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https://www.readbyqxmd.com/read/28428272/hur-small-molecule-inhibitor-elicits-differential-effects-in-adenomatosis-polyposis-and-colorectal-carcinogenesis
#1
Michaela Lang, David Berry, Katharina Passecker, Ildiko Mesteri, Sabin Bhuju, Florian Ebner, Vitaly Sedlyarov, Rayko Evstatiev, Kyle Dammann, Alexander Loy, Orest Kuzyk, Pavel Kovarik, Vineeta Khare, Martin Beibel, Guglielmo Roma, Nicole Meisner-Kober, Christoph Gasche
HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28424049/findings-in-young-adults-at-colonoscopy-from-a-hospital-service-database-audit
#2
Stephanie Wong, Ilmars Lidums, Christophe Rosty, Andrew Ruszkiewicz, Susan Parry, Aung Ko Win, Yoko Tomita, Sina Vatandoust, Amanda Townsend, Dainik Patel, Jennifer E Hardingham, David Roder, Eric Smith, Paul Drew, Julie Marker, Wendy Uylaki, Peter Hewett, Daniel L Worthley, Erin Symonds, Graeme P Young, Timothy J Price, Joanne P Young
BACKGROUND: Colorectal cancer (CRC) diagnosed at <50 years is predominantly located in the distal colon and rectum. Little is known about which lesion subtypes may serve as CRC precursors in young adults. The aim of this work was to document the prevalence and histological subtype of lesions seen in patients aged <50 years, and any associated clinical features. METHODS: An audit of the colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia over a 12-month period was undertaken...
April 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28410235/cysteinyl-leukotriene-receptor-1-facilitates-tumorigenesis-in-a-mouse-model-of-colitis-associated-colon-cancer
#3
Janina Osman, Sayeh Savari, Naveen Kumar Chandrashekar, Kishan Bellamkonda, Desiree Douglas, Anita Sjölander
Cysteinyl leukotriene receptor 1 (CysLT1R) has been shown to be up-regulated in the adenocarcinomas of colorectal cancer patients, which is associated with a poor prognosis. In a spontaneous model of colon cancer, CysLT1R disruption was associated with a reduced tumor burden in double-mutant female mice (ApcMin/+/Cysltr1-/-) compared to ApcMin/+ littermates. In the current study, we utilized a genetic approach to investigate the effect of CysLT1R in the induced azoxymethane/dextran sulfate sodium (AOM/DSS) model of colitis-associated colon cancer...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383667/inactivation-of-jnk2-as-carcinogenic-factor-in-colitis-associated-and-sporadic-colorectal-carcinogenesis
#4
Wiebke Lessel, Andrew Silver, Doerthe Jechorek, Thomas Guenther, Friedrich Wilhelm Roehl, Thomas Kalinski, Albert Roessner, Angela Poehlmann-Nitsche
We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis...
April 5, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28369422/ileal-pouch-anal-anastomosis-for-dysplasia-or-cancer-complicating-inflammatory-bowel-disease-is-total-mesorectal-excision-always-mandatory-an-analysis-of-36-consecutive-patients
#5
Chloé Coton, Léon Maggiori, Diane Mège, Clotilde Naudot, Justine Prost À la Denise, Yves Panis
Background & Aim: The extent of lymph node harvesting during surgery for colorectal neoplasm (dysplasia and/or cancer) complicating inflammatory bowel disease (IBD) is the matter of debate. This study aimed to assess the risk of invasive rectal cancer in patients undergoing ileal pouch-anal anastomosis (IPAA) for colonic neoplasm complicating IBD, and thus to clarify if a systematic total mesorectal excision (TME) should be systematically performed or not in those patients. Methods: From 1998 to 2015, all patients who underwent IPAA for colorectal neoplasm complicating IBD were included...
March 22, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28369329/vedolizumab-induces-long-term-mucosal-healing-in-patients-with-crohn-s-disease-and-ulcerative-colitis
#6
Maja Noman, Marc Ferrante, Raf Bisschops, Gert De Hertogh, Karolien Van den Broeck, Karen Rans, Paul J Rutgeerts, Séverine Vermeire, Gert Van Assche
Introduction.: Vedolizumab has proven efficacy in IBD, but long term mucosal healing in Crohn's disease (CD), as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Methods.: Surveillance colonoscopy was prospectively scheduled for patients with longstanding UC or CD at a tertiary referral center in the open label extension phase (vedolizumab 300 mg IV q 4 wks) of the Gemini studies (GEMINI LTS, study number NCT00790933)...
