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https://www.readbyqxmd.com/read/28475662/twoddpcr-an-r-bioconductor-package-and-shiny-app-for-droplet-digital-pcr-analysis
#1
Anthony Chiu, Mahmood Ayub, Caroline Dive, Ged Brady, Crispin J Miller
Summary: Droplet Digital PCR (ddPCR) is a sensitive platform used to quantify specific nucleic acid molecules amplified by polymerase chain reactions. Its sensitivity makes it particularly useful for the detection of rare mutant molecules, such as those present in a sample of circulating free tumour DNA obtained from cancer patients. ddPCR works by partitioning a sample into individual droplets for which the majority contain only zero or one target molecule. Each droplet then becomes a reaction chamber for PCR, which through the use of fluorochrome labelled probes allows the target molecules to be detected by measuring the fluorescence intensity of each droplet...
May 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28445469/phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#2
Christopher Abbosh, Nicolai J Birkbak, Gareth A Wilson, Mariam Jamal-Hanjani, Tudor Constantin, Raheleh Salari, John Le Quesne, David A Moore, Selvaraju Veeriah, Rachel Rosenthal, Teresa Marafioti, Eser Kirkizlar, Thomas B K Watkins, Nicholas McGranahan, Sophia Ward, Luke Martinson, Joan Riley, Francesco Fraioli, Maise Al Bakir, Eva GrÖnroos, Francisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M Fennessy, Nicole Sponer, Diana Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin Hiley, Siow Ming Lee, Martin D Forster, Tanya Ahmad, Mary Falzon, Elaine Borg, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Dina Hafez, Ashwini Naik, Apratim Ganguly, Stephanie Kareht, Rajesh Shah, Leena Joseph, Anne Marie Quinn, Phil 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, Dahmane Oukrif, Ayse U Akarca, John A Hartley, Helen L Lowe, Sara Lock, Natasha Iles, Harriet Bell, Yenting Ngai, Greg Elgar, Zoltan Szallasi, Roland F Schwarz, Javier Herrero, Aengus Stewart, Sergio A Quezada, Peter Van Loo, Caroline Dive, C Jimmy Lin, Matthew Rabinowitz, Hugo Jwl Aerts, Allan Hackshaw, Jacqui A Shaw, Bernhard G Zimmermann, Charles Swanton
The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#3
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/28442585/next-gen-sequencing-analysis-and-algorithms-for-pdx-and-cdx-models
#4
Garima Khandelwal, Maria Romina Girotti, Christopher Smowton, Sam Taylor, Chris Wirth, Marek Dynowski, Kristopher K Frese, Ged Brady, Caroline Dive, Richard Marais, Crispin Miller
Patient-derived xenograft (PDX) and CTC-derived explant (CDX) models are powerful methods for the study of human disease. In cancer research, these methods have been applied to multiple questions including the study of metastatic progression, genetic evolution and therapeutic drug responses. Since PDX and CDX models can recapitulate the highly heterogeneous characteristics of a patient tumor, as well as their response to chemotherapy, there is considerable interest in combining them with next-generation sequencing (NGS) in order to monitor the genomic, transcriptional, and epigenetic changes that accompany oncogenesis...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28340343/snapshot-circulating-tumor-cells
#5
Caroline Dive, Ged Brady
No abstract text is available yet for this article.
