Upconversion nanoparticle and gold nanocage satellite assemblies for sensitive ctDNA detection in serum

The Analyst ◽  
2020 ◽  
Vol 145 (16) ◽  
pp. 5553-5562
Author(s):  
Jiawei Wang ◽  
Guanping Hua ◽  
Lihuang Li ◽  
Danyang Li ◽  
Fanfan Wang ◽  
...  

A rapid molecular diagnostic technique targeting circulating tumor DNA (ctDNA) has become one of the most clinically significant liquid biopsy methods for non-invasive and timely diagnosis of cancer.

2020 ◽  
Vol 66 (4) ◽  
pp. 391-397
Author(s):  
T. Sokolova ◽  
T. Laidus ◽  
R. Meerovich ◽  
K. Zagorodnev ◽  
Aleksandr Martyanov ◽  
...  

«Liquid biopsy» is gradually becoming a mandatory procedure in cancer diagnostics. The aim of this procedure is to detect and monitor tumor-specific markers in various body fluids (blood, urine, pleural fluid, etc.). Significant efforts have been made to convert the most common mutational tests (EGFR, KRAS, BRAF) into non-invasive procedures. Despite some advantages, “liquid biopsy” is still not equivalent to traditional tissue analysis due to limited sensitivity and specificity; it cannot be routinely used in cancer medicine until the standardization of pre-analytical procedures is agreed. We intend to improve the performance of liquid biopsy for detection of a number of clinically relevant mutations (EGFR: ex19del and L858R; KRAS: 12, 13, 61, 146 codon nucleotide substitutions; BRAF: V600E). 417 plasma samples obtained from 88 patients (KRAS/NRAS/BRAF-mutated colorectal cancer (CRC): n= 57; EGFR-mutated lung adenocarcinomas (LC): n = 14; BRAF-mutated melanoma: n = 17) were analyzed by ddPCR for the presence of corresponding mutations in the circulating tumor DNA (ctDNA). Presence of tumor-specific mutations in plasma was confirmed in 32/57 (56%) CRC, 7/14 (50%) LC, and 4/17 (24%) melanoma cases. The proportion of mutation-positive plasma cases was tended to be higher in the group of patients with distant metastases compared to subjects with localized disease [34/56 (61%) vs. 5/15 (33%), р = 0.058]. 86 patients provided their blood at 9.00 (morning) and at 16.00 (afternoon). In addition, blood-takes were performed before and 15 minutes after usual breakfast as well as before and 15 minutes after moderate physical exercise. The detection rate of cancer-specific mutations in plasma was not significantly correlated with described above circumstances of blood-take. Meanwhile, the noticeable intrapatient variability of circulating mutation success rate has been detected. Thus, depending on clinical circumstances, at least negative ctDNA tests could be advised to be repeated in some patients, in order to ensure the reliability of results.


Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2198
Author(s):  
Saeko Sakaeda ◽  
Yoichi Naito

When somatic cells in the human body undergo apoptosis or necrosis, the released DNA enters the bloodstream. This type of DNA is called cell-free DNA (cfDNA). In patients with cancer, DNA released from tumor cells is called circulating tumor DNA (ctDNA), which carries genetic alterations specific to tumor cells. In recent years, ctDNA has attracted particular attention in terms of the concept of liquid biopsy in cancer care. Conventionally, tissue biopsy is required for the definitive diagnosis of cancer, and imaging examinations, such as CT, are performed for evaluating recurrence and residual lesions. Although the treatment burden on cancer patients is being slightly reduced due to advances in medicine, invasive examinations and medical exposure are still unavoidable. In addition, the prognosis of cancer varies considerably depending on the degree of progression at the time of detection. Therefore, the early detection of cancer is of utmost importance. With the increase in health consciousness, more people undergo regular health checkups, and it becomes necessary to diagnose cancer in a larger number of patients at an earlier stage. Although the accuracy of early detection has been improved by new imaging tests and examination techniques, each organ must be examined separately, and some organs are more difficult to examine than others in a regular health checkup. The process of cancer screening, diagnosis, and detection of recurrence after treatment is extensive. It can also be expensive, and some of the examinations may be invasive. If all of these processes can be replaced by the analysis of ctDNA in liquid biopsy, only a single blood sample is required. Under these circumstances, various studies are currently in progress on the use of ctDNA in clinical practice as an approach that may greatly reduce such burden. We present an overview of the current situation of ctDNA, as well as its future issues and prospects.


