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https://www.readbyqxmd.com/read/28629339/droplet-digital-pcr-for-detection-and-quantification-of-circulating-tumor-dna-in-plasma-of-head-and-neck-cancer-patients
#1
Joost H van Ginkel, Manon M H Huibers, Robert J J van Es, Remco de Bree, Stefan M Willems
BACKGROUND: During posttreatment surveillance of head and neck cancer patients, imaging is insufficiently accurate for the early detection of relapsing disease. Free circulating tumor DNA (ctDNA) may serve as a novel biomarker for monitoring tumor burden during posttreatment surveillance of these patients. In this exploratory study, we investigated whether low level ctDNA in plasma of head and neck cancer patients can be detected using Droplet Digital PCR (ddPCR). METHODS: TP53 mutations were determined in surgically resected primary tumor samples from six patients with high stage (II-IV), moderate to poorly differentiated head and neck squamous cell carcinoma (HNSCC)...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28625771/comparison-of-plasma-to-tissue-dna-mutations-in-surgical-patients-with-non-small-cell-lung-cancer
#2
Kezhong Chen, Jingbo Zhang, Tian Guan, Fan Yang, Feng Lou, Wei Chen, Mingyu Zhao, Jay Zhang, Siyi Chen, Jun Wang
OBJECTIVE: Noninvasive liquid biopsies of circulating tumor DNA (ctDNA) can be used to assess non-small cell lung cancer (NSCLC), but previous work focused on patients with advanced-stage cancer. Thus, we evaluated the feasibility and their potential clinical application of circulating tumor DNA approached for surgical patients with NSCLC. METHOD: Consecutive patients with suspected lung cancer who underwent curative-intent lung resection were enrolled prospectively in this study...
May 24, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28625641/emergence-of-novel-and-dominant-acquired-egfr-solvent-front-mutations-at-gly796-g796s-r-together-with-c797s-r-and-l792f-h-mutations-in-one-egfr-l858r-t790m-nsclc-patient-who-progressed-on-osimertinib
#3
Sai-Hong Ignatius Ou, Jean Cui, Alexa B Schrock, Michael E Goldberg, Viola W Zhu, Lee Albacker, Philip J Stephens, Vincent A Miller, Siraj M Ali
Acquired epidermal growth factor receptor (EGFR) resistance mutations to osimertinib are common, including the EGFR C797S that abolishes the covalent binding of osimertinib to EGFR. Here we report the emergence of novel EGFR solvent front mutations at Gly796 (G796S/R) in addition to a hinge pocket L792F/H mutations, and C797S/G all in cis with T790M in a single patient on progression on osimertinib as detected by plasma circulating tumor DNA (ctDNA) assay in the course of clinical care. A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625639/longitudinal-monitoring-of-ctdna-egfr-mutation-burden-from-urine-correlates-with-patient-response-to-egfr-tkis-a-case-series
#4
Nishan Tchekmedyian, Raja Mudad, Fernando F Blanco, Victoria M Raymond, Jordan Garst, Mark G Erlander, Eric Haura, David Berz
Targetable, somatic EGFR mutations are highly prevalent in patients with non-small cell lung cancer (NSCLC), making them eligible for tyrosine kinase inhibitor (TKI) therapy. Circulating tumor DNA (ctDNA), isolated from blood or urine, has been demonstrated to reliably identify somatic tumor associated EGFR mutations, specifically in patients with inconclusive biopsy. When conventional imaging modalities are inconclusive, quantitative assessment of systemic ctDNA burden has the potential to assess therapeutic response...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28624467/comprehensive-analysis-of-egfr-mutant-abundance-and-its-effect-on-efficacy-of-egfr-tkis-in-advanced-nsclc-with-egfr-mutations
#5
Xuefei Li, Weijing Cai, Guohua Yang, Chunxia Su, Shengxiang Ren, Chao Zhao, Rongjun Hu, Xiaoxia Chen, Guanghui Gao, Zhiwei Guo, Wei Li, Caicun Zhou, Fred R Hirsch
BACKGROUND: It is not enough sensitive to use a qualitative detection method with sensitivity of 1% to determine EGFR status in advanced NSCLC and guide precise therapy in clinical practice. OBJECTIVE: To explore the relationship between the abundance of EGFR mutations and efficacy of EGFR-TKIs. METHODS: We used ARMS plus (ARMS+) to quantitatively evaluate the abundance of EGFR mutations in 201 advanced NSCLC patients. A cut-off value of the abundance of EGFR mutations was determined by ROC analysis in training group and was validated in validation group...
