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https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#1
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147604/tap1-down-regulation-elicits-immune-escape-and-poor-prognosis-in-colorectal-cancer
#2
Agnes Ling, Anna Löfgren-Burström, Pär Larsson, Xingru Li, Maria L Wikberg, Åke Öberg, Roger Stenling, Sofia Edin, Richard Palmqvist
The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29137421/gper-mediates-differential-effects-of-estrogen-on-colon-cancer-cell-proliferation-and-migration-under-normoxic-and-hypoxic-conditions
#3
Viviana Bustos, Áine M Nolan, Anke Nijhuis, Harry Harvey, Alexandra Parker, Richard Poulsom, Jean McBryan, Warren Thomas, Andrew Silver, Brian J Harvey
The estrogen receptor ERβ is the predominant ER subtype expressed in normal well-differentiated colonic epithelium. However, ERβ expression is lost under the hypoxic microenvironment as colorectal cancer (CRC) malignancy progresses. This raises questions about the role of signalling through other estrogen receptors such as ERα or G-protein coupled estrogen receptor (GPER, GPR30) by the estrogen 17β-estradiol (E2) under hypoxic conditions after ERβ is lost in CRC progression. We tested the hypothesis that E2 or hypoxia can act via GPER to contribute to the altered phenotype of CRC cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130628/characterization-of-genetic-intratumor-heterogeneity-in-colorectal-cancer-and-matching-patient-derived-spheroid-cultures
#4
Sigrid Salling Árnadóttir, Maria Jeppesen, Philippe Lamy, Jesper Bertram Bramsen, Iver Nordentoft, Michael Knudsen, Søren Vang, Mogens Rørbaek Madsen, Ole Thastrup, Jacob Thastrup, Claus Lindbjerg Andersen
Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for DNA and RNA purification...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29118272/beyond-cancer-genes-colorectal-cancer-as-robust-intrinsic-states-formed-by-molecular-interactions
#5
Ruoshi Yuan, Suzhan Zhang, Jiekai Yu, Yanqin Huang, Demin Lu, Runtan Cheng, Sui Huang, Ping Ao, Shu Zheng, Leroy Hood, Xiaomei Zhu
Colorectal cancer (CRC) has complex pathological features that defy the linear-additive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular-cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis and modelling method has been developed previously and tested in various cancer studies. The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumour subtypes, identified by their different molecular signatures...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29114493/severe-blastocystis-subtype-3-infection-in-a-patient-with-colorectal-cancer
#6
Shashiraja Padukone, Jharna Mandal, Subhash Chandra Parija
Colorectal cancer (CRC), more of lifestyle-related disorder, is one of the deadliest types of cancer across the globe. Nevertheless, infectious agents could be responsible for 20% of cancer. Recent findings have indicated the association of Blastocystis in CRC and recommend routine screening for Blastocystis. Herein, we describe a case of CRC with severe Blastocystis infection.
July 2017: Tropical Parasitology
https://www.readbyqxmd.com/read/29108382/clinicopathologic-features-and-prognostic-factors-for-patients-with-colorectal-cancer-who-are-75-years-and-older
#7
Mingfang Zhao, Hans Liu, Yanqing Tang, Xin Meng, Jun Yu, Qi Wang, Qiao Zhou, Sean X Leng, Haiyan Zhang
Colorectal cancer (CRC) is common and can be considered as a disease of older adults. About one half of the cases were diagnosed in patients over 70 years of age. Decision-making about treatment for these older patients can be complicated by age-related physiological changes, impaired functional status, limited social support, and comorbidities. Many trials excluded patients using an upper limit of 75 years of age. Little is known about prognostic factors in patients who are over this age limit. In this study, we conducted an analysis in the Surveillance, Epidemiology and End Results (SEER) database to identify specific clinicopathologic features and prognostic factors for these vulnerable cancer patients (N= 293,616)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101300/pharmacoproteomic-characterisation-of-human-colon-and-rectal-cancer
#8
Martin Frejno, Riccardo Zenezini Chiozzi, Mathias Wilhelm, Heiner Koch, Runsheng Zheng, Susan Klaeger, Benjamin Ruprecht, Chen Meng, Karl Kramer, Anna Jarzab, Stephanie Heinzlmeir, Elaine Johnstone, Enric Domingo, David Kerr, Moritz Jesinghaus, Julia Slotta-Huspenina, Wilko Weichert, Stefan Knapp, Stephan M Feller, Bernhard Kuster
Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome-guided pre-clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype...
