食品の違いが卵巣がんの進展に影響を及ぼすメカニズムの解析

2016 Fiscal Year Research-status Report

• Project/Area Number: 16K15707
• Research Institution: Kyoto University
• Principal Investigator: 松村 謙臣 京都大学, 医学研究科, 准教授 (20452336)
• Co-Investigator(Kenkyū-buntansha): 安彦 郁 京都大学, 医学研究科, 助教 (20508246) ; 越山 雅文 京都大学, 医学研究科, 客員研究員 (50724390) ; 小西 郁生 京都大学, 医学研究科, 名誉教授 (90192062)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 卵巣癌 / 動物性タンパク質 / 植物性タンパク質

Outline of Annual Research Achievements

HM-1マウス卵巣癌細胞株をB6C3F1マウス皮下に接種し、マウスの食餌中のタンパク質の種類と量を変えることで、腫瘍の増殖が異なるかを調べた。食餌の種類を動物性タンパク質20%、動物性タンパク質10%、植物性タンパク質20%、植物性タンパク質10%の４群に分けて、HM-1細胞を皮下接種した腫瘍のサイズを比較したところ、動物性タンパク質20%群は、動物性タンパク質10%群や植物性タンパク質20%群よりも有意に腫瘍のサイズが大きかった。また、この結果は、腫瘍を接種後２週間過ぎた時点で、食餌の種類を変えても同様であった。
HM-1マウス卵巣癌細胞株をB6C3F1マウス腹腔内に投与し、癌性腹膜炎を生じさせ、食餌の種類を動物性タンパク質20%、植物性タンパク質20%の２群の間で腹水の貯留（腹囲で評価）やマウスの生存期間が異なるかを調べた。その結果、植物性タンパク質20%群は動物性タンパク質20%群に比して、腹囲の増大が有意に少なく、マウスの生存期間が有意に延長した。同様の結果は、ID-8マウス卵巣癌細胞株をC57BL/6マウスの腹腔内に接種したモデルでも再現できた。
以上より、マウス卵巣癌細胞の皮下接種モデル、癌性腹膜炎モデルいずれにおいても、食餌内の動物性タンパク質は植物性タンパク質に比して、腫瘍増殖を促進させることが明らかとなった。本結果により、動物性タンパク質を植物性タンパク質に変えることが、卵巣癌の予防や、卵巣癌と診断された患者の予後の改善につながる可能性がある。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

食餌内のタンパク質の種類の違いによる腫瘍増殖の違いについて、マウスモデルで再現性をもって明らかにすることができた。今年度は、その実験系をもとに、メカニズムを探索することができる。

Strategy for Future Research Activity

タンパク質の種類の違いは、血清中のIGF-1、グルコース、インシュリンの濃度の違いや、腫瘍細胞のmTOR活性をもたらす可能性がある。本年度は、マウスモデルを用いて、それらを評価する。

