Suitability of the woodchuck HCC as a preclinical model for evaluation of intra‐arterial therapies

Kim, Alexander Y.; Yacoub, Joseph; Field, D.; Park, Byoung Uk; Kallakury, Bhaskar; Korolowicz, Kyle E.; Menne, Stephan

doi:10.1002/ame2.12100

Cited by 7 publications

(9 citation statements)

References 16 publications

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“…The eastern woodchuck (Marmota monax) is acknowledged as a clinically relevant in vivo experimental model in the investigation of HBV-associated diseases such as HCC [152]. This model spontaneously develops chronic hepatitis advancing to HCC during adulthood after neonatal exposure to woodchuck hepatitis virus (WHV) [153,154]. Several similarities have been established between WHV and human HBV with respect to the viral life cycles, mechanisms of infection and replication, nucleotide sequence, genome organization, and virion morphology [154,155].…”

Section: Woodchuck Hcc Modelmentioning

confidence: 99%

“…Several similarities have been established between WHV and human HBV with respect to the viral life cycles, mechanisms of infection and replication, nucleotide sequence, genome organization, and virion morphology [154,155]. Following the inoculation, liver cancer development occurs within an approximate period of 24-32 months [153].…”

Section: Woodchuck Hcc Modelmentioning

confidence: 99%

“…Thus far, woodchucks with established HCC tumors have been used in various applications. As compared to mice or rats, which are limited by their small size, this particular model is ideal in the evaluation of HCC intra-arterial therapies [153]. Additionally, HCC-bearing woodchucks have been effectively used in the evaluation of novel therapeutic strategies, improvement of current imaging and ablation techniques, and prevention of HCC initiation and progression [155].…”

Section: Woodchuck Hcc Modelmentioning

confidence: 99%

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Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Blidișel

Marcovici

Coricovac

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

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Section: Woodchuck Hcc Modelmentioning

confidence: 99%

Section: Woodchuck Hcc Modelmentioning

confidence: 99%

Section: Woodchuck Hcc Modelmentioning

confidence: 99%

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Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Blidișel

Marcovici

Coricovac

et al. 2021

Cancers

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“…Woodchucks also possess a hepatic arterial anatomy that can be accessed via the femoral artery and allows catheterization with clinically used microcatheters[ 151 ]. Accordingly, three studies explored IAT in woodchucks with or without liver tumors[ 157 - 159 ]. In these studies, arterial access via the femoral artery with human standard catheters allowed delivery of contrast agents for the localization of HCCs by CT or MRI.…”

Section: Introductionmentioning

confidence: 99%

“…Lobar embolization with 355–500 µm polyvinyl alcohol (PVA) particles (Boston Scientific) was successful in woodchucks without liver tumors[ 158 ]. In addition, liver tumor embolization for the targeted delivery of 100-300 µm PVA microspheres (LC- Bead; BTG, London, United Kingdom) produced a heterogeneous distribution of embolic particles in the hepatic neoplasms[ 157 ]. Moreover, chemoembolization with drug-eluting embolic 70-150 µm radiopaque PVA microspheres (LC Bead LUMI; BGT) loaded with doxorubicin resulted in a targeted drug delivery into liver tumors[ 159 ].…”

Section: Introductionmentioning

confidence: 99%

Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

Suresh¹,

Menne²

2021

WJGO

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This review describes woodchucks chronically infected with the woodchuck hepatitis virus (WHV) as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma (HCC) induced by the hepatitis B virus (HBV). Since laboratory animal models susceptible to HBV infection are limited, woodchucks experimentally infected with WHV, a hepatitis virus closely related to HBV, are increasingly used to enhance our understanding of virus-host interactions, immune response, and liver disease progression. A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established, which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans. HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size, morphology, and molecular gene signature to those of HBV-infected patients. Accordingly, woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC. In addition, drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs, alone or in combination with other compounds, minimizes the risk of liver disease progression to HCC. More recently, woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute, self-limited and chronic infections. Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae, including the onset of HCC. Therefore, woodchucks with chronic WHV infection constitute a well-characterized, fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities, which are based on chemo, gene, and immune therapy, for the prevention and treatment of HCC in patients for which current treatment options are dismal.

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