Chemoresistance of non-small cell lung cancer-Its prediction by combination of tumor characteristics and personal predisposition

• Project/Area Number: 25460431
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Akita University
• Principal Investigator: Goto Akiteru 秋田大学, 医学(系)研究科(研究院), 教授 (90317090)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肺癌 / 化学療法感受性 / マイクロRNA / 遺伝子多型 / 肺腺癌 / Keap1-Nrf2系 / 化学療法反応性 / 非小細胞肺がん / 術後化学療法 / 免疫組織化学 / マイクロＲＮＡ

Outline of Final Research Achievements

To clarify the factors related to chemoresistance of non-small cell lung cancer (NSCLC), histopathological, molecular pathological, and gene polymorphism studies were performed. Histopathologically, high nuclear grade was correlated with resistance to adjuvant chemotherapy in lung adenocarcinoma. Molecular pathological analyses revealed lower expression of mir-451 was correlated to the resistance. We also analysed immunohistochemical expressions of Keap1 and Nrf2 proteins, which are involved in detoxification of chemotherapeutic reagents in lung adenocarcinoma. The immunohistochemical study confirmed inverse expressions of these proteins. As mir-17-92 cluster was hypothesized to target the Keap1/Nrf2 system, the genetic polymorphisms of target sequence were searched with the database for Keap1/Nrf2-related genes. The genotyping data of the cases are under correaltion analyses between chemoresistance, status of Keap1/Nrf2 system, and expressions of mir-17-92 cluster in NSCLC.

