Cellular origins of regenerating liver and hepatocellular carcinoma

Holczbauer, Ágnes; Wangensteen, Kirk J.; Shin, Soona

doi:10.1016/j.jhepr.2021.100416

Cited by 22 publications

(19 citation statements)

References 134 publications

(192 reference statements)

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“…In healthy mice CSF1-Fc-induced liver growth was associated with an increase in Ki67+ hepatocytes as well as non-parenchymal cells, whereas the large increase in hepatic Ki67+ cells in TAA-treated mice was largely in the non-parenchymal compartment, consistent with evidence of impaired hepatocytemediated regeneration in chronically injured liver (Holczbauer et al, 2021). We hypothesized this may reflect a role for HPC.…”

Section: Discussionmentioning

confidence: 74%

“…Hence, we do not provide support for direct engagement of recruited macrophages with HPC in this setting. Alternative mechanisms that may contribute to liver growth, especially in fibrotic liver, may include hepatocyte hypertrophy, reductive cell division and immature hepatocytes (distinct from the ductular reaction) ( Holczbauer et al, 2021 ; Miyaoka et al, 2012 ; Nakano et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease

Keshvari

Genz

Teakle

et al. 2022

Disease Models &Amp; Mechanisms

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Resident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, utilizing a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodeling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease

Keshvari

Genz

Teakle

et al. 2022

Disease Models &Amp; Mechanisms

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“…The mortality rate continues to increase, and the 5 year relative survival rate is just 18%, with only pancreatic cancer having a lower mortality rate. 5,6 It follows that there is an urgent need to improve the survival outcome of HCC. Nonetheless great progress in immunotherapy, especially immune checkpoint blockade (ICB) treatment, has been made as a first-line strategy for late HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of secretory pathway‐related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma

Wang,

Shi,

Huang

et al. 2023

The Journal of Gene Medicine

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BackgroundThe dysfunction of secretory pathways may represent biomarkers or therapeutic targets of cancer. The hepatocellular carcinoma (HCC) phenotype was studied in relation to the genes in the secretory pathway and to screen for a combination of genes that may be a viable therapeutic target for HCC and connected to the pathophysiological features of the tumor.MethodsUsing the HCC information from The Cancer Genome Atlas, somatic mutation and prognostic association analysis were performed on the secretory pathway genes. Based on prognostic genes in the secretory pathway, the samples were consensus clustered, and a Random Forest model was built. The clinical characteristics, tumor mutation burden, functional status and potential responses to immunotherapy and tumor suppressor medications of various subtypes and risk groups were discussed.ResultsOf the 84 genes for secretory pathway, 32 were prognostic genes related to HCC, which divided HCC into two categories: C1 and C2. By comparing the two types of HCC samples, it was found that the survival outcome of C1 was inferior, with stronger adaptive and innate immunity, but less sensitive to immunotherapy than C2. The constructed prognostic signature included seven of the 32 prognostic genes in the secretory pathway, which showed significant correlation with the prognosis, somatic mutation, biological pathway status, potential response to immunotherapy and sensitivity of 72 tumor suppressor drugs from different HCC cohorts, and had a feasible prognostic effect for 31 types of cancer and immunotherapy cohorts.ConclusionsIn this study, HCC was divided into two molecular subtypes according to prognostic genes in the secretory pathway, and seven of them were combined into one signature, which produced significant results in evaluating the prognosis of different HCC cohorts, pan‐cancer cohorts and immunotherapy cohorts, and had potential guiding significance for prophylactic immunotherapy in patients with HCC.

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“…The progression of the disease includes a passage through a cirrhotic stage in a large majority of HCC cases (up to 90%) (11). Oxidative damage (12), inflammation (13), hepatocyte compensatory regeneration (14), with consequent accumulation of gene mutations, are typical HCC features. Mutational HCC landscape includes many genes with different mutation frequency, such as TP53 (30%), CTNNB1/b-catenin (26%), ARID1A (8%), ARID2 (6%), AXIN (6%) (15).…”

Section: Introductionmentioning

confidence: 99%

Role of exosomal microRNAs in cancer therapy and drug resistance mechanisms: focus on hepatocellular carcinoma

Zelli

Compagnoni²,

Capelli³

et al. 2022

Front. Oncol.

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Extracellular vesicles (EVs), defined as intercellular messengers that carry their cargos between cells, are involved in several physiological and pathological processes. These small membranous vesicles are released by most cells and contain biological molecules, including nucleic acids, proteins and lipids, which can modulate signaling pathways of nearby or distant recipient cells. Exosomes, one the most characterized classes of EVs, include, among others, microRNAs (miRNAs), small non-coding RNAs able to regulate the expression of several genes at post-transcriptional level. In cancer, exosomal miRNAs have been shown to influence tumor behavior and reshape tumor microenvironment. Furthermore, their possible involvement in drug resistance mechanisms has become evident in recent years. Hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for 75-85% of all liver tumors. Although the improvement in HCC treatment approaches, low therapeutic efficacy in patients with intermediate-advanced HCC is mainly related to the development of tumor metastases, high risk of recurrence and drug resistance. Exosomes have been shown to be involved in pathogenesis and progression of HCC, as well as in drug resistance, by regulating processes such as cell proliferation, epithelial-mesenchymal transition and immune response. Herein, we summarize the current knowledge about the involvement of exosomal miRNAs in HCC therapy, highlighting their role as modulators of therapeutic response, particularly chemotherapy and immunotherapy, as well as possible therapeutic tools.

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Cellular origins of regenerating liver and hepatocellular carcinoma

Cited by 22 publications

References 134 publications

Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease

Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease

Identification of secretory pathway‐related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma

Role of exosomal microRNAs in cancer therapy and drug resistance mechanisms: focus on hepatocellular carcinoma

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