Hepatic radiofrequency ablation: markedly reduced systemic effects by modulating periablational inflammation via cyclooxygenase-2 inhibition.

Objectives: To determine whether celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can potentiate hepatic radiofrequency ablation (RFA)-induced local cellular infiltration and distant tumour growth.Methods: First, COX-2 expression was evaluated using immunohistochemistry in the local periablational r...

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Publicado en:European Radiology Vol. 27; no. 3; pp. 1238 - 1248
Autores principales: Kumar, Gaurav, Goldberg, S., Wang, Yuanguo, Velez, Erik, Gourevitch, Svetlana, Galun, Eithan, Ahmed, Muneeb, Goldberg, S Nahum
Formato: Journal Article
Publicado: Springer Nature Mar2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2017
      vid: 27
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      pub: Springer Nature
      place: New York, New York
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        121148713
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        10.1007/s00330-016-4405-4
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        atl: Hepatic radiofrequency ablation: markedly reduced systemic effects by modulating periablational inflammation via cyclooxygenase-2 inhibition.
      aug:
        au:
          Kumar, Gaurav
          Goldberg, S.
          Wang, Yuanguo
          Velez, Erik
          Gourevitch, Svetlana
          Galun, Eithan
          Ahmed, Muneeb
          Goldberg, S Nahum
        affil: Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology , Beth Israel Deaconess Medical Center/Harvard Medical School , Boston USA
      sug:
        subj:
          Inflammation Prevention and Control
          Liver Surgery
          Cox-2 Inhibitors Pharmacodynamics
          Catheter Ablation Methods
          Cell Physiology Drug Effects
          Mice
          Rats
          Male
          Animals
          Models, Biological
          Male
      ab: Objectives: To determine whether celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can potentiate hepatic radiofrequency ablation (RFA)-induced local cellular infiltration and distant tumour growth.Methods: 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.Results: 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.Conclusions: 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.Key Points: • 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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