Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells

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Notch Signaling: Cell Fate Control and Signal Integration in Development

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THE WNT SIGNALING PATHWAY IN DEVELOPMENT AND DISEASE

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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

2004 • 3,873 citations

Wnt signalling in stem cells and cancer

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Hedgehog signaling in animal development: paradigms and principles

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Notch signalling: a simple pathway becomes complex

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TGFβ Signaling in Growth Control, Cancer, and Heritable Disorders

2000 • 2,354 citations

The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype

2001 • 2,274 citations

A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain

1999 • 2,051 citations

In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship.

2003 • 1,939 citations

Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling

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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells

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Discovery and development of sorafenib: a multikinase inhibitor for treating cancer

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Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.

1997 • 1,590 citations

Induction of Tumor Immunity by Removing CD25+CD4+ T Cells: A Common Basis Between Tumor Immunity and Autoimmunity

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Caught up in a Wnt storm: Wnt signaling in cancer

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Selective Blockade of MicroRNA Processing by Lin28

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An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation

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A distinct “side population” of cells with high drug efflux capacity in human tumor cells

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Identification and Characterization of Tumorigenic Liver Cancer Stem/Progenitor Cells

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EpCAM-Positive Hepatocellular Carcinoma Cells Are Tumor-Initiating Cells With Stem/Progenitor Cell Features

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Hedgehog-Regulated Processing of Gli3 Produces an Anterior/Posterior Repressor Gradient in the Developing Vertebrate Limb

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The Notch Ligands Dll4 and Jagged1 Have Opposing Effects on Angiogenesis

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Asymmetric cell divisions promote stratification and differentiation of mammalian skin

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AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1

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Notch signalling regulates stem cell numbers in vitro and in vivo

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CD4⁺CD25⁺ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative

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PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration.

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The Cold Shock Domain Protein LIN-28 Controls Developmental Timing in C. elegans and Is Regulated by the lin-4 RNA

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Sunitinib: From Rational Design to Clinical Efficacy

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The Hedgehog Response Network: Sensors, Switches, and Routers

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Lin28 promotes transformation and is associated with advanced human malignancies

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Exploring the role of cancer stem cells in radioresistance

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WNT Signaling Pathway and Stem Cell Signaling Network

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The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching

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A Randomized Trial Comparing Radiofrequency Ablation and Surgical Resection for HCC Conforming to the Milan Criteria

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CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway

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Stem Cells and Cancer

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The Structure of the β-Catenin/E-Cadherin Complex and the Molecular Basis of Diverse Ligand Recognition by β-Catenin

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Liver regeneration and repair: Hepatocytes, progenitor cells, and stem cells

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Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties

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AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer

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Identification of metastasis-related microRNAs in hepatocellular carcinoma

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EpCAM and α-Fetoprotein Expression Defines Novel Prognostic Subtypes of Hepatocellular Carcinoma

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miR-221 overexpression contributes to liver tumorigenesis

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Nuclear signalling by tumour-associated antigen EpCAM

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Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties

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Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis

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Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex

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Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells

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Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor

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Human hepatic stem cells from fetal and postnatal donors

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CD13 is a therapeutic target in human liver cancer stem cells

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Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

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CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity

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Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas

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Sonic Hedgehog-induced Activation of the Gli1Promoter Is Mediated by GLI3

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Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells

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The Emerging Role of EpCAM in Cancer and Stem Cell Signaling

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Phase II Trial Evaluating the Clinical and Biologic Effects of Bevacizumab in Unresectable Hepatocellular Carcinoma

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BAY 43-9006 Inhibition of Oncogenic RET Mutants

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Mutational spectrum of β-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas

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Multiple Drug Resistance in Cancer Revisited: The Cancer Stem Cell Hypothesis

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Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

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Oval Cell Numbers in Human Chronic Liver Diseases Are Directly Related to Disease Severity

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Cancer Stem Cells and Self-renewal

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MicroRNA-223 Is Commonly Repressed in Hepatocellular Carcinoma and Potentiates Expression of Stathmin1

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Sorafenib (BAY 43‐9006, Nexavar®), a Dual‐Action Inhibitor That Targets RAF/MEK/ERK Pathway in Tumor Cells and Tyrosine Kinases VEGFR/PDGFR in Tumor Vasculature