November 3, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/29100436/meta-analysis-of-the-mutational-status-of-circulation-tumor-cells-and-paired-primary-tumor-tissues-from-colorectal-cancer-patients
#9
Yong Liu, Stefano Meucci, Liming Sheng, Ulrich Keilholz
As predictive markers for anti-EGFR therapy, KRAS and BRAF mutations are routinely detected in primary and metastatic colorectal cancer (CRC) cells, but seldom in circulating tumor cells (CTCs). Detecting mutations in CTCs could help explain mutational differences between tumor cells at local sites and distant metastases, thereby improving treatment outcomes. Here, we conducted a systematic review and meta-analysis to compare KRAS and BRAF mutations in paired CTCs and primary tumors from CRC patients, to detect any possible discordance...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100312/molecular-signatures-reflecting-microenvironmental-metabolism-and-chemotherapy-induced-immunogenic-cell-death-in-colorectal-liver-metastases
#10
Olga Østrup, Vegar Johansen Dagenborg, Einar Andreas Rødland, Veronica Skarpeteig, Laxmi Silwal-Pandit, Krzysztof Grzyb, Audun Elnæs Berstad, Åsmund Avdem Fretland, Gunhild Mari Mælandsmo, Anne-Lise Børresen-Dale, Anne Hansen Ree, Bjørn Edwin, Vigdis Nygaard, Kjersti Flatmark
Background: Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29064420/immunogenomic-classification-of-colorectal-cancer-and-therapeutic-implications
#11
REVIEW
Jessica Roelands, Peter J K Kuppen, Louis Vermeulen, Cristina Maccalli, Julie Decock, Ena Wang, Francesco M Marincola, Davide Bedognetti, Wouter Hendrickx
The immune system has a substantial effect on colorectal cancer (CRC) progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies) is influenced by the immune system. The molecular characterization of colorectal cancer (CRC) has led to the identification of favorable and unfavorable immunological attributes linked to clinical outcome. With the definition of consensus molecular subtypes (CMSs) based on transcriptomic profiles, multiple characteristics have been proposed to be responsible for the development of the tumor immune microenvironment and corresponding mechanisms of immune escape...
October 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29061646/kras-mutation-and-consensus-molecular-subtypes-2-and-3-are-independently-associated-with-reduced-immune-infiltration-and-reactivity-in-colorectal-cancer
#12
Neeraj Lal, Brian S White, Ghaleb Goussous, Oliver J Pickles, Michael Mason, Andrew D Beggs, Philippe Taniere, Benjamin E Willcox, Justin Guinney, Gary Middleton
PURPOSE: KRAS mutation is a common canonical mutation in CRC, found at differing frequencies in all Consensus Molecular Subtypes (CMS). The independent immunobiological impacts of RAS mutation and CMS are unknown. Thus, we explored the immunobiological effects of KRAS mutation across the CMS spectrum. EXPERIMENTAL DESIGN: Transcriptional analysis of immune genes/signatures was performed with RNA-seq using The Cancer Genome Atlas (TCGA) and the KFSYSCC data set. Multivariate analysis included KRAS status, CMS, tumour location, MSI status, and neoantigen load...
October 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29045527/braf-mutant-colorectal-cancer-prognosis-treatment-and-new-perspectives
#13
E Sanz-Garcia, G Argiles, E Elez, J Tabernero
The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant melanoma, efficacy observed with BRAF inhibitors in monotherapy in mCRC is poor...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28989591/familial-colorectal-cancer-type-x-in-central-iran-a-new-clinicopathologic-description
#14
Mehrdad Zeinalian, Mahdi Hadian, Morteza Hashemzadeh-Chaleshtori, Rasoul Salehi, Mohammad Hassan Emami
Background: Familial colorectal cancer type X (FCCX) is a subtype of mismatch repair (MMR)-proficient colorectal cancerin which the patients are clinically at risk for Lynch syndrome (LS), a common hereditary cancer predisposing syndrome. In this study, we described a new clinicopathological feature of the condition in central Iran. Materials and Methods: We designed a descriptive, retrospective study to screenat-risk colorectal cancer (CRC) patients, using Amsterdam II criteria and Molecular analysis in Isfahan (central Iran) throughout 2000-2013 period...
