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- W3129687130 abstract "Purpose While systemic tumor-stimulating effects can occur following ablation of normal liver linked to the IL-6/HGF/VEGF cytokinetic pathway, the potential for tumor cells themselves to produce these unwanted effects is currently unknown. Here, we study whether partially treated tumors induce increased tumor growth post-radiofrequency thermal ablation (RFA).Methods Tumor growth was measured in three immunocompetent, syngeneic tumor models following partial RFA of the target tumor (in subcutaneous CT26 and MC38 mouse colorectal adenocarcinoma, N = 14 each); and in a distant untreated tumor following partial RFA of target subcutaneous R3230 rat breast adenocarcinoma (N = 12). Tumor cell proliferation (ki-67) and microvascular density (CD34) was assessed. In R3230 tumors, in vivo mechanism of action was assessed following partial RFA by measuring IL-6, HGF, and VEGF expression (ELISA) and c-Met protein (Western blot). Finally, RFA was performed in R3230 tumors with adjuvant c-Met kinase inhibitor or VEGF receptor inhibitor (at 3 days post-RFA, N = 3/arm, total N = 12).Results RFA stimulated tumor growth in vivo in residual, incompletely treated surrounding CT26 and MC38 tumor at 3–6 days (p < 0.01). In R3230, RFA increased tumor growth in distant tumor 7 days post treatment compared to controls (p < 0.001). For all models, Ki-67 and CD34 were elevated (p < 0.01, all comparisons). IL-6, HGF, and VEGF were also upregulated post incomplete tumor RFA (p < 0.01). These markers were suppressed to baseline levels with adjuvant c-MET kinase or VEGF receptor inhibition.Conclusion Incomplete RFA of a target tumor can sufficiently stimulate residual tumor cells to induce accelerated growth of distant tumors via the IL-6/c-Met/HGF pathway and VEGF production." @default.
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- W3129687130 date "2021-01-01" @default.
- W3129687130 modified "2023-10-05" @default.
- W3129687130 title "Incomplete thermal ablation of tumors promotes increased tumorigenesis" @default.
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- W3129687130 doi "https://doi.org/10.1080/02656736.2021.1887942" @default.
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