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https://www.readbyqxmd.com/read/28445469/phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#1
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/28444740/chronic-lymphocytic-leukaemia-genomics-and-the-precision-medicine-era
#2
REVIEW
Hussein Ghamlouch, Florence Nguyen-Khac, Olivier A Bernard
Massive genomic analyses have underscored the diversity of chronic lymphocytic leukaemia (CLL) between patients. Genetic heterogeneity of tumour clones within a patient may fuel tumour evolution. Several recurrently deregulated intra-cellular pathways are candidates for targeted therapies that are very promising and are dramatically changing clinical patients' perspectives. In this review we present an overview of the genetic and epigenetic features of CLL and their clinical and biological implications.
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28444558/evolution-of-surgical-treatment-for-rectal-cancer-a-review
#3
Sanjeev Dayal, Nick Battersby, Tom Cecil
Surgery that produces an optimal total mesorectal excision (TME) resection specimen remains the cornerstone of curative rectal cancer management. In the modern era, despite the results of recent randomised trials, laparoscopic TME is a crucial technique in the TME surgery armamentarium. Laparoscopic surgery offers the benefit of magnified views that aid sharp and precise dissection. However operating in the confines of a narrow pelvis, particularly when the mesorectum is bulky, requires significant technical skill...
April 25, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#4
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28429102/improved-systemic-treatment-for-early-breast-cancer-improves-cure-rates-modifies-metastatic-pattern-and-shortens-post-metastatic-survival-35-year-results-from-the-munich-cancer-registry
#5
Dieter Hölzel, Renate Eckel, Ingo Bauerfeind, Bernd Baier, Thomas Beck, Michael Braun, Johannes Ettl, Ulrich Hamann, Marion Kiechle, Sven Mahner, Christian Schindlbeck, Johann de Waal, Nadia Harbeck, Jutta Engel
PURPOSE: Systemic therapies (ATHs) in early breast cancer have improved the survival of breast cancer (BC) patients in recent decades. The magnitude of the changes in overall, metastasis-free (MFS) and post-metastatic (PMS) survival and in the metastasis (MET) pattern will be described. PATIENT AND METHODS: We analysed 60,227 patients with a diagnosis of T-N-M0 BC between 1978 and 2013 and 11,983 patients with metastases (MET) in the Munich Cancer Registry. Patients will be divided into four time periods to identify relationships between BC and METs...
April 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28416802/rna-editing-dependent-epitranscriptome-diversity-in-cancer-stem-cells
#6
REVIEW
Qingfei Jiang, Leslie A Crews, Frida Holm, Catriona H M Jamieson
Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli...
April 18, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28400402/molecular-targeted-therapies-in-adrenal-pituitary-and-parathyroid-malignancies
#7
Anna Angelousi, Georgios K Dimitriadis, Gn Zografos, Svenja Nölting, Gregory A Kaltsas, Ashley B Grossman
Tumourigenesis is a relatively common event in endocrine tissues. Currently, specific guidelines have been developed for common malignant endocrine tumours which also incorporate advances in molecular targeted therapies (MTT), as in thyroid cancer and gastrointestinal neuroendocrine malignancies. However, there is little information regarding the role and efficacy of MTT in the relatively rare malignant endocrine tumours mainly involving the adrenal medulla, adrenal cortex, pituitary and parathyroid glands...
April 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28386771/potential-neoplastic-evolution-of-vero-cells-in-vivo-and-in-vitro-characterization
#8
N A Andreani, S Renzi, G Piovani, P Ajmone Marsan, L Bomba, R Villa, M Ferrari, S Dotti
Vero cell lines are extensively employed in viral vaccine manufacturing. Similarly to all established cells, mutations can occur during Vero cells in vitro amplification which can result in adverse features compromising their biological safety. To evaluate the potential neoplastic evolution of these cells, in vitro transformation test, gene expression analysis and karyotyping were compared among low- (127 and 139 passages) and high-passage (passage 194) cell lines, as well as transformed colonies (TCs). In vivo tumorigenicity was also tested to confirm preliminary in vitro data obtained for low passage lines and TCs...
April 6, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28383788/replication-stress-dna-damage-signalling-and-cytomegalovirus-infection-in-human-medulloblastomas
#9
Jiri Bartek, Olesja Fornara, Joanna Maria Merchut-Maya, Apolinar Maya-Mendoza, Afshar Rahbar, Giuseppe Stragliotto, Helle Broholm, Mikael Svensson, Astrid Sehested, Cecilia Söderberg Naucler, Jiri Bartek, Jirina Bartkova
Medulloblastomas are the most common, and often fatal, paediatric brain tumours that feature high genomic instability, frequent infection by human cytomegalovirus (HCMV) and resistance to radiation and chemotherapy. The causes of the pronounced chromosomal instability and its potential links with HCMV infection and/or resistance to genotoxic therapies remain largely unknown. To address these issues, here we have combined immunohistochemical analysis of a series of 25 paediatric medulloblastomas, complemented by medulloblastoma cell culture models including experimental HCMV infection...
