title: The Clinical Impact of Transcatheter Arterial Chemoembolization (TACE)-Induced c-Met Upregulation on TACE Refractoriness in Hepatocellular Carcinoma.
abstract: Transcatheter arterial chemoembolization (TACE) is a widely used and well-established treatment for hepatocellular carcinoma (HCC). However, TACE loses its therapeutic efficacy when performed repeatedly, a phenomenon termed TACE refractoriness. c-Met is associated with malignant potential and with resistance to anti-tumor therapies in some kinds of cancers.
  
  
  
  The aim of this study is to investigate the clinical impact of TACE on c-Met expression with the aim of understanding the mechanism underlying TACE refractoriness.
  
  
  
  The effect of TACE on the c-Met expression level was investigated in vitro in HCC cell lines, and it was shown that c-Met expression is upregulated in HCC cell lines cultured under hypoxia and/or exposed to chemotherapeutic agents. The in vitro results were validated using 82 clinical samples of HCC with and without preoperative TACE treatment.
  
  
  
  c-Met upregulation was observed significantly more frequently in clinical samples of HCC that were treated with preoperative TACE than in samples with no TACE treatment. Increased c-Met expression was significantly associated with poor prognosis. Furthermore, the incidence of c-Met-positive expression was significantly higher in TACE-refractory HCC samples.
  
  
  
  TACE treatment upregulates c-Met expression in HCC and the upregulated c-Met expression may be responsible for TACE refractoriness.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kajihara
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan. heguchi@gesurg.med.osaka-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yamada
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tomokuni
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Asaoka
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D019859:Proto-Oncogene Proteins c-met
keywords: Hepatocellular carcinoma; Refractoriness; Transcatheter arterial chemoembolization; c-Met