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The Effects of Ranibizumab on Surgically Induced Endometriosis in a Rat Model: A Preliminary Study

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Abstract

Objective

To examine the effect of ranibizumab on surgically induced endometriosis in rat models.

Study Design

Endometrial tissue was implanted onto the abdominal peritoneum of 20 rats that were randomized into 2 groups. The rats in group 1 (n = 9) were given 0.6 mg/kg ranibizumab on the 1st and 14th days after the second operation. The rats in group 2 (control group, n = 9) received no medication. All the rats were observed for a total of 28 days.

Results

At the end of the treatment, the mean volume and weight of the explants in group 1 (11.49 ± 6.87 mm3 and 36.61 ± 17.84 mg) were significantly lower than that of the control group (190.6 ± 177.4 mm3 and 187.3 ± 174.5 mg; both Ps < .01). Mean epithelial histologic scores were significantly lower in group 1 (1.11 ± 0.78) than that of the control group (2.33 ± 0.71; P < .01). When compared with the control group, vascular endothelial growth factor (VEGF) immunoreactivities in group 1 showed statistically significant reductions (1.67 ± 0.50; 2.67 ± 0.50; P < .01).

Conclusion

Ranibizumab has significantly regressed the size of the endometriotic implants and caused atrophy of these lesions in rats by decreasing explant levels of VEGF.

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References

  1. Frackiewicz EJ. Endometriosis: an overview of the disease and its treatment. J Am Pharm Assoc. 2000;40(5):645–657.

    CAS  Google Scholar 

  2. Bajaj P, Madsen H, Arendt-Nielsen L. Endometriosis is associated with central sensitization: a psychophysical controlled study. J Pain. 2003;4(7):372–380.

    Article  Google Scholar 

  3. Howard FM. Chronic pelvic pain. Obstet Gynecol. 2003;101(3): 594–611.

    PubMed  Google Scholar 

  4. Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14:422–469.

    Article  Google Scholar 

  5. Gleicher N, El-Roeiy A, Confino E, Friberg J. Is endometriosis an autoimmune disease? Obstet Gynecol. 1987;70(1):115–121.

    CAS  PubMed  Google Scholar 

  6. Machado DE, Abrao MS, Berardo PT, Takiya CM, Nasciutti LE. Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum. Fertil Steril. 2008;90(1):148–155.

    Article  CAS  Google Scholar 

  7. Hull ML, Charnock-Jones DS, Chan CL, et al. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab. 2003;88(6):2889–2899.

    Article  CAS  Google Scholar 

  8. Nap AW, Griffioen AW, Dunselman GA, et al. Antiangiogenesis therapy for endometriosis. J Clin Endocrinol Metab. 2004;89(3): 1089–1095.

    Article  CAS  Google Scholar 

  9. Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998;13(6):1686–1690.

    Article  CAS  Google Scholar 

  10. Kenneth TE, Kertes PJ. Ranibizumab in neovascular age-related macular degeneration. Clin Interv Aging. 2006;1(4):451–466.

    Article  Google Scholar 

  11. Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril. 1985;44(5):684–694.

    Article  CAS  Google Scholar 

  12. Uygur D, Aytan H, Zergeroğlu S, Batioğlu S. Leflunomide-an immunomodulator induces regression of endometrial explant in a rat model of endometriosis. J Soc Gynecol Investi. 2006; 13(5):378–383.

    Article  CAS  Google Scholar 

  13. Lebovic DI, Kir M, Casey CL. Peroxisome proliferator–activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril. 2004;82(suppl 3): 1008–1013.

    Article  CAS  Google Scholar 

  14. Yilmaz B, Sucak A, Kilic S, et al. Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9. Am J Obstet Gynecol. 2010;202(4):368.e1–368.e1.

    Article  Google Scholar 

  15. Mota A, Carneiro A, Breda J, et al. Combination of intravitreal ranibizumab and laser photocoagulation for aggressive posterior retinopathy of prematurity. Case Rep Ophthalmol. 2012;3(1): 136–141.

    Article  Google Scholar 

  16. Keenan JA, Williams-Boyce PK, Massey PJ, Chen TT, Caudle MR, Bukovsky A. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril. 1999;72(1):135–141.

    Article  CAS  Google Scholar 

  17. Vercellini P, Crosignani PG, Somigliana E, Berlanda N, Barbara G, Fedele L. Medical treatment for rectovaginal endometriosis: what is the evidence? Hum Reprod. 2009;24(10):2504–2514.

    Article  Google Scholar 

  18. Ferrero S, Remorgida V, Venturini PL. Current pharmacotherapy for endometriosis. Expert Opin Pharmacother. 2010;11(7): 1123–1134.

    Article  CAS  Google Scholar 

  19. Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev. 2007;(3):CD000155.

  20. Groothuis PG, Nap AW, Winterhager E, Grummer R. Vascular development in endometriosis. Angiogenesis. 2005;8(2):147–156.

    Article  CAS  Google Scholar 

  21. Goss PE, Strasser-Weippl K. Prevention strategies with aromatase inhibitors. Clin Cancer Res. 2004;10(1 pt 2):372–379.

    Article  Google Scholar 

  22. Collette T, Bellehumeur C, Kats, et al. Evidence for an increased release of proteolytic activity by the eutopic endometrial tissue in women with endometriosis and for involvement of matrix metalloproteinase-9. Hum Reprod. 2004;19(6):1257–1264.

    Article  CAS  Google Scholar 

  23. Ge YL, Zhang X, Zhang JY, Hou L, Tian RH. The mechanisms on apoptosis by inhibiting VEGF expression in human breast cancer cells. Int Immunopharmacol. 2009;9(4):389–395.

    Article  CAS  Google Scholar 

  24. Carneiro A, Falcao M, Pirraco A, Milheiro-Oliveira P, Falcao-Reis F, Soares R. Comparative effects of bevacizumab, ranibizumab and pegaptanib at intravitreal dose range on endothelial cells. Exp Eye Res. 2009;88(3):522–527.

    Article  CAS  Google Scholar 

  25. Wang Y, Fei D, Vanderlaan M, Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis. 2004;7(4):335–345.

    Article  CAS  Google Scholar 

  26. Ricci AG, Olivares CN, Bilotas MA, Meresman GF, Barañao RI. Effect of vascular endothelial growth factor inhibition on endometrial implant development in a murine model of endometriosis. Reprod Sci. 2011;18(7):614–622.

    Article  CAS  Google Scholar 

  27. Cho HJ, Baek JS, Lee DW, Kim CG, Kim JW. Short-term effectiveness of intravitreal bevacizumab vs. ranibizumab injections for patients with polypoidal choroidal vasculopathy. Korean J Ophthalmol. 2012;26(3):157–162.

    Article  CAS  Google Scholar 

  28. Krzystolik MG, Afshari MA, Adamis AP, et al. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol. 2002;120(3):338–346.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Bezmialem Vakif University, School of Medicine, Vatan Street, 34128, Istanbul, Turkey

    Osman Sevket MD, Taner Molla MD, Gokhan Kilic MD, Seda Ates MD & Ramazan Dansuk MD

  2. Department of Obstetrics and Gynecology, Safa Hospital, Istanbul, Turkey

    Asli Sevket MD

  3. Department of Pathology, Bezmialem Vakif University, School of Medicine, Istanbul, Turkey

    Nur Buyukpinarbasili MD

Authors
  1. Osman Sevket MD
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  2. Asli Sevket MD
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  3. Nur Buyukpinarbasili MD
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  4. Taner Molla MD
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  5. Gokhan Kilic MD
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  6. Seda Ates MD
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  7. Ramazan Dansuk MD
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Correspondence to Osman Sevket MD.

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Sevket, O., Sevket, A., Buyukpinarbasili, N. et al. The Effects of Ranibizumab on Surgically Induced Endometriosis in a Rat Model: A Preliminary Study. Reprod. Sci. 20, 1224–1229 (2013). https://doi.org/10.1177/1933719113483012

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