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https://www.readbyqxmd.com/read/28067073/translating-genomic-profiling-to-gastrointestinal-cancer-treatment
#1
Kazuto Harada, Dilsa Mizrak Kaya, Yusuke Shimodaira, Shumei Song, Hideo Baba, Jaffer A Ajani
Next-generation sequencing enables faster, cheaper and more accurate whole-genome sequencing, allowing genome profiling and discovery of molecular features. As molecular targeted drugs are developed, treatment can be tailored according to molecular subtype. Gastric and colorectal cancers have each been divided into four subtypes according to molecular features. Profiling of the esophageal cancer genome is underway and its classification is anticipated. To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions...
January 9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28031408/predictive-outcomes-for-her2-enriched-cancer-using-growth-and-metastasis-signatures-driven-by-sparc
#2
Leandro N Guttlein, Lorena G Benedetti, Cristobal Fresno, Raul G Spallanzani, Sabrina F Mansilla, Cecilia Rotondaro, Ximena L Raffo Iraolagoitia, Edgardo Salvatierra, Alicia I Bravo, Elmer A Fernandez, Vanessa Gottifredi, Norberto W Zwirner, Andrea S Llera, Osvaldo L Podhajcer
: Understanding the mechanism of metastatic dissemination is crucial for the rational design of novel therapeutics. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein which has been extensively associated with human breast cancer aggressiveness although the underlying mechanisms are still unclear. Here, shRNA-mediated SPARC knockdown greatly reduced primary tumor growth and completely abolished lung colonization of murine 4T1 and LM3 breast malignant cells implanted in syngeneic BALB/c mice...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28006847/dietary-flavonoid-intake-and-colorectal-cancer-risk-in-the-european-prospective-investigation-into-cancer-and-nutrition-epic-cohort
#3
Raul Zamora-Ros, Dinesh Barupal, Joseph A Rothwell, Mazda Jenab, Veronika Fedirko, Isabelle Romieu, Krasimira Aleksandrova, Kim Overvad, Cecilie Kyrø, Anne Tjønneland, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Verena Katzke, Tilman Kühn, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Maria Kritikou, Calogero Saieva, Claudia Agnoli, Maria Santucci de Magistris, Rosario Tumino, Francesca Fasanelli, Elisabete Weiderpass, Guri Skeie, Susana Merino, Paula Jakszyn, Maria-José Sánchez, Miren Dorronsoro, Carmen Navarro, Eva Ardanaz, Emily Sonestedt, Ulrika Ericson, Lena Maria Nilsson, Stina Bodén, H Bas Bueno-de-Mesquita, Petra H Peeters, Aurora Perez-Cornago, Nicholas J Wareham, Kay-Thee Khaw, Heinz Freisling, Amanda J Cross, Elio Riboli, Augustin Scalbert
Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development is still sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries...
December 22, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27993681/lysophosphatidic-acid-lpa-signaling-via-lpa4-and-lpa6-negatively-regulates-cell-motile-activities-of-colon-cancer-cells
#4
Kaede Takahashi, Kaori Fukushima, Yuka Onishi, Karin Inui, Yusuke Node, Nobuyuki Fukushima, Kanya Honoki, Toshifumi Tsujiuchi
Lysophosphatidic acid (LPA) is an extracellular biological lipid and interacts with six subtypes of G protein-coupled LPA receptors (LPA1 to LPA6). LPA receptors exhibit a variety of cellular functions, depending on types of cancer cells. In this study, to assess the roles of LPA4 and LPA6 in cell growth and motile activities of colon cancer cells, LPA4 and LPA6 knockdown cells were established from DLD1 and HCT116 cells. LPA treatment increased the cell growth activities of LPA4 and LPA6 knockdown cells, compared with control cells...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27943267/lifetime-alcohol-intake-is-associated-with-an-increased-risk-of-kras-and-braf-kras-but-not-braf-colorectal-cancer
#5
Harindra Jayasekara, Robert J MacInnis, Elizabeth J Williamson, Allison M Hodge, Mark Clendenning, Christophe Rosty, Rhiannon Walters, Robin Room, Melissa C Southey, Mark A Jenkins, Roger L Milne, John L Hopper, Graham G Giles, Daniel D Buchanan, Dallas R English
Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study...
