Hepatic radiofrequency ablation: markedly reduced systemic effects by modulating periablational inflammation via cyclooxygenase-2 inhibition
| Autor: | Muneeb Ahmed, Yuanguo Wang, S. Nahum Goldberg, Eithan Galun, Gaurav Kumar, Svetlana Gourevitch, Erik Velez |
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| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Radiofrequency ablation Inflammation 030218 nuclear medicine & medical imaging law.invention Mice 03 medical and health sciences 0302 clinical medicine law Internal medicine medicine Animals Radiology Nuclear Medicine and imaging Cell Proliferation Cyclooxygenase 2 Inhibitors biology business.industry Cell growth General Medicine medicine.disease Rats Inbred F344 Rats Mice Inbred C57BL Cellular infiltration Disease Models Animal surgical procedures operative Endocrinology medicine.anatomical_structure Liver Celecoxib 030220 oncology & carcinogenesis Hepatocyte Catheter Ablation Cancer research Hepatic stellate cell biology.protein Radiology Cyclooxygenase medicine.symptom business therapeutics medicine.drug |
| Zdroj: | European Radiology. 27:1238-1247 |
| ISSN: | 1432-1084 0938-7994 |
| DOI: | 10.1007/s00330-016-4405-4 |
| Popis: | To determine whether celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can potentiate hepatic radiofrequency ablation (RFA)-induced local cellular infiltration and distant tumour growth. First, COX-2 expression was evaluated using immunohistochemistry in the local periablational rim 24 h after hepatic RFA without/with intraperitoneal celecoxib in normal Fisher 344 rat liver. Next, local cellular infiltration of macrophages, stellate cells, and hepatocyte proliferation were quantified in C57BL6 mice 3–7d after RFA without/with celecoxib. c-Met, HGF, and VEGF levels after RFA were also measured. Finally, distant tumour growth and proliferation (Ki67 and CD34) were observed in subcutaneous R3230 tumours after hepatic RFA with/without celecoxib. Hepatic RFA-induced local activation of COX-2 was significantly suppressed using celecoxib. Celecoxib also reduced RFA-associated a) increased c-Met expression at 24 h, b) HGF and VEGF levels at 72 h, c) periablational macrophage and stellate cells at 3d, and d) hepatocyte proliferation at 7d. Similarly, celecoxib with RFA reduced distant tumour growth, tumour cell proliferation, and tumour microvascular density to sham levels, compared to increases observed with hepatic RFA alone. Increased activation of COX-2 after hepatic RFA contributes to periablational cellular infiltration and inflammation-mediated distant tumour growth, which can be successfully suppressed with a COX-2 inhibitor. • Thermal ablation of liver tissue can increase local inflammation and COX-2 expression. • Ablation-induced local inflammation can contribute to stimulation of distant tumour growth. • Local COX-2 inhibition with celecoxib can block ablation-induced distant tumour growth. |
| Databáze: | OpenAIRE |
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