April 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28376306/structure-guided-discovery-of-potent-and-selective-inhibitors-of-erk1-2-from-a-modestly-active-and-promiscuous-chemical-start-point
#10
Richard A Ward, Paul Bethel, Calum Cook, Emma Davies, Judit E Debreczeni, Gary Fairley, Lyman Feron, Vikki Flemington, Mark A Graham, Ryan Greenwood, Nicola Griffin, Lyndsey Hanson, Philip Hopcroft, Tina D Howard, Julian Hudson, Michael James, Clifford D Jones, Christopher R Jones, Scott Lamont, Richard Lewis, Nicola Lindsay, Karen Roberts, Iain Simpson, Steve St-Gallay, Steve Swallow, Jia Tang, Michael Tonge, Zhenhua Wang, Baochang Zhai
There are a number of small-molecule inhibitors targeting the RAS/RAF/MEK/ERK signaling pathway that have either been approved or are in clinical development for oncology across a range of disease indications. The inhibition of ERK1/2 is of significant current interest, as cell lines with acquired resistance to BRAF and MEK inhibitors have been shown to maintain sensitivity to ERK1/2 inhibition in preclinical models. This article reports on our recent work to identify novel, potent, and selective reversible ERK1/2 inhibitors from a low-molecular-weight, modestly active, and highly promiscuous chemical start point, compound 4...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28374866/overexpression-of-chromatin-assembly-factor-1-p60-predicts-biological-behaviour-of-laryngeal-carcinomas
#11
M Mesolella, B Iorio, M Landi, M Cimmino, G Ilardi, M Iengo, M Mascolo
This study analysed the immunohistochemical expression of the CAF-1/p60 protein in laryngeal cancers. CAF-1/p60 assumes an independent discriminative and prognostic value in laryngeal neoplasms; the presence of this protein in carcinoma in situ compared with laryngeal precancerous and larynx infiltrating tumours. We assessed the immunohistochemical expression of CAF-1/p60 in 30 cases of moderate and/or severe dysplasia, 30 cases of carcinoma in situ and 30 cases of laryngeal squamous cell carcinoma (LSCCs)...
February 2017: Acta Otorhinolaryngologica Italica
https://www.readbyqxmd.com/read/28369925/cousins-not-twins-intra-and-inter-tumoral-heterogeneity-in-syndromic-neuroendocrine-tumours
#12
Aidan Flynn, Trisha Dwight, Diana Benn, Siddhartha Deb, Andrew J Colebatch, Stephen Fox, Jessica Harris, Emma L Duncan, Bruce Robinson, Annette Hogg, Jason Ellul, Henry To, Cuong Duong, Julie A Miller, Christopher Yates, Paul James, Alison Trainer, Anthony J Gill, Roderick Clifton-Bligh, Rodney J Hicks, Richard W Tothill
Hereditary endocrine neoplasias, including phaeochromocytoma/paraganglioma and medullary thyroid cancer, are caused by autosomal dominant mutations in several familial cancer genes. A common feature of these diseases is the presentation of multiple primary tumours, or multifocal disease representing independent tumour clones that have arisen from the same initiating genetic lesion, but have undergone independent clonal evolution. Such tumours provide an opportunity to discover common co-operative changes required for tumorigenesis, while controlling for the genetic background of the individual...
March 31, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28362812/extensive-telomere-erosion-is-consistent-with-localised-clonal-expansions-in-barrett-s-metaplasia
#13
Boitelo T Letsolo, Rhiannon E Jones, Jan Rowson, Julia W Grimstead, W Nicol Keith, Gareth J S Jenkins, Duncan M Baird
Barrett's oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett's oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information...
2017: PloS One
https://www.readbyqxmd.com/read/28359078/safety-and-utility-of-image-guided-research-biopsies-in-relapsed-high-grade-serous-ovarian-carcinoma-experience-of-the-britroc-consortium
#14
T Goranova, D Ennis, A M Piskorz, G Macintyre, L A Lewsley, J Stobo, C Wilson, D Kay, R M Glasspool, M Lockley, E Brockbank, A Montes, A Walther, S Sundar, R Edmondson, G D Hall, A Clamp, C Gourley, M Hall, C Fotopoulou, H Gabra, S Freeman, L Moore, M Jimenez-Linan, J Paul, J D Brenton, I A McNeish
BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA...