June 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28622291/predicting-lung-cancer-recurrence-from-circulating-tumour-dna-commentary-on-phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#6
Daniel J Murphy, Kevin G Blyth
No abstract text is available yet for this article.
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28614831/liquid-biopsies-for-monitoring-temporal-genomic-heterogeneity-in-breast-and-colon-cancers
#7
Tiziana Venesio, Giulia Siravegna, Alberto Bardelli, Anna Sapino
Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the "liquid biopsy" was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term "liquid biopsy" generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28609695/what-do-we-need-to-make-circulating-tumour-dna-ctdna-a-routine-diagnostic-test-in-lung-cancer
#8
REVIEW
Reyes Bernabé, Nicholas Hickson, Andrew Wallace, Fiona Helen Blackhall
The gold standard test for detection of epidermal growth factor receptor (EGFR) mutation is to genotype somatic DNA extracted from a tissue biopsy or cytology specimen. Yet, in at least 20% of patients this is not possible for various reasons including insufficient availability of neoplastic tissue, lack of fitness of the available tissue for a biopsy or that a biopsy is not technically feasible. Consequently, there has been intense investigation of circulating tumour DNA (ctDNA), released into the plasma fraction of blood from cancer cells during apoptosis/necrosis, as a minimally invasive 'liquid biopsy' and surrogate for cancer tissue...
June 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28600478/clinical-implications-of-monitoring-circulating-tumor-dna-in-patients-with-colorectal-cancer
#9
Lone V Schøler, Thomas Reinert, Mai-Britt W Ørntoft, Christine Gaasdal Kassentoft, Sigrid S Árnadóttir, Søren Vang, Iver Nordentoft, Michael Knudsen, Philippe Lamy, Ditte Andreasen, Frank V Mortensen, Anders Riegels Knudsen, Katrine Stribolt, Kim Sivesgaard, Peter Mouritzen, Hans Jørgen Nielsen, Søren Laurberg, Torben F Ørntoft, Claus L Andersen
We investigated if detection of circulating tumor DNA (ctDNA) after resection of colorectal cancer (CRC) identifies the patients with the highest risk of relapse, and furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention.<br /><br />Experimental Design: In this longitudinal cohort study we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a three year follow-up period...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28600337/high-throughput-sequencing-for-noninvasive-disease-detection-in-hematologic-malignancies
#10
Florian Scherer, David M Kurtz, Maximilian Diehn, Ash A Alizadeh
Noninvasive monitoring of minimal residual disease (MRD) has led to significant advances in personalized management of patients with hematologic malignancies. Improved therapeutic options and prolonged survival have further increased the need for sensitive tumor assessment that can inform treatment decisions and patient outcomes. At diagnosis or relapse of most hematologic neoplasms, malignant cells are often easily accessible in the blood as circulating tumor cells (CTCs), making them ideal targets to noninvasively profile the molecular features of each patient...
