CINXE.COM
Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo | Anticancer Research
<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//d1bxh8uas1mnw7.cloudfront.net" /> <link rel="dns-prefetch" href="//cdn.jsdelivr.net" /> <link rel="dns-prefetch" href="//cdn.foxycart.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <link rel="canonical" href="https://ar.iiarjournals.org/content/39/11/5973" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/39/11/5973.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/39/11/5973.full.txt" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/39/11/5973.ppt" /> <meta name="issue_cover_image" content="https://ar.iiarjournals.org/sites/default/files/highwire/default/covers/acr_default_cover_0.gif" /> <meta name="type" content="article" /> <meta name="category" content="research-article" /> <meta name="HW.identifier" content="/anticanres/39/11/5973.atom" /> <meta name="HW.pisa" content="anticanres;39/11/5973" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo" /> <meta name="DC.Identifier" content="10.21873/anticanres.13802" /> <meta name="DC.Date" content="2019-11-01" /> <meta name="DC.Publisher" content="International Institute of Anticancer Research" /> <meta name="DC.Rights" content="Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved" /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="Background/Aim: Lenvatinib is a potent inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), KIT, and RET. Here, we investigated the antiproliferative effects of lenvatinib in liver cancer cells in vitro and in vivo. Materials and Methods: Eleven hepatocellular carcinoma cell lines and two combined hepatocellular/cholangiocarcinoma cell lines were treated with 0-30 μM lenvatinib. Cell growth, apoptosis and the expression of FGFR1-4, FGF19, fibroblast growth factor receptor substrate (FRS)2α and RET were examined. Two HCC cell lines were subcutaneously implanted on nude mice and mice were treated with 3, 10, 30 mg/kg/day of lenvatinib or vehicle for 14 consecutive days. Tumor volume was measured every 3 days. Mice were sacrificed on day 15 and tumors were processed for histological examination. Blood vessels, microvessel density, necrosis, and apoptosis were also examined. Results: Lenvatinib dose- and time-dependently inhibited growth of all cell lines; however, sensitivity to lenvatinib varied. Apoptosis was not observed in any cell line, and expression of FGFR1, -2, -3 and -4, FGF19, FRS2α, and RET were observed in these cell lines. Cell lines with high expression of these factors showed higher response to lenvatinib. In mice, lenvatinib dose-dependently suppressed tumor growth. Blood vessels and microvessel density were significantly reduced and the rate of necrosis was significantly increased by lenvatinib; apoptosis was not observed. Conclusion: Antiproliferative effects of lenvatinib on liver cancer cells were observed in vitro and in vivo. Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells." /> <meta name="DC.Contributor" content="SACHIKO OGASAWARA" /> <meta name="DC.Contributor" content="YUTARO MIHARA" /> <meta name="DC.Contributor" content="REIICHIRO KONDO" /> <meta name="DC.Contributor" content="HIRONORI KUSANO" /> <meta name="DC.Contributor" content="JUN AKIBA" /> <meta name="DC.Contributor" content="HIROHISA YANO" /> <meta name="article:published_time" content="2019-11-01" /> <meta name="article:section" content="Experimental Studies" /> <meta name="citation_title" content="Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo" /> <meta name="citation_abstract" lang="en" content="<p>Background/Aim: Lenvatinib is a potent inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), KIT, and RET. Here, we investigated the antiproliferative effects of lenvatinib in liver cancer cells in vitro and in vivo. Materials and Methods: Eleven hepatocellular carcinoma cell lines and two combined hepatocellular/cholangiocarcinoma cell lines were treated with 0-30 μM lenvatinib. Cell growth, apoptosis and the expression of FGFR1-4, FGF19, fibroblast growth factor receptor substrate (FRS)2α and RET were examined. Two HCC cell lines were subcutaneously implanted on nude mice and mice were treated with 3, 10, 30 mg/kg/day of lenvatinib or vehicle for 14 consecutive days. Tumor volume was measured every 3 days. Mice were sacrificed on day 15 and tumors were processed for histological examination. Blood vessels, microvessel density, necrosis, and apoptosis were also examined. Results: Lenvatinib dose- and time-dependently inhibited growth of all cell lines; however, sensitivity to lenvatinib varied. Apoptosis was not observed in any cell line, and expression of FGFR1, -2, -3 and -4, FGF19, FRS2α, and RET were observed in these cell lines. Cell lines with high expression of these factors showed higher response to lenvatinib. In mice, lenvatinib dose-dependently suppressed tumor growth. Blood vessels and microvessel density were significantly reduced and the rate of necrosis was significantly increased by lenvatinib; apoptosis was not observed. Conclusion: Antiproliferative effects of lenvatinib on liver cancer cells were observed in vitro and in vivo. Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells.</p>" /> <meta name="citation_journal_title" content="Anticancer Research" /> <meta name="citation_publisher" content="International Institute of Anticancer Research" /> <meta name="citation_publication_date" content="2019/11/01" /> <meta name="citation_mjid" content="anticanres;39/11/5973" /> <meta name="citation_id" content="39/11/5973" /> <meta name="citation_public_url" content="https://ar.iiarjournals.org/content/39/11/5973" /> <meta name="citation_abstract_html_url" content="https://ar.iiarjournals.org/content/39/11/5973.abstract" /> <meta name="citation_full_html_url" content="https://ar.iiarjournals.org/content/39/11/5973.full" /> <meta name="citation_pdf_url" content="https://ar.iiarjournals.org/content/anticanres/39/11/5973.full.pdf" /> <meta name="citation_issn" content="0250-7005" /> <meta name="citation_issn" content="1791-7530" /> <meta name="citation_doi" content="10.21873/anticanres.13802" /> <meta name="citation_pmid" content="31704822" /> <meta name="citation_volume" content="39" /> <meta name="citation_issue" content="11" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="Experimental Studies" /> <meta name="citation_firstpage" content="5973" /> <meta name="citation_lastpage" content="5982" /> <meta name="citation_author" content="SACHIKO OGASAWARA" /> <meta name="citation_author_institution" content="Department of Pathology, Kurume University School of Medicine, Kurume, Japan" /> <meta name="citation_author_email" content="sachiko@med.kurume-u.ac.jp" /> <meta name="citation_author" content="YUTARO MIHARA" /> <meta name="citation_author_institution" content="Department of Pathology, Kurume University School of Medicine, Kurume, Japan" /> <meta name="citation_author" content="REIICHIRO KONDO" /> <meta name="citation_author_institution" content="Department of Pathology, Kurume University School of Medicine, Kurume, Japan" /> <meta name="citation_author" content="HIRONORI KUSANO" /> <meta name="citation_author_institution" content="Department of Pathology, Kurume University School of Medicine, Kurume, Japan" /> <meta name="citation_author" content="JUN AKIBA" /> <meta name="citation_author_institution" content="Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan" /> <meta name="citation_author" content="HIROHISA YANO" /> <meta name="citation_author_institution" content="Department of Pathology, Kurume University School of Medicine, Kurume, Japan" /> <meta name="citation_reference" content="citation_journal_title=Int J Cancer;citation_author=J. Ferlay;citation_author=I. Soerjomataram;citation_author=R. Dikshit;citation_author=S. Eser;citation_author=C. Mathers;citation_author=M. Rebelo;citation_author=DM. Parkin;citation_author=D. Forman;citation_author=F. Bray;citation_title=Cancer incidence and mortality worldwide: Sources, methods and major patterns in globocan 2012;citation_pages=E359-386;citation_volume=136;citation_year=2015;citation_issue=5;citation_pmid=25220842;citation_doi=10.1002/ijc.29210" /> <meta name="citation_reference" content="citation_journal_title=CA Cancer J Clin;citation_author=LA. Torre;citation_author=F. Bray;citation_author=RL. Siegel;citation_author=J. Ferlay;citation_author=J. Lortet-Tieulent;citation_author=A. Jemal;citation_title=Global cancer statistics, 2012;citation_pages=87-108;citation_volume=65;citation_year=2015;citation_issue=2;citation_pmid=25651787;citation_doi=10.3322/caac.21262" /> <meta name="citation_reference" content="citation_journal_title=Journal of hepatology;citation_journal_abbrev=J Hepatol;citation_author=D. Semela;citation_author=JF. Dufour;citation_title=Angiogenesis and hepatocellular carcinoma.;citation_pages=864-880;citation_volume=41;citation_year=2004;citation_issue=5;citation_pmid=15519663;citation_doi=10.1016/j.jhep.2004.09.006" /> <meta name="citation_reference" content="citation_journal_title=Cancer Research;citation_journal_abbrev=Cancer Res.;citation_author=SM. Wilhelm;citation_author=C. Carter;citation_author=L. Tang;citation_author=D. Wilkie;citation_author=A. McNabola;citation_author=H. Rong;citation_author=C. Chen;citation_author=X. Zhang;citation_author=P. Vincent;citation_author=M. McHugh;citation_author=Y. Cao;citation_author=J. Shujath;citation_author=S. Gawlak;citation_author=D. Eveleigh;citation_author=B. Rowley;citation_author=L. Liu;citation_author=L. Adnane;citation_author=M. Lynch;citation_author=D. Auclair;citation_author=I. Taylor;citation_author=R. Gedrich;citation_author=A. Voznesensky;citation_author=B. Riedl;citation_author=LE. Post;citation_author=G. Bollag;citation_author=PA. Trail;citation_title=BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis;citation_pages=7099-7109;citation_volume=64;citation_year=2004;citation_issue=19;citation_pmid=15466206;citation_doi=10.1158/0008-5472.CAN-04-1443" /> <meta name="citation_reference" content="citation_journal_title=J Thyroid Res;citation_author=O. Tohyama;citation_author=J. Matsui;citation_author=K. Kodama;citation_author=N. Hata-Sugi;citation_author=T. Kimura;citation_author=K. Okamoto;citation_author=Y. Minoshima;citation_author=M. Iwata;citation_author=Y. Funahashi;citation_title=Antitumor activity of lenvatinib (e7080): An angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models;citation_pages=638747;citation_volume=2014;citation_year=2014;citation_pmid=25295214;citation_doi=10.1155/2014/638747" /> <meta name="citation_reference" content="citation_journal_title=New England Journal of Medicine;citation_journal_abbrev=NEJM;citation_author=JM. Llovet;citation_author=S. Ricci;citation_author=V. Mazzaferro;citation_author=P. Hilgard;citation_author=E. Gane;citation_author=JF. Blanc;citation_author=AC. de Oliveira;citation_author=A. Santoro;citation_author=JL. Raoul;citation_author=A. Forner;citation_author=M. Schwartz;citation_author=C. Porta;citation_author=S. Zeuzem;citation_author=L. Bolondi;citation_author=TF. Greten;citation_author=PR. Galle;citation_author=JF. Seitz;citation_author=I. Borbath;citation_author=D. Haussinger;citation_author=T. Giannaris;citation_author=M. Shan;citation_author=M. Moscovici;citation_author=D. Voliotis;citation_author=J. Bruix;citation_title=Sorafenib in Advanced Hepatocellular Carcinoma;citation_pages=378-390;citation_volume=359;citation_year=2008;citation_issue=4;citation_pmid=18650514;citation_doi=10.1056/NEJMoa0708857" /> <meta name="citation_reference" content="citation_journal_title=The lancet oncology;citation_journal_abbrev=Lancet Oncol;citation_author=A-L. Cheng;citation_author=Y-K. Kang;citation_author=Z. Chen;citation_author=C-J. Tsao;citation_author=S. Qin;citation_author=JS. Kim;citation_author=R. Luo;citation_author=J. Feng;citation_author=S. Ye;citation_author=T-S. Yang;citation_author=J. Xu;citation_author=Y. Sun;citation_author=H. Liang;citation_author=J. Liu;citation_author=J. Wang;citation_author=WY. Tak;citation_author=H. Pan;citation_author=K. Burock;citation_author=J. Zou;citation_author=D. Voliotis;citation_author=Z. Guan;citation_title=Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.;citation_pages=25-34;citation_volume=10;citation_year=2009;citation_issue=1;citation_pmid=19095497;citation_doi=10.1016/S1470-2045(08)70285-7" /> <meta name="citation_reference" content="citation_journal_title=J Clin Oncol;citation_author=AL. Cheng;citation_author=YK. Kang;citation_author=DY. Lin;citation_author=JW. Park;citation_author=M. Kudo;citation_author=S. Qin;citation_author=HC. Chung;citation_author=X. Song;citation_author=J. Xu;citation_author=G. Poggi;citation_author=M. Omata;citation_author=S. Pitman Lowenthal;citation_author=S. Lanzalone;citation_author=L. Yang;citation_author=MJ. Lechuga;citation_author=E. Raymond;citation_title=Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial;citation_volume=31;citation_year=2013;citation_issue=32;citation_pmid=24081937;citation_doi=10.1200/JCO.2012.45.8372" /> <meta name="citation_reference" content="citation_journal_title=J Clin Oncol;citation_author=PJ. Johnson;citation_author=S. Qin;citation_author=JW. Park;citation_author=RT. Poon;citation_author=JL. Raoul;citation_author=PA. Philip;citation_author=CH. Hsu;citation_author=TH. Hu;citation_author=J. Heo;citation_author=J. Xu;citation_author=L. Lu;citation_author=Y. Chao;citation_author=E. Boucher;citation_author=KH. Han;citation_author=SW. Paik;citation_author=J. Robles-Avina;citation_author=M. Kudo;citation_author=L. Yan;citation_author=A. Sobhonslidsuk;citation_author=D. Komov;citation_author=T. Decaens;citation_author=WY. Tak;citation_author=LB. Jeng;citation_author=D. Liu;citation_author=R. Ezzeddine;citation_author=I. Walters;citation_author=AL. Cheng;citation_title=Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study;citation_volume=31;citation_year=2013;citation_issue=28;citation_pmid=23980084;citation_doi=10.1200/JCO.2012.48.4410" /> <meta name="citation_reference" content="citation_journal_title=J Clin Oncol;citation_author=C. Cainap;citation_author=S. Qin;citation_author=WT. Huang;citation_author=IJ. Chung;citation_author=H. Pan;citation_author=Y. Cheng;citation_author=M. Kudo;citation_author=YK. Kang;citation_author=PJ. Chen;citation_author=HC. Toh;citation_author=V. Gorbunova;citation_author=FA. Eskens;citation_author=J. Qian;citation_author=MD. McKee;citation_author=JL. Ricker;citation_author=DM. Carlson;citation_author=S. El-Nowiem;citation_title=Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial;citation_volume=33;citation_year=2015;citation_issue=2;citation_pmid=25488963;citation_doi=10.1200/JCO.2013.54.3298" /> <meta name="citation_reference" content="citation_journal_title=J Clin Oncol;citation_author=AX. Zhu;citation_author=O. Rosmorduc;citation_author=TR. Evans;citation_author=PJ. Ross;citation_author=A. Santoro;citation_author=FJ. Carrilho;citation_author=J. Bruix;citation_author=S. Qin;citation_author=PJ. Thuluvath;citation_author=JM. Llovet;citation_author=MA. Leberre;citation_author=M. Jensen;citation_author=G. Meinhardt;citation_author=YK. Kang;citation_title=Search: A phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma;citation_volume=33;citation_year=2015;citation_issue=6;citation_pmid=25547503;citation_doi=10.1200/JCO.2013.53.7746" /> <meta name="citation_reference" content="citation_journal_title=Clinical Cancer Research;citation_journal_abbrev=Clin. Cancer Res.;citation_author=J. Matsui;citation_author=Y. Funahashi;citation_author=T. Uenaka;citation_author=T. Watanabe;citation_author=A. Tsuruoka;citation_author=M. Asada;citation_title=Multi-Kinase Inhibitor E7080 Suppresses Lymph Node and Lung Metastases of Human Mammary Breast Tumor MDA-MB-231 via Inhibition of Vascular Endothelial Growth Factor-Receptor (VEGF-R) 2 and VEGF-R3 Kinase;citation_pages=5459-5465;citation_volume=14;citation_year=2008;citation_issue=17;citation_pmid=18765537;citation_doi=10.1158/1078-0432.CCR-07-5270" /> <meta name="citation_reference" content="citation_journal_title=Vasc Cell;citation_author=Y. Yamamoto;citation_author=J. Matsui;citation_author=T. Matsushima;citation_author=H. Obaishi;citation_author=K. Miyazaki;citation_author=K. Nakamura;citation_author=O. Tohyama;citation_author=T. Semba;citation_author=A. Yamaguchi;citation_author=SS. Hoshi;citation_author=F. Mimura;citation_author=T. Haneda;citation_author=Y. Fukuda;citation_author=JI. Kamata;citation_author=K. Takahashi;citation_author=M. Matsukura;citation_author=T. Wakabayashi;citation_author=M. Asada;citation_author=KI. Nomoto;citation_author=T. Watanabe;citation_author=Z. Dezso;citation_author=K. Yoshimatsu;citation_author=Y. Funahashi;citation_author=A. Tsuruoka;citation_title=Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage;citation_pages=18;citation_volume=6;citation_year=2014;citation_pmid=25197551;citation_doi=10.1186/2045-824X-6-18" /> <meta name="citation_reference" content="citation_journal_title=Lancet;citation_author=M. Kudo;citation_author=RS. Finn;citation_author=S. Qin;citation_author=KH. Han;citation_author=K. Ikeda;citation_author=F. Piscaglia;citation_author=A. Baron;citation_author=JW. Park;citation_author=G. Han;citation_author=J. Jassem;citation_author=JF. Blanc;citation_author=A. Vogel;citation_author=D. Komov;citation_author=TRJ. Evans;citation_author=C. Lopez;citation_author=C. Dutcus;citation_author=M. Guo;citation_author=K. Saito;citation_author=S. Kraljevic;citation_author=T. Tamai;citation_author=M. Ren;citation_author=AL. Cheng;citation_title=Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial;citation_pages=1163-1173;citation_volume=391;citation_year=2018;citation_issue=10126;citation_pmid=29433850;citation_doi=10.1016/S0140-6736(18)30207-1" /> <meta name="citation_reference" content="citation_journal_title=Act Hepatol Jpn;citation_author=T. Murakami;citation_title=Establishment and characterization of human hepatoma cell line (KIM-1);citation_pages=532-539;citation_volume=25;citation_year=1984" /> <meta name="citation_reference" content="citation_journal_title=Acta pathologica japonica;citation_journal_abbrev=Acta Pathol Jpn;citation_author=H. Yano;citation_author=M. Maruiwa;citation_author=T. Murakami;citation_author=K. Fukuda;citation_author=Y. Ito;citation_author=S. Sugihara;citation_author=M. Kojiro;citation_title=A new human pleomorphic hepatocellular carcinoma cell line, KYN-2.;citation_pages=953-966;citation_volume=38;citation_year=1988;citation_issue=8;citation_pmid=2847482;citation_doi=10.1111/j.1440-1827.1988.tb02368.x" /> <meta name="citation_reference" content="citation_journal_title=Jpn J Cancer Res Proc Jpn Cancer Assoc;citation_title=Establishment and characterization of a new human hepatoma cell line (KYN-3) derived from the ascites of the hepatoma patient (Abstract);citation_author=T. Murakami;citation_author=M. Maruiwa;citation_author=K. Fukuda;citation_author=M. Kojiro;citation_author=M. Tanaka;citation_author=K. Tanikawa;citation_pages=292;citation_year=1988" /> <meta name="citation_reference" content="citation_journal_title=Hepatology (Baltimore, Md.);citation_journal_abbrev=Hepatology;citation_author=H. Yano;citation_author=A. Iemura;citation_author=K. Fukuda;citation_author=A. Mizoguchi;citation_author=M. Haramaki;citation_author=M. Kojiro;citation_title=Establishment of two distinct human hepatocellular carcinoma cell lines from a single nodule showing clonal dedifferentiation of cancer cells;citation_pages=320-327;citation_volume=18;citation_year=1993;citation_issue=2;citation_pmid=8393423;citation_doi=10.1016/0270-9139(93)90015-F" /> <meta name="citation_reference" content="citation_journal_title=Human cell : official journal of Human Cell Research Society;citation_journal_abbrev=Hum Cell;citation_author=M. Haramaki;citation_author=H. Yano;citation_author=A. Iemura;citation_author=S. Momosaki;citation_author=S. Ogasawara;citation_author=M. Inoue;citation_author=R. Yamaguchi;citation_author=A. Kusaba;citation_author=I. Utsunomiya;citation_author=M. Kojiro;citation_title=A new human hepatocellular