Identification of sensitivity determinant factors of srafenib treatment in hepatocellular carcinoma.

• Project/Area Number: 23650627
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: Kinki University
• Principal Investigator: NISHIO Kazuto 近畿大学, 医学部, 教授 (10208134)
• Co-Investigator(Kenkyū-buntansha): KUDO Masatoshi 近畿大学, 医学部, 教授 (10298953)
• Project Period (FY): 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 肝細胞癌 / 遺伝子増幅 / FGFRシグナル / ソラフェニブ / バイオマーカー

Research Abstract

A real-time PCR-based copy number assay revealed that FGF3/FGF4 amplification was observed in responders to sorafenib, but not observed in non-responders(p=0.006). The clinicopathological features showed that multiple lung metastases and a poorly differentiated histological type were frequently observed in responders. Our findings may provide a novel insight into the molecular background of HCC and sorafenib responders, warranting further prospective biomarker studies.

Research Products

• [Journal Article] Expression changes in arrestin ss1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients (2012)
  • Author(s): Matsuoka, H., Arao, T., Makimura, C., Takeda, M., Kiyota, H., Tsurutani, J., Fujita, Y., Matsumoto, K., Kimura, H., Otsuka, M., Koyama, A., Imamura, CK., Tanigawara, Y., Yamanaka, T., Tanaka, K., Nishio, K., Nakagawa, K
  • Journal Title: Oncol Rep Volume: 27(5) Pages: 1393-9
• [Journal Article] Marked response to both S-1 and pemetrexed in a patient with echinoderm icrotubule-associated protein-like 4-anaplastic lymphoma kinase-positive lung adenocarcinoma (2012)
  • Author(s): Kaneda, H., Okamoto, I., Sakai, K., Tanizaki, J., Takeda, M., Nishio, K., Nakagawa, K
  • Journal Title: Acta Oncol
• [Journal Article] Slug is upregulated during wound healing and regulates cellular phenotypes in corneal epithelial cells (2012)
  • Author(s): Aomatsu, K., Arao, T., Abe, K., Kodama, A., Sugioka, K., Matsumoto, K., Kudo, K., Kimura, H., Fujita, Y., Hayashi, H., Nagai, T., Shimomura, Y., Nishio, K
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53(2) Pages: 751-6
• [Journal Article] SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in fastrointestinal cancer (2012)
  • Author(s): Tanaka, K., Arao, T., Tamura, D., Aomatsu, K., Furuta, K., Matsumoto, K., Kaneda, H., Kudo, K., Fujita, Y., Kimura, H., Yanagihara, K., Yamada, Y., Okamoto, I., Nakagawa, K., Nishio, K
  • Journal Title: Plos One Volume: 7(1)
• [Journal Article] FGFR2 gene amplification and clinicopathological featuers in gastric cancer (2012)
  • Author(s): Matsumoto, K., Arao, T., Hamaguchi, T., Shimada, Y., Kato, K., Oda, I., Taniguchi, H., Koizumi, F., Yanagihara, K., Sasaki, H., Nishio, K., Yamada, Y
  • Journal Title: Br J Cancer Volume: 106(4) Pages: 727-32
• [Journal Article] Combined effect of ALK and MEK inhibotors in EML4-ALK-positive non-small-cell lung cancer cells (2012)
  • Author(s): Tanizaki, J., Okamoto, I., Takezawa, K., Sakai, K., Azuma, K., Kuwata, K., Yamaguchi, H., Hatashita, E., Nishio, K., Janne, PA., Nakagawa, K
  • Journal Title: Br J Cancer Volume: 106(4) Pages: 763-7
• [Journal Article] Plasuma concentrations of angiogenesis-related molecules in patients with pancreatic cancer (2012)
  • Author(s): Sakamoto, H., Kimura, H., Sekijima, M., Matsumoto, K., Arao, T., Chikugo, T., Yamada, Y., Kitano, M., Ito, A., Takeyama, Y., Kudo, M., Nishio, K
