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Cell free tumour DNA

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https://www.readbyqxmd.com/read/27903276/accurate-prediction-of-response-to-endocrine-therapy-in-breast-cancer-patients-current-and-future-biomarkers
#1
REVIEW
Cigdem Selli, J Michael Dixon, Andrew H Sims
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27902986/the-presence-of-hpv-dna-in-neck-lymph-node-metastasis-correlates-with-improved-overall-survival-of-patients-with-oropharyngeal-cancer-undergoing-surgical-treatment
#2
Eiji Shimura, Takanori Hama, Toshihito Suda, Masahiro Ikegami, Mitsuyoshi Urashima, Hiromi Kojima
BACKGROUND: Few studies have addressed how human papilloma virus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) affects the outcome of surgical therapy; furthermore, the relationship between the presence of HPV DNA and neck lymph node (LN) metastasis has not been well established. METHODS: A total of 65 patients who underwent surgery as a first-line therapy for OPSCC were enrolled in this study. In HPV-positive patients, the presence of HPV DNA in metastatic neck LN lesions was evaluated...
December 1, 2016: Oncology
https://www.readbyqxmd.com/read/27899805/circulating-tumour-dna-analysis-demonstrates-spatial-mutational-heterogeneity-that-coincides-with-disease-relapse-in-myeloma
#3
S Mithraprabhu, T Khong, M Ramachandran, A Chow, D Klarica, L Mai, S Walsh, D Broemeling, A Marziali, M Wiggin, J Hocking, A Kalff, B Durie, A Spencer
Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multi-focal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed [RR] and 15 newly diagnosed [ND] patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget™ Mutation Detection (OMD) platform...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27891190/cell-free-dna-promoter-hypermethylation-in-plasma-as-a-diagnostic-marker-for-pancreatic-adenocarcinoma
#4
Stine Dam Henriksen, Poul Henning Madsen, Anders Christian Larsen, Martin Berg Johansen, Asbjørn Mohr Drewes, Inge Søkilde Pedersen, Henrik Krarup, Ole Thorlacius-Ussing
BACKGROUND: Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagnostic biomarker for pancreatic cancer will have a major impact on patient survival by facilitating early detection and the possibility for curative treatment. DNA promoter hypermethylation is a mechanism of early carcinogenesis, which can cause inactivation of tumour suppressor genes...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27862318/genome-wide-dna-methylation-analysis-identifies-megf10-as-a-novel-epigenetically-repressed-candidate-tumour-suppressor-gene-in-neuroblastoma
#5
Jessica Charlet, Ayumi Tomari, Anthony R Dallosso, Marianna Szemes, Martina Kaselova, Thomas J Curry, Bader Almutairi, Heather C Etchevers, Carmel McConville, Karim T A Malik, Keith W Brown
Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome-wide mutation analyses, many primary neuroblastomas do not contain recognisable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome-wide DNA methylation analysis...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27789654/titanium-dioxide-food-additive-e171-induces-ros-formation-and-genotoxicity-contribution-of-micro-and-nano-sized-fractions
#6
Héloïse Proquin, Carolina Rodríguez-Ibarra, Carolyn G J Moonen, Ismael M Urrutia Ortega, Jacob J Briedé, Theo M de Kok, Henk van Loveren, Yolanda I Chirino
Since 1969, the European Union approves food-grade titanium dioxide (TiO2), also known as E171 colouring food additive. E171 is a mixture of micro-sized particles (MPs) and nano-sized particles (NPs). Previous studies have indicated adverse effects of oral exposure to E171, i.e. facilitation of colon tumour growth. This could potentially be partially mediated by the capacity to induce reactive oxygen species (ROS). The aim of the present study is to determine whether E171 exposure induces ROS formation and DNA damage in an in vitro model using human Caco-2 and HCT116 cells and to investigate the contribution of the separate MPs and NPs TiO2 fractions to these effects...