March 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28349819/adam-17-fhl2-colocalisation-suggests-interaction-and-role-of-these-proteins-in-colorectal-cancer
#7
Laurine Verset, Joke Tommelein, Christine Decaestecker, Elly De Vlieghere, Marc Bracke, Isabelle Salmon, Olivier De Wever, Pieter Demetter
FHL2 is a multifunctional scaffolding protein; its expression is associated with poor prognosis in colorectal cancer. ADAM-17 is a metalloprotease implicated in ectodomain shedding. FHL2 regulates ADAM-17 plasma membrane localisation, and FHL2 deficiency leads to decreased activity of ADAM-17 in mouse macrophages. Presence and relationship of the ADAM-17/FHL2 complex with colorectal cancer progression is unknown. We studied FHL2 and ADAM-17 expression in several colon cancer cell lines by immunocytochemistry and western blot...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28347226/colorectal-polypoid-lesions-and-expression-of-vascular-endothelial-growth-factor-in-a-consecutive-series-of-endoscopic-and-surgical-patients
#8
Cesare Ruffolo, Luisa Toffolatti, Fabio Canal, Andromachi Kotsafti, Giulia Pagura, Anna Pozza, Marta Campo Dell'Orto, Francesco Ferrara, Marco Massani, Angelo P Dei Tos, Carlo Castoro, Nicolò Bassi, Marco Scarpa
Colorectal cancer incidence in patients undergoing screening protocols is decreasing because of the higher rate of discovered preneoplastic colonic lesions; however, adenomatous polyps may not always be removable endoscopically and surgery may still be necessary. The aim of this study was to assess the vascular endothelial growth factor expression in the different steps of colorectal carcinogenesis to explore its potential role as a marker of malignancy in polypoid lesions. A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28325827/sessile-serrated-polyps-and-colon-cancer-prevention
#9
Shahrooz Rashtak, Rafaela Rego, Seth R Sweetser, Frank A Sinicrope
Evidence suggests that up to one fifth of colorectal carcinomas (CRC) develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic CRCs with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps...
March 21, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28321155/pseudopolyps-in-inflammatory-bowel-diseases-have-we-learned-enough
#10
REVIEW
Dimitrios S Politis, Konstantinos H Katsanos, Epameinondas V Tsianos, Dimitrios K Christodoulou
Pseudopolyps are a well described entity in the literature and even though the exact pathogenesis of their formation is not completely understood, they are considered non-neoplastic lesions originating from the mucosa after repeated periods of inflammation and ulceration associated with excessive healing processes. Their occurrence is less common in Crohn's disease than in ulcerative colitis, and their overall prevalence ranges from 4% to 74%; moreover, they are found more often in colon but have been detected in other parts of the gastrointestinal tract as well...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28316214/-expression-of-tyrosine-and-threonine-protein-kinase-in-carcinogenic-process-of-colorectal-cancer-and-its-relationship-with-prognosis
#11
X L Zhang, W X Han, Y M Ma, H W Y Baohan, X H Zhao, H Y Wang
Objective: To investigate the expression of TTK (tyrosine and threonine protein kinase) in the process of colorectal cancer (CRC) development and its relationship to prognosis in CRC patients. Methods: Colitis-associated colon cancer model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice at four different stages of colon cancer development were obtained, named AD1 (inflammation of the recovery), AD2 (mild dysplasia), AD3 (adenoma) and AD4 (adenocarcinoma), as well as negative control (no treatment)...
March 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28301579/a-novel-model-of-colitis-associated-cancer-in-samp1-yitfc-mice-with-crohn-s-disease-like-ileitis
#12
Paola Menghini, Luca Di Martino, Loris R Lopetuso, Daniele Corridoni, Joshua C Webster, Wei Xin, Kristen O Arseneau, Minh Lam, Theresa T Pizarro, Fabio Cominelli
Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal cancer. Evidence suggests that colonic dysplasia and colitis-associated cancer (CAC) are often linked to repeated cycles of epithelial cell injury and repair in the context of chronic production of inflammatory cytokines. Several mouse models of CAC have been proposed, including chemical induction through exposure to dextran sulfate sodium (DSS) with the genotoxic agents azoxymethane (AOM), 1,2-dymethylhydrazine (DHM) or targeted genetic mutations...
2017: PloS One
https://www.readbyqxmd.com/read/28295534/mucin-rich-variant-of-traditional-serrated-adenoma-mrtsa-a-distinct-morphological-variant
#13
Sangeetha N Kalimuthu, Stefano Serra, Sara Hafezi-Bakhtiari, Richard Colling, Lai Mun Wang, Runjan Chetty
Traditional serrated adenomas (TSAs) account for 5% of serrated polyps, have villiform architecture, eosinophilic cells with a brush border and indented, flat-topped luminal serrations. However, some are composed of mucin-filled goblet cells (GC): a mucin-rich variant (MrTSA). The aim of this study was to determine if this variant has unique features compared to classic TSA (cTSA). 156 TSAs were retrieved from 2010-2016. Patient demographics, site of polyps, and 16 microscopic variables, were evaluated. TSAs containing 50% or more GCs were classified as MrTSAs...
