title: Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment.
abstract: Death rates from hepatocellular carcinoma (HCC) are steadily increasing, yet therapeutic options for advanced HCC are limited. We identify a subset of mouse and human HCCs harboring VEGFA genomic amplification, displaying distinct biologic characteristics. Unlike common tumor amplifications, this one seems to work via heterotypic paracrine interactions; stromal VEGF receptors (VEGFR), responding to tumor VEGF-A, produce hepatocyte growth factor (HGF) that reciprocally affects tumor cells. VEGF-A inhibition results in HGF downregulation and reduced proliferation, specifically in amplicon-positive mouse HCCs. Sorafenib-the first-line drug in advanced HCC-targets multiple kinases, including VEGFRs, but has only an overall mild beneficial effect. We found that VEGFA amplification specifies mouse and human HCCs that are distinctly sensitive to sorafenib. FISH analysis of a retrospective patient cohort showed markedly improved survival of sorafenib-treated patients with VEGFA-amplified HCCs, suggesting that VEGFA amplification is a potential biomarker for HCC response to VEGF-A-blocking drugs.
  
  
  CONCLUSIONS
  Using a mouse model of inflammation-driven cancer, we identified a subclass of HCC carrying VEGFA amplification, which is particularly sensitive to VEGF-A inhibition. We found that a similar amplification in human HCC identifies patients who favorably responded to sorafenib-the first-line treatment of advanced HCC-which has an overall moderate therapeutic efficacy.
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Elad
authors.initials: E
authors.lastname: Horwitz
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, GermanyAuthors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Ilan
authors.initials: I
authors.lastname: Stein
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Andreozzi
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Nemeth
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Avivit
authors.initials: A
authors.lastname: Shoham
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Orit
authors.initials: O
authors.lastname: Pappo
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Schweitzer
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Naama
authors.initials: N
authors.lastname: Kanarek
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Quagliata
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Farid
authors.initials: F
authors.lastname: Zreik
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Rinnat M
authors.initials: RM
authors.lastname: Porat
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Rutie
authors.initials: R
authors.lastname: Finkelstein
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Reuter
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Koschny
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Ganten
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Oren
authors.initials: O
authors.lastname: Shibolet
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, GermanyAuthors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, GermanyAuthors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University
authors.forename: Jochen
authors.initials: J
authors.lastname: Hess
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Breuhahn
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Myriam
authors.initials: M
authors.lastname: Grunewald
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Vogel
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany peli@hadassah.org.il yinonb@ekmd.huji.ac.il.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Ben-Neriah
authors.affiliation: Authors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, GermanyAuthors' Affiliations:The Lautenberg Center for Immunology; Department of Developmental Biology and Cancer Research, IMRIC, Hadassah Medical School, Hebrew University;Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem; Liver Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Institute of Pathology, University Hospital Basel, Basel, Switzerland; Division of Signal Transduction and Growth Control (A100), Division of Molecular Genetics (B060), and Junior Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance; Institute of Pathology, University Hospital Heidelberg; Departments of Otolaryngology, Head and Neck Surgery and Internal Medicine, University Hospital Heidelberg, Heidelberg; and Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany peli@hadassah.org.il yinonb@ekmd.huji.ac.il.
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarsky
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D000077157:Sorafenib; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D009536:Niacinamide; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A; D000097202:ATP-Binding Cassette Sub-Family B Member 4