Trial for identification of targeting molecules in malignant pleural mesothelioma by proteomics

• Project/Area Number: 24501352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Yamaguchi University
• Principal Investigator: KURAMITSU Yasuhiro 山口大学, 医学(系)研究科(研究院), 准教授 (50281811)
• Co-Investigator(Kenkyū-buntansha): UEDA Kazuhiro 山口大学, 医学部附属病院, 講師 (90420520)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: バイオマーカー / 悪性胸膜中皮腫 / 分子標的 / プロテオミクス

Outline of Final Research Achievements

Proteomic differential display between malignant pleural mesothelioma cells and normal pleural cell identified HSP70、GRP78、PDX2、Protein disulfide isomerase A3、annexin A3 and 14kDa phosphohistidine phosphatase as up-regulated proteins in malignant pleural mesothelioma cells compared to normal pleural cell. Furthermore, by means of western blot analysis it was shown that in malignant pleural mesothelioma cells DDX39 was up-regulated compared to normal pleural cell. However, after knocking down these candidates the proliferation and moving were not down-regulated. After this we would like to investigate the function of these identified proteins in the tumorigenesis and pathogenesis of malignant pleural mesothelioma.

Research Products

• [Journal Article] High mobility group box 1 and Mitogen-activated protein kinase activated protein kinase-2 are up-regulated in gemcitabine-resistant pancreatic cancer cells. (2015)
  • Author(s): *Kuramitsu Y, Wang Y, Kitagawa T, Tokuda K, Akada J, Tokunaga M, Nakamura K.
  • Journal Title: Anticancer Research Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The histone deacetylase inhibitor Valproic Acid sensitizes gemcitabine-induced cytotoxicity in gemcitabine-resistant pancreatic cancer cells possibly through inhibition of the DNA repair protein gamma-H2AX. (2015)
  • Author(s): Wang Y, *Kuramitsu Y, Kitagawa T, Tokuda K, Baron B, Akada J, Nakamura K.
  • Journal Title: Targeted Oncology Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mutant screening for oncogenes of Ewing's sarcoma using yeast. (2015)
  • Author(s): Kitagawa T, Okita H, Baron B, Tokuda K, Nakamura M, Wang Y, Akada J, Hoshida H, Akada R, Kuramitsu Y, Nakamura K.
  • Journal Title: Applied Microbiology and Biotechnology Volume: in press
  • Peer Reviewed
• [Journal Article] Inflammation-related tumor progression in murine fibrosarcoma exhibited over-expression of Sex-determining region Y-box 2 (Sox2) compared to parental regressor cells. (2015)
  • Author(s): *Kuramitsu Y, Tanaka I, Wang Y, Okada F, Tokuda K, Kitagawa T, Akada J, Nakamura K.
  • Journal Title: Anticancer Research Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration. (2015)
  • Author(s): Wang Y, Kuramitsu Y, Kitagawa T, Baron B, Yoshino S, Maehara SI, Maehara Y, Oka M, Nakamura K.
  • Journal Title: Cancer Lett. Volume: 360 Issue: 2 Pages: 171-176
  • DOI: 10.1016/j.canlet.2015.02.015
  • Peer Reviewed / Open Access
• [Journal Article] Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis (2014)
  • Author(s): Kanda Y, Kawaguchi T, Kuramitsu Y, Kitagawa T, Kobayashi T, Takahashi N, Tazawa H, Habelhah H, Hamada J-I, Kobayashi M, Hirahata M, Onuma K, Osaki M, Nakamura K, Kitagawa T, Hosokawa M and Okada F.
  • Journal Title: Proteomics Volume: 14 Issue: 9 Pages: 1031-1041
  • DOI: 10.1002/pmic.201300414
  • Peer Reviewed
• [Journal Article] Proteomic analysis indicates that overexpression and nuclear translocation of lactoylglutathione lyase (GLO1) is associated with tumor progression in murine fibrosarcoma (2014)
  • Author(s): Wang Y, Kuramitsu Y, Tokuda K, Okada F, Baron B, Akada J, Kitagawa T, Nakamura K.
