Cancer gene therapy of Wnt and TM4SF to inhibit progression of lung cancer

• Project/Area Number: 18390379
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kagawa University
• Principal Investigator: HUANG Cheng-long Kagawa University, 医学部, 准教授 (10271511)
• Co-Investigator(Kenkyū-buntansha): ISHIKAWA Sinya 香川大学, 医学部, 講師 (20363210) ; YOKOMISE Hiroyasu 香川大学, 医学部, 教授 (80231728) ; UENO Masaki 香川大学, 医学部, 准教授 (30322267)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,000,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥2,700,000); Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2006: ¥6,300,000 (Direct Cost: ¥6,300,000)
• Keywords: 遺伝子治療 / Wntシグナル / TM4SF / アデノウィルスベクター / RNA干渉 / 癌転移抑制遺伝子 / 癌転移 / 肺癌

Research Abstract

Wnt抑制ベクター作製のため, shRNA配列をpBAsi-hU6 DNAプラスミドベクターに組入れ, COS-TPC法でWnt抑制shRNA発現アデノウィルスベクターを作製した. Wnt2b抑制ベクターは, in vitro実験でWnt2b高発現癌細胞株に対して細胞障害活性を認め, Wnt2b高発現癌細胞株を移植した担癌ヌードマウスによる実験でも強力な抗腫瘍効果を認めた. 我々はTM4SFのメンバーであるCD9 の発現誘導アデノウィルスベクターも用いて, 癌転移抑制遺伝子治療の研究も行い, 機能解析を行っている.

Research Products

• [Journal Article] Wnt1 overexpression promotes tumour progression in non-small cell lung cancer (2008)
  • Author(s): Huang C., Liu D., Ishikawa S., Nakashima T., Nakashima N., Yokomise H., Kadota K., Ueno M.
  • Journal Title: Eur. J. Cancer 44 Pages: 2680-2688
  • Peer Reviewed
• [Journal Article] The clinical significance of splice variants and subcellular localization of survivin in non-small cell lung cancers (2008)
  • Author(s): Nakano J., Huang C., Liu D., Masuya D., Yokomise H., Ueno M., Haba R.
  • Journal Title: Br. J. Cancer 98 Pages: 1109-1117
  • Peer Reviewed
• [Journal Article] The clinical significance of lymphangiogenesis and angiogenesis in non-small cell lung cancer patients (2008)
  • Author(s): Kadota K., Huang C., Liu D., Ueno M., Kushida Y., Haba R., Yokomise H.
  • Journal Title: Eur. J. Cancer 44 Pages: 1057-1067
  • Peer Reviewed
• [Journal Article] Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients (2008)
  • Author(s): Nakashima T., Liu D., Nakano J., Ishikawa S., Yokomise H., Ueno M., Kadota K., Huang, C.
  • Journal Title: Oncol. Rep. 19 Pages: 203-209
  • Peer Reviewed
• [Journal Article] The expression of osteopontin is increased in vessels with blood-brain barrier impairment (2008)
  • Author(s): Iwanaga Y., Ueno M., Ueki M., Huang C., et.al.
  • Journal Title: Neuropathol. Appl. Neurobiol 34 Pages: 145-154
  • Peer Reviewed
• [Journal Article] Wntl overexpression promotes tumour progression in non-small cell lung cancer (2008)
  • Author(s): Cheng-long Huang, et al.
  • Journal Title: European Journal of Cancer 44 Pages: 2680-2688
  • Peer Reviewed
• [Journal Article] The clinical significance of splice variants and subcellular localization of survivin in non-small cell lung cancers (2008)
  • Author(s): Jun Nakano, et al.
  • Journal Title: British Journal of Cancer 98 Pages: 1109-1117
  • Peer Reviewed
• [Journal Article] The clinical significance of lymphangiogenesis and angiogenesis in non-small cell lung cancer patients (2008)
  • Author(s): Kyuichi Kadota, et al.
  • Journal Title: European Journal of Cancer 44 Pages: 1057-1067
  • Peer Reviewed
• [Journal Article] Wnt1 overexpression associated with tumor proliferation and a poor Prognosis in non-smal cell lung cancer patients (2008)
  • Author(s): Takashi Nakashima, et. al.
  • Journal Title: Oncology Reports 19 Pages: 203-209
  • Peer Reviewed
• [Journal Article] E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non-small cell lung cancer (2007)
  • Author(s): Huang C., Liu D., Nakano J., Yokomise H., Ueno M., Kadota K., Wada H.
