☆ 4.7 Review

Friend or foe? The elusive role of hepatic stellate cells in liver cancer

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2023)

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Article Gastroenterology & Hepatology

Inflamed and non-inflamed classes of HCC: a revised immunogenomic classification

Carla Montironi et al.

Summary: This study characterizes the immunogenomic contexture of hepatocellular carcinoma (HCC) and defines inflamed and non-inflamed tumors. Two distinct patterns of CTNNB1 are associated with differential immune evasion and may help predict immune response in HCC.

GUT (2023)

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Article Gastroenterology & Hepatology

Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications

Miguel A. Martin-Serrano et al.

Summary: We present a comprehensive stratification of iCCA based on the tumor microenvironment (TME). The tumor is divided into five stable STIM classes, including 35% inflamed and 65% non-inflamed profiles. The inflamed classes, immune classical and inflammatory stroma, differ in oncogenic pathways and extent of desmoplasia. Analysis of cell-cell interactions highlights cancer-associated fibroblast subtypes as potential mediators of immune evasion. Among the non-inflamed classes, the desert-like class has the lowest immune infiltration with abundant regulatory T cells, while the hepatic stem-like class is enriched in 'M2-like' macrophages and specific mutations. Comparative analysis reveals high similarity between a KRAS/p19 murine model and the inflammatory stroma class. The KRAS-SOS inhibitor sensitizes a KRAS-mutant iCCA murine model to anti-PD1 therapy. Our findings provide valuable insights into the TME of iCCA and offer potential therapeutic targets for future research.

GUT (2023)

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Article Cell Biology

An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis

Shuang Wang et al.

Summary: Using single-nucleus RNA sequencing and tissue clearing in a murine NASH model, we identified a repertoire of antifibrotic drug targets underlying advanced fibrosis, including an autocrine HSC signaling circuit composed of 68 receptor-ligand interactions conserved between murine and human NASH. Inhibiting one such autocrine interaction reversed advanced murine NASH fibrosis and inhibited human HSC activation in culture, suggesting the potential for stage-specific therapies in patients with advanced hepatic fibrosis.

SCIENCE TRANSLATIONAL MEDICINE (2023)

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Article Gastroenterology & Hepatology

Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma

Fan Ying et al.

Summary: Primary liver cancer (PLC) is the sixth most common cancer worldwide with poor prognosis. Cancer-associated fibroblasts (CAFs) are a major component of the abundant stromal reaction in PLC. CAFs play a crucial role in tumor progression and are often correlated with poor clinical outcomes. However, the origins, heterogeneity, and specific markers of CAFs are not well understood, hindering efficient CAF-specific therapy. This review explores recent advances in understanding CAF diversity, their regulatory roles, and their crosstalk with immune cells in the tumor microenvironment in PLC. The review also discusses current CAF-targeted therapies and future perspectives.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2023)

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Review Cell & Tissue Engineering

ScRNA-seq and ST-seq in liver research

Jia He et al.

Summary: Spatial transcriptomics, combining gene expression data with spatial information, has greatly improved our understanding of liver development, regeneration, and diseases. However, there are still challenges to be addressed, such as sensitivity, limited single-cell information, and data processing methods. Advances in techniques like single-cell RNA sequencing and spatial transcriptome sequencing provide new opportunities for investigating fundamental questions in liver research.

CELL REGENERATION (2023)

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Review Gastroenterology & Hepatology

The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma

Romain Donne et al.

Summary: The liver is a common site for primary cancer and a major cause of cancer death. Hepatocellular carcinoma (HCC) accounts for the majority of liver cancers. Immune-checkpoint inhibitors have shown promise in the treatment of HCC, but further understanding of the tumor microenvironment and the development of additional biomarkers are needed. Other immune-targeting strategies are also being developed. This review provides an overview of the HCC immune microenvironment and current immunotherapies.

HEPATOLOGY (2023)

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Article Gastroenterology & Hepatology

A multisociety Delphi consensus statement on new fatty liver disease nomenclature

Mary E. Rinella et al.

Summary: This study aimed to determine if there was a need to change the nomenclature and definition of NAFLD and NASH. Through a Delphi process involving content experts and patient advocates, a consensus was reached to replace NAFLD with metabolic dysfunction-associated steatotic liver disease (MetALD) and modify the diagnostic criteria. The new nomenclature and criteria are widely supported, nonstigmatizing, and can improve awareness and patient identification.

HEPATOLOGY (2023)

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Review Gastroenterology & Hepatology

An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH

Frank Tacke et al.

Summary: The development of treatments for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) has been challenging due to the complexity of the disease and the involvement of multiple pathways. Current approaches target metabolic dysregulation, inflammation, fibrosis, and immune responses. Potential therapies include nuclear receptor agonists, lipotoxicity modulators, genetic variant modification, hormonal agonists, microbiota interventions, and lifestyle changes. Inhibiting activation of hepatic stellate cells, immune cell modulation, and cell therapy are strategies to attenuate fibrosis. However, the heterogeneity of NASH poses a challenge in developing effective drugs for all patients.

JOURNAL OF HEPATOLOGY (2023)

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Review Biochemistry & Molecular Biology

Challenges and opportunities in NASH drug development

Stephen A. Harrison et al.

Summary: This Review provides an overview of the challenges and potential solutions in clinical trials for NASH drugs, emphasizing the need for non-invasive tests and biomarkers to replace invasive liver biopsies as primary endpoints. While NAFLD and NASH are prevalent worldwide, no approved drugs are available currently. The histopathological assessment of liver biopsies, currently required for drug approval, presents a major challenge due to its variability, leading to high screen-failure rates. Non-invasive tests correlating with liver histology and outcomes show promise but require further validation for regulatory endorsement in phase 3 trials.

NATURE MEDICINE (2023)

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Review Gastroenterology & Hepatology

Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment

Josep M. Llovet et al.

Summary: Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. NASH-HCC, influenced by factors such as the immune microenvironment, PNPLA3 mutations, and the microbiome, has unique characteristics compared to other types of HCC and affects both men and women equally. The management of NASH-HCC involves surgery, locoregional therapies, and systemic therapies, with the future focus being on improving surveillance, developing targeted combination therapies, and identifying biomarkers for treatment responders.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2023)

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Article Biochemistry & Molecular Biology

Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling that induces hepatocyte proliferation

Vincent Quoc-Huy Trinh et al.

Summary: This study reveals that hepatocyte proliferation in the midlobular zone of the liver is supported by hepatic stellate cells (HSCs) through the production of neurotrophin-3 (Ntf-3). Loss of HSCs leads to reduced hepatocyte proliferation and liver mass, while treatment with Ntf-3 restores hepatocyte proliferation and increases liver mass.

SCIENCE SIGNALING (2023)

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Article Cell Biology

CD36+ cancer-associated fibroblasts provide immunosuppressive microenvironment for hepatocellular carcinoma via secretion of macrophage migration inhibitory factor

Gui-Qi Zhu et al.