carcinoma cell line (HAK-2) forms various structures in collagen gel matrices.;citation_pages=183-192;citation_volume=10;citation_year=1997;citation_issue=3;citation_pmid=9436038" /> <meta name="citation_reference" content="citation_journal_title=International journal of oncology;citation_journal_abbrev=Int J Oncol;citation_author=I. Utsunomiya;citation_author=A. Iemura;citation_author=H. Yano;citation_author=J. Akiba;citation_author=M. Kojiro;citation_title=Establishment and characterization of a new human hepatocellular carcinoma cell line, HAK-3, and its response to growth factors.;citation_pages=669-675;citation_volume=15;citation_year=1999;citation_issue=4;citation_pmid=10493947;citation_doi=10.3892/ijo.15.4.669" /> <meta name="citation_reference" content="citation_journal_title=Hepatology (Baltimore, Md.);citation_journal_abbrev=Hepatology;citation_author=T. Murakami;citation_author=H. Yano;citation_author=M. Maruiwa;citation_author=S. Sugihara;citation_author=M. Kojiro;citation_title=Establishment and characterization of a human combined hepatocholangiocarcinoma cell line and its heterologous transplantation in nude mice;citation_pages=551-556;citation_volume=7;citation_year=1987;citation_issue=3;citation_pmid=3032760;citation_doi=10.1002/hep.1840070322" /> <meta name="citation_reference" content="citation_journal_title=Journal of hepatology;citation_journal_abbrev=J Hepatol;citation_author=H. Yano;citation_author=A. Iemura;citation_author=M. Haramaki;citation_author=S. Momosaki;citation_author=S. Ogasawara;citation_author=K. Higaki;citation_author=M. Kojiro;citation_title=A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that shows the features of hepatocellular carcinoma or cholangiocarcinoma under different growth conditions.;citation_pages=413-422;citation_volume=24;citation_year=1996;citation_issue=4;citation_pmid=8738727;citation_doi=10.1016/s0168-8278(96)80161-9" /> <meta name="citation_reference" content="citation_journal_title=Hepatology (Baltimore, Md.);citation_journal_abbrev=Hepatology;citation_author=S. Ogasawara;citation_author=H. Yano;citation_author=A. Iemura;citation_author=T. Hisaka;citation_author=M. Kojiro;citation_title=Expressions of basic fibroblast growth factor and its receptors and their relationship to proliferation of human hepatocellular carcinoma cell lines.;citation_pages=198-205;citation_volume=24;citation_year=1996;citation_issue=1;citation_pmid=8707262;citation_doi=10.1002/hep.510240132" /> <meta name="citation_reference" content="citation_journal_title=Int J Oncol;citation_author=H. Kusano;citation_author=S. Ogasawara;citation_author=J. Akiba;citation_author=M. Nakayama;citation_author=K. Ueda;citation_author=H. Yano;citation_title=Antiproliferative effects of sorafenib and pegylated IFNalpha2b on human liver cancer cells in vitro and in vivo;citation_pages=1897-1903;citation_volume=42;citation_year=2013;citation_issue=6;citation_pmid=23588838" /> <meta name="citation_reference" content="citation_journal_title=N Engl J Med;citation_author=M. Schlumberger;citation_author=M. Tahara;citation_author=LJ. Wirth;citation_author=B. Robinson;citation_author=MS. Brose;citation_author=R. Elisei;citation_author=MA. Habra;citation_author=K. Newbold;citation_author=MH. Shah;citation_author=AO. Hoff;citation_author=AG. Gianoukakis;citation_author=N. Kiyota;citation_author=MH. Taylor;citation_author=SB. Kim;citation_author=MK. Krzyzanowska;citation_author=CE. Dutcus;citation_author=B. de las Heras;citation_author=J. Zhu;citation_author=SI. Sherman;citation_title=Lenvatinib versus placebo in radioiodine-refractory thyroid cancer;citation_pages=621-630;citation_volume=372;citation_year=2015;citation_issue=7;citation_pmid=25671254;citation_doi=10.1056/NEJMoa1406470" /> <meta name="citation_reference" content="citation_journal_title=J Clin Endocrinol Metab;citation_author=R. Elisei;citation_author=B. Cosci;citation_author=C. Romei;citation_author=V. Bottici;citation_author=G. Renzini;citation_author=E. Molinaro;citation_author=L. Agate;citation_author=A. Vivaldi;citation_author=P. Faviana;citation_author=F. Basolo;citation_author=P. Miccoli;citation_author=P. Berti;citation_author=F. Pacini;citation_author=A. Pinchera;citation_title=Prognostic significance of somatic ret oncogene mutations in sporadic medullary thyroid cancer: A 10-year follow-up study;citation_volume=93;citation_year=2008;citation_issue=3;citation_pmid=18073307;citation_doi=10.1210/jc.2007-1714" /> <meta name="citation_reference" content="citation_journal_title=British Journal of Cancer;citation_journal_abbrev=British Journal of Cancer;citation_author=MM. Moura;citation_author=BM. Cavaco;citation_author=AE. Pinto;citation_author=R. Domingues;citation_author=JR. Santos;citation_author=MO. Cid;citation_author=MJ. Bugalho;citation_author=V. Leite;citation_title=Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas.;citation_pages=1777-1783;citation_volume=100;citation_year=2009;citation_issue=11;citation_pmid=19401695;citation_doi=10.1038/sj.bjc.6605056" /> <meta name="citation_reference" content="citation_journal_title=Clin Cancer Res;citation_author=S. Kato;citation_author=V. Subbiah;citation_author=E. Marchlik;citation_author=SK. Elkin;citation_author=JL. Carter;citation_author=R. Kurzrock;citation_title=RET aberrations in diverse cancers: Next-generation sequencing of 4,871 patients;citation_volume=23;citation_year=2017;citation_issue=8;citation_pmid=27683183;citation_doi=10.1158/1078-0432.CCR-16-1679" /> <meta name="citation_reference" content="citation_journal_title=Hepatology;citation_author=DS. Sandhu;citation_author=E. Baichoo;citation_author=LR. Roberts;citation_title=Fibroblast growth factor signaling in liver carcinogenesis;citation_pages=1166-1173;citation_volume=59;citation_year=2014;citation_issue=3;citation_pmid=24716202;citation_doi=10.1002/hep.26679" /> <meta name="citation_reference" content="citation_journal_title=Cancer Med;citation_author=M. Matsuki;citation_author=T. Hoshi;citation_author=Y. Yamamoto;citation_author=M. Ikemori-Kawada;citation_author=Y. Minoshima;citation_author=Y. Funahashi;citation_author=J. Matsui;citation_title=Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models;citation_pages=2641-2653;citation_volume=7;citation_year=2018;citation_issue=6;citation_pmid=29733511" /> <meta name="citation_reference" content="citation_journal_title=Diseases;citation_author=D. Repana;citation_author=P. Ross;citation_title=Targeting FGF19/FGFR4 pathway: A novel therapeutic strategy for hepatocellular carcinoma;citation_pages=294-305;citation_volume=3;citation_year=2015;citation_issue=4;citation_pmid=28943626" /> <meta name="citation_reference" content="citation_journal_abbrev=PLoS ONE;citation_author=DM. French;citation_author=BC. Lin;citation_author=M. Wang;citation_author=C. Adams;citation_author=T. Shek;citation_author=K. Hotzel;citation_author=B. Bolon;citation_author=R. Ferrando;citation_author=C. Blackmore;citation_author=K. Schroeder;citation_author=LA. Rodriguez;citation_author=M. Hristopoulos;citation_author=R. Venook;citation_author=A. Ashkenazi;citation_author=LR. Desnoyers;citation_title=Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.;citation_pages=e36713-e36713;citation_volume=7;citation_year=2012;citation_issue=5;citation_pmid=22615798;citation_doi=10.1371/journal.pone.0036713" /> <meta name="citation_reference" content="citation_journal_title=Journal of hepatology;citation_journal_abbrev=J Hepatol;citation_author=HK. Ho;citation_author=S. Pok;citation_author=S. Streit;citation_author=JE. Ruhe;citation_author=S. Hart;citation_author=KS. Lim;citation_author=HL. Loo;citation_author=MO. Aung;citation_author=SG. Lim;citation_author=A. Ullrich;citation_title=Fibroblast growth factor receptor 4 regulates proliferation, anti-apoptosis and alpha-fetoprotein secretion during hepatocellular carcinoma progression and represents a potential target for therapeutic intervention.;citation_pages=118-127;citation_volume=50;citation_year=2009;citation_issue=1;citation_pmid=19008009;citation_doi=10.1016/j.jhep.2008.08.015" /> <meta name="citation_reference" content="citation_journal_title=Nat Rev Cancer;citation_author=IS. Babina;citation_author=NC. Turner;citation_title=Advances and challenges in targeting FGFR signalling in cancer;citation_pages=318-332;citation_volume=17;citation_year=2017;citation_issue=5;citation_pmid=28303906;citation_doi=10.1038/nrc.2017.8" /> <meta name="citation_reference" content="citation_journal_title=Oncol Rep;citation_author=SM. Ferrari;citation_author=G. Bocci;citation_author=T. Di Desidero;citation_author=G. Elia;citation_author=I. Ruffilli;citation_author=F. Ragusa;citation_author=P. Orlandi;citation_author=SR. Paparo;citation_author=A. Patrizio;citation_author=S. Piaggi;citation_author=C. La Motta;citation_author=S. Ulisse;citation_author=E. Baldini;citation_author=G. Materazzi;citation_author=P. Miccoli;citation_author=A. Antonelli;citation_author=P. Fallahi;citation_title=Lenvatinib exhibits antineoplastic activity in anaplastic thyroid cancer in vitro and in vivo;citation_pages=2225-2234;citation_volume=39;citation_year=2018;citation_issue=5;citation_pmid=29517103" /> <meta name="citation_reference" content="citation_journal_title=Exp Ther Med;citation_author=G. Wang;citation_author=J. Zhuang;citation_author=J. Ni;citation_author=Y. Ye;citation_author=S. He;citation_author=W. Xia;citation_title=Combined effects of lenvatinib and iodine-131 on cell apoptosis in nasopharyngeal carcinoma through inducing endoplasmic reticulum stress;citation_pages=3325-3332;citation_volume=16;citation_year=2018;citation_issue=4;citation_pmid=30233679" /> <meta name="citation_reference" content="citation_journal_title=Oncol Lett;citation_author=S. Ogasawara;citation_author=M. Nakayama;citation_author=J. Akiba;citation_author=H. Kusano;citation_author=H. Yano;citation_title=Effect of sorafenib on des-gamma-carboxyprothrombin secretion by a human hepatocellular carcinoma cell line;citation_pages=2170-2176;citation_volume=14;citation_year=2017;citation_issue=2;citation_pmid=28781657" /> <meta name="citation_reference" content="citation_journal_title=Journal of medicinal chemistry;citation_journal_abbrev=J Med Chem;citation_author=I. Kufareva;citation_author=R. Abagyan;citation_title=Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states.;citation_pages=7921-7932;citation_volume=51;citation_year=2008;citation_issue=24;citation_pmid=19053777;citation_doi=10.1021/jm8010299" /> <meta name="citation_reference" content="citation_journal_title=ACS Med Chem Lett;citation_author=K. Okamoto;citation_author=M. Ikemori-Kawada;citation_author=A. Jestel;citation_author=K. von Konig;citation_author=Y. Funahashi;citation_author=T. Matsushima;citation_author=A. Tsuruoka;citation_author=A. Inoue;citation_author=J. Matsui;citation_title=Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization;citation_pages=89-94;citation_volume=6;citation_year=2015;citation_issue=1;citation_pmid=25589937;citation_doi=10.1021/ml500394m" /> <meta name="citation_reference" content="citation_journal_title=J Cell Biol;citation_author=G. Seghezzi;citation_author=S. Patel;citation_author=CJ. Ren;citation_author=A. Gualandris;citation_author=G. Pintucci;citation_author=ES. Robbins;citation_author=RL. Shapiro;citation_author=AC. Galloway;citation_author=DB. Rifkin;citation_author=P. Mignatti;citation_title=Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contributing to angiogenesis;citation_volume=141;citation_year=1998;citation_issue=7;citation_pmid=9647657;citation_doi=10.1083/jcb.141.7.1659" /> <meta name="twitter:title" content="Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/default/covers/acr_default_cover_0.gif" /> <meta name="twitter:description" content="Background/Aim: Lenvatinib is a potent inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), KIT, and RET. Here, we investigated the antiproliferative effects of lenvatinib in liver cancer cells in vitro and in vivo. Materials and Methods: Eleven hepatocellular carcinoma cell lines and two combined hepatocellular/cholangiocarcinoma cell lines were treated with 0-30 μM lenvatinib. Cell growth, apoptosis and the expression of FGFR1-4, FGF19, fibroblast growth factor receptor substrate (FRS)2α and RET were examined. Two HCC cell lines were subcutaneously implanted on nude mice and mice were treated with 3, 10, 30 mg/kg/day of lenvatinib or vehicle for 14 consecutive days. Tumor volume was measured every 3 days. Mice were sacrificed on day 15 and tumors were processed for histological examination. Blood vessels, microvessel density, necrosis, and apoptosis were also examined. Results: Lenvatinib dose- and time-dependently inhibited growth of all cell lines; however, sensitivity to lenvatinib varied. Apoptosis was not observed in any cell line, and expression of FGFR1, -2, -3 and -4, FGF19, FRS2α, and RET were observed in these cell lines. Cell lines with high expression of these factors showed higher response to lenvatinib. In mice, lenvatinib dose-dependently suppressed tumor growth. Blood vessels and microvessel density were significantly reduced and the rate of necrosis was significantly increased by lenvatinib; apoptosis was not observed. Conclusion: Antiproliferative effects of lenvatinib on liver cancer cells were observed in vitro and in vivo. Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells." /> <meta name="og-title" property="og:title" content="Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo" /> <meta name="og-url" property="og:url" content="https://ar.iiarjournals.org/content/39/11/5973" /> <meta name="og-site-name" property="og:site_name" content="Anticancer Research" /> <meta name="og-description" property="og:description" content="Background/Aim: Lenvatinib is a potent inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), KIT, and RET. Here, we investigated the antiproliferative effects of lenvatinib in liver cancer cells in vitro and in vivo. Materials and Methods: Eleven hepatocellular carcinoma cell lines and two combined hepatocellular/cholangiocarcinoma cell lines were treated with 0-30 μM lenvatinib. Cell growth, apoptosis and the expression of FGFR1-4, FGF19, fibroblast growth factor receptor substrate (FRS)2α and RET were examined. Two HCC cell lines were subcutaneously implanted on nude mice and mice were treated with 3, 10, 30 mg/kg/day of lenvatinib or vehicle for 14 consecutive days. Tumor volume was measured every 3 days. Mice were sacrificed on day 15 and tumors were processed for histological examination. Blood vessels, microvessel density, necrosis, and apoptosis were also examined. Results: Lenvatinib dose- and time-dependently inhibited growth of all cell lines; however, sensitivity to lenvatinib varied. Apoptosis was not observed in any cell line, and expression of FGFR1, -2, -3 and -4, FGF19, FRS2α, and RET were observed in these cell lines. Cell lines with high expression of these factors showed higher response to lenvatinib. In mice, lenvatinib dose-dependently suppressed tumor growth. Blood vessels and microvessel density were significantly reduced and the rate of necrosis was significantly increased by lenvatinib; apoptosis was not observed. Conclusion: Antiproliferative effects of lenvatinib on liver cancer cells were observed in vitro and in vivo. Lenvatinib may suppress tumor formation by inhibiting angiogenesis, and via an additional direct antiproliferative effect in some liver cancer cells." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/default/covers/acr_default_cover_0.gif" /> <link rel="shortlink" href="/node/56184" /> <link rel="shortcut icon" href="https://ar.iiarjournals.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <title>Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo | Anticancer Research</title> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__2zPavjNI4URbm7YEOITlubDJzvajDzVbbhQ4q5-qmmI__uV7KmINrPipfZctdVFoJt8NS05a9GP5fLatYcltcPks__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <link type="text/css" rel="stylesheet" href="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.css" media="all" /> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__ymdntbpndmkKkn0luYEogHowFTfOCKFOYFYACuu9YLg__D7AqY1J-xdwH04mZNPe3_-LvzKf06inu1VB1VVwxv1I__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <style type="text/css" media="all"> /* <![CDATA[ */ #sliding-popup.sliding-popup-bottom,#sliding-popup.sliding-popup-bottom .eu-cookie-withdraw-banner,.eu-cookie-withdraw-tab{background:#0779bf}#sliding-popup.sliding-popup-bottom.eu-cookie-withdraw-wrapper{background:transparent}#sliding-popup .popup-content #popup-text h1,#sliding-popup .popup-content #popup-text h2,#sliding-popup .popup-content #popup-text h3,#sliding-popup .popup-content #popup-text p,.eu-cookie-compliance-secondary-button,.eu-cookie-withdraw-tab{color:#fff !important}.eu-cookie-withdraw-tab{border-color:#fff}.eu-cookie-compliance-more-button{color:#fff !important} /* ]]> */ </style> <!--[if lte IE 7]> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__ElJr3PIJEvw3qLXc1cnYiLj2G4KgDPSXFOfm6Phf8hw__JdWGm15cDWjsK6KrFlQVXQix9YgNeYysf22XZHj-Y-c__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <![endif]--> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__BuoDuzoWcz2CL9-rYVqiOwZYB0s9mtqPm1bLrGHX4Z4__WNptNuPkTJ2rxI9jvljwIQXeYY9GgnsTxhjOkFT4fEY__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__mUmW___dnl7OSMtILYPzgBjKI7YaVpe0imeaXFqxW3A__3w2axNic22mHLXKlqSmMAf1YBlV8oU_dFJFUcKN-kvI__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <!--[if (lt IE 9)&(!IEMobile)]> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__XH6bpcI0f2dImc-p674DLCZtWBGb-QwxJK1YexVGtno__vUceGprdo5nIhV6DH93X7fI3r8RcTJbChbas9TQXeW4__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <![endif]--> <!--[if gte IE 9]><!--> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__oWyrHF_mmv3c4PPGrsNSmh5Ub_1TfiuNA2i1_MOafWg__1kTjT7uqr7v6BlTbuE-4U2S8EzyEcBTxZhvp1VjA-qo__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <!--<![endif]--> <!--[if gte IE 9]><!--> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__-Kek3KTto4Kje1mJ9bp_-a_lv0D9QS29NgfFBV-inOY__90wksBfd5YlmG0UjedmGQFn8Ano49PMQRwGgVOM50YE__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <!--<![endif]--> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__mDLLoHdwQgUaxS5COkkpm0Sl2yy7M3e-p5Teg-HzKB4__iBfm7f9Zjr1nQCVzxlloL1f_WY5-IVR9o7sZ7ib2wp0__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.css" media="all" /> <script type="text/javascript" src="/sites/default/files/advagg_js/js__qC267sd2jkKakCeHpNn2j6GnEh317Wjy2VJcU0iqsL8__-pTqPNTL2eIJy025SeKlzwYdLCFUMpXqoeprt-cuMrM__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js"></script> <script type="text/javascript" src="https://d1bxh8uas1mnw7.cloudfront.net/assets/embed.js"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__WKIhpIdNXf5v0HFXU_afTESRg7B8IwK79GoSAkkjPFA__QwGQnRA1eYYXoE3FtpYd9Uos-BVLC8KPqZOy_WELG98__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js"></script> <script type="text/javascript" src="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.js"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__2GwUNGtNhA1ivH0hT8gyoPgs6QdcV5kqvwDrLrF0-Ds__X50Hz-tE_88YfXnEthfr_mMj-ScHu86xEXFQRucEVhQ__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js"></script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i<a.length;i++)j=a[i],e(j)?g(j,0,l,0):w(j)?B(j):Object(j)===j&&h(j,l);else Object(a)===a&&h(a,l)},B.addPrefix=function(a,b){z[a]=b},B.addFilter=function(a){x.push(a)},B.errorTimeout=1e4,null==b.readyState&&b.addEventListener&&(b.readyState="loading",b.addEventListener("DOMContentLoaded",A=function(){b.removeEventListener("DOMContentLoaded",A,0),b.readyState="complete"},0)),a.yepnope=k(),a.yepnope.executeStack=h,a.yepnope.injectJs=function(a,c,d,e,i,j){var k=b.createElement("script"),l,o,e=e||B.errorTimeout;k.src=a;for(o in d)k.setAttribute(o,d[o]);c=j?h:c||f,k.onreadystatechange=k.onload=function(){!l&&g(k.readyState)&&(l=1,c(),k.onload=k.onreadystatechange=null)},m(function(){l||(l=1,c(1))},e),i?k.onload():n.parentNode.insertBefore(k,n)},a.yepnope.injectCss=function(a,c,d,e,g,i){var e=b.createElement("link"),j,c=i?h:c||f;e.href=a,e.rel="stylesheet",e.type="text/css";for(j in d)e.setAttribute(j,d[j]);g||(n.parentNode.insertBefore(e,n),m(c,0))}})(this,document); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- yepnope({ test: Modernizr.matchmedia, nope: '/sites/all/libraries/media-match/media.match.min.js' }); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- document.createElement( "picture" ); //--><!]]