October 27, 2016: Mutagenesis
https://www.readbyqxmd.com/read/27753016/screening-of-kras-mutation-in-pre-and-post-surgery-serum-of-patients-suffering-from-colon-cancer-by-cold-pcr-hrm
#7
Elena Trujillo-Arribas, Hada C Macher, Pilar Jiménez-Arriscado, Fernando de la Portilla, Patrocinio Molinero, Juan M Guerrero, Amalia Rubio
Genomic characterization of cell-free circulating tumour DNA (ctDNA) may offer an opportunity to assess clonal dynamics throughout the course of a patient's illness. The existence of KRAS driver mutations in colon cancer patients is determinant to decide their treatment and to predict their outcome. DNA is extracted automatically from 400 μL of serum using the MagNa Pure Compact with the Nucleic Acid Isolation Kit I. DNA amplification, COLD-PCR and HRM were performed in the same run in the Light Cycler 480...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27753014/unbiased-detection-of-somatic-copy-number-aberrations-in-cfdna-of-lung-cancer-cases-and-high-risk-controls-with-low-coverage-whole-genome-sequencing
#8
Fiona Taylor, James Bradford, Penella J Woll, Dawn Teare, Angela Cox
Molecular profiling using low coverage whole genome sequencing of cell free DNA (cfDNA) represents a non-targeted approach to identify multiple somatic copy number alterations (SCNA) across different lung cancer subtypes. We aim to establish that SCNA can be detected in cfDNA of lung cancer cases.Standard protocols were followed to process matched cfDNA, formalin-fixed paraffin embedded (FFPE) tumour and lymphocyte DNA. Copy number profiles for cfDNA or FFPE DNA were normalised to profiles from matched lymphocyte DNA with the software CNAnorm...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27712975/decreased-plk1-expression-denotes-therapy-resistance-and-unfavourable-disease-free-survival-in-rectal-cancer-patients-receiving-neoadjuvant-chemoradiotherapy
#9
Arancha Cebrián, Teresa Gómez Del Pulgar, Maria Jesús Fernández-Aceñero, Aurea Borrero-Palacios, Laura Del Puerto-Nevado, Javier Martínez-Useros, Juan Pablo Marín-Arango, Cristina Caramés, Ricardo Vega-Bravo, María Rodríguez-Remírez, Felix Manzarbeitia, Jesús García-Foncillas
AIM: Polo-like kinase 1 (Plk1) plays a key role in mitotic cell division and DNA damage repair. It has been observed that either up-regulated or down-regulated Plk1 could induce mitotic defects that results in aneuploidy and tumorigenesis, probably depending on the context. Few previous reports have associated Plk1 expression with prognosis and response to radiotherapy in rectal carcinomas. The aim of this study is to investigate the prognostic impact of Plk1 expression and its role in predicting response to neoadjuvant cheomoradiotherapy in rectal cancer...
December 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27711974/next-generation-sequencing-based-detection-of-circulating-tumour-dna-after-allogeneic-stem-cell-transplantation-for-lymphoma
#10
Alex F Herrera, Haesook T Kim, Katherine A Kong, Malek Faham, Heather Sun, Aliyah R Sohani, Edwin P Alyea, Victoria E Carlton, Yi-Bin Chen, Corey S Cutler, Vincent T Ho, John Koreth, Chitra Kotwaliwale, Sarah Nikiforow, Jerome Ritz, Scott J Rodig, Robert J Soiffer, Joseph H Antin, Philippe Armand
Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes...
December 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27682877/tumour-suppressor-gene-cdkna2-status-on-chromosome-9p-in-resected-renal-tissue-improves-prognosis-of-localised-kidney-cancer
#11
Ismail El-Mokadem, Thomas Kidd, Norman Pratt, Stewart Fleming, Ghulam Nabi
BACKGROUND: Genetic alterations on chromosome 9p, including inactivation of the tumour suppressor gene, CDKN2A, result in cellular proliferation and growth of tumours. Our aim was to use microsatellite analysis and fluorescence in situ hybridization (FISH) to characterise the architecture of this region. RESULTS: Seventy-five out of 77 clear cell renal cell cancers (tumour/normal pairs) were interpretable for LOH analysis on chromosome 9p (two tumours were excluded, as all five primers were uninformative)...
September 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27619188/structural-and-functional-characterisation-of-foxo-acan-daf-16-from-the-parasitic-nematode-angiostrongylus-cantonensis
#12
Baolong Yan, Weiwei Sun, Lanzhu Yan, Liangliang Zhang, Yuan Zheng, Yuzhen Zeng, Huicong Huang, Shaohui Liang
Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C...
September 9, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27576846/tp53-mutations-emerge-with-hdm2-inhibitor-sar405838-treatment-in-de-differentiated-liposarcoma
#13
Joonil Jung, Joon Sang Lee, Mark A Dickson, Gary K Schwartz, Axel Le Cesne, Andrea Varga, Rastilav Bahleda, Andrew J Wagner, Edwin Choy, Maja J de Jonge, Madelyn Light, Steve Rowley, Sandrine Macé, James Watters
In tumours that harbour wild-type p53, p53 protein function is frequently disabled by the mouse double minute 2 protein (MDM2, or HDM2 in humans). Multiple HDM2 antagonists are currently in clinical development. Preclinical data indicate that TP53 mutations are a possible mechanism of acquired resistance to HDM2 inhibition; however, this resistance mechanism has not been reported in patients. Utilizing liquid biopsies, here we demonstrate that TP53 mutations appear in circulating cell-free DNA obtained from patients with de-differentiated liposarcoma being treated with an inhibitor of the HDM2-p53 interaction (SAR405838)...
August 31, 2016: Nature Communications
https://www.readbyqxmd.com/read/27535748/a-phase-1-window-of-opportunity-trial-testing-evofosfamide-th-302-a-tumour-selective-hypoxia-activated-cytotoxic-prodrug-with-preoperative-chemoradiotherapy-in-oesophageal-adenocarcinoma-patients
#14
Ruben T H M Larue, Lien Van De Voorde, Maaike Berbée, Wouter J C van Elmpt, Ludwig J Dubois, Kranthi M Panth, Sarah G J A Peeters, Ann Claessens, Wendy M J Schreurs, Marius Nap, Fabiënne A R M Warmerdam, Frans L G Erdkamp, Meindert N Sosef, Philippe Lambin
BACKGROUND: Neo-adjuvant chemoradiotherapy followed by surgery is the standard treatment with curative intent for oesophageal cancer patients, with 5-year overall survival rates up to 50 %. However, patients' quality of life is severely compromised by oesophagectomy, and eventually many patients die due to metastatic disease. Most solid tumours, including oesophageal cancer, contain hypoxic regions that are more resistant to chemoradiotherapy. The hypoxia-activated prodrug evofosfamide works as a DNA-alkylating agent under these hypoxic conditions, which directly kills hypoxic cancer cells and potentially minimizes resistance to conventional therapy...
