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tumour evolution

Elisa Vaiani, Cintia Morales, Florencia Soto, Yeny Blanco, Carlos Rugilo, Marta Ciaccio, Alicia Belgorosky
Giant prolactinomas are rare pituitary adenomas characterized by their great local invasion. In this paper, we report a 15-year-old male with left retro-ocular pain and ipsilateral exophthalmos of 4 months of evolution, secondary to a tumour in the base of the skull that invaded the orbit. Hormonal studies revealed serum prolactin of 6913,7 ng/ml (normal value < 20), confirming the diagnosis of giant prolactinoma. The patient started treatment with the dopaminergic agonist cabergoline in increasing doses...
April 1, 2018: Archivos Argentinos de Pediatría
Thomas D Lewin, Philip K Maini, Eduardo G Moros, Heiko Enderling, Helen M Byrne
Current protocols for delivering radiotherapy are based primarily on tumour stage and nodal and metastases status, even though it is well known that tumours and their microenvironments are highly heterogeneous. It is well established that the local oxygen tension plays an important role in radiation-induced cell death, with hypoxic tumour regions responding poorly to irradiation. Therefore, to improve radiation response, it is important to understand more fully the spatiotemporal distribution of oxygen within a growing tumour before and during fractionated radiation...
February 27, 2018: Bulletin of Mathematical Biology
Joël R Federer-Gsponer, Cristina Quintavalle, David C Müller, Tanja Dietsche, Valeria Perrina, Thomas Lorber, Darius Juskevicius, Elisabeth Lenkiewicz, Tobias Zellweger, Thomas Gasser, Michael T Barrett, Cyrill A Rentsch, Lukas Bubendorf, Christian Ruiz
Understanding the evolutionary mechanisms and genomic events leading to castration resistant (CR) prostate cancer (PC) is key to improve the outcome of this otherwise deadly disease. Here, we delineated the tumour history of seven patients progressing to castration resistance by analysing matched prostate cancer tissues before and after castration. We performed genomic profiling of DNA-content based flow-sorted populations in order to define the different evolutionary patterns. In one patient, we discovered that a catastrophic genomic event, known as chromothripsis, resulted in multiple CRPC tumour populations with distinct, potentially advantageous copy number aberrations, including an amplification of FK506 Binding Protein 4 (FKBP4, also known as FKBP52), a protein enhancing the transcriptional activity of androgen receptor signalling...
February 27, 2018: Journal of Pathology
Georgi Tchernev, Jose Carlos Cardoso, Ivan Pidakev, Uwe Wollina, Torello Lotti, Jacopo Lotti, Serena Gianfaldoni, Georgi Konstantinov Maximov, Ilia Lozev
The lip represents an anatomical area of the interface between the skin and oral mucosa. It is, therefore, not entirely surprising that SCC of the lip exhibits mixed features between cutaneous and oral mucosal SCC, namely regarding risk factors and biological behaviour. The main risk factors for lip SCC include ultraviolet radiation exposure, low phototype, tobacco and alcohol use, and immunosuppression. Lip SCC usually presents clinically as a nodule or a tumour with a keratotic surface that commonly ulcerates...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
John W Honour, E Conway, R Hodkinson, F Lam
The metabolites of cortisol, and the intermediates in the pathways from cholesterol to cortisol and the adrenal sex steroids can be analysed in a single separation of steroids by gas chromatography (GC) coupled to MS to give a urinary steroid profile (USP). Steroids individually and in profile are now commonly measured in plasma by liquid chromatography (LC) coupled with MS/MS. The steroid conjugates in urine can be determined after hydrolysis and derivative formation and for the first time without hydrolysis using GC-MS, GC-MS/MS and liquid chromatography with mass spectrometry (LC-MS/MS)...
February 23, 2018: Journal of Steroid Biochemistry and Molecular Biology
Maria Gonzalez-Cao, Clara Mayo de Las Casas, Nuria Jordana Ariza, Jose L Manzano, Miguel Á Molina-Vila, Virtudes Soriano, Teresa Puertolas, Ariadna Balada, Ainara Soria, Margarita Majem, Clara Montagut, Eva Muñoz, Delvys Rodriguez-Abreu, Elisabeth Perez, Almudena Garcia, Javier Cortes, Ana Drozdowskyj, Niki Karachaliou, Rafael Rosell
Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome...
