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https://www.readbyqxmd.com/read/29195807/parallel-evaluation-of-circulating-tumor-dna-and-circulating-tumor-cells-in-metastatic-colorectal-cancer
#1
Giovanni Germano, Gianluca Mauri, Giulia Siravegna, Caroline Dive, Jackie Pierce, Federica Di Nicolantonio, Maurizio D'Incalci, Alberto Bardelli, Salvatore Siena, Andrea Sartore-Bianchi
BACKGROUND: Tissue biopsy is the gold standard for tumor genotyping, but it is an invasive procedure providing a single snapshot into tumor heterogeneity. Liquid biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), have been proposed as an alternative, with the potential of providing a comprehensive portrait of the tumor molecular landscape. In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been investigated, but comparative analyses are limited...
November 1, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29173760/targeting-dna-damage-in-sclc
#2
REVIEW
Victoria Foy, Maximilian W Schenk, Katie Baker, Fabio Gomes, Alice Lallo, Kristopher K Frese, Martin Forster, Caroline Dive, Fiona Blackhall
SCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability...
December 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29133857/pdgfr-modulated-mir-23b-cluster-and-mir-125a-5p-suppress-lung-tumorigenesis-by-targeting-multiple-components-of-kras-and-nf-kb-pathways
#3
Srivatsava Naidu, Lei Shi, Peter Magee, Justin D Middleton, Alessandro Laganá, Sudhakar Sahoo, Hui Sun Leong, Melanie Galvin, Kristopher Frese, Caroline Dive, Vincenza Guzzardo, Matteo Fassan, Michela Garofalo
In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100543/characterization-of-a-thalamic-nucleus-mediating-habenula-responses-to-changes-in-ambient-illumination
#4
Ruey-Kuang Cheng, Seetha Krishnan, Qian Lin, Caroline Kibat, Suresh Jesuthasan
BACKGROUND: Neural activity in the vertebrate habenula is affected by ambient illumination. The nucleus that links photoreceptor activity with the habenula is not well characterized. Here, we describe the location, inputs and potential function of this nucleus in larval zebrafish. RESULTS: High-speed calcium imaging shows that light ON and OFF both evoke a rapid response in the dorsal left neuropil of the habenula, indicating preferential targeting of this neuropil by afferents conveying information about ambient illumination...
October 31, 2017: BMC Biology
https://www.readbyqxmd.com/read/28928667/thirty-five-day-fluoxetine-treatment-limits-sensory-motor-deficit-and-biochemical-disorders-in-a-rat-model-of-decompression-sickness
#5
Caroline Cosnard, Sébastien De Maistre, Jacques H Abraini, Laurent Chazalviel, Jean-Eric Blatteau, Jean-Jacques Risso, Nicolas Vallée
According to the OECD statistical base for 2014, anti-depressants will, on average, be distributed at a rate of 62 daily doses per 1,000 inhabitants for the 25 countries surveyed (Health at a glance: Europe 2014; OECD Health Statistics; World Health Organization and OECD Health Statistics, 2014). Divers must be concerned. On another hand, divers are potentially exposed to decompression sickness including coagulation inflammation and ischemia, which can result in neurological lesions or even death. The purpose of this study is to assess whether chronic treatment with anti-depressants may represent a contraindication to the practice of an at-risk activity, such as, scuba diving, or even presents a benefit by attenuating the severity of the symptoms...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28904885/the-clinical-utility-of-circulating-tumour-cells-in-patients-with-small-cell-lung-cancer
#6
REVIEW
Victoria Foy, Fabiola Fernandez-Gutierrez, Corinne Faivre-Finn, Caroline Dive, Fiona Blackhall
Small cell lung cancer (SCLC) accounts for 15% of lung cancer diagnosed worldwide. It is aggressive and characterised by early metastatic spread with rapid development of chemo resistance such that less than 5% of patients diagnosed survive 5 years. Surgery is rarely performed and failure to identify new effective treatments has been attributed in a large part to lack of good quality tumour biopsies available for translational research. Liquid biopsies provide a minimally invasive alternative to traditional tumour biopsy...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28904884/circulating-tumor-cells-and-cdx-models-as-a-tool-for-preclinical-drug-development
#7
REVIEW
Alice Lallo, Maximilian W Schenk, Kristopher K Frese, Fiona Blackhall, Caroline Dive
Lung cancers are the main cause of cancer-related deaths worldwide. Efforts placed to improve the survival of lung cancer patients and untangle the complexity of this disease, have resulted in the generation of hundreds of lung cancer cell lines and several genetically engineered mouse models (GEMMs). Although these research tools have extended our knowledge of lung cancer, improvement in the clinical care of lung cancer patients have been limited overall, with measured optimism regarding initial responses to targeted therapies in stratified subgroups of patients...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28904883/spotlight-on-circulating-tumour-cells
#8
Fiona Blackhall, Caroline Dive
No abstract text is available yet for this article.
