• 文章类型: Journal Article
    前列腺癌是男性中最常见和最致命的疾病之一,且其早期诊断可对治疗过程产生重大影响,预防死亡。由于它在早期没有明显的临床症状,很难诊断。此外,专家在分析磁共振图像方面的分歧也是一个重大挑战。近年来,各种研究表明,深度学习,尤其是卷积神经网络,已经成功地出现在机器视觉中(特别是在医学图像分析中)。在这项研究中,在多参数磁共振图像上使用了一种深度学习方法,研究了临床和病理数据对模型准确性的协同作用。数据是从德黑兰的Trita医院收集的,其中包括343例患者(在该过程中使用了数据增强和学习迁移方法).在设计的模型中,使用四个独立的ResNet50深度卷积网络分析了四种不同类型的图像,并将其提取的特征转移到完全连接的神经网络,并与临床和病理特征相结合。在没有临床和病理数据的模型中,最高准确率达到88%,但是通过添加这些数据,准确度提高到96%,临床和病理资料对诊断的准确性有显著影响。
    Prostate cancer is one of the most common and fatal diseases among men, and its early diagnosis can have a significant impact on the treatment process and prevent mortality. Since it does not have apparent clinical symptoms in the early stages, it is difficult to diagnose. In addition, the disagreement of experts in the analysis of magnetic resonance images is also a significant challenge. In recent years, various research has shown that deep learning, especially convolutional neural networks, has appeared successfully in machine vision (especially in medical image analysis). In this research, a deep learning approach was used on multi-parameter magnetic resonance images, and the synergistic effect of clinical and pathological data on the accuracy of the model was investigated. The data were collected from Trita Hospital in Tehran, which included 343 patients (data augmentation and learning transfer methods were used during the process). In the designed model, four different types of images are analyzed with four separate ResNet50 deep convolutional networks, and their extracted features are transferred to a fully connected neural network and combined with clinical and pathological features. In the model without clinical and pathological data, the maximum accuracy reached 88%, but by adding these data, the accuracy increased to 96%, which shows the significant impact of clinical and pathological data on the accuracy of diagnosis.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    前列腺磁共振成像(MRI)是诊断前列腺癌(PCa)的基石,提供卓越的检测能力,同时最大限度地减少不必要的活检。尽管发挥了关键作用,MRI诊断性能的全球差异仍然存在,源于图像质量和放射科医师专业知识的变化。这篇手稿回顾了提高前列腺MRI图像质量的挑战和策略。跨越患者准备,MRI单元优化,和放射科团队的参与。质量保证(QA)和质量控制(QC)过程至关重要,强调标准化协议,细致的耐心评估,MRI单元工作流程,和放射科团队的表现。此外,人工智能(AI)的进步为提高图像质量和减少采集时间提供了有希望的途径。前列腺成像质量(PI-QUAL)评分系统成为评估MRI图像质量的有价值的工具。解决技术问题的全面方法,程序,和解释性方面对于确保一致和可靠的前列腺MRI结果至关重要.
    Prostate magnetic resonance imaging (MRI) stands as the cornerstone in diagnosing prostate cancer (PCa), offering superior detection capabilities while minimizing unnecessary biopsies. Despite its critical role, global disparities in MRI diagnostic performance persist, stemming from variations in image quality and radiologist expertise. This manuscript reviews the challenges and strategies for enhancing image quality in prostate MRI, spanning patient preparation, MRI unit optimization, and radiology team engagement. Quality assurance (QA) and quality control (QC) processes are pivotal, emphasizing standardized protocols, meticulous patient evaluation, MRI unit workflow, and radiology team performance. Additionally, artificial intelligence (AI) advancements offer promising avenues for improving image quality and reducing acquisition times. The Prostate-Imaging Quality (PI-QUAL) scoring system emerges as a valuable tool for assessing MRI image quality. A comprehensive approach addressing technical, procedural, and interpretative aspects is essential to ensure consistent and reliable prostate MRI outcomes.
