Study of gene amplification and metastasis in melanoma

• Project/Area Number: 26461700
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Saitama Medical University (2016-2017); Takasaki University of Health and Welfare (2014-2015)
• Principal Investigator: Murakami Takashi 埼玉医科大学, 医学部, 教授 (00326852)
• Co-Investigator(Kenkyū-buntansha): 斎藤 克代 高崎健康福祉大学, 薬学部, 助手 (90455288)
• Co-Investigator(Renkei-kenkyūsha): SATO Atsuko 自治医科大学, 医学部, 助教 (50382916)
• Research Collaborator: HORIUCHI Yutaka 埼玉医科大学, 医学部, 講師 (30608906)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん / メラノーマ / 遺伝子機能 / 上皮間葉転換 / 細胞運動 / シグナル伝達 / 浸潤 / 転移 / 遺伝子増幅

Outline of Final Research Achievements

We developed a luciferase-based luminescent assay system to evaluate cell migration using transformed NIH3T3 cells, and the assay system allowed to screen chemicals to inhibit cell migration. Subsequently, the mevalonate pathway appeared critical for migration in cancerous cells, including melanoma. Furthermore, we examined an amplified gene expression pattern using human melanoma cell lines that xenogeneically metastasized to the brain of NOD/SCID mice. Data suggested that 99 candidate genes were highly expressed in progressed melanoma. Further in silico analysis also suggested that some of candidate genes are associated in the biology of melanoma. Perhaps, the function of these candidate genes may be implicated in melanoma-specific tumor progression and its therapeutic resistance.

Research Products

• [Journal Article] A third-generation oncolytic herpes simplex virus inhibits the growth of liver tumors in mice. (2018)
  • Author(s): Nakatake R, Kaibori M, Nakamura Y, Tanaka Y, Matushima H, Okumura T, Murakami T, Ino Y, Todo T, Kon M.
  • Journal Title: Cancer Sci Volume: 109 Issue: 3 Pages: 600-610
  • DOI: 10.1111/cas.13492
  • Peer Reviewed / Open Access
• [Journal Article] In vivo imaging xenograft models for the evaluation of anti-brain tumor efficacy of targeted drugs. (2017)
  • Author(s): Kita K, Arai S, Nishiyama A, Taniguchi H, Fukuda K, Wang R, Yamada T, Takeuchi S, Tange S, Tajima A, Nakada M, Yasumoto K, Motoo Y, Murakami T, Yano S.
  • Journal Title: Cancer Med Volume: 6 Issue: 12 Pages: 2972-2983
  • DOI: 10.1002/cam4.1255
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of highly metastatic KRAS mutant lung cancer cell sublines in long-term three-dimensional low attachment cultures. (2017)
  • Author(s): Nakano T, Kanai Y, Amano Y, Yoshimoto T, Matsubara D, Shibano T, Tamura T, Oguni S, Katashiba S, Ito T, Murakami Y, Fukayama M, Murakami T, Endo S, Niki T.
  • Journal Title: Plos One Volume: 12 Issue: 8 Pages: e0181342-e0181342
  • DOI: 10.1371/journal.pone.0181342
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ZEB1-regulated inflammatory phenotype in breast cancer cells (2017)
  • Author(s): Katsura A, Tamura Y, Hokari S, Harada M, Morikawa M, Sakurai T, Takahashi K, Mizutani A, Nishida J, Yokoyama Y, Morishita Y, Murakami T, Ehata S, Miyazono K, Koinuma D
  • Journal Title: Molecular oncology Volume: 11 Issue: 9 Pages: 1241-1262
  • DOI: 10.1002/1878-0261.12098
  • Peer Reviewed / Open Access
• [Journal Article] Maltotriose conjugated to a chlorin derivative enhances the antitumor effects of photodynamic therapy in peritoneal dissemination of pancreatic cancer. (2017)
  • Author(s): Kato A, Kataoka H, Yano S, Hayashi K, Hayashi N, Tanaka M, Naitoh I, Ban T, Miyabe K, Kondo H, Yoshida M, Fujita Y, Hori Y, Natsume M, Murakami T, Narumi A, Nomoto A, Naiki-Ito A, Takahashi S, Joh T
  • Journal Title: Mol Cnacer Ther Volume: 印刷中 Issue: 6 Pages: 1124-1132
  • DOI: 10.1158/1535-7163.mct-16-0670
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CXCR4-targeted nanoparticles reduce cell viability, induce apoptosis and inhibit SDF-1α induced BT-549-Luc cell migration in vitro. (2017)
  • Author(s): Chittasupho C, Kewsuwan P, Murakami T.