March 30, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28358668/evolution-of-18-f-fluorodeoxyglucose-and-18-f-fluoroazomycin-arabinoside-pet-uptake-distributions-in-lung-tumours-during-radiation-therapy
#15
Dario Di Perri, John A Lee, Anne Bol, François-Xavier Hanin, Guillaume Janssens, Daniel Labar, Annie Robert, Edmond Sterpin, Xavier Geets
BACKGROUND: Dose painting (DP) aims to improve radiation therapy (RT) outcome by targeting radioresistant tumour regions identified through functional imaging, e.g., positron emission tomography (PET). Importantly, the expected benefit of DP relies on the ability of PET imaging to identify tumour areas which could be consistently targeted throughout the treatment. In this study, we analysed the spatial stability of two potential DP targets in lung cancer patients undergoing RT: the tumour burden surrogate [(18)F]fluorodeoxyglucose (FDG) and the hypoxia surrogate [(18)F]fluoroazomycin arabinoside (FAZA)...
April 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28330704/an-update-on-non-extremity-soft-tissue-sarcomas
#16
S J Ford, L M Almond, A Gronchi
The management of soft tissue sarcoma is challenging and varied. Centralisation of management in high volume specialist centres has revolutionised outcomes. Surgery remains the mainstay of treatment and is currently the only potentially curative therapy. Retroperitoneal soft tissue sarcoma presents a particular challenge to the surgical oncologist and the concept of extended resection to include surrounding expendable organs taken en bloc with the tumour has now largely been adopted. The use of neoadjuvant and adjuvant therapies for retroperitoneal soft tissue sarcoma is still to be established, although they are employed on a case-specific basis...
March 19, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28303898/circulating-tumour-dna-reflects-treatment-response-and-clonal-evolution-in-chronic-lymphocytic-leukaemia
#17
Paul Yeh, Tane Hunter, Devbarna Sinha, Sarah Ftouni, Elise Wallach, Damian Jiang, Yih-Chih Chan, Stephen Q Wong, Maria Joao Silva, Ravikiran Vedururu, Kenneth Doig, Enid Lam, Gisela Mir Arnau, Timothy Semple, Meaghan Wall, Andjelija Zivanovic, Rishu Agarwal, Pasquale Petrone, Kate Jones, David Westerman, Piers Blombery, John F Seymour, Anthony T Papenfuss, Mark A Dawson, Constantine S Tam, Sarah-Jane Dawson
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28301871/a-unified-model-of-the-hierarchical-and-stochastic-theories-of-gastric-cancer
#18
REVIEW
Yanjing Song, Yao Wang, Chuan Tong, Hongqing Xi, Xudong Zhao, Yi Wang, Lin Chen
Gastric cancer (GC) is a life-threatening disease worldwide. Despite remarkable advances in treatments for GC, it is still fatal to many patients due to cancer progression, recurrence and metastasis. Regarding the development of novel therapeutic techniques, many studies have focused on the biological mechanisms that initiate tumours and cause treatment resistance. Tumours have traditionally been considered to result from somatic mutations, either via clonal evolution or through a stochastic model. However, emerging evidence has characterised tumours using a hierarchical organisational structure, with cancer stem cells (CSCs) at the apex...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28294139/imaging-to-study-solid-tumour-origin-and-progression-lessons-from-research-and-clinical-oncology
#19
REVIEW
Stefania Raimondo, Giovanni Zito
Biomedical imaging in recent decades has clarified our understanding of normal and pathological cellular processes in vivo. In particular, this approach recently provided insights into processes occurring at a molecular or genetic level rather than at the anatomical level. The evolution of this discipline by engineering have led to its integration into biomedical research to (1) increase sensitivity and resolution imaging and to (2) improve tissue and cell specificity. Currently, imaging approaches are used in three different biomedical areas: (a) identification of cellular processes in physiological and disease state, (b) in vivo single cell imaging, and (c) identification of new prognostic and therapeutical strategies...
March 15, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28279477/the-evolution-of-differentiated-thyroid-cancer
#20
REVIEW
Sylvia L Asa
Differentiated thyroid tumours of follicular cell derivation have traditionally been classified based on architecture, cytology, or both. The features that distinguish the various entities are controversial and diagnostic criteria are inconsistent and often irreproducible. The complexity of classification schemes has not been substantiated by molecular profiling. In this review, a simplistic approach to the diagnosis of well differentiated thyroid neoplasia is provided to challenge the dogma. The proposed classification matches the molecular profiles of these lesions and simplifies the criteria for diagnosis...
April 2017: Pathology
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