> </script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__GM3GJPR36rRIz0TRkjC5OQwrioSyN9aoYRivDhCO_AM__qAl84FcCv2jyN22yFGS5Oc85cjd9zKX6p_cFNLGhe-M__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js" async="async"></script> <script type="text/javascript" defer="defer" async="async" src="//cdn.foxycart.com/iiar.ecommerce.highwire.org/loader.js"></script> <script type="text/javascript" async="async" src="https://scholar.google.com/scholar_js/casa.js"></script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- jQuery.extend(Drupal.settings,{"basePath":"\/","pathPrefix":"","ajaxPageState":{"theme":"jcore_1","theme_token":"2giYC45snVqfpgajs3OBrKUG5CRBQREHp-v68RgdDqw","jquery_version":"1.8","css":{"modules\/system\/system.base.css":1,"modules\/system\/system.menus.css":1,"modules\/system\/system.messages.css":1,"modules\/system\/system.theme.css":1,"misc\/ui\/jquery.ui.core.css":1,"misc\/ui\/jquery.ui.theme.css":1,"misc\/ui\/jquery.ui.button.css":1,"misc\/ui\/jquery.ui.resizable.css":1,"misc\/ui\/jquery.ui.dialog.css":1,"misc\/ui\/jquery.ui.tooltip.css":1,"misc\/ui\/jquery.ui.accordion.css":1,"sites\/all\/modules\/contrib\/date\/date_api\/date.css":1,"sites\/all\/modules\/contrib\/date\/date_popup\/themes\/datepicker.1.7.css":1,"modules\/field\/theme\/field.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_draw\/css\/highwire-draw.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_folders\/highwire_folders.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_foxycart\/highwire_foxycart.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/css\/highwire-responsive.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_saved_searches\/highwire_saved_searches.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_user\/highwire_user.css":1,"modules\/node\/node.css":1,"sites\/all\/modules\/contrib\/picture\/picture_wysiwyg.css":1,"modules\/search\/search.css":1,"modules\/user\/user.css":1,"sites\/all\/modules\/contrib\/views\/css\/views.css":1,"sites\/all\/modules\/contrib\/ckeditor\/css\/ckeditor.css":1,"sites\/all\/modules\/contrib\/colorbox\/styles\/default\/colorbox_style.css":1,"sites\/all\/modules\/contrib\/ctools\/css\/ctools.css":1,"sites\/all\/modules\/contrib\/foxycart\/foxycart.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire.style.highwire.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/nlm-elements.css":1,"sites\/all\/modules\/contrib\/panels\/css\/panels.css":1,"public:\/\/ctools\/css\/263bfdb18936424f0ade19d6bd885f37.css":1,"sites\/all\/modules\/contrib\/panels_ajax_tab\/css\/panels_ajax_tab.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire.style.markup.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/layouts\/highwire_2col_stacked\/highwire-2col-stacked.css":1,"sites\/all\/modules\/contrib\/forward\/forward.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_share_link.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_copy_permalink.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_citing_links.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_reports_feed.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/highwire-article-citation-list.css":1,"\/\/cdn.jsdelivr.net\/qtip2\/2.2.1\/jquery.qtip.min.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/plugins\/styles\/highwire_responsive_toggle\/highwire_responsive_toggle.css.less":1,"sites\/all\/modules\/contrib\/nice_menus\/css\/nice_menus.css":1,"sites\/all\/modules\/contrib\/nice_menus\/css\/nice_menus_default.css":1,"sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css":1,"sites\/all\/modules\/contrib\/eu_cookie_compliance\/css\/eu_cookie_compliance.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/highwire.gtranslate.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/userbar-dropdown-menu.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_theme_tools\/css\/font-hwicons.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_theme_tools\/css\/font-hwicons-glyphs.css":1,"sites\/all\/themes\/highwire\/jcore_1\/eu_cookie_compliance.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/font-awesome-ie7.css":1,"sites\/all\/themes\/contrib\/omega\/alpha\/css\/alpha-reset.css":1,"sites\/all\/themes\/contrib\/omega\/alpha\/css\/alpha-mobile.css":1,"sites\/all\/themes\/contrib\/omega\/alpha\/css\/alpha-alpha.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/formalize.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-text.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-branding.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-menu.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-forms.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/highwire-forms.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/mobile-reset.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/font-awesome.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/forms.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/global.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/jquery-ui-elements.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/text.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/eletters.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/colors.css.less":1,"ie::normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"ie::normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-normal.css":1,"ie::normal::sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/normal\/jcore-default-normal-30.css":1,"narrow::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"narrow::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-narrow.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/narrow\/jcore-default-narrow-30.css":1,"normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-normal.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/normal\/jcore-default-normal-30.css":1,"wide::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"wide::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-wide.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/wide\/jcore-default-wide-30.css":1,"sites\/all\/modules\/shared\/jnl_iiar_styles\/css\/jnl_iiar_styles.css.less":1},"js":{"sites\/all\/libraries\/enquire.js\/enquire.min.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_panels_ajax_tab.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_user\/plugins\/content_types\/js\/highwire_user_salutation.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_foxycart\/highwire_foxycart.js":1,"sites\/all\/modules\/contrib\/eu_cookie_compliance\/js\/eu_cookie_compliance.js":1,"sites\/all\/libraries\/modernizr\/modernizr.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/jquery\/1.8\/jquery.min.js":1,"misc\/jquery-extend-3.4.0.js":1,"misc\/jquery.once.js":1,"misc\/drupal.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.core.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.widget.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.button.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.mouse.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.draggable.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.position.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.resizable.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.dialog.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/external\/jquery.cookie.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/misc\/jquery.form.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.tooltip.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.accordion.min.js":1,"sites\/all\/libraries\/jquery.bgiframe\/jquery.bgiframe.js":1,"sites\/all\/libraries\/jquery.hoverIntent\/jquery.hoverIntent.js":1,"sites\/all\/libraries\/superfish\/superfish.js":1,"sites\/all\/modules\/contrib\/nice_menus\/js\/nice_menus.js":1,"misc\/ajax.js":1,"sites\/all\/modules\/contrib\/jquery_update\/js\/jquery_update.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.equal-heights.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.panels-ajax-tab.js":1,"sites\/all\/libraries\/colorbox\/jquery.colorbox-min.js":1,"sites\/all\/modules\/contrib\/colorbox\/js\/colorbox.js":1,"sites\/all\/modules\/contrib\/colorbox\/styles\/default\/colorbox_style.js":1,"sites\/all\/modules\/contrib\/foxycart\/foxycart.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_log\/highwire_log.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_user\/js\/highwire_user_meta.js":1,"sites\/all\/modules\/contrib\/panels_ajax_tab\/js\/panels_ajax_tab.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js":1,"https:\/\/d1bxh8uas1mnw7.cloudfront.net\/assets\/embed.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_altmetrics.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_citing_links.js":1,"misc\/progress.js":1,"sites\/all\/modules\/contrib\/captcha\/captcha.js":1,"misc\/textarea.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_citation\/plugins\/content_types\/js\/highwire_citation_export.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/minipanel_dialog_link.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_share_dialog.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/clipboard.min.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_clipboard.js":1,"sites\/all\/modules\/contrib\/service_links\/js\/twitter_button.js":1,"sites\/all\/modules\/contrib\/service_links\/js\/facebook_like.js":1,"sites\/all\/modules\/contrib\/service_links\/js\/google_plus_one.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_article_nav.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_nav_float.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_search\/plugins\/content_types\/js\/highwire_search_similar_articles.js":1,"sites\/all\/modules\/contrib\/panels_accordion\/js\/panels_accordion.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.article-citation-access.js":1,"\/\/cdn.jsdelivr.net\/qtip2\/2.2.1\/jquery.qtip.min.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.article-citation-author-tooltip.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/plugins\/styles\/highwire_responsive_toggle\/highwire_responsive_toggle.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.gtranslate.js":1,"sites\/all\/themes\/highwire\/jcore_1\/js\/theme-scripts.js":1,"sites\/all\/themes\/contrib\/omega\/omega\/js\/jquery.formalize.js":1,"sites\/all\/themes\/contrib\/omega\/omega\/js\/omega-mediaqueries.js":1,"sites\/all\/themes\/contrib\/omega\/omega\/js\/omega-equalheights.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/js\/highwire-mediaqueries.js":1,"sites\/all\/modules\/contrib\/picture\/picturefill2\/picturefill.min.js":1,"sites\/all\/modules\/contrib\/picture\/picture.min.js":1,"\/\/cdn.foxycart.com\/iiar.ecommerce.highwire.org\/loader.js":1,"https:\/\/scholar.google.com\/scholar_js\/casa.js":1}},"colorbox":{"opacity":"0.85","current":"{current} of {total}","previous":"\u00ab Prev","next":"Next \u00bb","close":"Close","maxWidth":"98%","maxHeight":"98%","fixed":true,"mobiledetect":true,"mobiledevicewidth":"480px"},"highwire":{"markup":[{"requested":"short-text","variant":"abstract","view":"abstract","pisa":"anticanres;39\/11\/5973"},{"requested":"short-text","variant":"abstract","view":"abstract","pisa":"anticanres;39\/11\/5973"},{"requested":"full-text","variant":"full-text","view":"full","pisa":"anticanres;39\/11\/5973"},{"requested":"abstract","variant":"abstract","view":"abstract","pisa":"anticanres;39\/11\/5973"},{"requested":"full-text","variant":"full-text","view":"full","pisa":"anticanres;39\/11\/5973"}],"nid":"56184","apath":"\/anticanres\/39\/11\/5973.atom","pisa":"anticanres;39\/11\/5973","modal_window_width":"560","share_modal_width":"560","share_modal_title":"Share this Article"},"user_uid":0,"customer_email":"","cartstack_siteid":"","foxycart_subdomain":"iiar.ecommerce.highwire.org","foxycart_always_show_cart_link":1,"hw_fc_cookie_domain":".iiarjournals.org","highwire_panel_tabs":[{"panel_name":"jnl_iiar_tab_pdf","panel_ajax_tab":"jnl_iiar_tab_pdf"}],"panel_ajax_tab":{"path":"sites\/all\/modules\/contrib\/panels_ajax_tab"},"MutationObserver":{"js":"\/sites\/all\/libraries\/mutationobserver\/MutationObserver.js"},"ajax":{"edit-submit--3":{"callback":"highwire_alerts_login_form_submit","wrapper":"alerts-form-wrapper","event":"click","url":"\/system\/ajax","submit":{"_triggering_element_name":"op","_triggering_element_value":"Submit"}}},"urlIsAjaxTrusted":{"\/system\/ajax":true,"\/content\/39\/11\/5973\/tab-article-info":true},"ws_fl":{"width":100,"height":21},"ws_gpo":{"size":"","annotation":"","lang":"","callback":"","width":300},"highwire_search_similar_articles":{"highwire-search-similar-articles-list-1":{"conf":{"context":"requiredcontext_entity:node_1","override_title":1,"override_title_text":"\u003Ci class=\u0022icon-caret-right\u0022\u003E\u003C\/i\u003E Similar Articles","number_per_page":"5","show_pager":0,"more_link_path":"similar\/articles","more_link":1,"empty_message":"No similar articles are available.","citation_style":"jcore_standard","title_type":"prefer_short","title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","display_original_link":0,"display_access_indicator":0,"display_cme_link":0,"display_access_indicator_text":0,"display_highlight_image":"0","display_variants":0,"display_supplements":0,"display_abstract_tooltip":0,"display_author_tooltip":0,"override_title_heading":"h2","citation_settings_source":"citation_manager","citation_manager_wrapper":{"citation_manager_citation":"jcore_list_title_only"},"corpus_config_wrapper":{"corpus_config_citation_context":[]},"cache_enabled":1,"cache_time":"600","short_title_options":{"char_count":"50","add_ellipsis":0},"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"highlight_image_style":"","featured_image_variant":"large","featured_image_click_image":"colorbox","display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":0,"display_ads_search_tooltip":0,"display_agricola_tooltip":0,"author_site_search_path":"","display_translations":0,"display_translations_text":"","display_translations_text_icon":"","bundle_overrides_checkboxes":{"highwire_book_fragment":{"selector":0},"highwire_news_story":{"selector":0},"highwire_book_edition":{"selector":0},"highwire_article":{"selector":0},"highwire_issue":{"selector":0},"highwire_comment":{"selector":0},"highwire_fragment":{"selector":0},"highwire_book_section":{"selector":0},"highwire_journal":{"selector":0}},"bundle_overrides":{"highwire_book_fragment":{"selector":0,"citation_style":"jcore_title_and_author","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":"0","access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"thumbnail","display_fragment_caption":1,"display_parent_citation":1,"parent_citation_type":"highwire_book_section","parent_citation_settings":{"citation_style":"folio_book_sections_standard","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"author_site_search_path":"search\/"}},"highwire_news_story":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":"0","highlight_image_style":"","featured_image_click_image":"nothing","display_author_tooltip":0,"display_google_scholar_tooltip":0,"display_pubmed_tooltip":0,"display_advanced_search_tooltip":0},"highwire_book_edition":{"selector":0,"citation_style":"folio_books_standard","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":1,"author_site_search_path":"search\/"},"highwire_article":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":0,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":"0","highlight_image_style":"","featured_image_variant":"large","featured_image_click_image":"nothing","display_cme_link":0,"display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":1,"display_ads_search_tooltip":0,"display_agricola_tooltip":0,"author_site_search_path":"search\/","display_translations":0,"display_translations_text":"Translations Available","display_translations_text_icon":"icon-globe"},"highwire_issue":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","featured_image_click_image":"nothing","display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"display_orcid_tooltip":1,"author_site_search_path":"search\/"},"highwire_comment":{"selector":0,"citation_style":"highwire_comment","show_title":0,"title_as_link":0,"title_as_link_type":"tab_view","author_format_type":"fullname","author_format_custom":"","author_list_separator":", ","date_format":"(j F Y)","display_comment_body":1,"display_attachment":1,"display_conflict_of_interest":1},"highwire_fragment":{"selector":0,"citation_style":"jcore_title_and_author","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":"0","access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_fragment_caption":1,"fragment_image_settings":{"fragment_image_variant":"medium","fragment_click_image":"colorbox","show_download_links":1},"display_parent_citation":1,"parent_citation_type":"highwire_article","parent_citation_settings":{"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":0,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":"0","highlight_image_style":"","featured_image_variant":"large","featured_image_click_image":"nothing","display_cme_link":0,"display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":1,"display_ads_search_tooltip":0,"display_agricola_tooltip":0,"author_site_search_path":"search\/","display_translations":0,"display_translations_text":"Translations Available","display_translations_text_icon":"icon-globe"}},"highwire_book_section":{"selector":0,"citation_style":"folio_book_sections_standard","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"author_site_search_path":"search\/"},"highwire_journal":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"display_orcid_tooltip":1,"author_site_search_path":"search\/"}},"cpath_prefix":"\/content","ajax_loading_icon_classes":"icon-spinner icon-spin icon-2x","ajax_loading_text":"","highlight_image_toggle":0,"more_link_label":"See more","url_parameters":{"q":"node\/56184","panels_ajax_tab_tab":"jnl_iiar_tab_info","panels_ajax_tab_trigger":"tab-article-info"}},"nid":"56184"}},"panels_accordion":{"highwire_article_accordion_container":{"heightStyle":"content","autoHeight":false,"collapsible":0,"region_accordion_id":"highwire_article_accordion_container","active":0,"animated":"slide"}},"color":{"logo":"https:\/\/ar.iiarjournals.org\/sites\/default\/files\/ar-700_wide_0.png"},"HighWireFoxycart":{"link_text":"Add to Cart (%short-price)","link_icon":""},"instances":"{\u0022highwire_abstract_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:20,\u0022height\u0022:20,\u0022border\u0022:1,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-abstract-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-abstract-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022right center\u0022,\u0022my\u0022:\u0022left center\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022shift\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter click \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}},\u0022highwire_author_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:15,\u0022height\u0022:15,\u0022border\u0022:1,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-author-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-author-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022top center\u0022,\u0022my\u0022:\u0022bottom center\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}},\u0022highwire_reflinks_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:15,\u0022height\u0022:15,\u0022border\u0022:1,\u0022mimic\u0022:\u0022top center\u0022,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-ref-link-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-ref-link-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022bottom left\u0022,\u0022my\u0022:\u0022top left\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022flip\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}}}","qtipDebug":"{\u0022leaveElement\u0022:0}","nice_menus_options":{"delay":800,"speed":"fast"},"eu_cookie_compliance":{"popup_enabled":true,"popup_agreed_enabled":false,"popup_hide_agreed":false,"popup_clicking_confirmation":true,"popup_scrolling_confirmation":false,"popup_html_info":"\u003Cdiv\u003E\n \u003Cdiv class=\u0022popup-content info\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003Ch2\u003EWe use cookies on this site to enhance your user experience\u003C\/h2\u003E\u003Cp\u003EBy clicking any link on this page you are giving your consent for us to set cookies.