Summary: Hepatocellular carcinoma (HCC) is a type of cancer that is resistant to immunotherapy due to its high cellular heterogeneity. The heterogeneity of cancer-associated fibroblast (CAF) in HCC tumors was identified through single cell RNA sequencing. CD36(+) CAFs were found to have high-level lipid metabolism and expression of macrophage migration inhibitory factor (MIF). These cells were derived from hepatic stellate cells. CD36 mediated the expression of MIF through oxidized LDL uptake and activated the lipid peroxidation/p38/CEBPs axis in CD36(+) CAFs, which recruited myeloid-derived suppressor cells (MDSCs) in a MIF- and CD74-dependent manner. Co-implantation of CD36(+) CAFs with HCC cells promoted HCC progression in vivo. Furthermore, a CD36 inhibitor was shown to enhance the effect of anti-PD-1 immunotherapy by restoring antitumor T-cell responses in HCC.

CELL DISCOVERY (2023)

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Article Immunology

Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation

Thomas Fabre et al.

Summary: Macrophages are key regulators of the tissue response to injury and play important roles in fibrosis progression and resolution. A specific subset of CD9(+)TREM2(+) macrophages expressing SPP1, GPNMB, FABP5, and CD63 were identified in human fibrotic tissues. These macrophages were enriched at the edges of scarring and adjacent to activated mesenchymal cells, and their expansion was associated with the presence of neutrophils expressing MMP9, GM-CSF, and IL-17A. In vitro studies revealed that GM-CSF, IL-17A, and TGF-beta 1 promoted the differentiation of monocytes into scar-associated macrophages. In mouse models, blocking GM-CSF, IL-17A, or TGF-beta 1 reduced scar-associated macrophage expansion and hepatic or pulmonary fibrosis. This study provides valuable insights into the role of a specific macrophage population in fibrosis and suggests potential therapeutic targets.

SCIENCE IMMUNOLOGY (2023)

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Article Gastroenterology & Hepatology

Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis

Enis Kostallari et al.

Summary: The wound-healing response in liver increases stiffness, which in turn amplifies fibrogenesis. This study reveals heterogeneous distribution of stiffness in fibrotic liver at macroscopic and microscopic levels and its impact on hepatic stellate cell heterogeneity. Stiffness in high-density extracellular matrix areas is mainly responsible for high liver stiffness. Moreover, a specific protein, FHL2, is found to be upregulated in a stiffness-sensitive subpopulation of hepatic stellate cells, promoting extracellular matrix production.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Fibroblast-derived prolargin is a tumor suppressor in hepatocellular carcinoma

Barbara Chiavarina et al.

Summary: Cancer-associated fibroblasts (CAF) play important roles in tumor microenvironment and tumorigenesis. In hepatocellular carcinoma (HCC), there are three major CAF populations, one of which expresses prolargin protein. Prolargin acts as an angiogenesis modulator and tumor suppressor in HCC, inhibiting the activity of pro-angiogenic proteins. Stabilizing prolargin levels in the CAF_Port subpopulation may reverse their tumor-antagonizing properties.

ONCOGENE (2022)

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Article Multidisciplinary Sciences

CAR T cells produced in vivo to treat cardiac injury

Joel G. Rurik et al.

Summary: This study developed a therapeutic approach to generate antifibrotic CAR T cells in vivo by delivering modified mRNA in T cell-targeted nanoparticles. The efficacy of these in vivo-reprogrammed CAR T cells was evaluated in a mouse model of heart failure.

SCIENCE (2022)

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Article Gastroenterology & Hepatology

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Lin Lei et al.

Summary: This study identified portal mesenchymal progenitors of myofibroblasts in liver fibrosis and revealed their role in myofibroblast formation. Portal mesenchymal progenitors play a crucial role in the formation of fibrotic septa, along with neovessels and HSC-MFs that arise from a preexisting pool.

HEPATOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Emerging therapeutic opportunities for integrin inhibitors

R. J. Slack et al.

Summary: Integrins play crucial roles in cell adhesion and signaling, making them potential therapeutic targets. This review discusses the challenges and development of integrin inhibitors, particularly those targeting integrins with an alpha v-subunit. Opportunities exist for learning from previous trials and exploring new modalities in integrin drug design.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Multidisciplinary Sciences

Fibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis

Jaiwoo Lee et al.

Summary: This study reports a targeted anti-fibrotic peptide-delivery system that effectively reduces liver fibrosis by utilizing fibroblast activation protein to release an antifibrotic peptide.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Han Luo et al.

Summary: This study conducts pan-cancer analysis on 226 samples across 10 solid cancer types, illustrating the commonalities and plasticity of heterogeneous CAFs. It reveals that the activation trajectory of major CAF types is divided into three states, showing distinct interactions with other cell components and correlation with immunotherapy prognosis. Additionally, minor CAF components may originate from other TME components such as endothelial cells and macrophages.

NATURE COMMUNICATIONS (2022)

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Article Gastroenterology & Hepatology

Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target

Giorgia Alvisi et al.

Summary: This study found excessive activation of CD4+ Tregs in iCCA tumors and reduced effector functions of CD8+ T cells. The research indicated that MEOX1 is highly enriched in tumor-infiltrating Tregs, and overexpression of MEOX1 can reshape circulating Tregs to acquire the transcriptional and epigenetic features of tumor-infiltrating Tregs.

JOURNAL OF HEPATOLOGY (2022)

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Article Multidisciplinary Sciences

A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Yiming Lu et al.

Summary: The authors use single cell RNA sequencing to study the immune cell constituents and localization within human hepatocellular carcinoma, providing insights into the microenvironment of the cancer.

NATURE COMMUNICATIONS (2022)

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Article Oncology

Geospatial Immune Heterogeneity Reflects the Diverse Tumor-Immune Interactions in Intrahepatic Cholangiocarcinoma

Youpei Lin et al.

Summary: This study elucidates the impact of spatial immune heterogeneity upon tumor evolution of iCCA and reveals distinct immune evasion mechanisms developed in different immune microenvironments, which can be exploited for the development of personalized immunotherapy strategies.

CANCER DISCOVERY (2022)

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Article Multidisciplinary Sciences

Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis

Rikard G. Fred et al.

Summary: This study aims to identify specific transcriptional patterns in non-alcoholic steatohepatitis (NASH) to enhance our understanding of the disease. By performing single-cell RNA sequencing on liver biopsies from 10 NASH patients, the study provides comprehensive insights into the pathology of NASH in humans. The findings suggest that previously identified NASH-associated macrophages are actually subpopulations of liver macrophages that are up-regulated. Additionally, the study identifies two distinct populations of activated hepatic stellate cells associated with the level of fibrosis. Furthermore, the study reveals co-regulation of circulating markers of NAFLD with predicted effector genes from NAFLD genome-wide association studies (GWAS), as well as abnormalities in the complement system in hepatocytes.

SCIENTIFIC REPORTS (2022)

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Review Genetics & Heredity

An introduction to spatial transcriptomics for biomedical research

Cameron G. Williams et al.