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Activation of Hepatic Stem Cell Marker EpCAM by Wnt–β-Catenin Signaling in Hepatocellular Carcinoma

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Liver stem cells and their implication in hepatocellular and cholangiocarcinoma

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Dysregulation of growth factor signaling in human hepatocellular carcinoma

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miR-130b Promotes CD133+ Liver Tumor-Initiating Cell Growth and Self-Renewal via Tumor Protein 53-Induced Nuclear Protein 1

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Wnt/β-Catenin Signaling Contributes to Activation of Normal and Tumorigenic Liver Progenitor Cells

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Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

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Epidemiology of Hepatocellular Carcinoma

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Human hepatic stem cell and maturational liver lineage biology

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Phase I Clinical Study of AZD2171, an Oral Vascular Endothelial Growth Factor Signaling Inhibitor, in Patients With Advanced Solid Tumors

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Cancer stem cells: problems for therapy?

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Epithelial–Mesenchymal Transition in Hepatocellular Carcinoma

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Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin

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Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens

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Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma

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A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer

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CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers

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Disruption of Transforming Growth Factor-β Signaling in ELF β-Spectrin-Deficient Mice

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A Wnt signaling pathway controls Hox gene expression and neuroblast migration in C. elegans

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Liver Stem Cells: Implications for Hepatocarcinogenesis

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New concepts in liver regeneration

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Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma

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MiR-222 Overexpression Confers Cell Migratory Advantages in Hepatocellular Carcinoma through Enhancing AKT Signaling

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Activation of the hedgehog pathway in human hepatocellular carcinomas

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Successful Therapy Must Eradicate Cancer Stem Cells

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Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis.

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Brivanib Alaninate, a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Tyrosine Kinases, Induces Growth Inhibition in Mouse Models of Human Hepatocellular Carcinoma

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Multiple niches for Notch in cancer: context is everything

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EpCAM, a new marker for cancer stem cells in hepatocellular carcinoma

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Hypoxia and hepatocellular carcinoma: The therapeutic target for hepatocellular carcinoma

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Small-molecule modulators of the Sonic Hedgehog signaling pathway

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Hypoxia: A Link between Fibrogenesis, Angiogenesis, and Carcinogenesis in Liver Disease

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Enhanced Self-Renewal Capability in Hepatic Stem/Progenitor Cells Drives Cancer Initiation

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Regeneration of hepatocyte ‘buds’ in cirrhosis from intrabiliary stem cells

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Pluripotency and nuclear reprogramming

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The Polycomb Gene Product BMI1 Contributes to the Maintenance of Tumor-Initiating Side Population Cells in Hepatocellular Carcinoma

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Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor

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Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection

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Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival.

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Transforming Growth Factor-β Signaling in Stem Cells and Cancer

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Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4α gene

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Ci: a complex transducer of the Hedgehog signal

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Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma

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Smad2 and Smad4 gene mutations in hepatocellular carcinoma

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A Notch updated

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Ligand receptor interactions in the WNT signaling pathway in drosophila

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Lapatinib: A novel EGFR/HER2 tyrosine kinase inhibitor for cancer

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Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double‐fluorescence immunostaining evidence

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Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics

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Ras pathway signals are required for notch-mediated oncogenesis

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Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease

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Discovery of Brivanib Alaninate ((S)-((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), A Novel Prodrug of Dual Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1 Kinase Inhibitor (BMS-540215)

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Cancer-associated molecular signature in the tissue samples of patients with cirrhosis

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Identification of hepatocytic and bile ductular cell lineages and candidate stem cells in bipolar ductular reactions in cirrhotic human liver

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Granulin-Epithelin Precursor and ATP-Dependent Binding Cassette (ABC)B5 Regulate Liver Cancer Cell Chemoresistance

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Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma

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Sorafenib is a potent inhibitor of FIP1L1-PDGFRα and the imatinib-resistant FIP1L1-PDGFRα T674I mutant

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Liver Stem Cells and Prospects for Liver Reconstitution by Transplanted Cells

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The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma

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siRNA-Mediated β-Catenin Knockdown in Human Hepatoma Cells Results in Decreased Growth and Survival

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Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma

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Aberrant Notch3 and Notch4 expression in human hepatocellular carcinoma

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An Akt/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Mediates Hypoxia-Induced Chemoresistance in Liver Cancer Cells and Tumorigenic Hepatic Progenitor Cells

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Non-canonical Wnt signaling in Xenopus: regulation of axis formation and gastrulation

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Blocking the hedgehog pathway inhibits hepatoblastoma growth

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Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta-analysis

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Paracrine Signals from Mesenchymal Cell Populations Govern the Expansion and Differentiation of Human Hepatic Stem Cells to Adult Liver Fates

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Opposing roles of gp130-mediated STAT-3 and ERK-1/2 signaling in liver progenitor cell migration and proliferation

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Expansion of CD133-Expressing Liver Cancer Stem Cells in Liver-Specific Phosphatase and Tensin Homolog Deleted on Chromosome 10-Deleted Mice

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Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma

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Network of WNT and Other Regulatory Signaling Cascades in Pluripotent Stem Cells and Cancer Stem Cells

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Regulation of the Notch target gene Hes-1 by TGFα induced Ras/MAPK signaling in human neuroblastoma cells

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Identification and characterization of tumorigenic liver cancer stem/progenitor cells

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Oncostatin M Renders Epithelial Cell Adhesion Molecule–Positive Liver Cancer Stem Cells Sensitive to 5-Fluorouracil by Inducing Hepatocytic Differentiation

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Liver cancer stem cells: implications for a new therapeutic target

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Notch1 Signaling Sensitizes Tumor Necrosis Factor-related Apoptosis-inducing Ligand-induced Apoptosis in Human Hepatocellular Carcinoma Cells by Inhibiting Akt/Hdm2-mediated p53 Degradation and Up-regulating p53-dependent DR5 Expression

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Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies

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ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows antimetastatic activity using a hepatocellular carcinoma model.

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Modulation of wingless signaling by Notch in Drosophila

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Deregulated expression of Notch receptors in human hepatocellular carcinoma

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Notch Signalling and the Regulation of Angiogenesis

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Mutations of β‐catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis

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Dkk1 Stabilizes Wnt Co-Receptor LRP6: Implication for Wnt Ligand-Induced LRP6 Down-Regulation

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Bmi1promotes hepatic stem cell expansion and tumorigenicity in bothInk4a/Arf-dependent and -independent manners in Mice

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PTEN/Akt Signaling through Epidermal Growth Factor Receptor Is Prerequisite for Angiogenesis by Hepatocellular Carcinoma Cells That Is Susceptible to Inhibition by Gefitinib

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The Sonic Hedgehog–Patched–Gli Pathway in Human Development and Disease

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Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis

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miR-130b is preferentially upregulated in CD133+ liver cancer stem cells and regulates tumor growth and self-renewal via tumor protein 53-induced nuclear protein 1

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Adecatumumab: an anti-EpCAM monoclonal antibody, from the bench to the bedside

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Expression of beta-catenin in Hepatocellular Carcinoma in Relation to Tumor Cell Proliferation and Cyclin D1 Expression

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Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells

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Gefitinib and the modulation of the signaling pathways downstream of epidermal growth factor receptor in human liver cancer cells

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Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells

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Non-canonical Wnt signaling pathways in hematopoiesis

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Hepatic Stem Cells and Liver Development

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Expression of transforming growth factors in hepatocellular carcinoma and its relations with clinicopathological parameters and prognosis.

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A Randomized Trial Comparing Radiofrequency Ablation and Surgical Resection For HCC Conforming to the Milan Criteria

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Expression of Transforming Growth Factor beta - 1 in Chronic Hepatitis and Hepatocellular Carcinoma Associated with Hepatitis C Virus Infection

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Transforming growth factor‐β signaling and liver cancer stem cell

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Paracrine signals from mesenchymal cell populations govern the expansion and differentiation of human hepatic stem cells to adult liver fates

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Antiproliferative effects of interferon alpha on hepatic progenitor cells in vitro and in vivo

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Hepatic Stem Cells and Liver Development

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