Therapeutic strategy for peritoneal dissemination of ovarian cancer using dynamic phototherapy and clofibric acid

• Project/Area Number: 23592429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hirosaki University
• Principal Investigator: YOKOYAMA Yoshihito 弘前大学, 医学(系)研究科(研究院), 准教授 (90261453)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 光線力学的療法 / 卵巣癌 / 腹膜播種 / 5-アミノレブリン酸メチルエステル / プロトポルフィリンIX / ヘム合成・分解 / 腹腔内播種 / Carbonyl reductase / クロフィブリン酸 / 大網切除 / 血管新生 / アポトーシス / phagocytosis / 癌性腹膜炎

Research Abstract

This study aimed to investigate the reason why intracellular amount of protoporphyrin IX (PpIX) varies in ovarian cancer cells and the effect of Photodynamic therapy (PDT) on peritoneal carcinomatosa. 1) The amount of PpIX (microg/dl) was 67.7 in DISS cells and 22.4 in MCAS cells. 2) Expression of delta-ALA synthetic enzyme, heme oxygenase and biliverdin reductase B in MCAS increased more then 3 times compared with those in DISS. 3) The rats treated with a methyl ester of 5-aminolevulinic acid (Methyl-ALA)-PDT was significantly longer in survival than those of the control and debulking surgery (DS)-Methyl-ALA-PDT significantly prolonged survival compared with DS alone. These results suggest that PpIX is not accumulated in cells in which heme synthesis and resolution is active and that Methyl-ALA-PDT is promising in ovarian cancer treatment. The amount of PpIX in cells is important in PDT treatment.

