Elucidation of mechanisms of cancer metastasis via lymphatic stomata under physiological and pathological conditions

• Project/Area Number: 24590242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Tokyo Medical University
• Principal Investigator: OSHIRO Hisashi 東京医科大学, 医学部, 准教授 (60381513)
• Co-Investigator(Kenkyū-buntansha): NAGAO Toshitaka 東京医科大学, 医学部, 教授 (90276709) ; OKUDELA Koji 横浜市立大学, 医学部, 講師 (10326027)
• Co-Investigator(Renkei-kenkyūsha): OHTANI Osamu 東京医科大学, 医学部, 客員教授 (90127548) ; MIURA Masahiro 大分大学, 医学部, 講師 (50199957)
• Research Collaborator: SERIZAWA Hiromi 東京医科大学, 医学部, 准教授
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: lymphatic stomata / リンパ管小孔 / 逆行性リンパ行性癌転移 / rerouting / 癌性胸水 / 胸膜播種 / 癌性腹水 / 腹膜播種 / 漿膜 / 腹膜 / 胸膜 / 弁 / 逆行性リンパ行性転移 / rabbit / VX2 / cancer-bearing animal / gene transfer / GFP / comparative anatomy / functional anatomy / lymphology / 癌性腹膜炎 / 癌性胸膜炎

Outline of Final Research Achievements

To know characters of lymphatic stomata (LS) in the pleura and peritoneum under physiological and pathological conditions and to elucidate mechanisms of malignant pleural effusion/ascites (MPEA), human cases were pathologically examined. Regardless of the presence or absence of MPEA, a number of LS were observed in the pulmonary ligament and the diaphragmatic peritoneum. The structure that allows bi-directional flow of floating cells was confirmed among them. Multivariate analysis demonstrated that cancer metastasis to the LS is an independent and strong predictor of MPEA compared to cancer invasion or dissemination to the serosal membranes except for the pulmonary ligament and diaphragmatic peritoneum. Notably, cases with MPEA demonstrated larger diameters of LS and higher frequencies of cancer invasion into downstream lymphatics and lymph nodes compared to cases without MPEA, which may indicate the presence of bi-directional, retrograde or rerouting lymphatic spread of cancer cells.

Research Products

• [Journal Article] Assessment of various types of US findings after irreversible electroporation in porcine liver: comparison with radiofrequency ablation (2015)
  • Author(s): Sugimoto K, Moriyasu F, Kobayashi Y, Kasuya K, Nagakawa Y, Tsuchida A, Hara T, Iobe H, Oshiro H
  • Journal Title: J Vasc Interv Radiol Volume: 26 Issue: 2 Pages: 279-287
  • DOI: 10.1016/j.jvir.2014.11.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lymphatic Stomata in the Adult Human Pulmonary Ligament (2015)
  • Author(s): Oshiro H, Miura M, Iobe H, Kudo T, Shimazu Y, Aoba T, Okudela K, Nagahama K, Sakamaki K, Yoshida M, Nagao T, Nakaya T, Kurata A, Ohtani O.
  • Journal Title: Lymphat Res Biol Volume: 13 Issue: 2 Pages: 137-145
  • DOI: 10.1089/lrb.2014.0009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Two cases of sclerosing angiomatoid nodular transformation of the spleen with gradual growth: usefulness of diffusion-weighted imaging (2015)
  • Author(s): Yoshimura N, Saito K, Shirota N, Suzuki K, Akata S, Oshiro H, Nagao T, Sugimoto K, Tsuchida A, Tokuuye K
  • Journal Title: Clin Imaging Volume: 39 Issue: 2 Pages: 315-317
  • DOI: 10.1016/j.clinimag.2014.10.015
  • Peer Reviewed
• [Journal Article] The role of the lymphatic system in rabbit models for cancer metastasis research: a perspective from comparative anatomy (2014)
  • Author(s): Oshiro H
  • Journal Title: Okajimas Folia Anat Jpn Volume: 91 Pages: 25-28
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Radiologic-pathologic correlation of three-dimensional shear-wave elastographic findings in assessing the liver ablation volume after radiofrequency ablation (2014)
  • Author(s): Sugimoto K, Oshiro H, Ogawa S, Honjo M, Hara T, Moriyasu F
  • Journal Title: World J Gastroenterol Volume: 20 Issue: 33 Pages: 11850-11855
  • DOI: 10.3748/wjg.v20.i33.11850
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reappraisal of Mechanical Exfoliating Cytology for the Detection of Peritoneal Dissemination during the Surgical Staging of Epithelial Ovarian Carcinomas and Borderline Tumours (2014)
  • Author(s): Asai-Sato M, Oshiro H, Yamanaka S, Inayama Y, Hirahara F, Miyagi E.