December 10, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27943209/a-protocol-for-isolation-and-proteomic-characterization-of-distinct-extracellular-vesicle-subtypes-by-sequential-centrifugal-ultrafiltration
#6
Rong Xu, Richard J Simpson, David W Greening
Scientific and clinical interest in extracellular vesicles (EVs) has increased rapidly as evidence mounts that they may constitute a new signaling paradigm. Recent studies have highlighted EVs carry preassembled complex biological information that elicit pleiotropic responses in target cells. It is well recognized that cells secrete essentially two EV subtypes that can be partially separated by differential centrifugation (DC): the larger size class (referred to as "microvesicles" or "shed microvesicles," sMVs) is heterogeneous (100-1500 nm), while the smaller size class (referred to as "exosomes") is relatively homogeneous in size (50-150 nm)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27939606/typing-of-colon-and-lung-adenocarcinoma-by-high-throughput-imaging-mass-spectrometry
#7
Mark Kriegsmann, Rémi Longuespée, Petra Wandernoth, Cristina Mohanu, Katharina Lisenko, Wilko Weichert, Arne Warth, Hendrik Dienemann, Edwin De Pauw, Tiemo Katzenberger, Daniela Aust, Gustavo Baretton, Joerg Kriegsmann, Rita Casadonte
In advanced tumor stages, diagnosis is frequently made from metastatic tumor tissue. In some cases, the identification of the tumor of origin may be difficult by histology alone. In this setting, immunohistochemical and molecular biological methods are often required. In a subset of tumors definite diagnosis cannot be achieved. Thus, additional new diagnostic methods are required for precise tumor subtyping. Mass spectrometric methods are of special interest for the discrimination of different tumor types. We investigated whether it is possible to discern adenocarcinomas of colon and lung using high-throughput imaging mass spectrometry on formalin-fixed paraffin-embedded tissue microarrays...
December 8, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27927168/phosphodiesterases-in-non-neoplastic-appearing-colonic-mucosa-from-patients-with-colorectal-neoplasia
#8
Badar Mahmood, Morten Matthiesen Bach Damm, Thorbjørn Søren Rønn Jensen, Marie Balslev Backe, Mattias Salling Dahllöf, Steen Seier Poulsen, Niels Bindslev, Mark Berner Hansen
BACKGROUND: Intracellular signaling through cyclic nucleotides, both cyclic AMP and cyclic GMP, is altered in colorectal cancer. Accordingly, it is hypothesized that an underlying mechanism for colorectal neoplasia involves altered function of phosphodiesterases (PDEs), which affects cyclic nucleotide degradation. Here we present an approach to evaluate the function of selected cyclic nucleotide-PDEs in colonic endoscopic biopsies from non-neoplastic appearing mucosa. METHODS: Biopsies were obtained from patients with and without colorectal neoplasia...
December 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#9
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27917920/transcriptome-and-long-noncoding-rna-sequencing-of-three-extracellular-vesicle-subtypes-released-from-the-human-colon-cancer-lim1863-cell-line
#10
Maoshan Chen, Rong Xu, Hong Ji, David W Greening, Alin Rai, Keiichi Izumikawa, Hideaki Ishikawa, Nobuhiro Takahashi, Richard J Simpson
Previously we reported that LIM1863 colorectal cancer (CRC) cells secrete three distinct extracellular vesicle subtypes - two subpopulations of exosomes (apical EpCAM-Exos and basolateral A33-Exos) and shed microvesicles (sMVs) - with distinct protein and miRNA signatures. Here, we extend our omics approach to understand the fundamental role of LIM1863-derived EVs by performing a comprehensive analysis of their mRNAs and long non-coding RNAs (lncRNAs) using RNA-Seq. We show that 2,389 mRNAs, 317 pseudogene transcripts, 1,028 lncRNAs and 206 short non-coding RNAs selectively distributed to (i...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916893/the-interaction-between-dietary-fiber-and-fat-and-risk-of-colorectal-cancer-in-the-women-s-health-initiative
#11
Sandi L Navarro, Marian L Neuhouser, Ting-Yuan David Cheng, Lesley F Tinker, James M Shikany, Linda Snetselaar, Jessica A Martinez, Ikuko Kato, Shirley A A Beresford, Robert S Chapkin, Johanna W Lampe
Combined intakes of specific dietary fiber and fat subtypes protect against colon cancer in animal models. We evaluated associations between self-reported individual and combinations of fiber (insoluble, soluble, and pectins, specifically) and fat (omega-6, omega-3, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), specifically) and colorectal cancer (CRC) risk in the Women's Health Initiative prospective cohort (n = 134,017). During a mean 11.7 years (1993-2010), 1952 incident CRC cases were identified...
November 30, 2016: Nutrients
https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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