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28187292/snapshot-circulating-tumor-cells
#6
Caroline Dive, Ged Brady
Circulating tumor cells in the blood of patients are both signal flares for the existence of a tumor and harbingers of metastasis. With recent technological developments, these cells can be isolated and analyzed to provide insights into the biology of cancer spread and response to therapy and to offer new avenues for blood biomarker development.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/27903971/novel-risk-models-for-early-detection-and-screening-of-ovarian-cancer
#7
Matthew R Russell, Alfonsina D'Amato, Ciaren Graham, Emma J Crosbie, Aleksandra Gentry-Maharaj, Andy Ryan, Jatinderpal K Kalsi, Evangelia-Ourania Fourkala, Caroline Dive, Michael Walker, Anthony D Whetton, Usha Menon, Ian Jacobs, Robert L J Graham
PURPOSE: Ovarian cancer (OC) is the most lethal gynaecological cancer. Early detection is required to improve patient survival. Risk estimation models were constructed for Type I (Model I) and Type II (Model II) OC from analysis of Protein Z, Fibronectin, C-reactive protein and CA125 levels in prospectively collected samples from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). RESULTS: Model I identifies cancers earlier than CA125 alone, with a potential lead time of 3-4 years...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27869802/molecular-analysis-of-circulating-tumor-cells-identifies-distinct-copy-number-profiles-in-patients-with-chemosensitive-and-chemorefractory-small-cell-lung-cancer
#8
Louise Carter, Dominic G Rothwell, Barbara Mesquita, Christopher Smowton, Hui Sun Leong, Fabiola Fernandez-Gutierrez, Yaoyong Li, Deborah J Burt, Jenny Antonello, Christopher J Morrow, Cassandra L Hodgkinson, Karen Morris, Lynsey Priest, Mathew Carter, Crispin Miller, Andrew Hughes, Fiona Blackhall, Caroline Dive, Ged Brady
In most patients with small-cell lung cancer (SCLC)-a metastatic, aggressive disease-the condition is initially chemosensitive but then relapses with acquired chemoresistance. In a minority of patients, however, relapse occurs within 3 months of initial treatment; in these cases, disease is defined as chemorefractory. The molecular mechanisms that differentiate chemosensitive from chemorefractory disease are currently unknown. To identify genetic features that distinguish chemosensitive from chemorefractory disease, we examined copy-number aberrations (CNAs) in circulating tumor cells (CTCs) from pretreatment SCLC blood samples...
January 2017: Nature Medicine
https://www.readbyqxmd.com/read/27827359/vasculogenic-mimicry-in-small-cell-lung-cancer
#9
Stuart C Williamson, Robert L Metcalf, Francesca Trapani, Sumitra Mohan, Jenny Antonello, Benjamin Abbott, Hui Sun Leong, Christopher P E Chester, Nicole Simms, Radoslaw Polanski, Daisuke Nonaka, Lynsey Priest, Alberto Fusi, Fredrika Carlsson, Anders Carlsson, Mary J C Hendrix, Richard E B Seftor, Elisabeth A Seftor, Dominic G Rothwell, Andrew Hughes, James Hicks, Crispin Miller, Peter Kuhn, Ged Brady, Kathryn L Simpson, Fiona H Blackhall, Caroline Dive
Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27785665/iatrogenic-cerebral-air-embolism-revealing-an-atrial-esophageal-fistula
#10
EDITORIAL
Fabien Wuestenberghs, Nathalie Pirson, Pierre Bulpa, Caroline Fervaille, Alain Dive
No abstract text is available yet for this article.
October 26, 2016: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/27725679/imaging-biomarker-roadmap-for-cancer-studies
#11
REVIEW
James P B O'Connor, Eric O Aboagye, Judith E Adams, Hugo J W L Aerts, Sally F Barrington, Ambros J Beer, Ronald Boellaard, Sarah E Bohndiek, Michael Brady, Gina Brown, David L Buckley, Thomas L Chenevert, Laurence P Clarke, Sandra Collette, Gary J Cook, Nandita M deSouza, John C Dickson, Caroline Dive, Jeffrey L Evelhoch, Corinne Faivre-Finn, Ferdia A Gallagher, Fiona J Gilbert, Robert J Gillies, Vicky Goh, John R Griffiths, Ashley M Groves, Steve Halligan, Adrian L Harris, David J Hawkes, Otto S Hoekstra, Erich P Huang, Brian F Hutton, Edward F Jackson, Gordon C Jayson, Andrew Jones, Dow-Mu Koh, Denis Lacombe, Philippe Lambin, Nathalie Lassau, Martin O Leach, Ting-Yim Lee, Edward L Leen, Jason S Lewis, Yan Liu, Mark F Lythgoe, Prakash Manoharan, Ross J Maxwell, Kenneth A Miles, Bruno Morgan, Steve Morris, Tony Ng, Anwar R Padhani, Geoff J M Parker, Mike Partridge, Arvind P Pathak, Andrew C Peet, Shonit Punwani, Andrew R Reynolds, Simon P Robinson, Lalitha K Shankar, Ricky A Sharma, Dmitry Soloviev, Sigrid Stroobants, Daniel C Sullivan, Stuart A Taylor, Paul S Tofts, Gillian M Tozer, Marcel van Herk, Simon Walker-Samuel, James Wason, Kaye J Williams, Paul Workman, Thomas E Yankeelov, Kevin M Brindle, Lisa M McShane, Alan Jackson, John C Waterton
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification...