  • Journal Title: Electrophoresis Volume: 印刷中 Issue: 15 Pages: 3661-3665
  • DOI: 10.1002/elps.201300497
  • Peer Reviewed
• [Journal Article] Comparative Proteomics of Sera From HCC Patients With Different Origins. (2014)
  • Author(s): Sarvari J, Mojtahedi Z, Kuramitsu Y, Fattahi MR, Ghaderi A, Nakamura K, Erfani N.
  • Journal Title: Hepatitis Mothly Volume: 14(1) Issue: 1
  • DOI: 10.5812/hepatmon.13103
  • Peer Reviewed
• [Journal Article] Active hexose-correlated compound down-regulates HSP27 of pancreatic cancer cells, and helps the cytotoxic effect of gemcitabine. (2014)
  • Author(s): Suenaga S, Kuramitsu Y, Kaino S, Maehara S, Maehara Y, Sakaida I, Nakamura K.
  • Journal Title: Anticancer Res Volume: 34(1) Pages: 141-146
  • Peer Reviewed
• [Journal Article] Human pancreatic cancer cells with acquired gemcitabine resistance exhibit significant up-regulation of peroxiredoxin-2 compared to sensitive parental cells. (2013)
  • Author(s): Suenaga S, Kuramitsu Y, Wang Y, Baron B, Kitagawa T, Akada J, Tokuda K, Kaino S, Maehara S, Maehara Y, Sakaida I, Nakamura K.
  • Journal Title: Anticancer Res Volume: 33(11) Pages: 4821-4826
  • Peer Reviewed
• [Journal Article] Differentially Expressed Proteins in Chronic Active Hepatitis, Cirrhosis, and HCC Related to HCV Infection in Comparison With HBV Infection: A proteomics study. (2013)
  • Author(s): Sarvari J, Mojtahedi Z, Taghavi SA, Kuramitsu Y, Shamsi Shahrabadi M, Ghaderi A, Nakamura K.
  • Journal Title: Hepat Mon. Volume: 13(7) Issue: 7
  • DOI: 10.5812/hepatmon.8351
  • Peer Reviewed
• [Journal Article] Malignant progressive tumor cell clone exhibits significant up-regulation of cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone. (2013)
  • Author(s): Kuramitsu Y, Wang Y, Okada F, Baron B, Tokuda K, Kitagawa T, Akada J, Nakamura K.
  • Journal Title: Anticancer Res Volume: 33(9) Pages: 3661-3665
  • Peer Reviewed
• [Journal Article] Glyoxalase 1 as a candidate for indicating the metastatic potential of SN12C human renal cell carcinoma cell clones. (2013)
  • Author(s): Tanaka T, Kuramitsu Y, Wang Y, Baron B, Kitagawa T, Tokuda K, Hirakawa K, Yashiro M, Naito S, Nakamura K.
  • Journal Title: Oncol Rep. Volume: 30(5) Issue: 5 Pages: 2365-2370
  • DOI: 10.3892/or.2013.2699
  • Peer Reviewed
• [Journal Article] Chronic inflammation-derived nitric oxide causes conversion of human colonic adenoma cells into adenocarcinoma cells (2013)
  • Author(s): Tazawa H, Kawaguchi T, Kobayashi T, Kuramitsu Y, Wada S, Satomi Y, Nishino H, Kobayashi M, Kanda Y, Osaki M, Kitagawa T, Hosokawa M and Okada F
  • Journal Title: Exp Cell Res Volume: 319 Issue: 18 Pages: 2835-2844
  • DOI: 10.1016/j.yexcr.2013.08.006
  • Peer Reviewed
• [Journal Article] Up-regulation of DDX39 in human pancreatic cancer cells with acquired gemcitabine resistance compared to gemcitabine-sensitive parental cells. (2013)
  • Author(s): Kuramitsu Y, Suenaga S, Wang Y, Tokuda K, Kitagawa T, Tanaka T, Akada J, Maehara S, Maehara Y, Nakamura K.
