Colitis Associated Cancer

Matthew Peverelle, Sarang Paleri, Jed Hughes, Peter De Cruz, Paul J Gow
BACKGROUND: The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes. METHODS: One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD...
January 16, 2020: Inflammatory Bowel Diseases
Neil Stollman, Marcello Picchio, Sebastiano Biondo, Adi Lahat, Dan L Dumitrascu, Jaroslaw Regula, Marjorie Md Walker
In this session diverse critical issues in diverticular disease were considered, including "In or outpatient management of uncomplicated diverticulitis?", "Segmental colitis associated with diverticulosis: what is it?"and "Diverticular inflammation is a risk factor for colorectal cancer?". The conclusions drawn are outlined in the statements but in summary, outpatient management is safe in selected patients, as long as correct diagnosis and stage are assured, and this can allow a cost effective treatment...
January 8, 2020: Journal of Gastrointestinal and Liver Diseases: JGLD
Emanuelle Bellaguarda, Stephen Hanauer
Immune checkpoint inhibitors have revolutionized treatment and overall survival for several different types of cancer. Antibodies to cytotoxic T-lymphocyte-associated protein 4 and to programmed cell death protein 1 and its ligand enhance cytotoxic T-cell survival, thus augmenting antitumor action and consequently inducing immune-related adverse events, of which the most relevant is diarrhea and colitis. This review compiles recent data on pathophysiology, clinical manifestations, and treatment of immune-mediated colitis (IMC)...
January 9, 2020: American Journal of Gastroenterology
Meixin Chen, Zhiyao Zhao, Qingcai Meng, Puping Liang, Zexiong Su, Yaoxing Wu, Junjiu Huang, Jun Cui
The noncanonical NF-κB signaling pathway plays a critical role in a variety of biological functions including chronic inflammation and tumorigenesis. Activation of noncanonical NF-κB signaling largely relies on the abundance as well as the processing of the NF-κB family member p100/p52. Here, TRIM14 is identified as a novel positive regulator of the noncanonical NF-κB signaling pathway. TRIM14 promotes noncanonical NF-κB activation by targeting p100/p52 in vitro and in vivo. Furthermore, a mechanistic study shows that TRIM14 recruits deubiquitinase USP14 to cleave the K63-linked ubiquitin chains of p100/p52 at multiple sites, thereby preventing p100/p52 from cargo receptor p62-mediated autophagic degradation...
January 2020: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Sydney Lavoie, Eunyoung Chun, Sena Bae, Caitlin A Brennan, Carey Ann Gallini Comeau, Jessica K Lang, Monia Michaud, Hamid R Hoveyda, Graeme L Fraser, Miles H Fuller, Brian T Layden, Jonathan N Glickman, Wendy S Garrett
BACKGROUND & AIMS: Intestinal microbes and their metabolites affect development of colorectal cancer (CRC). Short-chain fatty acids are metabolites generated by intestinal microbes from dietary fiber. We investigated the mechanisms by which free fatty acid receptor 2 (FFAR2), a receptor for short-chain fatty acids that affects the composition of the intestinal microbiome, contributes to the pathogenesis of CRC. METHODS: We performed studies with ApcMin/+ mice, ApcMin/+ Ffar2-/- mice, mice with conditional disruption of Ffar2 in dendritic cells (DCs) (Ffar2fl/fl CD11c-Cre mice), ApcMin/+ Ffar2fl/fl CD11c-Cre mice, and Ffar2fl/fl mice (controls); some mice were given dextran sodium sulfate to induce colitis, with or without a FFAR2 agonist or an antibody against interleukin 27 (IL27)...
January 6, 2020: Gastroenterology
Yifan Wang, Xueyun Duan, Xingxing Liu, Yujin Liu, Heng Fan, Meng Xu, Qianyun Chen, Qing Tang
Inflammatory bowel disease (IBD) has received much attention due to its increasing worldwide incidence and potential increased risk of colorectal cancer. The protective function of a Rho-associated protein kinase inhibitor (Y-27632) against 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced mouse colitis has been proven in previous studies, but the concrete therapeutic mechanism of Y-27632 is still not completely illuminated. This current research is intended for further investigation of the effect and mechanism of Y-27632 in a mouse model of acute experimental ulcerative colitis induced by dextran sulfate sodium (DSS)...
January 8, 2020: Inflammation
Huiling Wang, Yiming Li, Gang Shi, Yuan Wang, Yi Lin, Qin Wang, Yujing Zhang, Qianmei Yang, Lei Dai, Lin Cheng, Xiaolan Su, Yang Yang, Shuang Zhang, Zhi Li, Jia Li, Yuquan Wei, Dechao Yu, Hongxin Deng
Therapeutic antibodies targeting vascular endothelial growth factor (VEGF) have become a critical regimen for tumor therapy, but the efficacy of monotherapy is usually limited by drug resistance and multiple angiogenic mechanisms. Complement proteins are becoming potential candidates for cancer-targeted therapy based on their role in promoting cancer progression and angiogenesis. However, the antitumor abilities of simultaneous VEGF and complement blockade were unknown. We generated a humanized soluble VEGFR-Fc fusion protein (VID) binding VEGFA/PIGF and a CR1-Fc fusion protein (CID) targeting C3b/C4b...