Research Products

• [Journal Article] Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer. (2014)
  • Author(s): Yokoyama Y, Matsushita Y, Shigeto T, Futagami M, Mizunuma H
  • Journal Title: J Gynecol Oncol Volume: 25 Issue: 1 Pages: 58-63
  • DOI: 10.3802/jgo.2014.25.1.58
  • Peer Reviewed
• [Journal Article] Redistribution of resistance and sensitivity to platinum during the observation period following treatment of epithelial ovarian cancer (2014)
  • Author(s): Yokoyama Y, Kurachi H
  • Journal Title: Mol clin oncol Volume: 2 Issue: 2 Pages: 212-218
  • DOI: 10.3892/mco.2013.223
  • Peer Reviewed
• [Journal Article] Inhibitory effects of aromatase inhibitor on estrogen receptor-alpha positive ovarian cancer in mice. (2014)
  • Author(s): Hirakawa H, Yokoyama Y, Yoshida H, Mizunuma H
  • Journal Title: J Ovarian Res Volume: 7 Issue: 1 Pages: 4-4
  • DOI: 10.1186/1757-2215-7-4
  • Peer Reviewed
• [Journal Article] Investigation of the clinicopathological features of fallopian tube malignancy (2013)
  • Author(s): Yokoyama Y, Kurachi H
  • Journal Title: Oncol Rep Volume: 30 Issue: 1 Pages: 79-84
  • DOI: 10.3892/or.2013.2439
  • Peer Reviewed
• [Journal Article] Yolk sac tumor of the ovary: a retrospective multicenter study of 33 Japanese women by Tohoku Gynecologic Cancer Unit (TGCU) (2013)
  • Author(s): Kojimahara T, Nakahara K, Takano T, Yaegashi N, Nishiyama H, Fujimori K, Sato N, Terada Y, Tase T, Yokoyama Y, Mizunuma H, Shoji T, Sugiyama T, Kurachi H
  • Journal Title: Tohoku J Exp Med Volume: 230 Issue: 8 Pages: 211-217
  • DOI: 10.1007/s00432-011-0993-1
  • NAID: 10031194084
• [Journal Article] Recurrent epithelial ovarian cancer and hormone therapy. (2013)
  • Author(s): Yokoyama Y, Mizunuma H
  • Journal Title: World J Clin Cases Volume: 1 Issue: 6 Pages: 187-190
  • DOI: 10.12998/wjcc.v1.i6.187
  • Peer Reviewed
• [Journal Article] Comparison of the outcome between cervical adenocarcinoma and squamous cell carcinoma patients with adjuvant radiotherapy following radical surgery: SGSG/TGCU Intergroup Surveillance. (2013)
  • Author(s): Shimada M, Nishimura R, Nogawa T, Hatae M, Takehara K, Yamada H, Kurachi H, Yokoyama Y, Sugiyama T, Kigawa J.
  • Journal Title: Mol Clin Oncol Volume: 1 Issue: 4 Pages: 780-784
  • DOI: 10.3892/mco.2013.112
  • Peer Reviewed
• [Journal Article] A case of small cell carcinoma of the vagina (2013)
  • Author(s): Tamura R, Yokoyama Y, Kobayashi A, Osawa Y, Shigeto T, Futagami M, Mizunuma H
  • Journal Title: Rare Tumors Volume: 5 Issue: 4 Pages: 189-191
  • DOI: 10.4081/rt.2013.e58
• [Journal Article] Enhanced inhibitory effect of meloxicam, a cyclooxygenase-2 inhibitor combined with cisplatin on the growth of human ovarian cancers (2013)
  • Author(s): Xin B, Yokoyama Y, Shigeto T, Masayuki F, Mizunuma H
  • Journal Title: J Tumor Volume: 1 Pages: 53-61
• [Journal Article] Yolk Sac Tumor of the Ovary: A Retrospective Multicenter Study of 33 Japanese Women by Tohoku Gynecologic Cancer Unit (TGCU) (2013)
  • Author(s): Kojimahara T, Nakahara K, Takano T, Yaegashi N, Nishiyama H, Fujimori K, Sato N, Terada Y, Tase T, Yokoyama Y, Mizunuma H, Shoji T, Sugiyama T, Kurachi H.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 230 Issue: 4 Pages: 211-217
  • DOI: 10.1620/tjem.230.211
  • NAID: 10031194084
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Enhanced inhibitory effect of meloxicam, a cyclooxygenase-2 inhibitor combined with cisplatin on the growth of human ovarian cancers. (2013)
  • Author(s): Xin B, Yokoyama Y, Shigeto T, Masayuki F, Mizunuma H.
  • Journal Title: J Tumor Volume: 1 Pages: 53-61
  • Peer Reviewed
• [Journal Article] Can malignant transformation in mature cystic teratoma be preoperatively predicted? (2012)
  • Author(s): Futagami M, Yokoyama Y, Mizukami H, Shigeto T, Mizunuma H
  • Journal Title: Eur J Gynaecol Oncol Volume: 33 Pages: 662-665
• [Journal Article] A case of granulosa cell tumor of the ovary detected from metastatic foci (2012)
  • Author(s): Yanagita T, Yokoyama Y, Tamura R, Taniguchi R, Shigeto T, Mizunuma H
  • Journal Title: Eur J Gynaecol Oncol Volume: 33 Pages: 648-651
• [Journal Article] Carcinosarcima of the fallopian tube: Report of four cases and review of literature. (2012)
  • Author(s): Yokoyama Y, Yokota M, Futagami M, Mizunuma H.
  • Journal Title: Asia Pac J Clin Oncol Volume: 8 Issue: 3 Pages: 303-311
  • DOI: 10.1111/j.1743-7563.2011.01513.x
  • Peer Reviewed
• [Journal Article] s omentectomy mandatory in the operation for ovarian cancer? (2012)
  • Author(s): Yokoyama Y, Hirakawa H, Wang H, Mizunuma H.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 164 Issue: 1 Pages: 89-92
  • DOI: 10.1016/j.ejogrb.2012.05.020
  • Peer Reviewed
• [Journal Article] A case of ovarian mucinous adenocarcinoma in a premenarcheal girl. (2012)
  • Author(s): Matsushita Y, Yokoyama Y, Taniguchi R, Abe K, Watanabe J, Mizunuma H.
