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Tumour heterogeneity

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https://www.readbyqxmd.com/read/28097409/genetic-and-epigenetic-intra-tumour-heterogeneity-in-colorectal-cancer
#1
Huw Geraint Jones, Gareth Jenkins, Namor Williams, Paul Griffiths, Phil Chambers, John Beynon, Dean Harris
INTRODUCTION: Colorectal cancer (CRC) is a highly heterogeneous disease, with pathologically similar cancers having completely different responses to treatment and patient survival. Intra-tumour heterogeneity (defined as distinct morphological and phenotypic differences) has recently been demonstrated to be an important factor in the development and behaviour of cancer cells and can be used to determine response to anticancer therapy. METHOD: Patients with resected CRC had DNA extracted from eight defined tumour areas which were analysed for two genetic mutations (BRAF and KRAS) and one epigenetic trait (CpG island methylator phenotype/CIMP)...
January 17, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28078376/ipsilateral-dual-site-same-sitting-percutaneous-lung-biopsy-a-feasibility-study
#2
Joseph Barnett, Aniket N Tavare, Sajid Khan, Ashish Saini, Dean D Creer, Samanjit S Hare
PURPOSE: Patients with thoracic malignancies often have more than one site of pulmonary, nodal or pleural disease within one hemithorax. In addition, large heterogeneous lesions may comprise distinct, mixed pathological entities. Histological analysis of these lesions can alter tumour staging and treatment options. We investigated the feasibility, safety and benefit of performing image-guided percutaneous lung biopsy (PLB) of two lesions in the same hemithorax at a single sitting. MATERIALS AND METHODS: Ten consecutive outpatients with two or more potential disease foci within the same hemithorax were analysed over a 15-month period...
January 11, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28077929/hnrnpa2b1-regulates-the-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-through-the-erk-snail-signalling-pathway
#3
Shengjie Dai, Jie Zhang, Shihao Huang, Bin Lou, Binbo Fang, Tingting Ye, Xince Huang, Bicheng Chen, Mengtao Zhou
BACKGROUND: Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is closely related to tumour occurrence and development, oncogene expression, apoptosis inhibition and invasion and metastasis capacities. However, its function in the epithelial-mesenchymal transition (EMT) of pancreatic cancer is not fully understood. METHODS: By comparing various wild-type pancreatic cancer cell lines, we determined which have a higher expression level of HNRNPA2B1 accompanied by the higher expression of N-cadherin and vimentin and lower expression of E-cadherin...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28076901/nuclear-factor-one-transcription-factors-as-epigenetic-regulators-in-cancer
#4
REVIEW
Mitchell Fane, Lachlan Harris, Aaron G Smith, Michael Piper
Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state...
January 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28075351/circulating-nucleosomes-and-nucleosome-modifications-as-biomarkers-in-cancer
#5
REVIEW
Peter McAnena, James A L Brown, Michael J Kerin
Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment...
January 8, 2017: Cancers
https://www.readbyqxmd.com/read/28071746/allergy-reduces-the-risk-of-meningioma-a-meta-analysis
#6
Peng-Fei Wang, Wen-Jun Ji, Xiao-Hui Zhang, Shou-Wei Li, Chang-Xiang Yan
Meningiomas are the most common brain tumours; however, little is known regarding their aetiology. The data are inconsistent concerning atopic disease and the risk of developing meningioma. Thus, we conducted a meta-analysis to investigate the association between allergic conditions and the risk of developing meningioma. A systematic literature search was conducted using PubMed and Web of SCI from Jan 1979 to Feb 2016. Two investigators independently selected the relevant articles according to the inclusion criteria...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069394/catch-my-drift-making-sense-of-genomic-intra-tumour-heterogeneity
#7
Andrea Sottoriva, Chris P Barnes, Trevor A Graham
The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two of these evolutionary components, the role of drift in cancer evolution has received little attention. Drift occurs when all individuals in the population have the same likelihood of producing surviving offspring, and so by definition a drifting population is one that is evolving neutrally. Here we focus on how neutral evolution is manifested in the cancer genome...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28068672/genomic-hallmarks-of-localized-non-indolent-prostate-cancer
#8
Michael Fraser, Veronica Y Sabelnykova, Takafumi N Yamaguchi, Lawrence E Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Fouad Yousif, Xihui Lin, Andre P Masella, Natalie S Fox, Michael Xie, Stephenie D Prokopec, Alejandro Berlin, Emilie Lalonde, Musaddeque Ahmed, Dominique Trudel, Xuemei Luo, Timothy A Beck, Alice Meng, Junyan Zhang, Alister D'Costa, Robert E Denroche, Haiying Kong, Shadrielle Melijah G Espiritu, Melvin L K Chua, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas B Buchner, Michèle Orain, Valérie Picard, Helène Hovington, Alexander Murison, Ken Kron, Nicholas J Harding, Christine P'ng, Kathleen E Houlahan, Kenneth C Chu, Bryan Lo, Francis Nguyen, Constance H Li, Ren X Sun, Richard de Borja, Christopher I Cooper, Julia F Hopkins, Shaylan K Govind, Clement Fung, Daryl Waggott, Jeffrey Green, Syed Haider, Michelle A Chan-Seng-Yue, Esther Jung, Zhiyuan Wang, Alain Bergeron, Alan Dal Pra, Louis Lacombe, Colin C Collins, Cenk Sahinalp, Mathieu Lupien, Neil E Fleshner, Housheng H He, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D McPherson, Robert G Bristow, Paul C Boutros
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries...
