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Biomarkers for renal cell carcinoma — a pragmatic approach 肾细胞癌的生物标志物-一种实用的方法
IF 15.3 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-30 DOI: 10.1038/s41585-025-01073-z
Ziad Bakouny, A. Ari Hakimi, Ed Reznik, Robert J. Motzer
The management of metastatic renal cell carcinoma (RCC) has undergone a major transformation, with median survival increasing from <1 year to ~5 years. However, biomarker development in RCC has lagged, largely because the most effective therapies, such as immune checkpoint inhibitors and VEGFR tyrosine kinase inhibitors, act on the tumour microenvironment rather than directly on tumour cells. Although predictive biomarker development in RCC remains challenging, selected tools such as circulating biomarkers and tissue-based RNA signatures are shaping a personalized approach to care, with some emerging biomarkers showing clinical potential, and additional biomarkers poised to enter clinical practice.
转移性肾细胞癌(RCC)的治疗经历了重大转变,中位生存期从1年增加到5年。然而,RCC的生物标志物发展滞后,主要是因为最有效的治疗方法,如免疫检查点抑制剂和VEGFR酪氨酸激酶抑制剂,作用于肿瘤微环境,而不是直接作用于肿瘤细胞。尽管预测RCC的生物标志物开发仍然具有挑战性,但循环生物标志物和基于组织的RNA标记等精选工具正在形成个性化的护理方法,一些新兴生物标志物显示出临床潜力,其他生物标志物准备进入临床实践。
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引用次数: 0
Iatrogenic upper urinary tract injuries during ureteroscopy for urolithiasis: a comprehensive review on incidence, mechanisms and preventative strategies 尿石症输尿管镜检查时医源性上尿路损伤:发生率、机制和预防策略的综合综述
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-29 DOI: 10.1038/s41585-025-01067-x
Orla Cullivan, Eva Browne, Sorcha O’Meara, Andreas Skolarikos, Bhaskar Somani, Eoghan M. Cunnane, Michael T. Walsh, Fergal J. O’Brien, Niall F. Davis
The incidence of urolithiasis is increasing globally, with a prevalence of 13% in North America and 9% in Europe. Ureteroscopy is a minimally invasive approach for treating conditions affecting the upper urinary tract, including urolithiasis, for which its efficacy and safety is well recognized. There is a risk of complications associated with ureteroscopy, including iatrogenic mechanical ureteric injuries. These injuries are multifactorial in nature, with ureteroscopes and auxiliary endoscopic equipment having an important role, in addition to patient and stone factors. Excessive friction and insertion forces during ureteroscope and ureteric access sheath insertion, apparatus malfunction or thermal injuries during laser lithotripsy might cause injury to the upper urinary tract. Ureteric avulsion is a serious event, which necessitates further intervention such as ureteric reimplantation or nephrectomy. Ureteric mucosal injuries can be managed with a period of ureteric stenting, although stent-related symptoms can be challenging for patients. The ability of endoscopic equipment to injure the ureter is an area that requires further study to reduce incidence and minimize patient morbidity. In this article, we review the operative mechanisms that contribute to iatrogenic mechanical ureteric injuries and discuss preventative strategies. This Review outlines the operative mechanisms that contribute to iatrogenic mechanical ureteric injuries. The authors aim to increase awareness among urologists of the aetiology of these injuries, so that they can be avoided in practice, ultimately enhancing patient safety.