Summary: Single-cell transcriptomics (scRNA-seq) has become essential in biomedical research, especially in the fields of developmental biology, cancer, immunology, and neuroscience. However, most available protocols require intact and viable cells, limiting the scope of study and destroying spatial context. This review introduces different methods of spatial transcriptomics and discusses their features, such as tissue area, spatial resolution, and gene profiling capabilities. It also provides guidance on platform selection, data analysis, and integration with existing scRNA-seq data, aiming to help researchers utilize spatial transcriptomics in their own biomedical research.

GENOME MEDICINE (2022)

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Article Immunology

Gasdermin D-mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma

Ryota Yamagishi et al.

Summary: In this study, the release mechanism of senescence-associated secretory phenotype (SASP) factors from senescent hepatic stellate cells (HSCs) was identified in a mouse model of obesity-induced hepatocellular carcinoma (HCC). IL-33 release from HSCs promoted HCC development via the activation of ST2-positive T-reg cells in the liver tumor microenvironment. These findings highlight the therapeutic potential of inhibitors of gasdermin D-mediated pore formation for HCC treatment.

SCIENCE IMMUNOLOGY (2022)

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Review Oncology

The importance of being CAFs (in cancer resistance to targeted therapies)

Sabrina Rizzolio et al.

Summary: In the last two decades, targeted drugs have revolutionized clinical oncology. However, primary and acquired resistance to these therapies has become a significant limitation, with cancer-associated fibroblasts (CAFs) playing a crucial role. CAFs not only contribute to tumor stroma structure, but also release various molecules that impact tumor properties, including response to drug treatment. The role of CAFs in resistance to targeted therapies, particularly molecular therapies, has been overlooked.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Multidisciplinary Sciences

Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis

Aveline Filliol et al.

Summary: The shift in HSC subpopulations during chronic liver disease is associated with a switch from HCC protection to promotion. Quiescent and cytokine-producing HSCs prevent hepatocyte death and HCC development, while activated myofibroblastic HSCs promote proliferation and tumor development through increased stiffness and TAZ and discoidin domain receptor 1 activation.

NATURE (2022)

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Article Multidisciplinary Sciences

Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome

Hua Su et al.

Summary: This study reveals the opposing effects of intact and cleaved collagen I (Col I) in regulating the bioenergetics, tumor growth, and metastasis of pancreatic ductal adenocarcinoma (PDAC) through the tumor microenvironment. Intact Col I inhibits tumor growth, while cleaved Col I promotes tumor growth. Patients with tumors enriched in intact Col I and low levels of related signaling molecules have a longer median survival. These findings shed light on the complex mechanisms of the tumor microenvironment in PDAC and provide new therapeutic targets.

NATURE (2022)

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Article Cell Biology

Single-cell atlas of human liver development reveals pathways directing hepatic cell fates

Brandon T. Wesley et al.

Summary: In this study, the developmental trajectories of human fetal liver cell types were described at single-cell resolution, and bipotential hepatoblast organoids were generated. This provides a platform for investigating human liver development and producing cell types for clinical applications.

NATURE CELL BIOLOGY (2022)

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Article Oncology

Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumor

John A. Grout et al.

Summary: This study identifies two populations of cancer-associated fibroblasts (CAF) in lung tumors that are associated with T-cell exclusion. These populations orchestrate a specific structural tissue organization and produce distinct matrix molecules. The findings highlight the importance of targeting these CAF populations to increase immunotherapy efficacy in patients with T cell-excluded tumors.

CANCER DISCOVERY (2022)

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Review Oncology

Cancer-associated fibroblasts in the single-cell era

Dor Lavie et al.

Summary: Cancer-associated fibroblasts (CAFs) play a central role in the microenvironment of solid tumors, and recent advances in single-cell technologies have provided insights into their complexity and heterogeneity. Understanding the subsets and functions of CAFs can potentially lead to better therapeutic strategies for cancer.

NATURE CANCER (2022)

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Review Endocrinology & Metabolism

Hepatic Stellate Cell-Immune Interactions in NASH

James K. Carter et al.

Summary: Nonalcoholic fatty liver disease (NAFLD) is the main cause of liver disease worldwide, and nonalcoholic steatohepatitis (NASH) is a more severe form characterized by significant hepatocellular injury, inflammation, and fibrosis. Recent research has shown that heightened immune cell activity and chronic inflammation play crucial roles in the development of NASH, with hepatic stellate cells (HSCs) being the key drivers of fibrosis.

FRONTIERS IN ENDOCRINOLOGY (2022)

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Article Gastroenterology & Hepatology

Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis

Brian K. Chung et al.

Summary: In this study, whole-tissue spatial transcriptomics combined with scRNAseq and gene deconvolution analysis were used to localize cell types and identify gene expression differences in cirrhotic liver tissues. The results showed that fibrotic liver regions contained enriched cell types compared to parenchymal areas, providing insights for the search of antifibrotic targets.

HEPATOLOGY COMMUNICATIONS (2022)

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Article Gastroenterology & Hepatology

Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity

Tallulah S. Andrews et al.

Summary: This study provides a comprehensive comparison of the transcriptomes captured by scRNA-seq and snRNA-seq, delivering a high-resolution map of the parenchymal cell populations in the healthy human liver. The use of both technologies revealed unique cell types and spatial distributions within the liver, highlighting the importance of applying multiple techniques for a complete understanding of tissue-resident cell populations.

HEPATOLOGY COMMUNICATIONS (2022)

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Review Oncology

TGFβ biology in cancer progression and immunotherapy

Rik Derynck et al.

Summary: TGF beta signaling plays a key role in cancer progression by promoting cancer cell invasion, dissemination, stem cell properties, therapeutic resistance, and the generation of an immunosuppressive environment. Inhibiting TGF beta signaling is considered a crucial avenue to enhance the efficacy of cancer immunotherapies. Understanding and targeting TGF beta signaling mechanisms in tumors and their microenvironment may provide valuable insights for cancer treatment.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Article Pathology

Prognostic value of desmoplastic stroma in intrahepatic cholangiocarcinoma

Nathalie Guedj et al.

Summary: In this study, the prognostic value of stromal compartment in iCC was evaluated using multiparametric morphological analysis. It was found that high proportionated stromal area was associated with better disease-free survival (DFS), while low activated stroma index was linked to a better DFS. On the other hand, high collagen reticulation index was associated with poorer overall survival, suggesting potential clinical relevance in evaluating collagen reticulation in patients with iCC.

MODERN PATHOLOGY (2021)

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Article Gastroenterology & Hepatology

Cancer-Associated Fibroblasts Provide a Stromal Niche for Liver Cancer Organoids That Confers Trophic Effects and Therapy Resistance

Jiaye Liu et al.

Summary: The study successfully established murine and human 3D co-culture models and demonstrated robust effects of cancer-associated fibroblasts (CAFs) in nurturing liver cancer and promoting treatment resistance.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2021)

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Article Biochemistry & Molecular Biology

Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination

Jiali Yu et al.

Summary: Liver metastases diminish the efficacy of immunotherapy by siphoning activated CD8(+) T cells from systemic circulation, creating systemic immune desert. Combining liver-directed radiotherapy with immunotherapy can promote systemic antitumor immunity.

