The Journal of Liquid Biopsy最新文献

英文中文

Liquid biopsy for evaluating mutations and chromosomal aberrations in cerebrospinal fluid from patients with primary or metastatic CNS tumors

The Journal of Liquid Biopsy

Pub Date : 2024-12-01 DOI: 10.1016/j.jlb.2024.100281

Ahmad Charifa , Sally Agersborg , Arash Mohtashamian , Andrew Ip , Andre Goy , Maher Albitar

Background

Cytopathology analysis of cerebrospinal fluid (CSF) is limited in detecting tumors in patients with suspected primary or metastatic central nervous system (CNS) malignancy. We investigated the use of CSF liquid biopsy (LBx) to detect neoplastic processes in the CNS.

Methods

Cell-free DNA (cfDNA) from the CSF of patients with suspected metastatic (N = 106) or primary CNS (N = 23) tumors was deep sequenced using a 302-gene panel.

Results

Four samples (3 %) (3 metastatic and 1 primary) failed sequencing quality control criteria. Metastatic tumor was confirmed in 84 (82 %) of the 103 patients suspected of metastatic tumor. Primary CNS tumor was confirmed in 11 of 22 (50 %) patients suspected of CNS tumor. Chromosomal abnormalities were detected in 55 samples (54 %). Germline mutations were detected in 23 (22 %) patients with metastatic tumors and in 1 (5 %) with a primary CNS tumor. Of the 29 patients with metastatic breast cancers, 2 (7 %) had mutations in ESR1 and 9 (31 %) had mutations in PIK3CA. Of the 21 patients with metastatic lung cancer, 9 (43 %) had EGFR mutations and 5 (24 %) had KRAS mutations. Upon comparing CSF LBx with peripheral blood LBx in 14 patients, 13 (93 %) showed only CHIP and one patient showed CNS primary tumor mutation. Serial samples from 14 patients demonstrate that CSF LBx can be used for monitoring therapy efficacy.

Conclusions

LBx using CSF is clinically reliable and provides informative results in a substantial proportion of patients with metastatic CNS tumors and to a lesser degree in patients with primary CNS tumors.

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引用次数: 0

Global requirements for manufacturing and validation of clinical grade extracellular vesicles

The Journal of Liquid Biopsy

Pub Date : 2024-12-01 DOI: 10.1016/j.jlb.2024.100278

Abhimanyu Thakur , Deepika Rai

Extracellular vesicles (EVs) are nanovesicles released from different cell types from biofluids such as blood, urine, and cerebrospinal fluid. They vary in size and biomarkers, and their biogenesis pathways allow them to be divided into three major types: exosomes, micro-vesicles, and apoptotic bodies. EVs have been studied in the context of diagnosis and therapeutic intervention of various pathological conditions such as cancer, neurodegenerative diseases, and pulmonary diseases. However, the production of EV-based therapeutics can be affected by the source, heterogeneity, or disease, raising questions about the manufacturing and validation of EVs of clinical grade and their scope regarding good manufacturing practice (GMP) in the industry. To address this, we have discussed the state-of-the-art requirements for EV production that must occur in a GMP-compliant environment with a reliable and traceable source. Additionally, EVs' homogeneity and the therapeutics' purity and stability must be analyzed and validated. Quality control measures must also be established to ensure the safety and efficacy of EVs. In conclusion, these considerations must be weighed carefully when manufacturing and validating EVs of clinical grade to ensure their safety and efficacy for therapeutic use.

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引用次数: 0

Liquid biopsy in gallbladder carcinoma: Current evidence and future prospective 胆囊癌液体活检：当前证据与未来展望

