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https://www.readbyqxmd.com/read/28087048/-characteristics-and-risk-factors-for-recurrence-of-cutaneous-squamous-cell-carcinoma-with-conventional-surgery-and-surgery-with-delayed-intraoperative-margin-assessment
#1
Judith Domínguez-Cherit, Georgina Rodríguez-Gutiérrez, Verónica Narváez Rosales, Sonia Toussaint Caire, Verónica Fonte Avalos
BACKGROUND: Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma (SCC). Basal cell carcinoma is the most common and least aggressive but in a low percentage of cases, despite appropriate wide surgical margins, it can be aggressive, producing local invasion, recurrences and distance metastasis. SCC has a more aggressive behaviour invading first the skin, the lymph nodes and less frequently produces distance metastasis OBJECTIVE: To identify the characteristics of recurrent SCC and frequency of new SCC after conventional surgical and primary closure or closure delayed until a histological reporting of tumour-free surgical margins, in order to achieve a better surgical option, in our Mexican population...
January 10, 2017: Cirugia y Cirujanos
https://www.readbyqxmd.com/read/28077607/anatomy-of-mdm2-and-mdm4-in-evolution
#2
REVIEW
Ban Xiong Tan, Hoe Peng Liew, Joy S Chua, Farid J Ghadessy, Yaw Sing Tan, David P Lane, Cynthia R Coffill
Mouse double minute (Mdm) genes span an evolutionary timeframe from the ancient eukaryotic placozoa Trichoplax adhaerens to Homo sapiens, implying a significant and possibly conserved cellular role throughout history. Maintenance of DNA integrity and response to DNA damage involve many key regulatory pathways, including precise control over the tumour suppressor protein p53. In most vertebrates, degradation of p53 through proteasomal targeting is primarily mediated by heterodimers of Mdm2 and the Mdm2-related protein Mdm4 (also known as MdmX)...
January 10, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28073890/pancreatic-cancer-cell-lines-as-patient-derived-avatars-genetic-characterisation-and-functional-utility
#3
Erik S Knudsen, Uthra Balaji, Brian Mannakee, Paris Vail, Cody Eslinger, Christopher Moxom, John Mansour, Agnieszka K Witkiewicz
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. DESIGN: 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28069394/catch-my-drift-making-sense-of-genomic-intra-tumour-heterogeneity
#4
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/28054381/rhabdoid-component-emerging-as-a-subclonal-evolution-of-paediatric-glioneuronal-tumours
#5
A Bertrand, C Rondenet, J Masliah-Planchon, P Leblond, A de la Fourchardière, D Pissaloux, K Aït-Raïs, D Lequin, A Jouvet, P Freneaux, H Sevestre, D Ranchere-Vince, A Tauziede-Espariat, C-A Maurage, K Silva, G Pierron, O Delattre, P Varlet, D Frappaz, F Bourdeaut
Atypical teratoid/rhabdoid tumors (AT/RT) are high-grade tumors partially composed of rhabdoid cells (1). The 1-year overall survival rate is 41% (2). Rhabdoid cells have large eccentric nuclei, a single prominent nucleolus, and abundant cytoplasm with eosinophilic inclusions. The immunohistochemical profile of these cells frequently includes loss of nuclear BAF47 expression due to loss of the SMARCB1 locus combined with a mutation of the other allele (3). This article is protected by copyright. All rights reserved...
January 5, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28050011/consensus-molecular-subtypes-and-the-evolution-of-precision-medicine-in-colorectal-cancer
#6
Rodrigo Dienstmann, Louis Vermeulen, Justin Guinney, Scott Kopetz, Sabine Tejpar, Josep Tabernero
Critical driver genomic events in colorectal cancer have been shown to affect the response to targeted agents that were initially developed under the 'one gene, one drug' paradigm of precision medicine. Our current knowledge of the complexity of the cancer genome, clonal evolution patterns under treatment pressure and pharmacodynamic effects of target inhibition support the transition from a one gene, one drug approach to a 'multi-gene, multi-drug' model when making therapeutic decisions. Better characterization of the transcriptomic subtypes of colorectal cancer, encompassing tumour, stromal and immune components, has revealed convergent pathway dependencies that mandate a 'multi-molecular' perspective for the development of therapies to treat this disease...
