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豊田 実*; 解良 恭一*; 大島 康宏; 石岡 典子; 紫野 正人*; 坂倉 浩一*; 高安 幸弘*; 高橋 克昌*; 富永 英之*; 織内 昇*; et al.
British Journal of Cancer, 110(10), p.2506 - 2513, 2014/05
被引用回数：106 パーセンタイル：95.14(Oncology)Amino-acid transporters are necessary for the tumor cell growth and survival, and play a crucial role in the development of cancer. But, it remains unclear about the prognostic significance of L-type amino acid transporter 1 (LAT1), System ASC amino acid transporter 2 (ASCT2) and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino acid transporters in tongue cancer. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, CD98, Ki-67, CD34 and p53. The expression of LAT1 and ASCT2 was significantly associated with disease staging, lymph node metastasis, lymphatic permeation, vascular invasion, CD98 expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumor factor, correlated with CD98. By univariate analysis, both LAT1 and ASCT2 had a significant relationship with prognosis. Multivariate analysis confirmed that LAT1 were independent prognostic factors for predicting poor prognosis. These results suggest that LAT1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may play an important role in the development and pathogenesis for tongue cancer.
-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer鈴木 茂正*; 解良 恭一*; 大島 康宏; 石岡 典子; 宗田 真*; 横堀 武彦*; 宮崎 達也*; 織内 昇*; 富永 英之*; 金井 好克*; et al.
British Journal of Cancer, 110(8), p.1985 - 1991, 2014/04
被引用回数：24 パーセンタイル：60.43(Oncology)Fluorine-18--methyltyrosine (FAMT) as an amino acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. FAMT is accumulated in tumor cells solely via L-type amino acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of FAMT uptake in patients with esophageal cancer. From April 2008 to December 2011, 42 patients with esophageal cancer underwent both FAMT PET and FDG PET before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. 
experiments were performed to examine the mechanism of FAMT uptake using LAT1 inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). High uptake of FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. experiments revealed that FAMT was specifically transported by LAT1. The uptake of FAMT within tumor cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in esophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of FAMT accumulation.
解良 恭一*; 須納瀬 豊*; 大島 康宏; 石岡 典子; 荒川 和久*; 小川 哲史*; 砂長 則明*; 清水 公裕*; 富永 英之*; 織内 昇*; et al.
BMC Cancer, 13, p.482_1 - 482_12, 2013/10
被引用回数：74 パーセンタイル：88.89(Oncology)The expression of L-type amino acid transporter 1 (LAT1) has been described to play essential roles in tumor growth and survival. However, it remains unclear about the clinicopathological significance of LAT1 expression in biliary tract cancer. This study was conducted to determine clinical significance of LAT1 expression and investigate whether LAT1 could be a new therapeutic target for biliary tract cancer. A total of 139 consecutive patients with resected pathologic stage I-IV biliary tract adenocarcinoma were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, CD98, Ki-67, microvessel density determined by CD34 and p53. Further, anti-tumor activity of LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) was investigated using cholangiocarcinoma cell line. The expression of LAT1 was recognized in 64% of total patients, and closely correlated with CD98 expression, lymphatic metastases, cell proliferation and angiogenesis, and was a significant indicator for predicting poor outcome after surgery. Experiments showed that BCH significantly suppressed the tumor growth and BCH yielded an additive therapeutic efficacy to gemcitabine and 5-FU. A cooperative high expression of LAT1 with CD98 is a promising pathological marker to predict the outcome in biliary tract adenocarcinoma. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.
中村 勤也*; 尾形 孝成*; 菊地 啓修; 岩井 孝; 中島 邦久; 加藤 徹也*; 荒井 康夫; 魚住 浩一*; 土方 孝敏*; 小山 正史*; et al.
日本原子力学会和文論文誌, 10(4), p.245 - 256, 2011/12
「常陽」での照射試験を目的として、金属ウラン,ウラン-プルトニウム合金及び金属ジルコニウムを原料に、U-20Pu-10Zr燃料スラグを射出鋳造法により製造した。いずれの燃料スラグも表面は滑らかであり、合金組成,密度,長さ,直径,不純物濃度も製造仕様を満足した。製造した燃料スラグを、熱ボンド材,熱遮へい体及び要素反射体とともに下部端栓付被覆管に充填してTIG溶接を行い、ナトリウムボンド型金属燃料要素6本を組み立てた。これらの燃料要素は、今後B型照射燃料集合体に組み立てられた後、「常陽」に装荷されて国内で初めてとなる金属燃料の照射試験が実施される予定である。
中村 勤也*; 尾形 孝成*; 菊地 啓修; 岩井 孝; 中島 邦久; 加藤 徹也*; 荒井 康夫; 小山 正史*; 板垣 亘; 曽我 知則; et al.