March 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27449544/hormetic-response-triggers-multifaceted-anti-oxidant-strategies-in-immature-king-penguins-aptenodytes-patagonicus
#12
Benjamin Rey, Cyril Dégletagne, Jacques Bodennec, Pierre-Axel Monternier, Mathieu Mortz, Damien Roussel, Caroline Romestaing, Jean-Louis Rouanet, Jeremy Tornos, Claude Duchamp
Repeated deep dives are highly pro-oxidative events for air-breathing aquatic foragers such as penguins. At fledging, the transition from a strictly terrestrial to a marine lifestyle may therefore trigger a complex set of anti-oxidant responses to prevent chronic oxidative stress in immature penguins but these processes are still undefined. By combining in vivo and in vitro approaches with transcriptome analysis, we investigated the adaptive responses of sea-acclimatized (SA) immature king penguins (Aptenodytes patagonicus) compared with pre-fledging never-immersed (NI) birds...
August 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27373157/identification-and-targeting-of-long-term-tumor-propagating-cells-in-small-cell-lung-cancer
#13
Nadine S Jahchan, Jing Shan Lim, Becky Bola, Karen Morris, Garrett Seitz, Kim Q Tran, Lei Xu, Francesca Trapani, Christopher J Morrow, Sandra Cristea, Garry L Coles, Dian Yang, Dedeepya Vaka, Michael S Kareta, Julie George, Pawel K Mazur, Thuyen Nguyen, Wade C Anderson, Scott J Dylla, Fiona Blackhall, Martin Peifer, Caroline Dive, Julien Sage
Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs...
July 19, 2016: Cell Reports
https://www.readbyqxmd.com/read/27351218/systematic-analysis-of-circulating-soluble-angiogenesis-associated-proteins-in-icon7-identifies-tie2-as-a-biomarker-of-vascular-progression-on-bevacizumab
#14
RANDOMIZED CONTROLLED TRIAL
Cong Zhou, Andrew Clamp, Alison Backen, Carlo Berzuini, Andrew Renehan, Rosamonde E Banks, Richard Kaplan, Stefan J Scherer, Gunnar B Kristensen, Eric Pujade-Lauraine, Caroline Dive, Gordon C Jayson
BACKGROUND: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use. METHODS: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined...
July 12, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27294525/cd47-blocking-immunotherapies-stimulate-macrophage-mediated-destruction-of-small-cell-lung-cancer
#15
Kipp Weiskopf, Nadine S Jahchan, Peter J Schnorr, Sandra Cristea, Aaron M Ring, Roy L Maute, Anne K Volkmer, Jens-Peter Volkmer, Jie Liu, Jing Shan Lim, Dian Yang, Garrett Seitz, Thuyen Nguyen, Di Wu, Kevin Jude, Heather Guerston, Amira Barkal, Francesca Trapani, Julie George, John T Poirier, Eric E Gardner, Linde A Miles, Elisa de Stanchina, Shane M Lofgren, Hannes Vogel, Monte M Winslow, Caroline Dive, Roman K Thomas, Charles M Rudin, Matt van de Rijn, Ravindra Majeti, K Christopher Garcia, Irving L Weissman, Julien Sage
Small-cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer with limited treatment options. CD47 is a cell-surface molecule that promotes immune evasion by engaging signal-regulatory protein alpha (SIRPα), which serves as an inhibitory receptor on macrophages. Here, we found that CD47 is highly expressed on the surface of human SCLC cells; therefore, we investigated CD47-blocking immunotherapies as a potential approach for SCLC treatment. Disruption of the interaction of CD47 with SIRPα using anti-CD47 antibodies induced macrophage-mediated phagocytosis of human SCLC patient cells in culture...
July 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27197306/inhibition-of-pi3k-bmx-cell-survival-pathway-sensitizes-to-bh3-mimetics-in-sclc
#16
Danielle S Potter, Melanie Galvin, Stewart Brown, Alice Lallo, Cassandra L Hodgkinson, Fiona Blackhall, Christopher J Morrow, Caroline Dive
Most small cell lung cancer (SCLC) patients are initially responsive to cytotoxic chemotherapy, but almost all undergo fatal relapse with progressive disease, highlighting an urgent need for improved therapies and better patient outcomes in this disease. The proapoptotic BH3 mimetic ABT-737 that targets BCL-2 family proteins demonstrated good single-agent efficacy in preclinical SCLC models. However, so far clinical trials of the BH3 mimetic Navitoclax have been disappointing. We previously demonstrated that inhibition of a PI3K/BMX cell survival signaling pathway sensitized colorectal cancer cells to ABT-737...
