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10.1038/s41598-018-26082-4

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suck abstract from ncbi


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pmid29795479      Sci+Rep 2018 ; 8 (ä): ä
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  • Role of Kupffer cells in the progression of CRC liver metastases after the first stage of ALPPS #MMPMID29795479
  • García-Pérez R; Ferrer Fábrega J; Varona-Bosque A; Martínez CM; Revilla-Nuin B; Cabellos L; Pena R; Vilana R; Gonzalez-Abós C; García-Valdecasas JC; Fuster Obregón J
  • Sci Rep 2018[]; 8 (ä): ä PMID29795479show ga
  • Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-? and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs). Interestingly, KCs expressed COX-2 (M1 polarization), while TAMs expressed mainly arginase-1 (M2 polarization). ALPPS also induced a decrease of tumor-infiltrating lymphocytes and an increase of intrahepatic T lymphocytes. Thus, ALPPS technique seems to induce a hypoxic environment, which enhances hepatic HIF1-? and VEGF expression and may promote KCs and TAMs polarization. Consequently, the regenerative stimulus seems to be driven by a pro-inflammatory and hypoxic environment, in which M1 intrahepatic macrophages expressing COX-2 and T-Lymphocytes play a key role, facts which may be related with the tumor progression observed.
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