\u003C\/p\u003E \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022OK, I agree\u0022\n class=\u0022agree-button eu-cookie-compliance-default-button\u0022\u003EOK, I agree\u003C\/button\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022More info\u0022\n class=\u0022find-more-button eu-cookie-compliance-more-button\u0022\u003EMore info\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E","use_mobile_message":false,"mobile_popup_html_info":"\u003Cdiv\u003E\n \u003Cdiv class=\u0022popup-content info\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022OK, I agree\u0022\n class=\u0022agree-button eu-cookie-compliance-default-button\u0022\u003EOK, I agree\u003C\/button\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022More info\u0022\n class=\u0022find-more-button eu-cookie-compliance-more-button\u0022\u003EMore info\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E","mobile_breakpoint":"768","popup_html_agreed":"\u003Cdiv\u003E\n \u003Cdiv class=\u0022popup-content agreed\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003Ch2\u003EThank you for accepting cookies\u003C\/h2\u003E\u003Cp\u003EYou can now hide this message or find out more about cookies.\u003C\/p\u003E \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 class=\u0022hide-popup-button eu-cookie-compliance-hide-button\u0022\u003EHide\u003C\/button\u003E\n \u003Cbutton type=\u0022button\u0022 class=\u0022find-more-button eu-cookie-compliance-more-button-thank-you\u0022 \u003EMore info\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E","popup_use_bare_css":false,"popup_height":"auto","popup_width":"100%","popup_delay":1000,"popup_link":"\/help\/cookie-policy","popup_link_new_window":1,"popup_position":null,"popup_language":"en","store_consent":false,"better_support_for_screen_readers":0,"reload_page":0,"domain":"","popup_eu_only_js":0,"cookie_lifetime":365,"cookie_session":false,"disagree_do_not_show_popup":0,"method":"default","whitelisted_cookies":"","withdraw_markup":"\u003Cbutton type=\u0022button\u0022 class=\u0022eu-cookie-withdraw-tab\u0022\u003EPrivacy settings\u003C\/button\u003E\n\u003Cdiv class=\u0022eu-cookie-withdraw-banner\u0022\u003E\n \u003Cdiv class=\u0022popup-content info\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003Ch2\u003EWe use cookies on this site to enhance your user experience\u003C\/h2\u003E\u003Cp\u003EYou have given your consent for us to set cookies.\u003C\/p\u003E \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 class=\u0022eu-cookie-withdraw-button\u0022\u003EWithdraw consent\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n","withdraw_enabled":false},"highwireResponsive":{"enquire_enabled":1,"breakpoints_configured":1,"breakpoints":{"zero":"all and (min-width: 0px)","xsmall":"all and (min-width: 380px)","narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 980px) and (min-device-width: 980px), all and (max-device-width: 1024px) and (min-width: 1024px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}},"omega":{"layouts":{"primary":"normal","order":["narrow","normal","wide"],"queries":{"narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 980px) and (min-device-width: 980px), all and (max-device-width: 1024px) and (min-width: 1024px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}}}}); //--><!]]> </script> <!--[if lt IE 9]><script src="http://html5shiv.googlecode.com/svn/trunk/html5.js"></script><![endif]--> </head> <body class="html not-front not-logged-in page-node page-node- page-node-56184 node-type-highwire-article context-content hw-default-jcode-anticanres hw-article-type-research-article hw-article-category-experimental-studies"> <div id="skip-link"> <a href="#main-content" class="element-invisible element-focusable">Skip to main content</a> </div> <div class="page clearfix page-box-shadows footer-borders panels-page panels-layout-jcore_2col" id="page"> <header id="section-header" class="section section-header"> <div id="zone-superheader-wrapper" class="zone-wrapper zone-superheader-wrapper clearfix mobile-only print-hidden"> <div id="zone-superheader" class="zone zone-superheader clearfix mobile-only print-hidden container-30"> <div class="grid-30 region region-superheader" id="region-superheader"> <div class="region-inner region-superheader-inner"> <div class="block block-panels-mini block-responsive-menu block-panels-mini-responsive-menu odd block-without-title" id="block-panels-mini-responsive-menu"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu"> <div class="panel-panel panel-col"> <div><div id="unique-id3" class="highwire-responsive-toggle-group"><div class="panel-pane pane-panels-mini pane-responsive-menu-main-menu" > <h2 class="pane-title"><span class="icon-reorder"></span><span class="element-invisible">Main menu</span></h2> <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu_main_menu"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-menu-tree pane-main-menu" > <div class="pane-content"> <div class="menu-block-wrapper menu-block-ctools-main-menu-1 menu-name-main-menu parent-mlid-main-menu:0 menu-level-1"> <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-734" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Home</a></li> <li class="expanded menu-mlid-736" role="menuitem"><a href="/content/current" data-hide-link-title="0" class="" data-icon-position="">Current Issue</a></li> <li class="leaf menu-mlid-738" role="menuitem"><a href="/content/by/year" class="" data-icon-position="" data-hide-link-title="0">Archive</a></li> <li class="expanded menu-mlid-739" role="menuitem"><a href="/content/instructions-authors-2024" data-hide-link-title="0" class="" data-icon-position="">Info for</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-740" role="menuitem"><a href="/content/instructions-authors-2024" class="" data-icon-position="" data-hide-link-title="0">Authors</a></li> <li class="leaf menu-mlid-1535" role="menuitem"><a href="/page/https%3A//ar.iiarjournals.org/content/editorial-policies-2024" data-hide-link-title="0" class="" data-icon-position="">Editorial Policies</a></li> <li class="leaf menu-mlid-742" role="menuitem"><a href="/content/subscriptions" data-hide-link-title="0" class="" data-icon-position="">Subscribers</a></li> <li class="leaf menu-mlid-744" role="menuitem"><a href="/content/information-advertisers" data-hide-link-title="0" class="" data-icon-position="">Advertisers</a></li> <li class="leaf menu-mlid-749" role="menuitem"><a href="/node/61603/" data-hide-link-title="0" class="" data-icon-position="">Editorial Board</a></li> <li class="last leaf menu-mlid-1699" role="menuitem"><a href="/content/special-issues-2025" data-hide-link-title="0" class="" data-icon-position="">Special Issues 2025</a></li> </ul></nav></li> <li class="leaf menu-mlid-1698" role="menuitem"><a href="/content/journal-metrics" data-hide-link-title="0" class="" data-icon-position="">Journal Metrics</a></li> <li class="expanded menu-mlid-1328" role="menuitem"><a href="/feedback" data-hide-link-title="0" title="Other Publications" class="" data-icon-position="">Other Publications</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-1329" role="menuitem"><a href="//iv.iiarjournals.org/" data-hide-link-title="0" title="In Vivo" class="" data-icon-position="">In Vivo</a></li> <li class="leaf menu-mlid-1330" role="menuitem"><a href="//cgp.iiarjournals.org/" data-hide-link-title="0" title="Cancer Genomics & Proteomics" class="" data-icon-position="">Cancer Genomics & Proteomics</a></li> <li class="last leaf menu-mlid-1446" role="menuitem"><a href="http://www.cancerdiagnosisprognosis.org/" data-hide-link-title="0" target="_blank" class="" data-icon-position="">Cancer Diagnosis & Prognosis</a></li> </ul></nav></li> <li class="expanded menu-mlid-750" role="menuitem"><a href="/content/advertising" class="" data-icon-position="" data-hide-link-title="0">More</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-1331" role="menuitem"><a href="https://iiar-anticancer.org/" data-hide-link-title="0" title="IIAR" class="" data-icon-position="">IIAR</a></li> <li class="leaf menu-mlid-1327" role="menuitem"><a href="http://www.iiar-anticancer.org/conference/" data-hide-link-title="0" title="Conferences" class="" data-icon-position="">Conferences</a></li> <li class="last leaf menu-mlid-1326" role="menuitem"><a href="/help/email-alert-change-email" data-hide-link-title="0" title="2008 Nobel Laureates" class="" data-icon-position="">2008 Nobel Laureates</a></li> </ul></nav></li> <li class="last expanded menu-mlid-746" role="menuitem"><a href="/content/general-policy" data-hide-link-title="0" class="" data-icon-position="">About Us</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-747" role="menuitem"><a href="/content/general-policy" data-hide-link-title="0" class="" data-icon-position="">General Policy</a></li> <li class="last leaf menu-mlid-753" role="menuitem"><a href="/feedback" data-hide-link-title="0" title="Contact us" class="" data-icon-position="">Contact</a></li> </ul></nav></li> </ul></nav></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-menu-tree pane-umbrella-menu" > <div class="pane-content"> <div class="menu-block-wrapper menu-block-ctools-umbrella-menu-1 menu-name-umbrella-menu parent-mlid-umbrella-menu:0 menu-level-1"> <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first last expanded menu-mlid-728" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Other Publications</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-729" role="menuitem"><a href="/" data-hide-link-title="0" class="" data-icon-position="">Anticancer Research</a></li> <li class="leaf menu-mlid-1384" role="menuitem"><a href="//iv.iiarjournals.org/" data-hide-link-title="0" class="" data-icon-position="">In Vivo</a></li> <li class="last leaf menu-mlid-1385" role="menuitem"><a href="//cgp.iiarjournals.org/" data-hide-link-title="0" class="" data-icon-position="">Cancer Genomics & Proteomics</a></li> </ul></nav></li> </ul></nav></div> </div> </div> </div> </div> </div> </div> </div> <div class="panel-pane pane-panels-mini pane-responsive-menu-user-menu" > <h2 class="pane-title"><span class="icon-gear"></span><span class="element-invisible">User menu</span></h2> <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu_user_menu"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-menu-tree pane-user-menu" > <div class="pane-content"> <div class="menu-block-wrapper menu-block-ctools-user-menu-1 menu-name-user-menu parent-mlid-user-menu:0 menu-level-1"> <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-762" role="menuitem"><a href="/user/register" class="" data-icon-position="" data-hide-link-title="0">Register</a></li> <li class="leaf menu-mlid-763" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Subscribe</a></li> <li class="leaf menu-mlid-764" role="menuitem"><a href="/alerts" class="" data-icon-position="" data-hide-link-title="0">My alerts</a></li> <li class="leaf menu-mlid-765" role="menuitem"><a href="/user/login?destination=/content/39/11/5973%3Fpanels_ajax_tab_tab%3Djnl_iiar_tab_info%26panels_ajax_tab_trigger%3Dtab-article-info" class="" data-icon-position="" data-hide-link-title="0">Log in</a></li> <li class="last leaf menu-mlid-1250" role="menuitem"><a href="/cart" class="link-icon-only link-icon"><span class="icon-shopping-cart"></span> <span class="title element-invisible">My Cart</span></a></li> </ul></nav></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-user-identities" > <div class="pane-content"> <div class="highwire-user-message" data-separator="|"><span class="highwire-user-institution" data-id-type="institution" data-identity="a%3A2%3A%7Bs%3A4%3A%22show%22%3Bi%3A1%3Bs%3A7%3A%22message%22%3Bs%3A50%3A%22Institution%3A%20%5Bidentity%3Ainstitutional_display_name%5D%22%3B%7D"></span></div> </div> </div> </div> </div> </div> </div> </div> <div class="panel-pane pane-panels-mini pane-responsive-menu-search" > <h2 class="pane-title"><span class="icon-search"></span><span class="element-invisible">Search</span></h2> <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu_search"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-seach-qsearch-nocontext" > <div class="pane-content"> <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/39/11/5973/tab-article-info" method="post" id="highwire-search-qsearch-nocontext-form" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords"> <label class="element-invisible" for="quick_search_header_keywords_940013515">Search for this keyword </label> <input placeholder="Search..." type="text" id="quick_search_header_keywords_940013515" name="keywords" value="" size="60" maxlength="128" class="form-text" /> </div> <div class="button-wrapper button-mini"><span class="icon-search"></span><input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="quick_search_header_submit_1945348003" name="op" value="Search" class="form-submit" /></div><input type="hidden" name="form_build_id" value="form-IBkGhgMAoRBPXigLb4zb124l9Vc9BKTU288Crw2nOaM" /> <input type="hidden" name="form_id" value="highwire_search_qsearch_nocontext_form" /> </div></form> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-5 highwire-responsive-advanced-search-link pane-menu-tree" > <div class="pane-content"> <ul class="menu"> <li><a href="/search" title="Advanced search">Advanced search</a></li> </ul> </div> </div> </div> </div> </div> </div> </div> </div></div> </div> </div> </div> </div> </div><div class="block block-panels-mini block-hw-small-logo block-panels-mini-hw-small-logo even block-without-title" id="block-panels-mini-hw-small-logo"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panel-1col clearfix" id="mini-panel-hw_small_logo"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-small-logo" > <div class="pane-content"> <a href="/" class="" data-icon-position="" data-hide-link-title="0"><img src="https://ar.iiarjournals.org/sites/default/files/ar-350_wide.png" alt="Anticancer Research" title="Anticancer Research" /></a> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div><div id="zone-user-wrapper" class="zone-wrapper zone-user-wrapper clearfix zone-wrapper-twotone-bg mobile-hidden print-hidden"> <div id="zone-user" class="zone zone-user clearfix equal-height-container zone-twotone-bg mobile-hidden print-hidden container-30"> <div class="twotone-bg-region twotone-bg-region-first"></div> <div class="twotone-bg-region twotone-bg-region-second"></div> <div class="grid-10 region region-user-first equal-height-element" id="region-user-first"> <div class="region-inner region-user-first-inner"> <div class="block block-nice-menus block-2 block-nice-menus-2 odd block-without-title" id="block-nice-menus-2"> <div class="block-inner clearfix"> <div class="content clearfix user-menu-dropdown"> <nav class="menubar-nav"><ul class="nice-menu nice-menu-down nice-menu-umbrella-menu" id="nice-menu-2" role="menu"><li class="menu-728 menuparent menu-path-front first odd last" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Other Publications</a><ul role="menu"><li class="menu-729 menu-path-front first odd " role="menuitem"><a href="/" data-hide-link-title="0" class="" data-icon-position="">Anticancer Research</a></li> <li class="menu-1384 menu-path---iviiarjournalsorg- even " role="menuitem"><a href="//iv.iiarjournals.org/" data-hide-link-title="0" class="" data-icon-position="">In Vivo</a></li> <li class="menu-1385 menu-path---cgpiiarjournalsorg- odd last" role="menuitem"><a href="//cgp.iiarjournals.org/" data-hide-link-title="0" class="" data-icon-position="">Cancer Genomics & Proteomics</a></li> </ul></li> </ul></nav> </div> </div> </div> </div> </div><div class="grid-20 region region-user-second equal-height-element" id="region-user-second"> <div class="region-inner region-user-second-inner"> <div class="block block-panels-mini highwire-uid-string block-jnl-iiar-uid-strng block-panels-mini-jnl-iiar-uid-strng odd block-without-title" id="block-panels-mini-jnl-iiar-uid-strng"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_uid_strng"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-user-identities" > <div class="pane-content"> <div class="highwire-user-message" data-separator=" | "><span class="highwire-user-institution" data-id-type="institution" data-identity="a%3A2%3A%7Bs%3A4%3A%22show%22%3Bi%3A1%3Bs%3A7%3A%22message%22%3Bs%3A85%3A%22%3Cspan%20class%3D%22narrow-hidden%22%3EInstitution%3A%20%3C%2Fspan%3E%5Bidentity%3Ainstitutional_display_name%5D%22%3B%7D"></span></div> </div> </div> <div class="panel-pane pane-block pane-system-user-menu links inline pane-system" > <div class="pane-content"> <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="/user/register" class="" data-icon-position="" data-hide-link-title="0">Register</a></li> <li class="leaf" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Subscribe</a></li> <li class="leaf" role="menuitem"><a href="/alerts" class="" data-icon-position="" data-hide-link-title="0">My alerts</a></li> <li class="leaf" role="menuitem"><a href="/user/login?destination=/content/39/11/5973%3Fpanels_ajax_tab_tab%3Djnl_iiar_tab_info%26panels_ajax_tab_trigger%3Dtab-article-info" class="" data-icon-position="" data-hide-link-title="0">Log in</a></li> <li class="last leaf" role="menuitem"><a href="/cart" class="link-icon-only link-icon"><span class="icon-shopping-cart"></span> <span class="title element-invisible">My Cart</span></a></li> </ul></nav> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div id="zone-branding" class="zone zone-branding clearfix mobile-hidden print-display-block container-30"> <div class="grid-19 prefix-1 region region-branding print-display-block" id="region-branding"> <div class="region-inner region-branding-inner"> <div class="branding-data clearfix"> <div class="logo-img"> <a href="/" rel="home" class="" data-icon-position="" data-hide-link-title="0"><img alt="Anticancer Research" src="https://ar.iiarjournals.org/sites/default/files/ar-700_wide_0.png" /></a> </div> </div> </div> </div><div class="grid-9 suffix-1 region region-branding-second print-hidden" id="region-branding-second"> <div class="region-inner region-branding-second-inner"> <div class="block block-panels-mini block-jnl-iiar-search-box block-panels-mini-jnl-iiar-search-box odd block-without-title" id="block-panels-mini-jnl-iiar-search-box"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_search_box"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-seach-quicksearch no-margin-bottom" > <div class="pane-content"> <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/39/11/5973/tab-article-info" method="post" id="highwire-search-quicksearch-form-0" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords"> <label class="element-invisible" for="search_rightsidebar_keywords_1304473126">Search for this keyword </label> <input placeholder="search" type="text" id="search_rightsidebar_keywords_1304473126" name="keywords" value="" size="60" maxlength="128" class="form-text" /> </div> <div class="button-wrapper button-mini"><span class="icon-search"></span><input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="search_rightsidebar_submit_1265747029" name="op" value="Search" class="form-submit" /></div><input type="hidden" name="form_build_id" value="form-CJ3elpQOk5JYb0D2CQIH1BZowTTpIfnGrWxD6K6dI9U" /> <input type="hidden" name="form_id" value="highwire_search_quicksearch_form_0" /> </div></form> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-6" > <div