  • Journal Title: Int J Clin Oncol Volume: 17 Issue: 5 Pages: 517-521
  • DOI: 10.1007/s10147-011-0333-0
  • NAID: 10031144341
  • Peer Reviewed
• [Journal Article] Presentation of two patients with malignant granulosa cell tumors, with a review of the literature. (2012)
  • Author(s): Tamura R, Yokoyama Y, Yanagita T, Matsumura Y, Abe K, Taniguchi R, Mizunuma H
  • Journal Title: World J Surg Oncol Volume: 10 Issue: 1 Pages: 185-185
  • DOI: 10.1186/1477-7819-10-185
  • Peer Reviewed
• [Journal Article] Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit (2012)
  • Author(s): Shoji T, Kumagai S, Yoshizaki A, Yokoyama Y, Fujimoto T, Takano T, Yaegashi N, Nakahara K, Nishiyama H, Sugiyama T
  • Journal Title: Eur J Gynaecol Oncol Volume: 28 Pages: 353-357
• [Journal Article] Decreased carbonyl reductase 1 expression promotes malignant behaviours by induction of epithelial mesenchymal transition and its clinical significance. (2012)
  • Author(s): Murakami A, Yakabe K, Yoshidomi K, Sueoka K, Nawata S, Yokoyama Y, Tsuchida S, Al-Mulla F, Sugino N.
  • Journal Title: Cancer Lett Volume: 323 Issue: 1 Pages: 69-76
  • DOI: 10.1016/j.canlet.2012.03.035
  • Peer Reviewed
• [Journal Article] Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma (2012)
  • Author(s): Ayhan A, Mao TL, Seckin T, Wu CH, Guan B, Ogawa H, Futagami M, Mizukami H, Yokoyama Y, Kurman RJ, Shih IM
  • Journal Title: Int J Gynecol Cancer Volume: 22 Issue: 8 Pages: 1310-1315
  • DOI: 10.1097/igc.0b013e31826b5dcc
• [Journal Article] Malignant ovarian tumors with induced expression of carbonyl reductase show spontaneous regression (2012)
  • Author(s): Wang H, Yokoyama Y, Tsuchida S Mizunuma H
  • Journal Title: Clin Med Insights: Oncology Volume: 6 Pages: 107-115
  • DOI: 10.4137/cmo.s9005
• [Journal Article] Efficacy of neoadjuvant chemotherapy followed by radical hysterectomy in locally advanced non-squamous carcinoma of the uterine cervix: a retrospective multicenter study of Tohoku Gynecologic Cancer Unit. (2012)
  • Author(s): Shoji T, Kumagai S, Yoshizaki A, Yokoyama Y, Fujimoto T, Takano T, Yaegashi N, Nakahara K, Nishiyama H, Sugiyama T
  • Journal Title: Eur J Gynaecol Oncol Volume: 28 Pages: 353-357
  • Peer Reviewed
• [Journal Article] Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma. (2012)
  • Author(s): Ayhan A, Mao TL, Seckin T, Wu CH, Guan B, Ogawa H, Futagami M, Mizukami H, Yokoyama Y, Kurman RJ, Shih IM.
  • Journal Title: Int J Gynecol Cancer Volume: 22 Pages: 1310-1315
  • Peer Reviewed
• [Journal Article] Malignant ovarian tumors with induced expression of carbonyl reductase show spontaneous regression. (2012)
  • Author(s): Wang H, Yokoyama Y, Tsuchida S, Mizunuma H
  • Journal Title: Clin Med Insights: Oncology Volume: 6 Pages: 107-115
  • Peer Reviewed
• [Journal Article] Combination of ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, and cisplatin enhances the inhibition of growth of human ovarian cancers. (2011)
  • Author(s): Yokoyama Y, Xin B, Shigeto T, Mizunuma H.
  • Journal Title: J Cancer Res Clin Oncol Volume: 137 Pages: 1219-1228
  • Peer Reviewed
• [Presentation] Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer (2013)
  • Author(s): Yokoyama Y, et al
  • Organizer: 第3回アジア婦人科腫瘍学会
  • Place of Presentation: 京都
• [Presentation] Redistribution of Resistance and Sensitivity to Platinum According to the Observation Period After the Treatment of Epithelial Ovarian Cancer (2013)
  • Author(s): Yokoyama Y, et al
  • Organizer: 第17回欧州癌会議
  • Place of Presentation: アムステルダム(オランダ)
• [Presentation] Decreased ARID1A expression is correlated with chemo-resistance in epithelial ovarian cancer (2013)
  • Author(s): Yoshihito Yokoyama, Yoko Matsushita, Tastuhiko Shigeto, Masayuki Futagami, Hideki Mizunuma
  • Organizer: 第3回アジア婦人科腫瘍学会
  • Place of Presentation: 京都
• [Presentation] A Redistribution of Resistance and Sensitivity to Platinum According to the Observation Period After the Treatment of Epithelial Ovarian Cancer (2013)
  • Author(s): Yoshihito Yokoyama
  • Organizer: European Cancer Congress
  • Place of Presentation: アムステルダム（オランダ）
• [Presentation] 卵巣癌の腹腔内播種・浸潤の制御を目指した治療法の開発 (2013)
  • Author(s): 横山良仁
  • Organizer: 日本願治療学会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 当科におけるダヴィンチ手術の現状と患者満足度 (2013)
  • Author(s): 横山良仁、福井淳史、福原理恵、樋口 毅、水沼英樹
  • Organizer: 日本婦人科ロボット研究会
  • Place of Presentation: 東京
• [Presentation] 上皮性卵巣癌の再発時期によるプラチナ抵抗性、感受性の再分布の試み (2013)
  • Author(s): 横山良仁
  • Organizer: 日本産科婦人科学術講演会
  • Place of Presentation: 札幌
• [Presentation] 婦人科悪性腫瘍術後管理 (2012)
  • Author(s): 横山良仁
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] 長期予後から眺めた産科婦人科疾患の健康管理３）婦人科悪性腫瘍術後管理 (2012)
  • Author(s): 横山良仁
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸
• [Presentation] パクリタキセルによる末梢神経障害に対する牛車腎気丸の予防効果 (2012)
  • Author(s): 松村由紀子、横山良仁、水沼英樹
  • Organizer: 第64回日本産科婦人科学会学術講演会
  • Place of Presentation: 神戸