Identifying several novel biomarkers of malignant tumors

• Project/Area Number: 25293130
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Chano Tokuhiro 滋賀医科大学, 医学部, 准教授 (40346028)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: biomarker / 悪性腫瘍 / RB1CC1 / p62/SQSTM1 / がん幹細胞 / 分子標的 / RAB39A / RXRB / バイオマーカー / 癌 / 臨床検査 / 放射線治療

Outline of Final Research Achievements

In order to renovate the clinical laboratory examination for malignant tumors, we clinically verified the originally developed biomarkers such as RB1CC1 and p62/SQSTM1, etc. In parallel, we also conducted the trial identification of unknown biomarkers for tumors using the model mice with genetic mutations caused by ENU.
From a different side, gene expression in cancer and the stem cells (CSCs) was investigated by comparisons with normal cells through global transcriptomics and principal component analyses. We found that novel molecules are selectively expressed in cancer cells of different histotypes, and we made an application for Japanese patents about these molecular candidatesas promising therapeutic targets for cancer.

Research Products

• [Int'l Joint Research] Bologna大学、Rizzoli研究所(イタリア)
• [Journal Article] p62/SQSTM1 levels predicts radiotherapy resistance in hypopharyngeal carcinomas. (2017)
  • Author(s): Arai A, Chano T, Ikebuchi K, Hama Y, Ochi Y, Tameno H, Shimada T.
  • Journal Title: Am J Cancer Res. Volume: 7(4) Pages: 881-891
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intratumoral acidosis fosters cancer-induced bone pain through the activation of the mesenchymal tumor-associated stroma in bone metastasis from breast carcinoma. (2017)
  • Author(s): Di Pompo G, Lemma S, Canti L, Rucci N, Ponzetti M, Errani C, Donati DM, Russell S, Gillies R, Chano T, Baldini N, Avnet S.
  • Journal Title: Oncotarget. Volume: Apr 13 Issue: 33 Pages: 1-19
  • DOI: 10.18632/oncotarget.17091
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effect of extracellular acidosis on the behaviour of mesenchymal stem cells in vitro. (2017)
  • Author(s): Massa A, Perut F, Chano T, Woloszyk A, Mitsiadis TA, Avnet S, Baldini N.
  • Journal Title: Eur Cell Mater. Volume: 33 Pages: 252-267
  • DOI: 10.22203/ecm.v033a19
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells in response to intratumoral acidosis via NF-κB activation. (2017)
  • Author(s): Avnet S, Di Pompo G, Chano T, Errani C, Ibrahim-Hashim A, Gillies RJ, Donati DM, Baldini N.
  • Journal Title: Int J Cancer. Volume: 140(6) Issue: 6 Pages: 1331-1345
  • DOI: 10.1002/ijc.30540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Altered pH gradient at the plasma membrane of osteosarcoma cells is a key mechanism of drug resistance. (2016)
  • Author(s): Avnet S, Lemma S, Cortini M, Pellegrini P, Perut F, Zini N, Kusuzaki K, Chano T, Grisendi G, Dominici M, De Milito A, Baldini N.
  • Journal Title: Oncotarget. Volume: 7(39) Issue: 39 Pages: 63408-63423
  • DOI: 10.18632/oncotarget.11503
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hydroxyl-HIF2-alpha is potential therapeutic target for renal cell carcinomas. (2016)
  • Author(s): Isono T, Chano T, Yoshida T, Kageyama S, Kawauchi A, Suzaki M, Yuasa T.
  • Journal Title: Am J Cancer Res. Volume: 6(10) Pages: 2263-2276
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells. (2016)
  • Author(s): Chano T, Avnet S, Kusuzaki K, Bonuccelli G, Sonveaux P, Rotili D, Mai A, Baldini N.
  • Journal Title: Am J Cancer Res. Volume: 6(4) Pages: 859-875
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Therapeutic inhibition of mitochondrial function induces cell death in starvation-resistant renal cell carcinomas. (2016)