class="pane-content"> <p><a href="/search">Advanced Search</a></p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div id="zone-menu" class="zone zone-menu clearfix mobile-hidden container-30"> <div class="grid-28 suffix-1 prefix-1 region region-menu main-menu-active-caret" id="region-menu"> <div class="region-inner region-menu-inner region-menu-bg-opaque"> <div class="block block-nice-menus block-1 block-nice-menus-1 odd block-without-title" id="block-nice-menus-1"> <div class="block-inner clearfix"> <div class="content clearfix"> <nav class="menubar-nav"><ul class="nice-menu nice-menu-down nice-menu-main-menu" id="nice-menu-1" role="menu"><li class="menu-734 menu-path-front first odd " role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Home</a></li> <li class="menu-736 menu-path-content-current even " role="menuitem"><a href="/content/current" data-hide-link-title="0" class="" data-icon-position="">Current Issue</a></li> <li class="menu-738 menu-path-content-by-year odd " role="menuitem"><a href="/content/by/year" class="" data-icon-position="" data-hide-link-title="0">Archive</a></li> <li class="menu-739 menuparent menu-path-node-1 even " role="menuitem"><a href="/content/instructions-authors-2024" data-hide-link-title="0" class="" data-icon-position="">Info for</a><ul role="menu"><li class="menu-740 menu-path-node-1 first odd " role="menuitem"><a href="/content/instructions-authors-2024" class="" data-icon-position="" data-hide-link-title="0">Authors</a></li> <li class="menu-1535 menu-path-node-75276 even " role="menuitem"><a href="/page/https%3A//ar.iiarjournals.org/content/editorial-policies-2024" data-hide-link-title="0" class="" data-icon-position="">Editorial Policies</a></li> <li class="menu-742 menu-path-node-3 odd " role="menuitem"><a href="/content/subscriptions" data-hide-link-title="0" class="" data-icon-position="">Subscribers</a></li> <li class="menu-744 menu-path-node-5 even " role="menuitem"><a href="/content/information-advertisers" data-hide-link-title="0" class="" data-icon-position="">Advertisers</a></li> <li class="menu-749 menu-path-node-61603- odd " role="menuitem"><a href="/node/61603/" data-hide-link-title="0" class="" data-icon-position="">Editorial Board</a></li> <li class="menu-1699 menu-path-node-81984 even last" role="menuitem"><a href="/content/special-issues-2025" data-hide-link-title="0" class="" data-icon-position="">Special Issues 2025</a></li> </ul></li> <li class="menu-1698 menu-path-node-81243 odd " role="menuitem"><a href="/content/journal-metrics" data-hide-link-title="0" class="" data-icon-position="">Journal Metrics</a></li> <li class="menu-1328 menuparent menu-path-node-10 even " role="menuitem"><a href="/feedback" data-hide-link-title="0" title="Other Publications" class="" data-icon-position="">Other Publications</a><ul role="menu"><li class="menu-1329 menu-path---iviiarjournalsorg- first odd " role="menuitem"><a href="//iv.iiarjournals.org/" data-hide-link-title="0" title="In Vivo" class="" data-icon-position="">In Vivo</a></li> <li class="menu-1330 menu-path---cgpiiarjournalsorg- even " role="menuitem"><a href="//cgp.iiarjournals.org/" data-hide-link-title="0" title="Cancer Genomics & Proteomics" class="" data-icon-position="">Cancer Genomics & Proteomics</a></li> <li class="menu-1446 menu-path-cancerdiagnosisprognosisorg- odd last" role="menuitem"><a href="http://www.cancerdiagnosisprognosis.org/" data-hide-link-title="0" target="_blank" class="" data-icon-position="">Cancer Diagnosis & Prognosis</a></li> </ul></li> <li class="menu-750 menuparent menu-path-node-9 odd " role="menuitem"><a href="/content/advertising" class="" data-icon-position="" data-hide-link-title="0">More</a><ul role="menu"><li class="menu-1331 menu-path-siiar-anticancerorg- first odd " role="menuitem"><a href="https://iiar-anticancer.org/" data-hide-link-title="0" title="IIAR" class="" data-icon-position="">IIAR</a></li> <li class="menu-1327 menu-path-iiar-anticancerorg-conference- even " role="menuitem"><a href="http://www.iiar-anticancer.org/conference/" data-hide-link-title="0" title="Conferences" class="" data-icon-position="">Conferences</a></li> <li class="menu-1326 menu-path-node-12 odd last" role="menuitem"><a href="/help/email-alert-change-email" data-hide-link-title="0" title="2008 Nobel Laureates" class="" data-icon-position="">2008 Nobel Laureates</a></li> </ul></li> <li class="menu-746 menuparent menu-path-node-7 even last" role="menuitem"><a href="/content/general-policy" data-hide-link-title="0" class="" data-icon-position="">About Us</a><ul role="menu"><li class="menu-747 menu-path-node-7 first odd " role="menuitem"><a href="/content/general-policy" data-hide-link-title="0" class="" data-icon-position="">General Policy</a></li> <li class="menu-753 menu-path-node-10 even last" role="menuitem"><a href="/feedback" data-hide-link-title="0" title="Contact us" class="" data-icon-position="">Contact</a></li> </ul></li> </ul></nav> </div> </div> </div><div class="block block-menu text-right block-menu-social-media block-menu-menu-social-media even block-without-title" id="block-menu-menu-social-media"> <div class="block-inner clearfix"> <div class="content clearfix"> <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="https://www.facebook.com/Anticancer-Research-115717456498174" target="_blank" class="link-icon-only link-icon"><span class="icon-facebook-sign icon-2x"></span> <span class="title element-invisible">Visit us on Facebook</span></a></li> <li class="last leaf" role="menuitem"><a href="https://www.linkedin.com/company/28898783/admin/" target="_blank" class="link-icon-only link-icon"><span class="icon-linkedin-sign icon-2x"></span> <span class="title element-invisible">Follow us on Linkedin</span></a></li> </ul></nav> </div> </div> </div> </div> </div> </div> <div id="zone-header" class="zone zone-header clearfix container-30"> </div> </header> <section id="section-content" class="section section-content"> <div id="zone-content" class="zone zone-content clearfix container-30"> <div class="grid-28 suffix-1 prefix-1 region region-content" id="region-content"> <div class="region-inner region-content-inner"> <a id="main-content"></a> <div class="block block-system block-main block-system-main odd block-without-title" id="block-system-main"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panels-960-layout jcore-2col-layout" > <div class="panel-row-wrapper panel-row-first clearfix"> <div class="top-wrapper"> <div class="panel-panel panel-region-top"> <div class="inside"><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node56184--7" data-node-nid="56184" id="top-node-56184--81018179021" data-pisa="anticanres;39/11/5973" data-pisa-master="anticanres;39/11/5973" data-apath="/anticanres/39/11/5973.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a"> <div class="highwire-cite-overline"><span class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Experimental Studies</span></span></div> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="anticanres;39/11/5973" data-atom-uri="/anticanres/39/11/5973.atom" data-request-view="full"></span></div> <h1 class="highwire-cite-title" id="page-title">Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines <em>In Vitro</em> and <em>In Vivo</em></h1> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">SACHIKO OGASAWARA</span>, <span class="highwire-citation-author" data-delta="1">YUTARO MIHARA</span>, <span class="highwire-citation-author" data-delta="2">REIICHIRO KONDO</span>, <span class="highwire-citation-author" data-delta="3">HIRONORI KUSANO</span>, <span class="highwire-citation-author" data-delta="4">JUN AKIBA</span> and <span class="highwire-citation-author" data-delta="5">HIROHISA YANO</span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">November 2019, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">5973-5982; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.21873/anticanres.13802 </span></div> <div class="highwire-cite-extras"><span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Add to Cart (%short-price)" data-apath="/anticanres/39/11/5973.atom" data-type="link" data-font-icon="" data-parent-id="56005"></span></div> </div> <div id="hw-article-author-popups-top-node-56184--81018179021" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">SACHIKO OGASAWARA </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Pathology, Kurume University School of Medicine, Kurume, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=SACHIKO%2BOGASAWARA%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=OGASAWARA%20S&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ASACHIKO%2BOGASAWARA%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-corresp-email-link last"><span>For correspondence: <a href="mailto:sachiko@med.kurume-u.ac.jp" class="" data-icon-position="" data-hide-link-title="0">sachiko@med.kurume-u.ac.jp</a></span></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">YUTARO MIHARA </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Pathology, Kurume University School of Medicine, Kurume, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=YUTARO%2BMIHARA%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=MIHARA%20Y&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AYUTARO%2BMIHARA%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">REIICHIRO KONDO </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Pathology, Kurume University School of Medicine, Kurume, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=REIICHIRO%2BKONDO%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=KONDO%20R&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AREIICHIRO%2BKONDO%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">HIRONORI KUSANO </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Pathology, Kurume University School of Medicine, Kurume, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=HIRONORI%2BKUSANO%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=KUSANO%20H&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AHIRONORI%2BKUSANO%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">JUN AKIBA </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span>Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=JUN%2BAKIBA%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=AKIBA%20J&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AJUN%2BAKIBA%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">HIROHISA YANO </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Pathology, Kurume University School of Medicine, Kurume, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=HIROHISA%2BYANO%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=YANO%20H&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AHIROHISA%2BYANO%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div></div></div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> <div class="panel-row-wrapper clearfix"> <div class="main-content-wrapper grid-17 suffix-1 alpha"> <div class="panel-panel panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-panel-tabs pane-panels-ajax-tab-tabs" > <div class="pane-content"> <div class="item-list"><ul class="tabs inline panels-ajax-tab"><li class="first"><a href="/content/39/11/5973" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_art" data-target-id="highwire_article_tabs" data-entity-context="node:56184" data-trigger="" data-url-enabled="1">Article</a><a href="/panels_ajax_tab/jnl_iiar_tab_art/node:56184/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/39/11/5973/tab-figures-data" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_data" data-target-id="highwire_article_tabs" data-entity-context="node:56184" data-trigger="tab-figures-data" data-url-enabled="1">Figures & Data</a><a href="/panels_ajax_tab/jnl_iiar_tab_data/node:56184/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/39/11/5973/tab-article-info" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_info" data-target-id="highwire_article_tabs" data-entity-context="node:56184" data-trigger="tab-article-info" data-url-enabled="1">Info & Metrics</a><a href="/panels_ajax_tab/jnl_iiar_tab_info/node:56184/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li class="last"><a href="/content/anticanres/39/11/5973.full.pdf" class="panels-ajax-tab-tab" data-panel-name="jnl_iiar_tab_pdf" data-target-id="highwire_article_tabs" data-entity-context="node:56184" data-trigger="tab-pdf" data-url-enabled="1"><i class="icon-file-alt"></i> PDF</a><a href="/panels_ajax_tab/jnl_iiar_tab_pdf/node:56184/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li></ul></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-panel-tabs-container" > <div class="pane-content"> <div data-panels-ajax-tab-preloaded="jnl_iiar_tab_info" id="panels-ajax-tab-container-highwire_article_tabs" class="panels-ajax-tab-container"><div class="panels-ajax-tab-loading" style ="display:none"><img class="loading" src="https://ar.iiarjournals.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-jnl_iiar_tab_info"><div class="panel-display panel-1col clearfix" > <div class="panel-panel panel-col"> <div><div class="panel-pane pane-panels-mini pane-jnl-iiar-art-info" > <div class="pane-content"> <div class="panel-display highwire-1col-stacked-layout" id="mini-panel-jnl_iiar_art_info"> <div class="panel-row-wrapper panel-row-first clearfix"> <div class="top-wrapper"> <div class="panel-panel panel-region-top"> <div class="inside"><div class="panel-pane pane-custom pane-4" > <h2 class="pane-title">Article Information</h2> <div class="pane-content"> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node56184" data-node-nid="56184" id="node-56184--2897245525" data-pisa="anticanres;39/11/5973" data-pisa-master="anticanres;39/11/5973" data-apath="/anticanres/39/11/5973.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-highwire-article-info clearfix"> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-volume highwire-cite-metadata">vol. 39 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">no. 11 </span><span class="highwire-cite-metadata-page-string highwire-cite-metadata">5973-5982 </span></div> </div> </div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> <div class="panel-row-wrapper clearfix"> <div class="content-wrapper"> <div class="panel-panel panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-doi" > <div class="pane-content"> <div class="field field-name-field-highwire-a-doi field-type-text field-label-inline clearfix"><div class="field-label">DOI </div><div class="field-items"><div class="field-item even"><a href="https://doi.org/10.21873/anticanres.13802" target="_blank" class="" data-icon-position="" data-hide-link-title="0">https://doi.org/10.21873/anticanres.13802</a></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-pubmed" > <div class="pane-content"> <div class="field field-name-field-highwire-article-pmid field-type-number-integer field-label-inline clearfix"><div class="field-label">PubMed </div><div class="field-items"><div class="field-item even"><a href="http://www.ncbi.nlm.nih.gov/pubmed/31704822" link_target="_blank" class="" data-icon-position="" data-hide-link-title="0">31704822</a></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-1" > <div class="pane-content"> <hr class="blank" /> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-journal-publisher" > <div class="pane-content"> <div class="field field-name-field-highwire-journal-pub field-type-text field-label-inline clearfix"><div class="field-label">Published By </div><div class="field-items"><div class="field-item even"><a href="http://www.iiarjournals.org" link_target="_blank" class="" data-icon-position="" data-hide-link-title="0">International Institute of Anticancer Research</a></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-issn" > <div class="pane-content"> <div class="field field-name-field-highwire-journal-pissn field-type-text field-label-inline clearfix"><div class="field-label">Print ISSN </div><div class="field-items"><div class="field-item even"><a href="http://www.worldcat.org/issn/0250-7005" link_target="_blank" class="" data-icon-position="" data-hide-link-title="0">0250-7005</a></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-issn" > <div class="pane-content"> <div class="field field-name-field-highwire-journal-eissn field-type-text field-label-inline clearfix"><div class="field-label">Online ISSN </div><div class="field-items"><div class="field-item even"><a href="http://www.worldcat.org/issn/1791-7530" link_target="_blank" class="" data-icon-position="" data-hide-link-title="0">1791-7530</a></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-publication-history" > <div class="pane-content"> <div class="field field-name-field-highwire-publication-history field-type-text field-label-inline clearfix"><div class="field-label">History </div><div class="field-items"><div class="field-item even"><ul class="publication-history"><li>Received October 1, 2019</li><li>Revision received October 17, 2019</li><li>Accepted October 21, 2019</li><li class="published"><span class="published-label">Published online</span> November 8, 2019.</li></ul></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-2" > <div class="pane-content"> <hr class="blank" /> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-copyright" > <div class="pane-content"> <div class="field field-name-field-highwire-copyright field-type-text field-label-inline clearfix"><div class="field-label">Copyright & Usage </div><div class="field-items"><div class="field-item even"><span class="nlm-copyright-statement" data-hwp-id="copyright-statement-1">Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved</span></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-3" > <div class="pane-content"> <hr class="blank" /> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-markup" > <h2 class="pane-title">Author Information</h2> <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div xmlns:xhtml="http://www.w3.org/1999/xhtml" class="contributors"><ol class="contributor-list" id="contrib-group-1"><li class="contributor" id="contrib-1"><span class="name">SACHIKO OGASAWARA</span><a id="xref-aff-1-1" class="xref-aff" href="#aff-1"><sup>1</sup></a><a id="xref-corresp-1-1" class="xref-up-link" href="#corresp-1"><span>⇑</span></a>, </li><li class="contributor" id="contrib-2"><span class="name">YUTARO MIHARA</span><a id="xref-aff-1-2" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-3"><span class="name">REIICHIRO KONDO</span><a id="xref-aff-1-3" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-4"><span class="name">HIRONORI KUSANO</span><a id="xref-aff-1-4" class="xref-aff" href="#aff-1"><sup>1</sup></a>, </li><li class="contributor" id="contrib-5"><span class="name">JUN AKIBA</span><a id="xref-aff-2-1" class="xref-aff" href="#aff-2"><sup>2</sup></a> and </li><li class="last" id="contrib-6"><span class="name">HIROHISA YANO</span><a id="xref-aff-1-5" class="xref-aff" href="#aff-1"><sup>1</sup></a></li></ol><ol class="affiliation-list"><li class="aff"><a id="aff-1" name="aff-1"></a><address><sup>1</sup>Department of Pathology, Kurume University School of Medicine, Kurume, Japan</address></li><li class="aff"><a id="aff-2" name="aff-2"></a><address><sup>2</sup>Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan</address></li></ol><ol class="corresp-list"><li class="corresp" id="corresp-1"> <em>Correspondence to:</em> Sachiko Ogasawara, Department of Pathology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. E-mail: <span class="em-link"><span class="em-addr">sachiko{at}med.kurume-u.ac.jp</span></span> </li></ol></div></div><a href="https://ar.iiarjournals.org/content/39/11/5973.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-altmetrics" > <h2 class="pane-title">Statistics from Altmetric.com</h2> <div class="pane-content"> <div data-badge-details="right" data-badge-type="medium-donut" data-doi="10.21873/anticanres.13802" data-hide-no-mentions="true" class="altmetric-embed"></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-cited-by" > <h2 class="pane-title">Cited By...