Analysis of the expression of drug resistance-related genes in tumor blood vessels

• Project/Area Number: 25462846
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Hokkaido University
• Principal Investigator: SUZUKI Yuko 北海道大学, 遺伝子病制御研究所, 学術研究員 (90646118)
• Co-Investigator(Kenkyū-buntansha): OHGA Noritaka 北海道大学, 大学院歯学研究科, 助教 (40548202) ; AKIYAMA Kosuke 北海道大学, 遺伝子病制御研究所, 客員研究員 (10609100) ; MAISHI Nako 北海道大学, 遺伝子病制御研究所, 助教 (00632423)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腫瘍血管 / 薬剤抵抗性 / トランスポーター / がん幹細胞

Outline of Final Research Achievements

We have reported that drug resistance-related gene, P-glycoprotein (P-gp) is upregulated in tumor endothelial cells (TECs). In this study, we examined the involvement of P-gp expression of TEC in cancer refractory. When TECs were treated with both paclitaxel and P-gp inhibitor, TEC proliferation was inhibited compared to paclitaxel alone group. Combination treatment with paclitaxel and P-gp inhibitor abrogated TEC resistance in mouse tumor model. These results suggested that inhibiting P-gp in TECs may be a good strategy for cancer therapy.

Research Products

• [Journal Article] Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma. (2016)
  • Author(s): Yamada S, Yanamoto S, Otani S, Hasegawa T, Miyakoshi M, Minamikawa T, Ohga N, Kamata T, Komori T, Kitagawa Y, Kurita H, Umeda M.
  • Journal Title: Int J Oral Maxillofac Surg Volume: 45(2) Issue: 2 Pages: 141-6
  • DOI: 10.1016/j.ijom.2015.09.005
  • Peer Reviewed / Open Access
• [Journal Article] CXCL 12-CXCR7 axis is important for tumor endothelial cell angiogenic property (2015)
  • Author(s): Yamada K., Maishi N., Akiyama K., Alam Mohammad Towfik, Ohga N., Kawamoto T., Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A. and Hida K.
  • Journal Title: Int J Cancer Volume: 137(12) Issue: 12 Pages: 2825-2836
  • DOI: 10.1002/ijc.29655
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel (2015)
  • Author(s): 1.Akiyama K., Maishi N., Ohga N., Hida Y., Ohba Y., Alam Mohammad Towfik, Kawamoto T., Ohmura H., Yamada K., Torii C., Shindoh M. and *Hida K.
  • Journal Title: Am J Pathol Volume: 185(2) Issue: 2 Pages: 572-580
  • DOI: 10.1016/j.ajpath.2014.10.017
  • Peer Reviewed / Open Access
• [Journal Article] Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: Part III of a cohort study. (2015)
  • Author(s): Sato J, Ohuchi M, Wada M, Ohga N, Asaka T, Yoshikawa K, Miyakoshi M, Hata H, Satoh A, Kitagawa Y.
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Volume: 120 Issue: 6 Pages: 751-60
  • DOI: 10.1016/j.oooo.2015.08.016
  • Peer Reviewed / Open Access
• [Journal Article] Marked bone production from the mandibular head to the reconstructed fibula after chemoradiotherapy for the recurrent tumor (2015)
  • Author(s): Satoh.A, Ohga.N＊, Asaka.T, Kitagawa.Y
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 27(6) Pages: 829-833
  • Peer Reviewed
• [Journal Article] Dose escalation effectiveness and tolerability of paroxetine in patients with burning mouth syndrome and depressive conditions. (2015)
  • Author(s): Ohga.N＊, Yamazaki.Y, Sato.J, Hata.H, Murata.T, Sakata.K, Inoue.T, Kitagawa.Y
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 27(3) Pages: 402-406
  • Peer Reviewed
• [Journal Article] Healing of osteonecrosis of the jaw (ONJ) after discontinuation of denosumab in a patient with bone metastases of colorectal cancer: a case report and hypothesis. (2015)
  • Author(s): Ohga N＊, Yamazaki Y, Tsuboi K, Kitagawa Y
  • Journal Title: Quintessence Int. Volume: 46(7) Pages: 621-626
  • Peer Reviewed
• [Journal Article] CRK adaptor protein induces epithelial-mesenchymal transition and metastasis of bladder cancer cells via HGF/c-Met feedback loop. (2015)
  • Author(s): Matsumoto R, Tsuda M, Wang L, Maishi N, Abe t, Kimura T, Tanino M, Nishihara H, Hida K, Ohba Y, Shinohara N, Nonomura K, Tanaka S.
