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British Journal of Cancer

Guillermo de Velasco, Stephanie A Wankowicz, Russell Madison, Siraj M Ali, Craig Norton, Audrey Duquette, Jeffrey S Ross, Dominick Bossé, Aly-Khan A Lalani, Vincent A Miller, Philip J Stephens, Lauren Young, A Ari Hakimi, Sabina Signoretti, Sumanta K Pal, Toni K Choueiri
BACKGROUND: The genomic landscape of primary clear cell renal cell carcinoma (ccRCC) has been well described. However, little is known about cohort genomic alterations (GA) landscape in ccRCC metastases, or how it compares to primary tumours in aggregate. The genomic landscape of metastases may have biological, clinical, and therapeutic implications. METHODS: We collected targeted next-generation sequencing mutation calls from two independent cohorts and described the metastases GA landscape and descriptively compared it to the GA landscape in primary tumours...
April 20, 2018: British Journal of Cancer
Jose Mario Gonzalez-Meljem, John Richard Apps, Helen Christina Fraser, Juan Pedro Martinez-Barbera
Senescent cells activate genetic programmes that irreversibly inhibit cellular proliferation, but also endow these cells with distinctive metabolic and signalling phenotypes. Although senescence has historically been considered a protective mechanism against tumourigenesis, the activities of senescent cells are increasingly being associated with age-related diseases, including cancer. An important feature of senescent cells is the secretion of a vast array of pro-inflammatory cytokines, chemokines, and growth factors collectively known as the senescence-associated secretory phenotype (SASP)...
April 19, 2018: British Journal of Cancer
Jennifer Anne Doherty, Laurie Grieshober, John R Houck, Matt J Barnett, Jean De Dieu Tapsoba, Mark D Thornquist, Ching-Yun Wang, Gary E Goodman, Chu Chen
BACKGROUND: Telomeres protect cells from genomic instability. We examined telomere length and lung cancer risk prospectively in heavy smokers. METHODS: In a nested case-control study with 709 cases and 1313 controls, conditional logistic regression was used to evaluate associations between telomere length (global, chromosome 5p, and 13q) and lung cancer risk by histotype, controlling for detailed smoking history. RESULTS: Risks of overall lung cancer and adenocarcinoma were suggestively elevated among individuals with telomere length in the longest tertile...
April 19, 2018: British Journal of Cancer
David L Phelps, Júlia Balog, Louise F Gildea, Zsolt Bodai, Adele Savage, Mona A El-Bahrawy, Abigail Vm Speller, Francesca Rosini, Hiromi Kudo, James S McKenzie, Robert Brown, Zoltán Takáts, Sadaf Ghaem-Maghami
BACKGROUND: Survival from ovarian cancer (OC) is improved with surgery, but surgery can be complex and tumour identification, especially for borderline ovarian tumours (BOT), is challenging. The Rapid Evaporative Ionisation Mass Spectrometric (REIMS) technique reports tissue histology in real-time by analysing aerosolised tissue during electrosurgical dissection. METHODS: Aerosol produced during diathermy of tissues was sampled with the REIMS interface. Histological diagnosis and mass spectra featuring complex lipid species populated a reference database on which principal component, linear discriminant and leave-one-patient-out cross-validation analyses were performed...
April 19, 2018: British Journal of Cancer
Julia Bergheim, Alexander Semaan, Heidrun Gevensleben, Susanne Groening, Andreas Knoblich, Jörn Dietrich, Julia Weber, Jörg C Kalff, Friedrich Bootz, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) methylation in circulating cell-free DNA (ccfDNA) are powerful biomarkers for colorectal cancer (CRC) screening, as well as head and neck squamous cell carcinoma staging and monitoring. In the present study, we investigated SEPT9 and SHOX2 ccfDNA methylation as auxiliary pre and post-therapeutic staging parameters in CRC patients. METHODS: ccfDNA methylation was quantified in 184 prospectively enrolled patients prior to and 3-10 days after surgery, and biomarker levels were associated with clinico-pathological parameters...
April 3, 2018: British Journal of Cancer
Antigoni Manousopoulou, Annette Hayden, Massimiliano Mellone, Diana J Garay-Baquero, Cory H White, Fergus Noble, Monette Lopez, Gareth J Thomas, Timothy J Underwood, Spiros D Garbis
BACKGROUND: Cancer-associated fibroblasts (CAFs) form the major stromal component of the tumour microenvironment (TME). The present study aimed to examine the proteomic profiles of CAFs vs. normal fibroblasts (NOFs) from patients with oesophageal adenocarcinoma to gain insight into their pro-oncogenic phenotype. METHODS: CAFs/NOFs from four patients were sub-cultured and analysed using quantitative proteomics. Differentially expressed proteins (DEPs) were subjected to bioinformatics and compared with published proteomics and transcriptomics  datasets...