</h2> <div class="pane-content"> <div class='highwire-list-footer'><ul class="links-with-logo"><li class="citing-isi-with-logo first"><a href="https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=hw-platform-svc&SrcAuth=WosAPI&KeyUT=WOS:000496129100014&DestLinkType=CitingArticles&DestApp=WOS_CPL" target="_blank" class="" data-icon-position="" data-hide-link-title="0"><span class="counter">43</span> Citations</a></li><li class="citing-cross-ref-with-logo"><a href="/crossref-forward-links/anticanres/39/11/5973#crossref" class="hw-crossref hw-crossref-link-ajax" data-list-wrapper="hw-crossref-list-wrapper" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="counter">40</span> Citations</a></li><li class="citing-google-scholar-with-logo last"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=citedby&path=content/39/11/5973" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Google Scholar</a></li></ul></div><div title="Crossref Cited-by Linking Search Results" style="display:none;" class="hw-crossref-list-wrapper"><p class = "hw-crossref-message">This article has been cited by the following articles in journals that are participating in Crossref Cited-by Linking.</p><div class="highwire-list-wrapper hw-crossref-linkcrossref-results highwire-article-citation-list"><div class="highwire-list"><ul><li class="first odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.bbcan.2020.188391" class="hw-crossref-link" title="Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy</a></div> <div class="highwire-cite-authors">Yan Zhao, Ya-Ni Zhang, Kai-Ting Wang, Lei Chen</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Biochimica et Biophysica Acta (BBA) - Reviews on Cancer</span> <span class="hw-cite-year">2020</span> <span class="hw-cite-volume">1874</span> <span class="hw-cite-issue">1</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1038/s41419-020-02749-7" class="hw-crossref-link" title="Anlotinib suppresses tumor progression via blocking the VEGFR2/PI3K/AKT cascade in intrahepatic cholangiocarcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Anlotinib suppresses tumor progression via blocking the VEGFR2/PI3K/AKT cascade in intrahepatic cholangiocarcinoma</a></div> <div class="highwire-cite-authors">Fei Song, Bo Hu, Jian-Wen Cheng, Yun-Fan Sun, Kai-Qian Zhou, Peng-Xiang Wang, Wei Guo, Jian Zhou, Jia Fan, Zhong Chen, Xin-Rong Yang</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cell Death & Disease</span> <span class="hw-cite-year">2020</span> <span class="hw-cite-volume">11</span> <span class="hw-cite-issue">7</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1007/s13402-021-00605-0" class="hw-crossref-link" title="MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis" target="_blank" data-icon-position="" data-hide-link-title="0">MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis</a></div> <div class="highwire-cite-authors">Ting Yu, Jiajian Yu, Lu Lu, Yize Zhang, Yadong Zhou, Yong Zhou, Fengling Huang, Lu Sun, Zhixian Guo, Guojun Hou, Zihui Dong, Bibo Wang</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cellular Oncology</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">44</span> <span class="hw-cite-issue">4</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1038/s41392-024-01823-2" class="hw-crossref-link" title="Tumor biomarkers for diagnosis, prognosis and targeted therapy" target="_blank" data-icon-position="" data-hide-link-title="0">Tumor biomarkers for diagnosis, prognosis and targeted therapy</a></div> <div class="highwire-cite-authors">Yue Zhou, Lei Tao, Jiahao Qiu, Jing Xu, Xinyu Yang, Yu Zhang, Xinyu Tian, Xinqi Guan, Xiaobo Cen, Yinglan Zhao</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Signal Transduction and Targeted Therapy</span> <span class="hw-cite-year">2024</span> <span class="hw-cite-volume">9</span> <span class="hw-cite-issue">1</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3389/fonc.2022.874473" class="hw-crossref-link" title="Efficacy and Safety of TACE Combined With Lenvatinib Plus PD-1 Inhibitors Compared With TACE Alone for Unresectable Hepatocellular Carcinoma Patients: A Prospective Cohort Study" target="_blank" data-icon-position="" data-hide-link-title="0">Efficacy and Safety of TACE Combined With Lenvatinib Plus PD-1 Inhibitors Compared With TACE Alone for Unresectable Hepatocellular Carcinoma Patients: A Prospective Cohort Study</a></div> <div class="highwire-cite-authors">Shuping Qu, Xiaobing Zhang, Yutian Wu, Yan Meng, Hongyu Pan, Qiang Fang, Lei Hu, Jin Zhang, Ruoyu Wang, Lixin Wei, Dong Wu</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Frontiers in Oncology</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">12</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3390/cancers13215583" class="hw-crossref-link" title="In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling" target="_blank" data-icon-position="" data-hide-link-title="0">In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling</a></div> <div class="highwire-cite-authors">Guilherme Ribeiro Romualdo, Kaat Leroy, Cícero Júlio Silva Costa, Gabriel Bacil Prata, Bart Vanderborght, Tereza Cristina da Silva, Luís Fernando Barbisan, Wellington Andraus, Lindsey Devisscher, Niels Olsen Saraiva Câmara, Mathieu Vinken, Bruno Cogliati</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cancers</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">13</span> <span class="hw-cite-issue">21</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1111/jfbc.14357" class="hw-crossref-link" title=" The therapeutic role of nutraceuticals targeting the Nrf2/ HO ‐1 signaling pathway in liver cancer " target="_blank" data-icon-position="" data-hide-link-title="0"> The therapeutic role of nutraceuticals targeting the Nrf2/ HO ‐1 signaling pathway in liver cancer </a></div> <div class="highwire-cite-authors">Khalid Saad Alharbi, Waleed Hassan Almalki, Mohammed Albratty, Abdulkarim M. Meraya, Asim Najmi, Govind Vyas, Sachin Kumar Singh, Kamal Dua, Gaurav Gupta</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Journal of Food Biochemistry</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">46</span> <span class="hw-cite-issue">10</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3389/fimmu.2022.946861" class="hw-crossref-link" title="Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China</a></div> <div class="highwire-cite-authors">Changying Shi, Yulong Li, Cheng Yang, Liang Qiao, Liukang Tang, Yuting Zheng, Xue Chen, Youwen Qian, Jiamei Yang, Dong Wu, Feng Xie</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Frontiers in Immunology</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">13</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1080/14737159.2021.1987217" class="hw-crossref-link" title="Predictive biomarkers for systemic therapy of hepatocellular carcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Predictive biomarkers for systemic therapy of hepatocellular carcinoma</a></div> <div class="highwire-cite-authors">Nurbubu T. Moldogazieva, Sergey P. Zavadskiy, Susanna S. Sologova, Innokenty M. Mokhosoev, Alexander A. Terentiev</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Expert Review of Molecular Diagnostics</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">21</span> <span class="hw-cite-issue">11</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3390/cells10030575" class="hw-crossref-link" title="The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects" target="_blank" data-icon-position="" data-hide-link-title="0">The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects</a></div> <div class="highwire-cite-authors">Hirotetsu Takagi, Kosuke Kaji, Norihisa Nishimura, Koji Ishida, Hiroyuki Ogawa, Hiroaki Takaya, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Akira Mitoro, Hitoshi Yoshiji</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cells</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">10</span> <span class="hw-cite-issue">3</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1111/jcmm.16363" class="hw-crossref-link" title="Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis</a></div> <div class="highwire-cite-authors">Hiroyuki Ogawa, Kosuke Kaji, Norihisa Nishimura, Hirotetsu Takagi, Koji Ishida, Hiroaki Takaya, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Hitoshi Yoshiji</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Journal of Cellular and Molecular Medicine</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">25</span> <span class="hw-cite-issue">8</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1080/21655979.2022.2074703" class="hw-crossref-link" title="Long non-coding RNA muskelin 1 antisense RNA as a potential therapeutic target in hepatocellular carcinoma treatment" target="_blank" data-icon-position="" data-hide-link-title="0">Long non-coding RNA muskelin 1 antisense RNA as a potential therapeutic target in hepatocellular carcinoma treatment</a></div> <div class="highwire-cite-authors">Xijun Chen, Qing Ye, Zhigao Chen, Qian Lin, Wen Chen, Chengrong Xie, Xiaomin Wang</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Bioengineered</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">13</span> <span class="hw-cite-issue">5</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.2174/1568009622666220428111327" class="hw-crossref-link" title="Resistance of Lenvatinib in Hepatocellular Carcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Resistance of Lenvatinib in Hepatocellular Carcinoma</a></div> <div class="highwire-cite-authors">Jinhui Guo, Junjun Zhao, Qiuran Xu, Dongsheng Huang</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Current Cancer Drug Targets</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">22</span> <span class="hw-cite-issue">11</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3389/fonc.2022.944537" class="hw-crossref-link" title="Co-administration of MDR1 and BCRP or EGFR/PI3K inhibitors overcomes lenvatinib resistance in hepatocellular carcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Co-administration of MDR1 and BCRP or EGFR/PI3K inhibitors overcomes lenvatinib resistance in hepatocellular carcinoma</a></div> <div class="highwire-cite-authors">Dawei Sun, Juan Liu, Yunfang Wang, Jiahong Dong</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Frontiers in Oncology</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">12</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.yexcr.2020.112390" class="hw-crossref-link" title="Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor" target="_blank" data-icon-position="" data-hide-link-title="0">Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor</a></div> <div class="highwire-cite-authors">Kensuke Suzuki, Hiroshi Iwai, Keita Utsunomiya, Yumiko Kono, Yoshiki Kobayashi, Dan Van Bui, Shunsuke Sawada, Yasutaka Yun, Akitoshi Mitani, Naoyuki Kondo, Tayo Katano, Noboru Tanigawa, Tomoya Akama, Akira Kanda</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Experimental Cell Research</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">398</span> <span class="hw-cite-issue">1</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3390/nano12122048" class="hw-crossref-link" title="Flower-like Composite Material Delivery of Co-Packaged Lenvatinib and Bufalin Prevents the Migration and Invasion of Cholangiocarcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Flower-like Composite Material Delivery of Co-Packaged Lenvatinib and Bufalin Prevents the Migration and Invasion of Cholangiocarcinoma</a></div> <div class="highwire-cite-authors">Zhouyu Ning, Yingke Zhao, Xia Yan, Yongqiang Hua, Zhiqiang Meng</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Nanomaterials</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">12</span> <span class="hw-cite-issue">12</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1080/17512433.2021.1958674" class="hw-crossref-link" title="Lenvatinib: established and promising drug for the treatment of advanced hepatocellular carcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib: established and promising drug for the treatment of advanced hepatocellular carcinoma</a></div> <div class="highwire-cite-authors">Martina Catalano, Andrea Casadei-Gardini, Gianmarco Vannini, Claudia Campani, Fabio Marra, Enrico Mini, Giandomenico Roviello</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Expert Review of Clinical Pharmacology</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">14</span> <span class="hw-cite-issue">11</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.taap.2021.115577" class="hw-crossref-link" title="Mitochondrial dynamics imbalance and mitochondrial dysfunction contribute to the molecular cardiotoxic effects of lenvatinib" target="_blank" data-icon-position="" data-hide-link-title="0">Mitochondrial dynamics imbalance and mitochondrial dysfunction contribute to the molecular cardiotoxic effects of lenvatinib</a></div> <div class="highwire-cite-authors">Aysenur Gunaydin Akyildiz, Tugce Boran, Ayse Tarbin Jannuzzi, Buket Alpertunga</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Toxicology and Applied Pharmacology</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">423</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.tox.2021.152951" class="hw-crossref-link" title="Lenvatinib exposure induces hepatotoxicity in zebrafish via inhibiting Wnt signaling" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib exposure induces hepatotoxicity in zebrafish via inhibiting Wnt signaling</a></div> <div class="highwire-cite-authors">Ling Huang, Jieping Liu, Wanbo Li, Fasheng Liu, Mengqi Wan, Guilan Chen, Meile Su, Chen Guo, Fang Han, Guanghua Xiong, Xinjun Liao, Huiqiang Lu, Zigang Cao</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Toxicology</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">462</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.bcp.2023.115489" class="hw-crossref-link" title="Lenvatinib inhibited HCC cell migration and invasion through regulating the transcription and ubiquitination of UHRF1 and DNMT1" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib inhibited HCC cell migration and invasion through regulating the transcription and ubiquitination of UHRF1 and DNMT1</a></div> <div class="highwire-cite-authors">Ting Fang, Zhen Jiao, Yuting You, Jiahao Cao, Chuanzheng Wang, Jingjing Liu, Wenxiu Zhao</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Biochemical Pharmacology</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">210</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1002/mc.23625" class="hw-crossref-link" title="The action and resistance mechanisms of Lenvatinib in liver cancer" target="_blank" data-icon-position="" data-hide-link-title="0">The action and resistance mechanisms of Lenvatinib in liver cancer</a></div> <div class="highwire-cite-authors">Anna Buttell, Wei Qiu</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Molecular Carcinogenesis</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">62</span> <span class="hw-cite-issue">12</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1111/cas.15743" class="hw-crossref-link" title="DKK1‐CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness" target="_blank" data-icon-position="" data-hide-link-title="0">DKK1‐CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness</a></div> <div class="highwire-cite-authors">Kosuke Iguchi, Ryota Sada, Shinji Matsumoto, Hirokazu Kimura, Yoh Zen, Masayuki Akita, Hidetoshi Gon, Takumi Fukumoto, Akira Kikuchi</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cancer Science</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">114</span> <span class="hw-cite-issue">5</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1038/s41401-022-01021-2" class="hw-crossref-link" title="Hepatocellular carcinoma cells loss lenvatinib efficacy in vitro through autophagy and hypoxia response-derived neuropilin-1 degradation" target="_blank" data-icon-position="" data-hide-link-title="0">Hepatocellular carcinoma cells loss lenvatinib efficacy in vitro through autophagy and hypoxia response-derived neuropilin-1 degradation</a></div> <div class="highwire-cite-authors">Paula Fernández-Palanca, Tania Payo-Serafín, Beatriz San-Miguel, Carolina Méndez-Blanco, María J. Tuñón, Javier González-Gallego, José L. Mauriz</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Acta Pharmacologica Sinica</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">44</span> <span class="hw-cite-issue">5</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1111/cas.15719" class="hw-crossref-link" title="Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+CD8+ T cells in HCC via blocking VEGFR2" target="_blank" data-icon-position="" data-hide-link-title="0">Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+CD8+ T cells in HCC via blocking VEGFR2</a></div> <div class="highwire-cite-authors">Zhibin Mei, Xingxing Gao, Caixu Pan, Qinchuan Wu, Shuai Wang, Junjie Qian, Zhentian Xu, Kangdi Xu, Lin Zhou, Shushen Zhen</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cancer Science</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">114</span> <span class="hw-cite-issue">4</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.ejphar.2022.175290" class="hw-crossref-link" title="Inhibition of neuropilin-1 enhances the therapeutic effects of lenvatinib in suppressing cholangiocarcinoma cells via the c-Met pathway" target="_blank" data-icon-position="" data-hide-link-title="0">Inhibition of neuropilin-1 enhances the therapeutic effects of lenvatinib in suppressing cholangiocarcinoma cells via the c-Met pathway</a></div> <div class="highwire-cite-authors">Chunning Zheng, Hongxu Wang, Shuchao Zhao, Chaoqun Ma, Hengjun Gao, Faji Yang, Xu Zhou, Jun Lu, Chunqing Zhang, Huaqiang Zhu</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">European Journal of Pharmacology</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">935</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3390/cancers13246310" class="hw-crossref-link" title="Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib" target="_blank" data-icon-position="" data-hide-link-title="0">Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib</a></div> <div class="highwire-cite-authors">Marie Decraecker, Caroline Toulouse, Jean-Frédéric Blanc</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cancers</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">13</span> <span class="hw-cite-issue">24</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1007/s12072-023-10484-2" class="hw-crossref-link" title="Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma</a></div> <div class="highwire-cite-authors">Ryo Ito, Koji Miyanishi, Tomohiro Kubo, Kota Hamaguchi, Takahiro Osuga, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Toru Mizuguchi, Ichiro Takemasa, Junji Kato</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Hepatology International</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">17</span> <span class="hw-cite-issue">3</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.4251/wjgo.v13.i12.2076" class="hw-crossref-link" title="Prospect of lenvatinib for unresectable hepatocellular carcinoma in the new era of systemic chemotherapy" target="_blank" data-icon-position="" data-hide-link-title="0">Prospect of lenvatinib for unresectable hepatocellular carcinoma in the new era of systemic chemotherapy</a></div> <div class="highwire-cite-authors">Takuya Sho, Kenichi Morikawa, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Mugumi Kimura, Masato Nakai, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">World Journal of Gastrointestinal Oncology</span> <span class="hw-cite-year">2021</span> <span class="hw-cite-volume">13</span> <span class="hw-cite-issue">12</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.2174/0115680266261150231110053650" class="hw-crossref-link" title="To Investigate Growth Factor Receptor Targets and Generate Cancer Targeting Inhibitors" target="_blank" data-icon-position="" data-hide-link-title="0">To