The study of correlation between biomarker and chemoradio-sensitivity on digestive cancer

• Project/Area Number: 15K10107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kagoshima University
• Principal Investigator: OKUMURA Hiroshi 鹿児島大学, 医歯学総合研究科, 客員研究員 (10398282)
• Co-Investigator(Kenkyū-buntansha): 盛 真一郎 鹿児島大学, 医歯学域附属病院, 助教 (00620519) ; 内門 泰斗 鹿児島大学, 医歯学域附属病院, 特任准教授 (30464465) ; 喜多 芳昭 鹿児島大学, 医学部・歯学部附属病院, その他(移行) (30570692) ; 夏越 祥次 鹿児島大学, 医歯学域医学系, 教授 (70237577) ; 石神 純也 鹿児島大学, 医歯学総合研究科, 客員研究員 (90325803)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 消化器癌 / 化学放射線療法 / 化学療法 / 幹細胞 / 活性酸素

Outline of Final Research Achievements

While chemoradiation therapy is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response before treatment by using markers. Fifty-nine patients with ESCC were treated with neoadjuvant chemoradiation therapy. The expression of seven kinds of biomarker candidate proteins (P53，CDC25B，14-3-3sigma，P53R2，ERCC１，Gli1，Nrf2) in biopsy specimens of untreated primary tumor was evaluated whether it correlates with the response and prognosis.
CRT was significantly effective in p53 (-), p53R2 (-), and ERCC1 (-) tumors and p53 (-), p53R2 (-) and ERCC1 (-) were independent correlated factors for effective histological response. Their combined expression of three or two negative expressions had 100% effective response, and was significant prognostic factor. Our results suggest that three or two negative expressions of p53, p53R2, ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC.

Research Products

• [Journal Article] Multidisciplinary therapy for metastatic primary malignant melanoma of the esophagus: A case report (2018)
  • Author(s): Sasaki K, Uchikado Y, Omoto I, Amatatsu M, Megumi K, Okumura H, Maemura K, Natsugoe S
  • Journal Title: Mol Clin Oncol Volume: 印刷中
  • DOI: 10.3892/mco.2018.1572
  • Peer Reviewed / Open Access
• [Journal Article] Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma (2017)
  • Author(s): Noda Masahiro、Uchikado Yasuto、Omoto Itaru、Sasaki Ken、Kita Yoshiaki、Owaki Tetsuhiro、Natsugoe Shoji
  • Journal Title: Annals of Surgical Oncology Volume: 25 Issue: 2 Pages: 449-455
  • DOI: 10.1245/s10434-017-6271-y
  • Peer Reviewed
• [Journal Article] Laparoscopic complete mesocolic excision via combined medial and cranial approaches for transverse colon cancer (2017)
  • Author(s): Mori S, Kita Y, Baba K, Yanagi M, Tanabe K, Uchikado Y, Kurahara H, Arigami T, Uenosono Y, Mataki Y, Okumura H, Nakajo A, Maemura K, Natsugoe S
  • Journal Title: Surg Today Volume: 47 Issue: 5 Pages: 643-649
  • DOI: 10.1007/s00595-016-1409-2
  • Peer Reviewed
• [Journal Article] Role of (18)F-FDG-PET/CT in Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy (2017)
  • Author(s): Sasaki K, Uchikado Y, Okumura H, Omoto I, Kita Y, Arigami T, Uenosono Y, Owaki T, Maemura K, Natsugoe S
  • Journal Title: Anticancer Res Volume: 37 Pages: 859-864
  • Peer Reviewed
• [Journal Article] Role of (18)F-FDG-PET/CT in Esophageal Squamous CellCarcinoma After Neoadjuvant Chemoradiotherapy (2017)
  • Author(s): １０）Sasaki K, Uchikado Y, Okumura H, Omoto I, Kita Y, Arigami T, Uenosono Y, Owaki T, Maemura K, Natsugoe S
