e902c195528e657636ce30ddf2c57a3c pmc_34200439.pdf 41711b92faf6c0e7d049c3871f065e58b5b4f08e pmc_34200439.pdf cf59b046ff89a03468fe719739bfbc6132b1ab3f7c4041be01612d9d966c5b64 pmc_34200439.pdf Title: Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde? Subject: The pro-tumorigenic activity of fibroblast growth factor (FGF) 19 (FGF15 in its rodent orthologue) in hepatocellular carcinoma (HCC), as well as the unsolved problem that ischemia-reperfusion (IR) injury supposes in liver surgeries, are well known. However, it has been shown that FGF15 administration protects against liver damage and regenerative failure in liver transplantation (LT) from brain-dead donors without tumor signals, providing a benefit in avoiding IR injury. The protection provided by FGF15/19 is due to its anti-apoptotic and pro-regenerative properties, which make this molecule a potentially beneficial or harmful factor, depending on the disease. In the present review, we describe the preclinical models currently available to understand the signaling pathways responsible for the apparent controversial effects of FGF15/19 in the liver (to repair a damaged liver or to promote tumorigenesis). As well, we study the potential pharmacological use that has the activation or inhibition of FGF15/19 pathways depending on the disease to be treated. We also discuss whether FGF15/19 non-pro-tumorigenic variants, which have been developed for the treatment of liver diseases, might be promising approaches in the surgery of hepatic resections and LT using healthy livers and livers from extended-criteria donors. Keywords: hepatocellular carcinoma; liver transplantation; ischemia-reperfusion injury; liver surgery; fibroblast growth factor Author: Albert Caballeria-Casals, Marc Micó-Carnero, Carlos Rojano-Alfonso, Cristina Maroto-Serrat, Araní Casillas-Ramírez, Ana I. Álvarez-Mercado, Jordi Gracia-Sancho and Carmen Peralta Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jun 10 08:59:44 2021 CEST ModDate: Thu Jun 10 09:11:40 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1425613 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OPETZR+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 EUNBMT+VnURWPalladioL Type 1 Custom yes yes no 15 0 NUOIHT+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 HALWWJ+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 ABDUZX+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 LHCXDL+EURM10 Type 1 Builtin yes yes no 81 0 GIZSCG+EURM7 Type 1 Builtin yes yes no 106 0 AINHDX+CMSY10 Type 1 Builtin yes yes no 110 0 DUJUUF+PazoMath-Italic Type 1 Builtin yes yes no 142 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:12:41 CEST RepresentationInformation: pmc_34200439.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:14:18 CEST Size: 1425613 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 668 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Role of FGF15/19 in Liver Tumorigenesis Destination: section.2 Children: Item: Title: Involvement of BA in the Effects of FGF15/19 on Tumorigenesis Destination: subsection.2.1 Item: Title: Involvement of FGF15/19 and Inflammation in the Hepatic Microenvironment Destination: subsection.2.2 Item: Title: FGF15/19: Prognostic Factor of HCC? Destination: subsection.2.3 Item: Title: Mechanisms of Action of FGF15/19-FGFR4 Destination: subsection.2.4 Item: Title: Involvement of Genetic and Epigenetic FGF15/19 and FGFR4 Alterations in Tumorigenesis Destination: subsection.2.5 Item: Title: Role of FGFR4 on Metastasis Destination: subsection.2.6 Item: Title: Role of FGF15/19 in Liver Regeneration Destination: section.3 Children: Item: Title: Involvement of BAs and YAP in the Effects of FGF15/19 Destination: subsection.3.1 Item: Title: Signaling Pathways (Different to BAs and YAP) Regulated by FGF15/19 Destination: subsection.3.2 Item: Title: Modulation of FGF15/19 Actions Destination: section.4 Children: Item: Title: Non-Protumorigenic Variants of FGF15/19 Destination: subsection.4.1 Item: Title: Other Drugs That Affect FGF15/19 Signaling Pathways Destination: subsection.4.2 Item: Title: Conclusions and Future Perspectives Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde? Author: Albert Caballeria-Casals, Marc Micó-Carnero, Carlos Rojano-Alfonso, Cristina Maroto-Serrat, Araní Casillas-Ramírez, Ana I. Álvarez-Mercado, Jordi Gracia-Sancho and Carmen Peralta Subject: The pro-tumorigenic activity of fibroblast growth factor (FGF) 19 (FGF15 in its rodent orthologue) in hepatocellular carcinoma (HCC), as well as the unsolved problem that ischemia-reperfusion (IR) injury supposes in liver surgeries, are well known. However, it has been shown that FGF15 administration protects against liver damage and regenerative failure in liver transplantation (LT) from brain-dead donors without tumor signals, providing a benefit in avoiding IR injury. The protection provided by FGF15/19 is due to its anti-apoptotic and pro-regenerative properties, which make this molecule a potentially beneficial or harmful factor, depending on the disease. In the present review, we describe the preclinical models currently available to understand the signaling pathways responsible for the apparent controversial effects of FGF15/19 in the liver (to repair a damaged liver or to promote tumorigenesis). As well, we study the potential pharmacological use that has the activation or inhibition of FGF15/19 pathways depending on the disease to be treated. We also discuss whether FGF15/19 non-pro-tumorigenic variants, which have been developed for the treatment of liver diseases, might be promising approaches in the surgery of hepatic resections and LT using healthy livers and livers from extended-criteria donors. 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SHA-256