January 9, 2017: Nature
https://www.readbyqxmd.com/read/28060738/the-prognostic-value-of-clonal-heterogeneity-and-quantitative-assessment-of-plasma-circulating-clonal-ig-vdj-sequences-at-diagnosis-in-patients-with-follicular-lymphoma
#9
Clémentine Sarkozy, Sarah Huet, Victoria E H Carlton, Bettina Fabiani, Alain Delmer, Fabrice Jardin, Marie-Helene Delfau-Larue, Maya Hacini, Vincent Ribrag, Stéphanie Guidez, Malek Faham, Gilles Salles
Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plasma samples at diagnosis were available for 34 patients registered in the PRIMA trial (NCT00140582). One tumour clonotype or more could be detected for 29 (85%) and 25 (74%) patients, respectively, in the tumour or plasma samples...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059901/conservative-surgery-for-laryngeal-chondrosarcoma-a-review-of-the-most-recently-proposed-approaches
#10
Cesare Piazza, Alberto Paderno, Piero Nicolai
PURPOSE OF REVIEW: The aim of this study was to describe the most recent technical nuances for resection and reconstruction of Grade 1 and 2 laryngeal chondrosarcomas, with a special emphasis on those located at the level of the cricoid plate, which is the site of origin of the vast majority of these rare tumours. RECENT FINDINGS: Even though inherently based on retrospective small clinical series or anecdotal case reports, a number of studies have been recently published focusing on conservative transoral and open-neck surgical procedures aimed at an oncologically sound removal of the tumour together with organ and function preservation...
January 3, 2017: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/28056859/molecular-chess-hallmarks-of-anti-cancer-drug-resistance
#11
REVIEW
Ian A Cree, Peter Charlton
BACKGROUND: The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years. REVIEW: Resistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28056463/soluble-ve-cadherin-in-metastatic-breast-cancer-an-independent-prognostic-factor-for-both-progression-free-survival-and-overall-survival
#12
Pauline Rochefort, Sylvie Chabaud, Jean-Yves Pierga, Olivier Tredan, Etienne Brain, François-Clément Bidard, Camille Schiffler, Helena Polena, Abir Khalil-Mgharbel, Isabelle Vilgrain, Thomas Bachelot
BACKGROUND: Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC. METHODS: Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study...
January 5, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28055248/review-article-functional-mri-for-quantitative-treatment-response-prediction-in-locally-advanced-rectal-cancer
#13
Trang T Pham, Gary P Liney, Karen Wong, Michael B Barton
Despite advances in multi-modality treatment strategies for locally advanced rectal cancer and improvements in loco-regional control, there is still a considerable variation in response to neo-adjuvant chemo-radiotherapy (CRT). Accurate prediction of response to neo-adjuvant CRT would enable early stratification of management according to good responders and poor responders, in order to adapt treatment to improve therapeutic outcomes in rectal cancer. Clinical studies in diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI have shown promising results for the prediction of therapeutic response in rectal cancer...
January 5, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28051134/validation-of-suitable-normalizers-for-mir-expression-patterns-analysis-covering-tumour-heterogeneity
#14
C Morata-Tarifa, M Picon-Ruiz, C Griñan-Lison, H Boulaiz, M Perán, M A Garcia, J A Marchal
Oncogenic microRNAs (miRs) have emerged as diagnostic biomarkers and novel molecular targets for anti-cancer drug therapies. Real-time quantitative PCR (qPCR) is one of the most powerful techniques for analyzing miRs; however, the use of unsuitable normalizers might bias the results. Tumour heterogeneity makes even more difficult the selection of an adequate endogenous normalizer control. Here, we have evaluated five potential referenced small RNAs (U6, rRNA5s, SNORD44, SNORD24 and hsa-miR-24c-3p) using RedFinder algorisms to perform a stability expression analysis in i) normal colon cells, ii) colon and breast cancer cell lines and iii) cancer stem-like cell subpopulations...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049579/tumour-infiltrating-lymphocytes-and-the-emerging-role-of-immunotherapy-in-breast-cancer
#15
Stephen J Luen, Peter Savas, Stephen B Fox, Roberto Salgado, Sherene Loi
Breast cancer has not previously been considered a highly immunogenic cancer. Observations of tumour-infiltrating lymphocytes (TILs) in and around neoplastic cells in tumour samples, and associations with improved pathological complete response and clinical survival end points have changed our perspective on this. Lymphocytic infiltrates have long been observed in breast cancer; however, more recently, retrospective analysis of prospectively collected tissue samples from clinical trials has demonstrated the potential role of host immunosurveillance in influencing the biology of breast cancer...