  • Journal Title: Cancer Sci Volume: in press Issue: 6 Pages: 709-17
  • DOI: 10.1111/cas.12662
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Tumor Endothelial Cells with High Aldehyde Dehydrogenase Activity and a Highly Angiogenic Phenotype (2014)
  • Author(s): 2.Ohmura-Kakutani H., Akiyama K., Maishi N., Ohga N., Hida Y., Kawamoto T., Iida J., Shindoh M., Tsuchiya K., Shinohara N., *Hida K
  • Journal Title: PLoS ONE Volume: 9(12) Issue: 12 Pages: e113910-e113910
  • DOI: 10.1371/journal.pone.0113910
  • NAID: 120005540289
  • Peer Reviewed / Open Access
• [Journal Article] Suprabasin as a novel tumor endothelial cell marker (2014)
  • Author(s): 3.Alam Mohammad Towfik，Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Taketomi A., Shindoh M., Hida Y. and *Hida K
  • Journal Title: Cancer Sci Volume: 105(12) Issue: 12 Pages: 1533-1540
  • DOI: 10.1111/cas.12549
  • NAID: 120005539218
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Novel Targets for Antiangiogenic Therapy by Comparing the Gene Expressions of Tumor and Normal Endothelial Cells (2014)
  • Author(s): Otsubo T., et al., Hida Y., Ohga N., Sato H., Kai T., Matsuki Y., Takasu H., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Nonomura K., Hida K.
  • Journal Title: Cancer Sci. Volume: (印刷中) Issue: 5 Pages: 560-567
  • DOI: 10.1111/cas.12394
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Novel Targets for Antiangiogenic Therapy by Comparing the Gene Expressions of Tumor and Normal Endothelial Cells (2014)
  • Author(s): Otsubo T., Hida Y., Ohga N., Sato H., Kai T., Matsuki Y., Takasu H., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Nonomura K., Hida K
  • Journal Title: Cancer Sci, Volume: in press
  • Peer Reviewed
• [Journal Article] The F-prostaglandin receptor is a novel marker for tumor endothelial cells in renal cell carcinoma (2013)
  • Author(s): Akiyama K., Ohga N., Maishi N., Hida Y., Kitayama K., Kawamoto T., Osawa T., Suzuki Y., Shinohara N., Nonomura K., Shindoh M., Hida K.
  • Journal Title: Pathol. Int. Volume: 63(1) Issue: 1 Pages: 37-44
  • DOI: 10.1111/pin.12031
  • Peer Reviewed
• [Journal Article] Lysyl oxidase secreted by tumour endothelial cells Promotes angiogenesis and metastasiso (2013)
  • Author(s): Osawa T., et al., Ohga N., Akiyama K., Hida Y., Kitayama K., Kawamoto T, , Yamamoto K., Maishi N., Kondoh M., Onodera Y., Fujie M., Nonomura K., Shindoh M., Hida K.
  • Journal Title: Br. J. Cancer Volume: 109(8) Issue: 8 Pages: 2237-2247
  • DOI: 10.1038/bjc.2013.535
  • Peer Reviewed
• [Journal Article] Hypoxia-induced reactive oxygen species cause chromosomal abnormalities in endothelial cells in the tumor microenvironment (2013)
  • Author(s): Kondoh M., Ohga N., Akiyama K., Hida Y., Maishi N., Alam Mohammad Towfik, Inoue N., Shindoh M. and Hida K
  • Journal Title: PLoS ONE Volume: 8(11) Issue: 11 Pages: e80349-e80349
  • DOI: 10.1371/journal.pone.0080349
  • NAID: 120005367415
  • Peer Reviewed
• [Presentation] Tumor Endothelial Cells Promote Metastasis via Biglycan (2016)
  • Author(s): Maishi N.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: Breckenridge (USA)
  • Year and Date: 2016-03-30
  • Int'l Joint Research
• [Presentation] 腫瘍分泌小胞miRNAによる血管内皮の薬剤耐性誘 (2016)
  • Author(s): 鳥居ちさほ，間石奈湖，樋田京子
  • Organizer: 第2回血管生物若手研究会
  • Place of Presentation: 東北大学加齢医学研究所スマートエージング国際共同研究センター国際会議室（宮城県・仙台市）
  • Year and Date: 2016-03-04
• [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion (2016)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
  • Organizer: Tenth AACR-JCA Joint Conference “Breakthroughs in Cancer Research: From Biology to Therapeutics”
  • Place of Presentation: Maui (USA)
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [Presentation] ROS によるbiglycan 発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進 (2015)
