investigation of molecular targeted therapy in gynecologic malignancies

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nara Medical University
• Principal Investigator: FURUKAWA naoto 奈良県立医科大学, 医学部, 講師 (50347556)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Hiroshi 奈良県立医科大学, 医学部, 教授 (40178330) ; YOSHIDA Shozo 奈良県立医科大学, 医学部, 助教 (40347555) ; NARUSE Katsuhiko 奈良県立医科大学, 医学部, 助教 (70453165) ; SHIGETOMI Hiroshi 奈良県立医科大学, 医学部, 助教 (20433336)
• Project Period (FY): 2011 – 2013
• Keywords: 卵巣癌 / 転写因子 / 細胞周期

Research Abstract

We investigated the molecular targeted therapy in a viewpoint of Hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell carcinoma of ovary. We found that G2 cell-cycle arrest is induced through adenoviral transfer of HNF-1beta. CHK1 kinase acts downstream of ATM/ATR kinase and plays an important role in the G2 checkpoint. G2 arrest of HNF-1beta (+) cells results from sustained CHK1 activation.Furthermore, HNF-1beta controls claspin expression, sustaining CHK1
protein phosphorylation.
These data indicated that the anticancer drug resistance of CCA may be caused by aberrant G2 arrest due to HNF-1A overexpression.