  • Journal Title: Acta Cytol Volume: (未定) Issue: 3 Pages: 255-261
  • DOI: 10.1159/000360412
  • Peer Reviewed
• [Journal Article] Cytological features of mammary analogue secretory carcinoma of salivary gland: Fine-needle aspiration of seven cases. (2014)
  • Author(s): Higuchi K, Urano M, Takahashi RH, Oshiro H, Matsubayashi J, Nagai T, Obikane H, Shimojo H, Nagao T.
  • Journal Title: Diagn Cytopathol Volume: (未定) Issue: 10 Pages: 846-855
  • DOI: 10.1002/dc.23139
  • Peer Reviewed
• [Journal Article] Establishment of successively transplantable rabbit VX2 cancer cells that express enhanced green fluorescent protein (2014)
  • Author(s): Oshiro H, Fukumura H, Nagahama K, Sato I, Sugiura K, Iobe H, Okiyama E, Nagao T, Nagashima Y, Aoki I, Yamanaka S, Murakami A, Maegawa J, Chishima T, Ichikawa Y, Ishikawa Y, Nagai T, Nomura M, Ohashi K and Okudela K
  • Journal Title: Med Mol Morphol Volume: 印刷中 Issue: 1 Pages: 13-23
  • DOI: 10.1007/s00795-014-0071-2
  • Peer Reviewed / Open Access
• [Journal Article] Focal nodular hyperplasia-like lesion of the liver with focal adenoma features associated with idiopathic portal hypertension (2014)
  • Author(s): Sugimoto K, Kondo F, Furuichi Y, Oshiro H, Nagao T, Saito K, Yoshida H, Imai Y, Fukusato T, Moriyasu F
  • Journal Title: Hepatol Res Volume: 印刷中 Issue: 10
  • DOI: 10.1111/hepr.12273
  • Peer Reviewed
• [Journal Article] EUS Elastographyの有用性と可能性. (2014)
  • Author(s): 糸川 文英, 糸井 隆夫, 森安 史典, 土田 明彦, 長尾 俊孝, 大城 久.
  • Journal Title: メディックス Volume: 60 Pages: 11-16
• [Journal Article] 肺転移巣より診断しえた胞巣状軟部肉腫の1例. (2014)
  • Author(s): 島田 ゆうか, 三宅 真司, 五百部 浩昭, 長嶋 洋治, 松林 純, 大城 久, 池田 徳彦, 長尾 俊孝.
  • Journal Title: 日本臨床細胞学会雑誌 Volume: 53 Pages: 28-34
  • NAID: 130004513229
  • Peer Reviewed
• [Journal Article] Serum p53 antibody is not associated with p53 immunoreactivity in patients with pancreatobiliary cancers (2013)
  • Author(s): Umeda J, Nagao T, Oshiro H, 他3名
  • Journal Title: J Oncol Volume: 170625 Pages: 1-6
  • DOI: 10.1155/2013/170625
  • Peer Reviewed
• [Journal Article] Relationship between the liver tissue shear modulus and histopathologic findings analyzed by intraoperative shear wave elastography and digital microscopically assisted morphometry in patients with hepatocellular carcinoma. (2013)
  • Author(s): Honjo M, Moriyasu F, Sugimoto K, Oshiro H, Sakamaki K, Kasuya K, Nagai T, Tsuchida A, Imai Y.