2018 ◽  
Vol 19 (10) ◽  
pp. 2877 ◽  
Author(s):  
José Marrugo-Ramírez ◽  
Mònica Mir ◽  
Josep Samitier

Cancer is one of the greatest threats facing our society, being the second leading cause of death globally. Currents strategies for cancer diagnosis consist of the extraction of a solid tissue from the affected area. This sample enables the study of specific biomarkers and the genetic nature of the tumor. However, the tissue extraction is risky and painful for the patient and in some cases is unavailable in inaccessible tumors. Moreover, a solid biopsy is expensive and time consuming and cannot be applied repeatedly. New alternatives that overcome these drawbacks are rising up nowadays, such as liquid biopsy. A liquid biopsy is the analysis of biomarkers in a non-solid biological tissue, mainly blood, which has remarkable advantages over the traditional method; it has no risk, it is non-invasive and painless, it does not require surgery and reduces cost and diagnosis time. The most studied cancer non-invasive biomarkers are circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. These circulating biomarkers play a key role in the understanding of metastasis and tumorigenesis, which could provide a better insight into the evolution of the tumor dynamics during treatment and disease progression. Improvements in isolation technologies, based on a higher grade of purification of CTCs, exosomes, and ctDNA, will provide a better characterization of biomarkers and give rise to a wide range of clinical applications, such as early detection of diseases, and the prediction of treatment responses due to the discovery of personalized tumor-related biomarkers.


Author(s):  
Pamela Pinzani ◽  
Valeria D’Argenio ◽  
Marzia Del Re ◽  
Cristina Pellegrini ◽  
Federico Cucchiara ◽  
...  

Abstract Despite advances in screening and therapeutics cancer continues to be one of the major causes of morbidity and mortality worldwide. The molecular profile of tumor is routinely assessed by surgical or bioptic samples, however, genotyping of tissue has inherent limitations: it represents a single snapshot in time and it is subjected to spatial selection bias owing to tumor heterogeneity. Liquid biopsy has emerged as a novel, non-invasive opportunity of detecting and monitoring cancer in several body fluids instead of tumor tissue. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), RNA (mRNA and microRNA), microvesicles, including exosomes and tumor “educated platelets” were recently identified as a source of genomic information in cancer patients which could reflect all subclones present in primary and metastatic lesions allowing sequential monitoring of disease evolution. In this review, we summarize the currently available information concerning liquid biopsy in breast cancer, colon cancer, lung cancer and melanoma. These promising issues still need to be standardized and harmonized across laboratories, before fully adopting liquid biopsy approaches into clinical practice.


2018 ◽  
Vol 2 (4) ◽  
pp. 117-128
Author(s):  
Antonio Marlos Duarte de Melo ◽  
Messias Silvano Da Silva Filho ◽  
Bárbara Torquato Alves ◽  
Kevellyn Cruz Aguilera ◽  
Ana Maria Correia Alencar ◽  
...  

Studies on the biology of cancer are multiplying and have been giving significant repercussions on the care of cancer patients, and there is a growing need to evaluate the biology of the tumor. Conventional tissue biopsies currently represent the gold standard in the diagnosis of cancer, but they are not suitable for serial analysis because of the need for invasive procedures, besides being able to present a high risk of life and also impossibility of reaching surgical in some tumors. To solve this obstacle, the use of the Liquid Biopsy, which analyzes the presence of biomarkers released by cancer cells, such as circulating tumor cells (CTCs), tumor cell DNA (ctDNA) and exosomes is being discussed. These techniques are non-invasive or minimally invasive and collect their samples from peripheral blood, plasma and serum, urine, saliva and cerebrospinal fluid (CSF). As they are already being used in the treatment of several histopathological types of cancer, these new techniques generally represent a revolution in the understanding of early diagnosis, choice of personalized treatment, follow-up of the treatment response in real time, detection of minimal residual disease and prognosis for malignant neoplasms. The objective of this study was to present a literature review to clarify the fundamental molecular and clinical aspects involved in this revolutionary diagnostic technique by extracting the data from the sample. Keywords: Liquid Biopsy. Oncology.: literature review


Author(s):  
Yan Li ◽  
Yuanyuan Zheng ◽  
Liwei Wu ◽  
Jingjing Li ◽  
Jie Ji ◽  
...  

AbstractThe conventional method used to obtain a tumor biopsy for hepatocellular carcinoma (HCC) is invasive and does not evaluate dynamic cancer progression or assess tumor heterogeneity. It is thus imperative to create a novel non-invasive diagnostic technique for improvement in cancer screening, diagnosis, treatment selection, response assessment, and predicting prognosis for HCC. Circulating tumor DNA (ctDNA) is a non-invasive liquid biopsy method that reveals cancer-specific genetic and epigenetic aberrations. Owing to the development of technology in next-generation sequencing and PCR-based assays, the detection and quantification of ctDNA have greatly improved. In this publication, we provide an overview of current technologies used to detect ctDNA, the ctDNA markers utilized, and recent advances regarding the multiple clinical applications in the field of precision medicine for HCC.


Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.


2021 ◽  
Vol 156 (0) ◽  
pp. 1-7
Author(s):  
Atsushi Imai ◽  
Kiyoshi Misawa ◽  
Satoshi Yamada ◽  
Jun Okamura ◽  
Daiki Mochizuki ◽  
...  

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