  • Journal Title: Anticancer Res Volume: 37 Pages: 859-864
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical features and treatment of patients with esophageal cancer and a history of gastrectomy: a multicenter, questionnaire survey in Kyushu, Japan (2016)
  • Author(s): Okumura H, Mori N, Tanaka T, Morita M, Toh Y, Saeki H, Maehara Y, Nakamura K, Honda H, Yoshida N, Baba H, Natsugoe S
  • Journal Title: Dis Esophagus Volume: 29 Issue: 8 Pages: 1135-1143
  • DOI: 10.1111/dote.12439
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical analysis of the diagnosis and treatment of esophageal perforation (2016)
  • Author(s): Okumura H, Uchikado Y, Kita Y, Omoto I, Hayashi N, Matsumoto M, Sasaki K, Setoyama T, Arigami T, Uenosono Y, Matsushita D, Desaki R, Noda M, Higo N, Okubo K, Urata M, Yamasaki Y, Owaki T, Ishigami S, Natsugoe S
  • Journal Title: Esophagus Volume: 13 Pages: 146-150
  • NAID: 40020807827
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Novel Scoring System Based on Fibrinogen and the Neutrophil-Lymphocyte Ratio as a Predictor of Chemotherapy Response and Prognosis in Patients with Advanced Gastric Cancer (2016)
  • Author(s): Takaaki Arigami
  • Journal Title: Oncology Volume: 90 Issue: 4 Pages: 1977-84
  • DOI: 10.1159/000444494
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Combined fibrinogen concentration and neutrophil-lymphocyte ratio as a prognostic marker of gastric cancer (2016)
  • Author(s): Arigami T, Uenosono Y, Matsushita D, Yanagita S, Uchikado Y, Kita Y, Mori S, Kijima Y, Okumura H, Maemura K, Ishigami S, Natsugoe S.
  • Journal Title: Oncol Lett Volume: 11 Pages: 1537-1544
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): Desaki R, Sawada G, Okumura H, Ikeda R, Tanabe K, Komatsu H, Mimori K, Mori M, Kita Y, Uchikado Y, Arigami T, Uenosono Y, Owaki T, Ishigami S, Natsugoe S.
  • Journal Title: Ann Surg Oncol. Volume: Epub Issue: 2 Pages: 586-593
  • DOI: 10.1245/s10434-015-5031-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ferredoxin Reductase Is Useful for Predicting the Effect of Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma (2015)
  • Author(s): Okumura H, Uchikado Y, Omoto I, Motomura M, Kita Y, Sasaki K, Noda M, Arigami T, Uenosono Y, Baba K, Mori S, Kijima Y, Nakajo A, Kurahara H, Maemura K, Sakoda M, Owaki T, Ishigami S, Natsugoe S
  • Journal Title: Anticancer Res. Volume: 35 Pages: 6471-6474
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical Significance of Circulating Tumor Cells in Peripheral Blood of Patients with Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): Matsushita D, Uenosono Y, Arigami T, Yanagita S, Nishizono Y, Hagihara T, Hirata M, Haraguchi N, Arima H, Kijima Y, Kurahara H, Maemura K, Okumura H, Ishigami S, Natsugoe S
  • Journal Title: Ann Surg Oncol Volume: 22 Issue: 11 Pages: 3674-3680
  • DOI: 10.1245/s10434-015-4392-8
  • Peer Reviewed
• [Journal Article] Correlation of Aurora-A expression with the effect of chemoradiation therapy on esophageal squamous cell carcinoma. (2015)
  • Author(s): Tamotsu K, Okumura H, Uchikado Y, Kita Y, Sasaki K, Omoto I, Owaki T, Arigami T, Uenosono Y, Nakajo A, Kijima Y, Ishigami S, Natsugoe S.
