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Colon cancer subtype

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
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
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
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
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
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
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
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...
September 15, 2016: International Journal of Cancer. Journal International du Cancer
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
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
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
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
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
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
Nicole de Rosa, Miguel A Rodriguez-Bigas, George J Chang, Jula Veerapong, Ester Borras, Sunil Krishnan, Brian Bednarski, Craig A Messick, John M Skibber, Barry W Feig, Patrick M Lynch, Eduardo Vilar, Y Nancy You
PURPOSE: DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jason M Knight, Eunji Kim, Ivan Ivanov, Laurie A Davidson, Jennifer S Goldsby, Meredith A J Hullar, Timothy W Randolph, Andrew M Kaz, Lisa Levy, Johanna W Lampe, Robert S Chapkin
The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs...
September 1, 2016: Physiological Genomics
Sang Jae Lee, Sung Chan Park, Min Jung Kim, Dae Kyung Sohn, Jae Hwan Oh
BACKGROUND: The vascular anatomy in the right colon varies; however, related studies are rare, especially on the laparoscopic vascular anatomy of living patients. OBJECTIVE: The purpose of this study was to describe vascular variations around the gastrocolic trunk, middle colic vein, and ileocolic vessels in laparoscopic surgery for right-sided colon cancer. DESIGN: This is a retrospective descriptive study of patients undergoing laparoscopic colectomy for right colon cancer...
August 2016: Diseases of the Colon and Rectum
Koichi Okamoto, Shinji Kitamura, Tetsuo Kimura, Tadahiko Nakagawa, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Tetsuji Takayama
Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers (CRCs). Accordingly, serrated polyps such as traditional serrated adenoma (TSA) and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into 3 subtypes, consisting of hyperplastic polyp (HP), SSA/P, and TSA, according to the World Health Organization (WHO) classification...
July 4, 2016: Journal of Gastroenterology and Hepatology
Roopa Kothapalli, Kodappully Sivaraman Siveen, Tuan Zea Tan, Jean Paul Thiery, Alan Prem Kumar, Gautam Sethi, Kunchithapadam Swaminathan
Considering the pathological significance of MMP-13 in breast and colon cancers, exosite-based inhibition of the C-terminal hemopexin (Hpx) domain could serve as an alternative strategy to develop selective inhibitors for MMP-13.Two of six lead compounds, compound 5 (2,3-dihydro-1,4-benzodioxine-5-carboxylic acid) and compound 6 (1-acetyl-4-hydroxypyrrolidine-2-carboxylic acid) exhibited considerable inhibitory activity against MMP-13. Complementing to this study, we have also shown the gene expression levels of MMP-13 within the subtypes of colon and breast cancers classified from patients' tissue samples to provide a better understanding on which subtype of breast cancer patients would get benefited by MMP-13 inhibitors...
June 29, 2016: Bioscience, Biotechnology, and Biochemistry
Susanne G Warner, Dana Haddad, Joyce Au, Joshua S Carson, Michael P O'Leary, Christina Lewis, Sebastien Monette, Yuman Fong
Stem-like tumor-initiating cells (TICs) are implicated in cancer progression and recurrence, and can be identified by sphere-formation and tumorigenicity assays. Oncolytic viruses infect, replicate in, and kill a variety of cancer cells. In this study, we seek proof of principle that TICs are susceptible to viral infection. HCT8 human colon cancer cells were subjected to serum-free culture to generate TIC tumorspheres. Parent cells and TICs were infected with HSV-1 subtype NV1066. Cytotoxicity, viral replication, and Akt1 expression were assessed...
2016: Molecular Therapy Oncolytics
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