Integrated analysis of cervical cancer using chemogenomics and radioimaging

• Project/Area Number: 26462521
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: Yoshioka Yumiko 京都大学, 医学研究科, 助教 (10402918)
• Co-Investigator(Kenkyū-buntansha): 小西 郁生 京都大学, 医学研究科, 名誉教授 (90192062)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 子宮頸癌 / 化学療法 / マイクロアレイ / MRI / 術前化学療法

Outline of Final Research Achievements

To investigate the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy for cervical cancer, translational research in vitro, in silica, and in vivo was conducted.
Microarray analysis revealed that the glutathione metabolic pathway was significantly associated with NAC-resistance, while serum genotyping revealed that UGT1A1 polymorphisms were associated favor-response. And activation of the TGF-β pathway via the interaction between cacner cells and surrounding cancer-associated fibroblasts facilitated tumor invasion, and increased pSMAD3 expression was a hallmark of metastasis. As the clinical efficacy of individualized therapy for locally advanced cervical cancer, less toxicity of NAC and modified surgery was retrospectively exhibited as a single institute study and a multi-institutional study, retrospectively.
Furthermore, radiomics exhibited magnetic resonance imaging was also a useful predictor of the tumor activity as well as a diagnostic tool.

Research Products

• [Journal Article] Feasibility of Computed Diffusion Weighted Imaging and Optimization of b-value in Cervical Cancer (2017)
  • Author(s): Moribata Y, Kido A, Fujimoto K, Himoto Y, Kurata Y, Shitano F, Kiguchi K,Konishi I, Togashi K
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 16 Issue: 1 Pages: 66-72
  • DOI: 10.2463/mrms.mp.2015-0161
  • NAID: 130005286864
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed
• [Journal Article] Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy. (2017)
  • Author(s): Koshiyama M, Matsumura N, Imai S, Yamanoi K, Abiko K, Yoshioka Y, Yamaguchi K, Hamanishi J, Baba T, Konishi I.
  • Journal Title: Med Sci Monit. Volume: 23 Pages: 826-33
  • DOI: 10.12659/msm.899741
  • NAID: 120005997749
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical efficacy of neoadjuvant chemotherapy with irinotecan (CPT-11) and nedaplatin followed by radical hysterectomy for locally advanced cervical cancer. (2016)
  • Author(s): Abou-Taleb HA, Koshiyama M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Abiko K, Yamanoi K, Murakami R, Horikawa N, Taha AA, Kitamura S, Konishi I.
  • Journal Title: J Int Med Res. Volume: 44 Issue: 2 Pages: 346-356
  • DOI: 10.1177/0300060515591858
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 2. Prognostic factors from a randomized phase III trial of paclitaxel and carboplatin versus paclitaxel and cisplatin in metastatic or recurrent cervical cancer: Japan Clinical Oncology Group (JCOG) trial: JCOG0505-S1. (2016)
  • Author(s): Nishio S, Kitagawa R, Shibata T, Yoshikawa H, Konishi I, Ushijima K, Kamura T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 78 Issue: 4 Pages: 785-90
  • DOI: 10.1007/s00280-016-3133-4
  • Peer Reviewed
• [Journal Article] 当科でのベバシズマブ使用26例の検討 (2016)
  • Author(s): 菅 智美, 山口 建, 安彦 郁, 吉岡 弓子, 濱西 潤三, 越山 雅文, 近藤 英治, 馬場 長, 松村 謙臣, 小西 郁生.
  • Journal Title: 産婦人科の進歩 Volume: 68 Pages: 314-6
  • NAID: 130005277100
  • Peer Reviewed
• [Journal Article] Clinical tumor diameter and prognosis of patients with FIGO stage IB1 cervical cancer (JCOG0806-A). (2015)
  • Author(s): Kato T,Yoshikawa H, Konishi I, Kamura T, et al;Gynecologic Oncology Study Group of the Japan Clinical Oncology Group.
  • Journal Title: Gynecol Oncol. Volume: 137 Issue: 1 Pages: 34-9
  • DOI: 10.1016/j.ygyno.2015.01.548
  • Peer Reviewed