March 29, 2018: British Journal of Cancer
Christopher J D Wallis, Gerard Morton, Sender Herschorn, Ronald T Kodama, Girish S Kulkarni, Sree Appu, Bobby Shayegan, Roger Buckley, Arthur Grabowski, Steven A Narod, Robert K Nam
BACKGROUND: Consultation with radiation oncologists, in addition to urologists, is advocated for patients diagnosed with prostate cancer. Treatment patterns for patients receiving consultation from radiation oncologists in addition to urologists have not previously been described. METHODS: We conducted a matched cohort study of men with newly diagnosed non-metastatic prostate cancer in Ontario, Canada. Patients who underwent consultation with a radiation oncologist prior to treatment were matched 1:1 with patients managed by a urologist alone based on tumour and patient characteristics...
March 29, 2018: British Journal of Cancer
Mariëtte N Verkissen, Dirk Houttekier, Joachim Cohen, Rik Schots, Kenneth Chambaere, Luc Deliens
BACKGROUND: The treatment of advanced cancer often involves potentially life-shortening end-of-life decisions (ELDs). This study aimed to examine the prevalence and characteristics of ELDs in different cancer types. METHODS: A nationwide death certificate study was conducted based on a large random sample of all deaths in Flanders, Belgium, between 1 January and 30 June 2013. All cancer deaths were selected (n = 2392). Attending physicians were sent a questionnaire about ELDs and the preceding decision-making process...
March 29, 2018: British Journal of Cancer
Chitra Joseph, Olivia Macnamara, Madeleine Craze, Roslin Russell, Elena Provenzano, Christopher C Nolan, Maria Diez-Rodriguez, Sultan N Sonbul, Mohammed A Aleskandarany, Andrew R Green, Emad A Rakha, Ian O Ellis, Abhik Mukherjee
BACKGROUND: Mediator complex (MED) proteins have a key role in transcriptional regulation, some interacting with the oestrogen receptor (ER). Interrogation of the METABRIC cohort suggested that MED7 may regulate lymphovascular invasion (LVI). Thus MED7 expression was assessed in large breast cancer (BC) cohorts to determine clinicopathological significance. METHODS: MED7 gene expression was investigated in the METABRIC cohort (n = 1980) and externally validated using bc-GenExMiner v4...
March 28, 2018: British Journal of Cancer
Andrés J Muñoz Martín, Israel Ortega, Carme Font, Vanesa Pachón, Victoria Castellón, Virginia Martínez-Marín, Mercedes Salgado, Eva Martínez, Julia Calzas, Ana Rupérez, Juan C Souto, Miguel Martín, Eduardo Salas, Jose M Soria
BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. Outpatients with cancer should be periodically assessed for VTE risk, for which the Khorana score is commonly recommended. However, it has been questioned whether this tool is sufficiently accurate at identifying patients who should receive thromboprophylaxis. The present work proposes a new index, TiC-Onco risk score to be calculated at the time of diagnosis of cancer, that examines patients' clinical and genetic risk factors for thrombosis...
March 28, 2018: British Journal of Cancer
Jue-Sheng Ong, Jiyuan An, Matthew H Law, David C Whiteman, Rachel E Neale, Puya Gharahkhani, Stuart MacGregor
BACKGROUND: Observational studies have shown that being taller is associated with greater cancer risk. However, the interpretation of such studies can be hampered by important issues such as confounding and reporting bias. METHODS: We used the UK Biobank resource to develop genetic predictors of height and applied these in a Mendelian randomisation framework to estimate the causal relationship between height and cancer. Up to 438,870 UK Biobank participants were considered in our analysis...
March 27, 2018: British Journal of Cancer
Elisabeth F P Peterse, Bertine Niessen, Ruben D Addie, Yvonne de Jong, Arjen H G Cleven, Alwine B Kruisselbrink, Brendy E W M van den Akker, Remco J Molenaar, Anne-Marie Cleton-Jansen, Judith V M G Bovée
INTRODUCTION: Chondrosarcoma is a malignant cartilage-forming bone tumour in which mutations in IDH1 and IDH2 frequently occur. Previous studies suggest an increased dependency on glutaminolysis in IDH1/2 mutant cells, which resulted in clinical trials with the drugs CB-839, metformin and chloroquine. In this study, the preclinical rationale for using these drugs as a treatment for chondrosarcoma was evaluated. METHODS: Expression of glutaminase was determined in 120 cartilage tumours by immunohistochemistry...
