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Colon cancer subtype

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https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#1
Paloma Cejas, Alessia Cavazza, Chandri Yandava, Víctor Moreno, David Horst, Juan Moreno-Rubio, Emilio Burgos, Marta Mendiola, Len Taing, Ajay Goel, Jaime Feliu, Ramesh A Shivdasani
Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27859268/heterogeneity-of-colorectal-cancer-risk-by-tumour-characteristics-large-prospective-study-of-uk-women
#2
Andrea Burón Pust, Rupert Alison, Roger Blanks, Kirstin Pirie, Kezia Gaitskell, Isobel Barnes, Toral Gathani, Gillian Reeves, Valerie Beral, Jane Green
Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK-based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across 3 anatomical sites and 4 morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow-up via record linkage to national cancer registry data...
November 18, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27849044/colon-cancer-subtypes-concordance-effect-on-survival-and-selection-of-the-most-representative-preclinical-models
#3
Zsófia Sztupinszki, Balázs Győrffy
Multiple gene-expression-based subtypes have been proposed for the molecular subdivision of colon cancer in the last decade. We aimed to cross-validate these classifiers to explore their concordance and their power to predict survival. A gene-chip-based database comprising 2,166 samples from 12 independent datasets was set up. A total of 22 different molecular subtypes were re-trained including the CCHS, CIN25, CMS, ColoGuideEx, ColoGuidePro, CRCassigner, MDA114, Meta163, ODXcolon, Oncodefender, TCA19, and V7RHS classifiers as well as subtypes established by Budinska, Chang, DeSousa, Marisa, Merlos, Popovici, Schetter, Yuen, and Watanabe (first authors)...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27846243/bacterially-associated-transcriptional-remodelling-in-a-distinct-genomic-subtype-of-colorectal-cancer-provides-a-plausible-molecular-basis-for-disease-development
#4
Katie S Lennard, Ryan W Goosen, Jonathan M Blackburn
The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC...
2016: PloS One
https://www.readbyqxmd.com/read/27821903/proteomic-approaches-to-biomarker-discovery-in-cutaneous-t-cell-lymphoma
#5
REVIEW
Alexandra Ion, Iris Maria Popa, Laura Maria Lucia Papagheorghe, Cristina Lisievici, Mihai Lupu, Vlad Voiculescu, Constantin Caruntu, Daniel Boda
Cutaneous T-cell lymphoma (CTCL) is the most frequently encountered type of skin lymphoma in humans. CTCL encompasses multiple variants, but the most common types are mycosis fungoides (MF) and Sezary syndrome (SS). While most cases of MF run a mild course over a period of many years, other subtypes of CTCL are very aggressive. The rapidly expanding fields of proteomics and genomics have not only helped increase knowledge concerning the carcinogenesis and tumor biology of CTCL but also led to the discovery of novel markers for targeted therapy...
2016: Disease Markers
https://www.readbyqxmd.com/read/27798442/the-genetics-and-molecular-biology-of-colonic-neoplasia-practical-implications-for-the-clinician
#6
Sanjib Chowdhury, Hemant K Roy
PURPOSE OF REVIEW: Despite the large investment of resources from screening, the fact that colorectal cancer remains the second leading cause of cancer deaths among Americans underscores the need for alternative strategies. Thus, a major clinical and research imperative is personalize clinical care, while focusing on risk stratification for screening, surveillance, chemoprevention, and therapeutic intervention. RECENT FINDINGS: A complicating factor that colorectal cancer is biologically heterogeneous for at least four consensus molecular subtypes presents clear challenges for developing robust molecular biomarkers...
October 27, 2016: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/27746011/physical-activity-and-incident-chronic-diseases-a-longitudinal-observational-study-in-16-european-countries
#7
Philipe de Souto Barreto, Matteo Cesari, Sandrine Andrieu, Bruno Vellas, Yves Rolland
INTRODUCTION: The minimum frequency of physical activity associated with reduced risk for onset of several chronic diseases is not well established. Therefore, this study examined, in a large sample of citizens from 16 European countries, the predictive value of physical activity frequency and intensity on the incidence of heart diseases, cerebrovascular diseases, diabetes, cancer of any subtype, breast cancer, and colon/rectum cancer. METHODS: Using data from the longitudinal Survey of Health, Ageing, and Retirement in Europe, the long-term associations of physical activity with incident diseases in people aged ≥50 years were investigated...
October 13, 2016: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/27737436/association-of-proton-pump-inhibitors-and-capecitabine-efficacy-in-advanced-gastroesophageal-cancer-secondary-analysis-of-the-trio-013-logic-randomized-clinical-trial
#8
Michael P Chu, J Randolph Hecht, Dennis Slamon, Zev A Wainberg, Yung-Jue Bang, Paulo M Hoff, Alberto Sobrero, Shukui Qin, Karen Afenjar, Vincent Houe, Karen King, Sheryl Koski, Karen Mulder, Julie Price Hiller, Andrew Scarfe, Jennifer Spratlin, Yingjie J Huang, Saba Khan-Wasti, Neil Chua, Michael B Sawyer
Importance: Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. Objective: To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. Design, Setting, and Participants: This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib...