  • Journal Title: Clin. Cancer Res. 13 Pages: 6938-6946
  • Peer Reviewed
• [Journal Article] Clinical significance of the p53 pathway and associated gene therapy in non-small cell lung cancers (2007)
  • Author(s): Huang C., Yokomise H., Mitake A.
  • Journal Title: Future Oncol 3 Pages: 83-93
  • Peer Reviewed
• [Journal Article] Overexpression of matrix metalloproteinase-7 (MMP-7) correlates with tumor proliferation, and a poor prognosis in non-small cell lung cancer (2007)
  • Author(s): Liu D., Nakano J., Ishikawa S., Yokomise H., Ueno M., Kadota K., Urushihara M., Huang C.
  • Journal Title: Lung Cancer 58 Pages: 384-391
  • Peer Reviewed
• [Journal Article] Induction chemoradiotherapy (Carboplatin-taxanes and concurrent 50 Gy radiation for bulky c-N2, N3 non-small-cell lung cancer (2007)
  • Author(s): Yokomise H., Gotoh M., Okamoto T., Yamamoto Y., Ishikawa S., Nakashima T., Masuya D., Liu D., Huang C.
  • Journal Title: J. Thorac. Cardiovasc. Surg. 133 Pages: 1179-1185
  • Peer Reviewed
• [Journal Article] En block partial vertebrectomy for lung cancer invading the spine after induction chemoradiotherapy (2007)
  • Author(s): Yokomise H., Gotoh M., Okamoto T., Yamamoto Y., Ishikawa S., Liu D., Oka S., Huang C.
  • Journal Title: Eur. J. Cardio-thorac. Surg. 31 Pages: 788-790
  • Peer Reviewed
• [Journal Article] Clinical application of infrared thoracoscopy to detect bullous or emphysematous lesions of the lung (2007)
  • Author(s): Gotoh M., Yamamoto Y., Igai H., Chang S., Huang C. and Yokomise H.
  • Journal Title: J. Thorac. Cardiovasc. Surg. 134 Pages: 1498-1501
  • Peer Reviewed
• [Journal Article] Accumulation of triosephosphate isomerase, with sequence homology to ・amyloid peptides, in vessel walls of the newborn piglet hippocampus (2007)
  • Author(s): Kusaka T., Ueno M., Miki T., Huang C., et.al.
  • Journal Title: Microsc. Res. Techniq 70 Pages: 648-655
  • Peer Reviewed
• [Journal Article] E2F1 overexpression correlates with thymidylate synthase and survivingene expressions and tumor proliferation in non-small cell lung cancer (2007)
  • Author(s): Cheng-long Huang, et. al.
  • Journal Title: Clinical Cancer Research 13 Pages: 6938-6946
  • Peer Reviewed
• [Journal Article] Overexpression of matrix metalloproteinase-7(MMP-7)correlates with tumor proliferation,and a poor prognosis in non-sman cell lung cancer (2007)
  • Author(s): Dage Liu, et. al.
  • Journal Title: Lung Cancer 58 Pages: 384-391
  • Peer Reviewed
• [Journal Article] MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the down-regulation of WAVE2 (2006)
  • Author(s): Huang C., Ueno M., Liu D., Masuya D., Nakano J., Yokomise H., Nakagawa T., Miyake M.
  • Journal Title: Oncogene 25 Pages: 6480-6488
  • Peer Reviewed
• [Journal Article] Tailor-made chemotherapy for non-small cell lung cancer patients (2006)
  • Author(s): Huang C., Yokomise H., Fukushima M., Kinoshita M.
  • Journal Title: Future Oncol 2 Pages: 289-299
  • Peer Reviewed
• [Journal Article] HAUSP gene plays an important role in carcinogenesis through p53 pathways in non-small cell lung cancers (2006)
  • Author(s): Masuya D., Huang C., Liu D., Nakashima T., Yokomise H., Ueno M., Nakashima N., Sumitomo S.
  • Journal Title: J. Pathol 208 Pages: 724-732
  • Peer Reviewed
• [Journal Article] Evaluations of biomarkers associated with 5-FU sensitivity for non-small cell lung cancer patients postoperatively treated with UFT (2006)
  • Author(s): Nakano J., Huang C., Liu D., Masuya D., Nakashima T., Yokomise H., Ueno M., Wada H., Fukushima M.
