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AS30D Model of Hepatocellular Carcinoma: Tumorigenicity and Preliminary Characterization by Imaging, Histopathology, and Immunohistochemistry

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Abstract

Purpose

This study was designed to determine the tumorigenicity of the AS30D HCC cell line following orthotopic injection into rat liver and preliminarily characterize the tumor model by both magnetic resonance imaging (MRI) and ultrasound (US) as well as histopathology and immunohistochemistry.

Materials

AS30D cell line in vitro proliferation was assessed by using MTT assay. Female rats (N = 5) underwent injection of the AS30D cell line into one site in the liver. Rats subsequently underwent MR imaging at days 7 and 14 to assess tumor establishment and volume. One rat underwent US of the liver at day 7. Rats were euthanized at day 7 or 14 and livers were subjected to gross, histopathologic (H&E), and immunohistochemical (CD31) analysis to assess for tumor growth and neovascularization.

Results

AS30D cell line demonstrated an in vitro doubling time of 33.2 ± 5.3 h. MR imaging demonstrated hyperintense T2-weighted and hypointense T1-weighted lesions with tumor induction in five of five and three of three sites at days 7 and 14, respectively. The mean (SD) tumor volume was 126.1 ± 36.2 mm3 at day 7 (N = 5). US of the liver demonstrated a well-circumscribed, hypoechoic mass and comparison of tumor dimensions agreed well with MRI. Analysis of H&E- and CD31-stained sections demonstrated moderate-high grade epithelial tumors with minimal tumor necrosis and evidence of diffuse intratumoral and peritumoral neovascularization by day 7.

Conclusions

AS30D HCC cell line is tumorigenic following orthotopic injection into rat liver and can be used to generate an early vascularizing, slower-growing rat HCC tumor model.

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Acknowledgments

Infrastructure support provided by NIH construction grant NIH C06 RR018898. This publication was made possible by CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. Additional research support provided in part by SIR Foundation Allied Scientist Training Grant (Mr. Scott Thompson) and RSNA Research Scholar Grant (Dr. David Woodrum).

Disclosures

Regarding disclosures, Mr. Scott Thompson has received a research grant from the SIR Foundation (SIR Allied Scientist Training Grant); Dr. Matthew Callstrom has received research grants from Siemens Medical Systems and Endocare, Inc.; Dr. Lewis Roberts has received research grants from Bristol Myers-Squibb, Merck, Nordion and Bayer; Dr. David Woodrum has received a research Grant from Visualase, Inc., and an RSNA Research Scholar Grant.

Conflict of interest

The authors report no conflicts of interest and have conducted this research in compliance with institutional ethical and regulatory guidelines.

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Authors and Affiliations

  1. Medical Scientist Training Program, Mayo Clinic, Rochester, MN, USA

    Scott M. Thompson

  2. Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA

    Matthew R. Callstrom & David A. Woodrum

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Bruce Knudsen, Kim A. Butters & Joseph P. Grande

  4. Division of Physiology and Bioengineering, Mayo Clinic, Rochester, MN, 55905, USA

    Jill L. Anderson

  5. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Lewis R. Roberts

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  1. Scott M. Thompson
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  2. Matthew R. Callstrom
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Correspondence to David A. Woodrum.

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Thompson, S.M., Callstrom, M.R., Knudsen, B. et al. AS30D Model of Hepatocellular Carcinoma: Tumorigenicity and Preliminary Characterization by Imaging, Histopathology, and Immunohistochemistry. Cardiovasc Intervent Radiol 36, 198–203 (2013). https://doi.org/10.1007/s00270-012-0466-1

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  • DOI: https://doi.org/10.1007/s00270-012-0466-1

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