Anti-angiogenic therapy as potential treatment for adenomyosis

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Marissa J. Harmsen, Lynda J. M. Juffermans, Muara O. Kroon, Arjan W. Griffioen, Judith A. F. Huirne
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Abstract

Adenomyosis is characterized by abnormal uterine bleeding, dysmenorrhea and subfertility. Increased expression of angiogenesis markers in adenomyosis presents a treatment opportunity and was studied in an adenomyosis mouse model. Mice were administered tamoxifen (1 mg/kg) on neonatal days 2–5. At six weeks of age, mice received oral treatment with axitinib 3 mg/kg (‘dose I/AX3’, n = 34), axitinib 25 mg/kg (‘dose II/AX25’ n = 34), or with vehicle-only (‘placebo’, n = 34). The prevalence and severity of adenomyosis were assessed. An adenomyosis severity index was calculated by multiplying mean grade/mouse by the percentage affected surface area. Angiogenesis-related gene expression was evaluated using real-time quantitative PCR. 101 mice completed adenomyosis induction and could be analyzed. The prevalence of adenomyosis was 30/33 (90.0%) in dose I, 29/34 (85.3%) in dose II, and 30/34 (88.2%) in placebo treated mice (p = 0.78). High grade (2/3) adenomyosis was significantly less prevalent in mice treated with axitinib dose II (n = 19, 55.9%) than in the placebo group (n = 27, 79.4%, p < 0.05). The adenomyosis severity index was reduced by 48% in the axitinib-treated groups (dose I, p < 0.05). The expression of angiogenic growth factors was reduced in the dose I and II axitinib-treated groups compared to the placebo-treated group. Following these promising first results, further research should focus on commonality among different angiostatic drugs, potential side effects, as well as the method and timing of application.

抗血管生成治疗作为子宫腺肌症的潜在治疗方法。
子宫腺肌症的特点是子宫异常出血,痛经和生育能力低下。在子宫腺肌症小鼠模型中,血管生成标记物的表达增加提供了治疗机会。小鼠在新生儿第2-5天给予他莫昔芬(1 mg/kg)。在6周龄时,小鼠接受口服阿西替尼3mg /kg(剂量I/AX3, n = 34)、阿西替尼25mg /kg(剂量II/AX25, n = 34)或仅给药(安慰剂,n = 34)。评估子宫腺肌症的患病率和严重程度。通过将平均等级/小鼠乘以受影响表面积百分比来计算子宫腺肌症严重性指数。实时定量PCR检测血管生成相关基因表达。101只小鼠完成子宫腺肌症诱导,可进行分析。第一剂量组子宫腺肌症患病率为30/33(90.0%),第二剂量组为29/34(85.3%),安慰剂组为30/34 (88.2%)(p = 0.78)。阿西替尼II剂量组高级别(2/3)子宫腺肌症发生率(n = 19, 55.9%)明显低于安慰剂组(n = 27, 79.4%, p
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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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