Author(s): Saito Y, Takaoka H, Funabashi N, Hasegawa H, Ozawa K, Omoto A, Usui H, Shozu M, and Kobayashi Y
  • Journal Title: Int J Cardiol Volume: 198 Pages: 170-173
  • DOI: 10.1016/j.ijcard.2015.06.128
  • Peer Reviewed
• [Journal Article] The clinical characteristics and early detection of postpartum choriocarcinoma (2015)
  • Author(s): Ryu N, Ogawa M, Matsui H, Usui H, and Shozu M
  • Journal Title: Int J Gynecol Cancer Volume: 25 Issue: 5 Pages: 926-930
  • DOI: 10.1097/igc.0000000000000184
  • Peer Reviewed
• [Journal Article] Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia (2015)
  • Author(s): Kizaki S, Hashimoto K, Matsui H, Usui H, and Shozu M
  • Journal Title: Gynecol Oncol Volume: 139 Issue: 3 Pages: 429-432
  • DOI: 10.1016/j.ygyno.2015.10.007
  • Peer Reviewed
• [Journal Article] Tubal pregnancy associated with additional conception in a contralateral tube (2015)
  • Author(s): Ishikawa H, Kiyokawa T, Okayama J, Usui H, and Shozu M
  • Journal Title: J Obstet Gynaecol Res Volume: 41 Issue: 9 Pages: 1487-1490
  • DOI: 10.1111/jog.12744
  • Peer Reviewed
• [Journal Article] Daily low-dose Cisplatin-based concurrent chemoradiotherapy for the treatment of cervical cancer in patients 70 years or older (2015)
  • Author(s): Hanawa S, Mitsuhashi A, Usui H, Yamamoto N, Watanabe-Nemoto M, Nishikimi K, Uehara T, Tate S, Uno T, and Shozu M
  • Journal Title: Int J Gynecol Cancer Volume: 25 Issue: 5 Pages: 891-896
  • DOI: 10.1097/igc.0000000000000436
  • Peer Reviewed
• [Presentation] 全胞状奇胎に対する選択的再掻爬による管理は続発症発生率を上昇させない (2017)
  • Author(s): 佐藤 明日香, 碓井 宏和, 羽生 裕二, 松岡 歩, 塙 真輔, 錦見 恭子, 楯 真一, 三橋 暁, 生水 真紀夫
  • Organizer: 第69回日本産科婦人科学会学術集会
• [Presentation] 妊娠性絨毛癌の診断へのCell-free DNAの利用 (2017)
  • Author(s): 碓井宏和、佐藤明日香、塙真輔、松岡歩、羽生裕二、 錦見恭子、楯真一、三橋暁、生水真紀夫
  • Organizer: 第69回日本産科婦人科学会学術講演会
• [Presentation] 胞状奇胎と卵巣奇形腫の発生機序 SNPアレイ解析による可視化 (2017)
  • Author(s): 碓井 宏和
  • Organizer: 第58回 日本臨床細胞学会総会（春季大会）
  • Invited
• [Presentation] 胞状奇胎除去術の方法(鉗子/吸引)に関する後方視的検討 (2017)
  • Author(s): 佐藤 明日香, 碓井 宏和, 羽生 裕二, 松岡 歩, 塙 真輔, 錦見 恭子, 楯 真一, 三橋 暁, 生水 真紀夫
  • Organizer: 第59回日本婦人科腫瘍学会
• [Presentation] 妊娠性絨毛癌診断へのCell-free DNAの利用 (2017)
  • Author(s): 碓井宏和、佐藤明日香、潘シ君、塙真輔、 松岡歩、羽生裕二、錦見恭子、楯真一、 三橋暁、生水真紀夫
  • Organizer: 第59回日本婦人科腫瘍学会
• [Presentation] 子宮体癌2018年版・子宮頸癌2017年版 癌肉腫/肉腫の治療・絨毛性疾患の治療 ガイドライン改訂のポイント (2017)
  • Author(s): 藤原 寛行, 碓井 宏和, 竹原 和宏, 山本 英子, 原野 謙一
  • Organizer: 第59回日本婦人科腫瘍学会
• [Presentation] Retrospective analysis of brain metastasis of gestational choriocarcinoma (2017)
