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tumour evolution

Qi Zhang, Zhongduo Wang, Feng Hou, Rachel Harding, Xinyi Huang, Aiping Dong, John R Walker, Yufeng Tong
BACKGROUND: Seven in absentia homologs (SIAHs) comprise a family of highly conserved E3 ubiquitin ligases that play an important role in regulating signalling pathways in tumorigenesis, including the DNA damage repair and hypoxia response pathways. SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high sequence identity of their substrate binding domains (SBDs). Ubiquitin-specific protease USP19 is a deubiquitinase that forms a complex with SIAHs and counteracts the ligase function...
October 21, 2016: Biochimica et Biophysica Acta
Andrew G Nicholson
No abstract text is available yet for this article.
February 2016: Pathology
Maria Zhivagui, Michael Korenjak, Jiri Zavadil
Mutation spectra in cancer genomes provide information on the disease aetiology and the causality underlying the evolution and progression of cancer. Genome-wide mutation patterns reflect the effects of mutagenic insults and can thus reveal past carcinogen-specific exposures and inform hypotheses on the causative factors for specific cancer types. In order to identify mutation profiles in human cancers, single genes studies were first employed, focusing mainly on the tumour suppressor gene TP53. Furthermore, experimental studies had been developed in model organisms...
October 18, 2016: Basic & Clinical Pharmacology & Toxicology
David Hamilton, Vinidh Paleri
Morbidity and mortality associated with increasingly radical doses of chemoradiotherapy have led many to question the current standard of care in head and neck cancer. Recently, surgeons have developed minimally invasive, transoral techniques which have demonstrated excellent survival and favourable functional outcomes. Transoral robotic surgery (TORS) is the most recent, cutting edge in the evolution of transoral techniques; TORS allows surgeons unprecedented access to and visualisation of the upper aerodigestive tract...
October 11, 2016: Surgeon: Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland
Trevor A Graham, Andrea Sottoriva
The temporal dynamics of cancer evolution remain elusive because it is impractical to longitudinally observe cancers unperturbed by treatment. Consequently, our knowledge of how cancers grow largely derives from inferences made from a single point in time - the end point in the cancer's evolution when it is removed from the body and studied in the lab. Fortuitously however, the cancer genome, by virtue of on-going mutations that uniquely mark clonal lineages within the tumour, provides a rich yet surreptitious record of cancer development...
October 14, 2016: Journal of Pathology
Fien Hoefkens, Charlotte Dehandschutter, Johan Somville, Paul Meijnders, Dirk Van Gestel
Soft tissue sarcomas are uncommon tumours of mesenchymal origin, most commonly arising in the extremities. Treatment includes surgical resection in combination with radiotherapy. Resection margins are of paramount importance in surgical treatment of soft tissue sarcomas but unambiguous guidelines for ideal margins of resection are still missing as is an uniform guideline on the use of radiotherapy.The present paper reviews the literature on soft tissue sarcomas of the extremities regarding the required resection margins, the impact of new radiotherapy techniques and the timing of radiotherapy, more particularly if it should be administered before or after surgical resection...
October 12, 2016: Radiation Oncology
Faiyaz Notta, Michelle Chan-Seng-Yue, Mathieu Lemire, Yilong Li, Gavin W Wilson, Ashton A Connor, Robert E Denroche, Sheng-Ben Liang, Andrew M K Brown, Jaeseung C Kim, Tao Wang, Jared T Simpson, Timothy Beck, Ayelet Borgida, Nicholas Buchner, Dianne Chadwick, Sara Hafezi-Bakhtiari, John E Dick, Lawrence Heisler, Michael A Hollingsworth, Emin Ibrahimov, Gun Ho Jang, Jeremy Johns, Lars G T Jorgensen, Calvin Law, Olga Ludkovski, Ilinca Lungu, Karen Ng, Danielle Pasternack, Gloria M Petersen, Liran I Shlush, Lee Timms, Ming-Sound Tsao, Julie M Wilson, Christina K Yung, George Zogopoulos, John M S Bartlett, Ludmil B Alexandrov, Francisco X Real, Sean P Cleary, Michael H Roehrl, John D McPherson, Lincoln D Stein, Thomas J Hudson, Peter J Campbell, Steven Gallinger
Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently...
