scholarly journals Translational Perspective in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Sivapatham Sundaresan ◽  
Palanirasu Rajapriya
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Liver Cancer ◽  
Clinical Research ◽  
Translational Research ◽  
Basic Science ◽  
Molecular Mechanisms ◽  
High Risk Group ◽  
Culture Systems ◽  
Hepatitis C Viruses

The burden of liver cancer is higher in Hispanics, African Americans, and Asians. Viral hepatitis (Hepatitis B and Hepatitis C viruses), non-alcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) are the most common etiological/risk factors for liver cancer. Approximately 80–90% of hepatocellular carcinoma (HCC) occurs in patients with underlying liver cirrhosis. Individuals with advanced cirrhosis represent a high-risk group for liver cancer. To fill the increasing gap between basic science and clinical research, translational research has been developed as an emerging technology. Basic science attempts to unravel the mechanisms of disease using tools (e.g., culture systems and animal models) that allow for easy manipulation of biological processes. Further, culture systems and animal models are useful to derive causal associations, but they generally do not include an endpoint directly applicable to clinical practice. Hence, development of new tools for early detection, including the evaluation of liquid biopsy, identification of tissue biomarkers of treatment response, execution of precision and enhancement of patient stratification in patients at risk for HCC development to enable chemoprevention clinical trials becomes important. It was identified as translational research has begun as an effective approach to facilitate the development of novel molecular-based biomarkers and to accelerate the implementation of laboratory discoveries into clinically applicable tools. Despite great advancement in diagnosis and management of HCC, the exact biology of the tumor remains poorly understood generally limiting the clinical outcome. Comprehensive analysis and characterization of the molecular mechanisms and subsequently individual prediction of corresponding prognostic traits would transform both diagnosis and treatment of HCC and is the key goal of modern medicine. To overcome the challenge and to accelerate the progress, a collaborative effort from various clinical research groups and translational approach is needed.

scholarly journals Profiling of tumour-associated microbiota in human hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seiga Komiyama ◽  
Takahiro Yamada ◽  
Nobuyuki Takemura ◽  
Norihiro Kokudo ◽  
Koji Hase ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver Disease ◽  
Primary Liver Cancer ◽  
Epithelial Barrier ◽  
Sequence Variants ◽  
Alcoholic Fatty Liver ◽  
Uncultured Bacterium ◽  
Hepatitis C Viruses ◽  
Alcoholic Fatty Liver Disease

AbstractLiver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

scholarly journals Translational Animal Models for Liver Cancer

2018 ◽  
Vol 2 ◽  
pp. 2 ◽  
Author(s):  
Michele Obeid ◽  
Ramzy C. Khabbaz ◽  
Kelly D. Garcia ◽  
Kyle M. Schachtschneider ◽  
Ron C. Gaba
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Research ◽  
Animal Models ◽  
Liver Cancer ◽  
Small Animal ◽  
Large Animal ◽  
Starting Point ◽  
Perfect Model ◽  
Small Animal Models ◽  
Human Primate

Animal models have become increasingly important in the study of hepatocellular carcinoma (HCC), as they serve as a critical bridge between laboratory-based discoveries and human clinical trials. Developing an ideal animal model for translational use is challenging, as the perfect model must be able to reproduce human disease genetically, anatomically, physiologically, and pathologically. This brief review provides an overview of the animal models currently available for translational liver cancer research, including rodent, rabbit, non-human primate, and pig models, with a focus on their respective benefits and shortcomings. While small animal models offer a solid starting point for investigation, large animal HCC models are becoming increasingly important for translation of preclinical results to clinical practice.

Bridging basic science and clinical research – The EASL Monothematic Conference on Translational Research in Viral Hepatitis

2014 ◽  
Vol 61 (3) ◽  
pp. 696-705 ◽  
Author(s):  
Tobias Boettler ◽  
Darius Moradpour ◽  
Robert Thimme ◽  
Fabien Zoulim
Keyword(s):  
Clinical Research ◽  
Viral Hepatitis ◽  
Translational Research ◽  
Basic Science

scholarly journals Mast Cells Resting-Related Prognostic Signature in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hao Zhang ◽  
Lin Sun ◽  
Xiao Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mast Cells ◽  
Liver Cancer ◽  
Differentially Expressed Genes ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
New Ideas ◽  
Cancer Genome Atlas

