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Cell free tumour DNA

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https://www.readbyqxmd.com/read/29330557/linear-doggybone-dna-vaccine-induces-similar-immunological-responses-to-conventional-plasmid-dna-independently-of-immune-recognition-by-tlr9-in-a-pre-clinical-model
#1
Alex Allen, Chuan Wang, Lisa J Caproni, Gessa Sugiyarto, Elena Harden, Leon R Douglas, Patrick J Duriez, Kinga Karbowniczek, Jon Extance, Paul J Rothwell, Ifeayinwa Orefo, John P Tite, Freda K Stevenson, Christian H Ottensmeier, Natalia Savelyeva
Vaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against cancer and has already shown promise in the clinical setting. Conventional plasmid DNA is commonly used which together with the encoded antigen also includes bacterial immunostimulatory CpG motifs to target the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNA™), have been developed without the use of bacteria. The cell-free process relies on the use of Phi29 DNA polymerase to amplify the template followed by protelomerase TelN to complete individual closed linear DNA...
January 12, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29306909/detection-of-egfr-kras-and-braf-mutations-in-metastatic-cells-from-cerebrospinal-fluid
#2
Diane Frankel, Isabelle Nanni-Metellus, Andrée Robaglia-Schlupp, Pascale Tomasini, Julien Guinde, Fabrice Barlesi, Philippe Astoul, L'Houcine Ouafik, Florent Amatore, Véronique Secq, Elise Kaspi, Patrice Roll
BACKGROUND: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed. METHODS: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF...
January 8, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29247383/adjusted-indirect-comparison-using-propensity-score-matching-of-osimertinib-to-platinum-based-doublet-chemotherapy-in-patients-with-egfrm-t790m-nsclc-who-have-progressed-after-egfr-tki
#3
Helen Mann, Frank Andersohn, Carolyn Bodnar, Tetsuya Mitsudomi, Tony S K Mok, James Chih-Hsin Yang, Christopher Hoyle
BACKGROUND AND OBJECTIVE: An adjusted indirect comparison was conducted to assess efficacy outcomes, particularly overall survival (OS), of osimertinib versus platinum-based doublet chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) T790M mutation-positive non-small-cell lung cancer (NSCLC) who had progressed following an EGFR tyrosine kinase inhibitor (TKI). Analysis of treatment effect from two separate trials had the potential to more accurately estimate the magnitude of OS benefit due to absence of confounding due to treatment switching from the control arm to the osimertinib arm of the ongoing randomized control trial, AURA3...
December 15, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29196748/cell-free-dna-kinetics-in-a-pre-clinical-model-of-head-and-neck-cancer
#4
Nidal Muhanna, Marco A Di Grappa, Harley H L Chan, Tahsin Khan, Cheng S Jin, Yangqiao Zheng, Jonathan C Irish, Scott V Bratman
In cancer patients, circulating tumour-derived DNA (ctDNA) levels imperfectly reflect disease burden apparent on medical imaging. Further evaluation of ctDNA levels over time is needed to better understand the correlation with tumour growth and therapeutic response. We describe ctDNA kinetics within an orthotopic, immunocompetent preclinical rabbit model of local-regionally advanced head and neck squamous cell carcinoma (HNSCC). Monitoring primary tumour and metastatic lymph node volume by computed tomography (CT), we observed a correlation between ctDNA levels and tumour burden...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175734/plasma-total-cell-free-dna-cfdna-is-a-surrogate-biomarker-for-tumour-burden-and-a-prognostic-biomarker-for-survival-in-metastatic-melanoma-patients
#5
S Valpione, G Gremel, P Mundra, P Middlehurst, E Galvani, M R Girotti, R J Lee, G Garner, N Dhomen, P C Lorigan, R Marais
INTRODUCTION: Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. MATERIALS AND METHODS: A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients...
November 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29122359/prognostic-impact-of-rita-expression-in-patients-with-anal-squamous-cell-carcinoma-treated-with-chemoradiotherapy
#6
Franz Rödel, Kerstin Steinhäuser, Nina-Naomi Kreis, Alexandra Friemel, Daniel Martin, Ulrike Wieland, Margret Rave-Fränk, Panagiotis Balermpas, Emmanouil Fokas, Frank Louwen, Claus Rödel, Juping Yuan
BACKGROUND: RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. MATERIALS AND METHODS: In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS)...