NATURE MEDICINE (2021)

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Editorial Material Biochemical Research Methods

Method of the Year: spatially resolved transcriptomics

Vivien Marx

Summary: Nature Methods has named spatially resolved transcriptomics as Method of the Year 2020.

NATURE METHODS (2021)

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Review Gastroenterology & Hepatology

Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention

Daniel Q. Huang et al.

Summary: The prevalence of NAFLD-related HCC is projected to continue rising globally, with NASH expected to increase and obesity as a major risk factor. Urgent measures are needed to address this growing problem.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Article Oncology

Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma

Qianfei Zhang et al.

Summary: The study demonstrates that gut dysbiosis can lead to the accumulation of PMN-MDSCs, promoting liver cancer development. However, treatment with neomycin can block this process and inhibit tumor growth, even in the absence of liver disease or colitis.

CANCER DISCOVERY (2021)

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Article Medicine, General & Internal

Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis

Ali Aminian et al.

Summary: Among patients with NASH and obesity, bariatric surgery was associated with a significantly lower risk of incident major adverse liver outcomes and MACE compared with nonsurgical management.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Medicine, General & Internal

Hepatocellular carcinoma

Josep M. Llovet et al.

Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global health challenge with rising incidence projected to exceed 1 million cases by 2025. Infection by hepatitis B and C viruses remains a major risk factor for HCC, while non-alcoholic steatohepatitis is emerging as a more common risk factor in Western countries. Advances in systemic therapies for HCC, including immunotherapies and targeted therapies, are expected to revolutionize the management of this disease.

NATURE REVIEWS DISEASE PRIMERS (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Oncology

Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer

Yang Chen et al.

Summary: The stromal desmoplastic reaction in pancreatic ductal adenocarcinoma involves significant accumulation of type I collagen (Col1). Deletion of Col1 specifically in myofibroblasts accelerates PDAC progression by increasing Cxcl5 expression in cancer cells and promoting recruitment of myeloid-derived suppressor cells. Targeting CXCR2 and CCR2 may help restrain accelerated PDAC progression in the absence of stromal Col1.

CANCER CELL (2021)

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Article Gastroenterology & Hepatology

Heterogeneity of HSCs in a Mouse Model of NASH

Sara Brin Rosenthal et al.

Summary: This study utilized single-cell RNA sequencing to characterize the phenotypic changes of hepatic stellate cells (HSCs) in a NASH model, revealing unexpected heterogeneity of HSC phenotypes under normal and injured states. The NASH livers showed four distinct HSC clusters, including one representing the classic fibrogenic myofibroblast, while livers with NASH regression had one cluster of inactivated HSCs similar to quiescent HSCs.

HEPATOLOGY (2021)

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Article Gastroenterology & Hepatology

Cancer-Associated Fibroblast-Mediated Cellular Crosstalk Supports Hepatocellular Carcinoma Progression

Mengjia Song et al.

Summary: This study revealed a cytokine-mediated cellular crosstalk and clinical network involving the CLCF1-CXCL6/TGF-beta axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. The up-regulation of the CLCF1-CXCL6/TGF-beta axis in clinical samples showed a correlation with increased cancer stem cells, N2-polarized TANs, tumor stage, and poor prognosis. This suggests the CLCF1 cascade could be a potential prognostic biomarker and targeting CLCF1/ ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.

HEPATOLOGY (2021)

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Article Multidisciplinary Sciences

Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion

Xiujie Sun et al.

Summary: The study identifies a new mechanism of immune exclusion mediated by DDR1-ECD through promoting collagen fiber alignment. Inhibition of DDR1 promotes intratumoral penetration of T cells and eradicates tumor growth in TNBC.

NATURE (2021)

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Article Cell Biology

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis

Gao Liu et al.

Summary: CAFs-derived cytokines can enhance hepatocellular carcinoma progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells, with CXCL11 playing a key role in this process.

CELL DEATH & DISEASE (2021)

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Review Medicine, General & Internal

CD8+ T Cell Responses during HCV Infection and HCC

Maike Hofmann et al.

Summary: CD8(+) T cell responses play a crucial role in chronic HCV infection and HCC, strong virus-specific CD8(+) T cell responses contribute to virus clearance while failure leads to chronic infection development. Tumor-associated and tumor-specific CD8(+) T cells are considered potential targets for immunotherapeutic strategies.

JOURNAL OF CLINICAL MEDICINE (2021)

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Article Oncology

Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations

Silvia Affo et al.

Summary: The study reveals that hepatic stellate cells (HSC) are the main source of cancer-associated fibroblasts (CAF), and HSC-derived CAF interact predominantly with tumor cells. In mouse models, CAF promote the progression of intrahepatic cholangiocarcinoma (ICC), while in patients, a high pan-CAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into distinct subpopulations, with different interactions with tumor cells and promoting ICC growth.

CANCER CELL (2021)

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Review Oncology

Tumor Immune Microenvironment during Epithelial-Mesenchymal Transition

Mana Taki et al.

Summary: Epithelial-mesenchymal transition (EMT) plays a critical role in tumor development by interacting with immune evasion mechanisms, leading to tumor progression. Combination therapy targeting EMT and immunosuppression may offer promising new therapeutic approaches in cancer treatment.

CLINICAL CANCER RESEARCH (2021)

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Article Gastroenterology & Hepatology

Perivenous Stellate Cells Are the Main Source of Myofibroblasts and Cancer-Associated Fibroblasts Formed After Chronic Liver Injuries

Shan-Shan Wang et al.

Summary: The study identified Tcf21 as a unique marker for quiescent HSCs and found that Tcf21(+) cells, targeted by Tcf21-CreER, play a key role in liver fibrosis and tumorigenesis. Deletion of Tgfbr2 by Tcf21-CreER inhibited HSC activation and liver tumor progression, highlighting the importance of TGF-beta signaling in the process.

HEPATOLOGY (2021)

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Article Multidisciplinary Sciences

Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver

Qi Su et al.

Summary: Single-cell transcriptome analysis identified cellular and molecular mechanisms of NAFLD, revealing dual roles of hepatic stellate cells and distinct expression profiles of Kupffer cells and monocyte-derived macrophages. The study also uncovered three chimeric NPCs, advancing the understanding of cellular heterogeneity in NAFLD livers.

ISCIENCE (2021)

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Article Multidisciplinary Sciences

Cross-tissue organization of the fibroblast lineage

Matthew B. Buechler et al.

Summary: Recent studies have identified fibroblast heterogeneity in different tissues, and constructed fibroblast atlases based on single-cell transcriptomic data to reveal universal and activated transcriptional subtypes in healthy and diseased states.

NATURE (2021)

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Article Multidisciplinary Sciences

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Dominik Pfister et al.

Summary: The study investigated the impact of NASH on immunotherapy response in HCC patients and found that NASH-HCC may be less responsive to immunotherapy. Aberrant T cell activation caused by NASH-related tissue damage led to impaired immune surveillance in HCC patients.

NATURE (2021)

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Article Multidisciplinary Sciences

Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH

Michael Dudek et al.

