Development of an immunosuppressed orthotopic hepatocellular carcinoma rat model for the evaluation of chemo- and radioembolization therapies
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Development of an immunosuppressed orthotopic hepatocellular carcinoma rat model for the evaluation of chemo- and radioembolization therapies. / Charles, Lovelyn; Sekar, Sathiya; Osooly, Maryam; Javed, Sumreen; Williams, Karla C.; Welch, Ian; Barta, Ingrid; Saatchi, Katayoun; Häfeli, Urs O.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 196, 114180, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Development of an immunosuppressed orthotopic hepatocellular carcinoma rat model for the evaluation of chemo- and radioembolization therapies
AU - Charles, Lovelyn
AU - Sekar, Sathiya
AU - Osooly, Maryam
AU - Javed, Sumreen
AU - Williams, Karla C.
AU - Welch, Ian
AU - Barta, Ingrid
AU - Saatchi, Katayoun
AU - Häfeli, Urs O.
N1 - Publisher Copyright: © 2024 Elsevier B.V.
PY - 2024
Y1 - 2024
N2 - Hepatocellular carcinoma (HCC) is widely known to be chemo-resistant and presents with significant liver disease resulting in low tolerability to systemic chemotherapy. As a counter measure, more targeted therapies such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been developed. To further optimize these therapies, animal models are critical in elucidating the molecular events in disease progression and test new treatment options. The present study focuses on the development of a hepatoma bearing rat model. N1S1 rat hepatoma cells were transfected by a lentiviral method and injected into the liver of Sprague Dawley (SD) and Rowett Nude (RNU) rats. Longitudinal tumor growth was observed by bioluminescence imaging (BLI) and liver/tumor histology. In both models, tumors were visible within 4 days post cell inoculation. Tumor take rates were 52 % and 73 % for male and female SD rats, respectively, and 100 % for male RNU rats. By day 12 and 15 post inoculation, we recorded complete tumor regression in male and female SD rats. Liver histology showed advanced fibrosis in the tumor regressed SD rats, whilst RNU rats exhibited the characteristic sheet pattern of Novikoff tumor with mild liver fibrosis. Increased CD3 and TUNEL staining observed in SD rat livers may be key factors for tumor regression. Our data reveal that the immunocompetent SD rats are not recommended as a model for therapeutic investigations. The immunosuppressed RNU rats, however, are characterized by consistent and reliable tumor growth and thus a desirable model for future therapeutic investigations.
AB - Hepatocellular carcinoma (HCC) is widely known to be chemo-resistant and presents with significant liver disease resulting in low tolerability to systemic chemotherapy. As a counter measure, more targeted therapies such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been developed. To further optimize these therapies, animal models are critical in elucidating the molecular events in disease progression and test new treatment options. The present study focuses on the development of a hepatoma bearing rat model. N1S1 rat hepatoma cells were transfected by a lentiviral method and injected into the liver of Sprague Dawley (SD) and Rowett Nude (RNU) rats. Longitudinal tumor growth was observed by bioluminescence imaging (BLI) and liver/tumor histology. In both models, tumors were visible within 4 days post cell inoculation. Tumor take rates were 52 % and 73 % for male and female SD rats, respectively, and 100 % for male RNU rats. By day 12 and 15 post inoculation, we recorded complete tumor regression in male and female SD rats. Liver histology showed advanced fibrosis in the tumor regressed SD rats, whilst RNU rats exhibited the characteristic sheet pattern of Novikoff tumor with mild liver fibrosis. Increased CD3 and TUNEL staining observed in SD rat livers may be key factors for tumor regression. Our data reveal that the immunocompetent SD rats are not recommended as a model for therapeutic investigations. The immunosuppressed RNU rats, however, are characterized by consistent and reliable tumor growth and thus a desirable model for future therapeutic investigations.
KW - Hepatocellular carcinoma
KW - N1S1-Luc cells
KW - Reliable animal model
KW - SD and RNU rats
KW - Tumor growth
U2 - 10.1016/j.ejpb.2024.114180
DO - 10.1016/j.ejpb.2024.114180
M3 - Journal article
C2 - 38237643
AN - SCOPUS:85183051444
VL - 196
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
M1 - 114180
ER -
ID: 381462540