October 13, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27729552/impaired-coordination-between-signaling-pathways-is-revealed-in-human-colorectal-cancer-using-single-cell-mass-cytometry-of-archival-tissue-blocks
#9
Alan J Simmons, Cherié R Scurrah, Eliot T McKinley, Charles A Herring, Jonathan M Irish, M Kay Washington, Robert J Coffey, Ken S Lau
Cellular heterogeneity poses a substantial challenge to understanding tissue-level phenotypes and confounds conventional bulk analyses. To analyze signaling at the single-cell level in human tissues, we applied mass cytometry using cytometry time of flight to formalin-fixed, paraffin-embedded (FFPE) normal and diseased intestinal specimens. This technique, called FFPE-DISSECT (disaggregation for intracellular signaling in single epithelial cells from tissue), is a single-cell approach to characterizing signaling states in embedded tissue samples...
October 11, 2016: Science Signaling
https://www.readbyqxmd.com/read/27712196/identifying-cancer-type-specific-oncogenes-and-tumor-suppressors-using-limited-size-data
#10
Ana B Pavel, Cristian I Vasile
Cancer is a complex and heterogeneous genetic disease. Different mutations and dysregulated molecular mechanisms alter the pathways that lead to cell proliferation. In this paper, we explore a method which classifies genes into oncogenes (ONGs) and tumor suppressors. We optimize this method to identify specific (ONGs) and tumor suppressors for breast cancer, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and colon adenocarcinoma (COAD), using data from the cancer genome atlas (TCGA). A set of genes were previously classified as ONGs and tumor suppressors across multiple cancer types (Science 2013)...
August 31, 2016: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/27687006/fatty-acid-binding-protein-1-is-preferentially-lost-in-microsatellite-instable-colorectal-carcinomas-and-is-immune-modulated-via-the-interferon-%C3%AE-pathway
#11
Stephanie M Wood, Anthony J Gill, Alexander S Brodsky, Shaolei Lu, Kenneth Friedman, Galina Karashchuk, Kara Lombardo, Dongfang Yang, Murray B Resnick
Fatty acid-binding protein 1 (FABP1) is an intracellular protein responsible for the transportation of long chain fatty acids. Aside from its functions in lipid metabolism and cellular differentiation, FABP1 also plays a role in inflammation through its interaction with peroxisome proliferator-activated receptors (PPARs). Previously, we compared expression of colonic epithelium genes in a subset of microsatellite instable (MSI) colorectal carcinomas (medullary carcinomas) to normal colonic mucosa and found that FABP1 expression was markedly decreased in the tumors...
September 30, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27663504/bcl-2-system-analysis-identifies-high-risk-colorectal-cancer-patients
#12
Andreas U Lindner, Manuela Salvucci, Clare Morgan, Naser Monsefi, Alexa J Resler, Mattia Cremona, Sarah Curry, Sinead Toomey, Robert O'Byrne, Orna Bacon, Michael Stühler, Lorna Flanagan, Richard Wilson, Patrick G Johnston, Manuel Salto-Tellez, Sophie Camilleri-Broët, Deborah A McNamara, Elaine W Kay, Bryan T Hennessy, Pierre Laurent-Puig, Sandra Van Schaeybroeck, Jochen H M Prehn
OBJECTIVE: The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). DESIGN: Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC...
September 23, 2016: Gut
https://www.readbyqxmd.com/read/27649552/a-stepwise-integrated-approach-to-personalized-risk-predictions-in-stage-iii-colorectal-cancer
#13
Manuela Salvucci, Maximilian L Würstle, Clare Morgan, Sarah Curry, Mattia Cremona, Andreas U Lindner, Orna Bacon, Alexa J Resler, Aine C Murphy, Robert O'Byrne, Lorna Flanagan, Sonali Dasgupta, Nadege Rice, Camilla Pilati, Elisabeth Zink, Lisa M Schöller, Sinead Toomey, Mark Lawler, Patrick G Johnston, Richard H Wilson, Sophie Camilleri-Broët, Manuel Salto-Tellez, Deborah A McNamara, Elaine W Kay, Pierre Laurent-Puig, Sandra Van Schaeybroeck, Bryan T Hennessy, Daniel B Longley, Markus Rehm, Jochen Hm Prehn
PURPOSE: Apoptosis is essential for chemotherapy responses. In this discovery and validation study, we evaluated the suitability of a mathematical model of apoptosis execution (APOPTO-CELL) as a stand-alone signature and as a constituent of further refined prognostic stratification tools. EXPERIMENTAL DESIGN: Apoptosis competency of primary tumor samples from n=120 stage III colorectal cancer patients was calculated by APOPTO-CELL from measured protein concentrations of Procaspase-3, Procaspase-9, SMAC and XIAP...
September 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27632639/plasma-mir-122-and-mir-200-family-are-prognostic-markers-in-colorectal-cancer
#14
Melanie Maierthaler, Axel Benner, Michael Hoffmeister, Harald Surowy, Lina Jansen, Phillip Knebel, Jenny Chang-Claude, Hermann Brenner, Barbara Burwinkel
Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards...
