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Acoustic enrichment of heterogenous circulating tumor cells and clusters from patients with metastatic prostate cancer 来自转移性前列腺癌患者的异质循环肿瘤细胞和肿瘤簇的声富集
Pub Date : 2023-12-04 DOI: 10.1101/2023.12.04.23299128
Cecilia Magnusson, Per Augustsson, Eva Undvall Anand, Andreas Lenshof, Andreas Josefsson, Karin Welen, Anders Bjartell, Yvonne Ceder, Hans Lilja, Thomas Laurell
Background: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality. Methods: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility) resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry. Results: Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM+, Cytokeratin+, DAPI+, CD45-/CD66b-) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogenous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC-clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding higher number of CTCs using acoustophoresis. Conclusion: Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC-clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables sensitive label-free enrichment of cells with epithelial phenotype in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.
背景:开发细胞富集技术,使单细胞和循环肿瘤细胞簇(ctc)的无偏见无标记分离具有异质谱系特异性,这是重要的未满足的临床需求。在这里,我们报告了一项基于微流控声控富集CTC的试点研究,使用CellSearch CTC检测作为参考模式。方法:声波电泳利用超声驻波场根据生物力学特性(大小、密度和可压缩性)分离细胞,从而获得固有的无标记和独立于表位的细胞富集。对12例转移性前列腺癌患者和20例健康对照者的6 mL全血进行了红细胞溶解和多聚甲醛固定处理。结果:在所有转移性前列腺癌患者中,声波电泳能够富集和表征表型ctc (EpCAM+、Cytokeratin+、DAPI+、CD45-/CD66b-),并在12例患者中检测到9例仅由ctc组成的ctc簇或与各种类型白细胞聚集的ctc异质聚集体。相比之下,CellSearch没有检测到任何ctc簇,但检测到相当数量的表型ctc作为声阻抗,并且使用声阻抗发现更多数量的ctc的趋势。结论:我们的初步数据表明,声阻抗为检测和表征ctc簇提供了极好的可能性,ctc簇被认为是转移性疾病和预后的标志。此外,声阻抗可以对血液中具有上皮表型的细胞进行敏感的无标记富集,并为检测和表征正在经历上皮到间质转变和谱系可塑性的ctc提供了机会。
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引用次数: 0
A Spatial Comparison of Molecular Features Associated with Resistance to Pembrolizumab in BCG Unresponsive Bladder Cancer 卡介苗无应答性膀胱癌患者派姆单抗耐药相关分子特征的空间比较
Pub Date : 2023-11-30 DOI: 10.1101/2023.11.28.23299093
Khyati Meghani, Noah Frydenlund, Yanni Yu, Bonnie Choy, Joshua J. Meeks
Background Intravenous immune checkpoint inhibition achieves a 40% three-month response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). Yet only half of early responders will continue to be disease free by 12 months, and resistance mechanisms are poorly defined.
背景:静脉注射免疫检查点抑制对bcg无反应的非肌肉浸润性膀胱癌(NMIBC)合并原位癌(CIS)的三个月应答率为40%。然而,只有一半的早期应答者能在12个月内持续无病,而且耐药机制也不明确。
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引用次数: 0
Identifying patients with rapid progression from hormone-sensitive to castration-resistant prostate cancer: a retrospective study 鉴别从激素敏感到去势抵抗性前列腺癌快速进展的患者:一项回顾性研究
Pub Date : 2022-10-24 DOI: 10.1101/2022.10.23.22281406
Chenxi Pan, YI He, He Wang, Yang Yu, Lu Li, Lingling Huang, Mengge Lv, Weigang Ge, Bo Yang, Yaoting Sun, Tiannan Guo, Zhiyu Liu
Background: Prostate cancer (PCa) is the second most prevalent malignancy and the fifth cause of cancer-related deaths in men. A crucial challenge is identifying the population at risk of rapid progression from hormone-sensitive PCa (HSPC) to the lethal castration-resistant PCa (CRPC).Methods: We collected 78 HSPC biopsies and measured their proteomes using pressure cycling technology and a pulsed data-independent acquisition pipeline. The proteomics data and clinical metadata were used to generate models for classifying HSPC patients and predicting the development of each case.Results: We quantified 7,961 proteins using the HSPC biopsies. A total of 306 proteins were differentially expressed between patients with a long- or short-term progression to CRPC. Using a random forest model, we identified ten proteins that significantly discriminated long- from short-term cases, which were used to classify PCa patients with an 86% accuracy. Next, two clinical parameters (Gleason sum and total PSA) and five proteins (DPT, ARGEF1, UTP23, CMAS, and ANAPC4) were found to be significantly associated with rapid disease progression. A nomogram model using these seven features was generated for stratifying patients into groups with significant progression disparities.Conclusion: We identified proteins associated with a fast progression to CRPC and an unfavorable prognosis. Based on these proteins, our machine learning and nomogram models stratified HSPC into high- and low-risk groups and predict their prognoses. These tools may aid clinicians in predicting the progression of patients, guiding individualized clinical management and decisions.