  • Journal Title: Anticancer Res Volume: 33(8) Pages: 3133-3136
  • Peer Reviewed
• [Journal Article] A new type of protein chip to detect hepatocellular carcinoma-related autoimmune antibodies in the sera of hepatitis C virus-positive patients. (2013)
  • Author(s): Akada J, Kamei S, Ito A, Ito M, Kitagawa T, Furumoto H, Kato Y, Tamesa M, Takashima M, Shirai M, Yamano H, Oka M, Kuramitsu Y, Nakamura K.
  • Journal Title: Proteome Sci. Volume: 11(1) Issue: 1 Pages: 33-33
  • DOI: 10.1186/1477-5956-11-33
  • Peer Reviewed
• [Journal Article] Up-regulation of DDX39 in human malignant pleural mesothelioma cell lines compared to normal pleural mesothelial cells. (2013)
  • Author(s): Kuramitsu Y, Tominaga W, Baron B, Tokuda K, Wang Y, Kitagawa T, Nakamura K.
  • Journal Title: Anticancer Res Volume: 33(6) Pages: 2557-2560
  • Peer Reviewed
• [Journal Article] Up-regulation of DDX39 in human malignant pleural mesothelioma cell lines compared to normal pleural mesothelial cells. (2013)
  • Author(s): Kuramitsu, Y., Tominaga, W., Baron, B., Tokuda, K., Wang, Y., Kitagawa, T. and Nakamura K
  • Journal Title: Anticancer Research Volume: -
  • Peer Reviewed
• [Journal Article] Induced defence in lima bean plants exposed to the volatiles from two-spotted spider mite-infested conspecifics is independent of the major protein expression. (2013)
  • Author(s): Sugimoto, K., Matsui, K., Ozawa, R., Kuramitsu, Y., Kley, J., David, A., Muck, A., Nakamura, K., Boland, W. and Junji Takabayashi, J.
  • Journal Title: Journal of Plant Interactions Volume: -
  • Peer Reviewed
• [Journal Article] Proteomic Analysis Showed Down-regulation of Nucleophosmin in Progressive Tumor Cells Compared to Regressive Tumor Cells. (2013)
  • Author(s): Takenawa, T., *Kuramitsu, Y., Wang, Y., Okada, F., Tokuda, K., Kitagawa, T., Ueyama, Y. and Nakamura, K.
  • Journal Title: Anticancer Research Volume: 33 Pages: 153-160
  • Peer Reviewed
• [Journal Article] Secretomic analysis of large cell lung cancer cell lines using two-dimensional gel electrophoresis coupled to mass spectrometry (2012)
  • Author(s): Yousefi, Z., Sarvari, J., Nakamura, K., Kuramitsu, Y., Ghaderi, A. and Mojtahedi, Z.
  • Journal Title: Folia Histochemica et Cytobiologica Volume: 50 Pages: 368-374
  • Peer Reviewed
• [Presentation] Proteomics analysis of human malignant pleural mesothelioma cells compared to normal mesotherial cells. (2013)
  • Author(s): Kuramitsu, Y., Tominaga, W., Baron, B., Kitagawa, T., Akada, J. and Nakamura, K.
  • Organizer: HUPO 12th Annual World Congress
  • Place of Presentation: Yokohama（パシフィコ横浜）
• [Presentation] Proteomics analysis displays overexpression of Lactoylglutathione (GLO1) is associated with tumor progression in murine fibrosarcoma. (2013)
  • Author(s): Wang. Y., Kuramitsu, Y., Tokuda, K., Ueno, T., Nakamura, K., Suzuki, N., Yoshino, S., Iizuka, N., Akada, J. and Oka, M.
