Development of imaging diagnosis system for oral cancer utilizing lesion-integrated nanobubbles and high frequency ultrasound

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390378
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tohoku University
• Principal Investigator: MORI Shiro 東北大学, 病院, 講師 (80230069)
• Co-Investigator(Kenkyū-buntansha): ONO Masao 東北大学, 医学系研究科, 教授 (20302218)
• Co-Investigator(Renkei-kenkyūsha): KODAMA Tetsuya 東北大学, 医工学研究科, 教授 (40271986) ; ONO Masao 東北大学, 医学系研究科, 教授 (20302218)
• Project Period (FY): 2010 – 2012
• Keywords: 口腔癌 / ナノバブル / 超音波 / 転移モデル / リンパ節転移 / 腫瘍血管 / リンパ管 / 画像診断

Research Abstract

The purpose of the present study is to develop a real-time imaging system using high frequency ultrasound and nanobubbles for the diagnosis of oral cancer. In order to evaluate the diagnostic accuracy of the high-frequency ultrasonic imaging analysis for oral cancer, we established a recombinant inbred strain of mouse showing a similar size of lymph node swelling as that of human. As a result, in the metastatic lymph nodes,it became clear that nanobubbles leake and integrate into the perivascular region of the lesion by enhanced permeability and retention (EPR) effect. This finding suggests that the image analysis using high-frequency ultrasound and nanobubbles isextremely useful in diagnosis of the metastatic lesions in the lymph node.

Research Products

• [Journal Article] Enhancedsonographic imaging to diagnose lymph node metastasis: importance of bloodvessel volume and density (2013)
  • Author(s): Li Li, Mori S, Kodama M, Sakamoto M, Takahashi S, Kodama T
  • Journal Title: Cancer Reseach Volume: 73 Pages: 2082-2092
  • DOI: doi:10.1158/0008-5472.CAN-12-4200
  • Peer Reviewed
• [Journal Article] Mouse model of lymph node metastasis via afferent lymphatic vessels for development of imagingmodalities (2013)
  • Author(s): Li Li, Mori S, Sakamoto M, Takahashi S, Kodama T
  • Journal Title: PLOS ONE Volume: 8
  • DOI: Doi:10.1371/joumal.pone.0055797
  • Peer Reviewed
• [Journal Article] Lymphatic mapping of mice withsystemic lymphoproliferative disorder: usefulness as aninter-lymph node metastasis model of cancer (2013)
  • Author(s): Lenan S, Mori S, Yagishita Y, Okuno T, Hatakeyama Y, Sato T, Kodama T
  • Journal Title: J Immunol Method Volume: 389(1-2) Pages: 69-78
  • DOI: doi:10.1016/j.jim.2013.01.004
  • Peer Reviewed
• [Journal Article] Genomics of Vasculitis: Lessons from Mouse Models (2013)
  • Author(s): Nose M, Komori H, Miyazaki T, Mori S
  • Journal Title: Annals of Vascular Diseases Volume: 6(1) Pages: 16-21
  • DOI: doi:10.3400/avd.ra.12.00096
  • Peer Reviewed
• [Journal Article] Sjogren's syndrome-like autoimmune sialadenitis in MRL-Faslpr mice is associated with expression of glucocorticoid-induced TNFreceptor-related protein (GITR)ligand and 4-1BB ligand (2013)
  • Author(s): Saito K, Mori S, Date F, Ono M
  • Journal Title: Autoimmunity
  • Peer Reviewed
• [Journal Article] Volumetric and angiogenicevaluation of antitumor effects with acoustic liposome and high-frequency ultrasound (2011)
  • Author(s): Kodama T, Tomita N, Yagishita Y, Horie S, Funamoto K, Hayase T, Sakamoto M, Mori S
  • Journal Title: Cancer Res Volume: 71 Pages: 6957-6964
  • Peer Reviewed
• [Journal Article] Evaluation of anti-tumor effects following tumor necrosis factor-alpha gene delivery using nanobubbles and ultrasound (2011)
  • Author(s): Horie S, Watanabe Y, Ono M, Mori S, Kodama T.