The Journal of Liquid Biopsy

Pub Date : 2024-11-21 DOI: 10.1016/j.jlb.2024.100280

Sridhar Mishra , Swati Kumari , Nuzhat Husain

Although there have been significant advances in the early detection and treatment of gallbladder cancer (GBC), it is still considered a leading cause of morbidity and mortality. Molecular profiling of tumors is generally performed using samples obtained during surgery or biopsy. However, tissue genotyping has its limitations as it only provides a single snapshot and is susceptible to spatial selection bias due to the tumor heterogeneity. Over the past decade, there has been a remarkable transition from invasive diagnostic methods to non-invasive alternatives, including liquid biopsy, for cancer diagnosis and monitoring. Liquid biopsies have ushered in a new era in clinical oncology, enabling convenient tumor sampling, continuous monitoring through repeated analysis, development of personalized treatment regimens, and assessment of therapy resistance. While peripheral blood is the primary medium for these biopsies, other biological fluids, including urine, saliva, and bile, also serve as valuable sources of information. Currently, the focus of blood-based biopsy analyses is on four main sources of biomarkers for cancer detection and stratification: circulating tumor DNA (ctDNA) or circulating free DNA (cfDNA), circulating tumor cells (CTCs), and extracellular vesicle (EVs). There are over 300 clinical trials either ongoing or actively recruiting participants to investigate the diagnostic and prognostic applications of ctDNA/cfDNA in the context of cancer. This review outlines the current standard of care for individuals with GBC, anticipates future treatment developments, and evaluates the potential applications of liquid biopsies in various clinical contexts. The review addresses ctDNA/cfDNA, CTC, and circulating microRNA and highlights their prospective roles in management of GBC.

尽管在胆囊癌（GBC）的早期检测和治疗方面取得了重大进展，但胆囊癌仍被认为是发病和死亡的主要原因。肿瘤的分子图谱分析通常使用手术或活检获得的样本。然而，组织基因分型有其局限性，因为它只能提供单一的快照，而且由于肿瘤的异质性，容易出现空间选择偏差。在过去十年中，癌症诊断和监测已从侵入性诊断方法显著过渡到非侵入性替代方法，包括液体活检。液体活检开创了临床肿瘤学的新纪元，实现了便捷的肿瘤采样、通过重复分析进行连续监测、开发个性化治疗方案以及评估耐药性。虽然外周血是这些活检的主要介质，但包括尿液、唾液和胆汁在内的其他生物液体也是有价值的信息来源。目前，血液活检分析的重点是用于癌症检测和分层的四大生物标记物来源：循环肿瘤 DNA（ctDNA）或循环游离 DNA（cfDNA）、循环肿瘤细胞（CTC）和细胞外囊泡（EVs）。目前有 300 多项临床试验正在进行或积极招募参与者，以研究 ctDNA/cfDNA 在癌症诊断和预后方面的应用。本综述概述了 GBC 患者目前的治疗标准，预测了未来的治疗发展，并评估了液体活检在各种临床环境中的潜在应用。综述探讨了ctDNA/cfDNA、CTC和循环microRNA，并强调了它们在GBC治疗中的潜在作用。

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引用次数: 0

Ultrasound mediated blood-brain barrier opening increases brain tumor biomarkers: A review of preclinical and clinical trials 超声波介导的血脑屏障开放可增加脑肿瘤生物标志物：临床前和临床试验综述

The Journal of Liquid Biopsy

Pub Date : 2024-11-17 DOI: 10.1016/j.jlb.2024.100277

Muhammad Izhar , Abhimanyu Thakur , David J. Park , Steven D. Chang

The diagnosis of brain tumors typically relies on magnetic resonance imaging (MRI), computed tomography (CT), and invasive procedures like biopsies or surgical resection for confirmation and genetic profiling. However, these methods have limitations, especially in distinguishing treatment effects like pseudo-progression from actual tumor progression, and repeated biopsies pose risks. Liquid biopsy (LB) offers a non-invasive alternative, detecting tumor-derived biomarkers in blood and cerebrospinal fluid (CSF). Despite its potential, the low concentration of brain tumor biomarkers in blood due to the blood-brain barrier (BBB), limits the clinical utility of LB. MRI-guided focused ultrasound (MRgFUS) combined with microbubbles provides a novel solution by temporarily disrupting the BBB, facilitating the passage of therapeutic agents, and enabling tumor biomarker detection. This technique, termed “sonobiopsy,” enables non-invasive biomarker collection for liquid biopsy, potentially improving brain tumor diagnosis and monitoring.

