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colitis associated carcinoma

Caitlyn W Barrett, Sarah P Short, Christopher S Williams
Selenium is an essential micronutrient that is incorporated into at least 25 selenoproteins encoded by the human genome, many of which serve antioxidant functions. Because patients with inflammatory bowel disease (IBD) demonstrate nutritional deficiencies and are at increased risk for colon cancer due to heightened inflammation and oxidative stress, selenoprotein dysfunction may contribute to disease progression. Over the years, numerous studies have analyzed the effects of selenoprotein loss and shown that they are important mediators of intestinal inflammation and carcinogenesis...
August 25, 2016: Cellular and Molecular Life Sciences: CMLS
Omar Khan, Saverio Ligato
Signet ring cell change of intestinal epithelial cells is a rare but well-known mimicker of signet ring cell carcinoma and is often associated with ischemic and/or pseudomembranous colitis. Instead, signet ring cell change involving nonepithelial cells in the subserosa of the intestine is an extremely rare finding with only a single case report in the literature to date. We report a new case of benign signet ring cell change localized in the subserosa of the large bowel incidentally identified in a resection specimen for Clostridium difficile colitis mimicking a metastatic signet ring cell carcinoma...
August 25, 2016: International Journal of Surgical Pathology
Abhishek Tripathi, Marina D Kaymakcalan, Nicole R LeBoeuf, Lauren C Harshman
PURPOSE OF REVIEW: Immune checkpoint inhibitors such as those that target the programmed cell death (PD)-1 pathway harness the host immune system to elicit an antitumor response. Their remarkable clinical benefit has led to regulatory approvals in several malignancies including the genitourinary cancers, renal cell carcinoma, and urothelial carcinoma. This review will focus on the management of the toxicities encountered with these agents. RECENT FINDINGS: Although generally well tolerated, a small proportion of patients (10-20%) treated with PD-1 directed agents as monotherapy can develop severe autoimmune manifestations, also known as, immune-related adverse events...
November 2016: Current Opinion in Urology
Dana M Hardbower, Kshipra Singh, Mohammad Asim, Thomas G Verriere, Danyvid Olivares-Villagómez, Daniel P Barry, Margaret M Allaman, M Kay Washington, Richard M Peek, M Blanca Piazuelo, Keith T Wilson
EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H...
September 1, 2016: Journal of Clinical Investigation
Meeta Desai, Aaron Reiprich, Nancy Khov, Zhaohai Yang, Abraham Mathew, John Levenick
Lower GI bleeding is a common cause for hospitalization in adults. Medication-associated mucosal injury is an important clinical entity that can result in significant morbidity and mortality. We present the case of a 45-year-old woman with a 3-month history of intermittent abdominal cramping and rectal bleeding. Her medical history was extensive and included end-stage renal disease and a remote history of endometrial carcinoma that was treated with radiation. Initial workup was concerning for ischemic and radiation colitis, however, histology was most consistent with acute inflammation and ulceration associated with crystal fragments...
May 2016: Case Reports in Gastroenterology
Shinichi Sameshima, Shinichiro Koketsu, Takashi Okuyama, Yawara Kubota, Yuko Ono, Tamaki Noie, Masatoshi Oya
BACKGROUND: Previous studies reported that nephrotic syndrome is associated with ulcerative colitis (UC) patients treated with mesalazine. Dysplasia associated with UC often develops into colorectal carcinoma. CASE PRESENTATION: A 17-year-old man was referred to our hospital, complaining of diarrhea and bloody stool. Total colonoscopy (TC) was performed and total-type UC was diagnosed. After treatment with mesalazine for 5 years, a low-grade dysplasia (LGD) was detected in the rectum by histological analysis of a biopsy sample...
2016: World Journal of Surgical Oncology
Anders Rönnblom, Tommy Holmström, Hans Tanghöj, Urban Karlbom, Mari Thörn, Daniel Sjöberg
OBJECTIVE: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality. MATERIAL AND METHODS: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study...