  • Journal Title: Br. J. Cancer 95 Pages: 607-615
  • Peer Reviewed
• [Journal Article] A useful protocol for analyses of mutations of the epidermal growth factor receptor gene (2006)
  • Author(s): Liu D., Nakano J., Ueno M., Masuya D., Nakashima T., Yokomise H., Yube K., Huang C.
  • Journal Title: Oncol. Rep. 15 Pages: 1503-1505
  • Peer Reviewed
• [Journal Article] Spontaneous elicitation of potent antitumor immunity and eradication of established tumors by administration of DNA encoding soluble transforming growth factor-beta II receptor without active antigen-sensitization (2006)
  • Author(s): Kontani K., Kajino K., Huang C., Fujino S., Taguchi O., Yamauchi A., Yokomise H., Ogasawara K.
  • Journal Title: Cancer Immunol. Immunother 55 Pages: 579-587
  • Peer Reviewed
• [Journal Article] Effects of aging and HIF-1・ deficiency on permeability of hippocampal vessels (2006)
  • Author(s): Ueno M., Tomita S., Nakagawa T., Huang C., et.al.
  • Journal Title: Microsc. Res. Techniq 69 Pages: 29-35
  • Peer Reviewed
• [Journal Article] Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1・-deficient mice (2006)
  • Author(s): Ueno M., Tomita S., Ueki M., Iwanaga Y., Huang C., Onodera M., Maekawa N., Gonzalez F.J., Sakamoto, H.
  • Journal Title: Histochem. Cell Biol. 125 Pages: 535-544
  • Peer Reviewed
• [Journal Article] MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2 (2006)
  • Author(s): Cheng-long Huang, et al.
  • Journal Title: Oncogene 25・49 Pages: 6480-6488
• [Journal Article] Tailor-made chemotherapy for non-small cell lung cancer patients (2006)
  • Author(s): Cheng-long Huang, et al.
  • Journal Title: Future Oncology 2・2 Pages: 289-299
• [Journal Article] Therapeutic strategy based on biological markers for non-small-cell lung cancers (2006)
  • Author(s): Cheng-long Huang, et al.
  • Journal Title: Enhancer - Biotherapy of Cancer 4・1 Pages: 19-21
• [Journal Article] The HAUSP gene plays an important role in non-small cell lung carcinogenesis through p53-dependent pathways (2006)
  • Author(s): Daiki Masuya, et al.
  • Journal Title: Journal of Pathology 208・5 Pages: 724-732
• [Journal Article] Evalutions of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT (2006)
  • Author(s): Jun Nakano, et al.
  • Journal Title: British Journal of Cancer 95・5 Pages: 607-615
• [Journal Article] A useful protocol for analyses of mutations of the epidermal growth factor receptor gene (2006)
  • Author(s): Dage Liu, et al.
  • Journal Title: Oncology Reports 15・6 Pages: 1503-1505
• [Presentation] Adenoviral vector expressing short hairpin RNA targeting Wnt2b has a strong antitumor activity against Wnt2b- overexpressing tumors (2009)
  • Author(s): 劉大革, 黄政龍, 他
  • Organizer: 100th Annual Meeting of America Association for Cancer Research
  • Place of Presentation: Denver, U.S.A.
  • Year and Date: 2009-04-21
• [Presentation] Combined therapy with an adenoviral vector expressing short hairpin RNA targeting thymidylate synthase and S-1 has effective antitumor activity against 5-FU-resistant tumors (2009)
  • Author(s): 門田球一, 黄政龍, 他
  • Organizer: 100th Annual Meeting of America Association for Cancer Research
  • Place of Presentation: Denver, U.S.A.
