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Annette R Kodahl, Sidse Ehmsen, Niels Pallisgaard, Anne Marie B Jylling, Jeanette Dupont Jensen, Anne-Vibeke Laenkholm, Ann S Knoop, Henrik J Ditzel
Liquid biopsies focusing on the analysis of circulating cell-free tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin-fixed, paraffin-embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly-sensitive, optimized droplet digital PCR (ddPCR) assay...
April 24, 2018: Molecular Oncology
Yi Jiang, Denong Wang
Liquid biopsy uses noninvasive blood test to assess tumor heterogeneity and evolution in real time. It looks for tumor components in the blood circulation, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), to provide tumor-specific information. By detecting multiplex tumor biomarkers, including nucleic acids, proteins, carbohydrates, and other tumor-derived substances, liquid biopsy helps with early tumor diagnosis, tumor evolution monitoring, and prognosis prediction. With the development of high-throughput OMICS tools like carbohydrate microarray and high-speed fiber-optic array scanning technology (FAST scan), it is now practical to identify glycan markers of CTCs and cancer stem cells (CSCs), especially those that are cell-surface exposed and readily accessible for immune recognition and targeting...
2018: Open access journal of biomedical engineering and its applications
Chi-Ju Kim, Juhee Park, Vijaya Sunkara, Tae-Hyeong Kim, Yongjin Lee, Kyusang Lee, Mi-Hyun Kim, Yoon-Kyoung Cho
The potential utility of circulating tumour DNA (ctDNA) in patient blood for cancer diagnostics and real-time monitoring of disease progression is highly recognized. However, the lack of automated and efficient methods for cell-free DNA (cfDNA) isolation from peripheral blood has remained a challenge for broader acceptance of liquid biopsy in general clinical settings. Here, we demonstrate a lab-on-a-disc system equipped with newly developed, electromagnetically actuated, and reversible diaphragm valves that allows fully automated and rapid (<30 min) isolation of cfDNA from whole blood (>3 ml) to achieve high detection sensitivity by minimizing the degradation of fragile ctDNA as well as contamination of wild-type DNA from abundant blood cells...
April 16, 2018: Lab on a Chip
Álvaro Taus, Laura Camacho, Pedro Rocha, Max Hardy-Werbin, Lara Pijuan, Gabriel Piquer, Eva López, Alba Dalmases, Raquel Longarón, Sergi Clavé, Marta Salido, Joan Albanell, Beatriz Bellosillo, Edurne Arriola
BACKGROUND: The assessment of epidermal growth factor receptor (EGFR) mutations is crucial for the management of patients with lung adenocarcinoma. Circulating tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity. PATIENTS AND METHODS: Consecutive patients diagnosed with EGFR-mutant lung adenocarcinoma in tumor biopsy were included in this study. Plasma samples were obtained at different time points during the course of the disease...
March 23, 2018: Clinical Lung Cancer
Everett J Moding, Maximilian Diehn, Heather A Wakelee
Circulating tumor DNA (ctDNA) shed from cancer cells into the peripheral blood can be non-invasively collected and tested for the presence of tumor-specific mutations. Mutations identified in ctDNA can predict responses to targeted therapies and emerging evidence suggests that changes in ctDNA levels over time can be used to monitor response to therapy and detect disease recurrence. Given the emergence of targeted therapies in advanced non-small cell lung cancer (NSCLC), liquid biopsies utilizing ctDNA testing represent a powerful approach to genotype tumors and monitor for the development of resistance...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression...
April 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Emilie Moati, Valérie Taly, Audrey Didelot, Géraldine Perkins, Hélène Blons, Julien Taieb, Pierre Laurent-Puig, Aziz Zaanan
Colorectal cancer is a major health burden with a prognosis that has been improved with the progresses in diagnosis and the advance of chemotherapy and personalized medicine. However, because of intra-tumor heterogeneity, clonal evolution and selection, tumors often develop resistance to treatments. "Liquid biopsy" is a minimally invasive method, based on analysis of tumor-specific material in peripheral blood samples of patients. Analysis of tumor specific genetic or epigenetic alterations in cell-free circulating nucleic acids may reflect the molecular heterogeneity of the underlying disease process and serial testing could allow to monitor its temporal genomic changing without using re-biopsy...