Summary: Liver resident CD8 T cells play an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis. These cells display specific phenotypic and metabolic characteristics in the liver, making them susceptible to metabolic stimuli and leading to auto-aggressive responses. This study sheds light on the mechanisms underlying liver damage in NASH and highlights the distinction between auto-aggressive and protective T cell immunity.

NATURE (2021)

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Article Gastroenterology & Hepatology

Single-Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell-Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice

Wu Yang et al.

Summary: The study found that in liver fibrosis, HSCs undergo significant transcriptomic changes rather than PFs, and HSCs are the exclusive source of myofibroblasts in CCL4-treated livers, while PFs are the major source in early cholestatic liver fibrosis. Single-cell RNA sequencing and lineage-tracing analysis uncovered differential gene-expression features between HSCs and PFs, providing evidence that these differences should be considered in developing antifibrotic therapeutic strategies.

HEPATOLOGY (2021)

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Article Multidisciplinary Sciences

Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy

Ana Luisa Correia et al.

Summary: The study investigates how different tissue-specific microenvironments can either inhibit or support the progression of breast cancer in the liver. It identifies the interplay between natural killer (NK) cells and activated hepatic stellate cells (aHSCs) as a master switch of cancer dormancy, suggesting that therapies aimed at normalizing the NK cell pool may be successful in preventing metastatic outgrowth.

NATURE (2021)

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Article Cell Biology

Heterogeneity of Hepatic Stellate Cells in Fibrogenesis of the Liver: Insights from Single-Cell Transcriptomic Analysis in Liver Injury

Wenjun Zhang et al.

Summary: This study identified multiple subpopulations of HSCs and characterized their unique roles and characteristics during liver injury, including differentiating into myofibroblasts and potential involvement in liver regeneration, immune reaction, and vascular remodeling. The scRNA-seq data provided insight into the dynamic transition from HSCs to myofibroblasts in response to liver injury, highlighting the heterogeneity and functional diversity of HSCs. The findings also suggest similarities between the heterogeneity of HSCs in injured mouse livers and cirrhotic human livers.

CELLS (2021)

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Review Oncology

Fibroblast Activation Protein-α as a Target in the Bench-to-Bedside Diagnosis and Treatment of Tumors: A Narrative Review

Lei Xin et al.

Summary: FAP, specifically expressed by activated fibroblasts, plays a crucial role in promoting tumor growth, invasion, metastasis, and immunosuppression. Through influencing extracellular matrix remodeling, intracellular signaling, and immunosuppression, CAF overexpression of FAP promotes tumor development and metastasis.

FRONTIERS IN ONCOLOGY (2021)

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Article Medicine, Research & Experimental

Tumor restriction by type I collagen opposes tumor- promoting effects of cancer-associated fibroblasts

Sonakshi Bhattacharjee et al.

Summary: This study reveals that cancer-associated fibroblasts (CAF) promote tumor growth by interacting with tumor cells through the secretion of different mediators. However, the overall tumor-promoting effects of CAF can be opposed by mechanical restriction from type I collagen. Therapeutic targeting of tumor-promoting CAF mediators while preserving type I collagen may shift the balance from tumor promotion to tumor restriction.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Gastroenterology & Hepatology

Single-cell RNA sequencing of human liver reveals hepatic stellate cell heterogeneity

Valery L. Payen et al.

Summary: This study used single-cell RNA sequencing to unravel the heterogeneity of human liver cells, particularly hepatocytes and hepatic stellate cells. The research revealed the existence of different cell populations in the liver with unique gene expression signatures and distinct intralobular localisation. These findings suggest the importance of metabolic zonation in determining transcriptomic heterogeneity of hepatocytes and highlight the diverse nature of hepatic stellate cells in the human liver.

JHEP REPORTS (2021)

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Review Gastroenterology & Hepatology

Cell of origin in biliary tract cancers and clinical implications

Agrin Moeini et al.

Summary: Biliary tract cancers (BTCs) are aggressive epithelial malignancies with rising incidence and mortality rates, emphasizing the need for improved diagnostic and therapeutic strategies. BTCs exhibit high inter- and intra-tumour heterogeneity at both morphological and molecular levels. Recent research has focused on histopathological subtyping and the cell of origin of these tumors, highlighting distinct molecular alterations and potential cells of origin.

JHEP REPORTS (2021)

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Article Multidisciplinary Sciences

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Dominik Pfister et al.

Summary: The text discusses the impact of NASH on the development of HCC and the effect of immunotherapy, revealing the accumulation of exhausted and unconventionally activated CD8(+)PD1(+) T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, anti-PD1 treatment led to an increase in HCC, with CD8(+) T cells contributing to this increase.

NATURE (2021)

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Article Gastroenterology & Hepatology

A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

Yasuhiro Nakano et al.

HEPATOLOGY (2020)

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Editorial Material Cell Biology

The 2019 WHO classification of tumours of the digestive system

Iris D. Nagtegaal et al.

HISTOPATHOLOGY (2020)

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Article Oncology

Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15+ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy

Claudia X. Dominguez et al.

CANCER DISCOVERY (2020)

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Article Oncology

Cancer statistics, 2020

Rebecca L. Siegel et al.

CA-A CANCER JOURNAL FOR CLINICIANS (2020)

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Article Gastroenterology & Hepatology

Identification of Lineage-Specific Transcription Factors That Prevent Activation of Hepatic Stellate Cells and Promote Fibrosis Resolution

Xiao Liu et al.

GASTROENTEROLOGY (2020)

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Article Gastroenterology & Hepatology

Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma

Sylvie Job et al.

HEPATOLOGY (2020)

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Review Gastroenterology & Hepatology

A Single-Cell Perspective of the Mammalian Liver in Health and Disease

Xuelian Xiong et al.

HEPATOLOGY (2020)

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Article Gastroenterology & Hepatology

Transcriptional Dynamics of Hepatic Sinusoid-Associated Cells After Liver Injury

Mike K. Terkelsen et al.

HEPATOLOGY (2020)

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Article

Origin and role of hepatic myofibroblasts in hepatocellular carcinoma

Betul Gok Yavuz et al.

Oncotarget (2020)

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Article Cell Biology

Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth

Sarah Davidson et al.

CELL REPORTS (2020)

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Article Oncology

Ivosidenib in IDH1-mutant, chemotherapy-refractory Croatia& cholangiocarcinoma (ClarlDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

Ghassan K. Abou-Alfa et al.

LANCET ONCOLOGY (2020)

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Article Oncology

Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study

Ghassan K. Abou-Alfa et al.

LANCET ONCOLOGY (2020)

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Article Biochemistry & Molecular Biology

Stromal cell diversity associated with immune evasion in human triple-negative breast cancer

Sunny Z. Wu et al.

EMBO JOURNAL (2020)

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Article Gastroenterology & Hepatology

Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis

Guillaume Lassailly et al.

GASTROENTEROLOGY (2020)

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Review Oncology

The role of fibroblast activation protein in health and malignancy

Allison A. Fitzgerald et al.

CANCER AND METASTASIS REVIEWS (2020)

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Article Oncology

Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer

Ying Shen et al.