  • Journal Title: J Ultrasound Med Volume: 33 Issue: 1 Pages: 61-71
  • DOI: 10.7863/ultra.33.1.61
  • Peer Reviewed
• [Journal Article] Primary large cell neuroendocrine carcinoma of the ureter (2013)
  • Author(s): Oshiro H, Odagaki Y, Iobe H, Ozu C, Takizawa I, Nagai T, Matsubayashi J, Nagao T
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 729-736
  • Peer Reviewed
• [Journal Article] Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies (2013)
  • Author(s): Arai H, Okudela K, Oshiro H, Komitsu N, Mitsui H, Nishii T, Tsuboi M, Nozawa A, Noishiki Y, Ohashi K, Inui K, Masuda M
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 395-410
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice (2012)
  • Author(s): Nagao T, Sato E, Inoue R, Oshiro H, H Takahashi R, Nagai T, Yoshida M, Suzuki F, Obikane H, Yamashina M, Matsubayashi J
  • Journal Title: Acta Histochem Cytochem Volume: 45 Pages: 269-282
  • NAID: 130001854259
  • Peer Reviewed
• [Journal Article] Quantification in molecular ultrasound imaging: a comparative study in mice between healthy liver and a human hepatocellular carcinoma xenograft (2012)
  • Author(s): Sugimoto K, Moriyasu F, Negishi Y, Hamano N, Oshiro H, Rognin NG, Yoshida T, Kamiyama N, Aramaki Y, Imai Y
  • Journal Title: J Ultrasound Med Volume: 31 Pages: 1909-1916
  • Peer Reviewed
• [Journal Article] Int6 silencing causes induction of angiogenic factors in neuronal cells via accumulation of hypoxia-inducible factor 2α and decreases brain damage in rats (2012)
  • Author(s): Miyashita R, Chen L, Oshiro H, Uchino H, Shibasaki F
  • Journal Title: Neurosci Lett Volume: 528 Pages: 83-88
  • Peer Reviewed
• [Journal Article] Comparison of preoperative images with gross and histopathological findings of liver slices in patients with liver metastases from colorectal cancer after chemotherapy (2012)
  • Author(s): Kasuya K, Oshiro H, Saito K, Suzuki Y, Kikuchi S, Kyo B, Matsudo T, Nagakawa Y, Itoi T, Tsuchida A
  • Journal Title: Hepatogastroenterology Volume: 59 Pages: 981-985
  • DOI: 10.5754/hge12197
  • Peer Reviewed
• [Journal Article] 局所再発を繰り返した乳腺多形腺腫の1例 (2012)
  • Author(s): 井上 英美, 千島 隆司, 木村 万里子, 市川 靖史, 大城 久, 遠藤 格
  • Journal Title: 日本臨床外科学会雑誌 Volume: 73 Pages: 3052-3056
  • NAID: 10031171191
  • Peer Reviewed
• [Journal Article] 膵臓の画像診断update: 膵疾患のEUS elastography (2012)
  • Author(s): 糸川 文英, 糸井 隆夫, 祖父尼 淳, 栗原 俊夫, 土屋 貴愛, 石井 健太郎, 辻 修二郎, 池内 信人, 田中 麗奈, 梅田 純子, 殿塚 亮祐, 本庄 三季, 森安 史典, 土田 明彦, 粕谷 和彦, 大城 久, 長尾 俊孝
  • Journal Title: 胆と膵 Volume: 33 Pages: 571-578
  • Peer Reviewed
• [Presentation] 胃原発Hepatoid AdenocarcinomaとNeuroendocrine Carcinomaを合併した一例 (2014)
  • Author(s): 高橋 恒輔, 星野 澄人, 西村 絵美, 太田 喜洋, 須田 健, 立花 慎吾, 勝又 健次, 土田 明彦, 大城 久, 松林 純, 長尾 俊孝
  • Organizer: 第76回日本臨床外科学会総会
  • Place of Presentation: 郡山市民文化センター (福島県郡山市)