April 4, 2018: Clinics and Research in Hepatology and Gastroenterology
Caitlin M Stewart, Dana W Y Tsui
Cell-free DNA (cfDNA) was first identified in human plasma in 1948 and is thought to be released from cells throughout the body into the circulatory system. In cancer, a portion of the cfDNA originates from tumour cells, referred to as circulating-tumour DNA (ctDNA), and can contain mutations corresponding to the patient's tumour, for instance specific TP53 alleles. Profiling of cfDNA has recently become an area of increasing clinical relevance in oncology, in particular due to advances in the sensitivity of molecular biology techniques and development of next generation sequencing technologies, as this allows tumour mutations to be identified and tracked non-invasively...
March 11, 2018: Cancer Genetics
E Arriola, A Paredes-Lario, R García-Gomez, P Diz-Tain, M Constenla, C García-Girón, G Márquez, M Reck, G López-Vivanco
PURPOSE: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. METHODS: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing...
April 5, 2018: Clinical & Translational Oncology
Shuangshuang Zhang, Hongqin Yang, Ludan Zhao, Ruixue Gan, Peixiao Tang, Qiaomei Sun, Xinnuo Xiong, Hui Li
The interaction mechanism and binding mode of capecitabine with ctDNA was extensively investigated using docking and molecular dynamics (MD) simulations, fluorescence and circular dichroism (CD) spectroscopy, DNA thermal denaturation studies, and viscosity measurements. The possible binding mode and acting forces on the combination between capecitabine and DNA had been predicted through molecular simulation. Results indicated that capecitabine could relatively locate stably in the G-C base-pairs-rich DNA minor groove by hydrogen bond and several weaker nonbonding forces...
April 5, 2018: Journal of Biomolecular Structure & Dynamics
Chenguang Li, Hailin Liu, Bin Zhang, Liqun Gong, Yanjun Su, Zhenfa Zhang, Changli Wang
PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma harboring EGFR-activating mutations will inevitably acquire resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). EGFR T790M mutation and cMET amplification are common mechanisms. Further study is needed to explore unknown genomic alterations contributing to drug resistance. METHODS: Tumor and blood samples from 69 stage IIIB-IV NSCLC patients defined as acquired resistance to first-generation EGFR TKIs (gefitinib, erlotinib or ecotinib) were collected...
April 3, 2018: Journal of Cancer Research and Clinical Oncology
Francisco Martínez-Ricarte, Regina Mayor, Elena Martínez-Sáez, Carlota Rubio-Pérez, Estela Pineda, Esteban Cordero, Marta Cicuéndez, Maria A Poca, Nuria Lopez-Bigas, Santiago Ramón Y Cajal, María Vieito, Joan Carles, Josep Tabernero, Ana Vivancos, Soledad Gallego, Francesc Graus, Juan Sahuquillo, Joan Seoane
PURPOSE: Diffuse gliomas are the most common primary tumour of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumour specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumour DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies...
April 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Camila Tavares Uchôa Guimarães, Nina Nayara Ferreira Martins, Kelly Cristina da Silva Oliveira, Caroline Martins Almeida, Thayanne Macedo Pinheiro, Carolina Oliveira Gigek, Sandro Roberto de Araújo Cavallero, Paulo Pimentel Assumpção, Marília Arruda Cardoso Smith, Rommel Rodríguez Burbano, Danielle Queiroz Calcagno
Liquid biopsies have great promise for precision medicine as they provide information about primary and metastatic tumors via a minimally invasive method. In gastric cancer patients, a large number of blood-based biomarkers have been reported for their potential role in clinical practice for screening, early diagnosis, prognostic evaluation, recurrence monitoring and therapeutic efficiency follow-up. This current review focuses on blood liquid biopsies' role and their clinical implications in gastric cancer patients, with an emphasis on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and circulating non-coding RNAs (ncRNAs)...
March 13, 2018: Oncotarget
Justin M Burgener, Ariana Rostami, Daniel D De Carvalho, Scott V Bratman
Circulating tumor DNA (ctDNA) consists of cell-free DNA (cfDNA) fragments that are released from tumor cells into the bloodstream. ctDNA harbors cancer-specific genetic and epigenetic alterations that allow its detection and quantification using a variety of emerging techniques. The promise of convenient non-invasive access to the complex and dynamic molecular features of cancer through peripheral blood has galvanized translational researchers around this topic with compelling routes to clinical implementation, particularly in the post-treatment surveillance setting...