November 6, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29113230/squamous-cell-transformation-and-egfr-t790m-mutation-as-acquired-resistance-mechanisms-in-a-patient-with-lung-adenocarcinoma-treated-with-a-tyrosine-kinase-inhibitor-a-case-report
#7
Rossella Bruno, Agnese Proietti, Greta Alì, Gianfranco Puppo, Alessandro Ribechini, Antonio Chella, Gabriella Fontanini
The present case report describes the infrequent coexistence of squamous cell transformation and the epidermal growth factor receptor (EGFR) T790M mutation as resistance mechanisms to first line treatment with tyrosine kinase inhibitors. The patient was a 44-year-old female, diagnosed with a primitive advanced lung adenocarcinoma with bone metastases. The tumor was positive for the EGFR exon 19 deletion, therefore the patient was treated with afatinib (40 mg/day, orally) and radiotherapy for bone lesions. After 16 months, the patient developed resistance...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110846/egfr-mutation-prevalence-in-asia-pacific-and-russian-patients-with-advanced-nsclc-of-adenocarcinoma-and-non-adenocarcinoma-histology-the-ignite-study
#8
Baohui Han, Sergei Tjulandin, Koichi Hagiwara, Nicola Normanno, Laksmi Wulandari, Konstantin Laktionov, Achmad Hudoyo, Yong He, Yi-Ping Zhang, Meng-Zhao Wang, Chien Ying Liu, Marianne Ratcliffe, Rose McCormack, Martin Reck
OBJECTIVES: Limited understanding exists of epidermal growth factor receptor (EGFR) mutation frequency in less common subgroups of advanced non-small-cell lung cancer (aNSCLC) (e.g. squamous cell carcinoma [SCC]), and to what extent local practices exclude patients from EGFR testing based on their clinical characteristics. MATERIALS AND METHODS: IGNITE (non-comparative/-interventional; NCT01788163) was conducted in 90 centres (Asia-Pacific/Russia). Eligible patients: local/metastatic aNSCLC; chemotherapy-naïve, newly-diagnosed/recurrent disease after resection; ineligible for curative treatment...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29075515/characterisation-of-the-changing-genomic-landscape-of-metastatic-melanoma-using-cell-free-dna
#9
Anthony Cutts, Oliver Venn, Alexander Dilthey, Avinash Gupta, Dimitris Vavoulis, Helene Dreau, Mark Middleton, Gil McVean, Jenny C Taylor, Anna Schuh
Cancer is characterised by complex somatically acquired genetic aberrations that manifest as intra-tumour and inter-tumour genetic heterogeneity and can lead to treatment resistance. In this case study, we characterise the genome-wide somatic mutation dynamics in a metastatic melanoma patient during therapy using low-input (50 ng) PCR-free whole genome sequencing of cell-free DNA from pre-treatment and post-relapse blood samples. We identify de novo tumour-specific somatic mutations from cell-free DNA, while the sequence context of single nucleotide variants showed the characteristic UV-damage mutation signature of melanoma...
September 4, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29061138/the-evidence-base-for-circulating-tumour-dna-blood-based-biomarkers-for-the-early-detection-of-cancer-a-systematic-mapping-review
#10
Ian A Cree, Lesley Uttley, Helen Buckley Woods, Hugh Kikuchi, Anne Reiman, Susan Harnan, Becky L Whiteman, Sian Taylor Philips, Michael Messenger, Angela Cox, Dawn Teare, Orla Sheils, Jacqui Shaw
BACKGROUND: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest...
October 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29022489/adar1-expression-is-associated-with-tumour-infiltrating-lymphocytes-in-triple-negative-breast-cancer
#11
In Hye Song, Young-Ae Kim, Sun-Hee Heo, In Ah Park, Miseon Lee, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28990231/ifi16-restoration-in-hepatocellular-carcinoma-induces-tumour-inhibition-via-activation-of-p53-signals-and-inflammasome
#12
Wei Lin, Zhiguang Zhao, Zhonglin Ni, Yaxin Zhao, Wenjun Du, Shijun Chen
OBJECTIVE: Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Hepatocellular carcinoma tissues (n = 20) and corresponding non-neoplastic tissues (n = 20) were collected to determine the expression of IFI16...
October 8, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28982739/discovery-of-methylated-circulating-dna-biomarkers-for-comprehensive-non-invasive-monitoring-of-treatment-response-in-metastatic-colorectal-cancer
#13
Ludovic Barault, Alessio Amatu, Giulia Siravegna, Agostino Ponzetti, Sebastian Moran, Andrea Cassingena, Benedetta Mussolin, Chiara Falcomatà, Alexandra M Binder, Carmen Cristiano, Daniele Oddo, Simonetta Guarrera, Carlotta Cancelliere, Sara Bustreo, Katia Bencardino, Sean Maden, Alice Vanzati, Patrizia Zavattari, Giuseppe Matullo, Mauro Truini, William M Grady, Patrizia Racca, Karin B Michels, Salvatore Siena, Manel Esteller, Alberto Bardelli, Andrea Sartore-Bianchi, Federica Di Nicolantonio
OBJECTIVE: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC)...