January 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27599396/clinical-significance-of-cd44-variant-9-expression-as-a-prognostic-indicator-in-bladder-cancer
#15
Keita Kobayashi, Hiroaki Matsumoto, Hideyasu Matsuyama, Nakanori Fujii, Ryo Inoue, Yoshiaki Yamamoto, Kazuhiro Nagao
CD44, a major surface receptor for hyaluronic acid, has multiple isoforms and represents a major cancer stem cell marker for various epithelial tumors. CD44 variant 9 (CD44v9) was correlated with recurrence and metastasis in gastric and colon cancer. We examined its role in invasion and as a biomarker for the basal muscle invasive molecular subtype showing worse prognosis, and for tumor progression in high risk (pT1/high grade) non‑muscle invasive bladder cancers (NMIBCs). CD44v9, cytokeratin 5/6 (CK5/6), and cytokeratin 20 (CK20) expression was evaluated by immunohistochemistry in 98 pathologically confirmed specimens (36 muscle and 62 high‑risk non‑muscle) and correlated to clinical outcome...
September 1, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27595862/elevated-risk-of-subsequent-malignancies-in-patients-with-appendiceal-cancer-a-population-based-analysis
#16
Adil Ayub, Om Parkash, Norberto Santana-Rodríguez, Wissam Raad, Faiz Y Bhora
BACKGROUND: Appendiceal cancer is extremely rare with excellent survival after curative resection. There is a concern for the development of additional cancers in survivors of appendiceal cancer. However, existing data is limited to small anecdotal reports on appendiceal carcinoid only. We aim to investigate the risk of subsequent malignancies in patients with appendiceal carcinoma and correlate the risk according to patient and clinical characteristics. METHODS: We identified 3788 patients with appendiceal cancer from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database between 1992 and 2011...
September 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/27589478/high-expression-of-the-notch-ligand-jagged-1-is-associated-with-poor-prognosis-after-surgery-for-colorectal-cancer
#17
Masakazu Sugiyama, Eiji Oki, Yu Nakaji, Satoshi Tsutsumi, Naomi Ono, Ryota Nakanishi, Masahiko Sugiyama, Yuichiro Nakashima, Hideto Sonoda, Kippei Ohgaki, Nami Yamashita, Hiroshi Saeki, Shinji Okano, Hiroyuki Kitao, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara
: The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS), and relapse-free survival (RFS) were evaluated...
September 2, 2016: Cancer Science
https://www.readbyqxmd.com/read/27582648/the-multidisciplinary-management-of-colorectal-cancer-present-and-future-paradigms
#18
REVIEW
Chelsie K Sievers, Jeremy D Kratz, Luke D Zurbriggen, Noelle K LoConte, Sam J Lubner, Natalya Uboha, Daniel Mulkerin, Kristina A Matkowskyj, Dustin A Deming
As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences...
September 2016: Clinics in Colon and Rectal Surgery
https://www.readbyqxmd.com/read/27563825/two-subtypes-of-colorectal-tumor-with-distinct-molecular-features-in-familial-adenomatous-polyposis
#19
Kiyoko Takane, Keisuke Matsusaka, Satoshi Ota, Masaki Fukuyo, Yao Yue, Motoi Nishimura, Eiji Sakai, Kazuyuki Matsushita, Hideaki Miyauchi, Hiroyuki Aburatani, Yukio Nakatani, Tadatoshi Takayama, Hisahiro Matsubara, Kiwamu Akagi, Atsushi Kaneda
While sporadic colorectal cancer (CRC) is classified into several molecular subtypes, stratification of familial colorectal tumors is yet to be well investigated. We previously established two groups of methylation markers through genome-wide DNA methylation analysis, which classified sporadic CRC and adenoma into three distinct subgroups: high-, intermediate-, and low-methylation epigenotypes. Here, we investigated familial adenomatous polyposis (FAP), through quantitative methylation analysis of 127 samples (16 cancers, 96 adenomas, and 15 benign mucosa from 14 patients with FAP) using six Group-1 and 14 Group-2 methylation markers, APC, BRAF, and KRAS mutation analysis, and CTNNB1 and TP53 immunohistochemical analysis...
August 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27529686/voltage-gated-sodium-channel-nav-1-7-promotes-gastric-cancer-progression-through-macc1-mediated-upregulation-of-nhe1
#20
Jianling Xia, Na Huang, Hongxiang Huang, Li Sun, Shaoting Dong, Jinyu Su, Jingwen Zhang, Lin Wang, Li Lin, Min Shi, Jianping Bin, Yulin Liao, Nailin Li, Wangjun Liao
Voltage-gated sodium channels (VGSCs), which are aberrantly expressed in several human cancers, affect cancer cell behavior; however, their role in gastric cancer (GC) and the link between these channels and tumorigenic signaling remain unclear. The aims of this study were to determine the clinicopathological significance and role of the VGSC Nav 1.7 in GC progression and to investigate the associated mechanisms. Here, we report that the SCN9A gene encoding Nav 1.7 was the most abundantly expressed VGSC subtype in GC tissue samples and two GC cell lines (BGC-823 and MKN-28 cells)...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
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