Investigate Growth Factor Receptor Targets and Generate Cancer Targeting Inhibitors</a></div> <div class="highwire-cite-authors">Debroop Basu, Riya Pal, Maitrayee Sarkar, Soubhik Barma, Sumit Halder, Harekrishna Roy, Sisir Nandi, Asmita Samadder</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Current Topics in Medicinal Chemistry</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">23</span> <span class="hw-cite-issue">30</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3390/ijms23031667" class="hw-crossref-link" title="Antitumor Effect of Regorafenib on MicroRNA Expression in Hepatocellular Carcinoma Cell Lines" target="_blank" data-icon-position="" data-hide-link-title="0">Antitumor Effect of Regorafenib on MicroRNA Expression in Hepatocellular Carcinoma Cell Lines</a></div> <div class="highwire-cite-authors">Kei Takuma, Shintaro Fujihara, Koji Fujita, Hisakazu Iwama, Mai Nakahara, Kyoko Oura, Tomoko Tadokoro, Shima Mimura, Joji Tani, Tingting Shi, Asahiro Morishita, Hideki Kobara, Takashi Himoto, Tsutomu Masaki</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">International Journal of Molecular Sciences</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">23</span> <span class="hw-cite-issue">3</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1186/s43556-024-00184-0" class="hw-crossref-link" title="Signaling pathways in liver cancer: pathogenesis and targeted therapy" target="_blank" data-icon-position="" data-hide-link-title="0">Signaling pathways in liver cancer: pathogenesis and targeted therapy</a></div> <div class="highwire-cite-authors">Yangtao Xue, Yeling Ruan, Yali Wang, Peng Xiao, Junjie Xu</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Molecular Biomedicine</span> <span class="hw-cite-year">2024</span> <span class="hw-cite-volume">5</span> <span class="hw-cite-issue">1</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.3892/br.2022.1561" class="hw-crossref-link" title="Effect of Lenvatinib treatment on the cell cycle and microRNA profile in hepatocellular carcinoma cells" target="_blank" data-icon-position="" data-hide-link-title="0">Effect of Lenvatinib treatment on the cell cycle and microRNA profile in hepatocellular carcinoma cells</a></div> <div class="highwire-cite-authors">Mai Nakahara, Shintaro Fujihara, Hisakazu Iwama, Kei Takuma, Kyoko Oura, Tomoko Tadokoro, Koji Fujita, Joji Tani, Asahiro Morishita, Hideki Kobara, Takashi Himoto, Tsutomu Masaki</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Biomedical Reports</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">17</span> <span class="hw-cite-issue">4</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.intimp.2023.110373" class="hw-crossref-link" title="Emerging roles of tyrosine kinases in hepatic inflammatory diseases and therapeutic opportunities" target="_blank" data-icon-position="" data-hide-link-title="0">Emerging roles of tyrosine kinases in hepatic inflammatory diseases and therapeutic opportunities</a></div> <div class="highwire-cite-authors">Mohamed E. Shaker, Hesham A.M. Gomaa, Mohamed A. Abdelgawad, Mohamed El-Mesery, Ahmed A. Shaaban, Sara H. Hazem</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">International Immunopharmacology</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">120</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.lungcan.2024.107557" class="hw-crossref-link" title="Long-term follow-up and exploratory analysis of lenvatinib in patients with metastatic or recurrent thymic carcinoma: Results from the multicenter, phase 2 REMORA trial" target="_blank" data-icon-position="" data-hide-link-title="0">Long-term follow-up and exploratory analysis of lenvatinib in patients with metastatic or recurrent thymic carcinoma: Results from the multicenter, phase 2 REMORA trial</a></div> <div class="highwire-cite-authors">Seiji Niho, Jun Sato, Miyako Satouchi, Shoichi Itoh, Yusuke Okuma, Hidenori Mizugaki, Haruyasu Murakami, Yasuhito Fujisaka, Toshiyuki Kozuki, Kenichi Nakamura, Ryunosuke Machida, Yuichiro Ohe, Toshiyuki Tamai, Hiroki Ikezawa, Noboru Yamamoto</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Lung Cancer</span> <span class="hw-cite-year">2024</span> <span class="hw-cite-volume">191</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.2957/kanzo.63.238" class="hw-crossref-link" title="Ruptured hepatocellular carcinoma following administration of Lenvatinib: an autopsy case" target="_blank" data-icon-position="" data-hide-link-title="0">Ruptured hepatocellular carcinoma following administration of Lenvatinib: an autopsy case</a></div> <div class="highwire-cite-authors">Kumichika Uchida, Toru Aoyama, Yuji Terai, Naomi Yamaguchi, Shingo Kato, Koji Yakabi, Jun Kikuchi, Sachiko Ogasawara, Hirohisa Yano, Sumiko Nagoshi</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Kanzo</span> <span class="hw-cite-year">2022</span> <span class="hw-cite-volume">63</span> <span class="hw-cite-issue">5</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.lungcan.2023.107193" class="hw-crossref-link" title="Tumor response like pseudo-progression to lenvatinib in advanced thymic carcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Tumor response like pseudo-progression to lenvatinib in advanced thymic carcinoma</a></div> <div class="highwire-cite-authors">Koki Ito, Ou Yamaguchi, Kyoichi Kaira, Hisao Imai, Hiroshi Kagamu</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Lung Cancer</span> <span class="hw-cite-year">2023</span> <span class="hw-cite-volume">179</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.biomaterials.2024.122778" class="hw-crossref-link" title="A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer" target="_blank" data-icon-position="" data-hide-link-title="0">A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer</a></div> <div class="highwire-cite-authors">Dan Wang, Wenqi Ma, Yuanyuan Zhang, Yufeng Wang, Lei Sun, Jue Jiang, Lianying Jiao, Runqing Li, Yujie Zhang, Mingzhen Zhang, Qi Zhou</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Biomaterials</span> <span class="hw-cite-year">2025</span> <span class="hw-cite-volume">313</span> </div></div></div></li><li class="even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1158/2767-9764.CRC-24-0304" class="hw-crossref-link" title="Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone" target="_blank" data-icon-position="" data-hide-link-title="0">Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone</a></div> <div class="highwire-cite-authors">Stefan Maksimovic, Nina C. Boscolo, Ludovica La Posta, Sergio Barrios, Mohammad Jad Moussa, Emanuela Gentile, Pedro I. Pesquera, Wenjiao Li, Jianfeng Chen, Javier A. Gomez, Akshay Basi, Jared K. Burks, Christopher Alvarez-Breckenridge, Jianjun Gao, Matthew T. Campbell, Eleonora Dondossola</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Cancer Research Communications</span> <span class="hw-cite-year">2024</span> <span class="hw-cite-volume">4</span> <span class="hw-cite-issue">10</span> </div></div></div></li><li class="odd"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1016/j.ijpharm.2024.124537" class="hw-crossref-link" title="Biotinylated polyaminoacid-based nanoparticles for the targeted delivery of lenvatinib towards hepatocarcinoma" target="_blank" data-icon-position="" data-hide-link-title="0">Biotinylated polyaminoacid-based nanoparticles for the targeted delivery of lenvatinib towards hepatocarcinoma</a></div> <div class="highwire-cite-authors">Paola Varvarà, Salvatore Emanuele Drago, Emanuela Esposito, Michela Campolo, Nicolò Mauro, Giovanna Calabrese, Sabrina Conoci, Dario Morganti, Barbara Fazio, Gaetano Giammona, Giovanna Pitarresi</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">International Journal of Pharmaceutics</span> <span class="hw-cite-year">2024</span> <span class="hw-cite-volume">662</span> </div></div></div></li><li class="last even"><div class = "highwire-article-citation"><div class="highwire-cite cite-type-journal"><div class="highwire-cite-title"><a href="https://dx.doi.org/10.1177/03008916241261484" class="hw-crossref-link" title="Personalized treatment using predictive biomarkers in solid organ malignancies: A review" target="_blank" data-icon-position="" data-hide-link-title="0">Personalized treatment using predictive biomarkers in solid organ malignancies: A review</a></div> <div class="highwire-cite-authors">Haoming Tang, Yi Xin Li, Jun Jie Lian, Hsin-Yueh Ng, Samuel Sherng Young Wang</div> <div class="highwire-cite-metadata"><span class="hw-cite-journal-title">Tumori Journal</span> <span class="hw-cite-year">2024</span> <span class="hw-cite-volume">110</span> <span class="hw-cite-issue">5</span> </div></div></div></li></ul></div></div></div> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-node-pager" > <div class="pane-content"> <div class="pager highwire-pager pager-mini clearfix highwire-node-pager highwire-article-pager"><span class="pager-prev"><a href="/content/39/11/5963" title="Identification of Matrix Metalloproteinase 11 as a Prognostic Biomarker in Pancreatic Cancer" rel="prev" class="pager-link-prev link-icon"><span class="icon-circle-arrow-left"></span> <span class="title">Previous</span></a></span><span class="pager-next"><a href="/content/39/11/5983" title="DJ-1 Contributes to Self-renewal of Stem Cells in the U87-MG Glioblastoma Cell Line" rel="next" class="pager-link-next link-icon-right link-icon"><span class="title">Next</span> <span class="icon-circle-arrow-right"></span></a></span></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-back-to-top" > <div class="pane-content"> <a href="#page" class="back-to-top" data-icon-position="" data-hide-link-title="0"><span class="icon-chevron-up"></span> Back to top</a> </div> </div> </div> </div> </div> <div class="sidebar-right-wrapper grid-10 omega"> <div class="panel-panel panel-region-sidebar-right"> <div class="inside"><div class="panel-pane pane-panels-mini pane-jnl-iiar-art-issue pane-style-alt-content" > <h2 class="pane-title">In this issue</h2> <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_art_issue"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-issue node56005" data-node-nid="56005" id="node-56005--2819333359" data-pisa="anticanres;39/11" data-pisa-master="anticanres;39/11" data-apath="/anticanres/39/11.atom"><div class="highwire-cite highwire-cite-highwire-issue highwire-citation-jcore-issue-widget clearfix"> <div class="highwire-cite-highlight"><a href="/content/39/11" class="highlight-image-linked"><img class="highlight-image" src="https://ar.iiarjournals.org/sites/default/files/styles/medium/public/highwire/default/covers/acr_default_cover_0.gif?itok=tOivawbp" alt="Anticancer Research: 39 (11)" /></a></div> <div class="highwire-cite-col"> <a href="/content/39/11" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">Anticancer Research</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 39</span>, <span class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 11 </span><div class="highwire-cite-metadata-pubdate highwire-cite-metadata">November 2019 </div></div> <div class="highwire-cite-extras"><div class='highwire-article-citation-variant-list'><ul class="links variants-list"><li class="toc first"><a href="/content/39/11.toc" class="highwire-variant-link variant-toc " title="Table of Contents" rel="alternate" type="text/html" data-icon-position="" data-hide-link-title="0">Table of Contents</a></li><li class="tocpdf"><a href="/content/39/11.toc.pdf" class="highwire-variant-link variant-tocpdf " title="Table of Contents (PDF)" rel="alternate" type="application/pdf" data-icon-position="" data-hide-link-title="0">Table of Contents (PDF)</a></li><li class="index-by-author"><a href="/content/39/11.index-by-author" class="highwire-variant-link variant-index-by-author " title="Index by author" rel="alternate" data-icon-position="" data-hide-link-title="0">Index by author</a></li><li class="enclosure-back-matter"><a href="/content/anticanres/39/11/local/back-matter.pdf" class="highwire-variant-link variant-enclosure" title="Back Matter (PDF)" rel="alternative" data-icon-position="" data-hide-link-title="0">Back Matter (PDF)</a></li><li class="enclosure-ed-board"><a href="/content/anticanres/39/11/local/ed-board.pdf" class="highwire-variant-link variant-enclosure" title="Ed Board (PDF)" rel="alternative" data-icon-position="" data-hide-link-title="0">Ed Board (PDF)</a></li><li class="enclosure-front-matter last"><a href="/content/anticanres/39/11/local/front-matter.pdf" class="highwire-variant-link variant-enclosure" title="Front Matter (PDF)" rel="alternative" data-icon-position="" data-hide-link-title="0">Front Matter (PDF)</a></li></ul></div></div> </div> </div></div> </div> </div> </div> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-iiar-art-tools" > <div class="pane-content"> <div id="mini-panel-jnl_iiar_art_tools" class="highwire-2col-stacked panel-display"> <div class="panel-row-wrapper clearfix"> <div class="content-left-wrapper content-column"> <div class="panel-panel panel-region-content-left"> <div class="inside"><div class="panel-pane pane-highwire-variant-link" > <div class="pane-content"> <a href="/content/anticanres/39/11/5973.full-text.print" target="_blank" rel="nofollow" class="link-icon"><span class="icon-print"></span> <span class="title">Print</span></a> </div> </div> <div class="panel-pane pane-highwire-variant-link text-no-wrap" > <div class="pane-content"> <a href="/content/anticanres/39/11/5973.full-text.pdf" target="_blank" class="link-icon"><span class="icon-download-alt"></span> <span class="title">Download PDF</span></a> </div> </div> <div class="panel-pane pane-minipanel-dialog-link pane-jnl-iiar-art-alert" > <div class="pane-content"> <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger link-icon" title="Alerts for this Article"><span class="icon-exclamation-sign"></span> <span class="title">Article Alerts</span></a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_art_alert"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-article-add-form" > <div class="pane-content"> <div id = "alerts-form-wrapper"><form action="/content/39/11/5973/tab-article-info" method="post" id="highwire-user-opportunity-login" accept-charset="UTF-8"><div><div class="form-item form-item-label-before form-type-textfield form-item-name"> <label for="edit-name">User Name <span class="form-required" title="This field is required.">*</span></label> <input type="text" id="edit-name" name="name" value="" size="60" maxlength="128" class="form-text required" /> </div> <div class="form-item form-item-label-before form-type-password form-item-pass"> <label for="edit-pass">Password <span class="form-required" title="This field is required.">*</span></label> <input type="password" id="edit-pass" name="pass" size="60" maxlength="128" class="form-text required" /> </div> <div id="alerts_email">Sign In to Email Alerts with your Email Address</div><div class="form-item form-item-label-before form-type-textfield form-item-highwire-alerts-email"> <label for="edit-highwire-alerts-email">Email <span class="form-required" title="This field is required.">*</span></label> <input type="text" id="edit-highwire-alerts-email" name="highwire_alerts_email" value="" size="60" maxlength="128" class="form-text required" /> </div> <input type="submit" id="edit-submit--3" name="op" value="Submit" class="form-submit" /><input type="hidden" name="form_build_id" value="form-y-Z_Gl-p3DQ1VgFZgqSaRh0BQgXVUmX8BH1SubD6ddI" /> <input type="hidden" name="form_id" value="highwire_alerts_article_sign_up_form" /> <input type="hidden" name="current_path" value="content/39/11/5973/tab-article-info" /> </div></form></div> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-pane pane-minipanel-dialog-link pane-jnl-iiar-art-email" > <div class="pane-content"> <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger link-icon" title="Email this Article"><span class="icon-envelope"></span> <span class="title">Email Article</span></a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_art_email"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-block pane-forward-form pane-forward" > <div class="pane-content"> <form action="/content/39/11/5973/tab-article-info" method="post" id="forward-form" accept-charset="UTF-8"><div><div id="edit-instructions" class="form-item form-item-label-before form-type-item"> <p>Thank you for your interest in spreading the word on Anticancer Research.</p><p>NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.</p> </div> <div class="form-item form-item-label-before form-type-textfield form-item-email"> <label for="edit-email">Your Email <span class="form-required" title="This field is required.">*</span></label> <input type="text" id="edit-email" name="email" value="" size="58" maxlength="256" class="form-text required" /> </div> <div class="form-item form-item-label-before form-type-textfield form-item-name"> <label for="edit-name--2">Your Name <span class="form-required" title="This field is required.">*</span></label> <input type="text" id="edit-name--2" name="name" value="" size="58" maxlength="256" class="form-text required" /> </div> <div class="form-item form-item-label-before form-type-textarea form-item-recipients"> <label for="edit-recipients">Send To <span class="form-required" title="This field is required.">*</span></label> <div class="form-textarea-wrapper resizable"><textarea id="edit-recipients" name="recipients" cols="50" rows="5" class="form-textarea required"></textarea></div> <div class="description">Enter multiple addresses on separate lines or separate them with commas.</div> </div> <div id="edit-page" class="form-item form-item-label-before form-type-item"> <label for="edit-page">You are going to email the following </label> <a href="/content/39/11/5973" class="active" data-icon-position="" data-hide-link-title="0">Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo</a> </div> <div id="edit-subject" class="form-item form-item-label-before form-type-item"> <label for="edit-subject">Message Subject </label> (Your Name) has sent you a message from Anticancer Research </div> <div id="edit-body" class="form-item form-item-label-before form-type-item"> <label for="edit-body">Message Body </label> (Your Name) thought you would like to see the Anticancer Research web site. </div> <div class="form-item form-item-label-before form-type-textarea form-item-message"> <label for="edit-message--2">Your Personal Message </label> <div class="form-textarea-wrapper resizable"><textarea id="edit-message--2" name="message" cols="50" rows="10" class="form-textarea"></textarea></div> </div> <input type="hidden" name="path" value="node/56184" /> <input type="hidden" name="path_cid" value="" /> <input type="hidden" name="forward_footer" value="" /> <input type="hidden" name="form_build_id" value="form-xKeV5auuKzIOXQ47ZKv7Chnq-Ay2BTWnk6dJ9IowneQ" /> <input type="hidden" name="form_id" value="forward_form" /> <fieldset class="captcha form-wrapper"><legend><span class="fieldset-legend">CAPTCHA</span></legend><div class="fieldset-wrapper"><div class="fieldset-description">This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.</div><input type="hidden" name="captcha_sid" value="304029800" /> <input type="hidden" name="captcha_token" value="724f016c4f59df55d7ac7c2316cfb962" /> <div class="form-item form-item-label-before form-type-textfield form-item-captcha-response"> <label for="edit-captcha-response">Math question <span class="form-required" title="This field is required.">*</span></label> <span class="field-prefix">5 + 14 = </span> <input type="text" id="edit-captcha-response" name="captcha_response" value="" size="4" maxlength="2" class="form-text required" /> <div class="description">Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.