• [Journal Article] Minimization of curative surgery for treatment of early cervical cancer: a review. (2015)
  • Author(s): Arimoto T, Kawana K, Adachi K, Ikeda Y, Nagasaka K, Tsuruga T, Yamashita A, Oda K, Ishikawa M, Kasamatsu T, Onda T, Konishi I, Yoshikawa H, Yaegashi N
  • Journal Title: Jpn J Clin Oncol Volume: 45 Issue: 7 Pages: 611-616
  • DOI: 10.1093/jjco/hyv048
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients. (2015)
  • Author(s): Horikawa N, Baba T, Matsumura N, Murakami R, Abiko K, Hamanishi J, Yamaguchi K, Koshiyama M, Yoshioka Y, Konishi I.
  • Journal Title: BMC Cancer. Volume: 15 Issue: 1 Pages: 739-739
  • DOI: 10.1186/s12885-015-1703-1
  • NAID: 120005749961
  • Peer Reviewed / Open Access
• [Journal Article] 当科で骨盤除臓術を施行した22症例の後方視的検討および文献的考察( (2015)
  • Author(s): 吉岡弓子,松村謙臣,植田彰彦,山口建,濱西潤三,安彦郁,馬場長,小西郁生
  • Journal Title: 産婦人科の進歩 Volume: 67 Pages: 254-263
  • NAID: 130005101919
  • Peer Reviewed
• [Journal Article] Pretreatment Mean Apparent Diffusion Coefficient Is Significantly Correlated With Event-Free Survival in Patients With International Federation of Gynecology and Obstetrics Stage Ib to IIIb Cervical Cancer. (2015)
  • Author(s): Himoto Y, Fujimoto K, Kido A, Baba T, Tanaka S, Morisawa N, Koyasu S, Konishi I, Togashi K.
  • Journal Title: Int J Gynecol Cancer. Volume: 25 Issue: 6 Pages: 1079-85
  • DOI: 10.1097/igc.0000000000000445
  • Peer Reviewed
• [Journal Article] MR Imaging-based Evaluation of Morphological Changes in the Uterus and Ovaries of Patients Following Neoadjuvant Chemotherapy for Cervical Cancer (2015)
  • Author(s): Himoto Y, Kido A, Fujimoto K, Daido S, Kiguchi K, Shitano F, Baba T, Matsumura N, Konishi I, Togashi K.
  • Journal Title: Magnetic Resonance in Medical Sciences Volume: 14 Issue: 1 Pages: 65-72
  • DOI: 10.2463/mrms.2014-0025
  • NAID: 130004935518
  • ISSN: 1347-3182, 1880-2206
  • Peer Reviewed
• [Journal Article] Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta. (2015)
  • Author(s): Nagura M, Matsumura N, Baba T, Murakami R, Kharma B, Hamanishi J, Yamaguchi K, Abiko K, Koshiyama M, Mandai M, et al.
  • Journal Title: Gynecol Oncol Volume: 136 Issue: 1 Pages: 104-111
  • DOI: 10.1016/j.ygyno.2014.11.075
  • Peer Reviewed / Open Access
• [Journal Article] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-a potential therapeutic target. (2015)
  • Author(s): Peng J, Yoshioka Y, Mandai M, et al
  • Journal Title: Mol Carcinog Volume: Epub ahead of print Issue: 4 Pages: 1-11
  • DOI: 10.1002/mc.22283
  • Peer Reviewed / Open Access
• [Journal Article] 妊娠中に術前化学療法を施行した子宮頸癌合併妊娠の2症例 (2015)
  • Author(s): 水野 林, 馬場 長, 吉岡 弓子, 近藤 英治, 山口 建, 濱西 潤三, 安彦 郁, 越山雅文, 松村 謙臣, 小西 郁生
  • Journal Title: 日本婦人科腫瘍学会雑誌 Volume: 33 Pages: 51-60
  • Peer Reviewed
• [Journal Article] Clinical approaches to treating papillary squamous cell carcinoma of the uterine cervix. (2014)
  • Author(s): Nagura M, Koshiyama M, Matsumura N, Kido A, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Mikami Y, Konishi I.
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 784-784
  • DOI: 10.1186/1471-2407-14-784
  • Peer Reviewed / Open Access
• [Presentation] ゲノム情報を用いた局所進行子宮頸癌におけるNACの有効性予測 (2014)
  • Author(s): 堀川直城、馬場長、松村謙臣、村上隆介、安彦郁、山口建、濱西潤三、吉岡弓子、小西郁生
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] 子宮頸癌細胞の浸潤能は間質細胞との相互作用により活性化したTGF-betaによって促進される (2014)
  • Author(s): 奈倉道和、松村謙臣、馬場長、吉岡弓子、濱西潤三、山口建、安彦郁、小西郁生、万代昌紀
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] The efficacy of Neoadjuvant chemotherapy (NAC) in the management of invasive cancer cervix (2014)
  • Author(s): Hisham Abou-Taleb, Ken Yamaguchi, Noriomi Matsumura, Koji Yamanoi, Ryusuke Murakami, Tsukasa Baba, Yumiko Yoshioka, Junzo Hamanishi, Ikuo Konishi
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-18 – 2014-04-20