CANCER CELL (2020)

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Article Oncology

Interaction with CD68 and Regulation of GAS6 Expression by Endosialin in Fibroblasts Drives Recruitment and Polarization of Macrophages in Hepatocellular Carcinoma

Fa Yang et al.

CANCER RESEARCH (2020)

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Review Gastroenterology & Hepatology

Single-cell genomics and spatial transcriptomics: Discovery of novel cell states and cellular interactions in liver physiology and disease biology

Antonio Saviano et al.

JOURNAL OF HEPATOLOGY (2020)

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Article Gastroenterology & Hepatology

Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma

Min Zhang et al.

JOURNAL OF HEPATOLOGY (2020)

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Article Biochemistry & Molecular Biology

Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma

Ankur Sharma et al.

CELL (2020)

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Article Multidisciplinary Sciences

Senolytic CAR T cells reverse senescence-associated pathologies

Corina Amor et al.

NATURE (2020)

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Article Gastroenterology & Hepatology

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Jesus M. Banales et al.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2020)

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Article Medicine, Research & Experimental

Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma

Emilien Loeuillard et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Article Multidisciplinary Sciences

Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer

Hemant M. Kocher et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma

Zhaohui Chen et al.

NATURE COMMUNICATIONS (2020)

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Article Cell & Tissue Engineering

Hepatic stellate cells contribute to liver regeneration through galectins in hepatic stem cell niche

Jian-Yun Ge et al.

STEM CELL RESEARCH & THERAPY (2020)

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Article Biochemistry & Molecular Biology

Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages

Jeremy Lotto et al.

CELL (2020)

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Article Oncology

A framework for advancing our understanding of cancer-associated fibroblasts

Erik Sahai et al.

NATURE REVIEWS CANCER (2020)

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Article Gastroenterology & Hepatology

Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma

Chun Jye Lim et al.

GUT (2019)

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Article Gastroenterology & Hepatology

Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy

Anthony Tanoto Tan et al.

GASTROENTEROLOGY (2019)

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Review Gastroenterology & Hepatology

Anatomical, histomorphological and molecular classification of cholangiocarcinoma

Timothy Kendall et al.

LIVER INTERNATIONAL (2019)

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Article Oncology

Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager

Jana de Sostoa et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2019)

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Article Gastroenterology & Hepatology

Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice

Takahiro Nishio et al.

JOURNAL OF HEPATOLOGY (2019)

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Article Cell Biology

Single Cell RNA Sequencing Identifies Subsets of Hepatic Stellate Cells and Myofibroblasts in Liver Fibrosis

Oliver Krenkel et al.

CELLS (2019)

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Article Cell Biology

Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis

Yoon Mee Yang et al.

SCIENCE TRANSLATIONAL MEDICINE (2019)

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Article Oncology

β-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma

Marina Ruiz de Galarreta et al.

CANCER DISCOVERY (2019)

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Article Oncology

Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

Ela Elyada et al.

CANCER DISCOVERY (2019)

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Article Biochemistry & Molecular Biology

Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis

Xuelian Xiong et al.

MOLECULAR CELL (2019)

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Article Oncology

Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

Lichun Ma et al.

CANCER CELL (2019)

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Article Biochemistry & Molecular Biology

Hepatic Stellate Cells Enhance Liver Cancer Progression by Inducing Myeloid-Derived Suppressor Cells through Interleukin-6 Signaling

Ching-Chuan Hsieh et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Multidisciplinary Sciences

Resolving the fibrotic niche of human liver cirrhosis at single-cell level

P. Ramachandran et al.

NATURE (2019)

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Article Multidisciplinary Sciences

Embryonic mesothelial-derived hepatic lineage of quiescent and heterogenous scar-orchestrating cells defined but suppressed by WT1

Timothy James Kendall et al.

NATURE COMMUNICATIONS (2019)

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Article Cell Biology

Single-Cell Transcriptomics Uncovers Zonation of Function in the Mesenchyme during Liver Fibrosis

Ross Dobie et al.

CELL REPORTS (2019)

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Article Oncology

IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma

Giulia Biffi et al.

CANCER DISCOVERY (2019)

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Article Oncology

Fibroblastic FAP promotes intrahepatic cholangiocarcinoma growth via MDSCs recruitment

Yuli Lin et al.

NEOPLASIA (2019)

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Article Medicine, Research & Experimental

Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution

Abdel Nasser Hosein et al.

JCI INSIGHT (2019)

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Article Oncology

Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer

Ana Costa et al.

CANCER CELL (2018)

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Article Oncology

Kras and Tp53 Mutations Cause Cholangiocyte- and Hepatocyte-Derived Cholangiocarcinoma

Margaret A. Hill et al.

CANCER RESEARCH (2018)

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Article Cell Biology

Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers

Ken Takai et al.

GENES & DEVELOPMENT (2018)

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Article Gastroenterology & Hepatology

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations

Christopher P. Wardell et al.

JOURNAL OF HEPATOLOGY (2018)

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Review Cell Biology

Mechanisms and impact of altered tumour mechanics

Hamid Mohammadi et al.

NATURE CELL BIOLOGY (2018)

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Review Biochemistry & Molecular Biology

Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics

Ellen Pure et al.

ONCOGENE (2018)

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Article Multidisciplinary Sciences

TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

Sanjeev Mariathasan et al.

NATURE (2018)

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Review Oncology

Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis

Isabel Fabregat et al.

FRONTIERS IN ONCOLOGY (2018)

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Article Multidisciplinary Sciences

Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

Sonya A. MacParland et al.

NATURE COMMUNICATIONS (2018)

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Article Multidisciplinary Sciences

Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing

Michael Bartoschek et al.

NATURE COMMUNICATIONS (2018)

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Article Oncology

Alteration of the Tumor Stroma Using a Consensus DNA Vaccine Targeting Fibroblast Activation Protein (FAP) Synergizes with Antitumor Vaccine Therapy in Mice

Elizabeth K. Duperret et al.

CLINICAL CANCER RESEARCH (2018)

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Review Oncology

Desmoplastic Tumor Microenvironment and Immunotherapy in Cholangiocarcinoma

Dan Hogdall et al.

TRENDS IN CANCER (2018)

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Editorial Material Immunology

Clearing liver metastases

Zoltan Fehervari

NATURE IMMUNOLOGY (2017)

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Article Gastroenterology & Hepatology

Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features

Daniela Sia et al.

GASTROENTEROLOGY (2017)

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Review Medicine, Research & Experimental

Liver inflammation and fibrosis

Yukinori Koyama et al.

JOURNAL OF CLINICAL INVESTIGATION (2017)

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Article Immunology

Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer

Daniel Ohlund et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2017)

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Article Multidisciplinary Sciences

Single-cell spatial reconstruction reveals global division of labour in the mammalian liver

Keren Bahar Halpern et al.

NATURE (2017)

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Article Genetics & Heredity

Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors

Huipeng Li et al.

NATURE GENETICS (2017)

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Letter Biochemical Research Methods

Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations

Susanne C. van den Brink et al.