  • Journal Title: Jpn J Clin Oncol Volume: 42(2) Pages: 105-12
• [Journal Article] Successful long-term treatment with pemetrexed of NSCLC associated with EML4-ALK and low thymidylate synthase expression (2012)
  • Author(s): Takeda, M., Okamoto, I., Sakai, K., Tanaka, K., Terashima, M., Nishio, K., Nakagawa, K
  • Journal Title: Clin Lung Cancer Volume: 13(2) Pages: 157-9
• [Journal Article] Integrated analysis of whole genome exon array and array-comparative genomic hybridization in gastric and colorectal cancer cells (2012)
  • Author(s): Furuta, K., Arao, T., Sakai, K., Kimura, H., Nagai, T., Tamura, D., Aomatsu, K., Kudo, K., Kaneda, H., Fujita, Y., Matsumoto, K., Yamada, Y., Yanagihara, K., Sekijima, M., Nishio, K
  • Journal Title: Cancer Sci Volume: 103(2) Pages: 221-7
• [Journal Article] Epidermal growth factor receptor mutation status in circulating free DNA in serum : from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer (2012)
  • Author(s): Goto, K., Ichinose, Y., Ohe, Y., Yamamoto, N., Negoro, S., Nishio, K., Itoh, Y., Jiang, H., Duffield, E., McCormack, R., Saijo, N., Mok, T., Fukuoka, M
  • Journal Title: J Thorac Oncol Volume: 7(1) Pages: 115-21
• [Journal Article] Marked response to both S-1 and pemetrexed in a patient with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-positive lung adenocarcinoma (2012)
  • Author(s): Kaneda, H.
  • Journal Title: Acta Oncol Volume: (E-pub ahead of print) Issue: 7 Pages: 942-944
  • DOI: 10.3109/0284186x.2011.653827
  • Peer Reviewed
• [Journal Article] SRFX2 iS a novel chondroitin sulfate proteoglycan that is overexpressed in fastrointestinal cancer (2012)
  • Author(s): Tanaka, K.
  • Journal Title: Plos One Volume: 7(1) Issue: 1 Pages: e27922-e27922
  • DOI: 10.1371/journal.pone.0027922
  • Peer Reviewed
• [Journal Article] Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors. (2012)
  • Author(s): Fujita Y, de Velasco MA, Nishio K. et. Al.
  • Journal Title: Invest New Drugs. Volume: 30 Issue: 5 Pages: 1878-1886
  • DOI: 10.1007/s10637-011-9749-7
  • Peer Reviewed
• [Journal Article] Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients (2011)
  • Author(s): Makimura, C., Arao, T., Matsumoto, K., Takeda, M., Kiyota, H., Tsurutani, J., Fujita, Y., Matsumoto, K., Kimura, H., Otsuka, M., Koyama, A., Imamura, CK., Yamanaka, T., Nishio, K., Nakagawa, K
  • Journal Title: Anticancer Res Volume: 31(12) Pages: 4561-8
• [Journal Article] What can and cannnot be done using a microarray analysis? Treatment stratification and clinical applications in oncology (2011)
  • Author(s): Arao, T., Matsumoto, K., Megawa, M., Nishio, K
  • Journal Title: Biol Pharm Bull Volume: 34(12) Pages: 1789-93
• [Journal Article] Phase I study of continuous afativib(BIBW2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib(LUX-Lung 4) (2011)
  • Author(s): Murakami, H., Tamura, T., Takahashi, T., Nokihara, H., Naito, T., Nakamura, Y., Nishio, K., Seki, Y., Sarashina, A., Shahidi, M., Yamamoto, N
  • Journal Title: Cancer Chemother Pharmacol
• [Journal Article] Serum heparan sulfate concertration is correlated with the failure of epidermal growth factor receptor tyrosine kinase inhibitor treatment in patients with lung adenocarcinoma (2011)
