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Cell-free tumor dna

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https://www.readbyqxmd.com/read/28454414/analysis-of-egfr-mutation-status-in-tissue-and-plasma-for-predicting-response-to-egfr-tkis-in-advanced-non-small-cell-lung-cancer
#1
Yuyan Wang, Jianchun Duan, Hanxiao Chen, Hua Bai, Tongtong An, Jun Zhao, Zhijie Wang, Minglei Zhuo, Shuhang Wang, Jie Wang
The detection of mutations in the epidermal growth factor receptor (EGFR) gene in tumor tissues has been established as the gold standard for predicting the efficacy of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer (NSCLC). The current study aimed to investigate whether the presence of co-existing EGFR mutations in tumor tissue and in cell-free tumor DNA (ctDNA) in the plasma predicts a more favorable outcome of EGFR-TKI treatment in advanced NSCLC. A total of 287 NSCLC patients who had undergone EGFR-TKI treatment were enrolled and stratified into four subgroups: Wild-type EGFR in plasma and tissue specimens (B-/T-); mutated EGFR in plasma and tissue specimens (B+/T+); mutated EGFR in only in plasma samples (B+/T-); or mutated EGFR in only tissue specimens (B-/T+)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#2
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#3
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28448587/collection-of-cell-free-dna-for-genomic-analysis-of-solid-tumors-in-a-clinical-laboratory-setting
#4
Christopher K Raymond, Jennifer Hernandez, Reynold Karr, Kay Hill, Mark Li
The breadth of diagnostic procedures that utilize cell free DNA (cfDNA) from human plasma has increased dramatically in recent years. Here, we confirm that tumor-derived cfDNA fragments are similar in size distribution to cfDNA derived from normal tissues. Therefore, collection procedures optimized with healthy donor specimens are likely to be applicable to the diagnosis and monitoring of many different cancer types. We verify that the distribution and DNA sequences of fragmentation sites in cfDNA from both normal-germline and tumor-derived cfDNA are non-random...
2017: PloS One
https://www.readbyqxmd.com/read/28445990/prognostic-value-of-tumor-mutations-in-radically-treated-locally-advanced-non-small-cell-lung-cancer-patients
#5
Angela Boros, Ludovic Lacroix, Benjamin Lacas, Julien Adam, Jean-Pierre Pignon, Caroline Caramella, David Planchard, Vincent de Montpreville, Eric Deutsch, Antonin Levy, Benjamin Besse, Cécile Le Pechoux
INTRODUCTION: Chemo-radiation is standard treatment in locally advanced non-small cell lung cancers (NSCLC). The prognostic value of mutations has been poorly explored in this population. RESULTS: Clinical data were collected from 190 patients and mutational profiles were obtained in 78 of them; 58 (74%) were males, 31 (40%) current smokers, 47/31 stage IIIA/IIIB and 40 (51%) adenocarcinoma. The following mutations were identified: EGFR 12% (9/78), KRAS 15% (12/78), BRAF 5% (3/65), PI3KCA 2% (1/57), NRAS 3% (1/32), and ALK+ (FISH) 4% (2/51)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#6
Mariam Jamal-Hanjani, Gareth A Wilson, Nicholas McGranahan, Nicolai J Birkbak, Thomas B K Watkins, Selvaraju Veeriah, Seema Shafi, Diana H Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D Forster, Tanya Ahmad, Crispin T Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M Quinn, Phil A Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O'Sullivan, Helen L Lowe, John A Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A Shaw, Javier Herrero, Zoltan Szallasi, Roland F Schwarz, Aengus Stewart, Sergio A Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy...
April 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28442298/how-to-study-and-overcome-tumor-heterogeneity-with-circulating-biomarkers-the-breast-cancer-case
#7
REVIEW
Valentina Appierto, Serena Di Cosimo, Carolina Reduzzi, Valentina Pala, Vera Cappelletti, Maria Grazia Daidone
Breast cancer ranks first among female cancer-related deaths in Western countries. As the primary tumor can often be controlled by surgical resection, the survival of women with breast cancer is closely linked to the incidence of distant metastases. Molecular screening by next generation sequencing highlighted the spatial and temporal heterogeneity of solid tumors as well as the clonal evolution of cancer cells during progression and under treatment pressure. Such findings question whether an optimal assessment of disease progression and a screening for druggable mutations should be based on molecular features of primary or recurrent/metastatic lesions and therefore represent a crucial element for failure or success of personalized medicine...
April 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28439692/the-presence-and-prognostic-significance-of-human-papillomavirus-in-squamous-cell-carcinoma-of-the-larynx
#8
Evren Erkul, Ismail Yilmaz, Gizem Narli, Mustafa Alparslan Babayigit, Atila Gungor, Dilaver Demirel
The aim of the present study was to evaluate the role of HPV in laryngeal squamous cell carcinoma and correlate it with patients' clinicopathological data. In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study. The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and 2015. All samples were also evaluated for p16 immunohistochemical staining. HPV DNA and p16 status were assessed in terms of location, smoking, alcohol consumption, lymph node status, tumor stage, overall survival, disease-free survival, perineural invasion, and vascular invasion retrospectively...