November 2016: Scandinavian Journal of Gastroenterology
Sarah P Short, Caitlyn Whitten-Barrett, Christopher S Williams
Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine.
May 2016: Molecular & Cellular Oncology
Deshun Wu, Qing Li, Guixiang Song, Jun Lu
PURPOSE: The aim of this study was to identify the altered biological pathways associated with ulcerative colitis (UC)-related colorectal carcinoma (CRC) by systematic tracking the dysregulated modules from re-weighted protein- protein interaction (PPI) networks based on the expression profiles from normal, UC and various stages of CRC. METHODS: We firstly recruited the UC- and CRC-related microarray data from ArrayExpress database, and obtained 8 expression profiles which contained 5 conditions (normal, UC, early stage CRC, stage II CRC and stage III CRC)...
March 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Bobak Parang, Caitlyn W Barrett, Christopher S Williams
Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer.
2016: Methods in Molecular Biology
Jordan E Axelrad, Simon Lichtiger, Vijay Yajnik
In patients with inflammatory bowel disease (IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course...
May 28, 2016: World Journal of Gastroenterology: WJG
H Oppel-Heuchel, M-O Grimm
Nivolumab was recently approved as the first inhibitor of the programmed death 1 (PD-1) receptor and its ligand (PD-L1) for the treatment of urological cancer, namely metastasized renal cell carcinoma after prior therapy. The use of this new immunotherapy requires special therapy monitoring and management of side effects. An increase of immune cells around the tumor can initially mimic progression (so-called pseudoprogression). Treatment-associated side effects of higher grade according to the common terminology criteria for adverse events (CTCAE grades 3 or 4) are relatively rare; however, new immune-mediated side effects can occur and affect the skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis) and endocrine organs (hyperthyroidism, hypothyroidism and hypophysitis)...
May 2016: Der Urologe. Ausg. A
Kazuma Rifu, Koji Koinuma, Hisanaga Horie, Mitsuaki Morimoto, Yoshihiko Kono, Makiko Tahara, Yasunaru Sakuma, Yoshinori Hosoya, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata, Tsukasa Suzuki, Noriyoshi Fukushima
INTRODUCTION: Neuroendocrine tumors of the colon and rectum are relatively rare compared to sporadic colorectal carcinoma. There are few reports of neuroendocrine tumors of the colon and rectum in patients with ulcerative colitis. PRESENTATION OF CASE: A patient with sigmoid colon carcinoma with focal neuroendocrine features is presented. A 32-year-old man, who had been followed for ulcerative colitis for 14 years, was found to have carcinoma of the sigmoid colon on routine annual colonoscopy, and he underwent laparoscopic total colectomy...
2016: International Journal of Surgery Case Reports
Katja Vouk, Ursula Benter, Mayur M Amonkar, Alessia Marocco, Ceilidh Stapelkamp, Sylvie Pfersch, Laure Benjamin
OBJECTIVE: To estimate per-event cost and economic burden associated with managing the most common and/or severe metastatic melanoma (MM) treatment-related adverse events (AEs) in Australia, France, Germany, Italy, and the UK. METHODS: AEs associated with chemotherapy (dacarbazine, paclitaxel, fotemustine), immunotherapy (ipilimumab), and targeted therapy (vemurafenib) were identified by literature review. Medical resource use data associated with managing AEs were collected through two blinded Delphi panel cycles in each of the five countries...
September 2016: Journal of Medical Economics
Florian Kuehn, Christina S Mullins, Mathias Krohn, Christine Harnack, Robert Ramer, Oliver H Krämer, Ernst Klar, Maja Huehns, Michael Linnebacher
Colitis-associated colorectal cancer (CAC) seems to be a rather unique entity and differs in its genetic alterations, tumour formation capacities, and clinical features from sporadic colorectal carcinoma. Most descriptions about tumour biology of CAC refer to ulcerative colitis; data about Crohn´s colitis related carcinomas are scarce. The majority of patients with Crohn´s disease are under immunosuppression which generates a different environment for tumour growth. We first describe the clinical case of a fast growing CAC in a long-term immunosuppressed patient with Crohn´s disease and successful establishment and characterization of carcinoma cell lines along with their corresponding patient-derived xenograft...
