caa a22 4500 445889233 CHVBK 20180317145610.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00535-010-0294-5 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0294-5 The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+ pegylated interferon α-2b therapy against advanced hepatocellular carcinoma [Elektronische Daten] [Satoru Hagiwara, Masatoshi Kudo, Kazuomi Ueshima, Hobyung Chung, Mami Yamaguchi, Masahiro Takita, Seiji Haji, Masatomo Kimura, Tokuzo Arao, Kazuto Nishio, Ah-Mee Park, Hiroshi Munakata] Background: Combination therapy with the oral fluoropyrimidine anticancer drug S1 and interferon is reportedly effective for the treatment of advanced hepatocellular carcinoma (HCC), but selection criteria for this therapy have not been clarified. In this study, we attempted to identify factors predicting the effectiveness of this combination therapy. Methods: Pathological specimens of HCC were collected before treatment from 31 patients with advanced HCC who underwent S1+ pegylated-interferon (PEG-IFN) α-2b therapy between January 2007 and January 2009. In these pathological specimens, the expression levels of CD133, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and interferon-receptor 2 (IFNR2) proteins were determined by Western blot assay. The presence or absence of p53 gene mutations was determined by direct sequencing. The relationships between these protein expression levels and the response rate (RR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: The CD133 protein expression level was significantly lower in the responder group than in the nonresponder group. Comparing the PFS and OS between high- and low-level CD133 expression groups (n=13 and 18, respectively) revealed that both parameters were significantly prolonged in the latter group. The expression levels of TS, DPD, and IFNR2 protein and the presence of p53 gene mutations did not correlate with the RR. Conclusions: CD133 was identified as a predictor of the therapeutic effect of S1+ PEG-IFN α-2b therapy against advanced HCC. Springer, 2010 5-Fluorouracil nationallicence Pegylated interferon nationallicence CD133 nationallicence Cancer stem cell nationallicence Hepatocellular carcinoma nationallicence 5FU : 5-Fluorouracil nationallicence DPD : Dihydropyrimidine dehydrogenase nationallicence HCC : Hepatocellular carcinoma nationallicence IFNR2 : Interferon-receptor 2 nationallicence NR : Nonresponder nationallicence OS : Overall survival nationallicence PD : Progressive disease nationallicence PEG-IFN : Pegylated interferon nationallicence PFS : Progression-free survival nationallicence PR : Partial response nationallicence RR : Response rate nationallicence SD : Stable disease nationallicence TS : Thymidylate synthase nationallicence Hagiwara Satoru Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut Kudo Masatoshi Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut Ueshima Kazuomi Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut Chung Hobyung Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut Yamaguchi Mami Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut Takita Masahiro Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut Haji Seiji Department of Surgery, Kinki University School of Medicine, Ōsakasayama, Japan aut Kimura Masatomo Department of Pathology, Kinki University School of Medicine, Ōsakasayama, Japan aut Arao Tokuzo Department of Genome Biology, Kinki University School of Medicine, Ōsakasayama, Japan aut Nishio Kazuto Department of Genome Biology, Kinki University School of Medicine, Ōsakasayama, Japan aut Park Ah-Mee Department of Biochemistry, Kinki University School of Medicine, Ōsakasayama, Japan aut Munakata Hiroshi Department of Biochemistry, Kinki University School of Medicine, Ōsakasayama, Japan aut Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 212-221 0944-1174 46:2<212 2011 46 535 https://doi.org/10.1007/s00535-010-0294-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0294-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hagiwara Satoru Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut NATIONALLICENCE 700 1- Kudo Masatoshi Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut NATIONALLICENCE 700 1- Ueshima Kazuomi Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut NATIONALLICENCE 700 1- Chung Hobyung Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut NATIONALLICENCE 700 1- Yamaguchi Mami Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut NATIONALLICENCE 700 1- Takita Masahiro Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, 377-2 Ohno-Higashi, 589-8511, Ōsakasayama, Osaka, Japan aut NATIONALLICENCE 700 1- Haji Seiji Department of Surgery, Kinki University School of Medicine, Ōsakasayama, Japan aut NATIONALLICENCE 700 1- Kimura Masatomo Department of Pathology, Kinki University School of Medicine, Ōsakasayama, Japan aut NATIONALLICENCE 700 1- Arao Tokuzo Department of Genome Biology, Kinki University School of Medicine, Ōsakasayama, Japan aut NATIONALLICENCE 700 1- Nishio Kazuto Department of Genome Biology, Kinki University School of Medicine, Ōsakasayama, Japan aut NATIONALLICENCE 700 1- Park Ah-Mee Department of Biochemistry, Kinki University School of Medicine, Ōsakasayama, Japan aut NATIONALLICENCE 700 1- Munakata Hiroshi Department of Biochemistry, Kinki University School of Medicine, Ōsakasayama, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/2(2011-02-01), 212-221 0944-1174 46:2<212 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence 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