Evolution of ovarian carcinoma cells through peritoneal dissemination ; genome-wide analysis and clinical application.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390452
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: KONISHI Ikuo 京都大学, 医学研究科, 教授 (90192062)
• Co-Investigator(Kenkyū-buntansha): MANDAI Masaki 京都大学, 医学研究科, 講師 (80283597) ; MATSUMURA Noriomi 京都大学, 医学研究科, 助教 (20452336) ; SUZUKI Ayako 京都大学, 医学研究科, 助教 (90378696) ; BABA Tsukasa 京都大学, 医学研究科, 助教 (60508240)
• Project Period (FY): 2009 – 2011
• Keywords: 婦人科腫瘍学

Research Abstract

1) Treatment of 39 ovarian cancer cell lines and 17 primary culture samples with the inhibitor of DNA methylation, followed by expression microarray, identified genes targeted by DNA methylation in ovarian cancer. This analysis revealed TGF-beta signaling pathway is regulated by genome-wide DNA methylation. 2) We found TGF-beta pathway activity is upregulated in the omental metastases of ovarian cancer. Then we demonstrated the inhibitor of TGF-beta signaling pathway is effective against disseminated metastasis of ovarian cancer using a mouse model. 3) We found expression of PDL-1 in ovarian cancer cells suppresses activity of CD8 positive T lymphocytes, causes immune escape, and facilitates peritoneal dissemination of ovarian cancer.

Research Products

• [Journal Article] Laeverin/amino peptidase Q induces trophoblast invasion during human early placentation (2012)
  • Author(s): Horie A, Fujiwara H, Sato Y, Suginami K, Matsumoto H, Maruyama M, Konishi I, Hattori A.
  • Journal Title: Hum Reprod Volume: 27 Pages: 1267-76
  • DOI: DOI:10.1093/humrep/des068
  • Peer Reviewed
• [Journal Article] Solitary fibrous tumor arising slowly in the vulva over 10 years : Case report and review (2012)
  • Author(s): Taki M, Baba T, Mandai M, Suzuki A, Mikami Y, Matsumura N, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 38(5) Pages: 884-8
  • DOI: DOI:10.1111/j.1447-0756.2011.01792.x
  • Peer Reviewed
• [Journal Article] Differential effects of inhibition of bone morphogenic protein(BMP) signalling on T-cell activation and differentiation (2012)
  • Author(s): Yoshioka Y, Ono M, Osaki M, Konishi I, Sakaguchi S.
  • Journal Title: Eur J Immunol Volume: 42(3) Pages: 749-59
  • DOI: DOI:10.1002/eji.201141702
  • Peer Reviewed
• [Journal Article] Advanced extragonadal yolk sac tumor serially followed up with(18) F-fluorodexyglucose-positoron emission tomography and computerized tomography and serum alpha-fetoprotein (2012)
  • Author(s): Baba T, Su S, Umeoka S, Abiko K, Nakamoto Y, Mandai M, Matsumura N, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 38(3) Pages: 605-9
  • DOI: DOI:10.1002/eji.201141702
  • Peer Reviewed
• [Journal Article] Phase II study of oral et oposide and intravenous irinotecan for patients with platinum-resistant and taxane-pretreated ovarian cancer : Japan Clinical Oncology Group Study 0503 (2012)
  • Author(s): Matsumoto K, Katsumata N, Saito I, Shibata T, Konishi I, Fukuda H, Kamura T.
  • Journal Title: Jpn J Clin Oncol Volume: 42(3) Pages: 222-5
  • DOI: DOI:10.1111/j.1447-0756.2011.01752.x
  • Peer Reviewed
• [Journal Article] Management of fetal death with placenta previa (2012)
  • Author(s): Taki M, Sato Y, Kakui K, Tatsumi K, Fujiwara H, Konishi I.
  • Journal Title: J Matern Fetal Neonatal Med Volume: 25(2) Pages: 196-9
  • DOI: DOI:10.3109/14767058.2011.560624
  • Peer Reviewed
• [Journal Article] Hypoxia up regulates ovarian cancer invasiveness via the binding of HIF-1αto a hypoxia-induced, methylation-free hypoxia response element of S100A4 gene (2012)
  • Author(s): Horiuchi A, Hayashi T, Kikuchi N, Hayashi A, Fuseya C, Shiozawa T, Konishi I.