  • Year and Date: 2009-04-21
• [Presentation] 非小細胞肺癌における腫瘍内Wnt1発現による腫瘍増殖亢進と血管新生 (2008)
  • Author(s): 黄政龍, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Wnt2b抑制アデノウィルスベクターによる癌遺伝子治療の基礎的研究 (2008)
  • Author(s): 劉大革, 黄政龍, 他
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Tailor-made chemotherapy and gene therapy based on biomarkers in non-small cell lung cancer (2008)
  • Author(s): 黄政龍
  • Organizer: Sixth Annual Congress of International Drug Discovery Science and Technology
  • Place of Presentation: 北京, 中国
  • Year and Date: 2008-10-20
• [Presentation] Overexpression of the Wnt family promotes carcinogenesis in non-small cell lung cancer (2008)
  • Author(s): 黄政龍
  • Organizer: First Annual World Cancer Congress
  • Place of Presentation: 上海, 中国
  • Year and Date: 2008-06-13
• [Presentation] 非小細胞肺癌における分子マーカーに基づく個別化化学療法と遺伝子治療の展開 (2008)
  • Author(s): 黄政龍, 他
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-16
• [Presentation] 非小細胞肺癌における分子マーカーに基づく個別化化学療法と遺伝子治療への展開 (2008)
  • Author(s): 黄 政龍, 他
  • Organizer: 第108回日本外科学会定期学術集会ワークショップ
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-16
• [Presentation] Wnt1 overexpression is associated with tumor proliferation and angiogenesis in non-small cell lung cancer (2008)
  • Author(s): 黄政龍, 他
  • Organizer: 99th Annual Meeting of America Association for Cancer Research
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2008-04-14
• [Presentation] Lymphangiogenesis is associated with nodal metastasis and a poor prognosis in non-small cell lung cancer patients (2008)
  • Author(s): 門田球一, 黄政龍, 他
  • Organizer: 99th Annual Meeting of America Association for Cancer Research
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2008-04-13
• [Presentation] 非小細胞肺癌におけるWntシグナルの過剰発現とその制御への試み (2007)
  • Author(s): 黄政龍, 他
  • Organizer: 第48回日本肺癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-08
• [Presentation] 非小細胞肺癌における腫瘍増殖能関連分子マーカーに関する臨床的検討 (2007)
  • Author(s): 門田球一, 黄政龍, 他
  • Organizer: 第66回日本癌学会学術総会, 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] 非小細胞肺癌におけるWnt1過剰発現の臨床的意義 (2007)
  • Author(s): 劉大革, 黄政龍, 他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] 非小細胞肺癌におけるE2F1過剰発現によるTS発現と腫瘍増殖能への関与 (2007)
  • Author(s): 黄政龍, 他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] E2F1 overexpression associated with TS and surviving gene expressions in non-small cell lung cancer (2007)
  • Author(s): 黄政龍, 他
  • Organizer: 43rd Annual Meeting of American Society of Clinical Oncology
  • Place of Presentation: Chicago, U.S.A.
  • Year and Date: 2007-06-03
• [Presentation] 非小細胞肺癌におけるWnt1及びWnt5aの腫瘍内発現とVEGF-A発現との関連 (2007)
  • Author(s): 劉大革, 黄政龍, 他
  • Organizer: 第24回日本呼吸器外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-05-17
• [Presentation] 非小細胞肺癌における腫瘍内survivin及びsurvivin delta Ex3発現の臨床的意義 (2007)
  • Author(s): 中野淳, 黄政龍, 他
  • Organizer: 第24回日本呼吸器外科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-05-17
• [Presentation] 非小細胞肺癌におけるバイオマーカーに基づく個別化化学療法の展開 (2007)
  • Author(s): 黄政龍, 他
  • Organizer: 第24回日本呼吸器外科総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-05-17
• [Presentation] WNT signal pathways and TM4SF in non-small cell lung cancer (2006)
  • Author(s): 黄政龍
  • Organizer: 11 World Congress on Advances in Oncology
  • Place of Presentation: Crete, Greece
  • Year and Date: 2006-10-12
• [Presentation] 癌転移抑制遺伝子MRP-1/CD9のWAVE2抑制を介した細胞運動抑制 (2006)
  • Author(s): 黄政龍, 他
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-29
• [Presentation] 非小細胞肺癌におけるバイオマーカーに基づいた個別化アジュヴァント化学療法 (2006)
  • Author(s): 黄政龍, 他
  • Organizer: 第23回日本呼吸器外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2006-05-26
• [Book] Motility, in Encyclopedia of Cancer Second Edition (2008)
  • Author(s): Huang C.
  • Publisher: Springer-Verlag
• [Book] Motility. In : Encyclopedia of Cancer Second Edition (2008)
  • Author(s): Cheng-long Huang
  • Publisher: Springer-Verlag
• [Book] Motlity.In:Encyclopedia of Cancer 2nd Edition (2008)
  • Author(s): Cheng-long Huang
  • Publisher: Springer