脑肿瘤的诊断通常依赖于磁共振成像（MRI）、计算机断层扫描（CT）以及活检或手术切除等侵入性程序进行确认和基因分析。然而，这些方法都有局限性，尤其是在区分假性进展和实际肿瘤进展等治疗效果方面，而且重复活检会带来风险。液体活检（LB）提供了一种无创替代方法，可检测血液和脑脊液（CSF）中的肿瘤生物标记物。尽管液体活检具有潜力，但由于血脑屏障（BBB）的影响，血液中脑肿瘤生物标记物的浓度较低，这限制了液体活检的临床应用。核磁共振成像引导下的聚焦超声（MRgFUS）与微气泡的结合提供了一种新的解决方案，它能暂时破坏血脑屏障，促进治疗药物的通过，并实现肿瘤生物标记物的检测。这种被称为 "声波活检 "的技术可为液体活检收集无创生物标记物，从而改善脑肿瘤的诊断和监测。

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引用次数: 0

Circulating adenoid cystic carcinoma associated MYB transcripts enable rapid and sensitive detection of metastatic disease in blood liquid biopsies 循环性腺样囊性癌相关 MYB 转录物可快速灵敏地检测血液液体活检中的转移性疾病

The Journal of Liquid Biopsy

Pub Date : 2024-11-15 DOI: 10.1016/j.jlb.2024.100276

Acadia H.M. Moeyersoms , Kendall W. Knechtel , Andrew J. Rong , Ryan A. Gallo , Michelle Zhang , Harper M. Marsh , Zoukaa B. Sargi , Jason M. Leibowitz , Francisco J. Civantos , Donald T. Weed , Sander R. Dubovy , David T. Tse , Daniel Pelaez

Adenoid cystic carcinoma (ACC) is a rare and lethal malignancy that originates in secretory glands of the head and neck. A prominent molecular feature of ACC is the overexpression of the proto-oncogene MYB. ACC has a poor long-term survival due to its high propensity for recurrence and protracted metastasis. Currently, clinical technologies lack the efficiency to distinguish patient prognosis prior to its redevelopment. We hypothesize that metastatic ACC can be detected by monitoring tumor-specific MYB expression in patients’ blood. We developed a quantitative polymerase chain reaction (qPCR) assay for MYB transcripts and screened blood samples from four patient cohorts: no history or evidence of ACC (n = 23), past history of ACC and no evidence of disease (NED) for greater than three years (n = 15), local ACC (n = 6), and metastatic ACC (n = 5). Our assay detected significantly elevated levels of MYB transcripts in the metastatic ACC cohort (p < 0.01). Receiver operating characteristic (ROC) curves comparing metastatic to NED and metastatic to local disease were significant, with p values < 0.0001 and 0.0008, respectively. Single-cell RNA sequencing (scRNA-seq) of blood from metastatic ACC identified a cluster of circulating tumor cells (CTCs) expressing MYB. Here, we report a sensitive, cost-effective, and minimally invasive diagnostic test that leverages tumor-specific signatures to screen for metastatic ACC disease, potentially enhancing detection earlier than the current clinical standard.

腺样囊性癌（ACC）是一种罕见的致命恶性肿瘤，起源于头颈部的分泌腺。腺样囊性癌的一个显著分子特征是原癌基因 MYB 的过度表达。ACC 复发率高、转移时间长，长期生存率低。目前，临床技术缺乏在再发展之前区分患者预后的效率。我们假设可以通过监测患者血液中肿瘤特异性 MYB 的表达来检测转移性 ACC。我们开发了一种针对 MYB 转录物的定量聚合酶链反应 (qPCR) 检测方法，并筛查了四组患者的血液样本：无 ACC 病史或证据（n = 23）、既往有 ACC 病史且三年以上无疾病证据（NED）（n = 15）、局部 ACC（n = 6）和转移性 ACC（n = 5）。我们的检测方法在转移性 ACC 群体中检测到了明显升高的 MYB 转录物水平（p < 0.01）。比较转移性与NED和转移性与局部疾病的接收者操作特征（ROC）曲线显示，P值分别为0.0001和0.0008。对转移性 ACC 患者的血液进行单细胞 RNA 测序（scRNA-seq）发现了一组表达 MYB 的循环肿瘤细胞（CTCs）。在这里，我们报告了一种灵敏、经济、微创的诊断测试，它利用肿瘤特异性特征来筛查转移性 ACC 疾病，有可能比目前的临床标准更早地发现疾病。

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引用次数: 0

Cancer-associated macrophage-like cells as a prognostic biomarker in solid tumors 作为实体瘤预后生物标志物的癌症相关巨噬细胞样细胞

The Journal of Liquid Biopsy

Pub Date : 2024-11-14 DOI: 10.1016/j.jlb.2024.100275

Anthony Pirrello , Murray Killingsworth , Kevin Spring , John E.J. Rasko , Dannel Yeo