  • Journal Title: Int J Cancer Volume: 27
  • DOI: DOI:10.1002/ijc.27448
  • Peer Reviewed
• [Journal Article] The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer (2012)
  • Author(s): Yamamura S, Matsumura N, Mandai M, Huang Z, Oura T, Baba T, Hamanishi J, Yamaguchi K, Kang HS, Okamoto T, Abiko K, Mori S, Murphy SK, Konishi I.
  • Journal Title: Int J Cancer Volume: 130(1) Pages: 20-8
  • DOI: DOI:10.1002/ijc.25961
  • Peer Reviewed
• [Journal Article] The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors (2011)
  • Author(s): Hamanishi J, Mandai M, Abiko K, Matsumura N, Baba T, Yoshioka Y, Kosaka K, Konishi I.
  • Journal Title: Clin Immunol Volume: 141(3) Pages: 338-47
  • DOI: DOI:10.1016/j.clim.2011.08.013
  • Peer Reviewed
• [Journal Article] Secondary postpartum hemorrhage due to uterine artery pseudo aneurysm rupture in von Will brand disease (2011)
  • Author(s): Shimizu M, Kondoh E, Ueda M, Kakui K, Tatsumi K, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(12) Pages: 1887-90
  • DOI: DOI:10.1111/j.1447-0756.2011.01674.x
  • Peer Reviewed
• [Journal Article] Adjuvant combined paclitaxel and carboplatin chemotherapy for glassy cell carcinoma of the uterine cervix : report of three cases with clinic pathological analysis (2011)
  • Author(s): Takahashi Y, Sasaki H, Mogami H, Hamada S, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(12) Pages: 1860-3
  • DOI: DOI:10.1111/j.1447-0756.2011.01643.x
  • Peer Reviewed
• [Journal Article] Alpha-fetoprotein producing ovarian clear cell carcinoma with a neometaplasia to hepatoid carcinoma arising from endometriosis : a case report (2011)
  • Author(s): Takahashi Y, Mogami H, Hamada S, Urasaki K, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(12) Pages: 1842-6
  • DOI: DOI:10.1111/j.1447-0756.2011.01622.x
  • Peer Reviewed
• [Journal Article] Ovarian clear cell carcinoma as a stress-responsive cancer : influence of the microenvironment on the carcinogenesis and cancer phenotype (2011)
  • Author(s): Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Konishi I.
  • Journal Title: Cancer Lett Volume: 310(2) Pages: 129-33
  • DOI: DOI:10.1016/j.canlet.2011.06.039
  • Peer Reviewed
• [Journal Article] CT and MR features of struma ovarii. (2011)
  • Author(s): Ikeuchi T, Koyama T, Tamai K, Fujimoto K, Mikami Y, Konishi I, Togashi K.
  • Journal Title: Abdom Imaging Volume: 4
  • DOI: DOI:10.1007/s00261-011-9817-7
  • Peer Reviewed
• [Journal Article] Disseminated intravascular coagulation as the presenting sign of gastric cancer during pregnancy (2011)
  • Author(s): Takai H, Kondoh E, Sato Y, Kakui K, Tatsumi K, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(11) Pages: 1717-9
  • DOI: DOI:10.1111/j.1447-0756.2011.01561.x
  • Peer Reviewed
• [Journal Article] Preoperative differential diagnosis of minimal deviation adenocarcinoma and lobular end cervical glandular hyperplasia of the uterine cervix : a multicenter study of clinico pathology and magnetic resonance imaging findings (2011)
  • Author(s): Takatsu A, Shiozawa T, Miyamoto T, Kurosawa K, Kashima H, Yamada T, Kaku T, Mikami Y, Kiyokawa T, Tsuda H, Ishii K, Togashi K, Koyama T, Fujinaga Y, Kadoya M, Hashi A, Susumu N, Konishi I.
  • Journal Title: Int J Gynecol Cancer Volume: 21(7) Pages: 1287-96
  • DOI: DOI:10.1097/IGC.0b013e31821f746c
  • Peer Reviewed
• [Journal Article] The history of the Gynecologic Cancer Study Group(GCSG) of the Japan Clinical Oncology Group(JCOG) (2011)
  • Author(s): Onda T, Konishi I, Yoshikawa H, Kamura T.
  • Journal Title: Jpn J Clin Oncol Volume: 41(10) Pages: 1156-61
  • DOI: DOI:10.1093/jjco/hyr111
  • Peer Reviewed
• [Journal Article] Laser-captured micro dissection-microarray analysis of the genes involved in endometrial carcinogenesis : stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance (2011)
  • Author(s): Miyamoto T, Kashima H, Suzuki A, Kikuchi N, Konishi I, Seki N, Shiozawa T.
