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

Özer, Hatice; Boztosun, Abdullah; Açmaz, Gökhan; Atılgan, Remzi; Akkar, Özlem Bozoklu; Koşar, Mehmet İlkay

doi:10.1177/1933719112452941

Cited by 55 publications

(50 citation statements)

References 34 publications

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“…We chose the number of follicles as the outcome measure. There were 5 experiments that reported the number of follicle alteration after administrating the agents [22, 28]. Taken together, angiogenesis inhibition therapy had no obvious effect on follicle number (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08) and the heterogeneity was high (I 2 = 71.3%, 95% CI 27% to 89%; H 2 = 2.49; Fig 3).…”

Section: Resultsmentioning

confidence: 95%

“…Endometriosis score outcomes after anti-VEGF/VEGFR therapy were reported in 9 experiments [20, 22, 23, 26–28]. Taken together, these experiments showed that anti-angiogenesis intervention was associated with a lower endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001) with a large heterogeneity in the estimates (I 2 = 50.3%, 95% CI 0% to 77%; H 2 = 1.01; Fig 2D).…”

Section: Resultsmentioning

confidence: 99%

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Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

et al. 2016

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Background/ObjectiveVascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis.MethodsA systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers.ResultsWe identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% CI –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08).ConclusionsAnti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

et al. 2016

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“…Similarly, sorafenib (Nexavar®, Bayer/Onyx Pharmaceuticals), another multikinase inhibitor that interferes with VEGF-R2, VEGF-R3, B-Raf and other tyrosine kinase receptors, was highly efficient in a rat model of induced endometriosis. 57 Despite the risk of cumulative toxicity that cannot be neglected, the concept of combined pathway targeting opens up perspectives for improved control of endometriosis.…”

Section: Pro-angiogenic Signaling Blockersmentioning

confidence: 99%

Angiogenesis as a Therapeutic Target in Endometriosis

Djokovic

Calhaz‐Jorge

2014

Acta Med Port

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RESUMOIntrodução: A angiogénese é um factor determinante no estabelecimento e desenvolvimento das lesões de endometriose. Material e Métodos:Foram revistos os artigos indexados na PubMed e incluídos os estudos mais relevantes, publicados até Janeiro de 2014, sobre a angiogénese nas lesões de endometriose e/ou estratégias anti-angiogénicas para o tratamento desta doença ginecológica.Resultados: O presente artigo fornece um resumo conciso dos mecanismos moleculares conhecidos que promovem a vascularização das lesões de endometriose, podendo servir como alvos terapêuticos potenciais. Apresenta-se também uma revisão sistemática dos agentes anti-angiogénicos, inclusivos e exclusivos, que já foram avaliados em culturas de células, modelos animais e/ou doentes com endometriose. Discussão e Conclusão: A integração das estratégias anti-angiogénicas na terapêutica multimodal de endometriose será condicionada pelos resultados de avaliações futuras da verdadeira eficácia desses tratamentos, do risco de desenvolvimento de resistência aos medicamentos e da incidência de efeitos colaterais inaceitáveis. Palavras-chave: Inibidores da Angiogénese/uso terapêutico; Endometriose/terapêutica. ABSTRACT Introduction:Angiogenesis is a key factor for the successful establishment and growth of endometriotic lesions. Material and Methods:We performed a literature search in PubMed and reviewed the most pertinent studies published until January 2014 and focused on the endometriosis-associated angiogenesis and/or anti-angiogenic strategies for the treatment of this gynecological disorder. Results:The present review provides a concise summary of the known molecular mechanisms that promote vascularization of endometriotic lesions and may serve as potential therapeutic targets. We also present a systematic overview of the inclusive and exclusive anti-angiogenic agents that have been already studied in cell cultures, animal models and/or endometriosis patients. Discussion and Conclusion:The integration of anti-angiogenic approaches in the multimodal management strategies for endometriosis patients will be conditioned by the outcomes of future assessments regarding the effectiveness of such treatments, the risk of drug resistance development and the incidence of unacceptable side effects.

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“…In contrast, there are interesting novel reports that describe ovarian reserve; the number of primordial follicles can be increased by stimulation of RA gene 8, and this occurs without changes in follicle growth activation or atresia [11]. Other authors claimed that RA may activate the reproductive capacity in Wistar albino rats, and they detected significantly high ovarian reserve in rats receiving RA, concluding that RA might be an anti-aging agent [12]. There are some rising concerns about the use of isotretinoin in young girls and particularly in women aged 35 years or more who are willing to have a baby with depleted ovarian reserve.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Isotretinoin on Ovarian Reserve Based on Hormonal Parameters, Ovarian Volume, and Antral Follicle Count in Women with Acne

Aksoy

Çınar

Açmaz

et al. 2015

Gynecol Obstet Invest

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Backgroud/Aims: Widely prescribed in routine practice, isotretinoin has an unknown impact on ovarian reserve. With a long history in acne treatment and numerous potential side effects, it is surprising that very few prospective studies have investigated its effect on ovarian reserve. Therefore, we aimed to evaluate the impact of oral isotretinoin on ovarian reserve based on hormonal parameters, anti-Müllerian hormone (AMH), ovarian volume (OV), and antral follicle count (AFC) in women of reproductive age with acne. Methods: Our study group consisted of 82 women of reproductive age with acne who were treated with oral isotretinoin. The patients were evaluated for ovarian reserve prior to therapy and reevaluated 6 months after isotretinoin treatment with regard to hormonal parameters, AMH, OV, and AFC. Results: Significant differences were found between the pre- and posttreatment period for AMH [2.20 ng/ml (25th-75th percentile 1.14-4.07) vs. 1.31 ng/ml (0.32-2.28)], total AFC [16 (14-18.25) vs. 12.5 (10-15)], and total OV [23 ml (18-29) vs. 15 ml (13-18); p < 0.001]. Conclusion: Our study is the first to analyze the levels of serum AMH, AFC, and OV together in patients treated with oral isotretinoin for acne. The results of our study demonstrated that oral isotretinoin had a significant negative effect on ovarian reserve.

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

Cited by 55 publications

References 34 publications

Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

Angiogenesis as a Therapeutic Target in Endometriosis

The Effect of Isotretinoin on Ovarian Reserve Based on Hormonal Parameters, Ovarian Volume, and Antral Follicle Count in Women with Acne

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