  • Author(s): Isono T, Chano T, Yonese J, Yuasa T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 25669-25669
  • DOI: 10.1038/srep25669
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification and Validation of Housekeeping Genes for Gene Expression Analysis of Cancer Stem Cells. (2016)
  • Author(s): Lemma S, Avnet S, Salerno M, Chano T, Baldini N.
  • Journal Title: PLoS One. Volume: 11(2) Issue: 2 Pages: e0149481-e0149481
  • DOI: 10.1371/journal.pone.0149481
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mammalian autophagy is essential for hepatic and renal ketogenesis during starvation. (2016)
  • Author(s): Takagi A, Kume S, Kondo M, Nakazawa J, Chin-Kanasaki M, Araki H, Araki S, Koya D, Haneda M, Chano T, Matsusaka T, Nagao K, Adachi Y, Chan L, Maegawa H, Uzu T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 18944-18944
  • DOI: 10.1038/srep18944
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dimethyl sulfoxide induces chemotherapeutic resistance in the treatment of testicular embryonal carcinomas. (2016)
  • Author(s): Kita H, Okamoto K, Kushima R, Kawauchi A, Chano T.
  • Journal Title: Oncol Lett. Volume: 10(2) Pages: 661-666
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glucose deprivation induces G2/M transition-arrest and cell death in N-GlcNAc2-modified protein-producing renal carcinoma cells. (2014)
  • Author(s): Isono T, Chano T, Kitamura A, Yuasa T.
  • Journal Title: PLoS One. Volume: 9(5) Issue: 5 Pages: e96168-e96168
  • DOI: 10.1371/journal.pone.0096168
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of p62/SQSTM1 excess and oral carcinogenesis. (2013)
  • Author(s): Inui T, Chano T, Takikita-Suzuki M, Nishikawa M, Yamamoto G, Okabe H.
  • Journal Title: PLoS One. Volume: 8(9) Issue: 9 Pages: e74398-e74398
  • DOI: 10.1371/journal.pone.0074398
  • Peer Reviewed
• [Journal Article] Study of global transcriptional changes of N-GlcNAc2 proteins-producing T24 bladder carcinoma cells under glucose deprivation. (2013)
  • Author(s): Isono T, Chano T, Okabe H, Suzaki M.
  • Journal Title: PLoS One. Volume: 8(4) Issue: 4 Pages: e60397-e60397
  • DOI: 10.1371/journal.pone.0060397
  • Peer Reviewed
• [Presentation] Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells. (2016)
  • Author(s): Chano T, Avnet S, Kusuzaki K, Mai A, Baldini N.
  • Organizer: EORS 2016 (European Orthopaedic Research Society)
  • Place of Presentation: Bologna, Italy
  • Year and Date: 2016-09-14
  • Int'l Joint Research
• [Presentation] Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells. (2015)
  • Author(s): Chano T.
  • Organizer: ISCaM2015 (2nd Annual Meeting of the International Society of Cancer Metabolism)
  • Place of Presentation: San Servolo, Venice, Italy
  • Year and Date: 2015-09-16
  • Int'l Joint Research / Invited
• [Presentation] Oral carcinogenesis proceeds through p62/SQSTM1 excess. (2013)
  • Author(s): Chano T, Inui T, Okabe H.
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] N-GlcNAc2 proteins-producing renal carcinoma cells induced G2/M transition arrest to deal with glucose deprivation. (2013)
  • Author(s): Isono T, Chano T, Yuasa T.
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] RB1CC1 SUPPRESSES TYPE II COLLAGEN SYNTHESIS IN CHONDROCYTES, AND CAUSES DWARFISM (2013)
  • Author(s): Chano T, Nishimura I, Kita H, Matsusue Y, Okabe H.
  • Organizer: CORS 2013
  • Place of Presentation: Venice, イタリア共和国
• [Patent(Industrial Property Rights)] 癌の検査方法、癌細胞増殖阻害剤、抗癌剤及び抗癌剤のスクリーニング方法 (2015)
  • Inventor(s): 茶野徳宏
  • Industrial Property Rights Holder: 茶野徳宏
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-123952
  • Filing Date: 2015-06-19