The identification of drug resistance-related exosome microRNA and the applications for diagnosis and treatment in oral cancer

• Project/Area Number: 15K11296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: Nakayama Hideki 熊本大学, 大学院生命科学研究部(医), 教授 (70381001)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: microRNA / マイクロRNA

Outline of Final Research Achievements

The prognostic significance of circulating miRNAs in oral cancer patients has not been fully explored. The purpose of this study was to determine the clinical significance of circulating miRNAs in patients with oral cancer. Oral cancer patients who underwent surgery following chemoradiotherapy were enrolled. And circulating miRNA-1290 in blood serum prior to treatment was determined by quantitative RT-PCR in 55 patients. The associations between miRNA-1290 expression and various clinicopathological features were examined, and the effects of miRNA-1290 on the prognosis were evaluated.A Cox regression analysis based on the disease-free survival (DFS) revealed miR-1290 expression and pathological response to chemoradiotherapy to be significant prognostic factors in oral cancer patients. We demonstrated that miRNA-1290 expression pattern in pretreatment serum of oral cancer patients may have potential as a biomarker for outcome of CRT.

Research Products

• [Journal Article] Bladder cancer-associated cancer-testis antigen-derived long peptides encompassing both CTL and promiscuous HLA class II-restricted Th cell epitopes induced CD4+ T cells expressing converged T-cell receptor genes in vitro (2018)
  • Author(s): Tsuruta Miki、Ueda Shohei、Yew Poh Yin、Fukuda Isao、Yoshimura Sachiko、Kishi Hiroyuki、Hamana Hiroshi、Hirayama Masatoshi、Yatsuda Junji、Irie Atsushi、Senju Satoru、Yuba Eiji、Kamba Tomomi、Eto Masatoshi、Nakayama Hideki、Nishimura Yasuharu
  • Journal Title: OncoImmunology Volume: 7 Issue: 4 Pages: 1415687-1415687
  • DOI: 10.1080/2162402x.2017.1415687
  • Peer Reviewed / Open Access
• [Journal Article] Tumor budding as a novel predictor of occult metastasis in cT2N0 tongue squamous cell carcinoma (2018)
  • Author(s): Sakata Junki、Yamana Keisuke、Yoshida Ryoji、Matsuoka Yuichiro、Kawahara Kenta、Arita Hidetaka、Nakashima Hikaru、Nagata Masashi、Hirosue Akiyuki、Kawaguchi Sho、Gohara Shunsuke、Nagao Yuka、Hiraki Akimitsu、Shinohara Masanori、Toya Ryo、Murakami Ryuji、Nakayama Hideki
  • Journal Title: Human Pathology Volume: 76 Pages: 1-8
  • DOI: 10.1016/j.humpath.2017.12.021
  • Peer Reviewed / Open Access
• [Journal Article] Mucinous adenocarcinoma with signet ring cell features of the sublingual gland: A case report with an immunohistochemical analysis (2018)
  • Author(s): Nagata Masashi、Kusafuka Kimihide、Yoshida Ryoji、Kawahara Kenta、Nakagawa Yoshihiro、Nakamoto Masafumi、Shinohara Masanori、Nakayama Hideki
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: - Issue: 3 Pages: 252-6
  • DOI: 10.1016/j.ajoms.2017.12.008
  • Peer Reviewed
• [Journal Article] Severe interstitial pneumonia associated with anti-PD-1 immune checkpoint antibody after talc slurry pleurodesis (2018)
  • Author(s): Sakata Shinya、Matsuoka Yuichiro、Kawahara Kenta、Kakiuchi Yosuke、Takaki Akira、Hirosue Akiyuki、Yoshida Ryoji、Saeki Sho、Fujii Kazuhiko、Nakayama Hideki
  • Journal Title: Respiratory Investigation Volume: 56 Issue: 2 Pages: 195-198
  • DOI: 10.1016/j.resinv.2017.11.006
  • Peer Reviewed / Open Access
• [Journal Article] Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell carcinoma (2018)
  • Author(s): Shinriki S, Jono H, Maeshiro M, Nakamura T, Guo J, Li JD, Ueda M, Yoshida R, Shinohara M, Nakayama H, Matsui H, Ando Y.
