Impact of Bevacizumab on Experimentally Induced Endometriotic Lesions: Angiogenesis, Invasion, Apoptosis, and Cell Proliferation

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Bevacizumab treatment reduced the area of experimentally induced endometriotic lesions in rats and decreased Tp63 gene expression, suggesting it reduces cell proliferation and differentiation.

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The study investigated how bevacizumab, an anti-VEGF angiogenesis inhibitor given at two different dosages, affects experimentally induced endometriotic lesions in rats over 4 weeks. After lesion induction, rats were assigned to a no-treatment control group or two treatment groups, and lesion area, endometrial tissue presence by microscopy, anti-VEGF antibody positivity by immunohistochemistry, and gene expression of Pcna, Mmp9, Tp63, and Vegfa were assessed. Bevacizumab significantly reduced lesion area and lowered Tp63 gene expression (with no significant effects reported for the other evaluations), and the authors conclude this aligns with reduced cell proliferation and differentiation. This paper is centrally about endometriosis — it tests whether bevacizumab modulates lesion growth and cell biology in a rat endometriosis model, with specific molecular readouts including Tp63.

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Abstract

Endometriosis is responsible for pain symptoms with great impact on the patient's quality of life. Several medication lines have been studied aiming at its definitive treatment. Among them, angiogenesis inhibitor factors may be effective given that angiogenesis has fundamental role in the establishment and growth of endometriotic lesions. In this study, we investigated the influence of bevacizumab, anti-factor drug of endothelial growth (anti-VEGF), used at two different dosages, in experimental endometriosis induced in rats. After the induction of endometriosis lesions in rats, they were divided in 3 groups: control group, no treatment, and two other groups were treated with different dosages of the same medication for 4 weeks. At the end of the treatment, endometriotic lesions were removed and evaluated regarding area of lesions, presence of endometrial tissue in microscopy, positivity for anti-VEGF antibody in immunohistochemistry, and gene expression of Pcna, Mmp9, Tp63, and Vegfa. Bevacizumab acted by reducing the area of lesions in the groups that received medication (p = 0.002) and reducing gene expression to Tp63 in lesions (p = 0.04). There was no significant result in other evaluations. We observed that there was significant reduction of the area of lesions among groups, suggesting that bevacizumab has a positive effect on disease control. The gene expression of Tp63 was significantly lower in the group that received high dose of the drug when compared with the other two groups; therefore, we concluded that bevacizumab acts by reducing cell proliferation and differentiation in lesions, constituting a real option for treating endometriosis.
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Abstract

Endometriosis is responsible for pain symptoms with great impact on the patient’s quality of life. Several medication lines have been studied aiming at its definitive treatment. Among them, angiogenesis inhibitor factors may be effective given that angiogenesis has fundamental role in the establishment and growth of endometriotic lesions. In this study, we investigated the influence of bevacizumab, anti-factor drug of endothelial growth (anti-VEGF), used at two different dosages, in experimental endometriosis induced in rats. After the induction of endometriosis lesions in rats, they were divided in 3 groups: control group, no treatment, and two other groups were treated with different dosages of the same medication for 4 weeks. At the end of the treatment, endometriotic lesions were removed and evaluated regarding area of lesions, presence of endometrial tissue in microscopy, positivity for anti-VEGF antibody in immunohistochemistry, and gene expression of Pcna, Mmp9, Tp63, and Vegfa. Bevacizumab acted by reducing the area of lesions in the groups that received medication (p = 0.002) and reducing gene expression to Tp63 in lesions (p = 0.04). There was no significant result in other evaluations. We observed that there was significant reduction of the area of lesions among groups, suggesting that bevacizumab has a positive effect on disease control. The gene expression of Tp63 was significantly lower in the group that received high dose of the drug when compared with the other two groups; therefore, we concluded that bevacizumab acts by reducing cell proliferation and differentiation in lesions, constituting a real option for treating endometriosis. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Zani, A.C.T., Valerio, F.P., Meola, J. et al. Impact of Bevacizumab on Experimentally Induced Endometriotic Lesions: Angiogenesis, Invasion, Apoptosis, and Cell Proliferation. Reprod. Sci. 27, 1943–1950 (2020). https://doi.org/10.1007/s43032-020-00213-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00213-7

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endometriosis

MeSH descriptors

Apoptosis Bevacizumab Cell Proliferation Endometriosis Neovascularization, Pathologic Animals Apoptosis Bevacizumab Bevacizumab Cell Proliferation Disease Models, Animal Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Matrix Metalloproteinase 9 Matrix Metalloproteinase 9 Neovascularization, Pathologic

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