Elucidation of heterogeneity in tumor endothelial cell in oral cancer and application for new antiangiogenic drug

• Project/Area Number: 26861694
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: Noritaka Ohga 北海道大学, 歯学研究科, 助教 (40548202)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腫瘍血管新生 / 腫瘍血管内皮マーカー / CXCR7 / 腫瘍血管内皮特異マーカー / 低酸素 / 腫瘍微小環境 / 口腔癌 / 分子標的薬

Outline of Final Research Achievements

In addition, we have reported that tumor endothelial cells (TECs) differ from normal endothelial cells (NECs) in many aspects, such as gene expression profiles. For example, CXCR7 is reportedly highly expressed in TECs of several tumors, such as renal carcinomas and colon cancers. However the expression of CXCR7 in oral squamous cell carcinoma (OSCC) has not been reported.In this study, we examined the relationship between CXCR7 expression in TECs and clinicopathological factors in OSCCs.CXCR7 expression in blood vessels was 42% and 19% in tumor tissue and in normal tissue, respectively, suggesting that CXCR7 expression is higher in TEC than in NEC in OSCC. The expression of CXCR7 in TEC were correlated with the T pathological stage (P=0.04).These results suggested that CXCR7 expression may be useful as a prognostic marker of OSCCs.

Research Products

• [Journal Article] Successful conservative treatment of osteonecrosis of jaw caused by denosumab in patients with multiple bone metastasis. (2017)
  • Author(s): Ohga.N, Sato.J , Asaka.T, Moritomoto.M, Yamazaki.Y, Kitagawa,Y
  • Journal Title: Journal of oral science Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Unusual maxillary osteoblastic and osteolytic lesions presenting as an initial manifestation of childhood acute myeloid leukemia: a case report (2017)
  • Author(s): Shimizu.R , Ohga.N＊, Miyakoshi.M , Asaka.T , Sato.J , Kitagawa.Y
  • Journal Title: Quintessence Int Volume: 48(2) Pages: 149-153
  • Peer Reviewed / Open Access
• [Journal Article] Vasohibin-1 as a Novel Prognostic Factor for Head and Neck Squamous Cell Carcinoma. (2017)
  • Author(s): Torii C, Hida Y, Shindoh M, Akiyama K, Ohga N, Maishi N, Ohiro Y, Ono M, Totsuka Y, Kitagawa Y, Tei K, Sato Y, Hida K.
  • Journal Title: Anticancer Re Volume: 37(3) Pages: 1219-1225
  • Peer Reviewed
• [Journal Article] Tumor endothelial cells express high pentraxin 3 levels (2016)
  • Author(s): Hida K., Maishi N., Kawamoto T., Akiyama K., Ohga N., Hida Y., Yamada K., Hojo T., Kikuchi H., Sato M., Torii C., Shinohara N., Shindoh M
  • Journal Title: Pathol Int Volume: 66 Issue: 12 Pages: 687-694
  • DOI: 10.1111/pin.12474
  • Peer Reviewed / Open Access
• [Journal Article] Elimination of oral candidiasis may increase stimulated whole salivary flow rate. (2016)
  • Author(s): Ohga N＊, Yamazaki Y, Sato J, Asaka T, Morimoto M, Hata H, Satoh C, Kitagawa Y
  • Journal Title: Arch Oral Biol Volume: 71 Pages: 129-133
  • DOI: 10.1016/j.archoralbio.2016.06.028
  • Peer Reviewed / Open Access
• [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] 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] 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] 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: 621-6
  • Peer Reviewed / Open Access
• [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 International Volume: in press
  • Peer Reviewed / Open Access
• [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] 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
• [Presentation] 腫瘍内低酸素環境と腫瘍血管内皮の異常性の関連 (2014)
  • Author(s): 大賀則孝、近藤美弥子、秋山廣輔、 間石奈湖、北川善政、進藤正信、樋田京子
  • Organizer: 口腔科学会
  • Place of Presentation: 京王プラザホテル(東京都、新宿区)
  • Year and Date: 2014-05-08 – 2014-05-09
• [Book] 別冊BIO Clinica 慢性炎症と疾患～慢性炎症とがん，5(1) (2015)
  • Author(s): 樋田京子，大賀則孝，間石奈湖，秋山廣輔，樋田泰浩
  • Total Pages: 4
  • Publisher: 北隆館