  • Organizer: HUPO 12th Annual World Congress
  • Place of Presentation: Yokohama（パシフィコ横浜）
• [Presentation] Comprehensive analysis of downstream targets of the novel protein E4TF-1 Binding Methyltransferase (EBM). (2013)
  • Author(s): Baron B., Kuramitsu, Y., Kitagawa, T., Nakamura, K. and Schembri-Wismayer, P
  • Organizer: HUPO 12th Annual World Congress
  • Place of Presentation: Yokohama（パシフィコ横浜）
• [Presentation] Immuno-proteomics of Helicobacter pylori antigens for IgG antibodies in H. pylori-positive Japanese child sera. (2013)
  • Author(s): Akada, J., Okuda, M., Fukuda, Y., Kitagawa, T., Kuramitsu, Y. and Nakamura, K.
  • Organizer: HUPO 12th Annual World Congress
  • Place of Presentation: Yokohama（パシフィコ横浜）
• [Presentation] Protein chip methodology to detect HSP70 autoimmune antibodies in the sera of hepatitis C virus-positive hepatocellular carcinoma patients. (2013)
  • Author(s): Akada, J., Kamei, S., Ito, A., Kitagawa, T., Oka, M., Kuramitsu, Y. and Nakamura, K.
  • Organizer: HUPO 12th Annual World Congress
  • Place of Presentation: Yokohama（パシフィコ横浜）
• [Presentation] Proteomic analysis showed heat shock 70 kDa protein and 78 kDa glucose-regulated protein were up-regulated in human malignant pleural mesothelioma cells. (2013)
  • Author(s): Yasuhiro Kuramitsu, Waka Tominaga, Byron Baron, Takao Kitagawa and Kazuyuki Nakamura
  • Organizer: European Multidisciplinary Conference in Thoracic Oncology (EMCTO)
  • Place of Presentation: Lugano, Switzerland
• [Presentation] Proteomic analysis showed heat shock 70 kDa protein and 78 kDa glucose-regulated protein were up-regulated in human malignant pleural mesothelioma cells. (2013)
  • Author(s): Yasuhiro Kuramitsu, Waka Tominaga, Byron Baron, Takao Kitagawa and Kazuyuki Nakamura
  • Organizer: European Multidisciplinary Conference in Thoracic Oncology (EMCTO)
  • Place of Presentation: ルガノ（スイス）
• [Presentation] Proteomic analysis of human malignant pleural mesothelioma cells compared to normal mesotherial cells. (2013)
  • Author(s): Yasuhiro Kuramitsu, Waka Tominaga, Byron Baron, Takao Kitagawa, Junko Akada and Kazuyuki Nakamura
  • Organizer: HUPO
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] Tanshinone IIA Doun-regulates Heat Shock Protein 27 in Pancreatic Cancer Cells and Enhances the Cytotoxic Effect of Gemcitabine (2012)
  • Author(s): Kuramitsu, Y., Suenaga, S., Baron, B., Wang, Y., Nakamura, K.
  • Organizer: 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
  • Place of Presentation: ダブリン（アイルランド）
• [Presentation] Combinatorial treatment of gemcitabine with HSP27 inhibitors to suppress resistance in pancreatic cancer cells. (2012)
  • Author(s): 藏滿保宏、末永成之、王宇峰、戒能聖治、坂井田功、中村和行
  • Organizer: 日本癌学会
  • Place of Presentation: ロイトン札幌(札幌）
• [Presentation] 抗癌剤耐性打開に向けた二次元電気泳動の実際例 (2012)
  • Author(s): 藏滿保宏
  • Organizer: 日本電気泳動学会
  • Place of Presentation: 沖縄コンベンションセンター（宜野湾）
  • Invited
• [Book] プロテオミクス辞典 (2013)
  • Author(s): 日本プロテオーム学会 編
  • Total Pages: 127
  • Publisher: 講談社