  • Author(s): Usui Hirokazu, Matsui Hideo, Sato Asuka, Habu Yuji, Matsuoka Ayumu, Nishikimi Kyoko, Tate Shinichi, Mitsuhashi Akira, Iwadate Yasuo, Uno Takashi, Shozu Makio
  • Organizer: XIX World Congress Gestational Trophpoblastic Disease
  • Int'l Joint Research
• [Presentation] Effect of routine second curettage for complete hydatidiform moles on the incidence of gestational trophoblastic neoplasia (2017)
  • Author(s): Asuka Sato, Hirokazu Usui, Pang Zijun, Yuji Habu, Ayumu Matsuoka, Kyoko Nishikimi, Shinichi Tate, Akira Mitsuhashi, Makio Shozu
  • Organizer: XIX World Congress Gestational Trophpoblastic Disease
  • Int'l Joint Research
• [Presentation] Investigation of inheritance of the mitochondrial DNA in hydatidiform moles (2017)
  • Author(s): Zijun Pan, Hirokazu Usui, Asuka Sato, Makio Shozu
  • Organizer: XIX World Congress Gestational Trophpoblastic Disease
  • Int'l Joint Research
• [Presentation] 絨毛癌脳転移症例の後方視的検討 (2017)
  • Author(s): 碓井 宏和, 松井 英雄, 佐藤 明日香, 羽生 裕二, 松岡 歩, 錦見 恭子, 楯 真一, 三橋 暁, 岩立 康男, 宇野 隆, 生水 真紀夫
  • Organizer: 第55回日本癌治療学会学術集会
• [Presentation] 胞状奇胎自然寛解後の妊娠転帰 (2017)
  • Author(s): 佐藤 明日香, 碓井 宏和, 曽根原 弘樹, 高木 亜由美, 森本 沙知, 石川 博士, 生水 真紀夫
  • Organizer: 第62回日本生殖医学会学術講演会
• [Presentation] ワークショップ「絨毛性疾患の疑問に答える」hCG低単位持続例の取り扱い (2017)
  • Author(s): 碓井 宏和
  • Organizer: 第25回日本胎盤学会学術集会・第35回日本絨毛性疾患研究会
  • Invited
• [Presentation] 絨毛癌脳転移症例の後方視的検討 (2017)
  • Author(s): 碓井宏和, 松井英雄，佐藤明日香，羽生裕二，松岡歩，錦見恭子，楯真一，三橋暁，岩立康男，宇野隆，生水真紀夫
  • Organizer: 第35回日本絨毛性疾患研究会
• [Presentation] 胞状奇胎自然寛解後の妊娠転帰 (2017)
  • Author(s): 佐藤明日香、碓井宏和、潘シ君、羽生裕二、松岡歩、錦見恭子、楯真一、三橋暁、生水真紀夫
  • Organizer: 第35回日本絨毛性疾患研究会
• [Presentation] 雄核発生奇胎は母由来ミトコンドリアDNAと父由来核DNAで構成される (2017)
  • Author(s): 潘シ君、碓井宏和、佐藤明日香、生水真紀夫
  • Organizer: 第35回日本絨毛性疾患研究会
• [Presentation] Brain metastasis of gestational choriocarcinoma: Retrospective analysis of seven cases (2017)
  • Author(s): Usui Hirokazu, Matsui Hideo, Sato Asuka, Habu Yuji, Matsuoka Ayumu, Nishikimi Kyoko, Tate Shinichi, Mitsuhashi Akira, Iwatate Yasuo, Uno Takashi, Shozu Makio
  • Organizer: The 5th Biennial Meeting of Asian Society of Gynecologic Oncology
  • Int'l Joint Research
• [Presentation] 当院における絨毛癌治療の 後方視的検討 (2016)
  • Author(s): 碓井宏和、佐藤明日香、潘し君、塙真輔、 松岡歩、羽生裕二、錦見恭子、楯真一、 三橋暁、生水真紀夫
  • Organizer: 第34回日本絨毛性疾患研究会
  • Place of Presentation: ホテルアバローム紀の国（和歌山県和歌山市）
  • Year and Date: 2016-11-25
• [Presentation] 妊娠性絨毛癌診断への Cell-free DNAの利用 (2016)
  • Author(s): 碓井宏和、佐藤明日香、潘し君、塙真輔、 松岡歩、羽生裕二、錦見恭子、楯真一、 三橋暁、生水真紀夫
  • Organizer: 第34回日本絨毛性疾患研究会
  • Place of Presentation: ホテルアバローム紀の国（和歌山県和歌山市）
  • Year and Date: 2016-11-25
• [Presentation] 侵入奇胎群先行妊娠の 遺伝学的検討 (2016)
  • Author(s): 碓井宏和、塙真輔、松岡歩、錦見恭子、楯真一、三橋暁、生水真紀夫