  • Journal Title: BMC Cancer Volume: 15 Issue: 1 Pages: 323-323
  • DOI: 10.1186/s12885-015-1329-3
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the Fibrinogen and Neutrophil-Lymphocyte Ratio in Esophageal Squamous Cell Carcinoma: A Promising Blood Marker of Tumor Progression and Prognosis. (2015)
  • Author(s): Arigami T, Okumura H, Matsumoto M, Uchikado Y, Uenosono Y, Kita Y, Owaki T, Mori S, Kurahara H, Kijima Y, Ishigami S, Natsugoe S
  • Journal Title: Medicine Volume: 94 Issue: 42 Pages: 1702-1702
  • DOI: 10.1097/md.0000000000001702
  • Peer Reviewed
• [Journal Article] As a Novel Prognostic Marker, Cysteine/histidine-rich 1 (CYHR1) is a Therapeutic Target in Patients with Esophageal Squamous Cell Carcinoma (2015)
  • Author(s): Desaki R, Sawada G, Okumura H, Ikeda R, Tanabe K, Komatsu H, Mimori K, Mori M, Kita Y, Uchikado Y, Arigami T, Uenosono Y, Owaki T, Ishigami S, Natsugoe S
  • Journal Title: Ann Surg Oncol Volume: ２２ Pages: 1-8
  • Peer Reviewed
• [Presentation] 食道扁平上皮癌における術前化学放射線療法の効果予測に関する検討 (2018)
  • Author(s): 野田昌宏 奥村浩 内門泰人 尾本至 佐々木健 喜多芳昭 盛真一郎 前村公成 夏越祥次
  • Organizer: 第51回制癌剤適応研究会
• [Presentation] 食道扁平上皮癌におけるフィールド癌化現象の機序 (2017)
  • Author(s): 奥村浩，内門泰斗，尾本至，佐々木健, 喜多芳昭, 瀬戸山徹郎, 上之園芳一, 有上貴明, 馬場研二, 樋渡清治，南幸次，大脇哲洋, 石神純也, 前之原茂穂, 夏越祥次
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 胃切除後食道癌に対するサルベージ手術を含む化学放射線療法症例の検討 (2017)
  • Author(s): 奥村浩，内門泰斗，尾本至，佐々木健，瀬戸山徹郎，樋渡清治，南幸次，南曲康太，前之原茂穂，夏越祥次
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 再発大腸癌化学療法におけるRAS遺伝子変異別臨床病理学的因子の検討 (2017)
  • Author(s): 奥村浩, 瀬戸山徹郎, 高取寛之, 樋渡清司, 南幸次, 鶴田祐介, 田中貴子, 前之原茂穂, 夏越祥次
  • Organizer: 第28回日本消化器癌発生学会総会
• [Presentation] 再発大腸癌におけるRAS遺伝子変異と臨床病理学的因子の検討 (2017)
  • Author(s): 奥村浩，瀬戸山徹郎，高取寛之，樋渡清司，南幸次，鶴田祐介，田中貴子，前之原茂穂，夏越祥次
  • Organizer: 第79回日本臨床外科学会総会
• [Presentation] 進行食道癌症例における転移リンパ節の画像診断解析と再発予測 (2016)
  • Author(s): 奥村浩，内門泰斗，尾本至，佐々木健, 喜多芳昭, 上之園芳一, 有上貴明, 瀬戸山徹郎, 樋渡清司, 安藤慶, 下村寛貴, 石神純也, 大脇哲洋, 前之原茂穂, 夏越祥次
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
• [Presentation] 胃切除後食道癌再建術式の検討 (2016)
  • Author(s): 奥村浩，森直樹、田中寿明、森田勝、藤也寸志、佐伯浩、前原喜彦、吉田直矢、馬場秀夫、内門泰斗，尾本至，佐々木健、前之原茂穂、夏越祥次
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: あわぎんホール（徳島県徳島市）
• [Presentation] 食道癌症例に対する縦隔鏡下食道切除術症例の治療成績と予後因子解析 (2016)
  • Author(s): 奥村浩、内門泰斗、尾本至、佐々木健、喜多芳昭、有上貴明、上之園芳一、大脇哲洋、前之原茂穂、夏越祥次