</div> </div> </div></fieldset> <div class="form-actions form-wrapper" id="edit-actions"><input type="submit" id="edit-submit--4" name="op" value="Send Message" class="form-submit" /></div></div></form> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-pane pane-minipanel-dialog-link pane-jnl-iiar-cite-tool" > <div class="pane-content"> <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/highwire/citation/56184/download" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger link-icon" title="Citation Tools"><span class="icon-globe"></span> <span class="title">Citation Tools</span></a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_cite_tool"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-citation-export" > <div class="pane-content"> <div class="highwire-citation-export"> <div class="highwire-citation-info"> <div class="highwire-article-citation highwire-citation-type-highwire-article cite-tool-node56184--3" data-node-nid="56184" id="citation-node-56184--4586059455" data-pisa="anticanres;39/11/5973" data-pisa-master="anticanres;39/11/5973" data-apath="/anticanres/39/11/5973.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard clearfix"> <div class="highwire-cite-title">Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines <em>In Vitro</em> and <em>In Vivo</em></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">SACHIKO</span> <span class="nlm-surname">OGASAWARA</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">YUTARO</span> <span class="nlm-surname">MIHARA</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">REIICHIRO</span> <span class="nlm-surname">KONDO</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">HIRONORI</span> <span class="nlm-surname">KUSANO</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">JUN</span> <span class="nlm-surname">AKIBA</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">HIROHISA</span> <span class="nlm-surname">YANO</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">Nov 2019, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">5973-5982; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.21873/anticanres.13802 </span></div> </div> </div> </div> <div class="highwire-citation-formats"> <h2>Citation Manager Formats</h2> <div class="highwire-citation-formats-links"> <span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.spage=5973&rft.epage=5982&rft.atitle=Antiproliferative%20Effect%20of%20Lenvatinib%20on%20Human%20Liver%20Cancer%20Cell%20Lines%20In%20Vitro%20and%20In%20Vivo&rft.volume=39&rft.issue=11&rft.date=2019-11-01%2000%3A00%3A00&rft.stitle&rft.jtitle=Anticancer%20Research&rft.au=OGASAWARA%2C+SACHIKO&rft.au=MIHARA%2C+YUTARO&rft.au=KONDO%2C+REIICHIRO&rft.au=KUSANO%2C+HIRONORI&rft.au=AKIBA%2C+JUN&rft.au=YANO%2C+HIROHISA"></span><ul class="hw-citation-links inline button button-alt button-grid clearfix"><li class="bibtext first"><a href="/highwire/citation/56184/bibtext" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">BibTeX</a></li><li class="bookends"><a href="/highwire/citation/56184/bookends" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Bookends</a></li><li class="easybib"><a href="/highwire/citation/56184/easybib" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EasyBib</a></li><li class="endnote-tagged"><a href="/highwire/citation/56184/endnote-tagged" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EndNote (tagged)</a></li><li class="endnote-8-xml"><a href="/highwire/citation/56184/endnote-8-xml" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EndNote 8 (xml)</a></li><li class="medlars"><a href="/highwire/citation/56184/medlars" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Medlars</a></li><li class="mendeley"><a href="/highwire/citation/56184/mendeley" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Mendeley</a></li><li class="papers"><a href="/highwire/citation/56184/papers" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Papers</a></li><li class="refworks-tagged"><a href="/highwire/citation/56184/refworks-tagged" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">RefWorks Tagged</a></li><li class="reference-manager"><a href="/highwire/citation/56184/reference-manager" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Ref Manager</a></li><li class="ris"><a href="/highwire/citation/56184/ris" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">RIS</a></li><li class="zotero last"><a href="/highwire/citation/56184/zotero" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Zotero</a></li></ul> </div> </div> </div> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-pane pane-highwire-permission-link" > <div class="pane-content"> <a href="https://www.copyright.com/openurl.do?contentIdType=doi&issn=17917530&contentId=10.21873/anticanres.13802" target="_blank" class="highwire-permission-link link-icon"><span class="icon-copyright"></span> <span class="title">Reprints and Permissions</span></a> </div> </div> </div> </div> </div> <div class="content-right-wrapper content-column"> <div class="panel-panel panel-region-content-right"> <div class="inside"><div class="panel-pane pane-highwire-share-link highwire_clipboard_link_ajax" id="shareit"> <div class="pane-content"> <a href="/" class="link-icon"><span class="icon-share-alt"></span> <span class="title">Share</span></a> </div> </div> <div class="panel-pane pane-panels-mini pane-jnl-iiar-share highwire_clipboard_form_ajax_shareit" > <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_share"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-article-citation large-margin-bottom" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node56184--5" data-node-nid="56184" id="share-node-56184--6424942881" data-pisa="anticanres;39/11/5973" data-pisa-master="anticanres;39/11/5973" data-apath="/anticanres/39/11/5973.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard clearfix"> <div class="highwire-cite-title">Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines <em>In Vitro</em> and <em>In Vivo</em></div> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">SACHIKO</span> <span class="nlm-surname">OGASAWARA</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">YUTARO</span> <span class="nlm-surname">MIHARA</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">REIICHIRO</span> <span class="nlm-surname">KONDO</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">HIRONORI</span> <span class="nlm-surname">KUSANO</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">JUN</span> <span class="nlm-surname">AKIBA</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">HIROHISA</span> <span class="nlm-surname">YANO</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">Nov 2019, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">39 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">5973-5982; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.21873/anticanres.13802 </span></div> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-article-clipboard-copy large-margin-bottom" > <div class="pane-content"> <div class = "clipboard-copy"> <span class="label-url"> <label for="dynamic">Share This Article:</label> </span> <span class="input-text-url"> <input type="text" id="dynamic" value="https://ar.iiarjournals.org/content/39/11/5973" size="50"/> </span> <span class="copy-button button"> <button id="copy-dynamic" class="clipboardjs-button" data-clipboard-target="#dynamic" data-clipboard-alert-style="tooltip" data-clipboard-alert-text="Copied!">Copy</button> </span> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-service-links" > <div class="pane-content"> <div class="service-links"><a href="https://twitter.com/share?url=https%3A//ar.iiarjournals.org/content/39/11/5973&text=Antiproliferative%20Effect%20of%20Lenvatinib%20on%20Human%20Liver%20Cancer%20Cell%20Lines%20In%20Vitro%20and%20In%20Vivo" id="twitter" title="Share this on Twitter" class="service-links-twitter" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="https://ar.iiarjournals.org/sites/all/modules/highwire/highwire/images/twitter.png" alt="Twitter logo" /></a> <a href="https://www.facebook.com/sharer.php?u=https%3A//ar.iiarjournals.org/content/39/11/5973&t=Antiproliferative%20Effect%20of%20Lenvatinib%20on%20Human%20Liver%20Cancer%20Cell%20Lines%20In%20Vitro%20and%20In%20Vivo" id="facebook" title="Share on Facebook" class="service-links-facebook" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="https://ar.iiarjournals.org/sites/all/modules/highwire/highwire/images/fb-blue.png" alt="Facebook logo" /></a> <a href="http://www.mendeley.com/import/?url=https%3A//ar.iiarjournals.org/content/39/11/5973&title=Antiproliferative%20Effect%20of%20Lenvatinib%20on%20Human%20Liver%20Cancer%20Cell%20Lines%20In%20Vitro%20and%20In%20Vivo" id="mendeley" title="Share on Mendeley" class="service-links-mendeley" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="https://ar.iiarjournals.org/sites/all/modules/highwire/highwire/images/mendeley.png" alt="Mendeley logo" /></a></div> </div> </div> </div> </div> </div> </div> </div> <div class="panel-pane pane-service-links" > <div class="pane-content"> <div class="service-links"><div class="item-list"><ul><li class="first"><a href="https://twitter.com/share?url=https%3A//ar.iiarjournals.org/content/39/11/5973&count=horizontal&via=&text=Antiproliferative%20Effect%20of%20Lenvatinib%20on%20Human%20Liver%20Cancer%20Cell%20Lines%20In%20Vitro%20and%20In%20Vivo&counturl=https%3A//ar.iiarjournals.org/content/39/11/5973" class="twitter-share-button service-links-twitter-widget" id="twitter_widget" title="Tweet This" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Tweet Widget</span></a></li><li><a href="https://www.facebook.com/plugins/like.php?href=https%3A//ar.iiarjournals.org/content/39/11/5973&layout=button_count&show_faces=false&action=like&colorscheme=light&width=100&height=21&font=&locale=" id="facebook_like" title="I Like it" class="service-links-facebook-like" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Facebook Like</span></a></li><li class="last"><a href="https://ar.iiarjournals.org/content/39/11/5973" id="google_plus_one" title="Plus it" class="service-links-google-plus-one" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Google Plus One</span></a></li></ul></div></div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-article-nav mobile-hidden pane-style-alt-content" > <h2 class="pane-title">Jump to section</h2> <div class="pane-content"> <div class="highwire-list-wrapper highwire-article-nav highwire-nav-float"><div class="highwire-list"><ul data-highwire-float="1" data-highwire-float-class="grid-10 alpha omega"><li class="parent first odd"><a href="/content/39/11/5973" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_art" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Article</a><div class="highwire-list"><ul><li class="first odd"><a href="#abstract-1" class="highwire-article-nav-jumplink first" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">Abstract</a></li><li class="even"><a href="#sec-1" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">Materials and Methods</a></li><li class="odd"><a href="#sec-2" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">Results</a></li><li class="even"><a href="#sec-3" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">Discussion</a></li><li class="odd"><a href="#ack-1" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">Acknowledgements</a></li><li class="even"><a href="#fn-group-1" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">Footnotes</a></li><li class="last odd"><a href="#ref-list-1" class="highwire-article-nav-jumplink last" data-panel-ajax-tab="jnl_iiar_tab_art" data-icon-position="" data-hide-link-title="0">References</a></li></ul></div></li><li class="even"><a href="/content/39/11/5973/tab-figures-data" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_data" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Figures & Data</a></li><li class="odd"><a href="/content/39/11/5973/tab-article-info" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_iiar_tab_info" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Info & Metrics</a></li><li class="last even"><a href="/content/39/11/5973.full.pdf" class="highwire-article-nav-jumplink" data-icon-position="" data-hide-link-title="0"><i class="icon-file-alt"></i> PDF</a></li></ul></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-iiar-accordion" > <div class="pane-content"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_accordion"> <div class="panel-panel panel-col"> <div><div id="highwire_article_accordion_container"><h3 ><i class="icon-caret-right"></i> Related Articles</h3><div><div class="highwire-list highwire-related-articles highwire-article-citation-list"><ul class="highwire-related-articles-list"><li class="first last odd"><div class="no-results">No related articles found.</div></li></ul></div><div class='highwire-list-footer'><div class="highwire-related-articles-footer"><ul class="links inline"><li class="related-pubmed first"><a href="/lookup/external-ref?link_type=MED_NBRS&access_num=31704822" target="_blank" class="" data-icon-position="" data-hide-link-title="0">PubMed</a></li><li class="related-google-scholar last"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=related&author%5B0%5D=SACHIKO%2BOGASAWARA&author%5B1%5D=YUTARO%2BMIHARA&author%5B2%5D=REIICHIRO%2BKONDO&author%5B3%5D=HIRONORI%2BKUSANO&author%5B4%5D=JUN%2BAKIBA&author%5B5%5D=HIROHISA%2BYANO&title=Antiproliferative%2BEffect%2Bof%2BLenvatinib%2Bon%2BHuman%2BLiver%2BCancer%2BCell%2BLines%2BIn%2BVitro%2Band%2BIn%2BVivo&publication_year=2019&path=content/39/11/5973" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Google Scholar</a></li></ul></div></div></div><h3 ><i class="icon-caret-right"></i> Cited By...</h3><div><div class="highwire-list highwire-cited-by"><ul><li class="first last odd"><a href="http://cgp.iiarjournals.org/cgi/content/full/21/3/260" class="" data-icon-position="" data-hide-link-title="0"><div class="highwire-cite-title">Genetic Analyses of Primary Liver Cancer Cell Lines: Correspondence With Morphological Features of Original Tumors</div></a><div class="variant-links"></div></li></ul></div><div class='highwire-list-footer'><ul class="links inline"><li class="citing-google-scholar first last"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=citedby&path=content/39/11/5973" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Google Scholar</a></li></ul></div></div><h3 ><i class="icon-caret-right"></i> More in this TOC Section</h3><div><div class="highwire-list highwire-article-citation-list"><ul><li class="first odd"><div class="highwire-article-citation highwire-citation-type-highwire-article node82116" data-node-nid="82116" id="node-82116--2770046271" data-pisa="anticanres;44/11/4789" data-pisa-master="anticanres;44/11/4789" data-apath="/anticanres/44/11/4789.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard-title-only clearfix"> <a href="/content/44/11/4789" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">Compound #41 Targets Acute Myelogenous Leukemia by Inhibiting the Wnt/β-catenin Signaling Pathway</span></a> </div> </div></li><li class="even"><div class="highwire-article-citation highwire-citation-type-highwire-article node82135" data-node-nid="82135" id="node-82135--22092531152" data-pisa="anticanres;44/11/4857" data-pisa-master="anticanres;44/11/4857" data-apath="/anticanres/44/11/4857.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard-title-only clearfix"> <a href="/content/44/11/4857" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">PAR1 Is a Candidate Target for the Treatment of Peritoneal Dissemination in Gastric Cancer</span></a> </div> </div></li><li class="last odd"><div class="highwire-article-citation highwire-citation-type-highwire-article node81989" data-node-nid="81989" id="node-81989--2707588291" data-pisa="anticanres;44/11/4813" data-pisa-master="anticanres;44/11/4813" data-apath="/anticanres/44/11/4813.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard-title-only clearfix"> <a href="/content/44/11/4813" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">Long Non-coding RNA TPRG1-AS1 Interacts With CLTC in Liver Cancer Cells</span></a> </div> </div></li></ul></div><div class='highwire-list-footer'><a href="/content/by/section/Experimental%20Studies" class="" data-icon-position="" data-hide-link-title="0">Show more <span class="wrapper">Experimental Studies</span></a></div></div><h3 ><i class="icon-caret-right"></i> Similar Articles</h3><div><div class="highwire-search-similar-ajax-wrapper" id="highwire-search-similar-articles-list-1"><div class="highwire-ajax-loading"><span class="icon-spinner icon-spin icon-2x"></span></div></div></div></div></div> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-term-full-title" > <h2 class="pane-title">Keywords</h2> <div class="pane-content"> <div class="highwire-list highwire-a-full-title"><ul class="field-items inline comma-separated"><li class="first odd"><a href="/keyword/liver-cancer" class="" data-icon-position="" data-hide-link-title="0"><span class="wrapper">liver cancer</span></a></li><li class="even"><a href="/keyword/tyrosine-kinase-inhibitor" class="" data-icon-position="" data-hide-link-title="0"><span class="wrapper">tyrosine kinase inhibitor</span></a></li><li class="odd"><a href="/keyword/lenvatinib" class="" data-icon-position="" data-hide-link-title="0"><span class="wrapper">lenvatinib</span></a></li><li class="even"><a href="/keyword/angiogenesis" class="" data-icon-position="" data-hide-link-title="0"><span class="wrapper">angiogenesis</span></a></li><li class="last odd"><a href="/keyword/fibroblast-growth-factor" class="" data-icon-position="" data-hide-link-title="0"><span class="wrapper">fibroblast growth factor</span></a></li></ul></div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> </div> </div> </div> </div> </section> <footer id="section-footer" class="section section-footer"> <div id="zone-footer" class="zone zone-footer clearfix container-30"> <div class="grid-28 suffix-1 prefix-1 region region-footer-first" id="region-footer-first"> <div class="region-inner region-footer-first-inner"> <div class="block block-panels-mini block-jnl-iiar-foot-info block-panels-mini-jnl-iiar-foot-info odd block-without-title" id="block-panels-mini-jnl-iiar-foot-info"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_iiar_foot_info"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-page-logo-footer" > <div class="pane-content"> <a href="/" class="linked-footer-logo" data-icon-position="" data-hide-link-title="0"><img class="footer-logo" src="https://ar.iiarjournals.org/sites/default/files/ar-footer.png" width="460" height="59" alt="Anticancer Research" /></a> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-snippet pane-footer-copyright-text" > <div class="pane-content"> <div class="snippet footer-copyright-text" id="footer-copyright-text"> <div class="snippet-content"> <p>© 2024 Anticancer Research</p> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-branding" > <div class="pane-content"> <a href="http://home.highwire.org" target="_blank" class="highwire-branding-link" data-icon-position="" data-hide-link-title="0"><img class="logo-highwire" src="https://ar.iiarjournals.org/sites/all/modules/highwire/highwire/plugins/content_types/images/logo_small_hw_white.png" width="190" height="31" alt="Powered by HighWire" /></a> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </footer> </div> <div class="region region-page-bottom" id="region-page-bottom"> <div class="region-inner region-page-bottom-inner"> </div> </div><script type="text/javascript" src="/sites/default/files/advagg_js/js__VQUrxbuMIxwGD05YzaEVaysrkxboVQcurWc0_TyeZ2g__DlwEBfr4TpnW-QH_c0_SYjDN4asJEvQ11N0heR6jBNQ__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__Jd5dsvNznZMdglFu8sSni1wCsUfzvQbApHPAZwt5TY4__65Mqa1DMRwcSvPxjJEn6BXgMm-ckF3oOvkUTG9HRADI__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js" defer="defer"></script> <script type="text/javascript" src="/sites/default/files/advagg_js/js__WcTpt-w0y1FyXrxZNriX8Ts1KjsFTDpdvZaw9yhRn24__aFJpdvsZPb1v9rWrq-WXbz_WQ9IThQN-mFTCdm1cfXc__hRizlJXedncVv5rdjtoqctDMz6OkI3LghM4uq8DNLG0.js"></script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- function euCookieComplianceLoadScripts() {} //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- var eu_cookie_compliance_cookie_name = ""; //--><!]]> </script> </body> </html>