  • Journal Title: Cancer Sci Volume: 102 Pages: 2082-2089
  • Peer Reviewed
• [Journal Article] Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy (2011)
  • Author(s): Kuwahara Y, Oikawa T, Ochiai Y,Roudkenar, M Fukumoto, T Shimura, Y Ohtake M H, Ohkubo Y, Mori S, Uchiyama Y, Fukumoto M
  • Journal Title: Cell Death Dis Volume: 2 Pages: e177
  • DOI: doi:10.1038/cddis.2011.56. Publishedonline 30 June 2011
  • Peer Reviewed
• [Journal Article] The Modified High-Density Survival Assay is the Useful Tool to Predict the Effectiveness of Fractioned Radiation Exposure (2010)
  • Author(s): Kuwahara Y, Mori M, Oikawa T, Shimura T, Ohtake Y, Mori S, Ohkubo Y, Fukumoto M
  • Journal Title: J Radiat Res Volume: 51 Pages: 297-302
  • Peer Reviewed
• [Journal Article] Development of localized gene delivery using a dual-intensity ultyrasound system in the bladder (2010)
  • Author(s): Horie S, Watabnabe Y, Chen R, Mori S, Matsumura Y, Kodama T
  • Journal Title: Ultrasound Med Biol Volume: 36(11) Pages: 1867-1875
  • Peer Reviewed
• [Journal Article] Evaluation of transfection efficiency in skeletal muscle using nano/microbubbles and ultrasound (2010)
  • Author(s): Kodama T, Aoi A, Watabnabe Y, Horie S, Kodama M, Li L, Chen R, Teramoto N, Morikawa H, Mori S, Fukumoto M
  • Journal Title: Ultrasound Med Biol Volume: 36(7) Pages: 1196-1205
  • Peer Reviewed
• [Journal Article] Delivery of Na/I symporter gene into skeletal muscle by using nanobubbles and ultrasound:Visualization of gene expression by positron emission tomography (2010)
  • Author(s): Watanabe Y, Horie S, Funaki Y, Kikuchi Y, Yamazaki H, Ishii K, Mori S, Vassaux G, Kodama T
  • Journal Title: J Nucl Med Volume: 51(6) Pages: 951-8
  • Peer Reviewed
• [Journal Article] Evaluating the Role of Rheumatoid Factors for the Development of Rheumatoid Arthritis in a Mouse Model with a Newly Established ELISA System (2010)
  • Author(s): Tanaka Y, Komori H, Mori S, Soga Y, Tsubaki T, Terada M, Miyazaki T, Fujino T, Nakamura S, Kanno H, Sawasaki T,Endo Y, Nose M
  • Journal Title: Tohoku J Exp Med Volume: 220 (3) Pages: 199-206
  • Peer Reviewed
• [Journal Article] Morphological study on Acoustic liposome using transmission electron microscopy (2010)
  • Author(s): Kodama T, Tomita N, Horie S, Sax N, Iwasaki H, Suzuki R, Maruyama K, Mori S, Fukumoto M
  • Journal Title: J Electron Microsc Volume: 59(3) Pages: 187-196
  • Peer Reviewed
• [Presentation] Molecualr delivery into lymph nodes using ultrasound and nanobubbles (2013)
  • Author(s): Shirai Y, Kato S, Kanzaki H, Mori S, Kodama T
  • Organizer: The 6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering
  • Place of Presentation: National University of Singapore , Singapore.
  • Year and Date: 20130323-24
• [Presentation] Early diagnosis of lymph nodemetastasis (2013)
  • Author(s): Hasegawa N, Kodama T, Sato T, Kochi T, Mori S
  • Organizer: The 6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering
  • Place of Presentation: National University of Singapore , Singapore.
