PETによるアミノ酸トランスポータ標的がん治療のモニタリング法の開発に関する研究

2014 Fiscal Year Research-status Report

• Project/Area Number: 25461801
• Research Institution: Gunma University
• Principal Investigator: 織内 昇 群馬大学, 医学(系)研究科(研究院), 客員教授 (40292586)
• Co-Investigator(Kenkyū-buntansha): 富永 英之 福島県立医科大学, 公私立大学の部局等, 准教授 (00393348) ; 大島 康宏 独立行政法人日本原子力研究開発機構, 量子ビーム応用研究センター, 研究員 (00588676) ; 解良 恭一 群馬大学, 医学(系)研究科(研究院), 講師 (40400783)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アミノ酸トランスポーター / LAT1 / 分子標的治療 / コンパニオン診断 / ASCT2

Outline of Annual Research Achievements

Studies in this project disclosed vital roles of LAT1 for the growth and prognosis of biliary tract cancer by in vitro experiment, animal studies, and clinical examination. These data suggests that LAT1 would be a molecular target of anti-cancer therapy in biliary tract cancer.
2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) inhibited [14C]L-leucine uptake in human cholangiocarcinoma cell line named HuCCT1, and significantly decreased proliferation of HuCCT1 cells in a concentration dependent manner, and also showed significant delay in the growth of HuCCT1 xenograft in nude mice without showing significant changes in the body weight of these mice.
Biological significance of LAT1 expression has also been elucidated in the variety of malignancy including head and neck cancer, multiple myeloma and hepatocellular carcinoma. Moreover, we have shown possibility of prognostic potential of ASC amino-acid transporter 2 (ASCT2) in cancers originated from lung, pancreas, liver, biliary tract, and tongue.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Clinical significance for assessing malignancy and prognosis of LAT1 expression in head and neck cancer, multiple myeloma, and hepatocellular carcinoma (HCC) as well as biliary tract cancer was elucidated. Clinical significance of another amino-acid transporter ASCT2 was also shown by the studies on HCC, pancreas cancer, biliary tract cancer, and tongue cancer.

Strategy for Future Research Activity

Based on the previous studies showing clinical significance of LAT1 expression in various malignant tumors such as head and neck cancer (HNC), non small cell lung cancer (NSCLC), and cancers of digestive organs, etc., further experiments should be performed to confirm potential of anticancer therapy with LAT1 inhibition.
Another focus of further study is to evaluate the biological significance of ASCT2 expression and the possibility as a therapeutic target, because the previous studies indicated the clinical significance of ASCT2 in HNC, NSCLC, etc.

Causes of Carryover

平成25年度に計画していた動物実験が順調に実施され、初期の目的が達成されたため、平成26年度の研究実施計画に記載した「適宜実験系を見直し追加する」必要がなくなったため、平成26年度は物品費の使用額が当初計画より少額となった。

Expenditure Plan for Carryover Budget

平成26年度には臨床研究で胆管癌の他に非小細胞肺癌、頭頚部癌、消化器癌などについてもLAT1発現の解析を行った。さらにアミノ酸トランスポーターとしてASC amino-acid transporter 2 (ASCT2)　も癌治療の標的となる可能性を示唆するデータが得られたため、平成27年度はその検討も推進する。そのために次年度使用額が生じた。免疫組織染色に使用する抗体などの消耗品の購入に使用して研究を行う計画である。

Research Products

• [Journal Article] Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer. (2014)
  • Author(s): Kaira K, Serizawa M, Koh Y, Takahashi T, Yamaguchi A, Hanaoka H, Oriuchi N, Endo M, Ohde Y, Nakajima T, Yamamoto N.
  • Journal Title: Lung Cancer Volume: 83 Pages: 197-204
  • DOI: 10.1016/j.lungcan.2013.11.025.
  • Peer Reviewed
• [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.
  • Journal Title: Br J Cancer Volume: 110 Pages: 2030-2039
  • DOI: 10.1038/bjc.2014.88.
  • 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: 1985-1991
  • DOI: 10.1038/bjc.2014.142.
  • Peer Reviewed / Open Access
• [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 Pages: 2506-2513
  • DOI: 10.1038/bjc.2014.178.
  • Peer Reviewed / Open Access
• [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, Oriuchi N, Tominaga H, Kanai Y.
  • Journal Title: Cancer Sci Volume: 105 Pages: 1496-1502
  • DOI: 10.1111/cas.12529.
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological significance of ASC amino acid transporter-2 expression in pancreatic ductal carcinoma. (2014)
  • 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 Pages: 234-243
  • DOI: 10.1111/his.12464.
  • Peer Reviewed
• [Journal Article] CD98 as a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma. (2014)
  • Author(s): Toyoda M, Kaira K, Shino M, Sakakura K, Takahashi K, Takayasu Y, Tominaga H, Oriuchi N, Nikkuni O, Suzuki M, Iijima M, Tsukamoto N, Nagamori S, Kanai Y,Oyama T, Chikamatsu K.
  • Journal Title: Head Neck Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1002/hed.23797.
  • Peer Reviewed
• [Journal Article] CD98 is a promising prognostic biomarker in biliary tract cancer. Hepatobiliary (2014)
  • Author(s): Kaira K, Sunose Y, Oriuchi N, Kanai Y, Takeyoshi I.
  • Journal Title: Hepatobiliary Pancreat Dis Int Volume: 13 Pages: 654-657
  • DOI: 10.1016/S1499-3872(14)60278-2
  • Peer Reviewed
• [Journal Article] Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma. (2014)
  • Author(s): Namikawa M, Kakizaki S, Kaira K, Tojima H, Yamazaki Y, Horiguchi N, Sato K, Oriuchi N, Tominaga H, Sunose Y, Nagamori S, Kanai Y, Oyama T, Takeyoshi I,Yamada M.
  • Journal Title: Hepatol Res Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1111/hepr.12431.
  • Peer Reviewed
• [Presentation] 胆管癌における新規治療標的としてのLAT1の可能性についての検討 (2014)
  • Author(s): 大島康宏、富永英之、永森収志、金井好克、織内 昇、石岡典子
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] FDG-PETで奇静脈浸潤が認められた食道癌の1症例 (2014)
  • Author(s): 織内 昇、清水淳史、友利彰寿、森主達夫、宮田佳典
  • Organizer: 第68回日本食道学会学術集会
  • Place of Presentation: 東京ドームホテル（東京都）
  • Year and Date: 2014-07-03 – 2014-07-04