Research Products

• [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: 826-833
  • DOI: 10.12659/MSM.899741
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor Cells. (2017)
  • Author(s): Horikawa N, Abiko K, Matsumura N, Hamanishi J, Baba T, Yamaguchi K, Yoshioka Y, Koshiyama M, Konishi I.
  • Journal Title: Clin Cancer Res. Volume: 23 Pages: 587-599
  • DOI: 10.1158/1078-0432.CCR-16-0387.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Groin lymph node detection and sentinel lymph node biopsy in vulvar cancer. (2016)
  • Author(s): Sakae C, Yamaguchi K, Matsumura N, Nakai H, Yoshioka Y, Kondoh E, Hamanishi J, Abiko K, Koshiyama M, Baba T, Kido A, Mandai M, Konishi I
  • Journal Title: J Gynecol Oncol. Volume: 27 Pages: e57
  • DOI: 10.3802/jgo.2016.27.e57.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical Efficacy of Ovarian Cancer Screening. (2016)
  • Author(s): Koshiyama M, Matsumura N, Konishi I
  • Journal Title: J Cancer. Volume: 7 Pages: 1311-1316
  • DOI: 10.7150/jca.14615. eCollection 2016.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma. (2016)
  • Author(s): Abou-Taleb H, Yamaguchi K, Matsumura N, Murakami R, Nakai H, Higasa K, Amano Y, Abiko K, Yoshioka Y, Hamanishi J, Koshiyama M, Baba T, Yamada R, Matsuda F, Konishi I, Mandai M.
  • Journal Title: Oncotarget. Volume: 7 Pages: 54758-54770
  • DOI: 10.18632/oncotarget.10181.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer. (2016)
  • Author(s): Yamanoi K, Matsumura N, Murphy SK, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Koshiyama M, Konishi I, Mandai M.
  • Journal Title: Oncotarget. Volume: 7 Pages: 47620-47636
  • DOI: 10.18632/oncotarget.9951.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Two cases of Wolffian tumor with novel magnetic resonance imaging findings reflecting characteristic pathology. (2016)
  • Author(s): Sakai M, Abiko K, Matsumura N, Kondoh E, Yamaguchi K, Minamiguchi S, Kurata Y, Kido A, Konishi I.
  • Journal Title: J Obstet Gynaecol Res. Volume: 42 Pages: 1046-1051
  • DOI: 10.1111/jog.13020.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports. (2016)
  • Author(s): Hino M, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Kondoh E, Koshiyama M, Baba T, Matsumura N, Minamiguchi S, Kido A, Konishi I.
  • Journal Title: Mol Clin Oncol. Volume: 4 Pages: 699-704
  • DOI: 10.3892/mco.2016.789
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tubo-ovarian abscess with endometrial cyst probably infected by Campylobacter fetus: Two cases. (2016)
  • Author(s): Kitamura S, Matsumura N, Ohtake N, Kita M, Konishi I.
  • Journal Title: J Obstet Gynaecol Res. Volume: 42 Pages: 1052-1057
  • DOI: 10.1111/jog.13004.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prediction of taxane and platinum sensitivity in ovarian cancer based on gene expression profiles. (2016)
  • Author(s): Murakami R, Matsumura N, Brown JB, Wang Z, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Baba T, Koshiyama M, Mandai M, Yamada R, Konishi I.
  • Journal Title: Gynecol Oncol. Volume: 141 Pages: 49-56
  • DOI: 10.1016/j.ygyno.2016.02.027.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes. (2016)
  • Author(s): Murakami R, Matsumura N, Mandai M, Yoshihara K, Tanabe H, Nakai H, Yamanoi K, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba T, Koshiyama M, Enomoto T, Okamoto A, Murphy SK, Mori S, Mikami Y, Minamiguchi S, Konishi I.
  • Journal Title: Am J Pathol. Volume: 186 Pages: 1103-1113
  • DOI: 10.1016/j.ajpath.2015.12.029.
  • Peer Reviewed / 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 Pages: 346-356
  • DOI: 10.1177/0300060515591858.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-a potential therapeutic target. (2016)
  • Author(s): Peng J, Yoshioka Y, Mandai M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Kharma B, Murakami R, Abiko K, Murphy SK, Konishi I.
  • Journal Title: Mol Carcinog. Volume: 55 Pages: 335-345
  • DOI: 10.1002/mc.22283.
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The resistance to anti-VEGF therapy in ovarian cancer is mediated through recruitment of hypoxia-induced MDSC. (2017)
  • Author(s): Naoki Horikawa, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Ken Yamaguchi, Ikuo Konishi, Noriomi Matsumura
  • Organizer: 第69回日本産科婦人科学会学術講演会
  • Place of Presentation: 広島グリーンアリーナ
  • Year and Date: 2017-04-13 – 2017-04-16
• [Presentation] The impact of anti-PD-1 antibody Nivolumab on chemo-sensitivity of platinum-resistant recurrent ovarian cancer. (2017)
  • Author(s): Yoshihide Inayama, Junzo Hamanishi, Masaki Mandai, Noriomi Matsumura, Kaoru Abiko, Ryusuke Murakami, Ken Yamaguchi, Tsukasa Baba, Ikuo Konishi
  • Organizer: 第69回日本産科婦人科学会学術講演会
  • Place of Presentation: 広島グリーンアリーナ
  • Year and Date: 2017-04-13 – 2017-04-16
• [Presentation] Suppression of Warburg effect enhances cisplatin sensitivity in ovarian clear cell carcinoma. (2017)
  • Author(s): Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura
  • Organizer: 第69回日本産科婦人科学会学術講演会
  • Place of Presentation: 広島グリーンアリーナ
  • Year and Date: 2017-04-13 – 2017-04-16
• [Presentation] Snail inhibits anti-tumor immunity through upregulation of CXCR2 ligands in ovarian cancer. (2017)
  • Author(s): Mana Taki, Kaoru Abiko, Tsukasa Baba, Junzo Hamanishi, Ken Yamaguchi, Ryusuke Murakami, Naoki Horikawa, Noriomi Matsumura
  • Organizer: 第69回日本産科婦人科学会学術講演会
  • Place of Presentation: 広島グリーンアリーナ
  • Year and Date: 2017-04-13 – 2017-04-16
• [Presentation] HER-2 expression in Gastric type adenocarcinoma of the uterine cervix. (2017)
  • Author(s): Ayano Holmes, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Eiji Kondo, Tsukasa Baba, Noriomi Matsumura
  • Organizer: 第69回日本産科婦人科学会学術講演会
  • Place of Presentation: 広島グリーンアリーナ
  • Year and Date: 2017-04-13 – 2017-04-16