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Polyposis colon

Miao Liu, Ling Zhou, Baiyu Zhang, Minhong He, Xiaoying Dong, Xiaojun Lin, Chunhong Jia, Xiaochun Bai, Yifan Dai, Yongchun Su, Zhipeng Zou, Hang Zheng
Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases...
October 19, 2016: Oncotarget
Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Juan Wang, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer. DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor...
September 2016: Journal of Hypertension
Liseth Rivero-Sanchez, Maria Lopez-Ceron, Sabela Carballal, Leticia Moreira, Xavier Bessa, Anna Serradesanferm, Angels Pozo, Josep Maria Augé, Teresa Ocaña, Ariadna Sánchez, María Liz Leoz, Míriam Cuatrecasas, Jaume Grau, Josep Llach, Antoni Castells, Francesc Balaguer, Maria Pellisé
Background and study aims: Serrated polyposis syndrome (SPS) is a high risk condition for colorectal cancer (CRC). Surveillance strategies for patients with serrated lesions remain controversial. We aimed to evaluate a diagnostic strategy to detect SPS consistently during reassessment colonoscopy in patients with proximal serrated lesions. Methods: This was a retrospective study of all individuals from a fecal immunochemical test (FIT)-based CRC screening program (2010 - 2013) with one or more serrated lesions of ≥ 5 mm proximal to the sigmoid colon on baseline colonoscopy...
October 14, 2016: Endoscopy
Furkan U Ertem, Wenqian Zhang, Kyle Chang, Wan Mohaiza Dashwood, Praveen Rajendran, Deqiang Sun, Ala Abudayyeh, Eduardo Vilar, Maen Abdelrahim, Roderick H Dashwood
Intervention strategies in familial adenomatous polyposis (FAP) patients and other high-risk colorectal cancer (CRC) populations have highlighted a critical need for endoscopy combined with safe and effective preventive agents. We performed transcriptome profiling of colorectal adenomas from FAP patients and the polyposis in rat colon (Pirc) preclinical model, and prioritized molecular targets for prevention studies in vivo. At clinically relevant doses in the Pirc model, the drug Clotam (tolfenamic acid, TA) was highly effective at suppressing tumorigenesis both in the colon and in the small intestine, when administered alone or in combination with Sulindac...
October 5, 2016: International Journal of Cancer. Journal International du Cancer
Ruthy Shaco-Levy, Kory W Jasperson, Katie Martin, N J Samadder, Randall W Burt, Jian Ying, Mary P Bronner
GOALS: To further characterize the gastrointestinal manifestations of Cowden syndrome in clinically well-annotated patients to improve the diagnosis of this syndrome. BACKGROUND: The gastrointestinal manifestations of Cowden Syndrome, an important heritable and multiorgan cancer syndrome, are not well defined. Proper diagnosis is essential for effective cancer surveillance and prevention in these patients. STUDY: Cowden patients with gastrointestinal polyps were selected for medical record and pathologic slide review...
September 22, 2016: Journal of Clinical Gastroenterology
Anchisa Kunawudhi, Alexandra K Wong, Tarik K Alkasab, Umar Mahmood
PURPOSE: We evaluated all PET/CTs acquired for patients without a primary diagnosis of colorectal cancer, and compared results for those who had subsequent colonoscopy within 6 months, to assess the accuracy of FDG PET/CT for detection of incidental pre-malignant polyps and malignant colon cancers. MATERIALS AND METHODS: Medical records of 9,545 patients who underwent F-18 FDG PET/CT studies over 3.5 years were retrospectively reviewed. Due to pre-existing diagnosis of colorectal cancer, 818 patients were excluded...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Juan Wang, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
OBJECTIVE: Constitutive activation of Wnt/β-catenin pathway plays an important role in the pathogenesis of colon cancer; however, recent studies have also indicated that elevated Wnt levels are essential. In the present study, we investigated the potential role of (pro) renin receptor in the pathophysiology of colon cancer. DESIGN AND METHOD: (P) RR expression in human colon tissues was measured by immunohistochemistry and Western blot analysis. Human colon cancer cell lines DLD-1 with adenomatous polyposis coli (APC) truncated mutation, and HCT116 withβ-catenin activating mutation, were transfected with scramble siRNA and siRNA against (pro) renin receptor...