March 26, 2018: British Journal of Cancer
Robert J Motzer, Bernard Escudier, Thomas Powles, Christian Scheffold, Toni K Choueiri
BACKGROUND: In the phase 3 METEOR trial (NCT01865747), cabozantinib significantly improved progression-free survival, overall survival, and objective response rate compared with everolimus in patients with advanced renal cell carcinoma (RCC) after prior antiangiogenic therapy. A statistically significant improvement in overall survival was observed at a second interim analysis with 320 recorded deaths. METHODS: 658 patients with advanced RCC who had received at least one prior VEGFR tyrosine kinase inhibitor were randomised 1:1 to cabozantinib (60 mg daily) or everolimus (10 mg daily)...
March 26, 2018: British Journal of Cancer
Isabel Quiros-Gonzalez, Michal R Tomaszewski, Sarah J Aitken, Laura Ansel-Bollepalli, Leigh-Ann McDuffus, Michael Gill, Lina Hacker, Joanna Brunker, Sarah E Bohndiek
BACKGROUND: Optoacoustic tomography (OT) of breast tumour oxygenation is a promising new technique, currently in clinical trials, which may help to determine disease stage and therapeutic response. However, the ability of OT to distinguish breast tumours displaying different vascular characteristics has yet to be established. The aim of the study is to prove OT as a sensitive technique for differentiating breast tumour models with manifestly different vasculatures. METHODS: Multispectral OT (MSOT) was performed in oestrogen-dependent (MCF-7) and oestrogen-independent (MDA-MB-231) orthotopic breast cancer xenografts...
March 26, 2018: British Journal of Cancer
Jin Won Kim, Yun-Gyoo Lee, In Gyu Hwang, Hong Suk Song, Su Jin Koh, Yoon Ho Ko, Seong Hoon Shin, In Sook Woo, Soojung Hong, Tae-Yong Kim, Sun Young Kim, Byung-Ho Nam, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Sung Hwa Bae, Dong-Hoe Koo, Kwang-Il Kim, Jee Hyun Kim
BACKGROUND: Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk. METHODS: Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables. RESULTS: 301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4...
March 26, 2018: British Journal of Cancer
Lin Xin, Wei-Feng Yang, Hou-Ting Zhang, Yi-Fan Li, Chuan Liu
BACKGROUND: To investigate the mechanism of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin. METHODS: Death receptors, anti-apoptotic protein, NF-κB, and TRAIL pathway-related factors were detected. The influence of LV-METase transfection on cell viability and pathway-related proteins were assessed by MTT method and western blot, respectively. Different treatments (NF-κB or caspase-3 inhibitor induction, TRAIL supplement, etc...
March 26, 2018: British Journal of Cancer
Katrina F Brown, Harriet Rumgay, Casey Dunlop, Margaret Ryan, Frances Quartly, Alison Cox, Andrew Deas, Lucy Elliss-Brookes, Anna Gavin, Luke Hounsome, Dyfed Huws, Nick Ormiston-Smith, Jon Shelton, Ceri White, D Max Parkin
BACKGROUND: Changing population-level exposure to modifiable risk factors is a key driver of changing cancer incidence. Understanding these changes is therefore vital when prioritising risk-reduction policies, in order to have the biggest impact on reducing cancer incidence. UK figures on the number of risk factor-attributable cancers are updated here to reflect changing behaviour as assessed in representative national surveys, and new epidemiological evidence. Figures are also presented by UK constituent country because prevalence of risk factor exposure varies between them...
March 23, 2018: British Journal of Cancer
Freddie Bray, Isabelle Soerjomataram
The population attributable fraction is a critical driver of evidence-based cancer prevention. With an increasing recognition of the need for high-level investment in cancer control, there is an overwhelming need for a new generation of descriptive studies that globally promote the long-term public health and economic benefits of cancer prevention.
March 23, 2018: British Journal of Cancer
Judith Offman, Francesca Pesola, Peter Sasieni
BACKGROUND: The aim of this study was to assess the incidence and trends of oesophageal adenocarcinomas (OACs) and squamous cell carcinomas (OSCCs) in England from 1971 to 2037. METHODS: Data on 220,026 oesophageal cancers diagnosed in England between 1971 and 2013 were extracted. Multiple imputation was used to predict morphology data were missing. Incidence rates were modelled and extrapolated to 2037 using age-period-cohort models. RESULTS: The OAC age-standardised incidence rate (ASRs) increase was greatest from 1972 to 1992 (from 4...
March 22, 2018: British Journal of Cancer
D H Palmer, Y T Ma, M Peck-Radosavljevic, P Ross, J Graham, L Fartoux, A Deptala, M Studeny, D Schnell, J Hocke, A-B Loembé, T Meyer
BACKGROUND: This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC). METHODS: Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression...
March 22, 2018: British Journal of Cancer
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