  • Organizer: 第70回日本食道学会学術集会
  • Place of Presentation: ザ・プリンスパークホテル（東京都港区）
• [Presentation] Treatment strategy of esophageal perforation basis on the clinical data analyses (2016)
  • Author(s): Okumura H, Uchikado Y, Kita Y, Omoto I, Sasaki K, Setoyama T, Arigami T, Uenosono Y, Hiwatashi K, Ando K, Wada M, Owaki T, Ishigami S, Maenohara S, Natsugoe S
  • Organizer: 15th ISDE
  • Place of Presentation: エキスポ（シンガポール）
  • Int'l Joint Research
• [Presentation] 全身状態に基づいた食道破裂・穿孔症例の治療法の検討 (2016)
  • Author(s): 奥村浩，内門泰斗、喜多芳昭、尾本至，佐々木健、瀬戸山徹郎、樋渡清司、安藤慶、大脇哲洋，石神純也，前之原茂穂、夏越祥次
  • Organizer: 第24回日本消化器関連学会週間
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
• [Presentation] 当院における胃GIST症例の検討 (2016)
  • Author(s): 奥村浩、瀬戸山徹郎、樋渡清司、安藤慶，和田真澄、前之原茂穂、夏越祥次、徳重浩一松木、田純香、鐘撞一郎
  • Organizer: 第54 回日本癌治療学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] 胃切除後食道癌症例の検討 (2016)
  • Author(s): 奥村浩，森直樹、田中寿明、森田勝、藤也寸志、佐伯浩司、前原喜彦、吉田直矢、馬場秀夫、内門泰斗，尾本至，佐々木健、前之原茂穂、夏越祥次
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 城山観光ホテル（鹿児島県鹿児島市）
• [Presentation] Ferredoxin reductase (Fdxr)発現による食道癌に対する化学療法放射線の効果予測 (2015)
  • Author(s): 奥村浩, 内門泰斗, 喜多芳昭, 尾本至, 佐々木健, 瀬戸山徹郎, 有上貴明, 上之園芳一, 盛真一郎、馬場研二, 大脇哲洋, 石神純也, 樋渡清司, 安藤慶, 前之原茂穂, 夏越祥次
  • Organizer: 第26 回日本消化器癌発生学会総会
  • Place of Presentation: 米子全日空ホテル（鳥取県米子市）
  • Year and Date: 2015-11-19
• [Presentation] 転移リンパ節転移制御を目的とした局所進行食道癌に対する術前化学放射線治療の意義 (2015)
  • Author(s): 奥村浩、内門泰斗、惠浩一、尾本至、喜多芳昭、 上之園芳一、 有上貴明、盛真一郎、馬場研二、石神純也、大脇哲洋、夏越祥次
  • Organizer: 第53 回日本癌治療学会,ワークショップ
  • Place of Presentation: 国際京都会議場（京都府）
  • Year and Date: 2015-10-29
• [Presentation] 転移リンパ節制御を目的とした局所進行食道癌に対する術前化学放射線治療の有用性の検討 (2015)
  • Author(s): 奥村浩，内門泰斗，尾本至，喜多芳昭，惠浩一, 上之園芳一, 有上貴明,石神純也,盛真一郎、大脇哲洋,夏越祥次
  • Organizer: 第23回日本消化器関連学会週間(JDDW), パネルディスカッション
  • Place of Presentation: グランドプリンス新高輪（東京都港区）
  • Year and Date: 2015-10-08
• [Presentation] 局所進行食道癌に対する治療戦略―リンパ節転移制御を目的とした術前化学放射線治療― (2015)
  • Author(s): 奥村浩，内門泰斗，尾本至，喜多芳昭，惠浩一, 上之園芳一, 有上貴明,石神純也,大脇哲洋,夏越祥次
  • Organizer: 第70回日本消化器外科学会総会, シンポジウム
  • Place of Presentation: アクトシティ浜松(静岡県浜松市）
  • Year and Date: 2015-07-15
• [Presentation] リンパ節転移個数からみた術前化学放射線療法の適応 －多発リンパ節転移を伴う進行食道癌症例の画像診断解析から－ (2015)
  • Author(s): 奥村浩，内門泰斗，惠浩一,尾本至，喜多芳昭，上之園芳一, 有上貴明,石神純也,大脇哲洋,夏越祥次
  • Organizer: 第69回日本食道学会学術集会, パネルディスカッション
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-07-02