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  • 文章类型: Journal Article
    目标:尽管有越来越多的证据表明双侧盆腔放疗(全骨盆RT,WPRT)几乎没有单侧RT(半骨盆RT,前列腺切除术后淋巴结复发前列腺癌患者的HPRT)。然而,在临床实践中,与WPRT相比,有时使用HPRT旨在减少副作用。前列腺特异性膜抗原正电子发射断层扫描/计算机断层扫描(PSMA-PET/CT)是目前这种临床情况下最好的成像方式。该分析比较了基于PSMA-PET/CT的WPRT和HPRT。
    方法:在多机构回顾性数据集中,对273例因淋巴结复发而接受盆腔RT治疗的患者进行了倾向评分匹配(214WPRT,59HPRT)。总的来说,最终分析包括102例患者(每组51例)。生化无复发生存率(BRFS)定义为前列腺特异性抗原(PSA)结果:中位随访时间为29个月。在倾向匹配之后,两组大多平衡。然而,在WPRT组中,仍有显著更多的患者在前列腺切除术后有额外的局部复发和生化持久性.两组的BRFS无显著差异(p=0.97),MFS(p=.43)和NRFS(p=.43)。两年后,BRFS,MFS和NRFS分别为61%,在WPRT组中分别为86%和88%和57%,HPRT组中的90%和82%,分别。加强淋巴结转移的应用,在单因素和多因素分析中,较高的淋巴途径RT剂量(>50GyEQD2α/β=1.5Gy)和伴随的雄激素剥夺治疗(ADT)与较长的BRFS显著相关.
    结论:总体而言,这项分析显示了HPRT在淋巴结复发前列腺癌患者中的结局,并表明与WPRT相比,HPRT可导致相似的肿瘤学结局.然而,WPRT患者的进展风险可能较高,因为组间存在一些持续性的失衡.因此,进一步的研究应前瞻性评估哪些患者亚组适合HPRT治疗,以及HPRT是否导致临床毒性显著降低.
    OBJECTIVE: Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT.
    METHODS: A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test.
    RESULTS: Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/β=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis.
    CONCLUSIONS: Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.
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  • 文章类型: Journal Article
    目的:肿瘤灌注是癌症代谢率与营养无关的生物标志物。复杂的图像采集限制了肿瘤灌注在癌症生长评估中的使用。图像分析和有限的视场扫描仪。使用[15O]H2O进行长轴向视场(LAFOV)PET扫描,允许定量评估全身肿瘤灌注。我们创建了一种用于在转移性癌症中自动创建定量参数化全身肿瘤灌注图像的工具。
    方法:10例转移性前列腺癌患者接受了动态LAFOV[15O]H2OPET(Siemens,Quadra),然后是[18F]PSMA-1007PET。使用单组织区室模型和自动捕获的心脏图像衍生的输入函数,将灌注测量为[15O]H2OK1(mL/min/mL)。参数灌注图像是使用具有初始体素延迟估计和前沿方法的基函数方法自动计算的。随后,可以直接从参数图像中提取感兴趣体积(VOI)的灌注。我们使用[18F]PSMA-1007SUV4固定阈值进行肿瘤描绘,并将这些VOI转移到灌注图中。
    结果:对于8个原发性肿瘤,64个淋巴结转移,85个骨转移,中位肿瘤灌注为0.19(0.15-0.27)mL/min/mL,0.16(0.13-0.27)mL/min/mL,和0.26(0.21-0.39),分别。根据时间-活动曲线计算的灌注与参数图像之间的相关性非常好(r=0.99,p<0.0001)。
    结论:使用[15O]H2O的LAFOVPET成像能够实现全身肿瘤灌注的真正定量参数图像,指导个性化治疗和监测治疗反应的潜在生物标志物。
    OBJECTIVE: Tumour perfusion is a nutrient-agnostic biomarker for cancer metabolic rate. Use of tumour perfusion for cancer growth assessment has been limited by complicated image acquisition, image analysis and limited field-of-view scanners. Long axial field-of-view (LAFOV) PET scan using [15O]H2O, allows quantitative assessment of whole-body tumour perfusion. We created a tool for automated creation of quantitative parametric whole-body tumour perfusion images in metastatic cancer.