June 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/26862749/sustained-effects-of-developmental-exposure-to-ethanol-on-zebrafish-anxiety-like-behaviour
#17
Matteo Baiamonte, Matthew O Parker, Gavin P Vinson, Caroline H Brennan
In zebrafish developmentally exposed to ambient ethanol (20mM-50mM) 1-9 days post fertilization (dpf), the cortisol response to stress has been shown to be significantly attenuated in larvae, juveniles and 6 month old adults. These data are somewhat at variance with similar studies in mammals, which often show heightened stress responses. To test whether these cortisol data correlate with behavioural changes in treated animals, anxiety-like behaviour of zebrafish larvae (9dpf and 10dpf) and juveniles (23dpf) was tested in locomotor assays designed to this end...
2016: PloS One
https://www.readbyqxmd.com/read/26849853/short-duration-immunochemotherapy-followed-by-radioimmunotherapy-consolidation-is-effective-and-well-tolerated-in-relapsed-follicular-lymphoma-5-year-results-from-a-uk-national-cancer-research-institute-lymphoma-group-study
#18
MULTICENTER STUDY
Tim M Illidge, Hayley S McKenzie, Sam Mayes, Andrew Bates, Andrew J Davies, Ruth Pettengell, Louise Stanton, Kelly Cozens, Grace Hampson, Caroline Dive, Maureen Zivanovic, Jill Tipping, Eve Gallop-Evans, John A Radford, Peter W M Johnson
UNLABELLED: We report a phase II study to evaluate the efficacy and toxicity of abbreviated immunochemotherapy followed by (90) Y Ibritumomab tiuxetan ((90) Y-IT) in patients with recurrent follicular lymphoma. Of the 52 patients enrolled, 50 were treated with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone), followed by (90) Y-IT regimen (15 MBq/kg, maximum 1200 MBq) preceded by two infusions of 250 mg/m(2) rituximab...
April 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/26829312/small-cell-lung-cancer-can-recent-advances-in-biology-and-molecular-biology-be-translated-into-improved-outcomes
#19
REVIEW
Paul A Bunn, John D Minna, Alexander Augustyn, Adi F Gazdar, Youcef Ouadah, Mark A Krasnow, Anton Berns, Elisabeth Brambilla, Natasha Rekhtman, Pierre P Massion, Matthew Niederst, Martin Peifer, Jun Yokota, Ramaswamy Govindan, John T Poirier, Lauren A Byers, Murry W Wynes, David G McFadden, David MacPherson, Christine L Hann, Anna F Farago, Caroline Dive, Beverly A Teicher, Craig D Peacock, Jane E Johnson, Melanie H Cobb, Hans-Guido Wendel, David Spigel, Julien Sage, Ping Yang, M Catherine Pietanza, Lee M Krug, John Heymach, Peter Ujhazy, Caicun Zhou, Koichi Goto, Afshin Dowlati, Camilla Laulund Christensen, Keunchil Park, Lawrence H Einhorn, Martin J Edelman, Giuseppe Giaccone, David E Gerber, Ravi Salgia, Taofeek Owonikoko, Shakun Malik, Niki Karachaliou, David R Gandara, Ben J Slotman, Fiona Blackhall, Glenwood Goss, Roman Thomas, Charles M Rudin, Fred R Hirsch
No abstract text is available yet for this article.
April 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/26815306/protein-z-a-putative-novel-biomarker-for-early-detection-of-ovarian-cancer
#20
MULTICENTER STUDY
Matthew R Russell, Michael J Walker, Andrew J K Williamson, Aleksandra Gentry-Maharaj, Andy Ryan, Jatinderpal Kalsi, Steven Skates, Alfonsina D'Amato, Caroline Dive, Maria Pernemalm, Phillip C Humphryes, Evangelia-Ourania Fourkala, Anthony D Whetton, Usha Menon, Ian Jacobs, Robert L J Graham
Ovarian cancer (OC) has the highest mortality of all gynaecological cancers. Early diagnosis offers an approach to achieving better outcomes. We conducted a blinded-evaluation of prospectively collected preclinical serum from participants in the multimodal group of the United Kingdom Collaborative Trial of Ovarian Cancer Screening. Using isobaric tags (iTRAQ) we identified 90 proteins differentially expressed between OC cases and controls. A second targeted mass spectrometry analysis of twenty of these candidates identified Protein Z as a potential early detection biomarker for OC...
June 15, 2016: International Journal of Cancer. Journal International du Cancer
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