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Vascular endothelial growth factor mRNA expression can be a marker for response to antiviral treatment of HCV

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Abstract

Angiogenesis has a significant pathogenic role in liver damage-associated hepatitis C virus infection. We evaluated whether chronic hepatitis C (CHC) is associated with elevated levels of angiogenesis marker (vascular endothelial growth factor) and whether it is modulated by therapy. Vascular endothelial growth factor (VEGF) mRNA was determined in the 36 CHC patients included in this study before therapy and 12 weeks after receiving antiviral combination therapy, pegylated interferon alpha-2b plus ribavirin, compared to 20 healthy controls. CHC patients showed elevated baseline VEGF level before and during treatment, but it was decreased in responder group, indicating a shift toward an “anti-angiogenic” process in CHC patients. In conclusion, this suggests that VEGF mRNA level could be useful as non-invasive, base markers of response to therapy.

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References

  • Ankoma-Sey V, Wang Y, Dai Z (2000) Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cells. Hepatol 31:141–148

    Article  CAS  Google Scholar 

  • Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M et al (1998) Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization. Circ Res 83:233–240

    Article  CAS  PubMed  Google Scholar 

  • Autiero M, Waltenberger J, Communi D et al (2003) Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 9:936–943

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660

    Article  CAS  PubMed  Google Scholar 

  • Carmeliet P, Jain R (2000) Angiogenesis in cancer and other diseases. Nat 407:249–257

    Article  CAS  Google Scholar 

  • Christopher JM, Michelle JF, Helen JH et al (2010) Hepatitis C virus infection reduces hepatocellular polarity in a vascular endothelial growth factor-dependent manner. Gastroenterol 138:1134–1142

    Article  Google Scholar 

  • Ferrara N (2004) Vascular endothelial growth factor as a target for anticancer therapy. Oncolo 9:2–10

    Article  CAS  Google Scholar 

  • Ferrara N, Houck K, Jakeman L, Leung DW (1992) Molecular and biological properties of the vascular endothelial-growth-factor family of proteins. Endocrine Res 13:8–31

    Google Scholar 

  • Ferrara N, Gerber H, Le Couter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  CAS  PubMed  Google Scholar 

  • Komorizono Y, Kohara K, Oketani M, Maeda M, Shibathou T, Shigenobu S et al (2003) Systemic combined chemotherapy with low dose of 5-fluorouracil, cisplatin, and interferon-alpha for advanced hepatocellular carcinoma: a pilot study. Dig Dis Sci 48:877–881

    Article  CAS  PubMed  Google Scholar 

  • Lai WK, Adams D (2005) Angiogenesis and chronic inflammation; the potential for novel therapeutic approaches in chronic liver disease. J Hepatol 42:7–11

    Article  CAS  PubMed  Google Scholar 

  • Marler JJ, Rubin J, Trede N, Connors S, Grier H, Upton J et al (2002) Successful antiangiogenic therapy of giant cell angioblastoma with interferon alfa 2b: report of 2 cases. Pedia 109:E37

    Article  Google Scholar 

  • Mazzanti R, Messerini L, Monsacchi L, Buzzelli G, Zignego A, Foschi M et al (1997) Chronic viral hepatitis induced by hepatitis C but not hepatitis B virus infection correlates with increased liver angiogenesis. Hepatol 25:229–234

    Article  CAS  Google Scholar 

  • Medina J, Caveda L, Sanz-Cameno P, Arroyo A, Martın-Vılchez S, Majano P et al (2003) Hepatocyte growth factor activates endothelial proangiogenic mechanisms relevant in chronic hepatitis C-associated neoangiogenesis. J Hepatol 38:660–667

    Article  CAS  PubMed  Google Scholar 

  • Moon EJ, Jeong C, Jeong J, Kim K, Yu D, Murakami S et al (2004) Hepatitis B virus X protein induces angiogenesis by stabilizing hypoxia-inducible factor 1alpha. FASEB J 18:382–384