  • Journal Title: Curr Drug Deliv. Volume: 14(8) Issue: 8 Pages: 1060-1070
  • DOI: 10.2174/1567201814666170216130448
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An in vivo screening system to identify tumorigenic genes. (2017)
  • Author(s): Ihara T, Hosokawa Y, Kumazawa K, Ishikawa K, Fujimoto J, Yamamoto M, Murakami T, Goshima N, Ito E, Watanabes S, Semba K.
  • Journal Title: Oncogene Volume: 36 Issue: 14 Pages: 2023-2029
  • DOI: 10.1038/onc.2016.351
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitors sensitize murine B16 melanoma cells to carbon ion irradiation by inducing G1 phase arrest. (2017)
  • Author(s): Saito K, Funayama T, Yokota Y, Murakami T, Kobayashi Y.
  • Journal Title: Biol. Pharm. Bull. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT) (2016)
  • Author(s): Kaneko R, Sato A, Hamada S, Yagi T, Ohsawa I, Ohtsuki M, Kobayashi E, Hirabayashi M, and Murakami T
  • Journal Title: Transgenic Research Volume: 17 Feb Issue: 4 Pages: 1-12
  • DOI: 10.1007/s11248-016-9939-3
  • Peer Reviewed / Open Access
• [Journal Article] High efficacy of third generation EGFR inhibitor AZD9291 in a leptomeningeal carcinomatosis model with EGFR-mutant lung cancer cells (2016)
  • Author(s): Nanjo S, Ebi H, Arai S, Takeuchi S, Yamada T, Mochizuki S, Okada Y, Nakada M, Murakami T, Yano S.
  • Journal Title: Oncotarget Volume: 7(4) Issue: 4 Pages: 3847-3856
  • DOI: 10.18632/oncotarget.6758
  • NAID: 120005830568
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies. (2016)
  • Author(s): Masuyama J, Murakami T, Iwamoto S, Fujita S.
  • Journal Title: Cytotherapy Volume: 18(1) Issue: 1 Pages: 80-90
  • DOI: 10.1016/j.jcyt.2015.09.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an anti-tumor effect on peritoneal carcinomatosis. (2015)
  • Author(s): Natatsuka R, Takahashi T, Serada S, Fujimoto M, Ookawara T, Nishida T, Hara H, Nishigaki T, Harada E, Murakami T, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Kishimoto T, Mori M, Doki Y, Naka T.
  • Journal Title: Br J Cancer Volume: 113(3) Issue: 3 Pages: 433-442
  • DOI: 10.1038/bjc.2015.229
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Design and function of engineered protein nanocages as a drug delivery system for targeting pancreatic cancer cells via neuropilin-1 (2015)
  • Author(s): Masaharu Murata, Sayoko Narahara, Takahito Kawano, Nobuhito Hamano, Jing Shu Piao, Jeong-Hun Kang, Kenoki Ohuchida, Takashi Murakami, Makoto Hashizume
  • Journal Title: Molecular Pharmaceutics Volume: in press Issue: 5 Pages: 1422-1430
  • DOI: 10.1021/mp5007129
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CXCL17 (chemokine (C-X-C motif) ligand 17) (2015)
  • Author(s): Matsui A, Murakami T.
