Elucidation of the molecular mechanisms and prognostic perspectives for ovarian cancer induced by iron overload due to endometriosis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nagoya City University (2012-2013); Nagoya University (2011)
• Principal Investigator: YAMASHITA Yoriko 名古屋市立大学, 医学(系)研究科(研究院), 講師 (90303643)
• Co-Investigator(Kenkyū-buntansha): TOYOKUNI Shinya 名古屋大学, 大学院医学系研究科, 教授 (90252460)
• Co-Investigator(Renkei-kenkyūsha): YATABE Yasushi 愛知県がんセンター中央病院, 遺伝子病理 診断部, 部長 (90280809)
• Project Period (FY): 2011 – 2013
• Keywords: 卵巣明細胞腺癌 / 子宮内膜症 / Met / 酸化ストレス / CBX7

Research Abstract

Previous reports indicated that ovarian endometrioid and clear cell adenocarcinoma develop in association with oxidative stress due to excess of iron deposit. In this term, we performed array CGH analysis to find Met gene amplification in a certain proportion of ovarian clear cell adenocarcinoma samples correlated with worse prognosis (Yamashita et al. PLoS One 2013). Expression of CBX7, which is known to collaborate with the ANRIL gene reported to be associated with endometriosis, also had relationship with worse prognosis of the patients (Shinjo K, Yamashita Y et al. Int J Cancer 2014). We also analyzed the role of ectopic stromal cells in endometriotic cysts (Kobayashi H, Yamashita Y et al Fertil Steril 2012).

Research Products

• [Journal Article] Napsin A is a specific marker for ovarian clear cell adenocarcinoma (2014)
  • Author(s): Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M, Takahashi S
  • Journal Title: Mod Pathol Volume: (Epub ahead of print) Pages: 61
  • Peer Reviewed
• [Journal Article] Connective tissue growth factor and beta-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma (2014)
  • Author(s): Jiang L, Yamashita Y, Chew SH, Akatsuka S, Ukai S, Wang S, Nagai H, Okazaki Y, Takahashi T, Toyokuni S
  • Journal Title: J Pathol Volume: (Epub ahead of print)
  • DOI: 10.1002/path.4377
  • Peer Reviewed
• [Journal Article] Establishment of an invasive prostate cancer model in transgenic rats by intermittent testosterone administration (2014)
  • Author(s): Sato S, Suzuki S, Naiki-Ito A, Komiya M, Ne L, Kato H, Sagawa H, Yamashita Y, Shirai T, Takahashi S
  • Journal Title: J Toxicol Pathol Volume: (Epub ahead of print)
  • DOI: 10.1293/tox.2013-0052
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of an O(6)-methylguanine-DNA methyltransferase-siRNA/liposome complex administered by convection-enhanced delivery to rat and porcine brains (2014)
  • Author(s): Tsujiuchi T, Natsume A, Motomura K, Kondo G, Ranjit M, Hachisu R, Sugimura I, Tomita S, Takehara I, Woolley M, Barua NU, Gill SS, Bienemann AS, Yamashita Y, Toyokuni S, Wakabayashi T
  • Journal Title: Am J Transl Res. Volume: 6巻2号 Pages: 169-78
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902228/
  • Peer Reviewed
• [Journal Article] Ovarian mucinous tumors arising from mature cystic teratomas-a molecular genetic approach for understanding the cellular origin (2014)
  • Author(s): Fujii K, Yamashita Y, Yamamoto T, Takahashi K, Hashimoto K, Miyata T, Kawai K, Kikkawa F, Toyokuni S, Nagasaka T
  • Journal Title: Hum Pathol Volume: 45巻4号 Pages: 717-24
  • DOI: 10.1016/j.humpath.2013.10.031
  • Peer Reviewed
• [Journal Article] Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation (2014)
  • Author(s): Shinjo K, Yamashita Y, Yamamoto E, Akatsuka S, Uno N, Kamiya A, Niimi K, Sakaguchi Y, Nagasaka T, Takahashi T, Shibata K, Kajiyama H, Kikkawa F, Toyokuni S
  • Journal Title: Int J Cancer Volume: 135巻2号 Pages: 308-18
  • DOI: 10.1002/ijc.28692
  • Peer Reviewed
• [Journal Article] Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production (2014)
  • Author(s): Chew SH, Okazaki Y, Nagai H, Misawa N, Akatsuka S, Yamashita K, Jiang L, Yamashita Y, Noguchi M, Hosoda K, Sekido Y, Takahashi T, Toyokuni S