  • Journal Title: Hum Pathol Volume: 42(9) Pages: 1265-74
  • DOI: DOI:10.1016/j.humpath.2010.07.027
  • Peer Reviewed
• [Journal Article] Japan Society of Obstetrics and Gynecology ; Japan Association of Obstetricians and Gynecologists. Guidelines for obstetrical practice in Japan : Japan Society of Obstetrics and Gynecology(JSOG) and Japan Association of Obstetricians and Gynecologists(JAO (2011)
  • Author(s): Minakami H, Hiramatsu Y, Koresawa M, Fujii T, Hamada H, Iitsuka Y, Ikeda T, Ishikawa H, Ishimoto H, Itoh H, Kanayama N, Kasuga Y, Kawabata M, Konishi I, Matsubara S, Matsuda H, Murakoshi T, Ohkuchi A, Okai T, Saito S, Sakai M, Satoh S, Sekizawa A, Suzuki
  • Journal Title: J Obstet Gynaecol Res Volume: 37(9) Pages: 1174-97
  • DOI: DOI:10.1111/j.1447-0756.2011.01653.x
  • Peer Reviewed
• [Journal Article] Involvement of proteasomeβ1i subunit, LMP2, on development of uterin leiomyosarcma (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Shiozawa T, Kanai Y, Yaegashi N, Aburatani H, Tonegawa S, Konishi I.
  • Journal Title: N Am J Med Sci Volume: 3(9) Pages: 394-9
  • DOI: DOI:10.4297/najms.2011.3394
  • Peer Reviewed
• [Journal Article] Successful recovery from delayed amniotic fluid embolism with prolonged cardiac resuscitation (2011)
  • Author(s): Hosono K, Matsumura N, Matsuda N, Fujiwara H, Sato Y, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(8) Pages: 1122-5
  • DOI: DOI:10.1111/j.1447-0756.2010.01470.x
  • Peer Reviewed
• [Journal Article] Primary squamous cell carcinoma of fallopian tube accompanied by gastric metaplasia of female genital tract : case report and review (2011)
  • Author(s): Satoh H, Baba T, Mandai M, Suzuki A, Matsumura N, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(8) Pages: 1106-11
  • DOI: DOI:10.1111/j.1447-0756.2010.01464.x
  • Peer Reviewed
• [Journal Article] Cerebral hemodynamics in newborn infants exposed to speech sounds : A whole-head optical topography study (2011)
  • Author(s): Sato H, Hirabayashi Y, Tsubokura H, Kanai M, Ashida T, Konishi I, Uchida-Ota M, Konishi Y, Maki A.
  • Journal Title: Hum Brain Mapp Volume: 28
  • DOI: DOI:10.1002/hbm.21350
  • Peer Reviewed
• [Journal Article] Clinical value of FDG-PET for preoperative evaluation of endometrial cancer (2011)
  • Author(s): Suga T, Nakamoto Y, Saga T, Higashi T, Hamanaka Y, Tatsumi M, Hayashida K, Hara T, Konishi I, Fujii S, Togashi K.
  • Journal Title: Ann Nucl Med Volume: 25(4) Pages: 269-75
  • DOI: DOI:10.1007/s12149-011-0474-2
• [Journal Article] EphrinA1 stimulates cell attachment and inhibits cell aggregation through the EphA receptor pathway in human endometrial carcinoma-derived Ishikawa cells (2011)
  • Author(s): Fujii H, Fujiwara H, Horie A, SuginamiK, Sato Y, Konishi I.
  • Journal Title: Hum Reprod Volume: 26(5) Pages: 1163-70
  • DOI: DOI:10.1093/humrep/der034
  • Peer Reviewed
• [Journal Article] Management of retained products of conception with marked vascularity (2011)
  • Author(s): Kitahara T, Sato Y, Kakui K, Tatsumi K, Fujiwara H, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(5) Pages: 458-64
  • DOI: DOI:10.1111/j.1447-0756.2010.01363.x
  • Peer Reviewed
• [Journal Article] GPR54 is a target for suppression of metastasis in endometrial cancer (2011)
  • Author(s): Kang HS, Baba T, Mandai M, Matsumura N, Hamanishi J, Kharma B, Kondoh E, Yoshioka Y, Oishi S, Fujii N, Murphy SK, Konishi I.
  • Journal Title: Mol Cancer Ther Volume: 10(4) Pages: 580-90
  • DOI: DOI:10.1158/1535-7163.MCT-10-0763
  • Peer Reviewed
• [Journal Article] Endometrial cancer implanted within a cesarean section scar (2011)
  • Author(s): Baba T, Mandai M, Yamanishi Y, Suzuki A, Kang HS, Konishi I.