尿石症的发病率在全球范围内呈上升趋势,北美的患病率为13%,欧洲为9%。输尿管镜检查是一种微创方法,用于治疗影响上尿路的疾病,包括尿石症,其有效性和安全性是公认的。输尿管镜检查有并发症的风险,包括医源性机械输尿管损伤。这些损伤本质上是多因素的,除患者和结石因素外,输尿管镜和辅助内镜设备也起着重要作用。输尿管镜及输尿管鞘插入过程中摩擦力过大、插入力过大、器械故障或激光碎石过程中热损伤均可引起上尿路损伤。输尿管撕脱是一种严重的事件,需要进一步的干预,如输尿管再植或肾切除术。输尿管粘膜损伤可以通过一段时间的输尿管支架置入术来治疗,尽管支架相关症状对患者来说可能具有挑战性。内窥镜设备损伤输尿管的能力是一个需要进一步研究的领域,以减少发病率和减少患者的发病率。在本文中,我们回顾了导致医源性机械性输尿管损伤的手术机制,并讨论了预防策略。
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引用次数: 0
Mechanisms and implications of epithelial cell plasticity in the bladder 膀胱上皮细胞可塑性的机制和意义
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-24 DOI: 10.1038/s41585-025-01066-y
Kan Wu, Xu Liu, Jiapeng Zhang, Xianding Wang, Xiang Li, Chong Chen
Cellular plasticity, the ability of cells to reprogramme and alter their fate, has a pivotal role in maintaining homeostasis and facilitating tissue regeneration after injury. The bladder urothelium, a dynamic transitional epithelial layer, displays a highly plastic phenotype that enables its remarkable regenerative capacity in response to wounding. During both development and repair, urothelial cells exhibit considerable plasticity through processes such as dedifferentiation, transdifferentiation and epithelial-to-mesenchymal transition. Urothelial plasticity is not only crucial for healthy tissue repair but is also involved in pathological conditions, including cancer. In bladder tumorigenesis, urothelial cells exploit plasticity to acquire new phenotypic and functional characteristics, transitioning between distinct cellular states. This plasticity contributes to tumour heterogeneity, subtype switching, progression, metastasis and resistance to therapies. These dynamic cellular transitions are regulated by intrinsic and extrinsic factors, including transcriptional and epigenetic mechanisms, as well as microenvironmental influences. Targeting urothelial plasticity could offer novel therapeutic strategies for bladder-related diseases. In this Review the authors describe current knowledge on cellular plasticity in the bladder urothelium, emphasizing its role in bladder repair and tumorigenesis, and explore the molecular mechanisms of urothelial plasticity and discuss its potential as a novel therapeutic target for bladder-related diseases.
细胞可塑性,即细胞重编程和改变自身命运的能力,在损伤后维持体内平衡和促进组织再生中起着关键作用。膀胱尿路上皮是一种动态的移行上皮,具有高度可塑性的表型,使其在损伤时具有显著的再生能力。在发育和修复过程中,尿路上皮细胞通过去分化、转分化和上皮向间质转化等过程表现出相当大的可塑性。尿路上皮的可塑性不仅对健康组织修复至关重要,而且还涉及包括癌症在内的病理状况。在膀胱肿瘤发生过程中,尿路上皮细胞利用可塑性获得新的表型和功能特征,在不同的细胞状态之间转换。这种可塑性有助于肿瘤的异质性、亚型转换、进展、转移和对治疗的抵抗。这些动态的细胞转变受到内在和外在因素的调节,包括转录和表观遗传机制,以及微环境影响。靶向尿路上皮可塑性可为膀胱相关疾病的治疗提供新的策略。
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引用次数: 0
iCAFs control chemoresistance icaf控制化学耐药
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-14 DOI: 10.1038/s41585-025-01068-w
Louise Lloyd
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引用次数: 0
Non-human primates as a translational model for the study of male reproductive health 非人灵长类动物作为雄性生殖健康研究的翻译模型
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-07 DOI: 10.1038/s41585-025-01062-2
R. Clayton Edenfield, Jasper C. Bash, Lyndsey E. Shorey-Kendrick, Rahul J. D’Mello, Travis L. Rice-Stitt, Olivia L. Hagen, Jason A. Graham, Kyle E. Orwig, Charles A. Easley, Jason C. Hedges, Carol B. Hanna, Jamie O. Lo
Male fertility is complex and influenced by genetic, hormonal, environmental and lifestyle factors. However, limitations to human studies necessitate the use of reliable preclinical models to better understand the underlying mechanisms of male fertility. Rhesus macaques (Macaca mulatta), with their close genetic and physiological similarities to humans, offer an invaluable model for male reproductive health studies. The suitability of rhesus macaques for studying male infertility is based on similarities in spermatogenesis, hormonal cycles and the way in which assisted reproductive technologies can be applied, and key differences and similarities between human and rhesus macaque sperm structure, function and cryopreservation techniques highlight the translational potential of findings derived from macaque models. Furthermore, insights into the epigenetic and proteomic characteristics of sperm in both species improve understanding of how these findings can help to advance clinical diagnostics, male contraception and fertility preservation and illuminate the regulatory omics of normal reproduction. Thus, the rhesus macaque model offers critical insights into male fertility and studies in this species could contribute to advances in therapies for male infertility. Non-human primates, especially the rhesus macaque, provide a good preclinical model for research into male fertility, owing to their physiological and genetic similarities to humans. In this article, the authors examine the value and limitations of using non-human primates in studies to improve understanding of spermatogenesis, reproductive endocrinology and innovations in assisted reproductive technologies.