September 2016: Journal of Hypertension
Felipe Carneiro DA Silva, Patrik Wernhoff, Constantino Dominguez-Barrera, Mev Dominguez-Valentin
In the past two decades, significant advances have been made in our understanding of colorectal (CRC) tumors with DNA mismatch (MMR) repair deficiency. The knowledge from molecular and genetic alterations in a variety of clinical conditions has refined the disease terminology and classification. Hereditary non-polyposis colorectal cancer (HNPCC) encompasses a spectrum of conditions that have significant phenotypic overlapping that makes clinical diagnosis a challenging task. Distinguishing among the HNPCC disorders is clinically important, as the approach to surveillance for patients and their at-risk family members differs according to risks for colonic and extracolonic cancer associated with each syndrome...
September 2016: Anticancer Research
S Liu, N R Tackmann, J Yang, Y Zhang
Inactivation of the adenomatous polyposis coli (APC) tumor suppressor is frequently found in colorectal cancer. Loss of APC function results in deregulation of the Wnt/β-catenin signaling pathway causing overexpression of the c-MYC oncogene. In lymphoma, both p19ARF and ribosomal proteins RPL11 and RPL5 respond to c-MYC activation to induce p53. Their role in c-MYC-driven colorectal carcinogenesis is unclear, as p19ARF deletion does not accelerate APC loss-triggered intestinal tumorigenesis. To determine the contribution of the ribosomal protein (RP)-murine double minute 2 (MDM2)-p53 pathway to APC loss-induced tumorigenesis, we crossed mice bearing MDM2(C305F) mutation, which disrupts RPL11- and RPL5-MDM2 binding, with Apc(min/+) mice, which are prone to intestinal tumor formation...
September 12, 2016: Oncogene
Sung-Min Ahn, Adnan Ahmad Ansari, Jihun Kim, Deokhoon Kim, Sung-Min Chun, Jiyun Kim, Tae Won Kim, Inja Park, Chang-Sik Yu, Se Jin Jang
Early-onset colorectal cancers (EOCRCs) may have biological or genomic features distinct from late-onset CRCs (LOCRCs). Previous studies have mostly focused on the germline predisposition conditions of EOCRCs, but we hypothesized that EOCRCs may have distinct somatic aberrations that accelerate cancer development. To identify the somatic aberrations that accelerate cancer development at an early age, we conducted whole exome sequencing for 28 polyposis-unrelated, microsatellite stable (MSS) EOCRCs with no known germline predisposition conditions...
September 6, 2016: Oncotarget
Tara Williamson, Ren-Yuan Bai, Verena Staedtke, David Huso, Gregory J Riggins
Inheritance of a gene mutation leads to the initiation of 5 to 10% of most cancers, including colon cancer cases. We developed a chemoprevention strategy using a novel combination of the non-steroidal anti-inflammatory (NSAID) sulindac plus the anthelminthic benzimidazole, mebendazole. This oral drug combination was effective in the ApcMin/+ mouse model of Familial Adenomatous Polyposis (FAP). Treatment with 35 mg/kg daily mebendazole reduced the number of intestinal adenomas by 56% (P = 0.0002), 160 ppm sulindac by 74% (P < 0...
September 6, 2016: Oncotarget
Qiang Ding, Panpan Lu, Shuping Ding, Yuhui Fan, Wei Yan, Ying Wang, Dean Tian, Yujia Xia, Mei Liu
INTRODUCTION: Ménétrier disease (MD) is rare that is involved in both the small bowel and entire colon. THE MAIN SYMPTOMS AND THE IMPORTANT CLINICAL FINDINGS: We describe a case of a 76-year-old male patient whose clinical presentations include intermittent diarrhea, epigastric pain, nausea, vomiting, asitia, and weight loss. An endoscopy was performed showing a large number of irregular forms and different sizes of polypoid lesions in the gastrointestinal tract, which is rare for MD...
