[Current and future medical treatment for endometriosis].

Masayo Hosokawa, Fuminori Taniguchi
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Abstract

Endometriosis is a chronic, progressive inflammatory disease that occurs in approximately 10% of women of reproductive age, resulting in a decreased quality of life due to dysmenorrhea, chronic pain, and other problems. The primary treatment is pain control and fertility preservation, and while preserving ovarian function through drug therapy and surgery, assisted reproductive technology (ART), including in vitro fertilization (IVF), is also utilized. Hormonal therapies such as low-dose estrogen/progestin (LEP), progestins, and GnRH analogs are often the drug of choice. We presented that IAP (inhibitor of apoptotic protein) inhibitors can potentially be novel agents for treating endometriosis. Our studies using cultured cells derived from human endometriotic lesions and mouse models have revealed that inflammatory cytokines and antiapoptotic factors (IAPs) produced by peritoneal macrophages or endometriosis cells are crucial and that NF-κB (nuclear factor-kappa B) plays a central role in the pathogenesis of endometriosis. The high expression of IAPs in human endometriotic tissues, its facilitative role in ectopic survival, and the effect of IAPs on drug-resistant apoptosis of human endometriotic cells indicate its potential as a novel drug for IAP inhibitors. We found that the medicinal herb parthenolide and selective estrogen receptor modulators (SERM) can reduce lesions through NF-κB inhibition. Recently, new findings were obtained by non-invasive observation of early lesions using bioluminescence technology and by applying knockout mouse models. We will show the possibility of new therapeutic agents for endometriosis.

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[子宫内膜异位症目前和未来的医学治疗]。
子宫内膜异位症是一种慢性、进行性炎症性疾病,约有 10%的育龄妇女会患上这种疾病,由于痛经、慢性疼痛和其他问题而导致生活质量下降。主要的治疗方法是控制疼痛和保留生育能力,在通过药物治疗和手术保留卵巢功能的同时,还采用辅助生殖技术(ART),包括体外受精(IVF)。低剂量雌激素/孕激素(LEP)、孕激素和 GnRH 类似物等激素疗法通常是首选药物。我们提出,IAP(凋亡蛋白抑制剂)抑制剂有可能成为治疗子宫内膜异位症的新型药物。我们利用来自人类子宫内膜异位症病灶和小鼠模型的培养细胞进行的研究发现,腹腔巨噬细胞或子宫内膜异位症细胞产生的炎性细胞因子和抗凋亡因子(IAPs)至关重要,而 NF-κB(核因子-卡巴 B)在子宫内膜异位症的发病机制中起着核心作用。IAPs 在人类子宫内膜异位症组织中的高表达、其在异位生存中的促进作用以及 IAPs 对人类子宫内膜异位症细胞耐药凋亡的影响,都表明其具有作为 IAP 抑制剂新型药物的潜力。我们发现,药草马钱子内酯(parthenolide)和选择性雌激素受体调节剂(SERM)可通过抑制 NF-κB 减少病变。最近,利用生物发光技术和基因敲除小鼠模型对早期病变进行非侵入性观察又有了新的发现。我们将展示子宫内膜异位症新治疗药物的可能性。
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来源期刊
Folia Pharmacologica Japonica
Folia Pharmacologica Japonica Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
0.40
自引率
0.00%
发文量
132
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[Deep brain imaging by using GRIN lens].
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