男性生育能力是复杂的,受遗传、激素、环境和生活方式等因素的影响。然而,人类研究的局限性需要使用可靠的临床前模型来更好地了解男性生育能力的潜在机制。恒河猴(Macaca mulatta)具有与人类密切的遗传和生理相似性,为男性生殖健康研究提供了宝贵的模型。恒河猴在精子发生、激素周期和辅助生殖技术应用方面的相似性是研究雄性不育症的适宜性的基础,人类和恒河猴精子结构、功能和冷冻保存技术之间的关键差异和相似性突出了恒河猴模型研究结果的转化潜力。此外,对这两个物种精子的表观遗传学和蛋白质组学特征的深入了解,有助于了解这些发现如何有助于推进临床诊断、男性避孕和生育保护,并阐明正常生殖的调控组学。因此,恒河猴模型为男性生育能力提供了重要的见解,对该物种的研究可能有助于男性不育症治疗的进展。
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引用次数: 0
Molecular and therapeutic landscape of non-clear cell renal carcinoma 非透明细胞肾癌的分子和治疗前景。
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-04 DOI: 10.1038/s41585-025-01056-0
Prerna R. Nepali, Ahmed Eraky, Kennedy E. Okhawere, Navneet Dogra, Reza Mehrazin, Ketan Badani, Natasha Kyprianou
Non-clear cell renal cell carcinomas (nccRCC) include diverse subtypes such as papillary, oncocytic and chromophobe, collecting duct, molecularly defined and other rare histological subtypes, each associated with unique clinical, pathological, genetic and molecular features as well as therapeutic challenges. Surgical resection remains the primary approach for the treatment of localized nccRCC but optimal outcomes depend on tumour stage and the patient’s overall health. Clinically established treatment guidelines tailored for patients diagnosed with nccRCC are limited owing to the molecular and histological heterogeneity of nccRCC. Progress has been made in systemic therapy for metastatic disease but nccRCC treatment still poses challenges as patients experience variable treatment responses to immunotherapy, targeted therapies, chemotherapy and some combination strategies. Molecular biomarkers as well as established techniques, such as immunohistochemical and genetic analysis, have a crucial role in early detection, prognosis prediction and personalization of targeted therapies for nccRCC. The increasing identification of potential signatures and actionable molecular targets will aid in the clinical decision-making for patients diagnosed with these rare tumours towards optimization of the therapeutic response and treatment outcomes. This Review discusses the different subtypes of non-clear cell renal cell carcinoma in terms of molecular, genetic and clinicopathological characteristics as well as response to therapy. The authors highlight challenges associated with the rarity and heterogeneity of this subset of tumours and how investing in future research to find reliable biomarkers will be essential to improve patient outcomes.
非透明细胞肾细胞癌(nccRCC)包括多种亚型,如乳头状、嗜瘤细胞和嫌色细胞、集管、分子定义和其他罕见的组织学亚型,每种亚型都具有独特的临床、病理、遗传和分子特征以及治疗挑战。手术切除仍然是局部nccRCC治疗的主要方法,但最佳结果取决于肿瘤分期和患者的整体健康状况。由于nccRCC的分子和组织学异质性,为诊断为nccRCC的患者量身定制的临床建立的治疗指南受到限制。转移性疾病的全身治疗已经取得了进展,但由于患者对免疫治疗、靶向治疗、化疗和一些联合策略的治疗反应不一,nccRCC治疗仍然面临挑战。分子生物标志物以及现有的技术,如免疫组织化学和遗传分析,在nccRCC的早期发现、预后预测和个性化靶向治疗中起着至关重要的作用。越来越多的潜在特征和可操作的分子靶点的识别将有助于诊断患有这些罕见肿瘤的患者的临床决策,以优化治疗反应和治疗结果。
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引用次数: 0
Mapping the human prostate at the cellular level 在细胞水平上绘制人类前列腺图谱
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-02 DOI: 10.1038/s41585-025-01057-z
Olivier Cussenot
Use of spatial transcriptomics has helped to create a functional map of cellular organization in the healthy and tumoural human prostate, creating new opportunities for understanding age-related prostatic diseases.
空间转录组学的使用有助于创建健康和肿瘤人类前列腺细胞组织的功能图,为了解与年龄相关的前列腺疾病创造了新的机会。
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引用次数: 0
Promise without practice — charting the path forward for bladder cancer biomarkers 没有实践的承诺-绘制膀胱癌生物标志物的前进道路
IF 15.3 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-07-02 DOI: 10.1038/s41585-025-01064-0
Marie-Pier St-Laurent, Peter C. Black
Bladder cancer is a biologically heterogeneous disease, and ongoing efforts in biomarker research aim to support personalized treatment approaches. Circulating tumour DNA is approaching clinical integration through prospective trials, whereas other markers remain investigational owing to technical limitations, inconsistent findings and lack of validation. Rigorous biomarker-driven trials and cost-effectiveness studies are needed to enable the integration of molecular tools into routine practice. Biomarkers might ultimately lead to rational treatment de-escalation or escalation, improving outcomes while minimizing harm and cost.