  • Journal Title: Journal of Pathology Volume: 244 Issue: 3 Pages: 367-379
  • DOI: 10.1002/path.5019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The glucocorticoid receptor regulates the ANGPTL4 gene in a CTCF-mediated chromatin context in human hepatic cells (2017)
  • Author(s): M. Nakamoto, K. Ishihara, T. Watanabe, A. Hirosue, S. Hino, M. Shinohara, H. Nakayama, and M. Nakao.
  • Journal Title: PLoS One Volume: 12 Issue: 1 Pages: e0169225-e0169225
  • DOI: 10.1371/journal.pone.0169225
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion. (2017)
  • Author(s): Takahashi N, Wei FY, Watanabe S, Hirayama M, Ohuchi Y, Fujimura A, Kaitsuka T, Ishii I, Sawa T, Nakayama H, Akaike T, Tomizawa K.
  • Journal Title: Nucleic Acids Res. Volume: 45 Issue: 1 Pages: 435-445
  • DOI: 10.1093/nar/gkw745
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma (2017)
  • Author(s): Murakami R.、Nakayama H.、Semba A.、Hiraki A.、Nagata M.、Kawahara K.、Shiraishi S.、Hirai T.、Uozumi H.、Yamashita Y.
  • Journal Title: British Journal of Oral and Maxillofacial Surgery Volume: 55 Issue: 1 Pages: 50-55
  • DOI: 10.1016/j.bjoms.2016.08.026
• [Journal Article] Predictive value of the combination of SMAD4 expression and lymphocyte infiltration in malignant transformation of oral leukoplakia. (2017)
  • Author(s): Sakata J, Yoshida R, Matsuoka Y, Nagata M, Hirosue A, Kawahara K, Nakamura T, Nakamoto M, Hirayama M, Takahashi N, Nakashima H, Arita H, Ogi H, Hiraki A, Shinohara M, Nakayama H
  • Journal Title: Cancer medicine Volume: 6 Issue: 4 Pages: 730-738
  • DOI: 10.1002/cam4.1005
  • Peer Reviewed / Open Access
• [Journal Article] Notch1 in oral squamous cell carcinoma. (2017)
  • Author(s): Yoshida R, Ito T, Hassan WA, Nakayama H
  • Journal Title: Histology and histopathology Volume: 32 Pages: 315-323
• [Journal Article] Soluble IL-6R expressed by myeloid cells reduces tumor-specific Th1 differentation and drives tumor progression (2017)
  • Author(s): Tsukamoto H, Fujieda K, Hirayama M, Ikeda T, Yuno A, Matsumura K, Fukuma D, Araki K, Mizuta H, Nakayama H, Senju S, Nishimura Y
  • Journal Title: Cancer Research Volume: 14 Issue: 9 Pages: 2279-2291
  • DOI: 10.1158/0008-5472.can-16-2446
  • Peer Reviewed / Open Access
• [Journal Article] Salivary duct carcinoma treated with cetuximab-based targeted therapy: A case report. (2017)
  • Author(s): Kawahara K, Hiraki A, Yoshida R, Arita H, Matsuoka Y, Yamashita T, Koga K, Nagata M, Hirosue A, Fukuma D, Nakayama H.
  • Journal Title: Molecular and clinical oncology Volume: 6 Issue: 6 Pages: 886-892
  • DOI: 10.3892/mco.2017.1226
  • Peer Reviewed
• [Journal Article] Concurrent chemoradiotherapy with S1 in patients with stage III;IV oral squamous cell carcinoma: A retrospective analysis of nodal classification based on the neck node level. (2017)
  • Author(s): MURAKAMI R, SEMBA A,KAWAHARA K, MATSUYAMA K, HIRAKI A, NAGATA M, TOYA R, YAMASHITA Y, OYA N, NAKAYAMA H.