背景:前列腺癌(PCa)是男性癌症相关死亡的第二大常见恶性肿瘤和第五大原因。一个关键的挑战是确定从激素敏感型前列腺癌(HSPC)快速发展为致命的去势抵抗型前列腺癌(CRPC)的风险人群。方法:我们收集了78例HSPC活检,并使用压力循环技术和脉冲数据独立采集管道测量其蛋白质组。蛋白质组学数据和临床元数据用于生成HSPC患者分类模型并预测每个病例的发展。结果:通过HSPC活检,我们定量了7961个蛋白。在长期或短期进展为CRPC的患者中,共有306种蛋白存在差异表达。使用随机森林模型,我们确定了10种显著区分长期和短期病例的蛋白质,用于对PCa患者进行分类,准确率为86%。接下来,两个临床参数(Gleason sum和total PSA)和五个蛋白(DPT, ARGEF1, UTP23, CMAS和ANAPC4)被发现与疾病的快速进展显著相关。使用这七个特征生成了一个nomogram模型,将患者按显著的进展差异进行分组。结论:我们发现了与CRPC快速进展和不良预后相关的蛋白。基于这些蛋白质,我们的机器学习和nomogram模型将HSPC分为高风险和低风险组,并预测其预后。这些工具可以帮助临床医生预测患者的进展,指导个性化的临床管理和决策。
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引用次数: 0
Ultrasound versus fluoroscopy as imaging guidance for percutaneous nephrolithotomy: A systematic review and meta-analysis 超声与透视作为经皮肾镜取石术的影像学指导:一项系统回顾和荟萃分析
Pub Date : 2022-10-13 DOI: 10.1101/2022.10.13.22281046
Razman Arabzadeh Bahri, Saba Maleki, Arman Shafiee, Parnian Shobeiri
Objectives: To determine whether the outcomes of ultrasound-guided percutaneous nephrolithotomy (UG-PCNL), an alternative to traditional fluoroscopy-guided percutaneous nephrolithotomy (FG-PCNL), are comparable.Methods: A systematic search of PubMed, Embase, and the Cochrane Library was carried out to discover investigations comparing UG-PCNL to FG-PCNL, and accordingly, a meta-analysis of those studies was performed. The primary outcomes included the stone-free rate (SFR), overall complications based on Clavien-Dindo classification, duration of surgery, duration of patients’ hospitalization, and hemoglobin (Hb) drop during the surgery. All statistical analyses and visualizations were implemented utilizing R software.Results: Nineteen studies, including eight randomized clinical trials (RCTs) and eleven observational cohorts, comprising 3016 patients (1521 UG-PCNL patients) and comparing UG-PCNL with FG-PCNL met the inclusion criteria of the current study. Considering SFR, overall complications, duration of surgery, duration of hospitalization, and Hb drop, our meta-analysis revealed no statistically significant difference between UG-PCNL and FG-PCNL patients, with p-values of 0.29, 0.47, 0.98, 0.28, and 0.42, respectively. Significant differences were discovered between UG-PCNL and FG-PCNL patients in terms of the length of time they were exposed to radiation (p-value< 0.0001). Moreover, FG-PCNL had shorter access time than UG-PCNL (p-value= 0.04).Conclusion: UG-PCNL provides the advantage of requiring less radiation exposure while being just as efficient as FG-PCNL; thus, this study suggests prioritizing the use of UG-PCNL.