    CAS  PubMed  Google Scholar 

  • Palmieri G, Montella L, Martignetti A, Bianco A (2000) Interferon alpha-2b at low doses as long-term antiangiogenic treatment of a metastatic intracranial hemangioendothelioma: a case report. Oncol Rep 7:145–149

    CAS  PubMed  Google Scholar 

  • Patt YZ, Hassan M, Lozano R, Brown T, Vauthey J, Curley S et al (2003) Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol 21:421–427

    Article  CAS  PubMed  Google Scholar 

  • Poon RT, Lau C, Yu W, Fan S, Wong J (2004) High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study. Oncol Rep 11:1077–1084

    CAS  PubMed  Google Scholar 

  • Poynard T, Ratziu V, Benhamou Y, Thabut D, Moussalli J (2005) Biomarkers as a first-line estimate of injury in chronic liver diseases: time for a moratorium on liver biopsy. Gastroenterol 128:1146–1148

    Article  Google Scholar 

  • Rosenberg WM, Voelker M, Thiel R, Becka M, Burt A, Schuppan D et al (2004) Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterol 127:1704–1713

    Article  Google Scholar 

  • Shimamatsu K, Wanless I (1997) Role of ischemia in causing apoptosis, atrophy, and nodular hyperplasia in human liver. Hepatol 26:343–350

    Article  CAS  Google Scholar 

  • Shimoda K, Mori M, Shibuta K, Banner B, Barnard G (1999) Vascular endothelial growth factor/vascular permeability factor mRNA expression in patients with chronic hepatitis C and hepatocellular carcinoma. Int J Oncol 14:353–359

    CAS  PubMed  Google Scholar 

  • Sidky YA, Borden E (1987) Inhibition of angiogenesis by interferons: effects on tumor and lymphocyte-induced vascular responses. Cancer Res 47:5155–5161

    CAS  PubMed  Google Scholar 

  • Slaton JW, Perrotte P, Inoue K, Dinney C, Fidler I (1999) Interferon alpha mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res 5:2726–2734

    CAS  PubMed  Google Scholar 

  • Strader DB, Wright T, Thomas D, Seeff L (2004) Diagnosis, management, and treatment of hepatitis C. Hepatolo 39:1147–1171

    Article  Google Scholar 

  • Tugues S, Fernandez-Varo G, Munoz-Luque J et al (2007) Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats. Hepatol 46:1919–1926

    Article  CAS  Google Scholar 

  • Von Marschall Z, Scholz A, Cramer T, Schafer G, Schirner M, Oberg K et al (2003) Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 95:437–448

    Article  Google Scholar 

  • White CW, Sondheimer H, Crouch E, Wilson H, Fan L (1989) Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 320:1197–1200

    Article  CAS  PubMed  Google Scholar 

  • Yoo YG, Cho S, Park S, Lee M (2004) The carboxy-terminus of the hepatitis B virus X protein is necessary and sufficient for the activation of hypoxia inducible factor-1alpha. FEBS Lett 577:121–126

    Article  CAS  PubMed  Google Scholar 

  • Yoshiji H, Kuriyama S, Fukui H (2007) Blockade of rennin-angiotensin system in antifibrotic therapy. J Gastroenterol Hepatol 22(suppl1):S93–S95

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical and Chemical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Ahmed M. El-Gohary & Fadia M. Attia

  2. Medical Microbiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Abeer Rabee Galal Eldin

  3. Infectious diseases, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Adel A. Hassen & Nader A. Nemer

  4. Internal Medicine Departments, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Fawzy A. Kalil

Authors
  1. Ahmed M. El-Gohary
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  2. Fadia M. Attia
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  3. Abeer Rabee Galal Eldin
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  4. Adel A. Hassen
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  5. Nader A. Nemer
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  6. Fawzy A. Kalil
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Correspondence to Fadia M. Attia.

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El-Gohary, A.M., Attia, F.M., Eldin, A.R.G. et al. Vascular endothelial growth factor mRNA expression can be a marker for response to antiviral treatment of HCV. Comp Clin Pathol 23, 923–928 (2014). https://doi.org/10.1007/s00580-013-1714-8

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  • DOI: https://doi.org/10.1007/s00580-013-1714-8

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