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Biomarker and Translational Research in Oncology and Liver Diseases
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Biomarker and Translational Research in Oncology and Liver Diseases

A special issue of International Journal of Translational Medicine (ISSN 2673-8937).

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 19563

Special Issue Editor

Prof. Dr. Matthias Ocker

E-Mail Website
Guest Editor
Medical Department, Division of Hematology, Oncology, and Cancer Immunology, Campus Charité Mitte, Charité University Medicine Berlin, 10117 Berlin, Germany
Interests: drug development; biomarker and translational research in oncology and liver diseases; cellular biology of cell death and epigenetics

Special Issue Information

Dear Colleagues,

Chronic liver diseases are a global medical burden. With the steep rise of non-alcoholic fatty liver disease (NAFLD) and subsequent steatohepatitis (NASH), the incidence and prevalence of fibrotic and end-stage liver disease and of hepatocellular carcinoma (HCC) are also expected to rise in the coming years. While some progress was made in identifying and validating diagnostic biomarkers, only a few advances have been achieved on predictive biomarkers that could also lead to innovative and novel treatment approaches. The focus on the inflammatory microenvironment in NASH, cirrhosis and HCC has further increased the complexity since novel approaches beyond T-cell targeting are maturing now. This also requires novel designs for clinical trials and the strong need to thoroughly characterize the disease and disease-modulating pathways in translational clinical and preclinical research and studies. It is important to highlight that translational studies go beyond the analysis of biomarkers but do also comprise bioinformatics, scheduling and clinical pharmacology applications.

In this Special Issue, we aim to summarize the current status and challenges of translational and biomarker research in preclinical and clinical research of liver diseases, including NAFLD, NASH, cirrhosis and HCC. We especially welcome papers focusing on artificial intelligence and translational approaches like modelling, molecular imaging or liquid biopsy technologies.

Prof. Dr. Matthias Ocker
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Translational Medicine is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • NAFLD
  • NASH
  • HCC
  • cirrhosis
  • fibrosis
  • liver cancer
  • biomarker
  • artificial intelligence
  • machine learning
  • bioinformatics
  • clinical pharmacology
  • modelling

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (4 papers)

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Research

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15 pages, 3188 KiB  
Article
Transcriptomic Analysis of Insulin-Secreting Murine Hepatocytes Transduced with an Integrating Adeno-Associated Viral Vector
by Alexandra L. G. Mahoney, Sergio Joshua, Najah T. Nassif and Ann M. Simpson
Int. J. Transl. Med. 2023, 3(3), 374-388; https://doi.org/10.3390/ijtm3030026 - 6 Sep 2023
Viewed by 1426
Abstract
Type 1 Diabetes (T1D) is a chronic metabolic disorder for which current treatments are unable to prevent the onset of complications. Previously, we used an adeno-associated viral vector (AAV8) to deliver furin-cleavable human insulin (INS-FUR) to the livers of diabetic non-obese diabetic (NOD) [...] Read more.
Type 1 Diabetes (T1D) is a chronic metabolic disorder for which current treatments are unable to prevent the onset of complications. Previously, we used an adeno-associated viral vector (AAV8) to deliver furin-cleavable human insulin (INS-FUR) to the livers of diabetic non-obese diabetic (NOD) mice to reverse T1D. The use of the traditional AAV8-INS-FUR vector could not bring about normoglycemia. However, this vector, coupled with a transposon system in the AAV8/piggyBac-INS-FUR vector, was able to do so. This study aimed to investigate the transcriptomic profiles of the livers of diabetic, AAV8-INS-FUR-transduced, and AAV8/piggyBac-INS-FUR-transduced NOD mice and compare these to the normal liver to identify genetic differences resulting from delivery of the AAV8/piggyBac-INS-FUR vector which produced normoglycemia. Differential gene expression was determined by RNA-Seq analysis and differentially expressed genes from each treatment were mapped onto cellular pathways to determine the treatments’ cell signaling and downstream effects. We observed distinct differences between the piggyBac-transduced and diabetic models, particularly in terms of metabolic function and the upregulation of key pancreatic markers in the liver of piggyBac-transduced animals. The success of the AAV8/piggyBac-INS-FUR vector in achieving normoglycemia through stable transduction was evident. However, further engineering is necessary to achieve complete pancreatic transdifferentiation of liver cells. Full article
(This article belongs to the Special Issue Biomarker and Translational Research in Oncology and Liver Diseases)
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10 pages, 1750 KiB  
Article
Sustained Virological Response Is the Most Effective in Preventing Hepatocellular Carcinoma Recurrence after Curative Treatment in Hepatitis C Virus-Positive Patients: A Study Using Decision Tree Analysis
by Kenji Imai, Koji Takai, Shinji Unome, Takao Miwa, Toshihide Maeda, Tatsunori Hanai, Yohei Shirakami, Atsushi Suetsugu and Masahito Shimizu
Int. J. Transl. Med. 2022, 2(3), 345-354; https://doi.org/10.3390/ijtm2030027 - 20 Jul 2022
Viewed by 1880
Abstract
This study evaluated the factors that affect the recurrence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients, who had received curative treatment for initial HCC, using decision tree analysis in 111 curative cases. The enrolled patients were divided into three groups [...] Read more.
This study evaluated the factors that affect the recurrence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients, who had received curative treatment for initial HCC, using decision tree analysis in 111 curative cases. The enrolled patients were divided into three groups by the decision tree analysis as follows: Patients who achieved sustained virological response (SVR) after curative treatment belonged to Group 1 (n = 33), those who did not achieve SVR and with alpha-fetoprotein (AFP) levels < 11 ng/mL belonged to Group 2 (n = 30), and those who did not achieve SVR and with AFP levels ≥ 11 ng/mL belonged to Group 3 (n = 48). The Kaplan–Meier method revealed that Group 1 had significantly longer recurrence-free survival than Group 2 or 3 (p = 0.004). Moreover, there was no significant difference between patients achieving SVR with direct-acting antivirals and interferon therapy (p = 0.251). Group 3 had significantly poorer recurrence-free survival than Group 2 (p < 0.001). The Cox proportional hazards model demonstrated that SVR achievement was the only independent factor associated with low HCC recurrence (p = 0.005). In conclusion, patients who achieved SVR were the least prone to HCC recurrence, whereas those who did not achieve SVR and had AFP levels ≥ 11 ng/mL were the most prone to HCC recurrence. Full article
(This article belongs to the Special Issue Biomarker and Translational Research in Oncology and Liver Diseases)
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Review