NATURE METHODS (2017)

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Review Gastroenterology & Hepatology

Mechanisms of hepatic stellate cell activation

Takuma Tsuchida et al.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2017)

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Review Multidisciplinary Sciences

Single-cell transcriptomics to explore the immune system in health and disease

Michael J. T. Stubbington et al.

SCIENCE (2017)

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Article Oncology

Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma

Wataru Shigeeda et al.

ONCOTARGET (2017)

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Article Oncology

The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer

Valentina Mele et al.

ONCOTARGET (2017)

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Review Gastroenterology & Hepatology

Pathology of intrahepatic cholangiocarcinoma

Sandrine Vijgen et al.

HEPATOBILIARY SURGERY AND NUTRITION (2017)

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Article Multidisciplinary Sciences

Glycosylation-dependent galectin-1/ neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells

Ming-Heng Wu et al.

SCIENTIFIC REPORTS (2017)

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Article Biochemistry & Molecular Biology

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

Sidharth V. Puram et al.

CELL (2017)

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Article Oncology

Molecular Pathways: Targeting the Microenvironment of Liver Metastases

Simon Milette et al.

CLINICAL CANCER RESEARCH (2017)

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Article Biochemistry & Molecular Biology

Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

Adrian Ally et al.

CELL (2017)

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Article Gastroenterology & Hepatology

Portal Fibroblasts Marked by the Surface Antigen Thy1 Contribute to Fibrosis in Mouse Models of Cholestatic Liver Injury

Len William Katsumata et al.

HEPATOLOGY COMMUNICATIONS (2017)

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Article Oncology

Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma

Ana L. Gomes et al.

CANCER CELL (2016)

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Article Oncology

Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes

Andriy Marusyk et al.

CANCER RESEARCH (2016)

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Article Oncology

FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling

Xuguang Yang et al.

CANCER RESEARCH (2016)

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Article Biochemistry & Molecular Biology

Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling

Hua Gao et al.

CELL (2016)

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Article Multidisciplinary Sciences

NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis

Chi Ma et al.

NATURE (2016)

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Article Multidisciplinary Sciences

Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion

Cristovao M. Sousa et al.

NATURE (2016)

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Article Multidisciplinary Sciences

ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Antonios Chronopoulos et al.

NATURE COMMUNICATIONS (2016)

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Article Oncology

Cellular apoptosis susceptibility (CAS) is linked to integrin β1 and required for tumor cell migration and invasion in hepatocellular carcinoma (HCC)

Juliane Winkler et al.

ONCOTARGET (2016)

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Article Multidisciplinary Sciences

The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis

Yoshitaka Kimura et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

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Article Oncology

Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells

Albert Lo et al.

CANCER RESEARCH (2015)

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Article Cell Biology

Internalization of the TGF-β type I receptor into caveolin-1 and EEA1 double-positive early endosomes

Kangmin He et al.

CELL RESEARCH (2015)

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Article Gastroenterology & Hepatology

Genetic Landscape and Biomarkers of Hepatocellular Carcinoma

Jessica Zucman-Rossi et al.

GASTROENTEROLOGY (2015)

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Article Cell Biology

A laminin 511 matrix is regulated by TAZ and functions as the ligand for the α6Bβ1 integrin to sustain breast cancer stem cells

Cheng Chang et al.

GENES & DEVELOPMENT (2015)

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Article Gastroenterology & Hepatology

Fibrosis Stage Is the Strongest Predictor for Disease-Specific Mortality in NAFLD After Up to 33 Years of Follow-Up

Mattias Ekstedt et al.

HEPATOLOGY (2015)

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Article Gastroenterology & Hepatology

β-PDGF receptor expressed by hepatic stellate cells regulates fibrosis in murine liver injury, but not carcinogenesis

Peri Kocabayoglu et al.

JOURNAL OF HEPATOLOGY (2015)

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Article Cell Biology

Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver

Bruno Costa-Silva et al.

NATURE CELL BIOLOGY (2015)

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Article Genetics & Heredity

Genomic spectra of biliary tract cancer

Hiromi Nakamura et al.

NATURE GENETICS (2015)

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Article Genetics & Heredity

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

Kornelius Schulze et al.

NATURE GENETICS (2015)

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Article Biochemistry & Molecular Biology

Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells

Laura J. Pallett et al.

NATURE MEDICINE (2015)

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Article Multidisciplinary Sciences

Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma

Daniela Sia et al.

NATURE COMMUNICATIONS (2015)

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Article Oncology

TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma

Tao Song et al.

ONCOTARGET (2015)

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Article Multidisciplinary Sciences

Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis

Hai-Yan Li et al.

SCIENTIFIC REPORTS (2015)

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Article Genetics & Heredity

YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers

Claudia Stein et al.

PLOS GENETICS (2015)

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Article Biochemistry & Molecular Biology

Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy

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CELL (2014)

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Review Gastroenterology & Hepatology

The Portal Fibroblast: Not Just a Poor Man's Stellate Cell

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GASTROENTEROLOGY (2014)

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Article Gastroenterology & Hepatology

Fibroblast Growth Factor Receptor 2 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Cholangiocarcinoma

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HEPATOLOGY (2014)

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Review Gastroenterology & Hepatology

Desmoplastic Stroma and Cholangiocarcinoma: Clinical Implications and Therapeutic Targeting

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HEPATOLOGY (2014)

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Article Gastroenterology & Hepatology

Lysyl Oxidase-Like 2 Is Critical to Tumor Microenvironment and Metastatic Niche Formation in Hepatocellular Carcinoma

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HEPATOLOGY (2014)

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Article Oncology

Paracrine activation of hepatic stellate cells in platelet-derived growth factor C transgenic mice: Evidence for stromal induction of hepatocellular carcinoma

Jocelyn H. Wright et al.

INTERNATIONAL JOURNAL OF CANCER (2014)

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Article Oncology

Kupffer cells decrease metastasis of colon cancer cells to the liver in the early stage

Hideki Matsumura et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2014)

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Article Biochemistry & Molecular Biology

Negative Regulation of NADPH Oxidase 4 by Hydrogen Peroxide-inducible Clone 5 (Hic-5) Protein

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JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

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Article Gastroenterology & Hepatology

A novel mouse model of depletion of stellate cells clarifies their role in ischemia/reperfusion- and endotoxin-induced acute liver injury

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JOURNAL OF HEPATOLOGY (2014)

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Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression

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NATURE MEDICINE (2014)

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Article Genetics & Heredity

Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma

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PLOS GENETICS (2014)

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Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity without Severe Toxicity

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CANCER IMMUNOLOGY RESEARCH (2014)

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Review Immunology

Liver fibrosis and repair: immune regulation of wound healing in a solid organ

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NATURE REVIEWS IMMUNOLOGY (2014)

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Identification of Two Distinct Carcinoma-Associated Fibroblast Subtypes with Differential Tumor-Promoting Abilities in Oral Squamous Cell Carcinoma

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CANCER RESEARCH (2013)

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Article Gastroenterology & Hepatology

Integrative Molecular Analysis of Intrahepatic Cholangiocarcinoma Reveals 2 Classes That Have Different Outcomes

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GASTROENTEROLOGY (2013)

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Article Gastroenterology & Hepatology

A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice

Juan E. Puche et al.

