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https://www.readbyqxmd.com/read/27903971/novel-risk-models-for-early-detection-and-screening-of-ovarian-cancer
#1
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...
November 26, 2016: 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
#2
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...
November 21, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27827359/vasculogenic-mimicry-in-small-cell-lung-cancer
#3
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
#4
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
#5
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...
October 11, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27449544/hormetic-response-triggers-multifaceted-anti-oxidant-strategies-in-immature-king-penguins-aptenodytes-patagonicus
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/26758680/somatically-mutated-abl1-is-an-actionable-and-essential-nsclc-survival-gene
#15
Ewelina Testoni, Natalie L Stephenson, Pedro Torres-Ayuso, Anna A Marusiak, Eleanor W Trotter, Andrew Hudson, Cassandra L Hodgkinson, Christopher J Morrow, Caroline Dive, John Brognard
The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells with ABL1 mutations are sensitive to ABL inhibitors and we verify that the drug-induced effects on cell viability are specific to pharmacological inhibition of the ABL1 kinase. Furthermore, we confirm that imatinib suppresses lung tumor growth in vivo, specifically in lung cancer cells harboring a gain-of-function (GOF) mutation in ABL1...
January 12, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/26715644/application-of-sequencing-liquid-biopsies-and-patient-derived-xenografts-for-personalized-medicine-in-melanoma
#16
Maria Romina Girotti, Gabriela Gremel, Rebecca Lee, Elena Galvani, Dominic Rothwell, Amaya Viros, Amit Kumar Mandal, Kok Haw Jonathan Lim, Grazia Saturno, Simon J Furney, Franziska Baenke, Malin Pedersen, Jane Rogan, Jacqueline Swan, Matthew Smith, Alberto Fusi, Deemesh Oudit, Nathalie Dhomen, Ged Brady, Paul Lorigan, Caroline Dive, Richard Marais
UNLABELLED: Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance...
March 2016: Cancer Discovery
https://www.readbyqxmd.com/read/26654130/development-of-a-circulating-mirna-assay-to-monitor-tumor-burden-from-mouse-to-man
#17
Alastair Greystoke, Mahmood Ayub, Dominic G Rothwell, Dan Morris, Deborah Burt, Cassandra L Hodgkinson, Christopher J Morrow, Nigel Smith, Kyaw Aung, Juan Valle, Louise Carter, Fiona Blackhall, Caroline Dive, Ged Brady
Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumor burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs were examined in mice bearing human SCLC tumor xenografts and SCLC patient derived circulating tumor cell explant models (CDX). We identified 49 miRNAs using human TaqMan Low Density Arrays readily detectable in 10 μl tail vein plasma from mice carrying H526 SCLC xenografts that were low or undetectable in non-tumor bearing controls...
February 2016: Molecular Oncology
https://www.readbyqxmd.com/read/26639657/genetic-profiling-of-tumours-using-both-circulating-free-dna-and-circulating-tumour-cells-isolated-from-the-same-preserved-whole-blood-sample
#18
Dominic G Rothwell, Nigel Smith, Daniel Morris, Hui Sun Leong, Yaoyong Li, Antoine Hollebecque, Mahmood Ayub, Louise Carter, Jenny Antonello, Lynsey Franklin, Crispin Miller, Fiona Blackhall, Caroline Dive, Ged Brady
Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification and monitoring. Blood, which can be sampled routinely, provides a means of inferring the current genetic status of patients' tumours via analysis of circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA). However, accurate assessment of both CTCs and ctDNA requires all blood cells to be maintained intact until samples are processed...
April 2016: Molecular Oncology
https://www.readbyqxmd.com/read/26605519/clinical-evaluation-of-a-novel-microfluidic-device-for-epitope-independent-enrichment-of-circulating-tumour-cells-in-patients-with-small-cell-lung-cancer
#19
Jakub Chudziak, Deborah J Burt, Sumitra Mohan, Dominic G Rothwell, Bárbara Mesquita, Jenny Antonello, Suzanne Dalby, Mahmood Ayub, Lynsey Priest, Louise Carter, Matthew G Krebs, Fiona Blackhall, Caroline Dive, Ged Brady
Circulating tumour cells (CTCs) have potential utility as minimally-invasive biomarkers to aid cancer treatment decision making. However, many current CTC technologies enrich CTCs using specific surface epitopes that do not necessarily reflect CTC heterogeneity. Here we evaluated the epitope-independent Parsortix system which enriches CTCs based on size and rigidity using both healthy normal volunteer blood samples spiked with tumour cells and blood samples from patients with small cell lung cancer (SCLC). Blood samples were maintained unfractionated at room temperature for up to 4 days followed by plasma removal for circulating free DNA (cfDNA) isolation and direct application of the remaining cell component to the Parsortix system...
January 21, 2016: Analyst
https://www.readbyqxmd.com/read/26474517/cediranib-combined-with-carboplatin-and-paclitaxel-in-patients-with-metastatic-or-recurrent-cervical-cancer-circca-a-randomised-double-blind-placebo-controlled-phase-2-trial
#20
RANDOMIZED CONTROLLED TRIAL
R Paul Symonds, Charlie Gourley, Susan Davidson, Karen Carty, Elaine McCartney, Debbie Rai, Susana Banerjee, David Jackson, Rosemary Lord, Mary McCormack, Emma Hudson, Nicholas Reed, Maxine Flubacher, Petra Jankowska, Melanie Powell, Caroline Dive, Catharine M L West, James Paul
BACKGROUND: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20-30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer...
November 2015: Lancet Oncology
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