%0 Journal Article
%T Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy
%A Kahori Seto
%A Junichi Shoda
%A Tomohisa Horibe
%A Eiji Warabi
%A Masayuki Kohno
%A Toru Yanagawa
%A Hiroki Bukawa
%A Yasuni Nakanuma
%A Koji Kawakami
%J International Journal of Hepatology
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/584650
%X It is known that the interleukin-4 receptor ¦Á (IL-4R¦Á) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R¦Á-lytic hybrid peptide composed of binding peptide to IL-4R¦Á and cell-lytic peptide and reported that the designed IL-4R¦Á-lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4R¦Á. Here, we evaluated the antitumor activity of the IL-4R¦Á-lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R¦Á-lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5£¿¦ÌM. We also showed that IL-4R¦Á-lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4R¦Á-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R¦Á-lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC. 1. Introduction Biliary tract cancer such as gallbladder cancer and extrahepatic bile duct cancer as well as intrahepatic bile duct cancer (one of the primary liver cancers) is likely to undergo metastasis to the peritoneum (peritoneal dissemination) or the liver at early stages and is often resistant to conventional chemotherapy and radiotherapy. These cancers have been thus viewed as intractable cancers unlikely to be cured completely. In Japan, the incidence of biliary tract cancer and intrahepatic bile duct cancer is about 10 out of every 100,000 people [1]. As for intrahepatic bile duct cancer, both the incidence and death rate have been rising in Japan in recent years, resembling the trend observed in western countries [2, 3]. In Japan, gemcitabine and S-1 have recently begun to be used for anticancer chemotherapy, and these drugs are expected to prolong the survival period of patients as compared to existing anticancer drugs [4]. However, because of frequent adverse events of the hematological system arising from these drugs and because of compromised hepatic function often noted in patients with intrahepatic bile duct cancer due to accompanying liver cirrhosis and in those with extrahepatic bile duct cancer or gallbladder cancer due to accompanying obstructive cholestasis, treatment with these drugs has to be discontinued or stopped. To improve the outcome of treatment of these cancers, it is very
%U http://www.hindawi.com/journals/ijh/2014/584650/