October 12, 2016: Nature
Giorgia A Osman, Alberto Ricci, Fabrizio Terzo, Carlo Falasca, Maria R Giovagnoli, Pierdonato Bruno, Andrea Vecchione, Salvatore Raffa, Sabatino Valente, Maria R Torrisi, Chiara De Dominicis, Simonetta Giovagnoli, Salvatore Mariotta
INTRODUCTION: Lipoid pneumonia is a clinical condition that may be initially asymptomatic or confused with an infectious or malignant lung disease. OBJECTIVES: We report four cases of this pathological condition. METHODS: The first case concerned an 85-year old woman with bilateral confluent pulmonary opacities, ground-glass type. Diagnosis was based on the cytology of the bronchoalveolar lavage (BAL) fluid followed by its ultrastructural examination...
September 22, 2016: Clinical Respiratory Journal
Shaileja Chopra, Andrés Palencia, Cornelia Virus, Sarah Schulwitz, Brenda R Temple, Stephen Cusack, John Reader
Antibiotic-producing microbes evolved self-resistance mechanisms to avoid suicide. The biocontrol Agrobacterium radiobacter K84 secretes the Trojan Horse antibiotic agrocin 84 that is selectively transported into the plant pathogen A. tumefaciens and processed into the toxin TM84. We previously showed that TM84 employs a unique tRNA-dependent mechanism to inhibit leucyl-tRNA synthetase (LeuRS), while the TM84-producer prevents self-poisoning by expressing a resistant LeuRS AgnB2. We now identify a mechanism by which the antibiotic-producing microbe resists its own toxin...
October 7, 2016: Nature Communications
Kazuhiro Takemoto, Masato Ii, Satoshi S Nishizuka
Elucidation of tumour suppression mechanisms is a major challenge in cancer biology. Therefore, Peto's paradox, or low cancer incidence in large animals, has attracted focus. According to the gene-abundance hypothesis, which considers the increase/decrease in cancer-related genes with body size, researchers evaluated the associations between gene abundance and body size. However, previous studies only focused on a few specific gene functions and have ignored the alternative hypothesis (metabolic rate hypothesis): in this hypothesis, the cellular metabolic rate and subsequent oxidative stress decreases with increasing body size...
September 2016: Royal Society Open Science
Raquel Sopeña-Sutil, Francesco Silan, Maria Teresa Butron-Vila, Felix Guerrero-Ramos, Emilio Lagaron-Comba, Juan Passas-Martinez
Primary paratesticular tumours are very rare and the spermatic cord (SCT) is the most frequent site of origin, with 20% of malignancy. Although liposarcoma is the most frequent histotype (46.6 %), less than 200 cases have been reported in the literature. We report the case of a 56-year-old man who presented a giant scrotal mass of 25 years of evolution and measuring 40 × 40 cm. It could be considered the greatest paratesticular liposarcoma described to date. Computed tomogaphy (CT) revealed mass features consistent with liposarcoma and the simultaneous presence of bilateral inguinal hernia with bladder involvement...
September 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Gustav van Niekerk, Lester M Davids, Suzèl M Hattingh, Anna-Mart Engelbrecht
The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells. Similarly, pro-survival or proliferation signalling often exhibited by stem cells is regularly reported as being upregulated by CSC. Here we review evidence suggesting that many aspects of CSCs are more readily described by clonal evolution...
September 27, 2016: International Journal of Cancer. Journal International du Cancer
Michael S Nakazawa, Brian Keith, M Celeste Simon
Oxygen availability, along with the abundance of nutrients (such as glucose, glutamine, lipids and albumin), fluctuates significantly during tumour evolution and the recruitment of blood vessels, leukocytes and reactive fibroblasts to complex tumour microenvironments. As such, hypoxia and concomitant nutrient scarcity affect large gene expression programmes, signalling pathways, diverse metabolic reactions and various stress responses. This Review summarizes our current understanding of how these adaptations are integrated in hypoxic tumour cells and their role in disease progression...
September 23, 2016: Nature Reviews. Cancer
Gemma K Alderton
No abstract text is available yet for this article.