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] 乳腺原発Giant cell tumor of borderline malignancyの1例 (2014)
  • Author(s): 山田 公人, 河手 敬彦, 海瀬 博史, 細永 真理, 河合 佑子, 宮原 か奈, 上田 亜衣, 佐藤 永一, 松林 純, 大城 久, 三宅 真司, 小池 悦子, 黒田 雅彦, 長尾 俊孝, 石川 孝
  • Organizer: 第53回日本臨床細胞学会秋期大会
  • Place of Presentation: 下関市民会館 (山口県下関市)
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] 乳腺分泌癌の1例 (2014)
  • Author(s): 桑原 淳, 三宅 真司, 片桐 仁子, 渡部 顕章, 礒本 愛子, 島田 ゆうか, 大塚 清花, 高橋 礼典, 大城 久, 松林 純, 長尾 俊孝
  • Organizer: 第53回日本臨床細胞学会秋期大会
  • Place of Presentation: 下関市民会館 (山口県下関市)
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] 乳腺原発腺様嚢胞癌3例の細胞像の検討 (2014)
  • Author(s): 鈴木 恵美子, 小池 悦子, 三宅 真司, 稲垣 敦史, 石原 里佳子, 山口 真由実, 忽滑谷 昌平, 五百部 浩昭, 山田 公人, 大城 久, 松林 純, 長尾 俊孝
  • Organizer: 第53回日本臨床細胞学会秋期大会
  • Place of Presentation: 下関市民会館 (山口県下関市)
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] 肝臓に対する不可逆電気穿孔法(Irreversible electroporation, IRE)による病理組織学的変化 (2014)
  • Author(s): 小林 功幸, 森安 史典, 杉本 勝俊, 安藤 真弓, 佐野 隆友, 宮田 祐樹, 平良 淳一, 今井 康晴, 中村 郁夫, 大城 久
  • Organizer: Japanese Digestive Disease Week 2014
  • Place of Presentation: 神戸国際展示場 (兵庫県神戸市)
  • Year and Date: 2014-10-23
• [Presentation] 悪性心嚢液貯留を予測する因子の検討 (2014)
  • Author(s): 小池 悦子, 大城 久, 松林 純, 三宅 真司, 片桐 仁子, 渡部 顕章, 鈴木 恵美子, 礒本 愛子, 石原 里佳子, 長尾 俊孝
  • Organizer: 第28回関東臨床細胞学会学術集会
  • Place of Presentation: ふじのくに千本松フォーラム (静岡県沼津市)
  • Year and Date: 2014-09-13
• [Presentation] 心嚢液細胞診症例の臨床病理学的検討 (2014)
  • Author(s): 小池 悦子, 大城 久, 松林 純, 三宅 真司, 片桐 仁子, 渡部 顕章, 鈴木 恵美子, 礒本 愛子, 石原 里佳子, 長尾 俊孝
  • Organizer: 第55回日本臨床細胞学会総会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] 肝Elastographyに影響を与える因子 Shear waveの伝搬速度に影響する肝臓の病理学的要因は? (2014)
  • Author(s): 杉本 勝俊, 本定 三季, 大城 久, 森安 史典
  • Organizer: 日本超音波医学会第87回学術集会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-05-09 – 2014-05-11
• [Presentation] 膵液細胞診が有用であった上皮内癌の1例. (2013)
  • Author(s): 向井 俊太郎, 糸井 隆夫, 祖父尼 淳, 糸川 文英, 土屋 貴愛, 栗原 俊夫, 石井 健太郎, 辻 修二郎, 池内 信人, 梅田 純子, 田中 麗奈, 殿塚 亮祐, 本定 三季, 大城 久, 長尾 俊考, 森安 史典.
  • Organizer: 第97回日本消化器内視鏡学会関東地方会
  • Place of Presentation: 東京
• [Presentation] 胸腺原発リンパ上皮腫様癌の1例. (2013)
  • Author(s): 稲垣 敦史, 松林 純, 桑原 淳, 三宅 真司, 渡部 顕章, 鈴木 恵美子, 石原 里佳子, 五百部 浩昭, 大城 久, 大平 達夫, 池田 徳彦, 長尾 俊孝.
  • Organizer: 第52回日本臨床細胞学会秋期大会
  • Place of Presentation: 大阪
• [Presentation] 分葉状頸管腺過形成が共存した子宮頸部胃型腺癌の一例. (2013)
  • Author(s): 島田 ゆうか, 永井 毅, 小池 悦子, 三宅 真司, 片桐 仁子, 礒本 愛子, 大塚 清花, 長谷部 俊二, 松林 純, 大城 久, 高橋 礼典, 佐川 泰一, 長尾 俊孝.
  • Organizer: 第52回日本臨床細胞学会秋期大会
  • Place of Presentation: 大阪
• [Presentation] 膵嚢胞切除後に発症した1型糖尿病の1例. (2013)
  • Author(s): 柿崎 雄介, 簡 健志, 志熊 淳平, 永田 卓美, 大澤 舞, 三輪 隆, 金澤 昭, 大城 久, 小田原 雅人.
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 長期生存中の退形成性膵管癌の1例. (2013)
  • Author(s): 刑部 弘哲, 土方 陽介, 松土 尊映, 菊池 哲, 許 文聰, 永川 裕一, 鈴木 芳明, 粕谷 和彦, 土田 明彦, 大城 久, 長尾 俊孝, 斎藤 準.
  • Organizer: 第75回日本臨床外科学会総会
  • Place of Presentation: 名古屋
• [Presentation] 尿道に発生した明細胞腺癌の1例. (2013)
  • Author(s): 片桐 仁子, 永井 毅, 三宅 真司, 小池 悦子, 桑原 淳, 渡部 顕章, 稲垣 敦史, 大城 久, 長尾 俊孝.