October 5, 2017: Gut
https://www.readbyqxmd.com/read/28972962/igf-1r-associates-with-adverse-outcomes-after-radical-radiotherapy-for-prostate-cancer
#14
Tamara Aleksic, Clare Verrill, Richard J Bryant, Cheng Han, Andrew Ross Worrall, Laurent Brureau, Stephane Larré, Geoff S Higgins, Fahad Fazal, Ahmad Sabbagh, Syed Haider, Francesca M Buffa, David Cole, Valentine M Macaulay
BACKGROUND: Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, sensitising prostate cancer cells to ionising radiation. Here we tested the clinical relevance of these findings. METHODS: We assessed associations between IGF-1R and clinical outcomes by immunohistochemistry in diagnostic biopsies of 136 men treated with 55-70 Gy external beam radiotherapy for prostate cancer, comparing results with publicly available transcriptional data in surgically treated patients...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28967905/akt-overactivation-can-suppress-dna-repair-via-p70s6-kinase-dependent-downregulation-of-mre11
#15
D Piscitello, D Varshney, S Lilla, M G Vizioli, C Reid, V Gorbunova, A Seluanov, D A Gillespie, P D Adams
Deregulated AKT kinase activity due to PTEN deficiency in cancer cells contributes to oncogenesis by incompletely understood mechanisms. Here, we show that PTEN deletion in HCT116 and DLD1 colon carcinoma cells leads to suppression of CHK1 and CHK2 activation in response to irradiation, impaired G2 checkpoint proficiency and radiosensitization. These defects are associated with reduced expression of MRE11, RAD50 and NBS1, components of the apical MRE11/RAD50/NBS1 (MRN) DNA damage response complex. Consistent with reduced MRN complex function, PTEN-deficient cells fail to resect DNA double-strand breaks efficiently after irradiation and show greatly diminished proficiency for DNA repair via the error-free homologous recombination (HR) repair pathway...
October 2, 2017: Oncogene
https://www.readbyqxmd.com/read/28845132/cell-free-dna-in-non-small-cell-lung-cancer
#16
Vaida Gedvilaitė, Diana Schveigert, Saulius Cicėnas
Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients' overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28841569/results-of-the-first-external-quality-assessment-scheme-eqa-for-isolation-and-analysis-of-circulating-tumour-dna-ctdna
#17
Verena Haselmann, Parviz Ahmad-Nejad, Wolf J Geilenkeuser, Angelika Duda, Merle Gabor, Romy Eichner, Simon Patton, Michael Neumaier
BACKGROUND: Circulating tumour DNA (ctDNA) is considered to have a high potential for future management of malignancies. This pilot external quality assessment (EQA) scheme aimed to address issues of analytical quality in this new area of laboratory diagnostics. METHODS: The EQA scheme consisted of three 2-mL EDTA-plasma samples spiked with fragmented genomic DNA with a mutant allele frequency ranging from 0% to 10% dedicated to the analysis of nine known sequence variations in KRAS codon 12/13 and of BRAF V600E...
August 25, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28827745/establishing-pnb-qpcr-for-quantifying-minimal-ctdna-concentrations-during-tumour-resection
#18
T Ehlert, S Tug, A Brahmer, V Neef, F Heid, C Werner, B Jansen-Winkeln, W Kneist, H Lang, I Gockel, P Simon
The analysis of blood plasma or serum as a non-invasive alternative to tissue biopsies is a much-pursued goal in cancer research. Various methods and approaches have been presented to determine a patient's tumour status, chances of survival, and response to therapy from serum or plasma samples. We established PNB-qPCR (Pooled, Nested, WT-Blocking qPCR), a highly specific nested qPCR with various modifications to detect and quantify minute amounts of circulating tumour DNA (ctDNA) from very limited blood plasma samples...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790338/statistical-analysis-of-mutant-allele-frequency-level-of-circulating-cell-free-dna-and-blood-cells-in-healthy-individuals
#19
Ligang Xia, Zhoufang Li, Bo Zhou, Geng Tian, Lidong Zeng, Hongyu Dai, Xiaohua Li, Chaoyu Liu, Shixin Lu, Feiyue Xu, Xiaonian Tu, Fang Deng, Yuancai Xie, Weiren Huang, Jiankui He
Cell-free DNA (cfDNA) in plasma has emerged as a potential important biomarker in clinical diagnostics, particularly in cancer. However, somatic mutations are also commonly found in healthy individuals, which interfere with the effectiveness for cancer diagnostics. This study examined the background somatic mutations in white blood cells (WBC) and cfDNA in healthy controls based on sequencing data from 821 non-cancer individuals and several cancer samples with the aim of understanding the patterns of mutations detected in cfDNA...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723472/human-prostate-tissue-derived-extracellular-matrix-as-a-model-of-prostate-microenvironment
#20
Walter Cazzaniga, Manuela Nebuloni, Erika Longhi, Irene Locatelli, Raffaele Allevi, Roberta Lucianò, Gelsomina Senatore, Eugenio Ventimiglia, Vito Cucchiara, Luca Genovese, Francesco Montorsi, Massimo Alfano, Andrea Salonia, Ilaria Cavarretta
BACKGROUND: Clinical experience highlights the wide heterogeneity of primary prostate cancer (PPCa), even when potentially related to the same grade and stage. Currently available prediction tools and biomarkers do not always allow for early recognition of PPCa aggressive phenotype, sometimes making it impossible to distinguish among men harbouring indolent tumours or life-threatening disease. OBJECTIVE: To establish a novel ex vivo/in vitro model suitable to estimate the invasive phenotype of PPCa cells (PPCaC)...
October 2016: European Urology Focus
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