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15 pages, 624 KiB  
Review
Advancements in the Diagnosis of Hepatocellular Carcinoma
by Natalia Salinas Parra, Heather M. Ross, Adnan Khan, Marisa Wu, Risa Goldberg, Lokesh Shah, Sarah Mukhtar, Jacob Beiriger, Alexis Gerber and Dina Halegoua-DeMarzio
Int. J. Transl. Med. 2023, 3(1), 51-65; https://doi.org/10.3390/ijtm3010005 - 11 Jan 2023
Cited by 14 | Viewed by 11235
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing global incidence. Morbidity and mortality associated with HCC remains high, and HCC is the leading cause of cancer death worldwide. Early detection and treatment of HCC can increase five-year survival by [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing global incidence. Morbidity and mortality associated with HCC remains high, and HCC is the leading cause of cancer death worldwide. Early detection and treatment of HCC can increase five-year survival by over 60%. Detection of HCC remains challenging, however, as HCC arises from a variety of environmental, genetic, and viral etiologies, and it demonstrates a complex pathophysiology and displays a heterogeneous morphology. Current diagnostic methods rely on abdominal ultrasound with or without concurrent AFP biomarker testing for high-risk individuals. This review provides an overview of HCC diagnostic modalities and highlights the promising nature of translational developments in biomarkers, next generation sequencing (NGS), artificial intelligence, molecular imaging, and liquid biopsy for earlier and more accurate diagnosis of HCC. Furthermore, we identify areas for improvement that must be addressed before the widespread usage and implementation of these methods. Full article
(This article belongs to the Special Issue Biomarker and Translational Research in Oncology and Liver Diseases)
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Other

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12 pages, 2150 KiB  
Case Report
Treatment of Refractory Checkpoint-Inhibitor-Induced Hepatitis with Tacrolimus: A Case and Review of the Literature
by Ruben De Wilde, Michael Saerens, Anne Hoorens, Anja Geerts and Celine Jacobs
Int. J. Transl. Med. 2023, 3(3), 274-285; https://doi.org/10.3390/ijtm3030019 - 30 Jun 2023
Cited by 1 | Viewed by 3982
Abstract
Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as [...] Read more.
Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as a second-line immunosuppressant in the case of the failure of corticosteroids. In rare cases, though, irH is also resistant to MMF and may lead to liver failure. There are no standard third-line treatments and current guidelines are based on a limited number of case reports. We present a case of a metastatic melanoma patient with an immune-related hepatitis refractory to corticosteroids and MMF, that was successfully reversed with tacrolimus. Unfortunately, this was complicated with a serious infection and progressive disease, which illustrates the complexity of treatment of steroid-refractory immunotherapy-related adverse events. Furthermore, we provided a literature review regarding the management of steroid-refractory hepatitis and proposed a strategy to circumvent the current uncertainties in the management of steroid-refractory irH. Full article
(This article belongs to the Special Issue Biomarker and Translational Research in Oncology and Liver Diseases)
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