October 2017: Seminars in Oncology
Hideaki Kinugasa, Kazuhiro Nouso, Soichiro Ako, Chihiro Dohi, Hiroshi Matsushita, Kazuyuki Matsumoto, Hironari Kato, Hiroyuki Okada
INTRODUCTION: Tissue sampling of gallbladder cancer (GBCa) is challenging because of the anatomy of the gallbladder. The aim of this study is to investigate the possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in addition to current diagnostic methods. METHODS: Thirty patients with GBCa were enrolled in this study. Cytological examination was performed in all patients. Using next generation sequencing (NGS), DNA isolated from the bile and tumor tissue was analyzed for mutations in 49 oncogenes...
March 26, 2018: Cancer Biology & Therapy
Subramani Karthikeyan, Ganesan Bharanidharan, Rajendiran Mangaiyarkarasi, Shanmugavel Chinnathambi, Ragavan Sriram, Krishnaswamy Gunasekaran, Kandasamy Saravanan, Mani Gopikrishnan, Prakasarao Aruna, Singaravelu Ganesan
In this study the interaction mechanism between newly synthesized 4-(3-acetyl-5-(acetylamino)-2-methyl-2, 3-dihydro-1,3,4-thiadiazole-2-yl) phenyl benzoate (thiadiazole derivative) anticancer active drug with calf thymus DNA was investigated by using various optical spectroscopy techniques along with computational technique. The absorption spectrum shows a clear shift in the lower wavelength region, which may be due to strong hypochromic effect in the ctDNA and the drug. The results of steady state fluorescence spectroscopy show that there is static quenching occurring while increasing the thiadiazole drug concentration in the ethidium bromide-ctDNA system...
March 26, 2018: Luminescence: the Journal of Biological and Chemical Luminescence
Theodore Gourdin, Guru Sonpavde
Prostate cancer is characterized by bone metastases and difficulty of objectively measuring disease burden. In this context, cell-free circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) quantitation and genomic profiling afford the ability to noninvasively and serially monitor the tumor. Recent data suggest that ctDNA and CTC quantitation are prognostic for survival. Indeed, CTC enumeration using the CellSearch® platform is validated as a prognostic factor and warrants consideration as a stratification factor in randomized trials...
March 20, 2018: Asian Journal of Andrology
Krzysztof Z Łączkowski, Joanna Anusiak, Marta Świtalska, Katarzyna Dzitko, Joanna Cytarska, Angelika Baranowska-Łączkowska, Tomasz Plech, Agata Paneth, Joanna Wietrzyk, Joanna Białczyk
Synthesis, characterization, and investigation of antiproliferative activities against human cancer cell lines (MV4-11, MCF-7, and A549) and Toxoplasma gondii parasite of twelve novel 2,4-diaminotriazine-thiazoles are presented. The toxicity of the compounds was studied at three different cell types, normal mouse fibroblast (Balb/3T3), mouse fibroblast (L929), and human VERO cells. The structures of novel compounds were determined using1 H and13 C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 4a - k showed very high activity against MV4-11 cell line with IC50 values between 1...
2018: Medicinal Chemistry Research
Jelena Belic, Ricarda Graf, Thomas Bauernhofer, Yauheniya Cherkas, Peter Ulz, Julie Waldispuehl-Geigl, Samantha Perakis, Michael Gormley, Jaymala Patel, Weimin Li, Jochen B Geigl, Denis Smirnov, Ellen Heitzer, Mitchell Gross, Michael R Speicher
In patients with metastatic castrate resistant prostate cancer (mCRPC), circulating tumor DNA (ctDNA) analysis offers novel opportunities for the development of non-invasive biomarkers informative of treatment response with novel agents targeting the androgen-receptor (AR) pathway, such as abiraterone or enzalutamide. However, the relationship between ctDNA abundance, detectable somatic genomic alterations and clinical progression of mCRPC remains unexplored. Our study aimed to investigate changes in plasma DNA during disease progression and their associations with clinical variables in mCRPC patients...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
Gareth J Morrison, Amir Goldkorn
PURPOSE OF REVIEW: Metastatic prostate cancer is a lethal and highly heterogeneous malignancy, associated with a broad spectrum of potentially actionable molecular alterations. In the past decade, disease profiling has expanded to include not only traditional tumor tissue, but also liquid biopsies of cells and genetic material circulating in the blood. These liquid biopsies offer a minimally invasive, repeatable source of tumor material for longitudinal disease profiling but also raise new technical and biological challenges...
March 23, 2018: Current Oncology Reports
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