  • Journal Title: Atlas Genet Cytogenet Oncol Haematol. Volume: 19(2) Issue: 2 Pages: 97-101
  • DOI: 10.4267/2042/56293
  • Open Access
• [Journal Article] Depsipeptide and roxithromycin induce apoptosis of lymphoma cells by blocking extracellular signal-regulated kinase activation. (2014)
  • Author(s): Morimura S, Sugaya M, Kai H, Miyagaki T, Asano Y, Tada Y, Kadono T, Murakami T, Sato S.
  • Journal Title: J Dermatol Volume: 41 Issue: 1 Pages: 57-62
  • DOI: 10.1111/1346-8138.12351
  • Peer Reviewed
• [Journal Article] ScreenFect Aによる遺伝子導入の特徴 (2014)
  • Author(s): 村上 孝
  • Journal Title: 和光純薬時報 Volume: 82 (3) Pages: 7-9
  • Acknowledgement Compliant
• [Presentation] ヒストン脱アセチル化酵素阻害剤による重粒子線感受 性の増強は、H2AX のリン酸化の増加に起因しない. (2017)
  • Author(s): 斎藤克代、舟山和夫、横田裕一郎、小林泰彦、村上 孝．
  • Organizer: 第137回日本薬学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] Minimal effect of soluble form of CEA on the disposition of membrane-bound form selective anti-CEA antibody, and its clinical relevance. (2017)
  • Author(s): Iwano J, Shinmi D, Masuda K, Murakami T, Kodaira H, Enokizono J.
  • Organizer: 第32回日本薬物動態学会
• [Presentation] In Vitro and In Vivo Characterization of KHK2455, a Highly Potent and Selective Indoleamine 2,3-dioxygenase 1 (IDO1) Inhibitor with a Novel Mechanism of Action. (2017)
  • Author(s): Mie M, Kunieda K, Koshiba S, Murakami T, Horita S, Fukuda Y, Ishii T, Nakai R, Nakamura K.
  • Organizer: Society for Immunotherapy of Cancer
  • Int'l Joint Research
• [Presentation] Pitabastation Modern Oncology. (2016)
  • Author(s): 村上 孝、斎藤克代、鳥澤保廣.
  • Organizer: 第34回メディシナルケミストリーシンポジウム.
  • Place of Presentation: つくば
  • Year and Date: 2016-11-30
• [Presentation] Radiosensitization by HDACi on heavy-ion irradiation is not related to increasing phosphorylation of H2AX． (2016)
  • Author(s): Saito K, Murakami T.
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] マウスTGF-β2を介した腫瘍進展と腫瘍休眠の生体内BLI評価． (2016)
  • Author(s): 飯塚一矢、野口沙斗美、原田 恩、斎藤克代、横尾英明、村上 孝.