HEPATOLOGY (2013)

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Article Gastroenterology & Hepatology

Reversal of cirrhosis: An achievable goal of hepatitis B antiviral therapy

Yun-Fan Liaw

JOURNAL OF HEPATOLOGY (2013)

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Article Cell Biology

Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts

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NATURE CELL BIOLOGY (2013)

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Article Genetics & Heredity

Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers

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NATURE GENETICS (2013)

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Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

Yuchen Jiao et al.

NATURE GENETICS (2013)

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Article Biochemistry & Molecular Biology

Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs

Neil C. Henderson et al.

NATURE MEDICINE (2013)

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Article Multidisciplinary Sciences

Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial-mesenchymal transition in liver injury

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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Article Multidisciplinary Sciences

Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology

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NATURE COMMUNICATIONS (2013)

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Article Multidisciplinary Sciences

High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions

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NATURE COMMUNICATIONS (2013)

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Article Oncology

Identification of Targetable FGFR Gene Fusions in Diverse Cancers

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CANCER DISCOVERY (2013)

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Hepatic Stellate Cells and Liver Fibrosis

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COMPREHENSIVE PHYSIOLOGY (2013)

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Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

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CANCER CELL (2012)

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Article Gastroenterology & Hepatology

Autophagy Releases Lipid That Promotes Fibrogenesis by Activated Hepatic Stellate Cells in Mice and in Human Tissues

Virginia Hernandez-Gea et al.

GASTROENTEROLOGY (2012)

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Article Gastroenterology & Hepatology

Deactivation of Hepatic Stellate Cells During Liver Fibrosis Resolution in Mice

Juliane S. Troeger et al.

GASTROENTEROLOGY (2012)

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Genomic and Genetic Characterization of Cholangiocarcinoma Identifies Therapeutic Targets for Tyrosine Kinase Inhibitors

Jesper B. Andersen et al.

GASTROENTEROLOGY (2012)

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Discoidin domain receptor 2 deficiency predisposes hepatic tissue to colon carcinoma metastasis

Iker Badiola et al.

GUT (2012)

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Article Medicine, Research & Experimental

Cholangiocarcinomas can originate from hepatocytes in mice

Biao Fan et al.

JOURNAL OF CLINICAL INVESTIGATION (2012)

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Article Medicine, Research & Experimental

Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes

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JOURNAL OF CLINICAL INVESTIGATION (2012)

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Article Immunology

IL-10-Producing Regulatory B Cells in the Pathogenesis of Chronic Hepatitis B Virus Infection

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JOURNAL OF IMMUNOLOGY (2012)

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Article Genetics & Heredity

Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma

Cecile Guichard et al.

NATURE GENETICS (2012)

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Article Oncology

Frequent Mutation of Isocitrate Dehydrogenase (IDH)1 and IDH2 in Cholangiocarcinoma Identified Through Broad-Based Tumor Genotyping

Darrell R. Borger et al.

ONCOLOGIST (2012)

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Article Multidisciplinary Sciences

Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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Review Pathology

Diagnosis of Well-differentiated Hepatocellular Lesions: Role of Immunohistochemistry and Other Ancillary Techniques

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ADVANCES IN ANATOMIC PATHOLOGY (2011)

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Review Biochemistry & Molecular Biology

Hallmarks of Cancer: The Next Generation

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CELL (2011)

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Article Multidisciplinary Sciences

Role of YAP/TAZ in mechanotransduction

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NATURE (2011)

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Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization

Nobutaka Kobayashi et al.

CANCER RESEARCH (2010)

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Immunotherapy targeting fibroblast activation protein inhibits tumor growth and increases survival in a murine colon cancer model

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CANCER SCIENCE (2010)

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Review Surgery

Liver Regeneration: Focus on Cell Types and Topographic Differences

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EUROPEAN SURGICAL RESEARCH (2010)

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Article Multidisciplinary Sciences

A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection

John A. Mengshol et al.

PLOS ONE (2010)

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Review Oncology

Integrins in cancer: biological implications and therapeutic opportunities

Jay S. Desgrosellier et al.

NATURE REVIEWS CANCER (2010)

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Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

Kandice R. Levental et al.

CELL (2009)

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Mesenchymal Origin of Hepatic Stellate Cells, Submesothelial Cells, and Perivascular Mesenchymal Cells During Mouse Liver Development

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HEPATOLOGY (2009)

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Regulation of sinusoidal perfusion in portal hypertension

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ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY (2008)

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Article Medicine, General & Internal

Brief communication: The relationship of regression of cirrhosis to outcome in chronic hepatitis C

Vincent Mallet et al.

ANNALS OF INTERNAL MEDICINE (2008)

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Focal gains of VEGFA and molecular classification of hepatocellular carcinoma

Derek Y. Chiang et al.

CANCER RESEARCH (2008)

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Article Biochemistry & Molecular Biology

Senescence of activated stellate cells limits liver fibrosis

Valery Krizhanovsky et al.

CELL (2008)

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Review Physiology

Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver

Scott L. Friedman

PHYSIOLOGICAL REVIEWS (2008)

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Article Gastroenterology & Hepatology

Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets

Sandrine Boyault et al.

HEPATOLOGY (2007)

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Review Medicine, Research & Experimental

Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ

John P. Iredale

JOURNAL OF CLINICAL INVESTIGATION (2007)

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Article Biochemistry & Molecular Biology

Force sensing by mechanical extension of the Src family kinase substrate p130Cas

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CELL (2006)

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Review Biochemistry & Molecular Biology

Tumor metastasis: mechanistic insights and clinical challenges

Patricia S. Steeg

NATURE MEDICINE (2006)

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A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells

JS Lee et al.

NATURE MEDICINE (2006)

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Fibroblast activation protein is expressed by rheumatoid myofibroblast-like synoviocytes

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ARTHRITIS RESEARCH & THERAPY (2006)

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Tensional homeostasis and the malignant phenotype

MJ Paszek et al.

CANCER CELL (2005)

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Article Biochemistry & Molecular Biology

Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion

A Orimo et al.

CELL (2005)

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Article Gastroenterology & Hepatology

Preferential loss of IL-2-secreting CD4+ T helper cells in chronic HCV infection

N Semmo et al.

HEPATOLOGY (2005)

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Article Gastroenterology & Hepatology

An immunomodulatory role for CD4+CD25+ regulatory T lymphocytes in hepatitis C virus infection

R Cabrera et al.

HEPATOLOGY (2004)

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Lamivudine for patients with chronic hepatitis B and advanced liver disease

YF Liaw et al.

NEW ENGLAND JOURNAL OF MEDICINE (2004)

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Article Gastroenterology & Hepatology

Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype

B Schnabl et al.

HEPATOLOGY (2003)

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Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B

YO Kweon et al.

JOURNAL OF HEPATOLOGY (2001)

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Article Medicine, General & Internal

Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy

Y Shiratori et al.

ANNALS OF INTERNAL MEDICINE (2000)

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