The immune microenvironment of liver cancer is of great significance for the treatment of liver cancer. After evaluating the content of mast cells resting in the transcriptome data of The Cancer Genome Atlas database by CIBERSORT analysis, this study aimed to group the samples according to the content of mast cells resting in different samples to find the differentially expressed genes in the two groups. Significant prognostic differences were found between high and low mast cells resting infiltration groups. The prognostic model was constructed according to the differentially expressed genes. The model was validated using external independent datasets. The results revealed that the constructed model was reliable. It could well distinguish the prognostic differences of patients in different characteristic groups. The high-risk group was mainly concentrated in metabolic pathways. The risk score of this model was closely related to some immune cells, immune function, and immune checkpoints. Therefore, this model may provide new ideas for immunotherapy of hepatocellular carcinoma.

scholarly journals Exosomal MiR-1290 Promotes Angiogenesis of Hepatocellular Carcinoma via Targeting SMEK1

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qiong Wang ◽  
Guanwen Wang ◽  
Lianjie Niu ◽  
Shaorong Zhao ◽  
Jianjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Liver Cancer ◽  
Blood Vessel ◽  
Tumor Angiogenesis ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Primary Liver Cancer ◽  
Human Endothelial Cells ◽  
Direct Target

Hepatocellular carcinoma (HCC), the most common primary liver cancer, relies on the formation of new blood vessel for growth and frequent intrahepatic and extrahepatic metastasis. Therefore, it is important to explore the underlying molecular mechanisms of tumor angiogenesis of HCC. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, the potential roles of tumor-derived exosomal microRNAs in regulating tumor angiogenesis remain to be elucidated. In this study, our miRNome sequencing demonstrated that miR-1290 was overexpressed in HCC patient serum-derived exosomes, and we found that delivery of miR-1290 into human endothelial cells enhanced their angiogenic ability. Our results further revealed that SMEK1 is a direct target of miR-1290 in endothelial cells. MiR-1290 exerted its proangiogenic function, at least in part, by alleviating the inhibition of VEGFR2 phosphorylation done by SMEK1. Collectively, our findings provide evidence that miR-1290 is overexpressed in HCC and promotes tumor angiogenesis via exosomal secretion, implicating its potential role as a therapeutic target for HCC.

scholarly journals Molecular Mechanisms and Animal Models of HBV-Related Hepatocellular Carcinoma: With Emphasis on Metastatic Tumor Antigen 1

2021 ◽  
Vol 22 (17) ◽  
pp. 9380
Author(s):  
Yung-Tsung Li ◽  
Hui-Lin Wu ◽  
Chun-Jen Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Tumor Antigen ◽  
Molecular Mechanisms ◽  
Viral Vector ◽  
Tree Shrew ◽  
Metastatic Tumor ◽  
Asia Pacific ◽  
Molecular Heterogeneity ◽  
Suitable Animal Model

Hepatocellular carcinoma (HCC) is an important cause of cancer death worldwide, and hepatitis B virus (HBV) infection is a major etiology, particularly in the Asia-Pacific region. Lack of sensitive biomarkers for early diagnosis of HCC and lack of effective therapeutics for patients with advanced HCC are the main reasons for high HCC mortality; these clinical needs are linked to the molecular heterogeneity of hepatocarcinogenesis. Animal models are the basis of preclinical and translational research in HBV-related HCC (HBV-HCC). Recent advances in methodology have allowed the development of several animal models to address various aspects of chronic liver disease, including HCC, which HBV causes in humans. Currently, multiple HBV-HCC animal models, including conventional, hydrodynamics-transfection-based, viral vector-mediated transgenic, and xenograft mice models, as well as the hepadnavirus-infected tree shrew and woodchuck models, are available. This review provides an overview of molecular mechanisms and animal models of HBV-HCC. Additionally, the metastatic tumor antigen 1 (MTA1), a cancer-promoting molecule, was introduced as an example to address the importance of a suitable animal model for studying HBV-related hepatocarcinogenesis.

scholarly journals Translational Science Research: Towards Better Health

2009 ◽  
Vol 9 (1) ◽  
Author(s):  
Emir Festic ◽  
Ognjen Gajic
Keyword(s):  
Clinical Research ◽  
Translational Research ◽  
Bosnia And Herzegovina ◽  
21St Century ◽  
Basic Science ◽  
Translational Medicine ◽  
Science Research ◽  
Research Centers ◽  
Research Knowledge ◽  
Basic Science Research