  • Journal Title: Carcinogenesis Volume: 35巻1号 Pages: 164-72
  • DOI: 10.1093/carcin/bgt267
  • Peer Reviewed
• [Journal Article] Lack of presence of the human cytomegalovirus in human glioblastoma (2013)
  • Author(s): Yamashita Y, Ito Y, Isomura H, Takemura N, Okamoto A, Motomura K, Tsujiuchi T, Natsume A, Wakabayashi T, Toyokuni S, Tsurumi T
  • Journal Title: Mod Pathol Volume: (Epub ahead of print)
  • DOI: 10.1038/modpathol.2013.219
  • Peer Reviewed
• [Journal Article] Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis (2013)
  • Author(s): Suzuki S, Shiraga K, Sato S, Punfa W, Naiki-Ito A, Yamashita Y, Shirai T, Takahashi S
  • Journal Title: Cancer Sci Volume: 104巻12号 Pages: 1711-7
  • DOI: 10.1111/cas.12292
  • Peer Reviewed
• [Journal Article] β4GalT6 is involved in the synthesis of lactosylceramide with less intensity thanβ4GalT5 (2013)
  • Author(s): Tokuda N, Numata S, Li X, Nomura T, Takizawa M, Kondo Y, Yamashita Y, Hashimoto N, Kiyono T, Urano T, Furukawa K, Furukawa K
  • Journal Title: Glycobiology Volume: 23巻10号 Pages: 1175-83
  • DOI: 10.1093/glycob/cwt054
  • Peer Reviewed
• [Journal Article] Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis (2013)
  • Author(s): Yamashita Y, Akatsuka S, Shinjo K, Yatabe Y, Kobayashi H, Seko H, Kajiyama H, Kikkawa F, Takahashi T, Toyokuni S
  • Journal Title: PLoS One Volume: 8巻3号 Pages: e57724
  • DOI: 10.1371/journal.pone.0057724
  • Peer Reviewed
• [Journal Article] Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer (2012)
  • Author(s): Akatsuka S, Yamashita Y, Ohara H, Liu YT, Izumiya M, Abe K, Ochiai M, Jiang L, Nagai H, Okazaki Y, Murakami H, Sekido Y, Arai E, Kanai Y, Hino O, Takahashi T, Nakagama H, Toyokuni S
  • Journal Title: PLoS One Volume: 7巻8号 Pages: e43403
  • DOI: 10.1371/journal.pone.0043403
  • Peer Reviewed
• [Journal Article] Iron overload signature in chrysotile-induced malignant mesothelioma (2012)
  • Author(s): Jiang L, Akatsuka S, Nagai H, Chew SH, Ohara H, Okazaki Y, Yamashita Y, Yoshikawa Y, Yasui H, Ikuta K, Sasaki K, Kohgo Y, Hirano S, Shinohara Y, Kohyama N, Takahashi T, Toyokuni S
  • Journal Title: J Pathol Volume: 228巻3号 Pages: 366-77
  • DOI: 10.1002/path.4075
  • Peer Reviewed
• [Journal Article] The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis (2012)
  • Author(s): Kobayashi H, Yamashita Y, Iwase A, Yoshikawa Y, Yasui H, Kawai Y, Uchida K, Uno N, Akatsuka S, Takahashi T, Kikkawa F, Toyokuni S
  • Journal Title: Fertil Steril Volume: 98巻2号 Pages: 415-22
  • DOI: 10.1016/j.fertnstert.2012.04.047
  • Peer Reviewed
• [Journal Article] Diameter and rigidity of multi-walled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis (2011)
  • Author(s): Nagai H, Okazaki Y, Chew SH, Misawa N, Yamashita Y, Akatsuka S, Ishihara T, Yamashita K, Yoshikawa Y, Yasui H, Jiang L, Ohara H, Takahashi T, Ichihara G, Kostarelos K, Miyata Y, Shinohara H and Toyokuni S
  • Journal Title: Proc Natl Acad Sci USA Volume: 108巻49号 Pages: E1330-8
  • DOI: 10.1073/pnas.1110013108
  • Peer Reviewed
• [Journal Article] XCR1 expression and biased VH gene usage are distinct features of diffuse large B-cell lymphoma initially manifesting in the bone marrow (2011)
  • Author(s): Yamashita Y, Kajiura D, Tang L, Hasegawa Y, Kinoshita T, Nakamura S, Akatsuka S, Toyokuni S, and Mori N
  • Journal Title: Am J Clin Pathol Volume: 135巻4号 Pages: 556-64
  • DOI: 10.1309/AJCPCTDC5PY3LXBP
  • Peer Reviewed
• [Journal Article] Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and N-(carboxymethyl)lysine in human epidermis (2011)
  • Author(s): Toyokuni S, Hirao A, Wada T, Nagai R, Date A, Yoshii T, Akatsuka S, Yamashita Y, Kawada A
  • Journal Title: J Clin Biochem Nutr Volume: 49巻2号 Pages: 121-4