    METHODS: Ten metastatic prostate cancer patients underwent dynamic LAFOV [15O]H2O PET (Siemens, Quadra) followed by [18F]PSMA-1007 PET. Perfusion was measured as [15O]H2O K1 (mL/min/mL) with a single-tissue compartment model and an automatically captured cardiac image-derived input function. Parametric perfusion images were automatically calculated using the basis-function method with initial voxel-wise delay estimation and a leading-edge approach. Subsequently, perfusion of volumes-of-interest (VOI) can be directly extracted from the parametric images. We used a [18F]PSMA-1007 SUV 4 fixed threshold for tumour delineation and transferred these VOIs to the perfusion map.
    RESULTS: For 8 primary tumours, 64 lymph node metastases, and 85 bone metastases, median tumour perfusion were 0.19 (0.15-0.27) mL/min/mL, 0.16 (0.13-0.27) mL/min/mL, and 0.26 (0.21-0.39), respectively. The correlation between calculated perfusion from time-activity-curves and parametric images was excellent (r = 0.99, p < 0.0001).
    CONCLUSIONS: LAFOV PET imaging using [15O]H2O enables truly quantitative parametric images of whole-body tumour perfusion, a potential biomarker for guiding personalized treatment and monitoring treatment response.
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  • 文章类型: Journal Article
    背景:通过筛选和教育(CHANGE)计划的癌症健康意识提供了癌症意识教育,重点是可改变的危险因素和导航到前列腺筛查,乳房,和结肠直肠癌对公共住房社区的居民来说,他们经历了显著的负面健康社会决定因素。
    方法:五个社区的居民参与。招募社区顾问委员会成员,并向当地环境变化项目提供反馈,招募,以及每个站点的社区参与。在每个站点,由训练有素的主持人提供了四次关于癌症风险因素和病因的教育课程,种族差异,癌症筛查的资格,参与临床试验。出席,知识,对癌症的态度和信念,和高度,体重,在基线和更改后1周测量腰围.
    结果:90名居民(60%65岁及以上,33%男性,60%高中教育,93%AA)参加了该计划。95%完成干预后评估。参与者有资格获得乳房(n=12),前列腺(n=15),和结肠直肠筛查(n=25)基于美国癌症协会指南,和22个戒烟;21个参与者接受了这些服务的导航援助。在测试后,参与者对肥胖/超重癌症风险的知识和行为显着增加,营养,和身体活动。结肠直肠,前列腺,乳腺癌知识得分也有所提高,但并不重要。
    结论:CHANGE参与者表现出改善的健康知识和改善其可改变的健康行为的意图。参与者报告说,他们对寻求预防性护理和对社区参与工作的满意度有积极性和信心。在类似社区中复制该项目可能会改善服务不足人群的知识和健康公平性。
    BACKGROUND: The Cancer Health Awareness through screeNinG and Education (CHANGE) initiative delivers cancer awareness education with an emphasis on modifiable risk factors and navigation to screening for prostate, breast, and colorectal cancers to residents of public housing communities who experience significant negative social determinants of health.
    METHODS: Residents of five communities participated. Community advisory board members were recruited and provided feedback to local environmental change projects, recruitment, and community engagement at each site. At each site, four education sessions were provided by trained facilitators on cancer risk factors and etiology, racial disparities, eligibility for cancer screening, and participation in clinical trials. Attendance, knowledge, attitudes and beliefs about cancer, and height, weight, and waist circumference were measured at baseline and 1-week post-CHANGE sessions.
    RESULTS: 90 residents (60% 65 and older years old, 33% male, 60% High School education, 93% AA) participated in the program. 95% completed post-intervention evaluation. Participants were eligible for breast (n = 12), prostate (n = 15), and colorectal screening (n = 25) based on American Cancer Society guidelines, and 22 for tobacco cessation; 21 participants accepted navigation assistance for these services. At post-test, participants significantly increased in knowledge and behaviors around obesity/overweight risk for cancer, nutrition, and physical activity. Colorectal, prostate, and breast cancer knowledge scores also increased, but were not significant.
    CONCLUSIONS: CHANGE participants demonstrated improved health knowledge and intentions to improve their modifiable health behaviors. Participants reported being motivated and confident in seeking preventive care and satisfaction with community engagement efforts. Replication of this project in similar communities may improve knowledge and health equity among underserved populations.