Cancer-associated macrophage-like cells (CAMLs) are myeloid-lineage cells associated with cancer-derived material that are detectable in the blood. In addition to circulating tumor cells, CAMLs are a promising liquid biopsy biomarker which may assist with prognostication for patient stratification and monitoring response to chemotherapy and radiotherapy in solid tumors. CAMLs have been detected in blood samples from patients with various tumors including lung, pancreas, breast, oesophageal, and colorectal cancers, and to date have not been detected in healthy individuals. However, the optimal method of detection, their origin, function in the circulation, and ultimate utility have not been fully elucidated. This review provides an overview of CAML-related studies and explores their future potential to guide clinical decision-making.

癌症相关巨噬细胞样细胞（CAMLs）是血液中可检测到的与癌症衍生物质相关的髓系细胞。除了循环肿瘤细胞外，CAMLs 还是一种很有前景的液体生物标记物，可帮助预后分层，监测实体瘤患者对化疗和放疗的反应。在肺癌、胰腺癌、乳腺癌、食道癌和结直肠癌等各种肿瘤患者的血液样本中都检测到了 CAMLs，但迄今为止尚未在健康人体内检测到 CAMLs。然而，最佳的检测方法、其来源、在血液循环中的功能以及最终用途尚未完全阐明。本综述概述了与 CAML 相关的研究，并探讨了其未来指导临床决策的潜力。

引用次数: 0

ESR1 CTDNA testing in HR+/HER2 metastatic breast cancer: A real-world perspective from a referral laboratory HR+/HER2 转移性乳腺癌的 ESR1 CTDNA 检测：来自转诊实验室的真实视角

The Journal of Liquid Biopsy

Pub Date : 2024-11-01 DOI: 10.1016/j.jlb.2024.100229

Dr. Konstantinos Venetis , Dr. Dario Trapani , Mr. Riccardo Adorisio , Dr. Alberto Ranghiero , Dr. Grazia Castellano , Mrs. Virginia Peruzzo , Dr. Davide Vacirca , Giuseppe Curigliano (Prof.) , Nicola Fusco (Prof.) , Elena Guerini Rocco (Prof.)

引用次数: 0

Automated analysis pipeline for HER2 expression profiling in CTCS: Computational potential for advancing personalized therapy for metastatic breast cancer CTCS 中 HER2 表达谱的自动分析管道：推进转移性乳腺癌个性化治疗的计算潜力

The Journal of Liquid Biopsy

Pub Date : 2024-11-01 DOI: 10.1016/j.jlb.2024.100264

Ms Sarah Henretta , Dr. Nadia Bayou , Dr. Laura Munoz-Arcos , Elisabetta Molteni , Dr. Mara Serena Serafini , Amanda Strickland , Dr. Caterina Gianni , Dr. Eleonora Nicolo , Dr. Massimo Cristofanilli , Dr. Carolina Reduzzi

引用次数: 0

Genomic-epigenomic CTDNA testing in metastatic breast cancer patients with no evidence of disease: Potential clinical utility from real-world data 对无疾病证据的转移性乳腺癌患者进行基因组-表观基因组 CTDNA 检测：来自真实世界数据的潜在临床实用性

The Journal of Liquid Biopsy

Pub Date : 2024-11-01 DOI: 10.1016/j.jlb.2024.100216

Dr. Caterina Gianni , Dr. Letizia Pontolillo , Dr. Eleonora Nicolo' , Dr. Laura S. Munoz-Arcos , Dr. Mara Serena Serafini , Lorenzo Gerratana (Prof.) , Eleni Andreopoulou (Prof.) , Ugo De Giorgi (Prof.) , Carolina Reduzzi (Asst.Prof.) , Massimo Cristofanilli (Prof.)

引用次数: 0

Liquid biopsy detection of gene Copy Number (CN) losses including existing and emerging clinical targets 通过液体活检检测基因拷贝数 (CN) 缺失，包括现有和新出现的临床目标

The Journal of Liquid Biopsy

Pub Date : 2024-11-01 DOI: 10.1016/j.jlb.2024.100221

Dr. Christian Rolfo , Jessica Lee , Dr. Lincoln Pasquina , Dr. Amaya Gasco , Dr. Alexa Schrock , Dr. Natasha Leighl

引用次数: 0

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数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

The Journal of Liquid Biopsy

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