膀胱癌是一种生物学异质性疾病,生物标志物研究的持续努力旨在支持个性化治疗方法。通过前瞻性试验,循环肿瘤DNA正在接近临床整合,而由于技术限制、不一致的发现和缺乏验证,其他标记仍处于研究阶段。需要严格的生物标志物驱动试验和成本效益研究,才能将分子工具整合到常规实践中。生物标志物可能最终导致合理的治疗降级或升级,改善结果,同时最大限度地减少伤害和成本。
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引用次数: 0
Why women are not treated equally in healthcare and what can be done 为什么妇女在医疗保健中得不到平等对待?可以做些什么
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-06-25 DOI: 10.1038/s41585-025-01063-1
Rajvinder Khasriya, Harry Horsley
Despite recognized sex-based differences in healthcare requirements, women continue to experience substantial disparities in treatment, diagnosis and research. This ‘gender health gap’ manifests through increased emergency wait times, dismissal of symptoms and inadequate research prioritization. Patient advocacy groups have emerged as powerful forces for change, successfully lobbying governments and raising awareness through social media. Addressing these disparities requires increased research funding, sex-specific study designs, improved medical education curricula and continued patient advocacy.
尽管在保健需求方面存在公认的性别差异,但妇女在治疗、诊断和研究方面仍然存在巨大差异。这种“性别健康差距”表现为急诊等待时间延长、症状被忽视和研究重点不充分。患者权益团体已成为推动变革的强大力量,它们成功地游说了政府,并通过社交媒体提高了人们的认识。要解决这些差异,就需要增加研究经费、设计针对性别的研究、改进医学教育课程并继续为患者宣传。
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引用次数: 0
Updated favourable-histology Wilms tumour risk stratification: rationale for future Children’s Oncology Group clinical trials 最新的有利组织学Wilms肿瘤风险分层:未来儿童肿瘤组临床试验的基本原理
IF 14.6 1区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-06-20 DOI: 10.1038/s41585-025-01055-1
Daniel J. Benedetti, Nicholas G. Cost, Peter F. Ehrlich, Nicholas Evageliou, Elizabeth Fialkowski, Lauren N. Parsons, Kelly L. Vallance, Lindsay A. Renfro, Andrew L. Hong, Jennifer H. Aldrink, Luke Pater, Arnold C. Paulino, Jesse K. Sandberg, Ethan A. Smith, Amy L. Treece, Jeffrey S. Dome, James I. Geller, Elizabeth A. Mullen
Patients with Wilms tumour have benefited from the results of decades of large collaborative clinical trials, leading to improved care. In the National Wilms Tumor Study Group and now Children’s Oncology Group (COG) trials, risk stratification evolved and expanded with each generation of studies and, therefore, ensuring that each patient receives the appropriate therapy has become increasingly complex. A new risk stratification system has been developed that forms the basis of the upcoming COG favourable-histology Wilms tumour (FHWT) study. Topics of diagnostic and prognostic uncertainty, such as the findings of tumour pulmonary emboli or extra-abdominal lymphadenopathy at diagnosis, will be integrated into the central review determination of staging of FHWT by committee consensus to facilitate clinical classification for therapeutic studies. Clear documentation of the elements of current risk stratification are of particular importance as refinement of the classification of patients with FHWT continues in an effort to optimize research, personalize treatment and provide an educational resource. In this Consensus Statement, the authors describe the details of the evolution of the risk-based treatment of favourable-histology Wilms tumour (FHWT) and outline the rationale for the new risk stratification that will be used in the now open Children’s Oncology Group therapeutic trial for FHWT, AREN2231.
Wilms肿瘤患者受益于数十年大型合作临床试验的结果,从而改善了护理。在国家Wilms肿瘤研究小组和现在的儿童肿瘤小组(COG)的试验中,风险分层随着每一代研究的发展和扩展,因此,确保每个患者接受适当的治疗变得越来越复杂。一种新的风险分层系统已经被开发出来,形成了即将到来的COG有利组织学Wilms肿瘤(FHWT)研究的基础。诊断和预后不确定的主题,如诊断时发现的肿瘤肺栓塞或腹外淋巴结病,将通过委员会共识纳入FHWT分期的中心审查确定,以促进临床治疗研究的分类。随着FHWT患者分类的不断细化,以优化研究、个性化治疗和提供教育资源,明确当前风险分层要素的文件尤为重要。
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引用次数: 0
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Nature Reviews Urology
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