December 31, 2016: Pathology
https://www.readbyqxmd.com/read/28047750/we-fg-206-08-pulmonary-functional-imaging-biomarkers-of-nsclc-to-guide-and-optimize-functional-lung-avoidance-radiotherapy
#16
Khadija Sheikh, Dante Pi Capaldi, Douglas A Hoover, David A Palma, Brian P Yaremko, Grace Parraga
PURPOSE: Functional lung avoidance radiotherapy promises optimized therapy planning by minimizing dose to well-functioning lung and maximizing dose to the rest of the lung. Patients with NSCLC commonly present with co-morbid COPD and heterogeneously distributed ventilation abnormalities stemming from emphysema, airways disease, and tumour burden. We hypothesized that pulmonary functional imaging methods may be used to optimize radiotherapy plans to avoid regions of well-functioning lung and significantly improve outcomes like quality-of-life and survival...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046700/mo-de-207b-11-reliability-of-pet-ct-radiomics-features-in-functional-and-morphological-components-of-nsclc-lesions-a-repeatability-analysis-in-a-prospective-multicenter-cohort
#17
M Desseroit, F Tixier, M Majdoub, W Weber, B Siegel, C Cheze Le Rest, D Visvikis, M Hatt
PURPOSE: The goal of this study was to evaluate the repeatability of radiomics features (intensity, shape and heterogeneity) in both PET and low-dose CT components of test-retest FDG-PET/CT images in a prospective multicenter cohort of 74 NSCLC patients from ACRIN 6678 and a similar Merck trial. METHODS: Seventy-four patients with stage III-IV NCSLC were prospectively included. The primary tumor and up to 3 additional lesions per patient were analyzed. The Fuzzy Locally Adaptive Bayesian algorithm was used to automatically delineate metabolically active volume (MAV) in PET...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28035703/human-papillomavirus-related-carcinoma-with-adenoid-cystic-like-features-of-the-sinonasal-tract-clinical-and-morphological-characterization-of-6-new-cases
#18
S Andreasen, J Bishop, T V O Hansen, W H Westra, A Bilde, C von Buchwald, K Kiss
AIMS: Human Papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also not infrequently found in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed HPV-related carcinoma with ACC-like features, only 9 cases have been reported...
December 30, 2016: Histopathology
https://www.readbyqxmd.com/read/28029685/immunoprofile-of-metaplastic-carcinomas-of-the-breast
#19
Emad A Rakha, Nuno D M Coimbra, Zsolt Hodi, Enaam Juneinah, Ian O Ellis, Andrew H S Lee
BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer and its diagnosis in routine practice can be challenging and may require immunohistochemical (IHC) characterisation if no conventional invasive or in situ carcinoma is present. Previous IHC studies of MBC often had a small sample size and did not investigate the different histological subtypes. This study aimed to assess the immunoprofile of MBC subtypes in a large series. METHODS: 172 MBC diagnosed in routine and referral practice in Nottingham over 26 years were reviewed by 3 breast pathologists...
December 28, 2016: Histopathology
https://www.readbyqxmd.com/read/28027312/the-subclonal-architecture-of-metastatic-breast-cancer-results-from-a-prospective-community-based-rapid-autopsy-program-cascade
#20
Peter Savas, Zhi Ling Teo, Christophe Lefevre, Christoffer Flensburg, Franco Caramia, Kathryn Alsop, Mariam Mansour, Prudence A Francis, Heather A Thorne, Maria Joao Silva, Nnennaya Kanu, Michelle Dietzen, Andrew Rowan, Maik Kschischo, Stephen Fox, David D Bowtell, Sarah-Jane Dawson, Terence P Speed, Charles Swanton, Sherene Loi
BACKGROUND: Understanding the cancer genome is seen as a key step in improving outcomes for cancer patients. Genomic assays are emerging as a possible avenue to personalised medicine in breast cancer. However, evolution of the cancer genome during the natural history of breast cancer is largely unknown, as is the profile of disease at death. We sought to study in detail these aspects of advanced breast cancers that have resulted in lethal disease. METHODS AND FINDINGS: Three patients with oestrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and one patient with triple negative breast cancer underwent rapid autopsy as part of an institutional prospective community-based rapid autopsy program (CASCADE)...
December 2016: PLoS Medicine
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