  • Organizer: 第11回日本分子イメージング学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-05-28
• [Presentation] マウスTGF-β2を介した腫瘍進展と腫瘍休眠の調節的役割 (2016)
  • Author(s): 飯塚一矢、野口沙斗美、原田 恩、斎藤克代、横尾英明、村上 孝
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] 糖尿病併発担がんマウスにおけるn―３系不飽和脂肪酸の宿主免疫系への影響 (2016)
  • Author(s): 中野貴史、吉田 文、原田 恩、斎藤克代、河原田律子、小浜智子、大室弘美、小濱一弘、村上 孝
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] スタチン系薬剤によるマウスがん細胞の増殖・運動能の抑制 (2016)
  • Author(s): 贄田大智、原田 恩、鳥澤保廣、斎藤克代、村上 孝
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] スタチン系薬剤はTGF-β1を介した上皮間葉転換を抑制する (2016)
  • Author(s): 久保 遼、松崎 準、原田 恩、鳥澤保廣、斎藤克代、村上 孝
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] ヒストン脱アセチル化酵素阻害剤は重粒子線誘発G2/M期停止に影響を及ぼす (2016)
  • Author(s): 斎藤克代、舟山和夫、小林泰彦、村上 孝
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] エパルレスタットによるがん細胞の増殖•運動能抑制効果 (2016)
  • Author(s): 佐藤千秋、原田 恩、根本尚夫、鳥澤保廣、斎藤克代、村上 孝
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] Histone deacetylase inhibitors potentially sensitize murine B16 melanoma cells for heavy-ion irradiation (2015)
  • Author(s): Saito K, Funayama K, Kobayashi Y, Murakami T
  • Organizer: 第28回日本放射線腫瘍学会
  • Place of Presentation: 前橋
  • Year and Date: 2015-11-19
• [Presentation] Role of HDACi as a potential radiosensitizer for heavy-ion therapy on refractory malignancy (2015)
  • Author(s): Saito K, Murakami T
  • Organizer: 第7４回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Epigenetic modification potentially sensitizes heavy-ion therapy for malignancy (2015)
  • Author(s): Saito K, Funayama K, Kobayashi Y, Murakami T
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 京都
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] マウス4T1乳癌細胞における腫瘍進展と腫瘍休眠に対するin vivo 発光イメージング (2015)
  • Author(s): 野口沙斗美、原田 恩、斎藤克代、横尾英明、村上 孝
  • Organizer: 第10回日本分子イメージング学会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-20
• [Presentation] In vivo発光イメージングを用いた糖尿病状態におけるマウス4T1乳癌細胞の腫瘍進展の特徴 (2015)
  • Author(s): 吉田 文、原田 恩、斎藤克代、河原田律子、小浜智子、大室弘美、小濱一弘、村上 孝
  • Organizer: 第10回日本分子イメージング学会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-20
• [Presentation] 過剰な上皮間葉転換刺激はマウス4T1乳がんの腫瘍休眠を誘導する (2015)
  • Author(s): 野口沙斗美、梶田昌裕、原田 忍、斎藤克代、村上 孝
  • Organizer: 第135回 日本薬学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] エピジェネティック修飾を介した難治性がんに対する重粒子線感受性の増強 (2015)
  • Author(s): 斎藤克代、舟山和夫、小林泰彦、村上 孝
  • Organizer: 第135回 日本薬学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 複素環ジェネリック薬の癌代謝調節効果 (2015)
  • Author(s): 鳥澤保廣、村上 孝、杉本八郎、藤田有紀、根本尚夫、笠原真一郎、堀内宏明
  • Organizer: 第135回 日本薬学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] Excessive stimulation of epithelial-mesenchymal transition induces tumor dormancy in murine 4T1 breast cancer cells (2014)
  • Author(s): Noguchi S, Kajita M, Murakami T
  • Organizer: 第73回 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-24 – 2014-09-27
• [Presentation] Dynamic analysis of circulating tumor genome (CTG) and circulating tumor cells (CTCs) in an animal model (2014)
  • Author(s): Kajita M, Murakami T, Hayashi M
  • Organizer: 第73回 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-24 – 2014-09-27
• [Presentation] ルシフェラーゼ発光を用いた細胞傷害活性と細胞運動能の評価 (2014)
  • Author(s): 村上 孝、松居 彩、梶田昌裕、横尾英明
  • Organizer: 第9回 日本分子イメージング学会
  • Place of Presentation: 大阪千里
  • Year and Date: 2014-05-22 – 2014-05-23
• [Book] Current Immunosuppressive Therapy in Organ Transplantation (Edited by Chen H & Qian S; Chapter 10: Immunomodulation Therapy by the Control of Immune Cell Trafficking) (2015)
  • Author(s): Murakami T, Kobayashi E.
  • Publisher: Nova Science Publishers, Inc.
• [Book] がんの分子イメージング（浦野泰照 編集）「生物発光モデル動物作製によるがん生物学研究（２７章）」 (2015)
  • Author(s): 村上 孝
  • Publisher: 化学同人(京都）