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https://www.readbyqxmd.com/read/28194445/diverse-repetitive-element-rna-expression-defines-epigenetic-and-immunologic-features-of-colon-cancer
#1
Niyati Desai, Dipti Sajed, Kshitij S Arora, Alexander Solovyov, Mihir Rajurkar, Jacob R Bledsoe, Srinjoy Sil, Ramzi Amri, Eric Tai, Olivia C MacKenzie, Mari Mino-Kenudson, Martin J Aryee, Cristina R Ferrone, David L Berger, Miguel N Rivera, Benjamin D Greenbaum, Vikram Deshpande, David T Ting
There is tremendous excitement for the potential of epigenetic therapies in cancer, but the ability to predict and monitor response to these drugs remains elusive. This is in part due to the inability to differentiate the direct cytotoxic and the immunomodulatory effects of these drugs. The DNA-hypomethylating agent 5-azacitidine (AZA) has shown these distinct effects in colon cancer and appears to be linked to the derepression of repeat RNAs. LINE and HERV are two of the largest classes of repeats in the genome, and despite many commonalities, we found that there is heterogeneity in behavior among repeat subtypes...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28187456/inhibition-and-deficiency-of-the-immunoproteasome-subunit-lmp7-suppress-the-development-and-progression-of-colorectal-carcinoma-in-mice
#2
Julia Koerner, Thomas Brunner, Marcus Groettrup
New treatment options and drug targets for colorectal carcinoma are a pressing medical need. Inflammation and pro-inflammatory cytokines produced by Th1 and Th17 cells like IL-6, TNF, IL-17 and IL-23 promote the development and growth of colorectal cancer (CRC). The immunoproteasome is a proteasome subtype highly expressed in immune cells but also in the intestine. Since the immunoproteasome promotes Th1 and Th17 differentiation and pro-inflammatory cytokine production, we investigated here whether deficiency or inhibition of the immunoproteasome subunit LMP7 would interfere with CRC development and exacerbation in preventive and therapeutic mouse models...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184012/chromosome-20q-amplification-defines-a-subtype-of-microsatellite-stable-left-sided-colon-cancers-with-wild-type-ras-raf-and-better-overall-survival
#3
Ryan N Ptashkin, Carlos Pagan, Rona Yaeger, Sumit Middha, Jinru Shia, Kevin P O'Rourke, Michael F Berger, Lu Wang, Robert Cimera, Jiajing Wang, David S Klimstra, Leonard Saltz, Marc Ladanyi, Ahmet Zehir, Jaclyn F Hechtman
: Here comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma (CRC) harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced CRC underwent next generation sequencing (NGS) via MSK-IMPACT and a subset of case samples were subjected to high resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) CRC data. Of the CRC patients sequenced (n=401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28125762/association-of-dietary-patterns-with-risk-of-colorectal-cancer-subtypes-classified-by-fusobacterium-nucleatum-in-tumor-tissue
#4
Raaj S Mehta, Reiko Nishihara, Yin Cao, Mingyang Song, Kosuke Mima, Zhi Rong Qian, Jonathan A Nowak, Keisuke Kosumi, Tsuyoshi Hamada, Yohei Masugi, Susan Bullman, David A Drew, Aleksandar D Kostic, Teresa T Fung, Wendy S Garrett, Curtis Huttenhower, Kana Wu, Jeffrey A Meyerhardt, Xuehong Zhang, Walter C Willett, Edward L Giovannucci, Charles S Fuchs, Andrew T Chan, Shuji Ogino
Importance: Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' immune response to tumor. Evidence also suggests that diet influences intestinal F nucleatum. However, the role of F nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown. Objective: To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F nucleatum in tumor tissue...
January 26, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28125730/the-influence-of-braf-and-kras-mutation-status-on-the-association-between-aspirin-use-and-survival-after-colon-cancer-diagnosis
#5
Martine A Frouws, Marlies S Reimers, Marloes Swets, Esther Bastiaannet, Bianca Prinse, Ronald van Eijk, Valery E P P Lemmens, Myrthe P P van Herk-Sukel, Tom van Wezel, Peter J K Kuppen, Hans Morreau, Cornelis J H van de Velde, Gerrit-Jan Liefers
BACKGROUND: Use of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis. METHODS: A random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined...
2017: PloS One
https://www.readbyqxmd.com/read/28123722/systematic-analysis-of-the-achaete-scute-complex-like-gene-signature-in-clinical-cancer-patients
#6
Chih-Yang Wang, Payam Shahi, John Ting Wei Huang, Nam Nhut Phan, Zhengda Sun, Yen-Chang Lin, Ming-Derg Lai, Zena Werb
The achaete-scute complex-like (ASCL) family, also referred to as 'achaete-scute complex homolog' or 'achaete-scute family basic helix-loop-helix transcription factor', is critical for proper development of the nervous system and deregulation of ASCL plays a key role in psychiatric and neurological disorders. The ASCL family consists of five members, namely ASCL1, ASCL2, ASCL3, ASCL4 and ASCL5. The ASCL1 gene serves as a potential oncogene during lung cancer development. There is a correlation between increased ASCL2 expression and colon cancer development...
January 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28097468/outcomes-of-primary-colorectal-sarcoma-a-national-cancer-data-base-ncdb-review
#7
Cornelius A Thiels, John R Bergquist, Adam C Krajewski, Hee Eun Lee, Heidi Nelson, Kellie L Mathis, Elizabeth B Habermann, Robert R Cima
INTRODUCTION: Primary colorectal sarcomas are a rare entity with anecdotally poor outcomes. We sought to inform surgeons, oncologists, and researchers of the characteristics and outcomes of these understudied and difficult-to-manage tumors. METHODS: The National Cancer Data Base (NCDB) was queried for patients with pathologically confirmed primary sarcoma of the colon or rectum (1998-2012). Gastrointestinal stromal tumors were excluded. Unadjusted overall survival was reported using the Kaplan-Meier method...
January 17, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28067073/translating-genomic-profiling-to-gastrointestinal-cancer-treatment
#8
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...
9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28031408/predictive-outcomes-for-her2-enriched-cancer-using-growth-and-metastasis-signatures-driven-by-sparc
#9
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
#10
Raul Zamora-Ros, Dinesh K 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 remains 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
#11
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...
January 29, 2017: 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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
Paloma Cejas, Alessia Cavazza, C N Yandava, Victor 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, as compared with corresponding benign precursor adenomas. Modification of certain colorectal cancer sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27859268/heterogeneity-of-colorectal-cancer-risk-by-tumour-characteristics-large-prospective-study-of-uk-women
#20
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 three anatomical sites and four 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...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
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