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 A Single Mutation in the VP1 of Enterovirus 71 Is Responsible for Increased Virulence and Neurotropism in Adult Interferon-Deficient Mice

2016 ◽  
Vol 90 (19) ◽  
pp. 8592-8604 ◽  
Author(s):  
Elizabeth A. Caine ◽  
Louise H. Moncla ◽  
Monica D. Ronderos ◽  
Thomas C. Friedrich ◽  
Jorge E. Osorio
Keyword(s):  
Animal Models ◽  
Reverse Genetics ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
Enterovirus 71 ◽  
Neurological Complications ◽  
Asia Pacific ◽  
Single Mutation ◽  
Content Type ◽  
Deficient Mice

ABSTRACTHand, foot, and mouth disease (HFMD) has spread throughout the Asia-Pacific region, affecting millions of young children, who develop symptoms ranging from painful blisters around their mouths and hands to neurological complications. Many members of the genusEnterovirus(familyPicornaviridae) cause HFMD. Enterovirus 71 (EV71) is one of the primary causative agents and has been linked to severe disease. Vaccine efficacy and pathogenesis studies for EV71 have been limited because there is a lack of suitable animal models. Previously, we generated a mouse-adapted EV71 (mEV71) capable of infecting 12-week-old interferon receptor-deficient AG129 mice and used the model to evaluate the efficacy of candidate HFMD vaccines. Here, we present data investigating the genetic correlates of EV71 adaptation and characterize the virus's tissue tropism in mice. Using reverse genetics, a VP1 mutation (K244E) was shown to be necessary for mEV71 virulence in adult mice. Another VP1 mutation (H37R) was required for mEV71 recovery on rhabdomyosarcoma (RD) cells. Viral loads determined by real-time reverse transcription (RT)-PCR confirmed the presence of mEV71 in the sera and multiple organs of mice. Histological analysis revealed signs of meningitis and encephalitis, characteristic of severe human disease. The further description of this model has provided insight into EV71 pathogenesis and demonstrates the importance of the VP1 region in facilitating mEV71 adaptation.IMPORTANCEEV71 is a reemerging pathogen, and little is known about the genetic determinants involved in its pathogenesis. The absence of animal models has contributed to this lack of knowledge. The data presented here improve upon the existing animal models by characterizing a mouse-adapted strain of EV71. We determined that a VP1 mutation (K244E) was needed for EV71 virulence in adult AG129 mice. While this mutation was found previously for EV71 adaptation in 5-day-old BALB/c mice, neurotropic disease did not develop. Using interferon-deficient mice, we raised the age of susceptibility beyond 6 weeks and provided clear evidence that our model mimics severe human infections. The model can be exploited to identify determinants of EV71 virulence and to reveal molecular mechanisms that control the virus-host interaction, especially those associated with neurotropic disease. Furthermore, these data provide useful information regarding the importance of VP1, specifically position 244, in host adaptation and tissue dissemination.

Metastatic tumor antigen in hepatocellular carcinoma: golden roads toward personalized medicine

2014 ◽  
Vol 33 (4) ◽  
pp. 965-980 ◽  
Author(s):  
Soo Hyung Ryu ◽  
Myoung Kuk Jang ◽  
Woo Jean Kim ◽  
Danbi Lee ◽  
Young-Hwa Chung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Personalized Medicine ◽  
Tumor Antigen ◽  
Metastatic Tumor

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.

Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma

Hepatology ◽  
2008 ◽  
Vol 47 (3) ◽  
pp. 929-936 ◽  
Author(s):  
Soo Hyung Ryu ◽  
Young-Hwa Chung ◽  
Hyunseung Lee ◽  
Jeong A. Kim ◽  
Hyun Deok Shin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Antigen ◽  
Metastatic Tumor ◽  
Postoperative Recurrence ◽  
Poor Survival
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