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4 results on '"Karin Oien"'

1. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Author

Stephan B. Dreyer, Rosie Upstill-Goddard, Viola Paulus-Hock, Clara Paris, Eirini-Maria Lampraki, Eloise Dray, Bryan Serrels, Giuseppina Caligiuri, Selma Rebus, Dennis Plenker, Zachary Galluzzo, Holly Brunton, Richard Cunningham, Mathias Tesson, Craig Nourse, Ulla-Maja Bailey, Marc Jones, Kim Moran-Jones, Derek W. Wright, Fraser Duthie, Karin Oien, Lisa Evers, Colin J. McKay, Grant A. McGregor, Aditi Gulati, Rachel Brough, Ilirjana Bajrami, Stephan Pettitt, Michele L. Dziubinski, Juliana Candido, Frances Balkwill, Simon T. Barry, Robert Grützmann, Lola Rahib, Amber Johns, Marina Pajic, Fieke E.M. Froeling, Phillip Beer, Elizabeth A. Musgrove, Gloria M. Petersen, Alan Ashworth, Margaret C. Frame, Howard C. Crawford, Diane M. Simeone, Chris Lord, Debabrata Mukhopadhyay, Christian Pilarsky, David A. Tuveson, Susanna L. Cooke, Nigel B. Jamieson, Jennifer P. Morton, Owen J. Sansom, Peter J. Bailey, Andrew V. Biankin, David K. Chang, Sarah Allison, Dario Beraldi, Euan Cameron, Stephan Dreyer, Paul Grimwood, Shane Kelly, John Marshall, Sancha Martin, Brian McDade, Daniel McElroy, Donna Ramsay, Derek Wright, Marc D. Jones, Jane Hair, Paul Westwood, Nicola Williams, Amber L. Johns, Amanda Mawson, Christopher J. Scarlett, Mary-Anne L. Brancato, Sarah J. Rowe, Skye H. Simpson, Mona Martyn-Smith, Michelle T. Thomas, Lorraine A. Chantrill, Venessa T. Chin, Angela Chou, Mark J. Cowley, Jeremy L. Humphris, R. Scott Mead, Adnan M. Nagrial, Jessica Pettit, Mark Pinese, Ilse Rooman, Jianmin Wu, Jiang Tao, Renee DiPietro, Clare Watson, Angela Steinmann, Hong Ching Lee, Rachel Wong, Andreia V. Pinho, Marc Giry-Laterriere, Roger J. Daly, Robert L. Sutherland, Sean M. Grimmond, Nicola Waddell, Karin S. Kassahn, David K. Miller, Peter J. Wilson, Ann-Marie Patch, Sarah Song, Ivon Harliwong, Senel Idrisoglu, Ehsan Nourbakhsh, Suzanne Manning, Shivangi Wani, Milena Gongora, Matthew Anderson, Oliver Holmes, Conrad Leonard, Darrin Taylor, Scott Wood, Christina Xu, Katia Nones, J. Lynn Fink, Angelika Christ, Tim Bruxner, Nicole Cloonan, Felicity Newell, John V. Pearson, Peter Bailey, Michael Quinn, Shivashankar Nagaraj, Stephen Kazakoff, Nick Waddell, Keerthana Krisnan, Kelly Quek, David Wood, Jaswinder S. Samra, Anthony J. Gill, Nick Pavlakis, Alex Guminski, Christopher Toon, Ray Asghari, Neil D. Merrett, Darren Pavey, Amitabha Das, Peter H. Cosman, Kasim Ismail, Chelsie O’Connnor, Vincent W. Lam, Duncan McLeod, Henry C. Pleass, Arthur Richardson, Virginia James, James G. Kench, Caroline L. Cooper, David Joseph, Charbel Sandroussi, Michael Crawford, James Gallagher, Michael Texler, Cindy Forest, Andrew Laycock, Krishna P. Epari, Mo Ballal, David R. Fletcher, Sanjay Mukhedkar, Nigel A. Spry, Bastiaan DeBoer, Ming Chai, Nikolajs Zeps, Maria Beilin, Kynan Feeney, Nan Q. Nguyen, Andrew R. Ruszkiewicz, Chris Worthley, Chuan P. Tan, Tamara Debrencini, John Chen, Mark E. Brooke-Smith, Virginia Papangelis, Henry Tang, Andrew P. Barbour, Andrew D. Clouston, Patrick Martin, Thomas J. O’Rourke, Amy Chiang, Jonathan W. Fawcett, Kellee Slater, Shinn Yeung, Michael Hatzifotis, Peter Hodgkinson, Christopher Christophi, Mehrdad Nikfarjam, Angela Mountain, Victorian Cancer Biobank, James R. Eshleman, Ralph H. Hruban, Anirban Maitra, Christine A. Iacobuzio-Donahue, Richard D. Schulick, Christopher L. Wolfgang, Richard A. Morgan, Mary Hodgin, Aldo Scarpa, Rita T. Lawlor, Stefania Beghelli, Vincenzo Corbo, Maria Scardoni, Claudio Bassi, Margaret A. Tempero, Janet S. Graham, and Basic (bio-) Medical Sciences