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  • 文章类型: Journal Article
    转录因子(TFs)是通过与基因上游的特定核苷酸序列结合来调节基因表达的必需蛋白质。在TF家族中,叉头盒(FOX)蛋白质,以保守的DNA结合结构域为特征,在各种细胞过程中发挥重要作用,包括癌症.FOXA亚科,FOXA1,FOXA2和FOXA3因其在哺乳动物发育中的关键作用而脱颖而出。最初在肝脏中发现的FOXA1,在多个器官组织中表现出不同的表达,并在细胞增殖中起关键作用,分化,和肿瘤的发展。它的结构组成包括反式激活域和DNA结合域,促进其作为先驱因素的功能,这对于染色质相互作用和招募其他转录调节因子至关重要。FOXA1在性激素相关肿瘤中的参与强调了其在癌症生物学中的重要性。这篇综述概述了FOXA1在正常发育中的多方面作用及其在激素相关癌症发病机理中的意义。尤其是乳腺癌和前列腺癌。
    Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the forkhead box (FOX) proteins, characterized by a conserved DNA-binding domain, play vital roles in various cellular processes, including cancer. The FOXA subfamily, encompassing FOXA1, FOXA2, and FOXA3, stands out for its pivotal role in mammalian development. FOXA1, initially identified in the liver, exhibits diverse expression across multiple organ tissues and plays a critical role in cell proliferation, differentiation, and tumor development. Its structural composition includes transactivation domains and a DNA-binding domain, facilitating its function as a pioneer factor, which is crucial for chromatin interaction and the recruitment of other transcriptional regulators. The involvement of FOXA1 in sex hormone-related tumors underscores its significance in cancer biology. This review provides an overview of multifaceted roles of FOXA1 in normal development and its implications in the pathogenesis of hormone-related cancers, particularly breast cancer and prostate cancer.
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  • 文章类型: Journal Article
    推进嵌合抗原受体(CAR)工程化T细胞用于治疗实体瘤是细胞免疫疗法领域的主要焦点。几个障碍阻碍了实体肿瘤中类似的CART细胞临床反应,如血液恶性肿瘤中所见。这些挑战包括靶点外肿瘤毒性,这激发了优化CAR以改善肿瘤抗原选择性和整体安全性的努力。我们最近开发了针对前列腺癌和胰腺癌的针对前列腺干细胞抗原(PSCA)的CART细胞疗法,通过优化细胞内共刺激结构域,显示出改善的临床前抗肿瘤活性和T细胞持久性。进行了类似的研究以优化HER2定向的CART细胞,并对细胞内共刺激结构域进行修饰,以选择性靶向乳腺癌脑转移。在本研究中,我们评估了这些CAR中的各种非信号细胞外间隔区,以进一步提高肿瘤抗原选择性.我们的发现表明,细胞外间隔区的长度和结构可以决定CAR选择性靶向具有高抗原密度的肿瘤细胞的能力。同时保留低抗原密度的细胞。这项研究有助于CAR构建体设计考虑因素,并扩展了我们调整实体肿瘤CART细胞疗法以提高安全性和有效性的知识。
    Advancing chimeric antigen receptor (CAR)-engineered T cells for the treatment of solid tumors is a major focus in the field of cellular immunotherapy. Several hurdles have hindered similar CAR T cell clinical responses in solid tumors as seen in hematological malignancies. These challenges include on-target off-tumor toxicities, which have inspired efforts to optimize CARs for improved tumor antigen selectivity and overall safety. We recently developed a CAR T cell therapy targeting prostate stem cell antigen (PSCA) for prostate and pancreatic cancers, showing improved preclinical antitumor activity and T cell persistence by optimizing the intracellular co-stimulatory domain. Similar studies were undertaken to optimize HER2-directed CAR T cells with modifications to the intracellular co-stimulatory domain for selective targeting of breast cancer brain metastasis. In the present study, we evaluate various nonsignaling extracellular spacers in these CARs to further improve tumor antigen selectivity. Our findings suggest that length and structure of the extracellular spacer can dictate the ability of CARs to selectively target tumor cells with high antigen density, while sparing cells with low antigen density. This study contributes to CAR construct design considerations and expands our knowledge of tuning solid tumor CAR T cell therapies for improved safety and efficacy.