  • Year and Date: 20130323-24
• [Presentation] Development of contrast-enhanced high-frequencyultrasound for early diagnosis of tumor (2013)
  • Author(s): Yanagisawa Y, Ito K, Noro K, Aoki T, Mori S, Kodama T
  • Organizer: The 6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering
  • Place of Presentation: National University of Singapore,Singapore
  • Year and Date: 20130323-24
• [Presentation] 金ナノロッドを利用した局所的熱療法のリンパ節転移治療への応用 (2013)
  • Author(s): 奥野竜希,加藤茂樹,畠山友梨子,阪本真弥,森士朗,小玉哲也
  • Organizer: 日本機械学会第25回バイオエンジニアリング講演会
  • Place of Presentation: 筑波
  • Year and Date: 20130109-11
• [Presentation] 超音波と微小気泡によるリンパ管を介したリンパ節内細胞への外来分子導入法の開発 (2013)
  • Author(s): 加藤茂樹,白井優子,佐藤琢磨,菅崎弘幸,本園千尋,宮澤正顯,森士朗,小玉哲也
  • Organizer: 日本超音波医学会東北地方会第45回学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2013-03-10
• [Presentation] プラズモン共鳴を利用した局所的熱療法のリンパ節転移治療への応用 (2012)
  • Author(s): 奥野竜希,長谷川奈保,畠山友梨子,加藤茂樹,阪本真弥,森士朗,小玉哲也
  • Organizer: 日本バイオマテリアル学会大会シンポジウム2012
  • Place of Presentation: 仙台
  • Year and Date: 20121126-27
• [Presentation] 乳がんにおける腫瘍周辺上皮組織リンパ管および血管分布に関する研究 (2012)
  • Author(s): 三浦由宣,佐藤琢磨,阪本真弥,森士朗,小玉哲也
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] 二光子顕微鏡をもちいたEPR効果による腫瘍内ナノ粒子流出特性の観察 (2012)
  • Author(s): 三ヶ田護,サックスニコラ,阪本真弥,森士朗,小玉哲也
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Pressure-driven flow characteristics in the lymphatic vessel for lymphatic drug delivery ststem (2012)
  • Author(s): Hatakeyama Y, Sax N, Kato S, Okuno T, Sakamoto M, Mori S, Kodama T
  • Organizer: The 9th International Conference on FlowDynamics. Proceedings
  • Place of Presentation: Sendai, Japan
  • Year and Date: 20120919-21
• [Presentation] Cancer treatment via the lymphatic vessel using nano/microbubbles (2012)
  • Author(s): Kato S, Nicolas S, Hatakeyama Y, Okuno T, Mori S, Sakamoto M, Kodama T
  • Organizer: The 9th International Conference on FlowDynamics
  • Place of Presentation: Sendai, Japan
  • Year and Date: 20120919-21
• [Presentation] Thermal therapy using plasmonic nano particles for lymph node metastasis (2012)
  • Author(s): Okuno T, Kato S, Hatakeyama Y, Sato T, Sakamoto M, Mori S, Kodama T
  • Organizer: The 9th International Conference on Flow Dynamics
  • Place of Presentation: Sendai, Japan
  • Year and Date: 20120919-21
• [Presentation] リンパ行性薬剤送達システムの開発 (2012)
  • Author(s): 畠山友梨子,李麗,サックスニコラ,奥野竜希,加藤茂樹,阪本真弥,森士朗,小玉哲也
  • Organizer: 日本機械学会2012年度年次大会
  • Place of Presentation: 金沢
  • Year and Date: 20120909-12
• [Presentation] 腫瘍の成長にともなう鼠径リンパ節内の間質液圧特性に関する研究 (2012)
  • Author(s): 三浦由宣,畠山友梨子,阪本真弥,森士朗,小玉哲也
  • Organizer: 日本機械学会2012年度年次大会
  • Place of Presentation: 金沢
  • Year and Date: 20120909-12
• [Presentation] 腫瘍移植とEPR効果に関する研究 (2012)
  • Author(s): 三ヶ田護,サックスニコラ,阪本真弥,森士朗,小玉哲也
  • Organizer: 日本機械学会2012年度年次大会
  • Place of Presentation: 金沢
  • Year and Date: 20120909-12
• [Presentation] Drug delivery system with acoustic liposomes via the lymphatic vessels (2012)
  • Author(s): Kato S, Horie S, Sakamoto M, Mori S, Kodama T