2016: Scientific Reports
Maurizio Romano, Francesco DE Francesco, Laura Zarantonello, Cesare Ruffolo, Giuseppe A Ferraro, Giacomo Zanus, Antonio Giordano, Nicolò Bassi, Umberto Cillo
Inflammatory bowel diseases (IBD) are associated with an increased risk of colitis-associated colorectal carcinoma (CAC). CAC is one of the most important causes of morbidity and mortality in patients with Crohn's disease and ulcerative colitis. The aim of the present review was to discuss the most important signaling pathways and genetic alterations involved in carcinogenesis related to IBD, focusing on the molecular aspects of cancer stem cell physiology and the impact of the inflammatory microenvironment...
April 2016: Anticancer Research
Y Yang, M M Huycke, T S Herman, X Wang
Glutathione S-transferase alpha 4 (GSTA4) is a phase II detoxifying enzyme that metabolizes electrophiles and carcinogens including 4-hydroxy-2-nonenal (4-HNE), an endogenous carcinogen that contributes to colorectal carcinogenesis. In this study, we investigated GSTA4 expression and regulation in murine primary colonic epithelial cells, microbiome-driven murine colitis and human carcinomas. Exposure of YAMC cells to 4-HNE induced Gsta4 expression. Using an inflammation-associated model of colorectal cancer (CRC), Gsta4 expression increased in vivo in colon macrophages and serum after 2 weeks of colonization of IL-10 deficient (Il10(-/-)) mice with Enterococcus faecalis...
April 11, 2016: Oncogene
Jochen K Lennerz, Kimberley W J van der Sloot, Long Phi Le, Julie M Batten, Jae Young Han, Kenneth C Fan, Corey A Siegel, Amitabh Srivastava, Do Youn Park, Jey-Hsin Chen, Bruce E Sands, Joshua R Korzenik, Robert D Odze, Dora Dias-Santagata, Darrell R Borger, Hamed Khalili, A John Iafrate, Gregory Y Lauwers
PURPOSE: It is now recognized that Crohn's disease (CD), similar to ulcerative colitis (UC), carries an up to 20-fold higher cancer risk, and the development of colorectal carcinoma (CRC) is a major long-term complication. Once CRC is present, molecular profiling is one of the components in selecting appropriate treatment strategies; however, in contrast to UC, genetic alterations in Crohn's colitis-associated CRC are poorly understood. METHODS: In a series of 227 patients with Crohn's colitis, we identified 33 cases of CRC (~14 %) and performed targeted mutational analysis of BRAF/KRAS/NRAS and determined microsatellite status as well as immunophenotype of the tumors...
May 2016: International Journal of Colorectal Disease
Rurong Maoa, Fangyuan Zou, Liyan Yang, Shengchao Lin, Yueqi Li, Mingxing Ma, Peihao Yin, Xin Liang, Jianwen Liu
MiR-139-5p down-regulation has frequently been implicated in colorectal carcinoma. However, there is little known about its biological function between inflammation and cancer in vivo. Here, a transgenic murine model of colorectal carcinoma was used to investigate pathogenetic role of miR-139-5p in colitis and colitis-associated tumorigenesis. We showed that miR-139-5p knockout mice were higher sensitive to DSS-induced colitis and enhanced formation of intestinal neoplasia was observed when mice were exposed to AOM/DSS treatment...
December 2015: International Journal of Biochemistry & Cell Biology
Chuannan Fan, Yancheng Lin, Yubin Mao, Zhengjie Huang, Allan Yi Liu, Handong Ma, Donghong Yu, Alaiyi Maitikabili, Hongjun Xiao, Chuankai Zhang, Fan Liu, Qi Luo, Gaoliang Ouyang
miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APCMin mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines...
April 19, 2016: Oncotarget
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