February 23, 2018: Melanoma Research
Thomas Melchardt, Teresa Magnes, Clemens Hufnagl, Aaron R Thorner, Matthew Ducar, Daniel Neureiter, Wolfgang Tränkenschuh, Eckhard Klieser, Alexander Gaggl, Sebastian Rösch, Gerd Rasp, Tanja N Hartmann, Lisa Pleyer, Gabriel Rinnerthaler, Lukas Weiss, Richard Greil, Alexander Egle
BACKGROUND: Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown. PATIENTS AND METHODS: For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer...
February 22, 2018: European Journal of Cancer
C Ricordel, L Friboulet, F Facchinetti, J-C Soria
Lung cancer represents the leading cause of cancer-related deaths worldwide. Despite great advances in its management with the recent emergence of molecular targeted therapies for non-small-cell lung cancer (NSCLC), relapse of the metastatic disease always occurs within approximately one year. Epidermal growth factor receptor (EGFR) mutant tumours are the prime example of oncogene addiction and clonal evolution in oncology, regarding the emergence of resistance to first- and second-generation EGFR inhibitors...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Paul B Sinclair, Helen H Blair, Sarra L Ryan, Lars Buechler, Joanna Cheng, Jake Clayton, Rebecca Hanna, Shaun Hollern, Zoe Hawking, Matthew Bashton, Claire J Schwab, Lisa Jones, Lisa J Russell, Helen Marr, Peter Carey, Christina Halsey, Olaf Heidenreich, Anthony V Moorman, Christine J Harrison
Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of childhood precursor B-cell acute lymphoblastic leukemia. There are no cell lines with iAMP21 and these abnormalities are too complex to faithfully engineer in animal models. As a resource for future functional and pre-clinical studies, we have created xenografts from intrachromosomal amplification of chromosome 21 leukemia patient blasts and characterised them by in-vivo and ex-vivo luminescent imaging, FLOW immunophenotyping, and histological and ultrastructural analysis of bone marrow and the central nervous system...
February 15, 2018: Haematologica
Sylvin Benjamin Ateba, Sadrine Tchoukouegno Ngeu, Marie Alfrede Mvondo, Job Tchoumtchoua, Charline Florence Awounfack, Liselotte Krenn, Dieudonne Njamen
BACKGROUND: The approval of Taxol® in 1993 marked the great entrance of terpenoids in the anti-cancer area and this drug is still highly important in the treatment of refractory ovarian, breast and other cancers. Over decades, other prominent natural terpenoids have become indispensable for the modern pharmacotherapy of breast cancer. However, given the rapid evolution of drug resistance, effective treatments for advanced breast cancers requiring cytotoxic chemotherapy represent a major unmet clinical need...
February 13, 2018: Current Medicinal Chemistry
Tracey Russell, Thomas Madsen, Frédéric Thomas, Nynke Raven, Rodrigo Hamede, Beata Ujvari
Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease (DFTD), a transmissible cancer, afflicting Tasmanian devils (Sarcophilus harrisii), provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts...
February 15, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Zhihao Tan, De Zhi Valerie Chu, Yong Jie Andrew Chan, Yi Ena Lu, Giulia Rancati
Polyploidization, a common event during the evolution of different tumours, has been proposed to confer selective advantages to tumour cells by increasing the occurrence of mutations promoting cancer progression and by conferring chemotherapy resistance. While conditions leading to polyploidy in cancer cells have been described, a general mechanism explaining the incidence of this karyotypic change in tumours is still missing. In this study, we tested whether a widespread tumour microenvironmental condition, low pH, could induce polyploidization in mammalian cells...
February 13, 2018: Scientific Reports
Balázs Sarkadi, Vince Kornél Grolmusz, Henriett Butz, Annamária Kövesdi, István Likó, Gábor Nyirő, Péter Igaz, Attila Patócs
The common features of hereditary endocrine tumour syndromes or multiple endocrine neoplasias (MEN) are the association of various tumours of different endocrine organs in one patient or within the same family. Different types can be distinguished from among which type 1 and type 2 are the most common. The mode of inheritance is autosomal dominant, meaning that there is a 50% chance to inherit the pathogenic alteration. The pathogenic variants of genes responsible for MEN syndromes have also been identified in sporadic endocrine tumours and many cases initially referred to as sporadic have been later categorized as familiar based on genetic analysis...