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28878044/progress-and-prospects-of-early-detection-in-lung-cancer
#9
REVIEW
Sean Blandin Knight, Phil A Crosbie, Haval Balata, Jakub Chudziak, Tracy Hussell, Caroline Dive
Lung cancer is the leading cause of cancer-related death in the world. It is broadly divided into small cell (SCLC, approx. 15% cases) and non-small cell lung cancer (NSCLC, approx. 85% cases). The main histological subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma, with the presence of specific DNA mutations allowing further molecular stratification. If identified at an early stage, surgical resection of NSCLC offers a favourable prognosis, with published case series reporting 5-year survival rates of up to 70% for small, localized tumours (stage I)...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28741788/molecular-analysis-of-single-circulating-tumour-cells-following-long-term-storage-of-clinical-samples
#10
Barbara Mesquita, Dominic G Rothwell, Deborah J Burt, Francesca Chemi, Fabiola Fernandez-Gutierrez, Daniel Slane-Tan, Jenny Antonello, Mathew Carter, Louise Carter, Marina Parry, Lynsey Franklin, Richard Marais, Fiona Blackhall, Caroline Dive, Ged Brady
The CellSearch® semi-automated CTC enrichment and staining system has been established as the "gold standard" for CTC enumeration with CellSearch® CTC counts recognized by the FDA as prognostic for a number of cancers. We and others have gone on to show that molecular analysis of CellSearch® CTCs isolated shortly after CellSearch® enrichment provides another valuable layer of information that has potential clinical utility including predicting response to treatment. Although CellSearch® CTCs can be readily isolated after enrichment, the process of analysing a single CellSearch® patient sample, which may contain many CTCs, is both time consuming and costly...
July 25, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28724705/apparent-changes-in-body-insulation-of-juvenile-king-penguins-suggest-an-energetic-challenge-during-their-early-life-at-sea
#11
Manfred R Enstipp, Charles-André Bost, Céline Le Bohec, Caroline Bost, Yvon Le Maho, Henri Weimerskirch, Yves Handrich
Little is known about the early life at sea of marine top predators, like deep-diving king penguins (Aptenodytes patagonicus), although this dispersal phase is probably a critical phase in their life. Apart from finding favourable foraging sites, they have to develop effective prey search patterns as well as physiological capacities that enable them to capture sufficient prey to meet their energetic needs. To investigate the ontogeny of their thermoregulatory responses at sea, we implanted 30 juvenile king penguins and 8 adult breeders with a small data logger that recorded pressure and subcutaneous temperature continuously for up to 2...
July 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28475662/twoddpcr-an-r-bioconductor-package-and-shiny-app-for-droplet-digital-pcr-analysis
#12
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...
September 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28445469/phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#13
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 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, 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, Karl S Peggs, Peter Van Loo, Caroline Dive, C Jimmy Lin, Matthew Rabinowitz, Hugo J W L 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, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also 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
#14
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...
June 1, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28442585/next-generation-sequencing-analysis-and-algorithms-for-pdx-and-cdx-models
#15
Garima Khandelwal, María Romina Girotti, Christopher Smowton, Sam Taylor, Christopher Wirth, Marek Dynowski, Kristopher K Frese, Ged Brady, Caroline Dive, Richard Marais, Crispin Miller
Patient-derived xenograft (PDX) and circulating tumor cell-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. As 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 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
#16
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
#17
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
#18
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
#19
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
#20
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
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