  • Organizer: 第58回婦人科腫瘍学会学術集会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2016-07-08
• [Presentation] The risk estimation of gestational trophoblastic neoplasia after cytogenetically defined hydatidiform molar pregnancy: A prospective cohort study (2016)
  • Author(s): Hirokazu Usui, Shinsuke Hanawa, Ayumu Matsuoka, Kyoko Nishikimi, Shinichi Tate, Akira Mitsuhashi, Makio Shozu
  • Organizer: 68th Annual Congress of the Japan Society of Obstetrics and Gynecology
  • Place of Presentation: Tokyo International Forum（Chiyoda, Tokyo）
  • Year and Date: 2016-04-22
• [Presentation] 絨毛性疾患登録について (2016)
  • Author(s): 碓井宏和, 生水真紀夫
  • Organizer: 千葉県産科婦人科医学会 平成２７年度冬期学術講演会
  • Place of Presentation: 千葉県医師会（千葉県千葉市）
  • Year and Date: 2016-02-14
• [Presentation] CYP19A1胎盤プロモーターは3つの点変異によりヒト型スプライシングバリアントを獲得した (2015)
  • Author(s): 小林 達也、碓井 宏和、生水 真紀夫
  • Organizer: 第23回 日本胎盤学会
  • Place of Presentation: JA共済ビル カンファレンスホール（東京都千代田区）
  • Year and Date: 2015-11-06
• [Presentation] Short tandem repeat多型解析による 胞状奇胎のDNA診断：臨床応用とPitfall (2015)
  • Author(s): 碓井宏和、瞿佳、生水真紀夫
  • Organizer: 第33回 日本絨毛性疾患研究会
  • Place of Presentation: JA共済ビル カンファレンスホール（東京都千代田区）
  • Year and Date: 2015-11-05
  • Invited
• [Presentation] 多剤併用化学療法および子宮全摘を要した難治性臨床的侵入奇胎の1例 (2015)
  • Author(s): 馬場七織 碓井宏和 松岡歩 塙真輔 錦見恭子 植原貴史 楯真一 三橋暁 生水真紀夫
  • Organizer: 第33回 日本絨毛性疾患研究会
  • Place of Presentation: JA共済ビル カンファレンスホール（東京都千代田区）
  • Year and Date: 2015-11-05
• [Presentation] Comparison between the pathological diagnosis and the cytogenetic classification by short tandem repeat polymorphism analysis of suspicious molar pregnancies (2015)
  • Author(s): Hirokazu Usui 1, Takako Kiyokawa 3, Jia Qu 1, Kyoko Nishikimi 1, Shinichi Tate 1, Akira Mitsuhashi 1, Yukio Nakatani 2, Makio Shozu 1
  • Organizer: XVIII WORLD CONGRESS ON GESTATIONAL TROPHOBLASTIC DISEASES
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] The polymorphism of the methylenetetrahydrofolate reductase gene in homozygous androgenetic complete moles predicts the failure of methotrexate treatment for low-risk gestational trophoblastic neoplasia (2015)
  • Author(s): Jia Qu, Hirokazu Usui, Makio Shozu
  • Organizer: XVIII WORLD CONGRESS ON GESTATIONAL TROPHOBLASTIC DISEASES
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Remarks] researchmap
  • URL: https://researchmap.jp/hirokazu-usui/
• [Remarks] 千葉大病院婦人科・周産期母性科・大学院生殖医学講座の 臨床研究のお知らせ
  • URL: http://www.m.chiba-u.ac.jp/class/gyne/rinsyo/index.html
• [Remarks] 千葉大学大学院医学研究院生殖医学 臨床研究
  • URL: http://www.m.chiba-u.ac.jp/class/gyne/rinsyo/index.html