April 21, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28431643/advances-in-circulating-tumor-dna-analysis
#9
Samantha Perakis, Martina Auer, Jelena Belic, Ellen Heitzer
The analysis of cell-free circulating tumor DNA (ctDNA) is a very promising tool and might revolutionize cancer care with respect to early detection, identification of minimal residual disease, assessment of treatment response, and monitoring tumor evolution. ctDNA analysis, often referred to as "liquid biopsy" offers what tissue biopsies cannot-a continuous monitoring of tumor-specific changes during the entire course of the disease. Owing to technological improvements, efforts for the establishment of preanalytical and analytical benchmark, and the inclusion of ctDNA analyses in clinical trial, an actual clinical implementation has come within easy reach...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28430711/evaluation-of-kdr-rs34231037-as-a-predictor-of-sunitinib-efficacy-in-patients-with-metastatic-renal-cell-carcinoma
#10
María Apellániz-Ruiz, Meta H Diekstra, Juan M Roldán, Epie Boven, Daniel Castellano, Hans Gelderblom, Ron H J Mathijssen, Jesse J Swen, Stefan Böhringer, Jesús García-Donás, Brian I Rini, Henk-Jan Guchelaar, Cristina Rodríguez-Antona
The identification of biomarkers able to predict clinical benefit from vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors is urgently needed. Recently, Maitland and colleagues described an association between KDR-rs34231037 and soluble VEGFR2 levels as well as pazopanib pharmacodynamics. We investigated in a well-characterized series of metastatic clear cell renal cell carcinoma patients whether rs34231037 could influence sunitinib response. Clinical data and DNA were available from an international series of 276 patients...
April 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28430637/clinical-utility-of-circulating-cell-free-epstein-barr-virus-dna-in-patients-with-gastric-cancer
#11
Katsutoshi Shoda, Daisuke Ichikawa, Yuji Fujita, Kiyoshi Masuda, Hidekazu Hiramoto, Junichi Hamada, Tomohiro Arita, Hirotaka Konishi, Toshiyuki Kosuga, Shuhei Komatsu, Atsushi Shiozaki, Kazuma Okamoto, Issei Imoto, Eigo Otsuji
Recent comprehensive molecular subtyping of gastric cancer (GC) identified Epstein-Barr virus (EBV)-positive tumors as a subtype with distinct salient molecular and clinical features. In this study, we aimed to determine the potential utility of circulating cell-free EBV DNA as a biomarker for the detection and/or monitoring of therapeutic response in patients with EBV-associated gastric carcinoma (EBVaGC). The EBV genes-to-ribonuclease P RNA component H1 ratios (EBV ratios) in the GC tumors and plasma samples were determined by quantitative real-time polymerase chain reaction in 153 patients with GC, including 14 patients with EBVaGC diagnosed by the conventional method...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430611/prognostic-value-of-egfr-and-kras-in-circulating-tumor-dna-in-patients-with-advanced-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#12
REVIEW
Gaowei Fan, Kuo Zhang, Jiansheng Ding, Jinming Li
EGFR (exon 19 and exon 21) mutations in patients with advanced non-small cell lung cancer (NSCLC) treated by EGFR-TKIs are associated with a better survival; while KRAS mutations predict a worse prognosis. However, there are divergent findings regarding the prognostic value of EGFR and KRAS mutations in circulating tumor DNA (ctDNA). We aimed to summarize the evidence for the use of circulating EGFR and KRAS mutations as prognostic factors in advanced NSCLC patients.We searched the network databases for studies reporting progression-free survival (PFS) and overall survival (OS) stratified by EGFR or KRAS mutations in ctDNA in advanced NSCLC patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424201/pik3ca-mutations-contribute-to-acquired-cetuximab-resistance-in-metastatic-colorectal-cancer-patients
#13
Jian Ming Xu, Yan Wang, You-Liang Wang, Yan Wang, Tao Liu, Ming Ni, Man-Sheng Li, Li Lin, Fei-Jiao Ge, Chun Gong, Jun-Yan Gu, Ru Jia, He-Fei Wang, Yu Ling Chen, Rong-Rui Liu, Chuan-Hua Zhao, Zhao-Li Tan, Yang Jin, Yunping Zhu, Shuji Ogino, Zhi Rong Qian
<p>Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential roles of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.</p> <br /><br />Experimental Design: <p>Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28420722/low-tumor-mitochondrial-dna-content-is-associated-with-better-outcome-in-breast-cancer-patients-receiving-anthracycline-based-chemotherapy
#14
Marjolein J A Weerts, Antoinette Hollestelle, Anieta M Sieuwerts, John A Foekens, Stefan Sleijfer, John W M Martens
In this study, we aimed to explore whether low levels of mitochondrial DNA (mtDNA) content in the primary tumor could predict better outcome for breast cancer patients receiving anthracycline-based therapies. We hypothesized that tumor cells with low mtDNA content are more susceptible to mitochondrial damage induced by anthracyclines, and thus are more susceptible to anthracycline treatment.<br /><br />Experimental Design: We measured mtDNA content by a quantitative PCR approach in 295 primary breast tumor specimens originating from two well-defined cohorts: 174 lymph node-positive patients who received adjuvant chemotherapy and 121 patients with advanced disease who received chemotherapy as first-line palliative treatment...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28417079/detection-of-copy-number-alterations-in-cell-free-tumor-dna-from-plasma
