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Investigation of GHSR methylation levels in thymomas from patients with Myasthenia Gravis.
重症肌无力患者胸腺瘤中GHSR甲基化水平的研究。
- 影响因子:2.60
- DOI:10.1016/j.gene.2020.144774
- 作者列表:"Coppedè F","Stoccoro A","Nicolì V","Gallo R","De Rosa A","Guida M","Maestri M","Lucchi M","Ricciardi R","Migliore L
- 发表时间:2020-08-20
Abstract
BACKGROUND:Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with Myasthenia Gravis (TAMG). MATERIAL AND METHODS:In the present study we collected DNA samples from circulating lymphocytes and surgically resected tumor tissues of 65 TAMG patients, and from the adjacent healthy thymic tissue available from 43 of them. We then investigated GHSR methylation levels in the collected tissues searching for correlation with the clinical characteristics of the samples. RESULTS:GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 × 10-4), and those samples were particularly enriched in advanced disease stages than stage I (94% were in stage II or higher). GHSR was demethylated in the remaining 47 thymomas, as well as in all the investigated healthy thymic samples and in circulating lymphocytes. CONCLUSIONS:GHSR hypermethylation is not a pan-cancer marker or an early event in TAMG, but occurs in almost 1/4 of them and mainly from stage II onward. Subsequent studies are required to clarify the molecular pathways leading to GHSR hypermethylation in TAMG tissues and their relevance to disease progression.
摘要
背景: 在人类癌症中越来越多地观察到生长激素促分泌素受体基因 (GHSR) 的高甲基化,表明它可能代表临床感兴趣的泛癌症生物标志物。然而,关于胸腺上皮肿瘤中GHSR甲基化水平,特别是重症肌无力 (TAMG) 患者的胸腺瘤中GHSR甲基化水平仍然知之甚少。 材料和方法: 在本研究中,我们从 65 例TAMG患者的循环淋巴细胞和手术切除的肿瘤组织中收集DNA样本,并从其中 43 例患者的邻近健康胸腺组织中收集DNA样本。然后我们在收集的组织中调查GHSR甲基化水平,寻找与样本临床特征的相关性。 结果: 18 例胸腺瘤标本 (28%) 与健康胸腺组织相比,GHSR高甲基化 (P < 1 × 10-4),这些样本在疾病晚期比I期特别富集 (94% 在II期或更高)。GHSR在其余 47 例胸腺瘤以及所有研究的健康胸腺样本和循环淋巴细胞中被去甲基化。 结论: GHSR高甲基化不是TAMG的泛癌标志物或早期事件,但几乎 1/4 的人发生,主要发生在II期以后。需要后续研究阐明导致TAMG组织中GHSR高甲基化的分子途径及其与疾病进展的相关性。
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METHODS::Purpose: To report on ocular Vogt-Koyanagi-Harada (VKH)-like syndrome under vemurafenib treatment for metastatic melanoma.Design: A case report.Method: Description of clinical and imaging manifestations including fundus photography, fluorescein, and indocyanine green angiography.Results: A 46-year-old Thai female was diagnosed with metastatic melanoma of the skin and had been treated with multiple surgical excisions, radiotherapy, and vemurafenib (initial dose 480 mg orally twice daily, subsequently increased to maximum dose of 960 mg twice daily). After 6 months of vemurafenib use, she complained of bilateral redness and photophobia and was diagnosed with bilateral anterior uveitis, which was topically treated. Two weeks later, her visual acuity (VA) sharply deteriorated to 20/80 and counting fingers. Ocular examination at that stage stronly resembled acute VKH disease. She exhibited intraocular inflammation, and her fundus examination revealed bilateral optic disc swelling and serous retinal detachment. Fluorescein angiogram showed disc leakage and multiple pinpoint hyperfluorescence leakage spots and indocyanine green demonstrated multiple hypofluorescent spots. Oral prednisolone 30 mg/day was commenced while vemurafenib medication was ceased. Three weeks later, her vision improved, and serous retinal detachment subsided. However, her cutaneous melanoma recurred.Conclusions: Vemurafenib, a potential adjunct treatment for metastatic melanoma, was complicated by the development of panuveitis, papillitis, and multiple serous detachments. These ocular symptoms were similar to the presentation of acute VKH syndrome.
METHODS::Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy. WHAT THIS PAPER ADDS: Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment. Further rational therapies are expected to become available in the short- to medium-term.
METHODS::Purpose: To report the efficacy of adalimumab in a case of chronic Vogt-Koyanagi-Harada (VKH) disease refractory to conventional corticosteroids and immunosuppressive therapy and complicated by central serous chorioretinopathy (CSC).Case report: A 66-year-old woman diagnosed with VKH was treated with intravenous corticosteroids followed by oral corticosteroids and cyclosporine. However, systemic corticosteroids could not be tapered because of recurrent ocular inflammation and systemic complications (diabetes mellitus, moon face, bone weakness), while CSC appeared in both eyes. A diagnosis of chronic VKH resistant to medications complicated by corticosteroid-induced CSC was made. Systemic corticosteroids and cyclosporine were tapered and adalimumab initiated. Bilateral ocular inflammation and CSC were gradually reduced and visual acuity improved without any adverse effect. Twelve months after starting adalimumab monotherapy, no signs of active VKH and CSC were present.Conclusions: Adalimumab is one of the effective therapeutic options for refractory VKH disease complicated with corticosteroid-induced adverse effects.
神经系统自身免疫性疾病是以自身免疫细胞、免疫分子等攻击神经系统为主要致病机制的自身免疫性疾病。在免疫反应中,作用于神经系统自身抗原的致病抗体统称为神经系统自身抗体。