  • DOI: 10.3164/jcbn.11-05
  • Peer Reviewed
• [Journal Article] Spatiotemporally Different DNA Repair Systems participating During Epstein-Barr Virus Genome Maturation (2011)
  • Author(s): Sugimoto A, Kanda T, Yamashita Y, Murata T, Saito S, Kawashima D, Isomura H, Nishiyama Y, Tsurumi T
  • Journal Title: J.Virol Volume: 85巻13号 Pages: 6127-35
  • DOI: 10.1128/JVI.00258-11
  • Peer Reviewed
• [Journal Article] The human cytomegalovirus gene products essential for late viral gene expression assemble into pre- replication complexes before viral DNA replication (2011)
  • Author(s): Isomura H, Stinski MF, Murata T, Yamashita Y, Kanda T, Toyokuni S, Tsurumi T
  • Journal Title: J.Virol Volume: 85巻13号 Pages: 6629-44
  • DOI: 10.1128/JVI.00384-11
  • Peer Reviewed
• [Presentation] 膠芽腫はヒトサイトメガロウイルス陰性である (2014)
  • Author(s): 山下依子
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 20140424-26
• [Presentation] 卵巣粘液性腫瘍は成熟奇形腫より発生する-分子遺伝学的アプローチによる組織起源の解明- (2014)
  • Author(s): 山下依子, 藤井佳穂, 高橋智, 豊國伸哉, 長坂徹郎
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 20140424-26
• [Presentation] CBX7 expression is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation (2014)
  • Author(s): Yamashita Y, Shinjo K, Akatsuka S, Toyokuni S
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International (SFRRI 2014)
  • Place of Presentation: 京都
  • Year and Date: 20140323-26
• [Presentation] 卵巣奇形腫に合併する粘液性腫瘍の遺伝学的解析 (2013)
  • Author(s): 山下依子, 藤井佳穂, 梶山広明, 吉川史隆, 高橋智, 豊國伸哉, 長坂徹郎
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] 卵巣明細胞腺癌におけるポリコーム蛋白CBX7の役割の解析 (2013)
  • Author(s): 山下依子, 新城加奈子, 豊國伸哉, 長坂徹郎
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
  • Year and Date: 20130606-08
• [Presentation] Expression of chromobox homolog 7 (Cbx7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via regulating TRAIL-induced apoptotic pathway (2013)
  • Author(s): Yamashita Y, Shinjo K, Yamamoto E, Akatuka S, Takahashi T, Kajiyama H, Kikkawa F, Toyokuni S
  • Organizer: 103th Annual meeting of the American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20130406-10
• [Presentation] 卵巣明細胞腺癌においてCBX7の発現は予後不良因子である。 (2012)
  • Author(s): 新城加奈子, 山下依子, 豊國伸哉, 吉川史隆
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] 卵巣明細胞性腺癌におけるnon-coding RNA'ANRIL'の発現の検討 (2012)
  • Author(s): 山下依子, 宇野希望, 赤塚慎也, 豊國伸哉
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] Array CGH Analysis Reveals Amplification of Met and AKT2 in Clear Cell Carcinoma of the Ovary (2012)
  • Author(s): Yamashita Y, Akatsuka S, Yatabe Y, Toyokuni S
  • Organizer: 101th Annual meeting of the United States and Canadian Academy of Pathology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20120317-23
• [Presentation] 異所性子宮間質細胞の卵巣明細胞腺癌発生における役割について (2011)
  • Author(s): 山下依子, 小林浩晴, 赤塚慎也, 永井裕崇, 吉川史隆, 高橋隆, 豊國伸哉
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111001-03
• [Presentation] Met Amplification is a Molecular Hallmark in Endometriosis-associated Ovarian Clear Cell Carcinoma and Correlates with Worse Prognosis (2011)
  • Author(s): Yamashita Y, Yatabe Y, Akatsuka S, Kajiyama H, Kikkawa F, Takahashi T, Toyokuni S
  • Organizer: 16^<th> European Multidisciplinary Cancer Congress
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20110922-27
• [Presentation] 子宮内膜症における発癌メカニズム解明の試み (2011)
  • Author(s): 山下依子, 小林浩晴, 赤塚慎也, 宇野希望, 谷田部恭, 豊國伸哉
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20110428-30
• [Book] 第18章女性生殖器ロビンス基礎病理学第9版,豊國伸哉監訳 (2014)
  • Author(s): 山下依子(訳)
  • Publisher: エルゼビア・ジャパン社
• [Book] Endometriosis associated ovarian cancer - the role of oxidative stress - (2012)
  • Author(s): Yoriko Yamashita and Shinya Toyokuni
  • Total Pages: 311-24
  • Publisher: Baidyanath Chakravarty
• [Book] 第19章女性生殖器ロビンス基礎病理学第8版,豊國伸哉, 高橋雅英監訳 (2011)
  • Author(s): 山下依子(訳)