Research Products

• [Journal Article] SKAP2 promotes podosome formation to facilitate tumor-associated macrophage infiltration and metastatic progression. (2016)
  • Author(s): Tanaka M, Shimamura S, Kuriyama S, Maeda D, Goto A and Aiba N.
  • Journal Title: Cancedr Research Volume: 176 Issue: 2 Pages: 358-369
  • DOI: 10.1158/0008-5472.can-15-1879
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hunner-Type (Classic) Interstitial Cystitis: A Distinct Inflammatory Disorder Characterized by Pancystitis, with Frequent Expansion of Clonal B-Cells and Epithelial Denudation. (2015)
  • Author(s): Maeda D, Akiyama Y, Morikawa T, Kunita A, Ota Y, Katoh H, Niimi A, Nomiya A, Ishikawa S, Goto A, Igawa Y, Fukayama M, Homma Y.
  • Journal Title: PLos One Volume: 10 Issue: 11 Pages: 1-16
  • DOI: 10.1371/journal.pone.0143316
  • NAID: 120007089047
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clusters of proliferating endothelial cells and smooth muscle cells in rabbit carotid arteries. (2015)
  • Author(s): Takahashi M, Masuda H, Yoshida M, Ito Y, Nanjo H, Sugiyama T, Maeda D, Goto A.
  • Journal Title: Pathology International Volume: 65 Issue: 11 Pages: 585-594
  • DOI: 10.1111/pin.12348
  • Peer Reviewed
• [Journal Article] LPP inhibits collective cell migration during lung cancer dissemination (2015)
  • Author(s): Kuriyama S., Yoshida M., Yano S., Aiba N., Kohno T., Minamiya Y., Goto A., Tanaka M.
  • Journal Title: Oncogene Volume: - Issue: 8 Pages: 952-964
  • DOI: 10.1038/onc.2015.155
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Agr2 mediates paracrine effects on stromal fibroblasts that promote invasion by gastric signet-ring carcinoma cells (2015)
  • Author(s): Tsuji T., Satoyoshi R., Aiba N., Kubo T., Yanagihara K., Maeda D., Goto A., Ishikawa K., Yashiro M., Tanaka M
  • Journal Title: Cancer Research Volume: ７５ Issue: 2 Pages: 356-366
  • DOI: 10.1158/0008-5472.can-14-1693
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors. (2015)
  • Author(s): Tanino M, Sasajima T, Nanjo H, Akesaka S, Kagaya M, Kimura T, Ishida Y, Oda M, Takahashi M, Sugawara T, Yoshioka T, Nishihara H, Akagami Y, Goto A, Minamiya Y, Tanaka S; R-IHC Study Group.
  • Journal Title: Brain Tumor Pathol. Volume: 32 Issue: 1 Pages: 12-19
  • DOI: 10.1007/s10014-014-0188-y
  • NAID: 120005682120
  • Peer Reviewed / Open Access
• [Journal Article] Development of FGF2-dependent pluripotent stem cells showing naive state characteristics from murine preimplantation inner cell mass. (2014)
  • Author(s): Ozawa, M., Kawakami, E., Sakamoto, R., Shibasaki, T., Goto, A. and Yoshida, N.
  • Journal Title: Stem Cell Research Volume: in press Issue: 1 Pages: 75-87
  • DOI: 10.1016/j.scr.2014.04.012
  • Peer Reviewed
• [Journal Article] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition. (2014)
  • Author(s): Ibrahim R, Matsubara D, Osman W, Morikawa T, Goto A, Morita S, Ishikawa S, Aburatani H, Takai D, Nakajima J, Fukayama M, Niki T, Murakami Y
  • Journal Title: Hum Pathol. Volume: 45 Issue: 7 Pages: 1397-405
  • DOI: 10.1016/j.humpath.2014.02.013
  • Peer Reviewed / Open Access
• [Journal Article] Genomic and transcriptional alterations of cholangiocarcinoma (2014)
  • Author(s): Ito T, Sakurai-Yageta M, Goto A, Pairojkul C, Yongvanit P, Murakami Y.
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 21(6) Issue: 6 Pages: 380-387
  • DOI: 10.1002/jhbp.67
  • Peer Reviewed
• [Journal Article] Genetic aberrations as the targets of oncology research: Involvement of paraffin-embedded tissues. (2014)
  • Author(s): Dobashi Y, Goto A, Endo T, Ooi A.
  • Journal Title: Histol Histopathol. Volume: 29 Pages: 191-205
  • Peer Reviewed
• [Journal Article] Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates eytokinesis, and its expression correlates with the prognosis of renal cell earcinoma. (2013)
  • Author(s): Shoji K, Mimura I, Murayama T, Wada T, Kume H, Goto A, Ohse T, Tanaka T, Inagi R, van der Hoorn FA, Manabe I, Homma Y, Fukayama M, Sakurai T, Hasegawa T, Aburatani H, Kodama T, Nangaku M.
  • Journal Title: American Journal of Pathology Volume: 182 Issue: 6 Pages: 2191-2203
  • DOI: 10.1016/j.ajpath.2013.02.024
  • Peer Reviewed
• [Journal Article] High-grade Lung Adenocarcinoma With Fetal Lung-like Morphology: Clinicopathologic, Immunohistochemical, and Molecular Analyses of 17 Cases (2013)