Research Products

• [Journal Article] Evaluation of the relation between patient characteristics and the state of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer receiving paclitaxel and carboplatin (2014)
  • Author(s): Furukawa N, Akasaka J, Shigemitsu A, Sasaki Y, Nagai A, Kawaguchi R, Kobayashi H
  • Journal Title: Arch Gynecol Obstet Volume: 289(4) Pages: 859-64
• [Journal Article] Inhibition of Cell Death and Induction of G2 Arrest Accumulation in Human Ovarian Clear Cells by HNF-1βTranscription Factor : Chemosensitivity Is Regulated by Checkpoint Kinase CHK1 (2014)
  • Author(s): Shigetomi H, Sudo T, Shimada K, Uekuri C, Tsuji Y, Kanayama S, Naruse K, Yamada Y, Konishi N, Kobayashi H
  • Journal Title: Int J Gynecol Cancer Volume: (Epub ahead of print)
• [Journal Article] Risk factors for wound complications after surgery for gynecologic malignancies (2013)
  • Author(s): Akasaka J, Furukawa N, Shigemitsu A, Kanayama S, Kawaguchi R, Kobayashi H
  • Journal Title: Int J Gynecol Cancer Volume: 23(8) Pages: 1501-5
• [Journal Article] Toward an understanding of the pathophysiology of clear cell carcinoma of the ovary (Review) (2013)
  • Author(s): Uekuri C, Shigetomi H, Ono S, Sasaki Y, Matsuura M, Kobayashi H
  • Journal Title: Oncol Lett Volume: 6(5) Pages: 1163-1173
• [Journal Article] Posttreatment cut-off levels of squamous cell carcinoma antigen as a prognostic factor in patients with locally advanced cervical cancer treated with radiotherapy (2013)
  • Author(s): Kawaguchi R, Furukawa N, Kobayashi H, Asakawa I
  • Journal Title: J Gynecol Oncol Volume: 24(4) Pages: 313-20
• [Journal Article] CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer (2013)
  • Author(s): Furukawa N, Sasaki Y, Shigemitsu A, Akasaka J, Kanayama S, Kawaguchi R, Kobayashi H
  • Journal Title: J Gynecol Oncol Volume: 24(2) Pages: 141-5
• [Journal Article] Modulation of estrogenic action in clear cell carcinoma of the ovary (Review) (2012)
  • Author(s): Tanase Y, Yamada Y, Shigetomi H, Kajihara H, Oonogi A, Yoshizawa Y, Furukawa N, Haruta S, Yoshida S, Sado T, Oi H, Kobayashi H
  • Journal Title: Exp Ther Med Volume: 3(1) Pages: 18-24
• [Journal Article] Molecular mechanisms linking endometriosis under oxidative stress with ovarian tumorigenesis and therapeutic modalities (2012)
  • Author(s): Shigetomi H, Tsunemi T, Haruta S, Kajihara H, Yoshizawa Y, Tanase Y, Furukawa N, Yoshida S, Sado T, Kobayashi H
  • Journal Title: Cancer Invest Volume: 30(6) Pages: 473-80
• [Journal Article] Phase II trial of paclitaxel and nedaplatin in patients with advanced/recurrent uterine cervical cancer : a Kansai Clinical Oncology Group study (2012)
  • Author(s): Takekuma M, Hirashima Y, Ito K, Tsubamoto H, Tabata T, Arakawa A, Itani Y, Furukawa N, Murakoshi H, Takeuchi S
  • Journal Title: Gynecol Oncol Volume: 126(3) Pages: 341-5
• [Journal Article] Cut-off value of D-dimer for prediction of deep venous thrombosis before treatment in ovarian cancer (2012)
  • Author(s): Kawaguchi R, Furukawa N, Kobayashi
  • Journal Title: J Gynecol Oncol Volume: 23(2) Pages: 98-102
• [Journal Article] Use of high-dose cisplatin with aprepitant in an outpatient setting (2012)
  • Author(s): Furukawa N, Kawaguchi R, Kobayashi
  • Journal Title: Eur J Cancer Care (Engl) Volume: 21(4) Pages: 436-41
• [Journal Article] Redox-active iron-induced oxidative stress in the pathogenesis of clear cell carcinoma of the ovary (2011)
  • Author(s): Yamada Y, Shigetomi H, Onogi A, Haruta S, Kawaguchi R, Yoshida S, Furukawa N, Nagai A, Tanase Y, Tsunemi T, Oi H, Kobayashi H
  • Journal Title: Int J Gynecol Cancer Volume: 21(7) Pages: 1200-7
• [Journal Article] Signaling pathway involved in cyclooxygenase-2 up-regulation by hepatocyte growth factor in endometrial cancer cells (2011)
  • Author(s): Yoshizawa Y, Yamada Y, Kanayama S, Shigetomi H, Kawaguchi R, Yoshida S, Nagai A, Furukawa N, Oi H, Kobayashi H
  • Journal Title: Oncol Rep Volume: 26(4) Pages: 957-64
• [Journal Article] Molecular genetics and epidemiology of epithelial ovarian cancer (Review) (2011)
  • Author(s): Haruta S, Furukawa N, Yoshizawa Y, Tsunemi T, Nagai A, Kawaguchi R, Tanase Y, Yoshida S, Kobayashi H
  • Journal Title: Oncol Rep Volume: 26(6) Pages: 1347-56
• [Journal Article] Evaluation of the vessels of the cardinal ligament by transrectal ultrasonography with color Doppler imaging (2011)
  • Author(s): Furukawa N, Kawaguchi R, Kajihara H, Kobayashi H
  • Journal Title: J Clin Ultrasound Volume: 39(9) Pages: 502-5
• [Journal Article] Carcinosarcoma of the uterine corpus with alpha-fetoprotein-producing hepatoid adenocarcinoma : a report of two cases (2011)
  • Author(s): Kawaguchi R, Furukawa N, Yamada Y, Ooi H, Kobayashi H
  • Journal Title: Case Rep Oncol Volume: 4(2) Pages: 358-62
• [Presentation] 明細胞腺癌における転写因子HNF-1betaが制御するDNA損傷チェックポイント機構の解明 (2013)
  • Author(s): 重富洋志,植栗千陽,梶原宏貴,棚瀬康仁,春田祥治,金山清二,川口龍二,吉田昭三,古川直人,大井豪一,小林浩,島田啓司,須藤保
  • Organizer: 2013日本婦人科がん分子標的研究会学術集会
  • Year and Date: 20130000
• [Presentation] 転写因子HNF-1betaは卵巣明細胞腺癌においてClaspinの発現を制御し、chk1タンパクのリン酸化を維持させる (2013)
  • Author(s): 重富洋志,須藤保,吉澤順子,金山清二,川口龍二,小林浩,山田嘉彦
  • Organizer: 2013日本癌学会学術総会
  • Year and Date: 20130000
• [Presentation] Evaluation of BRCA1 Gene Expression as a Prognostic Marker Peritoneal Cancer (2012)
  • Author(s): Furukawa N, Nagai A, Kasai T, Ohno S,Shigemitsu Y, Tanase Y, Haruta S, Kawaguchi R,Yoshida S, Oi H, Kobayashi H
  • Organizer: 2012 Biennial Meeting of the International Gynecologic Cancer Society
  • Year and Date: 20120000
• [Presentation] 明細胞腺癌におけるDNA損傷応答と転写因子HNF-1beta (2012)
  • Author(s): 重富洋志,須藤保,吉澤順子,棚瀬康仁,春田祥治,金山清二,永井景,川口龍二,吉田昭三,古川直人,大井豪一,小林浩
  • Organizer: 2012日本エンドメトリオーシス学会
  • Year and Date: 20120000
• [Presentation] 卵巣明細胞腺癌における転写因子HNF-1betaのDNA損傷チェックポイント機構の制御 (2012)
  • Author(s): 重富洋志,須藤保,吉澤順子,棚瀬康仁,春田祥治,金山清二,永井景,川口龍二,吉田昭三,古川直人,大井豪一,小林浩
  • Organizer: 2012日産婦
  • Year and Date: 20120000
• [Presentation] CA125 as a predictive marker for optimal interval debulking surgery in advanced ovarian cancer (2011)
  • Author(s): Furukawa N, Shigetomi H, Yoshida S, Kawaguchi R, Komeda S, Tanase Y, Yamada Y, Kobayashi H
  • Organizer: 2011 American Society of Clinical Oncology(ASCO)annual meeting
  • Year and Date: 20110000
• [Presentation] 卵巣明細胞腺癌に強発現する転写因子HNF-1Betaの生物作用の解明 (2011)
  • Author(s): 重富洋志,吉澤順子,梶原宏貴,山田嘉彦,川口龍二,吉田昭三,古川直人,大井豪一,小林浩,金山清二
  • Organizer: 2011日産婦
  • Year and Date: 20110000