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  • 文章类型: Journal Article
    尿细胞外囊泡(uEV)富含糖基化蛋白,已被广泛研究为泌尿系癌症的推定生物标志物。这里,我们表征了源自泌尿系癌细胞系的EV的糖基化和整合素谱。我们使用涂覆有凝集素和抗体的荧光铕掺杂纳米颗粒来鉴定由整联蛋白亚基α3(ITGA3)和岩藻糖组成的生物标志物组合。此外,我们使用相同的癌细胞系来源的EV作为分析标准来评估ITGA3-UEA测定的灵敏度.ITGA3-UEA分析的临床表现使用各种泌尿系统病理的尿样分析,包括诊断挑战性良性前列腺增生(BPH),前列腺癌(PCa)和膀胱癌(BlCa)。该测定法可以显着区分所有其他患者组的BlCa:PCa(9.2倍;p=0.00038),BPH(5.5倍;p=0.004)和健康个体(和23倍;p=0.0001)。我们的结果表明,在简单的生物亲和测定法中,可以用岩藻糖特异性凝集素UEA检测异常岩藻糖基化的uEV和整联蛋白ITGA3,以直接从未加工的尿液中检测BlCa。
    Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium-doped nanoparticles coated with lectins and antibodies to identify a biomarker combination consisting of integrin subunit alpha 3 (ITGA3) and fucose. In addition, we used the same cancer cell line-derived EVs as analytical standards to assess the sensitivity of the ITGA3-UEA assay. The clinical performance of the ITGA3-UEA assay was analysed using urine samples of various urological pathologies including diagnostically challenging benign prostatic hyperplasia (BPH), prostate cancer (PCa) and bladder cancer (BlCa). The assay can significantly discriminate BlCa from all other patient groups: PCa (9.2-fold; p = 0.00038), BPH (5.5-fold; p = 0.004) and healthy individuals (and 23-fold; p = 0.0001). Our results demonstrate that aberrantly fucosylated uEVs and integrin ITGA3 can be detected with fucose-specific lectin UEA in a simple bioaffinity assay for the detection of BlCa directly from unprocessed urine.
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  • 文章类型: Journal Article
    细胞外囊泡(EV)是参与癌症转移的局部和远程信号传导的细胞间通讯的重要介质。侵袭的开始是转移级联的关键步骤,但由于技术挑战,电动汽车的分泌在那个阶段仍未被探索。在这项研究中,我们提供了一个平台,利用基于体内模拟细胞外基质的3D培养物,在人前列腺癌细胞(PC3)肿瘤的侵袭性发展过程中追踪EV.使用这种电动汽车生产方法,结合蛋白质组学分析,我们显示PC3类肿瘤分泌具有先前未定义的蛋白质货物的EV。有趣的是,在肿瘤的侵入性转变后,检测到EV量的增加和EV蛋白组成的广泛变化。通过化学抑制侵袭来抵消EV蛋白货物的变化。这些结果揭示了肿瘤的侵袭性状态对EV分泌和货物的影响,并强调了体内模拟条件以发现新型癌症衍生的EV成分的必要性。
    Extracellular vesicles (EVs) are important mediators of intercellular communication involved in local and long-range signalling of cancer metastasis. The onset of invasion is the key step of the metastatic cascade, but the secretion of EVs has remained unexplored at that stage due to technical challenges. In this study, we present a platform to track EVs over the course of invasive development of human prostate cancer cell (PC3) tumoroids utilizing in vivo-mimicking extracellular matrix-based 3D cultures. Using this EV production method, combined with proteomic profiling, we show that PC3 tumoroids secrete EVs with previously undefined protein cargo. Intriguingly, an increase in EV amounts and extensive changes in the EV protein composition were detected upon invasive transition of the tumoroids. The changes in EV protein cargo were counteracted by chemical inhibition of invasion. These results reveal the impact of the tumoroids\' invasive status on EV secretion and cargo, and highlight the necessity of in vivo-mimicking conditions for uncovering novel cancer-derived EV components.
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