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Antiangiogenic Therapy Induces Hepatic Tumor Vascular Network Rearrangement to Receive Perfusion via the Portal Vein and Hepatic Artery

 Kang W.  ;  Lim J.S.  ;  Park M.  ;  Koh G.Y.  ;  Kim H. 
 Journal of Vascular Research, Vol.53(1~2) : 72-82, 2016 
Journal Title
 Journal of Vascular Research 
Issue Date
Angiogenesis Inhibitors/administration & dosage* ; Animals ; Carcinoma, Lewis Lung/blood supply ; Carcinoma, Lewis Lung/diagnostic imaging ; Carcinoma, Lewis Lung/drug therapy* ; Carcinoma, Lewis Lung/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm* ; Hepatic Artery*/diagnostic imaging ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Liver Neoplasms, Experimental/blood supply ; Liver Neoplasms, Experimental/diagnostic imaging ; Liver Neoplasms, Experimental/drug therapy* ; Liver Neoplasms, Experimental/pathology ; Male ; Mice, Inbred C57BL ; Neovascularization, Pathologic* ; Portal Vein*/diagnostic imaging ; Receptors, Vascular Endothelial Growth Factor/administration & dosage* ; Recombinant Fusion Proteins/administration & dosage* ; Time Factors
PURPOSE: Hepatic malignancies can easily develop resistance to antiangiogenic therapy, but the underlying mechanism remains poorly understood. This study explores whether antiangiogenic therapy influences the tumor vascular network and/or the vessels feeding the hepatic tumor. METHODS: Mice implanted with Lewis lung carcinoma (LLC) cells were subcutaneously injected 3 times (once every other day starting 1 week after LLC implantation) with either an antiangiogenic agent [vascular endothelial growth factor (VEGF)-Trap] or control agent (bovine serum albumin) at a dose of 25 mg/kg before performing angiography. Hepatic arteriography and portography were performed using a vascular cast method with vascular latex. RESULTS: Arteriography of the control-treated LLC-implanted mice showed marked staining of the mass with a prominent feeding artery, suggesting that the tumor is supplied by arterial perfusion. No significant staining was observed on portography. By contrast, 33% (n = 3/9) of the LLC-implanted mice treated with the antiangiogenic agent VEGF-Trap showed intratumoral staining during portography, indicating that these tumors received perfusion via the portal vein. CONCLUSION: Antiangiogenic treatment can induce rearrangement of the hepatic tumor vascular network to establish communication with the portal vein. This implies that hepatic tumors can develop resistance to antiangiogenic therapy by maintaining perfusion through portal venous perfusion.
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1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
김한솔(Kim, Hon Soul)
박미숙(Park, Mi-Suk) ORCID logo https://orcid.org/0000-0001-5817-2444
임준석(Lim, Joon Seok) ORCID logo https://orcid.org/0000-0002-0334-5042
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