  • Organizer: The 8th International Symposium on Cavitation
  • Place of Presentation: Novotel Clark Quay, Singapore
  • Year and Date: 20120813-16
• [Presentation] リンパ行性薬剤送達システム開発のためのリンパ節およびリンパ管内の流動特性 (2012)
  • Author(s): 畠山梨友子,サックスニコラ,奥野竜希,森士朗,阪本真弥,小玉哲也
  • Organizer: 第28回日本DDS学会
  • Place of Presentation: 札幌
  • Year and Date: 20120704-05
• [Presentation] Lymphatic network mapping in a novel lymph nodemetastasis model of mice (2012)
  • Author(s): Shao L, Okuno T, Hatakeyama Y, Kato S, Mori S, Kodama T
  • Organizer: Medical Physics and Biomedical Engineering in Beijing
  • Place of Presentation: Beijing, China
  • Year and Date: 20120526-31
• [Presentation] Flow characteristics of the lymphatic flow to the axillary lymph node driven by increasing pressures in the inguinal lymph node (2012)
  • Author(s): Hatakeyama Y, Nicolas S, Li L, Kato S, Okuno T, Miura Y, Shao L, Sakamoto M, Mori S, Fujikawa S, Kodama T
  • Organizer: Medical Physics andBiomedical Engineering
  • Place of Presentation: Beijing, China
  • Year and Date: 20120526-31
• [Presentation] Effects of the liposomal formuilation on the behavior and physical characteristicsof acoustic liposomes (2012)
  • Author(s): Sax N, Horie S, Li L, Li S, Kochi T, Chen R, Watanabe Y, Yagishita Y, Sakamoto M, Mori S, Kodam T
  • Organizer: The 19th International Symposium on Nonliner Acoustics
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20120521-24
• [Presentation] 鼠径リンパ節内の圧力上昇にともなう輸出リンパ管への流出特性 (2011)
  • Author(s): 畠山友梨子,李麗,サックスニコラ,阪本真弥,森士朗,小玉哲也
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-05
• [Presentation] 頭頸部癌遺伝子治療に向けたナノバブルと超音波によるNIS遺伝子導入と^<124>I-PETイメージング (2011)
  • Author(s): 渡邊夕紀子,森士朗,堀江佐知子,サックスニコラ,李麗,李深偉,柳下陽子,高地崇,船木善仁,菊池洋平,山崎浩道,石井慶造,阪本真弥,宮下仁,小玉哲也
  • Organizer: 第35回日本頭頸部癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 20110609-10
• [Presentation] 頭頸部癌所属リンパ節転移の診断・治療に向けたリンパ節腫大マウスを用いたリンパ節転移モデルの開発 (2011)
  • Author(s): 李麗,森士朗,柳下陽子,サックスニコラ,堀江佐知子,渡邊夕紀子,高地崇,李深偉,宮下仁,森川秀広,阪本真弥,小玉哲也
  • Organizer: 第35回日本頭頸部癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 20110609-10
• [Presentation] Contribution ofgenetic and non-genetic factors in the new inbred ankylosis model (2011)
  • Author(s): Yamamura MJ, Iikubo M, Sakamoto M, Mori S, Inui M, Shimoda S, Kobayashi K, Ono M, Sasano T.
  • Organizer: The 18th International Congress of Dento-Maxillo-Facial Radiology
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 20110525-29
• [Presentation] 超音波とナノバブルを使用した遺伝子導入法およびPETを使用した遺伝子発現の可視化法の開発 (2011)
  • Author(s): 渡邊夕紀子,堀江佐知子,船木善仁,菊池洋平,山崎浩道,石井慶造,森士朗,小玉哲也
  • Organizer: 第49回日本生体医工学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-29
• [Presentation] Chronological change of ankylosis in the newly developedrecombinant selective-congenic model (2010)
  • Author(s): Yamamura MJ, Iikubo M, Sakamoto M, Kojima I, Mori S, Date F, Shimoda K,Kobayashi K, Ono M, Sasano T.
  • Organizer: 8^<th> Asian congress of OMFR
  • Place of Presentation: Seoul,Korea
  • Year and Date: 20101114-16