目的:探讨超声引导下经皮肾镜取石术(UG-PCNL)与传统透视引导下经皮肾镜取石术(FG-PCNL)的疗效是否具有可比性。方法:系统检索PubMed、Embase和Cochrane图书馆,发现UG-PCNL与FG-PCNL的比较研究,并对这些研究进行荟萃分析。主要结局包括无结石率(SFR)、基于Clavien-Dindo分类的总并发症、手术时间、患者住院时间和手术期间血红蛋白(Hb)下降。所有统计分析和可视化均使用R软件实现。结果:19项研究,包括8项随机临床试验(RCTs)和11项观察性队列,共计3016例患者(1521例UG-PCNL患者),UG-PCNL与FG-PCNL的比较符合本研究的纳入标准。综合考虑SFR、总并发症、手术时间、住院时间、Hb下降等因素,我们的meta分析显示UG-PCNL与FG-PCNL患者的差异无统计学意义,p值分别为0.29、0.47、0.98、0.28、0.42。UG-PCNL和FG-PCNL患者在辐射暴露时间方面存在显著差异(p值<0.0001)。FG-PCNL的访问时间较UG-PCNL短(p值= 0.04)。结论:UG-PCNL具有与FG-PCNL相同的低辐射照射的优点;因此,本研究建议优先使用UG-PCNL。
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引用次数: 0
Impact of COVID-19 on the management and outcomes of ureteric stones in the UK: a multicentre retrospective study COVID-19对英国输尿管结石治疗和结局的影响:一项多中心回顾性研究
Pub Date : 2022-06-28 DOI: 10.1101/2022.06.27.22276955
Matthew H V Byrne, Fanourios Georgiades, Alexander Light, Catherine E Lovegrove, Catherine Dominic, Josephine Rahman, Senthooran Kathiravelupillai, Tobias Klatte, Kasra Saeb-Parsy, Rajeev Kumar, Sarah Howles, Grant D Stewart, Ben Turney, Oliver Wiseman, the COVID Stones Collaborative
Objectives To determine if management of ureteric stones in the United Kingdom changed during the COVID-19 pandemic and whether this affected patient outcomes.
目的确定2019冠状病毒病大流行期间英国输尿管结石的管理是否发生了变化,以及这是否影响了患者的预后。
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引用次数: 0
The expression of cancer stem cells and its effects on the propensity for recurrence and metastasis in bladder cancer: a systematic review 肿瘤干细胞的表达及其对膀胱癌复发和转移倾向的影响:系统综述
Pub Date : 2022-05-19 DOI: 10.1101/2022.05.18.22275252
Agus Rizal Ardy Hariandy Hamid, Yasmina Zahra Syadza, Oliver Emmanuel Yausep, Roberto Bagaskara Indy Christanto, Bayu Hernawan Rahmat Muharia, Chaidir Arif Mochtar
Bladder cancer is one of the most frequent cancers of the urinary tract, associated with high recurrence rates and metastasis. Cancer stem cells (CSCs) are a subpopulation of cancer cells characterized by high self-renewal and differentiation capacities, resulting in increased cancer recurrence, larger tumor size, higher rates of metastasis, higher resistance to treatment, and overall poorer prognosis. This study aimed to evaluate the role of CSCs as a prognostic tool to predict the risks of metastasis and recurrence in bladder cancer. A literature search was conducted across seven databases from January 2000 to February 2022 for clinical studies investigating the use of CSCs to determine the prognosis of bladder cancer. The following keywords were used: (“Bladder Cancer” OR “Transitional Cell Carcinoma” OR “Urothelial Carcinoma”) AND (“Stem Cell” OR “Stem Gene”) AND (“Metastasis” OR “Recurrence”). A total of 12 studies were deemed eligible for