  • Journal Title: Molecular and clinical oncology. Volume: 2 Issue: 1 Pages: 140-144
  • DOI: 10.3892/mco.2017.1276
  • Peer Reviewed
• [Journal Article] FBXW7 expression affects the response to chemoradiotherapy and overall survival among patients with oral squamous cell carcinoma: A single-center retrospective study. (2017)
  • Author(s): Hidetaka Arita, Masashi Nagata, Ryoji Yoshida, Yuichiro Matsuoka1, Akiyuki Hirosue, Kenta Kawahara, Junki Sakata, Hikaru Nakashima, Taku Kojima, Ryo Toya, Ryuji Murakami, Akimitsu Hiraki, Masanori Shinohara and Hideki Nakayama.
  • Journal Title: Tumour Biology Volume: 39 Issue: 10 Pages: 1-9
  • DOI: 10.1177/1010428317731771
  • Peer Reviewed / Open Access
• [Journal Article] A rare case of metachronous multiple supernumerary teeth in the bilateral premolar region of the mandible. (2016)
  • Author(s): Koga K, Yoshida R, Nakamura T, Matsuoka Y, Takeshita H, Takahashi N, Nakamoto M, Hiraki A, Shinohara M, Nakayama H.
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: ー Issue: 2 Pages: 132-135
  • DOI: 10.1016/j.ajoms.2016.08.007
  • Peer Reviewed
• [Journal Article] Pre-treatment neutrophil to lymphocyte ratio predicts the chemoradiotherapy outcome and survival in patients with oral squamous cell carcinoma (2016)
  • Author(s): Hikaru Nakashima, Yuichiro Matsuoka, Ryoji Yoshida, Masashi Nagata, Akiyuki Hirosue, Kenta Kawahara, Jyunki Sakata, Hidetaka Arita, Akimitsu Hiraki and Hideki Nakayama
  • Journal Title: BMC Cancer Volume: 26 Issue: 1 Pages: 41-41
  • DOI: 10.1186/s12885-016-2079-6
  • Peer Reviewed / Open Access
• [Journal Article] Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using CD14-ML Technology (2016)
  • Author(s): Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno1, Masatoshi Hirayama, Hideki Nakayama, Hiroshi Mizuta, Yasuharu Nishimura, Satoru Senju
  • Journal Title: Plos One Volume: 11 Issue: 4 Pages: e0152384-e0152384
  • DOI: 10.1371/journal.pone.0152384
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Factors affecting volume change of myocutaneous flaps in oral cancer. (2016)
  • Author(s): Hiraki Akimitsu
  • Journal Title: Int J Oral Maxillofac Surg Volume: 45 Issue: 11 Pages: 1395-1399
  • DOI: 10.1016/j.ijom.2016.04.014
  • Peer Reviewed
• [Journal Article] Sentinel lymph node biopsy reduces the incidence of secondary neck metastasis in patients with oral squamous cell carcinoma. (2016)
  • Author(s): Hiraki A, Fukuma D, Nagata M, Shiraishi S, Kawahara K, Matsuoka Y, Nakagawa Y, Yoshida R, Tanaka T, Yohitake Y, Shinohara M, Yamashita Y, Nakayama H.
  • Journal Title: Molecular and Clinical Oncology Volume: 5 Issue: 1 Pages: 57-60
  • DOI: 10.3892/mco.2016.882
  • Peer Reviewed
• [Journal Article] Enhancement of active MMP release and invasive activity of lymph node metastatic tongue cancer cells by elevated signaling via the TNF-α-TNFR1-NF-κB pathway and a possible involvement of angiopoietin-like 4 in lung metastasis. (2016)
  • Author(s): Tanaka, T., Imamura, T., Yoneda, M., Irie, A., Ogi, H., Nagata, M., Yoshida, R., Fukuma, D., Kawahara, K., Shinohara, M, & Nakayama, H.