June 9, 2017: Blood
https://www.readbyqxmd.com/read/28595065/new-quinoline-arylamidine-hybrids-synthesis-dna-rna-binding-and-antitumor-activity
#11
Luka Krstulović, Ivana Stolić, Marijana Jukić, Teuta Opačak-Bernardi, Kristina Starčević, Miroslav Bajić, Ljubica Glavaš-Obrovac
Four series of new hybrid molecules with 7-chloroquinoline and arylamidine moieties joined through the rigid -O- (groups I (2a-g) and II (5a-g)) or flexible -NH-CH2-CH2-O- (groups III (8a-g) and IV (10a-g)) linker were synthesized, and their DNA/RNA binding properties and cytotoxic activity were tested, against several human cancer lines. The compounds and their interaction with DNA and RNA were studied by UV-Vis and CD spectroscopy. The obtained results showed that the binding affinity of the investigated compounds increases proportionally with the increase of the length and number of groups able to form hydrogen bonds with ds-polynucleotides...
May 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28590268/ar-v7-liquid-biopsy-for-treatment-stratification-in-prostate-cancer-how-close-are-we
#12
Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
June 5, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28576867/early-evaluation-of-circulating-tumor-dna-as-marker-of-therapeutic-efficacy-in-metastatic-colorectal-cancer-patients-placol-study
#13
Fanny Garlan, Pierre Laurent-Puig, David Sefrioui, Nathalie Siauve, Audrey Didelot, Nasrin Sarafan-Vasseur, Pierre Michel, Geraldine Perkins, Claire Mulot, Hélène Blons, Julien Taieb, Frederic Di Fiore, Valerie Taly, Aziz Zaanan
Purpose. Markers of chemotherapy efficacy in metastatic colorectal cancer (mCRC) are essential for optimization of treatment strategies. We evaluated the applicability of early changes in circulating tumor DNA (ctDNA) as a marker of therapeutic efficacy. <p>Experimental design. This prospective study enrolled consecutive mCRC patients receiving a first- or second-line chemotherapy. CtDNA was assessed in plasma collected before the first (C0), second (C1) and/or third (C2) chemotherapy cycle, using picodroplet-digital PCR assays based either on detection of gene mutation (KRAS, BRAF, TP53) or hypermethylation (WIF1, NPY)...
June 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28552765/comprehensive-analysis-of-the-discordance-of-egfr-mutation-status-between-tumor-tissues-and-matched-circulating-tumor-dna-in-advanced-non-small-cell-lung-cancer
#14
Rui Wan, Zhijie Wang, J Jack Lee, Shuhang Wang, Qingqing Li, Fuchou Tang, Jin Wang, Yu Sun, Hua Bai, Di Wang, Jun Zhao, Jianchun Duan, Minglei Zhuo, Tongtong An, Meina Wu, Zhaoli Chen, Zhenlin Yang, Jie Wang
INTRODUCTION: This study aimed to address the underlying reasons and clinical significance of the discordant epidermal growth factor receptor mutation (EGFRm) status between tumor tissues (T) and circulating tumor DNA (ctDNA, C). METHODS: Three groups of EGFR tyrosine kinase inhibitors (EGFR-TKIs) treated patients whose EGFRm were determined by Amplification Refractory Mutation System (ARMS) were included (Group A: EGFRm T+/C+; Group B: EGFRm T-/C+; and Group C: EGFRm T+/C-)...
May 25, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28550027/exceptional-response-to-nivolumab-and-stereotactic-body-radiation-therapy-sbrt-in-neuroendocrine-cervical-carcinoma-with-high-tumor-mutational-burden-management-considerations-from-the-center-for-personalized-cancer-therapy-at-uc-san-diego-moores-cancer-center
#15
Andrew Sharabi, Sangwoo Shawn Kim, Shumei Kato, Philip D Sanders, Sandip Pravin Patel, Parag Sanghvi, Elizabeth Weihe, Razelle Kurzrock
Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into an emerging standard of care for several common disease types. Interestingly, in preclinical and retrospective clinical data, radiation therapy has been demonstrated to synergize with checkpoint inhibitors. Here we report a patient with metastatic, chemotherapy-refractory neuroendocrine carcinoma who presented with partial bowel obstruction due to a large tumor burden...