August 17, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27531099/sinvict-ultra-sensitive-detection-of-single-nucleotide-variants-and-indels-in-circulating-tumour-dna
#15
Can Kockan, Faraz Hach, Iman Sarrafi, Robert H Bell, Brian McConeghy, Kevin Beja, Anne Haegert, Alexander W Wyatt, Stanislav V Volik, Kim N Chi, Colin C Collins, S Cenk Sahinalp
MOTIVATION: Successful development and application of precision oncology approaches require robust elucidation of the genomic landscape of a patient's cancer and, ideally, the ability to monitor therapy-induced genomic changes in the tumour in an inexpensive and minimally invasive manner. Thanks to recent advances in sequencing technologies, "liquid biopsy", the sampling of patient's bodily fluids such as blood and urine, is considered as one of the most promising approaches to achieve this goal...
August 16, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27502704/distinct-subclonal-tumour-responses-to-therapy-revealed-by-circulating-cell-free-dna
#16
G Gremel, R J Lee, M R Girotti, A K Mandal, S Valpione, G Garner, M Ayub, S Wood, D G Rothwell, A Fusi, A Wallace, G Brady, C Dive, N Dhomen, P Lorigan, R Marais
BACKGROUND: The application of precision medicine in oncology requires in-depth characterisation of a patient's tumours and the dynamics of their responses to treatment. PATIENTS AND METHODS: We used next-generation sequencing of circulating cell-free DNA (cfDNA) to monitor the response of a KIT p.L576P-mutant metastatic vaginal mucosal melanoma to sequential targeted, immuno- and chemotherapy. RESULTS: Despite a KIT mutation, the response to imatinib was mixed...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27494709/progress-and-potential-of-ras-mutation-detection-for-diagnostics-and-companion-diagnostics
#17
Ian A Cree
The importance of RAS mutation in carcinogenesis is established, and knowledge of an individual cancer's mutation status is important for optimal treatment. Areas covered: This paper is restricted to RAS testing in cancer, and highlights papers relevant to current practice. Expert commentary: Multiple laboratory methods are available for RAS gene analysis. PCR is commonly used to determine RAS status, providing a robust and inexpensive technology for clinical use. Next generation sequencing (NGS) platforms are changing the way in which mutation status is determined, though they require considerable expertise...
October 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27465101/microsatellite-alteration-and-immunohistochemical-expression-profile-of-chromosome-9p21-in-patients-with-sporadic-renal-cell-carcinoma-following-surgical-resection
#18
Ismail El-Mokadem, Alison Lim, Thomas Kidd, Katherine Garret, Norman Pratt, David Batty, Stewart Fleming, Ghulam Nabi
BACKGROUND: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. METHODS: DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27404455/non-canonical-nf-%C3%AE%C2%BAb-pathway-activation-predicts-outcome-in-borderline-oestrogen-receptor-positive-breast-carcinoma
#19
Federico Rojo, Abel González-Pérez, Jessica Furriol, Ma Jesús Nicolau, Jaime Ferrer, Octavio Burgués, MohammadA Sabbaghi, Irene González-Navarrete, Ion Cristobal, Laia Serrano, Sandra Zazo, Juan Madoz, Sonia Servitja, Ignasi Tusquets, Joan Albanell, Ana Lluch, Ana Rovira, Pilar Eroles
BACKGROUND: NF-κB signalling appears deregulated in breast tumours. The purpose of this study was to determine whether the non-canonical NF-κB pathway, is activated in oestrogen receptor positive (ER+) breast cancer, to identify any correlation between its activity and the clinico-pathological phenotype and to explore whether NF-κB2 and RelB subunits and/or any of their target genes might be used as a predictive marker. METHODS: Two independent cohorts of ER+ early breast cancer patients treated with adjuvant endocrine therapy were included in the study...
July 26, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27393503/temporal-changes-of-egfr-mutations-and-t790m-levels-in-tumour-and-plasma-dna-following-azd9291-treatment
#20
Puey Ling Chia, Hongdo Do, Adrienne Morey, Paul Mitchell, Alexander Dobrovic, Thomas John
AZD9291, a T790M specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has demonstrated impressive response rates in tumours harbouring the EGFR T790M resistance mutation. Emergence of resistance to AZD9291 has been shown to occur through several different mechanisms including the development of new mutations (e.g. C797S) in the EGFR tyrosine kinase domain. We studied two patients with paired tumour biopsies and blood samples pre- and post-progression on AZD9291 to explore possible resistance mechanisms...
August 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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