  • Organizer: 第54回日本臨床細胞学会総会
  • Place of Presentation: 東京
• [Presentation] Radiologic-pathologic correlation of three-dimensional shearwave elastographic findings after radiofrequency ablation. (2013)
  • Author(s): Katsutoshi Sugimoto, Saori Ogawa, Hisashi Oshiro, Takeshi Hara, Yasuharu Imai, Fuminori Moriyasu.
  • Organizer: 99th Scientic Assembly and Annual Meeting of Radiological Society of North America.
  • Place of Presentation: Chicago
• [Presentation] Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers: a potential determinant of susceptibility to multiple malignancies. (2013)
  • Author(s): Hiromasa Arai, Koji Okudela, Hisashi Oshiro, Noriko Komitsu, Keita Fujii, Masahiro Tsuboi, Munetaka Masuda.
  • Organizer: 15th World Conference on Lung Cancer (IASLC 2013)
  • Place of Presentation: Sydney
• [Presentation] 尿管原発大細胞神経内分泌癌の臨床病理学的所見 (2012)
  • Author(s): 大城 久
  • Organizer: 日本臨床検査医学会
  • Place of Presentation: 京都市
• [Presentation] 捺印細胞診で多量のアミロイド様物質を認めた膵神経内分泌腫瘍の1例 (2012)
  • Author(s): 桑原 淳, 大城 久, 高橋 礼典, 片桐 仁子, 鈴木 恵美子, 大塚 清花, 三宅 真司, 松林 純, 長尾 俊孝
  • Organizer: 日本臨床細胞学会
  • Place of Presentation: 新潟市
• [Presentation] 尿管原発大細胞神経内分泌癌の自然排泄尿細胞診 (2012)
  • Author(s): 大城 久, 稲垣 敦史, 三宅 真司, 渡部 顕章, 五百部 浩昭, 永井 毅, 松林 純, 高橋 礼典, 小池 悦子, 長尾 俊孝
  • Organizer: 日本臨床細胞学会
  • Place of Presentation: 新潟市
• [Presentation] 甲状腺穿刺吸引細胞診パパニコロウ分類Class III症例のベセスダシステムを用いた再検討 (2012)
  • Author(s): 渡部 顕章, 大城 久, 小池 悦子, 三宅 真司, 稲垣 敦史, 島田 ゆうか, 石原 里佳子, 松林 純, 長尾 俊孝
  • Organizer: 日本臨床細胞学会
  • Place of Presentation: 新潟市
• [Presentation] SLEを背景として中枢神経系多発性梗塞を伴った悪性リンパ腫の1剖検例 (2012)
  • Author(s): 吉田 真希, 松林 純, 馬原 孝彦, 林 映, 沢田 哲治, 大城 久, 長尾 俊孝
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋市
• [Presentation] 肺癌領域における新知見と形態学 肺腺癌の新しい組織分類と細胞診 (2012)
  • Author(s): 三宅 真司, 松林 純, 赤田 壮市, 桑原 淳, 稲垣 敦史, 小池 悦子, 大城 久, 野村 将春, 池田 徳彦, 長尾 俊孝
  • Organizer: 日本臨床細胞学会
  • Place of Presentation: 千葉市
• [Presentation] Elevated microsatellite alterations at selected tetranucleotide (EMAST) in non-small cell lung cancers (2012)
  • Author(s): Hiromasa Arai, Koji Okudela, Hisashi Oshiro, Noriko Komitsu, Teppei Nishii, Masahiro Tsuboi, Akinori Nozawa, Yasuharu Noishiki, Kenji Inui, Munetaka Masuda
  • Organizer: Asia Pacific Lung Cancer Conference (5th APLCC)
  • Place of Presentation: Fukuoka City
• [Presentation] Quantification in ultrasound molecular imaging: comparative study in mice of normal liver and human hepatocellular carcinoma xenograft tumors (2012)
  • Author(s): Sugimoto K, Moriyasu F, Negishi Y, Hamano N, Oshiro H, Rognin N, Yoshida T, Kamiyama N, Aramaki Y, Imai Y
  • Organizer: The Radiological Society of North America (98th RSNA)
  • Place of Presentation: Chicago, Illinois
• [Book] 頭頸部腫瘍Ⅰ．腫瘍鑑別診断アトラス (2015)
  • Author(s): 大城 久
  • Total Pages: 247
  • Publisher: 文光堂