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Hepatocellular Carcinoma in the Era of Precision Oncology

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 4818

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Special Issue Editors

Dr. Anna Rossetto

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Guest Editor

General Surgery, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), San Daniele del Friuli, Udine, Italy
Interests: hepatocellular carcinoma; immunology in HCC; liver microenvironment

Prof. Dr. Alessandro Uzzau

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Guest Editor

Department of Experimental and Clinical Medical Sciences, Università degli Studi di Udine, Udine, Italy
Interests: hepatocellular carcinoma; hepatobiliopancreatic surgery; hepatic resection

Special Issue Information

Dear Colleagues,

Great strides have been made in the management of hepatocellular carcinoma in recent decades, but this condition remains a significant challenge due to its aggressiveness and complexity. The therapeutic options have been expanded thanks to studies on the pathways of carcinogenesis and disease progression. Early diagnosis is still key, as one of the main negative prognostic factors of advanced disease.

The use of strategies that allow hepatocellular carcinoma to be identified very early on is essential. The search for specific, accurate, and easily and minimally obtainable biomarkers such as circulating DNA and the identification of immunological pathways and bidirectional multiorgan pathways (e.g., gut–liver axis) with metabolites that can be utilized for diagnostic purposes are significantly changing the management of HCC.

In addition, technical advances established with the aim of achieving the greatest possible oncological accuracy using instruments such as fluorescence-guided surgery are increasingly being developed, together with the achievement of less surgical trauma during laparoscopic or robotic surgery.

The introduction of new systemic pharmacological therapies and the use of ablative therapies that are not new but that have aroused particular interest for the discovery of systemic effects are further shifting the field thanks to the possibility of new tailor-made and customizable therapeutic combinations that are helping to expand and greatly improve the therapeutic possibilities in the context of the new emerging discipline of precision oncology.

Dr. Anna Rossetto
Prof. Dr. Alessandro Uzzau
Guest Editors

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Keywords

hepatocellular carcinoma
liver resection
liver disease
liver surgery
gut-liver axis
gut microbiota
immunology in HCC
hepatocellular carcinoma
biomarkers

Published Papers (3 papers)

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Research

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13 pages, 4584 KiB

Open AccessArticle

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran, a Benzofuran Derivative, Suppresses Metastasis Effects in P53-Mutant Hepatocellular Carcinoma Cells

by Tsui-Hwa Tseng, Yi-Chia Shao, Yean-Jang Lee and Huei-Jane Lee

Biomedicines 2023, 11(7), 2027; https://doi.org/10.3390/biomedicines11072027 - 19 Jul 2023

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Abstract

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran (BMBF), a benzofuran derivative, is an intermediate found in the process of total synthesis of ailanthoidol. Benzofuran derivatives are a class of compounds that possess various biological and pharmacological activities. The present study explored the anti-metastasis effects of BMBF in hepatocellular carcinoma (HCC). Our preliminary findings indicate that BMBF suppresses the proliferation and changes the morphology of Huh7—an HCC cell line with a mutated p53 gene (Y220C). According to a scratching motility assay, non-cytotoxic concentrations of BMBF significantly inhibited the motility and migration in Huh7 cells. BMBF upregulated the expression of E-cadherin and downregulated the expression of vimentin, Slug, and MMP9, which are associated with epithelial–mesenchymal transition (EMT) and metastasis in Huh7 cells. BMBF decreased the expression of integrin α7, deactivated its downstream signal FAK/AKT, and inhibited p53 protein levels. Cell transfection with p53 siRNA resulted in the prevention of cell invasion because of the reduction in integrin α7, Slug, and MMP-9 in Huh7 cells. BMBF had anti-metastatic effects in PLC/PRF/5—an HCC cell line with R249S, a mutated p53 gene. Our findings indicate that BMBF has anti-metastatic effects in downregulating p53 and mediating the suppression of integrin α7, EMT, and MMP-9 in HCC cells with a mutated p53 gene. Full article

(This article belongs to the Special Issue Hepatocellular Carcinoma in the Era of Precision Oncology)

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14 pages, 995 KiB

Open AccessArticle

Combination of Hepatitis B Virus Pre-S2 Gene Deletion Mutation and Tumor-Node-Metastasis Stage Predicts Higher Hepatocellular Carcinoma Recurrence after Curative Surgical Resection

by Long-Bin Jeng, Tsai-Chung Li, Wen-Ling Chan and Chiao-Fang Teng

Biomedicines 2023, 11(3), 923; https://doi.org/10.3390/biomedicines11030923 - 16 Mar 2023

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Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent and life-threatening human cancers worldwide. Despite curative resection surgery, the high recurrence rate of HCC leads to poor patient survival. Chronic hepatitis B virus (HBV) infection is a major etiological factor for HCC. HBV pre-S2 gene deletion mutation leads to the expression of an important oncoprotein called a pre-S2 mutant. It represents an independent prognostic biomarker for HCC recurrence. This study aimed to identify other independent prognostic biomarkers from clinicopathological characteristics of 75 HBV-related HCC patients receiving resection surgery and to validate their potential to be combined with pre-S2 gene deletion mutation as a combination biomarker for HCC recurrence. Patients with both the presence of pre-S2 gene deletion mutation and tumor-node-metastasis (TNM) stage IIIA–IIIC had a higher HCC recurrence risk than patients with either one or none of these two factors. Moreover, the combination of pre-S2 gene deletion mutation and TNM stage exhibited better performance than either of these two factors alone in discriminating patients from patients without HCC recurrence. Collectively, this study proposed that the TNM stage held significance as a combination biomarker with pre-S2 gene deletion mutation with a greater performance in predicting HCC recurrence after curative surgical resection. Full article

(This article belongs to the Special Issue Hepatocellular Carcinoma in the Era of Precision Oncology)

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Review

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21 pages, 1285 KiB

Open AccessReview

Non-Classical HLA Class 1b and Hepatocellular Carcinoma

by Valli De Re, Maria Lina Tornesello, Vito Racanelli, Marcella Prete and Agostino Steffan

Biomedicines 2023, 11(6), 1672; https://doi.org/10.3390/biomedicines11061672 - 9 Jun 2023

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Abstract

A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host’s defense against pathogens and tumor cells. In addition, HLA-specific interactions with innate lymphoid cell receptors, such those present on natural killer cells and innate lymphoid cell type 2, have been shown to be important activators of immune function in the context of several liver diseases. More recent studies have highlighted the key role of members of the non-classical HLA-Ib and the transcript adjacent to the HLA-F locus, FAT10, in hepatocarcinoma. The present review analyzes the major contribution of these molecules to hepatic viral infection and hepatocellular prognosis. Particular attention has been paid to the association of natural killer and Vδ2 T-cell activation, mediated by specific HLA class Ib molecules, with risk assessment and novel treatment strategies to improve immunotherapy in HCC. Full article

(This article belongs to the Special Issue Hepatocellular Carcinoma in the Era of Precision Oncology)

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