July 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28936799/proteomic-features-of-colorectal-cancer-identify-tumor-subtypes-independent-of-oncogenic-mutations-and-independently-predict-relapse-free-survival
#15
Callisia N Clarke, Michael S Lee, Wei Wei, Ganiraju Manyam, Zhi-Qin Jiang, Yiling Lu, Jeffrey Morris, Bradley Broom, David Menter, Eduardo Vilar-Sanchez, Kanwal Raghav, Cathy Eng, George J Chang, Iris Simon, Rene Bernards, Michael Overman, Gordon B Mills, Dipen Maru, Scott Kopetz
BACKGROUND: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. METHODS: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis...
December 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28933597/microrna-1297-inhibits-the-growth-and-metastasis-of-colorectal-cancer-by-suppressing-cyclin-d2-expression
#16
Yanan Wang, Jinfang Xue, Haoyu Kuang, Xiaojun Zhou, Liya Liao, Fang Yin
microRNAs (miR) can potentially be used for categorizing the various subtypes of colorectal cancer (CRC) and predicting a patient's response to treatment with traditional anti-CRC therapies. We investigated how miR-1297 and its potential target molecule cyclin D2 (CCND2) might affect the progression of CRC. Thirty-two pairs of CRC specimens and corresponding samples of para-tumor tissue were collected and examined for their levels of miR-1297 and CCND2 expression. We also examined miR-1297 and CCND2 expression in cultured SW480 cells...
November 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28925398/functional-significance-and-therapeutic-implication-of-ring-type-e3-ligases-in-colorectal-cancer
#17
REVIEW
L Liu, C C Wong, B Gong, J Yu
Accumulative studies revealed that E3 ubiquitin ligases have important roles in colorectal carcinogenesis. The pathogenic mechanisms of colorectal cancer (CRC) initiation and progression are complex and heterogeneous, involving somatic mutations, abnormal gene fusion, deletion or amplification and epigenetic alteration, which may cause aberrant expression or altered function of E3 ligases in CRC. Defects of E3 ligases have been reported to be involved in the molecular etiology and pathogenesis of CRC. The aberrant expressed E3 ligases can function as either oncogenes or tumor suppressors depending on ubiquiting target substrates in CRC...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28921583/associations-of-alcohol-intake-smoking-physical-activity-and-obesity-with-survival-following-colorectal-cancer-diagnosis-by-stage-anatomic-site-and-tumor-molecular-subtype
#18
Harindra Jayasekara, Dallas R English, Andrew Haydon, Allison M Hodge, Brigid M Lynch, Christophe Rosty, Elizabeth J Williamson, Mark Clendenning, Melissa C Southey, Mark A Jenkins, Robin Room, John L Hopper, Roger L Milne, Daniel D Buchanan, Graham G Giles, Robert J MacInnis
The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990-1994) and wave 2 (2003-2007). We included participants diagnosed to 31 August 2015 with incident stages I-III CRC within 10-years post exposure assessment...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28912574/distinct-gut-microbiome-patterns-associate-with-consensus-molecular-subtypes-of-colorectal-cancer
#19
Rachel V Purcell, Martina Visnovska, Patrick J Biggs, Sebastian Schmeier, Frank A Frizelle
Colorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28901507/%C3%AE-7-nicotinic-acetylcholine-receptor-in-tumor-associated-macrophages-inhibits-colorectal-cancer-metastasis-through-the-jak2-stat3-signaling-pathway
#20
Rushan Fei, Yuanwei Zhang, Saisai Wang, Tao Xiang, Wenbin Chen
Considerable evidence has implied that α7 nicotinic receptor subtypes play an important role in chronic inflammatory and neuropathic pain signaling. The aim of the present study was to determine the role of endogenous α7nAChR signaling in tumor-associated macrophages (TAMs) in human colorectal cancer (CRC) metastasis and prognosis. α7nAChR expression in primary tumor cells and adjacent stroma cells especially in TAMs in 51 CRC patients was observed. Using a human monocyte THP-derived macrophages (TMs) with α7nAChR-siRNA knockdown (TMα7-/-) and a CRC cell Transwell co-culture model, the migration and invasion of two CRC cells, LoVo and SW620, were determined...
November 2017: Oncology Reports
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