January 4, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28045083/pulsation-limited-oxygen-diffusion-in-the-tumour-microenvironment
#7
Edoardo Milotti, Sabrina Stella, Roberto Chignola
Hypoxia is central to tumour evolution, growth, invasion and metastasis. Mathematical models of hypoxia based on reaction-diffusion equations provide seemingly incomplete descriptions as they fail to predict the measured oxygen concentrations in the tumour microenvironment. In an attempt to explain the discrepancies, we consider both the inhomogeneous distribution of oxygen-consuming cells in solid tumours and the dynamics of blood flow in the tumour microcirculation. We find that the low-frequency oscillations play an important role in the establishment of tumour hypoxia...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28040505/dlg1-polarity-protein-expression-associates-with-the-disease-progress-of-low-grade-cervical-intraepithelial-lesions
#8
Ana Laura Cavatorta, Alejandra Di Gregorio, Marina Bugnon Valdano, Federico Marziali, Mariela Cabral, Hebe Bottai, Jorge Cittadini, Ana Lia Nocito, Daniela Gardiol
Human Discs large tumour suppressor (DLG1) participates in regulating cell polarity and proliferation, suggesting an important connection between epithelial organization and cellular growth control. However, it was demonstrated that DLG1 could acquire oncogenic attributes in some specific contexts. In this work, we evaluated the expression of DLG1 and its contribution to the progress of cervical lesions in order to investigate a potential role of this polarity protein in human oncogenic processes. We analyzed cervical biopsies from women with low-grade squamous intraepithelial lesion (LSIL) diagnosis (n=30), for DLG1 expression by immunohistochemistry...
December 29, 2016: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28028655/computer-aided-volumetric-assessment-of-malignant-pleural-mesothelioma-on-ct-using-a-random-walk-based-method
#9
Mitchell Chen, Emma Helm, Niranjan Joshi, Fergus Gleeson, Michael Brady
OBJECTIVE: The aim of this study is to assess the performance of a computer-aided semi-automated algorithm we have adapted for the purpose of segmenting malignant pleural mesothelioma (MPM) on CT. METHODS: Forty-five CT scans were collected from 15 patients (M:F [Formula: see text] 10:5, mean age 62.8 years) in a multi-centre clinical drug trial. A computer-aided random walk-based algorithm was applied to segment the tumour; the results were then compared to radiologist-drawn contours and correlated with measurements made using the MPM-adapted Response Evaluation Criteria in Solid Tumour (modified RECIST)...
December 27, 2016: International Journal of Computer Assisted Radiology and Surgery
https://www.readbyqxmd.com/read/28028387/her2-neu-protein-expression-and-oncogene-amplification-in-gastric-carcinoma-with-clinico-pathological-correlation-in-egyptian-patients
#10
Ahmed Abdel Hadi, Ali El Hindawi, Amal Hareedy, Heba Khalil, Ranya Al Ashiry, Shady Elia, Ahmed Sadek, Mona Magdy, Rafatt Atta, Amgad Anas, Hisham Bakr, Olfat Hammam
AIM: Amplification of the Her2/neu gene and overexpression of the Her2/neu protein in gastric carcinoma (GC) is a golden criterion for target therapy with trastuzumab (Herceptin). We aim to evaluate the immunohistochemical protein expression and amplification of the oncogene Her2/neu by FISH technique in the epithelial gastric carcinoma and to compare their association with different clinicopathologic parameters aiming at identifying positive cases that may benefit from targeted therapy...
December 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28027312/the-subclonal-architecture-of-metastatic-breast-cancer-results-from-a-prospective-community-based-rapid-autopsy-program-cascade
#11
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
https://www.readbyqxmd.com/read/27974798/mechanism-of-early-dissemination-and-metastasis-in-her2-mammary-cancer
#12
Kathryn L Harper, Maria Soledad Sosa, David Entenberg, Hedayatollah Hosseini, Julie F Cheung, Rita Nobre, Alvaro Avivar-Valderas, Chandandaneep Nagi, Nomeda Girnius, Roger J Davis, Eduardo F Farias, John Condeelis, Christoph A Klein, Julio A Aguirre-Ghiso
Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant. Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours. However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases. These findings, and those in pancreatic cancer and melanoma models, indicate that dissemination might occur during the early stages of tumour evolution...
December 14, 2016: Nature
https://www.readbyqxmd.com/read/27957584/evolution-of-laparoscopic-liver-resection-at-singapore-general-hospital-a-nine-year-experience-of-195-consecutive-resections
#13
Brian Kp Goh, Jin-Yao Teo, Chung-Yip Chan, Ser-Yee Lee, Peng-Chung Cheow, Pierce Kh Chow, London Lpj Ooi, Alexander Yf Chung
INTRODUCTION: We aimed to analyse the changing trends, safety and outcomes associated with the adoption of laparoscopic liver resection (LLR) at a single centre. METHODS: A retrospective review was carried out of 195 patients who underwent LLR from 2006 to 2014 at our institution. To explore the evolution of LLR, the study was divided into three equal consecutive time periods (period 1: 2006-2008; period 2: 2009-2011; and period 3: 2012-2014). RESULTS: Among 195 patients who underwent LLR, 24 (12...