#15
Olga Østrup, Lise Barlebo Ahlborn, Ulrik Lassen, Morten Mau-Sørensen, Finn Cilius Nielsen
BACKGROUND: Somatic copy number alterations (SCNAs) occurring in tumors can provide information about tumor classification, patient's outcome or treatment targets. Liquid biopsies, incl. plasma samples containing circulating cell-free tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however specify and reliability of methods have to be tested. METHODS: SNP microarrays (Affymetrix) were used to generate whole-genome copy number profiles from plasma ccfDNA (OncoScan) and paired tumor biopsies (CytoScan) from ten patients with metastatic cancers...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28415895/the-value-of-liquid-biopsy-in-diagnosis-and-monitoring-of-diffuse-large-b-cell-lymphoma-recent-developments-and-future-potential
#16
Vincent Camus, Fabrice Jardin, Herve Tilly
Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous subset of non-Hodgkin lymphomas (NHL) that demonstrate many molecular alterations and somatic mutations, all of which are targets for the recent development of biomarkers that use various molecular biological techniques. These non-invasive emerging biomarkers will be used in the next few years to better monitor the response to immunochemotherapeutic treatments with the aim of completely eradicating the disease in order to cure it. Areas covered: In this review, the authors conducted a literature search to identify and summarize the major advances in liquid biopsy techniques for DLBCL that are useful for diagnosis and monitoring minimal residual disease (MRD)...
April 27, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28415741/enhancement-of-radiosensitivity-by-the-novel-anticancer-quinolone-derivative-vosaroxin-in-preclinical-glioblastoma-models
#17
Giovanni Luca Gravina, Andrea Mancini, Claudia Mattei, Flora Vitale, Francesco Marampon, Alessandro Colapietro, Giulia Rossi, Luca Ventura, Antonella Vetuschi, Ernesto Di Cesare, Judith A Fox, Claudio Festuccia
PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). RESULTS: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415658/diagnostic-and-prognostic-value-of-blood-samples-for-kras-mutation-identification-in-lung-cancer-a-meta-analysis
#18
REVIEW
Hongchang Shen, Keying Che, Lei Cong, Wei Dong, Tiehong Zhang, Qi Liu, Jiajun Du
Circulating tumor DNA (ctDNA) and tumor cells (CTC) are novel approaches for identifying genomic alterations. Thus, we designed a meta-analysis to evaluate the diagnostic value and prognostic significance of a KRAS proto-oncogene, GTPase (KRAS) mutation for lung cancer patients. All included articles were from PubMed, EMBASE, Web of Science and Cochrane Library. Twelve articles that described 1,131 patients were reviewed. True positives (TP), false positives (FP), true negatives (TN), and false negatives (FN) were used to calculate pooled sensitivity, specificity, the positive likelihood ratio (PLR), the negative likelihood ratio (NLR), a diagnostic odds ratio (DOR), the area under the curve (AUC) and corresponding 95% confidence intervals (95% CI)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414925/reversion-of-brca1-2-germline-mutations-detected-in-circulating-tumor-dna-from-patients-with-high-grade-serous-ovarian-cancer
#19
Elizabeth L Christie, Sian Fereday, Ken Doig, Swetansu Pattnaik, Sarah-Jane Dawson, David D L Bowtell
Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous ovarian cancer (HGSC) are associated with favorable responses to chemotherapy. However, secondary intragenic (reversion) mutations that restore protein function lead to clinically significant rates of acquired resistance. The goal of this study was to determine whether reversion mutations could be found in an unbiased manner in circulating cell-free DNA (cfDNA) to predict treatment response in HGSC. Patients and Methods Plasma and tumor samples were obtained from 30 patients with HGSC with either BRCA1 or BRCA2 germline mutation...
April 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28414074/a-novel-chemotherapy-drug-free-delivery-system-composed-of-three-therapeutic-aptamers-for-the-treatment-of-prostate-and-breast-cancers-in-vitro-and-in-vivo
#20
Khalil Abnous, Noor Mohammad Danesh, Mohammad Ramezani, Rezvan Yazdian-Robati, Mona Alibolandi, Seyed Mohammad Taghdisi
In this study, a novel chemotherapy drug-free DNA nanocomplex composed of three therapeutic aptamers (IDA, AS1411 and apMNK2F) was designed for treatment of cancer cells. For MTT assay, PC-3 and 4T1 cells (target cells) and CHO cells (nontarget cells) were treated with apMNK2F-AS1411-IDA complex (DNA nanocomplex), as well as AS1411, IDA and apMNK2F alone. Internalization of apMNK2F-AS1411-IDA complex was analyzed by fluorescence imaging and flow cytometry analysis. In the last step, the presented DNA nanocomplex was applied for prohibition of tumor growth in vivo...
April 13, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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