March 13, 2017: Histopathology
https://www.readbyqxmd.com/read/28289479/colorectal-adenoma-and-carcinoma-specific-mirna-profiles-in-biopsy-and-their-expression-in-plasma-specimens
#14
Zsófia Brigitta Nagy, Barnabás Wichmann, Alexandra Kalmár, Orsolya Galamb, Barbara Kinga Barták, Sándor Spisák, Zsolt Tulassay, Béla Molnár
BACKGROUND: MiRNA expression markers are well characterized in colorectal cancer (CRC), but less is known about miRNA expression profiles in colorectal adenomas. Genome-wide miRNA and mRNA expression analyses were conducted through the colorectal adenoma dysplasia sequence. Furthermore, analysis of the expression levels of miRNAs in matched plasma samples was performed, focusing on biomarker candidates; miRNA and mRNA expression analyses were performed on colorectal biopsies and plasma samples (20 normals; 11 tubular and 9 tubulovillous adenomas; 20 colorectal carcinomas) by miRNA 3...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28288169/the-mir-200-family-is-increased-in-dysplastic-lesions-in-ulcerative-colitis-patients
#15
Amy Lewis, Carla Felice, Tomoko Kumagai, Cecilia Lai, Kriti Singh, Rosemary R Jeffery, Roger Feakins, Eleni Giannoulatou, Alessandro Armuzzi, Noor Jawad, James O Lindsay, Andrew Silver
BACKGROUND: Colorectal cancer (CRC) is a life-threatening complication of ulcerative colitis (UC), and patients are routinely screened for the development of precancerous lesions (dysplasia). However, rates of CRC development in patients with confirmed low-grade dysplasia vary widely between studies, suggesting a large degree of heterogeneity between these lesions that is not detectable macroscopically. A better understanding of the underlying molecular changes that occur in dysplasia will help to identify lesions at higher risk of malignancy...
2017: PloS One
https://www.readbyqxmd.com/read/28263971/egfr-mediated-macrophage-activation-promotes-colitis-associated-tumorigenesis
#16
D M Hardbower, L A Coburn, M Asim, K Singh, J C Sierra, D P Barry, A P Gobert, M B Piazuelo, M K Washington, K T Wilson
Epidermal growth factor receptor (EGFR) signaling is a known mediator of colorectal carcinogenesis. Studies have focused on the role of EGFR signaling in epithelial cells, although the exact nature of the role of EGFR in colorectal carcinogenesis remains a topic of debate. Here, we present evidence that EGFR signaling in myeloid cells, specifically macrophages, is critical for colon tumorigenesis in the azoxymethane-dextran sodium sulfate (AOM-DSS) model of colitis-associated carcinogenesis (CAC). In a human tissue microarray, colonic macrophages demonstrated robust EGFR activation in the pre-cancerous stages of colitis and dysplasia...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28261835/systematic-review-with-meta-analysis-use-of-5-aminosalicylates-and-risk-of-colorectal-neoplasia-in-patients-with-inflammatory-bowel-disease
#17
REVIEW
S Bonovas, G Fiorino, T Lytras, G Nikolopoulos, L Peyrin-Biroulet, S Danese
BACKGROUND: The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research. AIM: To investigate this association through an updated meta-analysis of observational studies. METHODS: PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity...
May 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28257790/the-diagnostic-performance-of-jnet-classification-for-differentiation-among-noninvasive-superficially-invasive-and-deeply-invasive-colorectal-neoplasia
#18
Kyoku Sumimoto, Shinji Tanaka, Kenjiro Shigita, Nana Hayashi, Daiki Hirano, Yuzuru Tamaru, Yuki Ninomiya, Shiro Oka, Koji Arihiro, Fumio Shimamoto, Masaharu Yoshihara, Kazuaki Chayama
BACKGROUNDS AND AIMS: The Japan NBI Expert Team (JNET) classification is the first universal narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors. Considering each type in this classification, the diagnostic ability of Type 2B is the weakest. Generally, clinical behavior is thought to be different in each gross type of colorectal tumor. We evaluated the differences in the diagnostic performance of JNET classification for each gross type (polypoid and superficial) and examined whether the diagnostic performance of Type 2B could improve by subtyping...
February 28, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28217374/plecanatide-mediated-activation-of-guanylate-cyclase-c-suppresses-inflammation-induced-colorectal-carcinogenesis-in-apc-min-fccc-mice
#19
Wen-Chi L Chang, Shet Masih, Anusha Thadi, Viren Patwa, Apoorva Joshi, Harry S Cooper, Vaseem A Palejwala, Margie L Clapper, Kunwar Shailubhai
AIM: To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc(+/Min-FCCC) mice with dextran sodium sulfate (DSS)-induced inflammation. METHODS: Inflammation driven colorectal carcinogenesis was induced in Apc(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide (0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid, flat and indeterminate dysplasia was evaluated...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28175019/p162-early-onset-of-disease-and-higher-risk-for-colorectal-dysplasia-in-ibd-patients-with-coincidental-primary-sclerosing-cholangitis-evidence-from-a-large-cohort-study
#20
A F Cordes, T Laumeyer, J Gerß, T Kucharzik, D Bettenworth
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
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