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Development of immunocompetent and immunosuppressed orthotopic rat model of hepatocellular carcinoma Charles, Lovelyn


Hepatocellular carcinoma (HCC) accounts for over 500,000 deaths per year and is the most common form of primary liver cancer. It has a very dismal prognosis with incidence rates almost equal to prevalence rates. In North America, incidence is on the increase due to increasing hepatitis C virus infections. More than 75% of patients diagnosed with HCC do not qualify for potentially curative therapies such as surgical resection, radiofrequency ablation and liver transplantation, and thus require management by trans-catheter procedures like radioembolization. Radioembolization is performed in more than 75% of patients and involves injecting radioactive microspheres through a catheter directly into the vessel that supplies blood to the tumor. Since the tumor and healthy liver tissue get their blood supply from two different sources, this procedure preferentially irradiates the tumor while sparing the healthy liver tissue. Therefore, we hypothesize that an orthotopic rat model of hepatocellular carcinoma can be used for non-invasive monitoring of tumor growth and development. Rat hepatoma cells (N1S1) were transfected by a lentiviral method and injected into the liver of Sprague Dawley and Rowett Nude (RNU) rats using ultrasound guidance and an alternative method respectively. Longitudinal tumor growth was followed by bioluminescence imaging (BLI). In both models, tumors were visible within 3 to 4 days post cell inoculation by BLI. Tumor take rates were 52% and 73% for male and female Sprague Dawley rats, respectively, and 100% for RNU rats. Day 12 and 15 post inoculation, we recorded complete tumor regression in all Sprague Dawley rats but continuous tumor growth for up to 21 days post induction in the RNU rats. The immunocompetent Sprague Dawley rat model is not ideal for investigation of catheterization techniques like radioembolization. The RNU rat model, however, is characterized iv by consistent and reliable tumor growth and thus a desirable method for future therapeutic investigations.

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