  • Author(s): Nishio, M., Yamanaka, T., Matsumoto, K., Kimura, H., Sakai, K., Sakai, A., Sone, T., Horiike, A., Koizumi, F., Kasahara, K., Ohira, T., Ikeda, N., Saijo, N., Arao, T., Nishio, K
  • Journal Title: J Thorac Oncol Volume: 6(11) Pages: 1889-94
• [Journal Article] Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors (2011)
  • Author(s): Fujita, Y., Islam, R., Kaneda, H., Kudo, K., Tamura, D., Aomatsu, K., Nagai, T., Kimura, H., Matsutmoto, K., Velasco, MA., Arao, T., Okawara, T., Nishio, K
  • Journal Title: Invest New Drugs
• [Journal Article] Activation of ERBB2 signaling causes resistance to the EGFR-derected therapeutic antibody cetuximab (2011)
  • Author(s): Yonesaka, K., Zejmullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., Fujisaka, Y., Philips, J., Shimizu, T., Maenishi, O, Cho, Y., Sun, J., Destro, A., Taira, K., Takeda, K., Okabe, T., Swanson, J., Shivdasani, RA., Nishio, K., Fukuoka, M., Verella-Garcia, M., Nakagawa, K., Janne, PA
  • Journal Title: Sci Transl Med Volume: 3(99)
• [Journal Article] Activin a inhibits vascular endothelial cell growth and suppresses tumor angiogensis in gastric cancer (2011)
  • Author(s): Kaneda, H., Arao, T., Matsumoto, K., Velasco, MA., Tamura, D., Aomatsu, K., Kudo, K., Sakai, K., Nagai, T., Fujita, Y., Tanaka, K., Yanagihara, K., Yamada, Y., Okamoto, I., Nakagawa, K., Nishio, K
  • Journal Title: Br J Cancer Volume: 5(8) Pages: 1210-7
• [Journal Article] Acquired drug resistanc eto vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor in human vascular enothelial cells (2011)
  • Author(s): Arao, T., Matsumoto, K., Furuta, K., Kudo, K., Kaneda, H., Nagai, T., Sakai, K., Fujita, Y., Tamura, D., Aomatsu, K., Koizumi, F., Nishio, K
  • Journal Title: Anticancer Res Volume: 31(9) Pages: 2787-96
• [Journal Article] Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3 (2011)
  • Author(s): Kodera, Y., Katanasaka, Y., Kitamura, Y., Hitoshi, T., Nishio, K., Tamura, T., Koizumi, F
  • Journal Title: Breast Cancer Res Volume: 13(3)
• [Journal Article] Roles of BIM induction and survivin downregulation in lapatinib-induced apoptosis in breast cancer cells with HER2 amplification (2011)
  • Author(s): Tanizaki, J., Okamoto, I., Fumita, S., Okamoto, W., Nishio, K., Nakagawa, K
  • Journal Title: Oncogene Volume: 30(39) Pages: 4097-106
• [Journal Article] Expression changes in arrestin β1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients (2011)
  • Author(s): H.Matsuoka, T.Arao, C.Makimura, M.Takeda, H.Kiyota, J.Tsurutani, Y.Fujita, K.Matsumoto, H.Kimura, M.Otsuka, A.Koyama, CK.Imamura, Y.Tanigawara, T.Yamanaka, K.Tanaka, K.Nishio, K.Nakagawa
  • Journal Title: Oncology Reports Volume: 27(5) Pages: 1393-9
  • DOI: 10.3892/or.2012.1660
  • Peer Reviewed
• [Journal Article] Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients (2011)
  • Author(s): Makimura, C.
  • Journal Title: Anticancer Res Volume: 31(12) Issue: 4 Pages: 972-125
  • DOI: 10.1007/s00280-011-1738-1
  • Peer Reviewed
• [Journal Article] What can and cannnot be done using a microarray analysis? Treatment stratification and clinical applications in oncology (2011)
  • Author(s): Arao, T.
  • Journal Title: Biol Pharm Bull Volume: 34812 Pages: 1789-93
  • Peer Reviewed
• [Journal Article] Activation of ERBB2 signaling causes resistance to the EGFR-derected therapeutic antibody cetuximab (2011)
  • Author(s): Yonesaka, K.
