Chemo-resistance of xCT expression in NSCLC

• Project/Area Number: 26461154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: Kaira Kyoichi 群馬大学, 大学院医学系研究科, 特任教授 (40400783)
• Co-Investigator(Renkei-kenkyūsha): Kanai Yoshikatsu 大阪大学, 大学院医学系研究科, 教授 (60204533)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: xCT / アミノ酸トランスポーター / 薬剤耐性 / 肺癌 / 呼吸器 / 腫瘍 / 化学療法 / 免疫組織学的染色

Outline of Final Research Achievements

Our in vitro study showed that the expression of xCT mRNA was significantly higher in non-small cell lung cancer (NSCLC) cells than in small-cell lung cancer (SCLC) cells. By drug sensitivity experimental approach, tumor cell proliferation rate was lower in SCLC cells, regardless of the quantitative amount of xCT expression. However, NSCLC cells yielded a high expression of xCT mRNA, suggesting a drug resistance. In SCLC cells, xCT expression may not be associated with chemotherapy resistance, whereas, the expression of xCT seemed to be linked to the resistance of any chemotherapy. The quantitative amount of xCT expression was assessed in 110 patients who underwent surgical resection. The patients with high xCT expression displayed a worse prognosis compared to those with a low xCT expression.

Research Products

• [Journal Article] Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer. (2017)
  • Author(s): Satoh T, Kaira K, Takahashi K, Takahashi N, Kanai Y, Asao T, Horiguchi J, Oyama T.
  • Journal Title: Anticancer Res Volume: 32 Pages: 631-636
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma. (2017)
  • Author(s): Shimizu A, Kaira K, Okubo Y, Utsumi D, Yasuda M, Tominaga H, Oriuchi N, Kanai Y, Takahashi K, Ishikawa O.
  • Journal Title: Neoplasma Volume: 64 Issue: 02 Pages: 283-288
  • DOI: 10.4149/neo_2017_216
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer. (2017)
  • Author(s): Kaira K, Tomizawa Y, Imai H, Sakurai R, Matsuura M, Yoshii A, Ochiai M, Kotake M, Ebara T, Saitoh JI, Sunaga N, Minato K, Saito R, Hisada T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 79 Issue: 1 Pages: 165-171
  • DOI: 10.1007/s00280-016-3217-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Successful afatinib treatment of advanced non-small-cell lung cancer patients undergoing hemodialysis. (2017)
  • Author(s): Imai H, Kaira K, Naruse I, Hayashi H, Iihara H, Kita Y, Mizusaki N, Asao T, Itoh Y, Sugiyama T, Minato K, Yamada M.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 79 Issue: 1 Pages: 209-213
  • DOI: 10.1007/s00280-016-3201-9
• [Journal Article] Usefulness of 18F-α-Methyltyrosine PET for Therapeutic Monitoring of Patients with Advanced Lung Cancer. (2016)
  • Author(s): Kaira K, Higuchi T, Sunaga N, Arisaka Y, Hisada T, Tominaga H, Oriuchi N, Asao T, Tsushima Y, Yamada M.
  • Journal Title: Anticancer Res Volume: 36 Pages: 6481-6490
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 1.Kaira K, Toyoda M, Shimizu A, Imai H, Sakakura K, Nikkuni O, Suzuki M, Iijima M, Asao T, Chikamatsu K. (2016)
  • Author(s): 1.Kaira K, Toyoda M, Shimizu A, Imai H, Sakakura K, Nikkuni O, Suzuki M, Iijima M, Asao T, Chikamatsu K.
  • Journal Title: Head Neck Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma. (2016)
  • Author(s): Honjo H, Kaira K, Miyazaki T, Yokobori T, Kanai Y, Nagamori S, Oyama T, Asao T, Kuwano H.
  • Journal Title: J Surg Oncol. Volume: 113 Issue: 4 Pages: 381-9
  • DOI: 10.1002/jso.24160
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical significance of coexpression of L-type amino acid transporter 1 (LAT1) and ASC amino acid transporter 2 (ASCT2) in lung adenocarcinoma (2015)