June 2017: Oncologist
https://www.readbyqxmd.com/read/28549321/studies-on-free-radical-scavenging-cancer-cell-antiproliferation-and-calf-thymus-dna-interaction-of-schiff-bases
#16
Cleiton M da Silva, Marina M Silva, Fabiano S Reis, Ana Lúcia T G Ruiz, João E de Carvalho, Josué C C Santos, Isis M Figueiredo, Rosemeire B Alves, Luzia V Modolo, Ângelo de Fátima
Thirty-nine Schiff bases were synthesized by performing microwave-assisted condensation of the corresponding aldehydes and aromatic amines. Their reactive nitrogen species (RNS) scavenging activity and inhibitory effects against cancer cell growth were then subsequently investigated. Additionally, the interaction between the calf thymus DNA (ctDNA) and selected Schiff bases was evaluated using fluorescence spectroscopy, and their binding parameters were determined. The yields of the various compounds ranged from moderate to excellent (43-99%) after only a 2-min reaction...
May 17, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28547116/groove-binding-of-vanillin-and-ethyl-vanillin-to-calf-thymus-dna
#17
Kaixin Xia, Guowen Zhang, Song Li, Deming Gong
Vanillin (VAN) and ethyl vanillin (EVA) are widely used food additives as flavor enhancers, but may have a potential security risk. In this study, the properties of binding of VAN or EVA with calf thymus DNA (ctDNA) were characterized by multi-spectroscopic methods, multivariate curve resolution-alternating least-squares (MCR-ALS) algorithm and molecular simulation. The concentration profiles for the components (VAN or EVA, ctDNA and VAN-ctDNA or EVA-ctDNA complex) by the MCR-ALS analysis showed that VAN or EVA interacted with ctDNA and formed VAN-ctDNA or EVA-ctDNA complex...
May 25, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28544964/biophysical-and-biological-studies-of-some-polymer-grafted-metallo-intercalators
#18
Yesaiyan Manojkumar, Subramanian Ambika, Rajendran Senthilkumar, Sankaralingam Arunachalam
Two water-soluble polymer-copper(II) complexes, [Cu(ip)2(BPEI)](ClO4)2·H2O (Complex 1) and [Cu(dppz)2BPEI](ClO4)2·H2O (Complex 2) with different degree of coordination have been synthesized and characterized. The interaction between the prepared complexes and CTDNA has been assessed by various physico-chemical methods The spectroscopic and the cyclic voltammetry studies have revealed that both the complexes interact with CTDNA through intercalation binding mode. Among the two complexes, Complex 2 has higher binding affinity with CTDNA...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544042/forced-degradation-studies-of-lansoprazole-using-lc-esi-hrms-and-1-h-nmr-experiments-in-vitro-toxicity-evaluation-of-major-degradation-products
#19
G Shankar, R M Borkar, S Udutha, L Guntuku, V G M Naidu, N Nagesh, R Srinivas
Regulatory agencies from all over the world have set up stringent guidelines with regard to drug degradation products due to their toxic effects or carcinogenicity. Lansoprazole, a proton-pump inhibitor, was subjected to forced degradation studies as per ICH guidelines Q1A (R2). The drug was found to degrade under acidic, basic, neutral hydrolysis and oxidative stress conditions, whereas it was found to be stable under thermal and photolytic conditions. The chromatographic separation of the drug and its degradation products were achieved on a Hiber Purospher, C18 (250 X 4...
May 20, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28543104/circulating-tumor-dna-profiling-reveals-clonal-evolution-and-real-time-disease-progression-in-advanced-hepatocellular-carcinoma
#20
Zhi-Xiong Cai, Geng Chen, Yong-Yi Zeng, Xiu-Qing Dong, Min-Jie Lin, Xin-Hui Huang, Da Zhang, Xiao-Long Liu, Jing-Feng Liu
Circulating tumor DNA (ctDNA) provides a potential non-invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis...
May 22, 2017: International Journal of Cancer. Journal International du Cancer
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