inclusion. SOX2, IGF1R, SOX4, ALDH1, CD44, Cripto-1, OCT4, ARRB1, ARRB2, p-TFCP2L1, CDK1, DCLK1, and NANOG, which were all identified as CSC markers, have been implicated in the recurrence and metastasis of tumor in bladder cancer, which played a role as prognostic factor of bladder cancer. Given the pluripotent and highly proliferative properties of CSCs. CSCs may play a role in the complex biological behavior of bladder cancer, including, but not limited to, its high rates of recurrence, metastasis, and resistance to treatment. The detection of cancer stem cell markers offers a promising approach in determining the prognosis of bladder cancer. Further studies in this area are thus warranted and may contribute significantly to the overall management of bladder cancer.Cancer stem cells; Bladder cancer; Recurrency of bladder cancer; Metastasis of bladder cancer; Prognosis factor of bladder cancer
膀胱癌是泌尿道最常见的癌症之一,具有较高的复发率和转移率。癌症干细胞(Cancer stem cells, CSCs)是一种具有高度自我更新和分化能力的癌细胞亚群,其特点是癌症复发率高,肿瘤体积大,转移率高,对治疗的抵抗力高,总体预后较差。本研究旨在评估CSCs作为预测膀胱癌转移和复发风险的预后工具的作用。从2000年1月到2022年2月,对七个数据库进行了文献检索,以调查使用CSCs确定膀胱癌预后的临床研究。使用以下关键词:(膀胱癌)或(移行细胞癌)或(尿路上皮癌)和(干细胞或干细胞基因)和(转移或复发)。共有12项研究被认为符合纳入条件。SOX2、IGF1R、SOX4、ALDH1、CD44、Cripto-1、OCT4、ARRB1、ARRB2、p-TFCP2L1、CDK1、DCLK1、NANOG等均被鉴定为CSC标志物,参与膀胱癌肿瘤的复发和转移,是膀胱癌的预后因素。鉴于干细胞的多能性和高增殖性。CSCs可能在膀胱癌的复杂生物学行为中发挥作用,包括但不限于其高复发、转移率和对治疗的耐药性。肿瘤干细胞标志物的检测为膀胱癌的预后判断提供了一种很有前景的方法。因此,这一领域的进一步研究是有必要的,并可能对膀胱癌的整体治疗做出重大贡献。癌症干细胞;膀胱癌;膀胱癌复发;膀胱癌的转移;膀胱癌的预后因素
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引用次数: 0
Intraoperative calculus or hemorrhage in transurethral seminal vesiculoscopy as a risk factor for recurrent hemospermia 经尿道精囊镜术中结石或出血是复发性血精症的危险因素
Pub Date : 2022-04-29 DOI: 10.1101/2022.04.28.22274431
Cheng-En Mei, Ju-Chuan Hu, Jian-Ri Li, Kun-Yuan Chiu, Shian-Shiang Wang, Chuan-Shu Chen
We summarized our experience regarding Transurethral Seminal Vesiculoscopy (TUSV) and analyzed both recurrence status and risk factors for recurrence. From January 2010 to December 2020, 48 patients with intractable hemospermia received successful TUSV at Taichung Invalids General Hospital. For the intraoperative findings, the five-year Disease-free Survival rates (DFS) were 74.1% in the no calculus group compared to 37.1% in the calculus group with a significant difference (log-rank p = 0.015), 75.0% in the no hemorrhage or no blood clot group compared to 43.2% in the hemorrhage or blood clot group with significant difference (log-rank p = 0.032). Univariate analysis showed intraoperative calculus (p = 0.040; HR: 2.94, 95% CI: 1.05–8.21) to be significantly associated with recurrence (p < 0.05). Patients with intractable hemospermia who were diagnosed with stones or blood clots found during TUSV experienced a higher rate of hemospermia recurrence.