  • Author(s): 12.Yazawa T, Shimizu K, Kaira K, Nagashima T, Ohtaki Y, Atsumi J, Obayashi K, Nagamori S, Kanai Y, Oyama T, Takeyoshi I.
  • Journal Title: Am J Transl Res Volume: 7 Pages: 1126-39
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological significance of ASC amino acid transporter-2 expression in pancreatic ductal carcinoma. (2015)
  • Author(s): Kaira K, Sunose Y, Arakawa K, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Takeyoshi I.
  • Journal Title: Histopathology. Volume: 66 Issue: 2 Pages: 234-43
  • DOI: 10.1111/his.12464
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma. (2014)
  • Author(s): Isoda A, Kaira K, Iwashina M, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Oyama T, Asao T, Matsumoto M, Sawamura M.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 11 Pages: 1496-502
  • DOI: 10.1111/cas.12529
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. (2014)
  • Author(s): Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
  • Journal Title: Br J Cancer. Volume: 110 Issue: 10 Pages: 2506-13
  • DOI: 10.1038/bjc.2014.178
  • Peer Reviewed / Open Access
• [Journal Article] Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer. (2014)
  • Author(s): Suzuki S, Kaira K, Ohshima Y, Ishioka NS, Sohda M, Yokobori T, Miyazaki T, Oriuchi N, Tominaga H, Kanai Y, Tsukamoto N, Asao T, Tsushima Y, Higuchi T, Oyama T, Kuwano H.
  • Journal Title: Br J Cancer Volume: 110 Pages: 1985-91
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer (2014)
  • Author(s): Shimizu K, Kaira K, Tomizawa Y, Sunaga N, Kawashima O, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yamada M, Oyama T, Takeyoshi I
  • Journal Title: Br J Cancer Volume: Epub Issue: 8 Pages: 2030-2039
  • DOI: 10.1038/bjc.2014.88
  • Peer Reviewed / Open Access
• [Presentation] 夜間化学療法と就労支援 (2016)
  • Author(s): 解良恭一、成清一郎、徳満葉子、茂木正彦、浅尾高行
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-10-20
• [Presentation] PD-L1 expression and possibility of its therapeutic target in cutaneous angiosarcoma (2016)
  • Author(s): Kaira K, Shimizu A, Yasuda M, Ohkubo Y, Asao T, Takahashi K, Ishikawa O
  • Organizer: 2016 ASCO Annual Meeting
  • Place of Presentation: シカゴ
  • Year and Date: 2016-06-03
  • Int'l Joint Research
• [Presentation] 既治療・再発非小細胞肺癌におけるアムルビシンとタキソールの第１相試験 (2015)
  • Author(s): 解良恭一
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県、横浜市）
  • Year and Date: 2015-11-26
• [Presentation] 悪性皮膚黒色腫におけるL-type amino acid transporter 1 (LAT1)発現の臨床病理学的意義 (2015)
  • Author(s): 解良恭一
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（北海道、札幌市）
  • Year and Date: 2015-07-16
• [Presentation] 日常診療における進行非小細胞肺癌の治療戦略 (2015)
  • Author(s): 解良恭一
  • Organizer: 日本呼吸器学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2015-04-17 – 2015-04-19
  • Invited
• [Presentation] PETによる肺癌の予後予測 (2015)
  • Author(s): 解良恭一
  • Organizer: 日本呼吸器学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2015-04-17 – 2015-04-19
  • Invited
• [Presentation] 進行肺癌におけるL-[3-18F]-α-methyl tyrosine (18F-FAMT) PETの治療モニタリングの有用性 (2014)
  • Author(s): 解良恭一、織内昇、砂長則明、今井久雄、桑子智人、増田友美、久田剛志、浅尾高行、山田正信
  • Organizer: 日本肺癌学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-11-14 – 2014-11-16
  • Invited
• [Book] Molecular Targeted Therapy of Lung Cancer. Springer eBook 2017 (2017)
  • Author(s): 1.Yuichi Takiguchi
  • Publisher: Springer
• [Book] 肺癌内科 診療マニュアル (2015)
  • Author(s): 赤松弘朗 他
  • Total Pages: 499
  • Publisher: 医薬ジャーナル社