An attempt to establish a new treatment for non-squamous cell carcinoma of the uterine cervix

• Project/Area Number: 17K11265
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tohoku University
• Principal Investigator: SHIMADA Muneaki 東北大学, 未来型医療創成センター, 教授 (40362892)
• Co-Investigator(Kenkyū-buntansha): 徳永 英樹 東北大学, 医学系研究科, 准教授 (30595559) ; 北谷 和之 東北大学, 東北メディカル・メガバンク機構, 講師 (40539235) ; 永井 智之 東北大学, 医学系研究科, 非常勤講師 (00704298)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 子宮頸癌 / 組織亜型 / 難治性がん / メタボローム解析 / 化学療法 / 集学的治療 / 個別化医療 / 非扁平上皮癌 / 化学療法感受性 / 放射線感受性

Outline of Final Research Achievements

In an attempt to establish a new treatment for non-squamous carcinoma of the cervix, one of the most refractory gynecologic malignancies, we conducted a clinico-pathological study utilizing real-world data based on a large number of surgical cases and demonstrated "clinic-pathological features based on histological subtypes" that directly lead to appropriate treatment selection. We have identified candidate metabolic profiles to predict prognosis and therapeutic efficacy, and candidate target metabolites associated with therapeutic resistance, using convenient and relatively inexpensive metabolomic analysis.

Academic Significance and Societal Importance of the Research Achievements

組織亜型により子宮頸癌の分子生物学的特徴が異なることは指摘されているものの、組織亜型が子宮頸癌の生存成績に与える影響については一定の見解が得られていないことから、組織亜型やゲノムシグネチャーに基づいた治療法は推奨されていない。
今回の研究成果により、難治性婦人科悪性腫瘍である子宮頸部非扁平上皮癌に着眼した治療の精緻化が実装され、検診事業の促進、ワクチンプログラムの浸透と合わせた「俯瞰的治療戦略」により、子宮頸癌制圧の実現が大きく期待される。