  • Journal Title: J Obstet Gynaecol Res Volume: 37(3) Pages: 245-9
  • DOI: DOI:10.1111/j.1447-0756.2010.01381.x
  • Peer Reviewed
• [Journal Article] Distinguishing primary from secondary mucinous ovarian tumors : an algorithm using the novel marker DPEP1 (2011)
  • Author(s): Okamoto T, Matsumura N, Mandai M, Oura T, Yamanishi Y, Horiuchi A, Hamanishi J, Baba T, Koshiyama M, Shiozawa T, Konishi I.
  • Journal Title: Mod Pathol Volume: 24(2) Pages: 267-76
  • DOI: DOI:10.1038/modpathol.2010.204
  • Peer Reviewed
• [Journal Article] Epigenetic suppression of the TGF-beta pathway revealed by transcript me profiling in ovarian cancer (2011)
  • Author(s): Matsumura N, Huang Z, Mori S, Baba T, Fujii S, Konishi I, Iversen ES, Berchuck A, Murphy SK.
  • Journal Title: Genome Res Volume: 21(1) Pages: 74-82
  • DOI: DOI:10.1101/gr.108803.110
  • Peer Reviewed
• [Journal Article] Molecular Approach to Uterine Leiomyosarcoma : LMP2-Deficient Mice as an Animal Model of Spontaneous Uterine Leiomyosarcoma (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Sarcoma Volume: 2011 Pages: 476498
  • DOI: DOI:10.1155/2011/476498
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy (2011)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Sudo T, Tagawa Y, Nishimura R, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Konishi I.
  • Journal Title: Sci Rep Volume: 1 Pages: 180
  • DOI: DOI:10.1038/srep00180
  • Peer Reviewed
• [Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic grade and degree of differentiation (2010)
  • Author(s): Abiko K, Mandai M, Hamanishi J, Matsumura N, Baba T, Horiuchi A, Mikami Y, Yoshioka S, Wakasa T, Shiozawa T, Konishi I.
  • Journal Title: Am J Surg Pathol Volume: 34(12) Pages: 1842-8
  • DOI: DOI:10.1097/PAS.0b013e3181fcd707
  • Peer Reviewed
• [Journal Article] Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcripto me profiling (2010)
  • Author(s): Matsumura N, Mandai M, Okamoto T, Yamaguchi K, Yamamura S, Oura T, Baba T, Hamanishi J, Kang HS, Matsui S, Mori S, Murphy SK, Konishi I.
  • Journal Title: Cancer Sci Volume: 101(12) Pages: 2658-63
  • DOI: DOI:10.1111/j.1349-7006.2010.01736.x
  • Peer Reviewed
• [Journal Article] Suppression of metastatic murine ovarian cancer cells by transduced embryonic progenitor cells (2010)
  • Author(s): Mandai M, Hamanishi J, Abiko K, Matsumura N, Baba T, Yoshioka Y, Konishi I.
  • Journal Title: Horm Cancer Volume: 1(6) Pages: 291-6
  • DOI: DOI:10.1007/s12672-010-0046-2
  • Peer Reviewed
• [Journal Article] Type-specific roles of his tone deacetylase(HDAC) over expression in ovarian carcinoma : HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with down regulation of E-cadherin (2010)
  • Author(s): Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, Konishi I, Shiozawa T.
  • Journal Title: Int J Cancer Volume: 127(6) Pages: 1332-46
  • DOI: DOI:10.1002/ijc.25151
  • Peer Reviewed
• [Journal Article] Shiozawa T. Cyclin A2 confers cisplatin resistance to endometrial carcinoma cells via up-regulation of an Akt-binding protein, periplakin (2010)
  • Author(s): Suzuki A, Horiuchi A, Ashida T, Miyamoto T, Kashima H, Nikaido T, Konishi I
  • Journal Title: J Cell Mol Med Volume: 14(9) Pages: 2305-17
  • DOI: DOI:10.1111/j.1582-4934.2009.00839.x
  • Peer Reviewed
• [Journal Article] Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma (2010)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Protein Cell Volume: 1(8) Pages: 711-7
  • DOI: DOI:10.1007/s13238-010-0095-x
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of his tone deacetylases in endometrial carcinoma : involvement of his tone deacetylase 2 in the proliferation of endometrial carcinoma cells (2010)
  • Author(s): Fakhry H, Miyamoto T, Kashima H, Suzuki A, Ke H, Konishi I, Shiozawa T.