December 13, 2016: Singapore Medical Journal
https://www.readbyqxmd.com/read/27943259/mir-203-and-mir-205-expression-patterns-identify-subgroups-of-prognosis-in-cutaneous-squamous-cell-carcinoma
#14
J Cañueto, E Cardeñoso-Álvarez, J L García-Hernández, P Galindo-Villardón, P Vicente-Galindo, J L Vicente-Villardón, D Alonso-López, J De Las Rivas, J Valero, E Moyano-Sáez, E Fernández-López, J H Mao, A Castellanos-Martín, C Román-Curto, J Pérez-Losada
Cutaneous squamous cell carcinoma is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as poor-prognosis diseases, and therefore it is important to identify new markers to better predict its clinical evolution. Here, we identified the expression pattern of miRNAs at different stages of skin cancer progression in a panel of murine skin cancer cell lines. We determined that miR-203 and miR-205 are differentially expressed in this panel, and evaluated their potential use as biomarkers of prognosis in human tumours...
December 11, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27929064/acquired-ras-or-egfr-mutations-and-duration-of-response-to-egfr-blockade-in-colorectal-cancer
#15
Beth O Van Emburgh, Sabrina Arena, Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Giorgio Corti, Benedetta Mussolin, Federica Baldi, Michela Buscarino, Alice Bartolini, Emanuele Valtorta, Joana Vidal, Beatriz Bellosillo, Giovanni Germano, Filippo Pietrantonio, Agostino Ponzetti, Joan Albanell, Salvatore Siena, Andrea Sartore-Bianchi, Federica Di Nicolantonio, Clara Montagut, Alberto Bardelli
Blockade of the epidermal growth factor receptor (EGFR) with the monoclonal antibodies cetuximab or panitumumab is effective in a subset of colorectal cancers (CRCs), but the emergence of resistance limits the efficacy of these therapeutic agents. At relapse, the majority of patients develop RAS mutations, while a subset acquires EGFR extracellular domain (ECD) mutations. Here we find that patients who experience greater and longer responses to EGFR blockade preferentially develop EGFR ECD mutations, while RAS mutations emerge more frequently in patients with smaller tumour shrinkage and shorter progression-free survival...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27927582/clonal-haemopoiesis-and-therapy-related-myeloid-malignancies-in-elderly-patients-a-proof-of-concept-case-control-study
#16
Nancy K Gillis, Markus Ball, Qing Zhang, Zhenjun Ma, YuLong Zhao, Sean J Yoder, Maria E Balasis, Tania E Mesa, David A Sallman, Jeffrey E Lancet, Rami S Komrokji, Alan F List, Howard L McLeod, Melissa Alsina, Rachid Baz, Kenneth H Shain, Dana E Rollison, Eric Padron
BACKGROUND: Clonal haemopoiesis of indeterminate potential (CHIP) is an age-associated genetic event linked to increased risk of primary haematological malignancies and increased all-cause mortality, but the prevalence of CHIP in patients who develop therapy-related myeloid neoplasms is unknown. We did this study to investigate whether chemotherapy-treated patients with cancer who have CHIP are at increased risk of developing therapy-related myeloid neoplasms. METHODS: We did a nested, case-control, proof-of-concept study to compare the prevalence of CHIP between patients with cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls)...
December 2, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#17
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27909934/current-achievements-and-future-perspectives-of-metronomic-chemotherapy
#18
REVIEW
Adriana Romiti, Rosa Falcone, Michela Roberto, Paolo Marchetti
In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated...
December 1, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27905446/genomic-evolution-and-chemoresistance-in-germ-cell-tumours
#19
Amaro Taylor-Weiner, Travis Zack, Elizabeth O'Donnell, Jennifer L Guerriero, Brandon Bernard, Anita Reddy, G Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L Carter, Michelle S Hirsch, Anthony Letai, Christopher Sweeney, Eliezer M Van Allen
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27903276/accurate-prediction-of-response-to-endocrine-therapy-in-breast-cancer-patients-current-and-future-biomarkers
#20
REVIEW
Cigdem Selli, J Michael Dixon, Andrew H Sims
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells...
December 1, 2016: Breast Cancer Research: BCR
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