Even though it is considered a 21st century term, translational research has been present for much longer. Idea of translating experimental discovery to its’ clinical application and use is old as research itself. However, it is the understanding of missing links between the basic science research and clinical research that emerged in the past decade and mobilized scientific and clinical communities and organizations worldwide. Hence term, translational research, which represents an “enterprise of harnessing knowledge from basic sciences to produce new drugs, devices, and treatment options for patients” (1). It has been also characterized as “effective translation of the new knowledge, mechanisms, and techniques generated by advances in basic science research into new approaches for prevention, diagnosis, and treatment of disease, which is essential for improving health” (2).This translation is a complex process and involves more than one step for transfer of research knowledge. At least 3 such roadblocks have been identified (Figure 1) ; T1 translation: “The transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans”, T2 translation: “The translation of results from clinical studies into everyday clinical practice and health decision making”, and T3 translation: “Practice-based research, which is often necessary before distilled knowledge (e.g., systematic reviews, guidelines) can be implemented in practice” (3-5).The international research community rapidly recognized importance for promotion of translational research and made it their priority(5). In the USA, National Institutes of Health, (NIH) expects to fund 60 translational research centers with a budget of $500 million per year by 2012 (6). Besides academic centers, foundations, industry, disease-related organizations, and individual hospitals and health systems have also established translational research programs and at least 2 journals (Translational Medicine and the Journal of Translational Medicine) are devoted to the topic. In Europe, translational research has become a centerpiece of the European Commission’s €6 billion budget for health related research, and the United Kingdom has invested £450 million over 5 years to establish translational research centers (7).In this issue of Bosnian Journal of Basic Medical Sciences, members of medical section of Bosnian and Herzegovinian-American Academy of Arts and Sciences (BHAAAS), contributed their own work and expertise to bridge the gap between basic and clinical research, between inventing the treatments and getting them used in practice, and laid down foundations for future collaborative development of translational research in Bosnia and Herzegovina, as well as in the region (8).At the first glance of this issue’s table of content, a reader will easily notice the variety and breadth of topics and themes, from medical informatics and genetics, to hematology and oncology, pulmonary and critical care medicine, orthopedics, trauma surgery and neurosurgery. However, all of the articles share common ideas of translation of knowledge, from bench to bedside and back, and individualized approach to medicine, which are the true hallmarks of the 21st century medicine.Deeper under the surface and titles, there lies our common privilege and honor to be part of a broader mission of BHAAAS: to connect with our fellow physicians and scientists, and to build bridges of cooperation with our homeland, to promote the spirit of intellectual diversity and free exchange of ideas with the strong belief that this knowledge sharing will promote betterment of health in Bosnia and Herzegovina

scholarly journals LncRNA SNHG8 Promotes Liver Cancer Proliferation and Metastasis by Sponging miR-542-3p and miR-4701-5p

2021 ◽  
Author(s):  
He Tong ◽  
Shuang He ◽  
Kexin Li ◽  
qirile Sa ◽  
Kefan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Cancer Proliferation ◽  
Competing Endogenous Rnas ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Nucleolar Rna

Abstract Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs). LncRNA small nucleolar RNA host gene 8 (LncRNA SNHG8) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the molecular mechanisms by which lncRNA SNHG8 contributes to hepatocellular carcinoma (HCC) still remains unclear. In the present study, we reported that lncRNA SNHG8 was abnormally up-regulated in liver cancer tissues and HCC cell lines. Moreover, knockdown of lncRNA SNHG8 significantly attenuated the proliferation, migration, invasion process of HCC cell line HepG2 in vitro. Mechanistically, we first reported that suppression of lncRNA SNHG8 evidently enhanced miR-542-3p and miR-4701-5p expression and decreased TET3 expression at posttranscriptional level. Furthermore, lncRNA SNHG8 upregulated TET3 expression by sponging miR-542-3p and miR-4701-5p by competing binding. Taken together, our results confirmed the oncogene role of lncRNA SNHG8 and discovered the underlying mechanism that lncRNA SNHG8 upregulated TET3 through the sponging or decaying of miR-542-3p and miR-4701-5p in human hepatocellular carcinoma, suggesting that lncRNA SNHG8 may serve as a potential diagnostic marker and therapeutic target for patients with hepatocellular carcinoma.

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