Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy
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Shibasaki, Yuta
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Shibasaki, Yuta
[1
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Yokobori, Takehiko
[2
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Sohda, Makoto
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Sohda, Makoto
[1
]
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Shioi, Ikuma
[1
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Ozawa, Naoya
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Ozawa, Naoya
[1
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Komine, Chika
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Komine, Chika
[1
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Suga, Kunihiko
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Suga, Kunihiko
[1
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Nakazawa, Nobuhiro
[1
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Osone, Katsuya
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Osone, Katsuya
[1
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Shiraishi, Takuya
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Shiraishi, Takuya
[1
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Okada, Takuhisa
[1
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Sano, Akihiko
[1
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Sakai, Makoto
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Sakai, Makoto
[1
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Ogawa, Hiroomi
[1
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Kaira, Kyoichi
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Saitama Univ Hosp, Comprehens Canc Ctr, Int Med Ctr, Dept Resp Med, Hidaka 3501298, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Kaira, Kyoichi
[3
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Shirabe, Ken
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Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, JapanGunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
Shirabe, Ken
[1
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Saeki, Hiroshi
[1
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[1] Gunma Univ, Grad Sch Med, Dept Gen Surg Sci, Maebashi 3718510, Japan
[2] Gunma Univ Initiat Adv Res GIAR, Div Integrated Oncol Res, Maebashi 3718511, Japan
[3] Saitama Univ Hosp, Comprehens Canc Ctr, Int Med Ctr, Dept Resp Med, Hidaka 3501298, Japan
The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.
机构:
Seoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Lee, Dae-Won
Han, Sae-Won
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Seoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Han, Sae-Won
Cha, Yongjun
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Seoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Cha, Yongjun
Bae, Jeong Mo
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Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Bae, Jeong Mo
Kim, Hwang-Phill
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Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Kim, Hwang-Phill
Lyu, Jaemyun
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Celemics Inc, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Lyu, Jaemyun
Han, Hyojun
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Celemics Inc, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Han, Hyojun
Kim, Hyoki
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Celemics Inc, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Kim, Hyoki
Jang, Hoon
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Yonsei Univ, Coll Sci, Dept Chem, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Jang, Hoon
Bang, Duhee
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Yonsei Univ, Coll Sci, Dept Chem, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Bang, Duhee
Won, Jae-Kyung
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Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Won, Jae-Kyung
Jeong, Seung-Yong
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Seoul Natl Univ Hosp, Dept Surg, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Jeong, Seung-Yong
Park, Kyu Joo
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Seoul Natl Univ Hosp, Dept Surg, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Park, Kyu Joo
Kang, Gyeong Hoon
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Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Kang, Gyeong Hoon
Kim, Tae-You
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Seoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South KoreaSeoul Natl Univ Hosp, Dept Internal Med, 101 Daehang Ro, Seoul 110744, South Korea
机构:
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Heidelberg Univ, Med Fac, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Park, Hanla
Seibold, Petra
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German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Seibold, Petra
Edelmann, Dominic
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German Canc Res Ctr, Div Biostat, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Edelmann, Dominic
Benner, Axel
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German Canc Res Ctr, Div Biostat, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Benner, Axel
Jansen, Lina
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German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Jansen, Lina
Canzian, Federico
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German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Canzian, Federico
Schneider, Martin
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Heidelberg Univ, Surg Oncol Clin Gen Visceral & Transplantat Surg, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Schneider, Martin
Hoffmeister, Michael
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German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Hoffmeister, Michael
Brenner, Hermann
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German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany
Natl Ctr Tumor Dis NCT, Div Prevent Oncol, Heidelberg, Germany
German Canc Consortium DKTK, Heidelberg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Brenner, Hermann
Chang-Claude, Jenny
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German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Canc Epidemiol Grp, Hamburg, GermanyGerman Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
机构:
Saitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Ishibashi, Keiichiro
Aoyama, Toru
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Yokohama City Univ, Dept Surg, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Aoyama, Toru
Kotaka, Masahito
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Sano Hosp, Dept Gastrointestinal, Canc Ctr, Kobe, Hyogo, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Kotaka, Masahito
Satake, Hironaga
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Kansai Med Univ Hosp, Canc Treatment Ctr, Hirakata, Osaka, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Satake, Hironaga
Tsuji, Yasushi
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KKR Tonan Hosp, Dept Med Oncol, Sapporo, Hokkaido, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Tsuji, Yasushi
Kataoka, Masato
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Natl Hosp Org Nagoya Med Ctr, Dept Surg, Nagoya, Aichi, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Kataoka, Masato
Nakamura, Masato
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Aizawa Hosp, Dept Chemotherapy, Comprehens Canc Ctr, Nagano, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Nakamura, Masato
Nagata, Naoki
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Kitakyushu Gen Hosp, Kitakyushu, Fukuoka, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Nagata, Naoki
Sakamoto, Junichi
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Tokai Cent Hosp, Kakamigahara, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan
Sakamoto, Junichi
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Oba, Koji
Mishima, Hideyuki
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Aichi Med Univ, Canc Ctr, Nagakute, Aichi, JapanSaitama Med Univ, Dept Digest Tract & Gen Surg, Saitama Med Ctr, Saitama, Japan