Subjects
0301 basic medicine, HRD, homologous recombination deficiency, DNA Repair, PDAC, pancreatic ductal adenocarcinoma, Cell Culture Techniques, DMSO, dimethyl sulfoxide, Transcriptome, 0302 clinical medicine, Molecular Targeted Therapy, SV, structural variation, Original Research, Cancer, PDCL, patient-derived cell line, Gastroenterology, Organoids, PC, pancreatic cancer, oncology, PARP inhibitor, RNAseq, RNA sequencing, 030211 gastroenterology & hepatology, DNA Damage Response, ICGC, International Cancer Genome Consortium, DNA Replication, DNA repair, DNA damage, RPPA, reverse-phase protein array, EC50, median effective concentration, MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, Adenocarcinoma, Biology, DDR, DNA damage response, TOM, topological overlap measure, 03 medical and health sciences, Pancreatic Cancer, Cell Line, Tumor, Pancreatic cancer, GO, Gene Ontology, medicine, Humans, PDX, patient-derived xenograft, Hepatology, DNA replication, Personalized Medicine, Replication Stress, medicine.disease, Xenograft Model Antitumor Assays, Pancreatic Neoplasms, body regions, 030104 developmental biology, siRNA, small interfering RNA, Cancer research, Full Report: Basic and Translational—Pancreas, HR, homologous recombination, Homologous recombination, Biomarkers, DNA Damage
Abstract

Background & Aims Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. Methods We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. Results Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. Conclusions Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy., Graphical abstract

Published
2021
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2. Training and accreditation standards for pathologists undertaking clinical trial work

Author

Gabrielle Rees, Manuel Salto‐Tellez, Jessica L Lee, Karin Oien, Clare Verrill, Alex Freeman, Ilaria Mirabile, Nicholas P West, and on behalf of the National Cancer Research Institute (NCRI) Cellular‐Molecular Pathology (CM‐Path) clinical trials working group

Subjects
education, Translational research, Pathology and Forensic Medicine, Accreditation, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, lcsh:Pathology, Medicine, Humans, Good clinical laboratory practice, NCRI CM‐Path, NCRI CM-Path, 030304 developmental biology, 0303 health sciences, Medical education, clinical trials, Data collection, Pathology, Clinical, business.industry, Clinical study design, Reproducibility of Results, Research Personnel, United Kingdom, 3. Good health, Clinical trial, Pathologists, 030220 oncology & carcinogenesis, Good clinical practice, Perspective, training and accreditation, business, Laboratories, lcsh:RB1-214, Perspectives
Abstract