Proceedings of International Conference on Toward and Over the Fukushima Daiichi Accident (GLOBAL 2011) (CD-ROM), 8 Pages, 2011/12
電力中央研究所と原子力機構の共同研究の下で、国内では初めてとなる照射試験用のNaボンド型U-Pu-Zr金属燃料要素を製造した。高速実験炉「常陽」での照射試験は、被覆管最高温度が873K以上の条件における燃料挙動とステンレス鋼被覆管の内面腐食の評価を目的としている。燃料要素1本あたり200mmのU-20wt%-10wt%Zr金属燃料スラグは、U金属,U-Pu合金及びZr金属を原料に用いて、射出鋳造法により製造した。この金属燃料スラグを、ボンドNa及び熱遮へい体や要素反射体などの部材とともに被覆管に挿入したうえで、上下端栓を溶接することにより燃料要素を組立てた。引続きNaボンディングにより、ボンド材のNaを、金属燃料スラグと被覆管の空隙に充填した。製造した6本の金属燃料要素は、検査により製造仕様を満足していることを確認した後、「常陽」の照射装置組立検査施設に運搬された。
中村 勤也*; 尾形 孝成*; 中島 邦久; 加藤 徹也*; 岩井 孝; 荒井 康夫; 小山 正史*; 板垣 亘; 曽我 知則
no journal, ,
高速実験炉「常陽」において金属燃料の照射試験を計画している。これまでの製造技術開発によって確立した鋳造技術,組立技術,分析・検査技術を適用して、国内初の金属燃料要素を製造した。本稿では、射出鋳造法によるU-Pu-Zr合金燃料スラグの製造結果について報告する。燃料スラグは、U金属,U-Pu合金及びZr金属を原料にして、アルゴンガス雰囲気グローブボックス内に整備した射出鋳造装置を用いて製造した。検査の結果、仕様を満たしていることを確認した。
中村 勤也*; 尾形 孝成*; 中島 邦久; 加藤 徹也*; 岩井 孝; 荒井 康夫; 小山 正史*; 板垣 亘; 曽我 知則
no journal, ,
高速実験炉「常陽」において金属燃料要素の照射試験を計画している。これまでの製造技術開発によって確立した鋳造技術,組立技術,分析・検査技術を適用して、国内初の金属燃料要素を製造した。本稿では、射出鋳造法によるU-Pu-Zr合金燃料スラグの製造結果について報告する。燃料スラグは、U金属,U-Pu合金及びZr金属を原料にして、アルゴンガス雰囲気グローブボックス内に整備した射出鋳造装置を用いて製造した。検査の結果、仕様を満たしていることを確認した。
解良 恭一*; 豊田 実*; 大島 康宏; 織内 昇*; 金井 好克*; 小山 徹也*; 山田 正信*; 浅尾 高行*; 近松 一朗*
no journal, ,
This study was conducted to determine biological significance of L-type amino acid transporter 1 (LAT1) expression and investigate whether LAT1 could be a prognostic biomarker for tongue cancer. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, CD98, CD147, Ki-67, microvessel density determined by CD34, and p53. Biological significance of LAT1 expression was investigated by 
experiments with LAT inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) using tongue cell line. LAT1, ASCT2, xCT, CD98 and CD147 were highly expressed in 61%, 59%, 21%, 45% and 33%, respectively. The expression of LAT1 was significantly associated with disease staging, lymph node metastasis, lymphatic permeation, cell proliferation (Ki-67), and the expression level of CD98, ASCT2 and CD147 as amino acid transporter complexes. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis. preliminary experiment indicated that BCH significantly suppressed growth of the tumor and yielded an additive therapeutic efficacy to cisplatin. These rusults suggests that LAT1 can serve as a promising pathological marker to predict the outcome in patients with tongue cancer. Inhibition of LAT1 may be an effective targeted therapy for this distressing disease.