September 23, 2016: Nature Reviews. Cancer
Thomas B Brunner
This article aims to review the rationale behind the combination of radiotherapy and chemotherapy. Theoretical concepts describing the principles of the joint effects of chemoradiotherapy are reviewed. Preclinical and clinical evidence are collected and summarised demonstrating the co-operation between the two modalities which form the mainstay of the treatment of most solid tumours. Initially, the evolution of chemoradiotherapy was mostly empirically driven which is true for both, the early studies and the experimental investigations, rather than relying on scientific rationale...
August 2016: Best Practice & Research. Clinical Gastroenterology
Megan B Barnet, Sandra O'Toole, Lisa G Horvath, Christina Selinger, Bing Yu, Chiu Chin Ng, Michael Boyer, Wendy A Cooper, Steven Kao
OBJECTIVES: The evolution of EGFR tyrosine kinase inhibitors (TKIs) has changed the landscape of disease for a subset of patients with NSCLC. Most patients with an EGFR mutation respond to these drugs; however, a proportion show limited or no tumor response. We explored the impact of co-mutation (double or multiple mutation), compared with a single mutation, of the EGFR gene on response to TKIs in a series of patients with metastatic NSCLC. METHODS: We retrospectively analyzed the mutation profiles of nonsquamous NSCLC tested at Royal Prince Alfred Hospital between 2012 and 2015 by MassArray using the OncoCarta v1...
September 14, 2016: Journal of Thoracic Oncology
Nicole M Aiello, David L Bajor, Robert J Norgard, Amine Sahmoud, Neha Bhagwat, Minh N Pham, Toby C Cornish, Christine A Iacobuzio-Donahue, Robert H Vonderheide, Ben Z Stanger
Most cancer-associated deaths result from metastasis. However, it remains unknown whether the size, microenvironment or other features of a metastatic lesion dictate its behaviour or determine the efficacy of chemotherapy in the adjuvant (micrometastatic) setting. Here we delineate the natural history of metastasis in an autochthonous model of pancreatic ductal adenocarcinoma (PDAC), using lineage tracing to examine the evolution of disseminated cancer cells and their associated microenvironment. With increasing size, lesions shift from mesenchymal to epithelial histology, become hypovascular and accumulate a desmoplastic stroma, ultimately recapitulating the primary tumours from which they arose...
2016: Nature Communications
Adriana Rosé, Nicolas André, Viviana R Rozados, Leandro E Mainetti, Mauricio Menacho Márquez, María José Rico, Paula Schaiquevich, Milena Villarroel, Lauro Gregianin, Jaume Mora Graupera, Wendy Gómez García, Sidnei Epelman, Carlos Alasino, Daniel Alonso, Guillermo Chantada, O Graciela Scharovsky
Following previous metronomic meetings in Marseille (2011), Milano (2014), and Mumbai (2016), the first Latin American metronomic meeting was held in the School of Medical Sciences, National University of Rosario, Rosario, Argentina on 27 and 28 of May, 2016. For the first time, clinicians and researchers with experience in the field of metronomics, coming from different countries in Latin America, had the opportunity of presenting and discussing their work. The talks were organised in three main sessions related to experience in the pre-clinical, and clinical (paediatric and adult) areas...
2016: Ecancermedicalscience
Chelsie K Sievers, Luli S Zou, Perry J Pickhardt, Kristina A Matkowskyj, Dawn M Albrecht, Linda Clipson, Jeffery W Bacher, B Dustin Pooler, Fouad J Moawad, Brooks D Cash, Mark Reichelderfer, Tien N Vo, Michael A Newton, Bret R Larget, Richard B Halberg
OBJECTIVE AND DESIGN: The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6-9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness...
September 8, 2016: Gut
Sergii Ivakhno, Camilla Colombo, Stephen Tanner, Philip Tedder, Stefano Berri, Anthony J Cox
MOTIVATION: Large-scale rearrangements and copy number changes combined with different modes of clonal evolution create extensive somatic genome diversity, making it difficult to develop versatile and scalable variant calling tools and create well-calibrated benchmarks. RESULTS: We developed a new simulation framework tHapMix that enables the creation of tumour samples with different ploidy, purity and polyclonality features. It easily scales to simulation of hundreds of somatic genomes, while re-use of real read data preserves noise and biases present in sequencing platforms...
September 7, 2016: Bioinformatics
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