  • Journal Title: Hum Pathol Volume: 41(6) Pages: 848-58
  • DOI: DOI:10.1016/j.humpath.2009.11.012
  • Peer Reviewed
• [Journal Article] Targeting slow-proliferating ovarian cancer cells (2010)
  • Author(s): Kondoh E, Mori S, Yamaguchi K, Baba T, Matsumura N, Cory Barnett J, Whitaker RS, Konishi I, Fujii S, Berchuck A, Murphy SK.
  • Journal Title: Int J Cancer Volume: 126(10) Pages: 2448-56
  • DOI: DOI:10.1002/ijc.24919
  • Peer Reviewed
• [Journal Article] Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer : a proposal for patient selection (2010)
  • Author(s): Satoh T, Hatae M, Watanabe Y, Yaegashi N, Ishiko O, Kodama S, Yamaguchi S, Ochiai K, Takano M, Yokota H, Kawakami Y, Nishimura S, Ogishima D, Nakagawa S, Kobayashi H, Shiozawa T, Nakanishi T, Kamura T, Konishi I, Yoshikawa H.
  • Journal Title: J Clin Oncol Volume: 28(10) Pages: 1727-32
  • DOI: DOI:10.1200/JCO.2009.24.8617
  • Peer Reviewed
• [Journal Article] Inverse correlation between Skp2 and p27(Kip1) in normal endometrium and endometrial carcinoma (2010)
  • Author(s): Miyamoto T, Horiuchi A, Kashima H, Suzuki A, Yamada T, Kurai M, Konishi I, Shiozawa T.
  • Journal Title: Gynecol Endocrinol Volume: 26(3) Pages: 220-9
  • DOI: DOI:10.1080/09513590903215482
  • Peer Reviewed
• [Journal Article] Transcription factor POU6F1 is important for proliferation of clear cell adenocarcinoma of the ovary and is a potential new molecular target (2010)
  • Author(s): Suzuki N, Yoshioka N, Uekawa A, Matsumura N, Tozawa A, Koike J, Konishi I, Kiguchi K, Ishizuka B.
  • Journal Title: Int J Gynecol Cancer Volume: 20(2) Pages: 212-9
  • DOI: DOI:10.1111/IGC.0b013e3181c97ae0
  • Peer Reviewed
• [Journal Article] Minimal deviation mucinous adenocarcinoma(' adenoma malignum') of the uterine corpus (2010)
  • Author(s): Abiko K, Baba T, Ogawa M, Mikami Y, Koyama T, Mandai M, Konishi I.
  • Journal Title: Pathol Int Volume: 60(1) Pages: 42-7
  • DOI: DOI:10.1111/j.1440-1827.2009.02473.x
  • Peer Reviewed
• [Journal Article] Activated local immunity by CC chemokine ligand 19-transduced embryonic endothelial progenitor cells suppresses metastasis of murine ovarian cancer (2010)
  • Author(s): Hamanishi J, Mandai M, Matsumura N, Baba T, Yamaguchi K, Fujii S, Konishi I
  • Journal Title: Stem Cells Volume: 28(1) Pages: 164-73
  • DOI: DOI:10.1002/stem.256
  • Peer Reviewed
• [Journal Article] Ovarian cancer in endometriosis : molecular biology, pathology, and clinical management (2009)
  • Author(s): Mandai M, Yamaguchi K, Matsumura N, Baba T, Konishi I.
  • Journal Title: Int J Clin Oncol Volume: 14(5) Pages: 383-91
  • DOI: DOI:10.1007/s10147-009-0935-y
  • Peer Reviewed
• [Journal Article] Ovarian cancer in endometriosis (2009)
  • Author(s): Konishi I
  • Journal Title: Int J Clin Oncol Volume: 14(5) Pages: 377
  • DOI: DOI:10.1007/s10147-009-0930-3
  • Peer Reviewed
• [Journal Article] Changes in the expression of E-cadherin repressors, Snail, Slug, SIP1, and Twist, in the development and progression of ovarian carcinoma : the important role of Snail in ovarian tumori genesis and progression (2009)
  • Author(s): Yoshida J, Horiuchi A, Kikuchi N, Hayashi A, Osada R, Ohira S, Shiozawa T, Konishi I.
  • Journal Title: Med Mol Morphol Volume: 42(2) Pages: 82-91
  • DOI: DOI:10.1007/s00795-008-0436-5
  • Peer Reviewed