  • Journal Title: Sci Transl Med Volume: 3(99) Pages: 99-86
  • Peer Reviewed
• [Journal Article] Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3 (2011)
  • Author(s): Kodera, Y.
  • Journal Title: Breast Cancer Res Volume: 13(3)
  • Peer Reviewed
• [Journal Article] Roles of BIM induction and survivin downregulation in lapatinib-induced apoptosis in breast cancer cells with HER2 amplification, cancer model through inhibition of vascular endothelial growth factor receptor 3 (2011)
  • Author(s): Tanizaki, J.
  • Journal Title: Oncogene Volume: 30(39) Issue: 39 Pages: 4097-106
  • DOI: 10.1038/onc.2011.111
  • Peer Reviewed
• [Presentation] 血清ヘパラン硫酸濃度とEGRチロシンキナーゼ阻害薬耐性 (2011)
  • Author(s): 松本和子、西尾和人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] 大腸がんにおけるHS6ST2発現とその臨床的特徴 (2011)
  • Author(s): 木村英晴、西尾和人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] 肝細胞癌におけるTJP-1とTwist発現の肝癌切除後の予後への影響 (2011)
  • Author(s): 永井知行、工藤正俊、西尾和人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] 非小細胞肺がんにおけるEGFR T790の変異の新規検出法 (2011)
  • Author(s): 藤田至彦、西尾和人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] 胃癌のEMT関連遺伝子発現と化学療法治療予後 (2011)
  • Author(s): 荒尾徳三、西尾和人
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
• [Presentation] An analysis of serum heparan sulfate concentration and EGFR tyrosine kinase inhibitor treatment in patients with non-small cell lung adenocarcinoma (2011)
  • Author(s): Yamamoto, N., Nishio, K
  • Organizer: American Society of Clinical Oncology Annual Meeting 2011
  • Place of Presentation: Chicago
• [Presentation] Slug is upregulated during wound healing and downregulates TP63 in corneal epithelial cell (2011)
  • Author(s): Aomatsu, K., Nishio, K
  • Organizer: ARVO 2011 Vision Genomics
  • Place of Presentation: Florida
• [Presentation] A phase II trial of afatinib (BIBW 2992) in patinets (pts) with advanced non-small cell lung cancer previously treated with erkiubub (E) or (2011)
  • Author(s): Yamamoto, N.
  • Organizer: American Society of Clinical Oncology Annual Meeting 2011
  • Place of Presentation: Chicago
• [Presentation] An analysis of serum heparan sulfate concentration and EGFR tyrosine kinase inhibitor treatment in patients with non-small cell lung (2011)
  • Author(s): Nishio, M.
  • Organizer: American Society of Clinical Oncology Annual Meeting 2011
  • Place of Presentation: Chicago
• [Presentation] 血清ヘパラン硫酸濃度とEGRチロシンキナーゼ阻害薬耐性 (2011)
  • Author(s): 松本和子
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市名古屋国際会議場
• [Presentation] 大腸がんにおけるHS6ST2発現とその臨床的特徴 (2011)
  • Author(s): 木村英晴
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市名古屋国際会議場
• [Presentation] 肝細胞癌におけるTJP-1とTwist発現の肝癌切除後の予後への影響 (2011)
  • Author(s): 永井知行
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市名古屋国際会議場
• [Presentation] 非小細胞肺がんにおけるEGFR T790の変異の新規検出法 (2011)
  • Author(s): 藤田至彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市名古屋国際会議場
• [Presentation] 胃癌のEMT関連遺伝子発現と化学療法治療予後 (2011)
  • Author(s): 荒尾徳三
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市名古屋国際会議場
• [Patent(Industrial Property Rights)] ソラフェニブの効果予測方法 (2011)
  • Inventor(s): 西尾和人, 他
  • Industrial Property Rights Holder: 近畿大学, 他
  • Industrial Property Number: 2011-104275
  • Filing Date: 2011-05-09