February 2018: Orvosi Hetilap
Melanie Werner-Klein, Sebastian Scheitler, Martin Hoffmann, Isabelle Hodak, Klaus Dietz, Petra Lehnert, Veronika Naimer, Bernhard Polzer, Steffi Treitschke, Christian Werno, Aleksandra Markiewicz, Kathrin Weidele, Zbigniew Czyz, Ulrich Hohenleutner, Christian Hafner, Sebastian Haferkamp, Mark Berneburg, Petra Rümmele, Anja Ulmer, Christoph A Klein
Mouse models indicate that metastatic dissemination occurs extremely early; however, the timing in human cancers is unknown. We therefore determined the time point of metastatic seeding relative to tumour thickness and genomic alterations in melanoma. Here, we find that lymphatic dissemination occurs shortly after dermal invasion of the primary lesion at a median thickness of ~0.5 mm and that typical driver changes, including BRAF mutation and gained or lost regions comprising genes like MET or CDKNA2, are acquired within the lymph node at the time of colony formation...
February 9, 2018: Nature Communications
Patrizia Burra, Alberto Zanetto, Giacomo Germani
Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized...
February 9, 2018: Cancers
Kent W Hunter, Ruhul Amin, Sarah Deasy, Ngoc-Han Ha, Lalage Wakefield
Tumour heterogeneity poses a substantial problem for the clinical management of cancer. Somatic evolution of the cancer genome results in genetically distinct subclones in the primary tumour with different biological properties and therapeutic sensitivities. The problem of heterogeneity is compounded in metastatic disease owing to the complexity of the metastatic process and the multiple biological hurdles that the tumour cell must overcome to establish a clinically overt metastatic lesion. New advances in sequencing technology and clinical sample acquisition are providing insights into the phylogenetic relationship of metastases and primary tumours at the level of somatic tumour genetics while also illuminating fundamental mechanisms of the metastatic process...
February 9, 2018: Nature Reviews. Cancer
Gabriel Santpere, Ana Alcaráz-Sanabria, Verónica Corrales-Sánchez, Atanasio Pandiella, Balázs Győrffy, Alberto Ocaña
In breast cancer, it is unclear the functional modifications at a transcriptomic level that are associated with the evolution from epithelial cells and ductal carcinoma in situ (DCIS) to basal-like tumors. By applying weighted gene co-expression network analysis (WGCNA), we identified 17 gene co-expression modules in normal, DCIS and basal-like tumor samples. We then correlated the expression pattern of these gene modules with disease progression from normal to basal-like tumours and found eight modules exhibiting a high and statistically significant correlation...
January 2, 2018: Oncotarget
Jeong Hwan Park, Minsun Jung, Kyung Chul Moon
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and it has an unfavourable prognosis compared to other RCCs. Plant homeodomain finger 2 (PHF2) and CCATT/enhancer binding protein α (C/EBPα) play a role in the epigenetic regulation of adipogenesis, and their tumour suppressive functions have been elucidated. This study aimed to assess the nuclear expression of PHF2 and C/EBPα in ccRCC and to evaluate their role in pathogenesis and prognosis. The nuclear expression of PHF2 and C/EBPα was evaluated in 344 cases of ccRCC by immunohistochemistry, and adipogenesis was assessed based on cytoplasmic features...
January 2, 2018: Oncotarget
Kez Cleal, Kevin Norris, Duncan Baird
Telomeres are progressively eroded during repeated rounds of cell division due to the end replication problem but also undergo additional more substantial stochastic shortening events. In most cases, shortened telomeres induce a cell-cycle arrest or trigger apoptosis, although for those cells that bypass such signals during tumour progression, a critical length threshold is reached at which telomere dysfunction may ensue. Dysfunction of the telomere nucleoprotein complex can expose free chromosome ends to the DNA double-strand break (DSB) repair machinery, leading to telomere fusion with both telomeric and non-telomeric loci...
February 6, 2018: International Journal of Molecular Sciences
Maneka Hoonjan, Vaibhav Jadhav, Purvi Bhatt
Arsenic and its various forms have been in use in ancient Chinese medicine for more than 2000 years. Arsenicals have gained importance for having remedial effects for various diseases from syphilis to cancer thus highlighting its role as a therapeutic agent even though it has been labelled as a potential 'poison'. The ability of arsenic, specifically arsenic trioxide, to treat acute promyelocytic leukaemia has radically changed the perception of this poison and has been the main factor for the re-emergence of this candidate to Western medicine for the treatment of leukaemia and other solid tumours...
February 2, 2018: Journal of Biological Inorganic Chemistry: JBIC
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