  • Journal Title: Int. J. Oncol. Volume: 49 Issue: 4 Pages: 1377-1384
  • DOI: 10.3892/ijo.2016.3653
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma. (2016)
  • Author(s): Matsuoka Yuichiro
  • Journal Title: Br J Cancer Volume: 115 Issue: 10 Pages: 1234-1244
  • DOI: 10.1038/bjc.2016.327
  • Peer Reviewed
• [Journal Article] Notch1 in oral squamous cell carcinoma. (2016)
  • Author(s): Yoshida R, Ito T, Hassan WA, Nakayama H.
  • Journal Title: Histol Histopathol. Volume: ー
  • Peer Reviewed
• [Journal Article] The tumour stromal features are associated with resistance to 5-FU-based chemoradiotherapy and a poor prognosis in patients with oral squamous cell carcinoma. (2015)
  • Author(s): Matsuoka Y, Yoshida R, Nakayama H, Nagata M, Hirosue A, Tanaka T, Kawahara K, Nakagawa Y, Sakata J, Arita H, Hiraki A, Shinohara M.
  • Journal Title: APMIS Volume: 3 Issue: 3 Pages: 205-14
  • DOI: 10.1111/apm.12344
  • Peer Reviewed / Open Access
• [Journal Article] Intrinsic TGF-β2-triggered SDF-1-CXCR4 signaling axis is crucial for drug resistance and a slow-cycling state in bone marrow-disseminated tumor cells. (2015)
  • Author(s): Nakamura T, Shinriki S, Jono H, Guo J, Ueda M, Hayashi M, Yamashita S, Zijlstra A, Nakayama H, Hiraki A, Shinohara M, Ando Y.
  • Journal Title: Oncotarget Volume: 6 Issue: 2 Pages: 1008-19
  • DOI: 10.18632/oncotarget.2826
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS (2015)
  • Author(s): Yoshitake, Y., Fukuma, D., Yuno, A., Hirayama, M., Nakayama, H., Tanaka. T., Nagata, M., Takamune, Y., Kawahara, K., Nakagawa, Y., Yoshida, R., Hirosue, A., Ogi, H., Hiraki, A. , Jono, H., Hamada, A., Yoshida, K., Nishimura, Y., Nakamura, Y., Shinohara, M.
  • Journal Title: Clinical Cancer Research Volume: 21 Issue: 2 Pages: 312-321
  • DOI: 10.1158/1078-0432.ccr-14-0202
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Osteopontin-integrin αvβ3 axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma. (2015)
  • Author(s): Nakamura T, Shinriki S, Jono H, Ueda M, Nagata M, Guo J, Hayashi M , Yoshida R, Ota T, Ota K, Kawahara K, Nakagawa Y, Yamashita S, Nakayama H, Hiraki A, Shinohara M, Ando Y.
  • Journal Title: FEBS Lett. Volume: 589 Pages: 231-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Investigation of the clinical significance of circulating miRNA-1290 in oral squamous cell carcinoma. (2017)
  • Author(s): Nakashima H, Yoshida R, Matsuoka Y, Kawahara K, Sakata J, Arita H, Nagata M, Hirosue A, Nakayama H, Shinohara M
  • Organizer: 第29回台湾口腔顎顔面外科学会年次総会・学術集会
• [Presentation] 近況報告と今後の抱負について (2016)
  • Author(s): 中山秀樹
  • Organizer: 第49回NPO法人 日本口腔科学会九州地方部会
  • Place of Presentation: 沖縄県男女共同参画センター「てぃるる」ホール
• [Presentation] IL-6 confers radioresistance via Nrf2 antioxidant pathway in oral squamous cell carcinoma cells (2015)
  • Author(s): Nakayama H, Matsuoka Y, Yoshida R, Hirosue A, Tanaka T, Nagata M, Kawahara K, Ogi H, Hiraki A, Shinohara M
  • Organizer: The 63rd Annual Meeting of Japanese Association for Dental Research
  • Place of Presentation: INTERNATIONAL CONGRESS CENTER Fukuoka
  • Year and Date: 2015-10-31
  • Int'l Joint Research