我们总结了经尿道精囊镜检查(TUSV)的经验,并分析了复发情况和复发的危险因素。2010年1月至2020年12月,在台中荣民总医院对48例顽固性血精患者进行了成功的TUSV治疗。术中发现,无结石组5年无病生存率(DFS)为74.1%,结石组为37.1%,差异有统计学意义(log-rank p = 0.015);无出血或无血栓组为75.0%,出血或有血栓组为43.2%,差异有统计学意义(log-rank p = 0.032)。单因素分析显示术中结石(p = 0.040;HR: 2.94, 95% CI: 1.05-8.21)与复发显著相关(p <0.05)。顽固性血精症患者在TUSV期间被诊断为结石或血凝块,其血精症复发率较高。
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引用次数: 0
Glucose and lipid profiles in men with non-obstructive azoospermia 非阻塞性无精子症患者的葡萄糖和脂质谱
Pub Date : 2022-03-15 DOI: 10.1101/2022.03.14.22272336
Ponco Birowo, Dimas Tri Prasetyo, Dwi Ari Pujianto, Widi Atmoko, Nur Rasyid
The impact of a low testosterone level among men with non-obstructive azoospermia with various testicular histopathological patterns on the regulation of glucose and lipid metabolism is less well known than among the general population. The aim of this retrospective study was to examine the association between testicular histopathology and components of the metabolic profile among men with non-obstructive azoospermia. Participants were divided into two groups: men with non-obstructive azoospermia and men with obstructive azoospermia. Testicular biopsies were performed among those with non-obstructive azoospermia. We included 115 patients in this study: 83 (72.2%) had non-obstructive azoospermia and 32 (27.8%) had obstructive azoospermia. The plasma glucose concentration, glycated hemoglobin level, and lipid profile were similar between patients with non-obstructive azoospermia and those with obstructive azoospermia. Upon subgroup analysis of patients with non-obstructive azoospermia, those with Sertoli-cell-only syndrome had the lowest testosterone (431 ± 238 ng/dL; P=0.039) and highest follicle-stimulating hormone (23.4 ± 18.2 mIU/mL; P=0.002) concentrations. They also had the highest triglyceride concentration (163 ± 114 mg/dL; P=0.001). Interestingly, patients with Sertoli-cell-only syndrome had a lower fasting plasma glucose concentration (92 ± 11 mg/dL; P<0.001) and glycated hemoglobin level (5.9 ± 0.8%; P=0.022) than those with histopathological patterns of maturation arrest and hypospermatogenesis. In conclusion, differences in glucose and lipid metabolism are evident between men with non-obstructive azoospermia with different spermatogenesis patterns.
与普通人群相比,具有不同睾丸组织病理学模式的非阻塞性无精子症患者睾酮水平低对糖脂代谢调节的影响尚不清楚。本回顾性研究的目的是检查非阻塞性无精子症男性睾丸组织病理学和代谢谱组成部分之间的关系。参与者被分为两组:非阻塞性无精子症男性和阻塞性无精子症男性。非梗阻性无精子症患者行睾丸活检。本研究纳入115例患者:83例(72.2%)为非阻塞性无精子症,32例(27.8%)为阻塞性无精子症。非梗阻性无精子症患者的血糖浓度、糖化血红蛋白水平和血脂水平与梗阻性无精子症患者相似。在非阻塞性无精子症患者亚组分析中,仅支持细胞综合征患者睾酮水平最低(431±238 ng/dL;P=0.039),促卵泡激素最高为23.4±18.2 mIU/mL;P = 0.002)浓度。他们的甘油三酯浓度也最高(163±114 mg/dL;P = 0.001)。有趣的是,仅支持细胞综合征患者的空腹血糖浓度较低(92±11 mg/dL;P<0.001)和糖化血红蛋白水平(5.9±0.8%;P=0.022)比成熟阻滞和低精子发生的组织病理学模式的患者多。综上所述,不同精子发生方式的非阻塞性无精子症患者的糖脂代谢存在明显差异。
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引用次数: 0
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medRxiv - Urology
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