September 2016: Medicine (Baltimore)
María Arriba, Ricardo Sánchez, Daniel Rueda, Laura Gómez, Juan L García, Yolanda Rodríguez, José Antonio Pajares, Jessica Pérez, Miguel Urioste, Rogelio González Sarmiento, José Perea
BACKGROUND: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood. PATIENTS AND METHODS: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor...
August 9, 2016: Clinical Colorectal Cancer
Fady Daniel, Hazem I Assi, Walid Karaoui, Jean El Cheikh, Sami Bannoura, Samer Nassif
Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma (NHL) comprising around 7% of adult NHL. It is characterized by a chromosomal translocation t(11:14) and overexpression of Cyclin D1. The incidence of secondary gastrointestinal tract involvement in MCL ranges from 10 to 28% in various series. However primary gastrointestinal MCL is very rare, accounting for only 1 to 4% of primary gastrointestinal lymphomas. The most common endoscopic feature of primary intestinal MCL is multiple lymphomatous polyposis...
2016: Case Reports in Gastrointestinal Medicine
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
John Hilkens, Nikki C Timmer, Mandy Boer, Gerjon J Ikink, Matthias Schewe, Andrea Sacchetti, Martijn A J Koppens, Ji-Ying Song, Elvira R M Bakker
OBJECTIVE: The gross majority of colorectal cancer cases results from aberrant Wnt/β-catenin signalling through adenomatous polyposis coli (APC) or CTNNB1 mutations. However, a subset of human colon tumours harbour, mutually exclusive with APC and CTNNB1 mutations, gene fusions in RSPO2 or RSPO3, leading to enhanced expression of these R-spondin genes. This suggested that RSPO activation can substitute for the most common mutations as an alternative driver for intestinal cancer. Involvement of RSPO3 in tumour growth was recently shown in RSPO3-fusion-positive xenograft models...
August 10, 2016: Gut
Ye Li, Shu-Xiang Cui, Shi-Yue Sun, Wen-Na Shi, Zhi-Yu Song, Shu-Qing Wang, Xin-Feng Yu, Zu-Hua Gao, Xian-Jun Qu
Myricetin is a natural dietary flavonoid compound. We evaluated the efficacy of myricetin against intestinal tumorigenesis in adenomatous polyposis coli multiple intestinal neoplasia (APCMin/+) mice. Myricetin was given orally once a day for 12 consecutive weeks. APCMin/+ mice fed with myricetin developed fewer and smaller polyps without any adverse effects. Histopathological analysis showed a decreased number of dysplastic cells and degree of dysplasia in each polyp. Immunohistochemical and western blot analysis revealed that myricetin selectively inhibits cell proliferation and induces apoptosis in adenomatous polyps...
August 6, 2016: Oncotarget
Emily Y He, Lucy Wyld, Mathew A Sloane, Karen Canfell, Robyn L Ward
Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of colorectal cancer. Knowledge of the molecular characteristics of colonic lesions which develop in this syndrome is fragmented, making it difficult to understand the underlying genetic basis of this condition. We conducted a systematic review and meta-analysis of all studies which evaluated the molecular characteristics of colorectal neoplasms found in individuals with serrated polyposis...
July 2016: Journal of Pathology. Clinical Research
Andrea Hodgson, Eric M Wier, Kai Fu, Xin Sun, Fengyi Wan
Animal models of colon cancer are widely used to understand the molecular mechanisms and pathogenesis of the disease. These animal models require a substantial investment of time and traditionally necessitate the killing of the animal to measure the tumor progression. Several in vivo imaging techniques are being used in both human clinics and preclinical studies, albeit at high cost and requiring particular expertise. Here, we report that the progression of splenomegaly coincides with and positively correlates to colon tumor development in Apc(min716/+) mice expressing a mutant gene encoding an adenomatous polyposis coli protein truncated at amino acid 716...
September 2016: Cancer Medicine
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