  • Author(s): 北條敬之，間石奈湖，Mohammad T Alam，秋山廣輔，大賀則孝，進藤正信，樋田泰浩，藤澤俊明，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 高転移性腫瘍miRNA はIL-6 ならびにALDH の発現亢進を介して血管内皮に薬剤耐性を誘導する (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭漢忠，戸塚靖則，進藤正信，樋田泰浩，南敬，小坂展慶，落谷孝広，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 腫瘍血管内皮細胞はbiglycan の分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖，大場雄介，秋山廣輔，大賀則孝，浜田淳一，北本(永尾）宗子，Mohammad Alam T.，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Tumor endothelial cells promote metastasis via biglycan secretion (2015)
  • Author(s): Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Mohammad Towfik Alam, Shindoh M., Hida Y., Hida K
  • Organizer: The European Cancer Congress 2015
  • Place of Presentation: Vienna (Austria)
  • Year and Date: 2015-09-27
  • Int'l Joint Research
• [Presentation] Tumor Endothelial cell-secreted protein activates a DNA damage response (2015)
  • Author(s): Annan Dorcas A., 間石奈湖，北條敬之，鳥居ちさほ，Mohammad T Alam.，Habiba Umma，樋田泰浩，樋田京子
  • Organizer: 第112回北海道癌談話会例会
  • Place of Presentation: 北海道大学医学部学友会館［フラテ」（北海道・札幌市）
  • Year and Date: 2015-09-12
• [Presentation] 高転移性腫瘍miRによらう血管内皮におけるIL-6を介した薬剤耐性誘導 (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，Alam Mohammad Towfik，鄭 漢忠，戸塚靖則，進藤正信，樋田泰浩，南 敬，小坂展慶，落谷孝広，樋田京子
  • Organizer: 第112回北海道癌談話会例会
  • Place of Presentation: 北海道大学医学部学友会館［フラテ」（北海道・札幌市）
  • Year and Date: 2015-09-12
• [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖，大場雄介，秋山廣輔，大賀則孝，浜田淳一，北本宗子，Alam Mohammad Towfik，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 高転移性腫瘍miRNAはIL-6ならびにALDHの発現亢進を介して血管内皮に薬剤耐性を誘導する (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭 漢忠，戸塚靖則，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-31
• [Presentation] Suprabasin as a novel tumor endothelial cell marker (2015)
  • Author(s): Alam Mohammad Towfik，Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T, Shinohara N., Taketomi A., Shindoh M, Hida Y, Hida K
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学学術交流会下院（北海道・札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 活性酸素種によるBiglycan発現誘導を介した腫瘍血管内皮細胞の血管新生能亢進 (2015)
  • Author(s): 北條敬之，間石奈湖，秋山廣輔，大賀則孝，進藤正信，樋田泰浩，藤澤俊明，樋田京子
  • Organizer: 第26回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 北海道大学学術交流会館（北海道・札幌市）
  • Year and Date: 2015-07-31
• [Presentation] 腫瘍血管内皮細胞はbiglycanの分泌を介してがんの転移を促進する (2015)
  • Author(s): 間石奈湖
  • Organizer: 第24回日本がん転移学会学術集会・総会
  • Place of Presentation: シティプラザ大阪（大阪府・大阪市）
  • Year and Date: 2015-07-23
• [Presentation] 腫瘍微小環境において，腫瘍由来のmiRX により血管内皮はIL-6 をオートクラインで利用し，薬剤耐性や幹細胞性を獲得している (2015)
  • Author(s): 鳥居ちさほ，秋山廣輔，川本泰輔，間石奈湖，鄭 漢忠，進藤正信，樋田泰浩，樋田京子
  • Organizer: 第69回日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2015-05-14
• [Presentation] Tumor endothelial cells instigate metastasis of indolent tumors (2015)
  • Author(s): Maishi N., Hida K.
  • Organizer: Spring Special Symposium of the Japanese Vascular Biology and Medicine Organization
  • Place of Presentation: 大阪大学微生物病研究所谷口記念講堂（大阪府・吹田市）
  • Year and Date: 2015-05-13
  • Int'l Joint Research / Invited
• [Presentation] 腫瘍血管内皮細胞を標的としたメトロノミックケモセラピーとP-gp阻害剤の併用療法の有効性の検討 (2013)
  • Author(s): 秋山廣輔，大賀則孝，樋田泰浩，間石奈湖，Alam Mohammad Towfik, 川本泰輔，大村 瞳，山田健司，鳥居ちさほ，進藤正信，大場雄介，樋田京子
  • Organizer: 第46回北海道病理談話会
  • Place of Presentation: 北海道大学医学部学友会館（札幌市）
• [Presentation] P-gp阻害剤はメトロノミックケモセラピーの血管新生阻害効果を強める (2013)
  • Author(s): 秋山廣輔，大賀則孝，樋田泰浩，間石奈湖，Alam MohammadTowfik，川本泰輔，大村瞳，山田健司，鳥居ちさほ，進藤正信，大場雄介，樋田京子
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] 腫瘍血管を標的としたMetronomic ChemotherapyとP-gp阻害剤の併用療法の有効性の検討 (2013)
  • Author(s): 秋山廣輔，大賀則孝，樋田泰浩，間石奈湖，Alam MohammadTowfik，川本泰輔，大村瞳，山田健司，鳥居ちさほ，進藤正信，大場雄介，樋田京子
  • Organizer: 第108回北海道癌談話会例会
  • Place of Presentation: 旭川グランドホテル（旭川市）
• [Book] 別冊BIO Clinica 慢性炎症と疾患～慢性炎症とがん (2016)
  • Author(s): 樋田京子，大賀則孝，間石奈湖，秋山廣輔，樋田泰浩
  • Total Pages: 172
  • Publisher: 北隆館