  • Author(s): Morita S, Yoshida A, Goto A, Ota S, Tsuta K, Yokozawa K, Asamura H, Nakajima J, Takai D, Mori M, Oka T, Tamaru J, Itoyama S, Furuta K, Fukayama M, Tsuda H.
  • Journal Title: Am J Surg Pathol Volume: 37(6) Issue: 6 Pages: 924-932
  • DOI: 10.1097/pas.0b013e31827e1e83
  • Peer Reviewed
• [Journal Article] Bronchioloalveolar invasion in non-small cell lung cancer is associated with expression of transforming growth factor-β1. (2013)
  • Author(s): Imai, K., Minamiya, Y., Goto, A., Nanjo, H., Saito, H., Motoyama, S., Sato, Y., Kudo, S., Takashima, S., Kawaharada, Y., Kurihara, N., Orino, K., Ogawa, J.
  • Journal Title: World J. Surg., Oncol. Volume: 11 Issue: 1 Pages: 113-113
  • DOI: 10.1186/1477-7819-11-113
  • Peer Reviewed
• [Presentation] The cyclic morphological changes of the intercarated disc with the cardiac overload and its removal (2016)
  • Author(s): Makoto Yoshida, Daichi Maeda, Yukinobu Ito, Hirotake Masuda, Akiteru Goto
  • Organizer: The First JSPS Core to Core Seminar. Establishing International Research Network of Mathematical Oncology
  • Place of Presentation: 奈良市
  • Year and Date: 2016-03-09
  • Int'l Joint Research / Invited
• [Presentation] In vivo Induction of Angiogenesis in Rabbits (2016)
  • Author(s): Yukinobu Ito, Makoto Yoshida,Daichi Maeda, Akiteru Goto,
  • Organizer: The First JSPS Core to Core Seminar. Establishing International Research Network of Mathematical Oncology
  • Place of Presentation: 奈良市
  • Year and Date: 2016-03-09
  • Int'l Joint Research / Invited
• [Presentation] B-cell 異常に着目した間質性膀胱炎の病理組織学的研究 (2015)
  • Author(s): 前田大地、秋山佳之、森川鉄平、後藤明輝、深山正久
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] 迅速免疫組織化学染色を用いた膠腫におけるIDH1染色の術中応用 (2015)
  • Author(s): 廣嶋優子、南條 博、前田大地、後藤明輝、笹嶋寿郎、清水宏明、津田真寿美、田中伸哉
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] 肺癌でAKT遺伝子増幅に伴い変動するmicroRNAとその意義 (2015)
  • Author(s): 土橋 洋、後藤明輝、椙村春彦、山田茂樹、大井章史
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] MDM2増幅を示す心左室原発intimal sarcomaの一剖検例 (2015)
  • Author(s): 伊藤行信、前田大地、浅部幸紹、吉田誠、高橋正人、南條 博、増田弘毅、吉田朗彦、後藤明輝
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] 心臓右心室内腔に占拠性の転移巣を形成した胃癌の剖検例 (2015)
  • Author(s): 吉田 誠、前田大地、伊藤行信、浅部幸紹、南條 博、増田弘毅、後藤明輝
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] 小細胞肺癌におけるp16発現とパピローマウイルス感染 (2014)
  • Author(s): 後藤明輝，吉田 誠，伊藤行信，前田大地，南條 博，今井一博，南谷佳弘
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] 悪性黒色腫，甲状腺乳頭癌，肺腺癌および肺非定型カルチノイドを含む5重癌の1例 (2014)
  • Author(s): 伊藤行信，南條 博，吉田 誠，前田大地，南谷佳弘，後藤明輝
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] 多発する炎症性偽腫瘍を合併した特発性血小板減少性紫斑病の一剖検例 (2014)
  • Author(s): 吉田 誠，小松正代，波田野 善明，南條 博，伊藤行信，後藤明輝
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 静脈への動脈パッチ移植により発生した新生血管の研究 (2014)
  • Author(s): 伊藤行信，吉田 誠，高橋正人，南條 博，杉山達朗，川村公一，増田弘毅，後藤明輝
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] EBV陽性大型異型リンパ球の増生が目立ったAITLの一剖検例 (2014)
  • Author(s): 廣嶋優子，高橋正人，南條 博，鵜生川 久美，亀岡吉弘，伊藤行信，吉田 誠，川村公一，大田泰徳，後藤 明輝
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 電界非接触撹拌迅速免疫染色技術を用いた術中病理迅速診断 (2014)
  • Author(s): 南條 博，吉岡 年明，南谷佳弘，笹嶋寿郎，廣嶋優子，吉田 誠，後藤明輝，赤上陽一
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 新生児に発症したFetal lung interstitial tumor (FLIT) の一例 (2014)
  • Author(s): 吉岡年明，南條 博，伊藤智夫，蛇口 琢，矢野道広，新井浩和，吉野裕顕，後藤明輝，大森泰文
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 多彩な組織を呈した原発性肝腫瘍の一例 (2013)
  • Author(s): 吉田 誠，南條 博，吉岡年明，渡辺 剛，山本 雄造，高橋正人，柴原純二，後藤明輝
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
• [Presentation] 静脈への動脈パッチ移植することにより発生した新生血管の研究 (2013)
  • Author(s): 伊藤 行信，吉田 誠，高橋正人，南條 博，川村公一，後藤 明輝(
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
• [Presentation] 秋田で開発した迅速免疫染色技術を用いた術中迅速病理診断の有用性 (2013)
  • Author(s): 南條 博，吉岡年明，高橋正人，吉田 誠，廣島優子，笹嶋 寿郎，南谷 佳弘，赤上陽一，後藤 明輝
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
• [Presentation] 子宮原発PNET/Ewing’s sarcomaの一例 (2013)
  • Author(s): 島優子，南條 博，高橋正人，吉田 誠，藤本俊郎，後藤 明輝
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
• [Presentation] 肺腺癌の腫瘍間質おけるmiR-21の発現に関する検討 (2013)
  • Author(s): 盛田茂樹，国田朱子，後藤 明輝，佐久間 慶，山村はるみ，深山正
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
• [Presentation] 動脈リモデリングの解析-血流負荷家兎総頸動脈における内弾性板ギャップの発生メカニズム (2013)
  • Author(s): 増田弘毅，吉田 誠，高橋正人，伊藤 行信，川村公一，後藤 明輝
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌市
• [Presentation] 肺の非腫瘍性疾患の病理像と染色技術 (2013)
  • Author(s): 後藤明輝
  • Organizer: 第20回東北臨床検査技師会病理検査部門研修会
  • Place of Presentation: 秋田市
  • Invited