Research Products

• [Journal Article] Prognostic factors of 2018 FIGO stage IB-IIA cervical cancer with absence of high/ intermediate surgical-pathological risk factors. (2022)
  • Author(s): Shibuya Y, Shimada M, Tsuji K, Shigeta S, Tanase Y, Matsuo K, Yamaguchi S, Kanao H, Saito T, Mikami M
  • Journal Title: Jpn J Clin Oncol Volume: 52(11) Pages: 1289-1296
  • DOI: 10.1093/jjco/hyac125
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk assessment in the patients with uterine cervical cancer harboring intermediate risk factors after radical hysterectomy: a multicenter, retrospective analysis by the Japanese Gynecologic Oncology Group. (2022)
  • Author(s): Shigeta S, Shimada N,Tsuji K, Nagai T, Tanase Y, Matsuo K, Kamiura S, Iwata T, Yokota H, Mikami M
  • Journal Title: Int J Clin Oncol Volume: 27(9) Issue: 9 Pages: 1507-1515
  • DOI: 10.1007/s10147-022-02198-6
  • Peer Reviewed / Open Access
• [Journal Article] Clinico-pathological characteristics of patients with stage IB1-IB2 (FIGO 2018) uterine cervical cancer: a nationwide study in Japan. (2021)
  • Author(s): Tsuji K, Shimada M, Takahashi F, Tokunaga H, Deura I, Yamaguchi S, Nakanishi T, Matsuo K, Yaegashi N, Mikami M.
  • Journal Title: Int J Clin Oncol. Volume: 26(8) Issue: 8 Pages: 1541-1552
  • DOI: 10.1007/s10147-021-01938-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Docetaxel and carboplatin chemotherapy for treating patients with stage IVB or recurrent non-squamous cell carcinoma of the uterine. (2021)
  • Author(s): Shimada M, Sato S, Shoji T, Nagao S, Tokunaga H, Sueoka K, Takehara K, Nakamura K, Yamaguchi S, Kigawa J.
  • Journal Title: Int J Clin Oncol Volume: 26 Issue: 7 Pages: 1314-1321
  • DOI: 10.1007/s10147-021-01903-1
  • Peer Reviewed / Open Access
• [Journal Article] The Impact of Histological Subtype on Survival Outcome of Patients with Stage IIB-IVA Cervical Cancer Who Received Definitive Radiotherapy (2021)
  • Author(s): Miyahara S, Tsuji K, Shimada M, Shibuya Y, Shigeta S, Nagai T, Umezawa R, Tokunaga H, Jingu K, Yaegashi N.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 255 Issue: 4 Pages: 303-313
  • DOI: 10.1620/tjem.255.303
  • NAID: 130008129404
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] A Single Arm Prospective Pilot Study Examining the Efficacy and Safety of Bevacizumab Single Maintenance Therapy Following Platinum-Based Chemotherapy in Patients with Advanced or Recurrent Cervical Cancer. (2021)
  • Author(s): Toyoshima M, Shimada M, Sasaki S, Ishibashi M, Shigeta S, Tsuji K, Nagai T, Tokunaga H, Niikura H, Yaegashi N.
  • Journal Title: Tohoku J Exp Med. Volume: 254(3) Issue: 3 Pages: 145-153
  • DOI: 10.1620/tjem.254.145
  • NAID: 130008061848
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Histopathological Risk Factors on the Treatment of Stage IB-IIB Uterine Cervical Cancer (2020)
  • Author(s): Shimada Muneaki、Tokunaga Hideki、Kigawa Junzo、Yaegashi Nobuo
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 252 Issue: 4 Pages: 339-351
  • DOI: 10.1620/tjem.252.339
  • NAID: 130007953560
  • Peer Reviewed / Open Access
• [Journal Article] Perioperative treatments for stage IB-IIB uterine cervical cancer (2020)
  • Author(s): Shimada Muneaki、Tokunaga Hideki、Kobayashi Hiroaki、Ishikawa Mitsuya、Yaegashi Nobuo
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 50 Issue: 2 Pages: 99-103
  • DOI: 10.1093/jjco/hyz200
  • Peer Reviewed / Open Access
• [Journal Article] Management of Stage IIB Cervical Cancer: an Overview of the Current Evidence. (2020)
  • Author(s): Matsuzaki S, Klar M, Mikami M, Shimada M, Grubbs BH, Fujiwara K, Roman LD, Matsuo K
  • Journal Title: Curr Oncol Rep Volume: 22(3) Issue: 3 Pages: 28-28
  • DOI: 10.1007/s11912-020-0888-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significance of Malignant Peritoneal Cytology on the Survival of Women with Early-Stage Cervical Cancer: A Japanese Gynecologic Oncology Group Study (2019)
  • Author(s): Matsuo Koji、Shimada Muneaki、Matsuzaki Shinya、Machida Hiroko、Nagase Yoshikazu、Saito Toshiaki、Kamiura Shoji、Iwata Takashi、Sugiyama Toru、Mikami Mikio
  • Journal Title: Journal of Clinical Medicine Volume: 8 Issue: 11 Pages: 1822-1822
  • DOI: 10.3390/jcm8111822
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of Radical Hysterectomy Surgical Volume and Survival for Early-Stage Cervical Cancer (2019)
  • Author(s): Matsuo Koji、Shimada Muneaki、Yamaguchi Satoshi、Matoda Maki、Nakanishi Toru、Kikkawa Fumitaka、Ohmichi Masahide、Okamoto Aikou、Sugiyama Toru、Mikami Mikio
  • Journal Title: Obstetrics & Gynecology Volume: 133 Issue: 6 Pages: 1086-1098
  • DOI: 10.1097/aog.0000000000003280
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Predictors for pathological parametrial invasion in clinical stage IIB cervical cancer. (2019)
  • Author(s): Matsuo K, Shimada M, Nakamura K, Takei Y, Ushijima K, Sumi T, Ohara T, Yahata H, Mikami M, Sugiyama T.
  • Journal Title: Eur J Sur Oncol Volume: - Issue: 8 Pages: 1417-1424
  • DOI: 10.1016/j.ejso.2019.02.019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neoadjuvant chemotherapy with taxane and platinum followed by radical hysterectomy for stage IB2-IIB cervical cancer: Impact of histology type on survival. (2019)
  • Author(s): Matsuo K, Shimada M, Yamaguchi S, Kigawa J, Tokunaga H, Tabata T, Kodama J, Kawana K, Mikami M, Sugiyama T.
  • Journal Title: Journal of Clinical Medicine Volume: 30: 8(2) Issue: 2 Pages: 156-169
  • DOI: 10.3390/jcm8020156
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk stratification models for peri-aortic lymph node metastasis and recurrence in stage IB-IIB cervical cancer. (2018)
  • Author(s): Matsuo K, Shimada M, Tsuyoshi Saito T, Takehara K, Tokunaga H, Watanabe Y, Todo Y, Morishige K, Mikami M, Sugiyama T.
  • Journal Title: J Gynecol Oncol. Volume: 29 (1):e11. Issue: 1
  • DOI: 10.3802/jgo.2018.29.e11
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chemoresistance of gastric-type mucinous carcinoma of the uterine cervix: a study of the Sankai Gynecology Study Group. (2018)
  • Author(s): Kojima A, Shimada M, Mikami Y, Nagao S, Takeshima N, Sugiyama T, Teramoto N, Kiyokawa T, Kigawa J, Nishimura R, Sankai Gynecology Study Group (SGSG)
  • Journal Title: Int J Gynecol Cancer Volume: 28(1) Issue: 1 Pages: 99-106
  • DOI: 10.1097/igc.0000000000001145
  • Peer Reviewed
• [Journal Article] Comparison of adjuvant therapy for node-positive clinical stage IB-IIB cervical cancer: Systemic chemotherapy versus pelvic irradiation. (2017)
  • Author(s): Matsuo K, Shimada M, Aoki Y, Sakamoto M, Takeshima N, Fujiwara H, Matsumoto T, Mikami M, Sugiyama T.
  • Journal Title: Int J Cancer Volume: 141 (5) Issue: 5 Pages: 1042-1051
  • DOI: 10.1002/ijc.30793
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effectiveness of adjuvant systemic chemotherapy for intermediate-risk stage IB cervical cancer (2017)
  • Author(s): Matsuo Koji、Shimada Muneaki、Yokota Harushige、Satoh Toyomi、Katabuchi Hidetaka、Kodama Shoji、Sasaki Hiroshi、Matsumura Noriomi、Mikami Mikio、Sugiyama Toru
  • Journal Title: Oncotarget Volume: 8 Issue: 63 Pages: 106866-106875
  • DOI: 10.18632/oncotarget.22437
  • NAID: 120007134533
  • Peer Reviewed / Open Access / Int'l Joint Research