Abstract 1380: Clinical relevance of cell-free DNA analysis for bile juice assessed through amplicon-based deep sequencing in bile duct and pancreatic cancer patients with obstructive jaundice

Author(s):  
Marie Muramatsu ◽  
Marie Muramatsu ◽  
Hiromichi Ito ◽  
Hitoshi Zembutsu
2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23026-e23026
Author(s):  
Bo Song ◽  
Ling Fung Paul Tang ◽  
Grace Q. Zhao ◽  
Shengrong Lin ◽  
Kang Ying ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Filippo Martignano ◽  
Uday Munagala ◽  
Stefania Crucitta ◽  
Alessandra Mingrino ◽  
Roberto Semeraro ◽  
...  

AbstractIn the “precision oncology” era the characterization of tumor genetic features is a pivotal step in cancer patients’ management. Liquid biopsy approaches, such as analysis of cell-free DNA from plasma, represent a powerful and noninvasive strategy to obtain information about the genomic status of the tumor. Sequencing-based analyses of cell-free DNA, currently performed with second generation sequencers, are extremely powerful but poorly scalable and not always accessible also due to instrumentation costs. Third generation sequencing platforms, such as Nanopore sequencers, aim at overcoming these obstacles but, unfortunately, are not designed for cell-free DNA analysis.Here we present a customized workflow to exploit low-coverage Nanopore sequencing for the detection of copy number variations from plasma of cancer patients. Whole genome molecular karyotypes of 6 lung cancer patients and 4 healthy subjects were successfully produced with as few as 2 million reads, and common lung-related copy number alterations were readily detected.This is the first successful use of Nanopore sequencing for copy number profiling from plasma DNA. In this context, Nanopore represents a reliable alternative to Illumina sequencing, with the advantages of minute instrumentation costs and extremely short analysis time.The availability of protocols for Nanopore-based cell-free DNA analysis will make this analysis finally accessible, exploiting the full potential of liquid biopsy both for research and clinical purposes.


Author(s):  
M. Cisneros-Villanueva ◽  
L. Hidalgo-Pérez ◽  
M. Rios-Romero ◽  
A. Cedro-Tanda ◽  
C. A. Ruiz-Villavicencio ◽  
...  

AbstractCell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms ‘cfDNA’, ‘ctDNA’, ‘liquid biopsy’ AND ‘cancer OR neoplasm’ in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.


2020 ◽  
Author(s):  
Filippo Martignano ◽  
Stefania Crucitta ◽  
Alessandra Mingrino ◽  
Roberto Semeraro ◽  
Marzia Del Re ◽  
...  

ABSTRACTAlterations in the genetic content, such as Copy Number Variations (CNVs) is one of the hallmarks of cancer and their detection is used to recognize tumoral DNA. Analysis of cell-free DNA from plasma is a powerful tool for non-invasive disease monitoring in cancer patients. Here we exploit third generation sequencing (Nanopore) to obtain a CNVs profile of tumoral DNA from plasma, where cancer-related chromosomal alterations are readily identifiable.Compared to Illumina sequencing -the only available alternative- Nanopore sequencing represents a viable approach to characterize the molecular phenotype, both for its ease of use, costs and rapid turnaround (6 hours).


Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 182-186 ◽  
Author(s):  
Yohei Hisada ◽  
Nigel Mackman

Abstract Cancer patients have an increased risk of venous thromboembolism (VTE). The rate of VTE varies with cancer type, with pancreatic cancer having one of the highest rates, suggesting that there are cancer type–specific mechanisms of VTE. Risk assessment scores, such as the Khorana score, have been developed to identify ambulatory cancer patients at high risk of VTE. However, the Khorana score performed poorly in discriminating pancreatic cancer patients at risk of VTE. Currently, thromboprophylaxis is not recommended for cancer outpatients. Recent clinical trials showed that factor Xa (FXa) inhibitors reduced VTE in high-risk cancer patients but also increased major bleeding. Understanding the mechanisms of cancer-associated thrombosis should lead to the development of safer antithrombotic drugs. Mouse models can be used to study the role of different prothrombotic pathways in cancer-associated thrombosis. Human and mouse studies support the notion that 2 prothrombotic pathways contribute to VTE in pancreatic cancer patients: tumor-derived, tissue factor–positive (TF+) extracellular vesicles (EVs), and neutrophils and neutrophil extracellular traps (NETs). In pancreatic cancer patients, elevated levels of plasma EVTF activity and citrullinated histone H3 (H3Cit), a NET biomarker, are independently associated with VTE. We observed increased levels of circulating tumor-derived TF+ EVs, neutrophils, cell-free DNA, and H3Cit in nude mice bearing human pancreatic tumors. Importantly, inhibition of tumor-derived human TF, depletion of neutrophils, or administration of DNAse I to degrade cell-free DNA (including NETs) reduced venous thrombosis in tumor-bearing mice. These studies demonstrate that tumor-derived TF+ EVs, neutrophils, and cell-free DNA contribute to venous thrombosis in a mouse model of pancreatic cancer.


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