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Fibroblast growth factors induce hepatic tumorigenesis post radiofrequency ablation.
Markezana, Aurelia; Paldor, Mor; Liao, Haixing; Ahmed, Muneeb; Zorde-Khvalevsky, Elina; Rozenblum, Nir; Stechele, Matthias; Salvermoser, Lukas; Laville, Flinn; Goldmann, Salome; Rosenberg, Nofar; Andrasina, Tomas; Ricke, Jens; Galun, Eithan; Goldberg, Shraga Nahum.
Afiliación
  • Markezana A; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel. aureliahakoune@gmail.com.
  • Paldor M; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Liao H; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Ahmed M; Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA, USA.
  • Zorde-Khvalevsky E; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Rozenblum N; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Stechele M; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Salvermoser L; Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
  • Laville F; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Goldmann S; Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
  • Rosenberg N; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Andrasina T; Department of Radiology, University Hospital, LMU Munich, Munich, Germany.
  • Ricke J; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Galun E; The Goldyne Savad Institute of Gene and Cell Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem, Israel.
  • Goldberg SN; Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic.
Sci Rep ; 13(1): 16341, 2023 09 28.
Article en En | MEDLINE | ID: mdl-37770545
Image-guided radiofrequency ablation (RFA) is used to treat focal tumors in the liver and other organs. Despite potential advantages over surgery, hepatic RFA can promote local and distant tumor growth by activating pro-tumorigenic growth factor and cytokines. Thus, strategies to identify and suppress pro-oncogenic effects of RFA are urgently required to further improve the therapeutic effect. Here, the proliferative effect of plasma of Hepatocellular carcinoma or colorectal carcinoma patients 90 min post-RFA was tested on HCC cell lines, demonstrating significant cellular proliferation compared to baseline plasma. Multiplex ELISA screening demonstrated increased plasma pro-tumorigenic growth factors and cytokines including the FGF protein family which uniquely and selectively activated HepG2. Primary mouse and immortalized human hepatocytes were then subjected to moderate hyperthermia in-vitro, mimicking thermal stress induced during ablation in the peri-ablational normal tissue. Resultant culture medium induced proliferation of multiple cancer cell lines. Subsequent non-biased protein array revealed that these hepatocytes subjected to moderate hyperthermia also excrete a similar wide spectrum of growth factors. Recombinant FGF-2 activated multiple cell lines. FGFR inhibitor significantly reduced liver tumor load post-RFA in MDR2-KO inflammation-induced HCC mouse model. Thus, Liver RFA can induce tumorigenesis via the FGF signaling pathway, and its inhibition suppresses HCC development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ablación por Catéter / Carcinoma Hepatocelular / Ablación por Radiofrecuencia / Hipertermia Inducida / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ablación por Catéter / Carcinoma Hepatocelular / Ablación por Radiofrecuencia / Hipertermia Inducida / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido