The Efficacy of Bevacizumab, Sorafenib, and Retinoic Acid on Rat Endometriosis Model

Hatice Ozer, Hatice Özer, Abdullah Boztosun, Gökhan Açmaz, Remzi Atılgan, Remzi Atilgan, Ozlem Bozoklu Akkar, Özlem Bozoklu Akkar, Mehmet Ilkay Kosar, Mehmet İlkay Koşar
Reproductive sciences (Thousand Oaks, Calif.) · 2012 · vol. 20(1) , pp. 26–32 · doi:10.1177/1933719112452941 · PMID:22895024 · W1971284794
article OA: closed CC0 ⤵ 65 in-corpus citations
Full text JSON View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06+body, 2026-06-13 ⓘ

Bevacizumab, sorafenib, and retinoic acid all decreased endometriotic implant volume in rats without affecting ovarian reserve, with retinoic acid additionally inducing reproductive capacity.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This paper studied whether bevacizumab, sorafenib, and all-trans retinoic acid (RA) inhibit endometriosis in a rat model. Forty-three rats with induced endometriosis were randomly assigned to control, bevacizumab, sorafenib, or RA groups, and outcomes included microvessel density, VEGF and soluble tyrosine-kinase receptor levels, ovarian reserve, and changes in endometriotic implant volume. All three medications significantly decreased endometriotic implant volume, and ovarian reserve was not affected; additionally, RA increased reproductive capacity, with VEGF-related angiogenesis measures reportedly used to assess treatment effects. Limitations included the reliance on an animal model and the specified set of endpoints (rather than broader longitudinal outcomes). This paper is centrally about endometriosis — it tests anti-angiogenic drugs (bevacizumab and sorafenib) and retinoic acid in a rat endometriosis model, linking drug effects to VEGF-regulated vascular changes.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Full text 8,180 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Blood vessels are necessary for development and maintenance of the endometriosis and blood flow supplies oxygen and essential nutrient to the disease. Local angiogenesis is regulated by vascular endothelial growth factor (VEGF) and inhibitors of VEGF may be a novel therapeutic approach. We inducted endometriosis in 43 rats and they were randomly allocated into 4 groups. The rats in group I (control n = 11) were given no medication. The rats in group II (n = 11) were given bevacizumab. The rats in group III (n = 11) were given Sorafenib, and the rats in group IV (n = 10) were given retinoic acid (RA). Then groups were compared for microvessel density, VEGF, soluble tyrosine-kinase receptor, ovarian reserve, and treatment effectivity. All these medications were effective on endometriosis and we detected that volume of endometriotic implants were significantly decreased. Ovarian reserve was not affected from the medication, in addition RA have induced reproductive capacity. Similar content being viewed by others

References

Rodgers PA, D’Hooghe TM, Fazleabas A, et al. Priorities for endometriosis research: recommendation from an international consensus workshop. Reprod Sci. 2009;16(4):335–346. Bondza PK, Mahenx R, Akoum A. Insights into endometriosis-associated endometrial dysfunctions: a review. Front Biosci (Elite Ed). 2009;1:415–428. Nap AW, Groothuis PG, Demir AY, Evers JLH, Dunselman GAJ. Pathogenesis of endometriosis. Best Pract Res Clin Obstet Gynecol. 2004;18(2):233–244. Braundmeier AG, Fazleabas AT, Lessey BA, Guo H, Toole BP, Nowak RA. Extracellular matrix metalloproteinase inducer regulates metalloproteinases in human uterine endometrium. J Clin Endocrin Metab. 2006;91(6):2358–2365. Groothuis PG, Nap AW, Winterhager E, Grümmer R. Vascular development in endometriosis. Angiogenesis. 2005;8(2):147–156. 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. McLaren J, Prentice A, Charnock-Jones DS, Smith SK. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod. 1996;11(1):220–223. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–2342. Grothey A, Ellis LM. Targeting angiogenesis driven by vascular endothelial growth factors using antibody-based therapies. Cancer J. 2008;14(3):170–177. Young-Hoon Park, Roh SY, Lee YC. Effect of sorafenib on experimental choroidal neovascularization in the rat. Clin Exp Ophthalmol. 2010;38(7):718–726. Adnane L, Trail PA, Taylor I, Wilhelm SM. Sorafenib (BAY 43-9006, Nexavar®), a dual-action inhibitor that targets RAF/MEK/ ERK pathway in tumor cells and tyrosine kinases VEGFR/ PDGFR in tumor vasculature. Methods Enzymol. 2006;407: 597–612. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/ MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64: 7099–7109. Escudier B, Eisen T, Stadier WM, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312–3318. Tee MK, Vigne JL, Taylor RN. All-trans retinoic acid inhibits vascular endothelial growth factor expression in a cell model of neutrophil activation. Endocrinology. 2006;147(3):1264–1270. Yucebilgin MS, Terek MC, Ozsaran A, et al. Effect of chemotherapy on primordial follicular reserve of rat: an animal model of premature ovarian failure and infertility Aust N Z J Obstet Gynaecol. 2004;44(1):6–9. Basbug M, Bulbuller N, Camci C, et al. The effect of antivascular endothelial growth factor on the development of adhesion formation in laparotomized rats: experimental study. Gastroenterol Res Pract. 2011;2011:578691. Park YH, Roh SY, Lee YC. Effect of sorafenib on experimental choroidal neovascularization in the rat. Clin Experiment Ophthalmol. 2010;38(7):718–726. O’Dwyer PJ, Ravikumar TS, McCabe DP, Steele G Jr. Effect of 13-cis-retinoic acid on tumor prevention, tumor growth, and metastasis in experimental colon cancer. J Surg Res. 1987; 43(6):550–557. 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. Smith BJ, Plowchalk DR, Sipes IG, Mattison DR. Comparison of random and serial sections in assessment of ovarian toxicity. Reprod Toxicol. 1991;5(4):379–383. Sharpe-Timms KL. Using rats as a research model for the study of endometrosis. Ann N Y Acad Sci. 2002;955:318–327. Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev. 2000;(2):CD000155. Griffioen AW, Molema G. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev. 2000; 52(2):237–268. 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. Becker CM, Sampson DA, Rupnick MA, et al. Endostatin inhibits the growth of endometriotic lesions but does not affect fertility. Fertil Steril. 2005;84(suppl 2):1144–1155. Papathanassiou M, Theodossiadis PG, Liarakos VS, Rouvas A, Giamarellos-Bourboulis EJ, Vergados IA. Inhibition of corneal neovascularization by subconjunctival bevacizumab in an animal model. Am J Ophthalmol. 2008;145(3):424–431. 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. Park ACP, Ferin M, Xiao E, Zeitoun K. Inhibition of endometriosis development in Rhesus monkeys by blocking VEGF receptor: a novel treatment for endometriosis. Fertil Steril. 2004;82:71. Pavone ME, Reierstad S, Sun H, Milad M, Bulun SE, Cheng YH. Altered retinoid uptake and action contributes to cell survival in endometriosis. J Clin Endocrinol Metab. 2010; 95(11):E300–E309. Moraloglu O, Isik H, Kilic S, et al. Effect of bevacizumab on postoperative adhesion formation in a rat uterine horn adhesion model and the correlation with vascular endothelial growth factor and Ki-67 immunopositivity. Fertil Steril. 2011;95(8):2638–2641. Tee MK, Vigne JL, Taylor RN. All-trans retinoic acid inhibits vascular endothelial growth factor expression in a cell model of neutrophil activation. Endocrinology. 2006;147(3): 1264–1270. Mueller MD, Lebovic DI, Garrett E, Taylor RN. Neutrophils infiltrating the endometrium express vascular endothelial growth factor: potential role in endometrial angiogenesis. Fértil Steril. 2000; 74(1):107–112. Gargett CE, Lederman F, Heryanto B, Gambino LS, Rogers PA. Focal vascular endothelial growth factor correlates with angiogenesis in human endometrium. Role of intravascular neutrophils. Hum Reprod. 2001;16(6):1065–1075. Na SY, Kang BY, Chung S, et al. Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NF kB. J Biol Chem. 1999;274(12): 7674–7680. Bollag W, Majewski S, Jablonska S. Cancer combination chemotherapy with retinoids: experimental rationale. Leukemia. 1994;8(9):1453–1457. Niikura Y, Niikura T, Wang N, Satirapod C, Tilly JL. Systemic signals in aged males exert potent rejuvenating effects on the ovarian follicle reserve in mammalian females. Aging (Albany NY). 2010;2(12):999–1003. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Ozer, H., Boztosun, A., Açmaz, G. et al. The Efficacy of Bevacizumab, Sorafenib, and Retinoic Acid on Rat Endometriosis Model. Reprod. Sci. 20, 26–32 (2013). https://doi.org/10.1177/1933719112452941 Published: Issue date: DOI: https://doi.org/10.1177/1933719112452941

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Antibodies, Monoclonal, Humanized Disease Models, Animal Endometriosis Niacinamide Phenylurea Compounds Tretinoin Administration, Oral Animals Antibodies, Monoclonal, Humanized Bevacizumab Endometriosis Endometriosis Female Microvessels Microvessels Microvessels Niacinamide Niacinamide Phenylurea Compounds Random Allocation

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (35)

Cited by (50)

Source provenance

europepmc
last seen: 2026-06-13T06:22:48.782012+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:16:04.919516+00:00
License: CC0 · commercial use OK