Clinical trials rely on multidisciplinary teams for successful delivery. Pathologists should be involved in clinical trial design from the outset to ensure that protocols are optimised to deliver maximum data collection and translational research opportunities. Clinical trials must be performed according to the principles of Good Clinical Practice (GCP) and the trial sponsor has an obligation to ensure that all of the personnel involved in the trial have undergone training relevant to their role. Pathologists who are involved in the delivery of clinical trials are often required to undergo formal GCP training and may additionally undergo Good Clinical Laboratory Practice training if they are involved in the laboratory analysis of trials samples. Further training can be provided via trial‐specific investigator meetings, which may be either multidisciplinary or discipline‐specific events. Pathologists should also ensure that they undertake External Quality Assurance schemes relevant to the area of diagnostic practice required in the trial. The level of engagement of pathologists in academia and clinical trials research has declined in the United Kingdom over recent years. This paper recommends the optimal training and accreditation for pathologists undertaking clinical trials activities with the aim of facilitating increased engagement. Clinical trials training should ideally be provided to all pathologists through centrally organised educational events, with additional training provided to pathologists in training through local postgraduate teaching. Pathologists in training should also be strongly encouraged to undertake GCP training. It is hoped that these recommendations will increase the number of pathologists who take part in clinical trials research in order to ensure a high level and standard of data collection and to maximise the translational research opportunities.

Published
2019
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3. Quality assurance guidance for scoring and reporting for pathologists and laboratories undertaking clinical trial work

Author

Max Robinson, Jacqueline James, Gareth Thomas, Nicholas West, Louise Jones, Jessica Lee, Karin Oien, Alex Freeman, Clare Craig, Philip Sloan, Philip Elliot, Maggie Cheang, Manuel Rodriguez‐Justo, Clare Verrill, and on behalf of the UK National Cancer Research Institute (NCRI) Cellular‐Molecular Pathology (CM‐Path) clinical trials working group

Subjects
0301 basic medicine, medicine.medical_specialty, Neoplasm, Residual, Quality Assurance, Health Care, quality assurance, Laboratory testing, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Secondary outcome, lcsh:Pathology, Humans, Medicine, Medical physics, Complete response, clinical trials, Pathology, Clinical, business.industry, Reproducibility of Results, biomarkers, Pathologists, Clinical trial, 030104 developmental biology, Work (electrical), 030220 oncology & carcinogenesis, Perspective, immunohistochemistry, pathology, Analysis tools, Laboratories, business, Quality assurance, Perspectives, lcsh:RB1-214
Abstract

While pathologists have always played a pivotal role in clinical trials ensuring accurate diagnosis and staging, pathology data from prognostic and predictive tests are increasingly being used to enrol, stratify and randomise patients to experimental treatments. The use of pathological parameters as primary and secondary outcome measures, either as standalone classifiers or in combination with clinical data, is also becoming more common. Moreover, reporting of estimates of residual disease, termed ‘pathological complete response’, have been incorporated into neoadjuvant clinical trials. Pathologists have the expertise to deliver this essential information and they also understand the requirements and limitations of laboratory testing. Quality assurance of pathology‐derived data builds confidence around trial‐specific findings and is necessarily focused on the reproducibility of pathological data, including ‘estimates of uncertainty of measurement’, emphasising the importance of pathologist education, training, calibration and demonstration of satisfactory inter‐observer agreement. There are also opportunities to validate objective image analysis tools alongside conventional histological assessments. The ever‐expanding portfolio of clinical trials will demand more pathologist engagement to deliver the reliable evidence‐base required for new treatments. We provide guidance for quality assurance of pathology scoring and reporting in clinical trials.

Published
2019
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4. Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme

Author

Colin R. Lindsay, Emily C. Shaw, Fiona Blackhall, Kevin G. Blyth, James D. Brenton, Anshuman Chaturvedi, Noel Clarke, Craig Dick, Thomas R.J. Evans, Geoff Hall, Andrew M. Hanby, David J. Harrison, Stephen R.D. Johnston, Malcolm D. Mason, Dion Morton, Julia Newton-Bishop, Andrew G. Nicholson, Karin A. Oien, Sanjay Popat, Doris Rassl, Rowena Sharpe, Phillipe Taniere, Ian Walker, William A. Wallace, Nicholas P. West, Rachel Butler, David Gonzalez de Castro, Mike Griffiths, Peter W.M. Johnson, Pauline Rehal, Samantha Butler, Matthew Smith, Rachel Doak, Anna Tanska, Graham Halford, Lisa James, Chris Kotara, Gareth Masson, Sam Clokie, Jennie Bell, Fiona Macdonald, David Gonzalez De Castro, Lisa Thompson, Debbie Mair, Suzanne Lillis, Dorte Wren, Robert Hollifield, Keeda Dover, Manisha Maurya, Damian Brooks, Belen Gomez, Lisa Grady, Thomas Jones, Chantal Hooper, Daphne Webster, Jolyon Travis, Stephanie Ogwuru, Jana Gazdova, Denise Collins, Elaine Chapman, Lisa Leavey, Paula Proszek, Sanna Hulkki, V.Peter Collins, Ash Ibrahim, Kat Brown, Jo Burge, Karen Burnett, Ginny Devonshire, Ellen Moseley, Bev Haynes, Charlotte Hodgkin, Merche Jimenez-linan, Linda Jones, Gilly Kenyon, Betania Mahler-araujo, Karen Payne, Jo Piper, Sue Richardson, Ed Rytina, Anne Warren, Liz Coker, Gemma Godsall, Mark Arends, Amanda O’Neill, Katy Rintoul, Donna Goymer, Julie Taylor, Claire Matthews, Harshil Bhayani, Tina Osalador, Zakiya Niwaz, Anna Higgins, Olivia Bamsey, Janine Salter, Louise Renouf, Glenn Noel-Storr, Helen Roberts, Kasia Gierejko, Paola Knapman, Andrew Wotherspoon, Gordon Stamp, Ayoma Attygailye, Steve Hazell, Peter Osin, Ash Nerurkar, Steven Francis, Marion Runde, Jo Arch, Xavier Chitnis, Bernard Siu, Debra Townsend, Laura Hennelly, Natalie Taylor, Bernadette Johnson, Susie Banerjee, Lynda Pyle, Monica Hamill, Jenny Gyertson, Angela George, Krishna Patel, Karla Pearce, Kim Edmonds, Sarah Sarker, Rosalind Eeles, Liz Bancroft, Sarah Thomas, Yukie Kano, Lisa Rowland, Karen Brooks, Mary O’brien, Jaishree Bhosle, Kathy Priest, Bee Ayite, Jo Severn, Helen Beedham, Nicky Lucas, Kim Tye, Alison Lorentzos, Janine Webb, Sarah Kerr, Lisa Corestav, Diego Bottero, Laura Jell, Janet Thomas, Cheryl Marriott, Neil Rajah, Andy Cole, Dieu Ly, Philippe Taniere, Brendan O’sullivan, Clare Swift, Frances Hughes, Desley Neil, Andrew Hanby, Roz Banks, Dolapo Ajayi, Alison Barclay, Julia Newton Bishop, Debbie Beirne, Andrew Bernard, Maxine Berry, Jo Bentley, Tim Bishop, Amy Chambers, Jude Clarke, Anne Crossley, Narinder Gahir, Debbie Gibson, Rona Good, Konstantina Grosios, Pat Harnden, Kate Hasler, Damien Hindmarch, Sharon Jackson, Colin Johnstone, Anne-marie Jones, Gil Lambert, Sally Lane, Nicola Mcnicholas, Rebecca Millican-Slater, Cath Moriaty, Alex Newsham, Kara O’connell, Lisa Ripley, David Sebag-Montefiore, Mary Simpson, Val Speirs, Joh Sugden, Lauren Tate, Emma Tidswell, Chris Twelves, Christy Walker, Barry Waterhouse, Martin Waugh, Louise White, Elizabeth Wright, Jane Rogan, Garry Ashton, Caron Abbey, Michelle Greenhalgh, Daisuke Nonaka, Elwyn Shing, Carmen Gibbard, Georgina Burton, Naomi Fawkes, Angela Marsden, Rachael Waddington, Phil Harrison, Shahrzad Moghadam, Kate Murray, Sarah Brown, Christy Mitchinson, Richard Booton, Rajesh Shah, David Harrison, Anca Oniscu, William Wallace, Frances Rae, Craig Marshall, Linda Mcleod, Morag Charles, Sarah Jane Sutherland, Carol Dawson, Paul Mitchell, Alex Maclellan, Sandra Muir, Lynne Johnstone, John O’connor, Shirley Johnstone, Jim Mcpherson, Jane Hair, Massimo Pignatelli, Roma Armstrong, Karin Oien, Jeff Evans, Margaret Burgoyne, Karen Blessing, Fraser Duthie, Colin Moyes, Elizabeth Mallon, David Millan, Fiona Roberts, Morag Seywright, Siobhan Fraser, Ian Ford, Sharon Kean, Marion Flood, David Grant, Claire Mcdonald, Tom Moffat, Hugh Mclelland, Alistair Kyle, Graham Cameron, Martin Wright, Stephen Kenny, Karen Mcauslan, Andrew Jones, Ted Fitzsimons, Fiona Graham, Alexandra Bell, Phil Duffy, Alec Fisher, Alexis Smith, Elaine Shannon, Bryan Woods, Colin Hutchison, Angela Booth, Lyndsay Duffy, Gillian Mcculloch, Hudda Sadiq, Susan Deakin, Steven Haywood, Malcolm Mason, John Chester, Alison Parry-jones, Abby Macarthur, Suzanne Williams, David Griffiths, Fiona Morgan, Hazel Bailey, University of St Andrews. School of Medicine, and University of St Andrews. Cellular Medicine Division

