Radiofrequency ablation suppresses distant tumour growth in a novel rat model of multifocal hepatocellular carcinoma

Erös de Bethlenfalva - Hora, Caroline; Mertens, Joachim C.; Piguet, Anne Christine; Kettenbach, Joachim; Schmitt, Johannes; Terracciano, Luigi; Weimann, Rosemarie; Dufour, Jean-François; Geier, Andreas (2014). Radiofrequency ablation suppresses distant tumour growth in a novel rat model of multifocal hepatocellular carcinoma. Clinical science, 126(3), pp. 243-252. Portland 10.1042/CS20130089

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RFA (radiofrequency ablation) is an established therapy for HCC (hepatocellular carcinoma). The multikinase inhibitor sorafenib prolongs survival in advanced HCC. We examined the effects of RFA alone and in combination with sorafenib on a bystanding tumour in a two-tumour rat model of HCC. A total of 80 rats were implanted with two liver tumours and randomized to four treatment groups: vehicle and sham operation (control), sorafenib and sham operation (Sora/Sham), vehicle and RFA (Vh/RFA), and sorafenib and RFA (Sora/RFA) (n=10/group per time point). RFA or sham-operation was performed on the left lobe tumour on day 15. Animals were killed at day 18 and day 30. Non-RFA-targeted right lobe tumours were analysed for angiogenesis, growth factors [HGF (hepatocyte growth factor), EGF (epidermal growth factor) and VEGF (vascular endothelial growth factor)] and infiltrating immune cells (CD3 and CD68). At day 30, the non-RFA-targeted tumours were significantly smaller in all three treatment groups compared with control (Sora/Sham P≤0.0001, Vh/RFA P=0.005 and Sora/RFA P≤0.0001). The smallest tumours were observed in animals treated with a combination of sorafenib and RFA, whereas the size reduction seen in the RFA-only group indicated an RFA-mediated distant suppression of tumour growth. Growth factor measurement revealed transiently decreased EGF levels after RFA (P=0.008), whereas sorafenib treatment decreased HGF levels (P=0.001). MVD (microvessel density) was reduced by sorafenib (P=0.002) despite increased VEGF levels (P≤0.0001). The immune parameters revealed augmented T-cells and IL-10 (interleukin 10) levels in all three treatment groups; sorafenib additionally increased macrophage numbers (P≤0.0001). RFA and sorafenib alone resulted in significant volume reduction of the non-RFA-targeted tumour; this effect was enhanced when both modalities were combined.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research (discontinued)

UniBE Contributor:

Erös de Bethlenfalva - Hora, Caroline; Piguet, Anne Christine; Terracciano, Luigi; Weimann, Rosemarie and Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0143-5221

Publisher:

Portland

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

21 Sep 2016 11:09

Last Modified:

21 Sep 2016 11:09

Publisher DOI:

10.1042/CS20130089

PubMed ID:

23822114

BORIS DOI:

10.7892/boris.87527

URI:

https://boris.unibe.ch/id/eprint/87527

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