European urology最新文献

Re: Preventative Function-sparing Radical Prostatectomy: Experience in a Tertiary Referral Centre 关于：保留功能的预防性根治性前列腺切除术：三级转诊中心的经验

IF 23.4 1区医学

European urology Pub Date : 2025-05-16 DOI: 10.1016/j.eururo.2025.05.009

Jan Adamowicz, Krzysztof Koper, Tomasz Drewa

引用次数: 0

The Critical Role of FLCN, TFE3, and TFEB in Bioenergetic and Nutrient Sensing, Renal Cancer Tumorigenesis and Metabolic Health FLCN、TFE3和TFEB在生物能量和营养感知、肾癌肿瘤发生和代谢健康中的关键作用

IF 23.4 1区医学

European urology Pub Date : 2025-05-16 DOI: 10.1016/j.eururo.2025.05.003

W. Marston Linehan, Christopher J. Ricketts, Daniel R. Crooks, Laura S. Schmidt

{"title":"The Critical Role of FLCN, TFE3, and TFEB in Bioenergetic and Nutrient Sensing, Renal Cancer Tumorigenesis and Metabolic Health","authors":"W. Marston Linehan, Christopher J. Ricketts, Daniel R. Crooks, Laura S. Schmidt","doi":"10.1016/j.eururo.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.003","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>FLCN function</h2>FLCN is an ancient cellular bioenergetic and nutrient sensor that controls activation of the TFE3 and TFEB transcription factors and regulates lysosomal and mitochondrial biogenesis and function. FLCN, and its binding partner FNIP1, act as a GTP-activating protein (GAP) for the small GTPase Ras-related GTP-binding protein C (RagC). FLCN and FNIP activate a noncanonical mTORC1 signaling pathway that leads to phosphorylation of members of the microphthalmia/transcription factor E (MiT/TFE) family</section></section><section><section><h2><em>FLCN</em> mutation in BHD RCC</h2>BHD-associated hybrid RCC, chromophobe RCC, and oncocytoma tumors are characterized by biallelic inactivation of <em>FLCN</em> due to a combination of the germline pathogenic variation and somatic loss of function of the remaining allele via “second hit” mutation or deletion events. FLCN loss in BHD renal tumors leads to dephosphorylation and nuclear translocation of TFE3 [7] and TFEB, resulting in increased lysosomal and mitochondrial biogenesis (Fig. 1D). This is reflected in immunohistochemical</section></section><section><section><h2>Dysregulation of MiT/TFE transcription factors in renal cancer</h2>Activation of TFE3 and/or TFEB is recognized as an important driver event in many different types of renal cancer, including sporadic RCC's resulting from somatic TFE3/TFEB translocation or amplification of TFEB, as well as hereditary RCCs caused by germline variants in <em>MITF</em>, <em>TSC1</em>, <em>TSC2</em>, and <em>PRDM10</em>. These tumor types demonstrate overlapping histologies with BHD-associated RCCs, with TFE3/TFEB translocation RCC and PRDM10-associated RCC strongly reflecting the rarer but more aggressive</section></section><section><section><h2>Clinical management and therapy</h2>Identification of the <em>FLCN</em> gene, which was made possible by studying patients affected by BHD, has enabled clinicians to improve clinical management and surgical care for these patients. It also provides a foundation for the development of therapeutic or preventive approaches for BHD using small molecules that target TFE3/TFEB stability, agents targeting PGC1α transcriptional activity, antibody-drug conjugates and CAR-T cell therapies targeting cell-surface GPNMB expression.</section></section><section><section><h2>Implications of the physiologic role of FLCN on metabolic health</h2>As a sensor of bioenergetic and nutrient stress, FLCN is thought to potentially have significant importance in human health. FLCN is likely to play a critical role in the body’s response to exercise and restriction of caloric intake on long-term health. Gosis et al [8] showed that a decrease in FLCN in the liver could reverse nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in animals fed a diet high in fructose, cholesterol, and trans fats. Zhang et al [9] demonstrated that</section></section>","PeriodicalId":12223,"journal":{"name":"European urology","volume":"30 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Precision Radiotherapy for Kidney Cancer: A Rising Ally in Multidisciplinary Care 精确放疗治疗肾癌：多学科治疗的新兴领域

IF 23.4 1区医学

European urology Pub Date : 2025-05-16 DOI: 10.1016/j.eururo.2025.04.027

Barbara Alicja Jereczek-Fossa, Federico Mastroleo, Giulia Marvaso

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Re: Assessment of a Polygenic Risk Score in Screening for Prostate Cancer 多基因风险评分在前列腺癌筛查中的评估

IF 23.4 1区医学

European urology Pub Date : 2025-05-16 DOI: 10.1016/j.eururo.2025.05.012

Guangdi Chu, Zhiqiang Li, Haitao Niu

引用次数: 0

Belzutifan in Europe: A New Targeted Therapy for Clear Cell Renal Cancer 贝尔祖替芬在欧洲：透明细胞肾癌的一种新的靶向治疗