Subjects
0301 basic medicine, Cancer Research, Colorectal cancer, stratified medicine, NDAS, Context (language use), cruk, lung, RC0254, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, medicine, cancer, Lung cancer, Manchester Cancer Research Centre, Molecular pathology, business.industry, RC0254 Neoplasms. Tumors. Oncology (including Cancer), ResearchInstitutes_Networks_Beacons/mcrc, Cancer, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Adenocarcinoma, genetic, Ovarian cancer, business
Abstract

This study was supported by Cancer Research UK, AstraZeneca and Pfizer UK. Introduction: Phase I of the Cancer Research UK Stratified Medicine Programme (SMP1) was designed to roll out molecular pathology testing nationwide at the point of cancer diagnosis, as well as facilitate an infrastructure where surplus cancer tissue could be used for research. It offered a non-trial setting to examine common UK cancer genetics in a real-world context. Methods: A total of 26 sites in England, Wales and Scotland, recruited samples from 7814 patients for genetic examination between 2011 and 2013. Tumour types involved were breast, colorectal, lung, prostate, ovarian cancer and malignant melanoma. Centralised molecular testing of surplus material from resections or biopsies of primary/metastatic tissue was performed, with samples examined for 3-5 genetic alterations deemed to be of key interest in site-specific cancers by the National Cancer Research Institute Clinical Study groups. Results: 10 754 patients (98% of those approached) consented to participate, from which 7814 tumour samples were genetically analysed. In total, 53% had at least one genetic aberration detected. From 1885 patients with lung cancer, KRAS mutation was noted to be highly prevalent in adenocarcinoma (37%). In breast cancer (1873 patients), there was a striking contrast in TP53 mutation incidence between patients with ductal cancer (27.3%) and lobular cancer (3.4%). Vast inter-tumour heterogeneity of colorectal cancer (1550 patients) was observed, including myriad double and triple combinations of genetic aberrations. Significant losses of important clinical information included smoking status in lung cancer and loss of distinction between low-grade and high-grade serous ovarian cancers. Conclusion: Nationwide molecular pathology testing in a non-trial setting is feasible. The experience with SMP1 has been used to inform ongoing CRUK flagship programmes such as the CRUK National Lung MATRIX trial and TRACERx. Publisher PDF

Published
2018
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