March 27, 2020: Molecular Therapy Oncolytics
Alaa A A Aljabali, Hamid A Bakshi, Faruk L Hakkim, Yusuf A Haggag, Khalid M Al-Batanyeh, Mazhar S Al Zoubi, Bahaa Al-Trad, Mohamed M Nasef, Saurabh Satija, Meenu Mehta, Kavita Pabreja, Vijay Mishra, Mohammed Khan, Salem Abobaker, Ibrahim M Azzouz, Harish Dureja, Ritesh M Pabari, Ashref Ali K Dardouri, Prashant Kesharwani, Gaurav Gupta, Shakti Dhar Shukla, Parteek Prasher, Nitin B Charbe, Poonam Negi, Deepak N Kapoor, Dinesh Kumar Chellappan, Mateus Webba da Silva, Paul Thompson, Kamal Dua, Paul McCarron, Murtaza M Tambuwala
Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α...
January 1, 2020: Cancers
J Pierrard, E Seront
Background: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice. Methods: We performed a systematic review in medline to determine■ whether antibiotics affect ici efficacy,■ whether baseline gm composition and ici efficacy show any correlations,■ whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and■ whether gm manipulation can alleviate the iraes...
December 2019: Current Oncology
Michael Dougan, Massimo Pietropaolo
Immunotherapy has transformed the treatment landscape for a wide range of human cancers. Immune checkpoint inhibitors (ICIs), monoclonal antibodies that block the immune-regulatory "checkpoint" receptors CTLA-4, PD-1, or its ligand PD-L1, can produce durable responses in some patients. However, coupled with their success, these treatments commonly evoke a wide range of immune-related adverse events (irAEs) that can affect any organ system and can be treatment-limiting and life-threatening, such as diabetic ketoacidosis, which appears to be more frequent than initially described...
January 2, 2020: Journal of Clinical Investigation
Toshiaki Tanaka, Takashi Kobunai, Yoko Yamamoto, Koji Murono, Shigenbu Emoto, Masaya Hiyoshi, Manabu Kaneko, Kazuhito Sasaki, Yasutaka Shuno, Takeshi Nishikawa, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa, Soichiro Ishihara
BACKGROUND: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer. MATERIALS AND METHODS: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer...
January 2020: Anticancer Research
Yuhua Li, Sheng Wang, Yang Sun, Wenqi Xu, Hongnan Zheng, Yan Wang, Yuan Tang, Xiaowei Gao, Can Song, Yin Long, Jiayun Liu, Li Liu, Qibing Mei
The study tried to investigate whether apple polysaccharide (AP) could prevent colitis associated colorectal cancer (CACC) through the regulation of intestinal microbiota disorders. 10 % AP (w/v) was administrated to ICR mice by gavage for 15 wk. It was found that AP treatment protected against CACC in mice effectively. The level of Lactobacillus in the intestine of AOM/DSS-treated mice was significantly decreased and that of Fusobacterium increased; while AP could reverse this trend and increase the intestinal microbiota diversity...
February 15, 2020: Carbohydrate Polymers
Masayoshi Kobayashi, Nagahide Matsubara, Yutaka Nakachi, Yasushi Okazaki, Motoi Uchino, Hiroki Ikeuchi, Jihyng Song, Kei Kimura, Michiko Yasuhara, Akihito Babaya, Tomoki Yamano, Masataka Ikeda, Hiroki Nishikawa, Ikuo Matsuda, Seiichi Hirota, Naohiro Tomita
BACKGROUND/AIM: The difficulty of early diagnosis of colitis associated colorectal cancer (CACRC) due to colonic mucosal changes in long-standing ulcerative colitis (UC) patients is often experienced in daily clinical practice. Noninvasive objective monitoring for cancer development is advantageous for optimizing treatment strategies in UC patients. We aimed to examine the epigenetic alterations occurring in CACRC, focusing on DNA hypermethylation of CpG islands. MATERIALS AND METHODS: The level of DNA methylation in CpG cites was compared between CACRC and the counterpart non-tumorous mucosa using Infinium HumanMethylation 450K BeadChip...
January 2020: In Vivo
Charlotte Gröschel, Maximilian Prinz-Wohlgenannt, Ildiko Mesteri, Sobha Karuthedom George, Lena Trawnicek, Denise Heiden, Abhishek Aggarwal, Samawansha Tennakoon, Maximilian Baumgartner, Christoph Gasche, Michaela Lang, Rodrig Marculescu, Teresa Manhardt, Martin Schepelmann, Enikö Kallay
Inflammatory bowel disease increases the odds of developing colitis-associated cancer. We hypothesized that Western-style diet (WD) aggravates azoxymethane (AOM)/dextran sulfate sodium salt (DSS)-induced colitis-associated tumorigenesis and that switching to the standard AIN93G diet will ameliorate disease symptoms even after cancer initiation. Female BALB/c mice received either WD (WD group) or standard AIN93G diet (AIN group) for the whole experimental period. After five weeks, the mice received 12.5 mg/kg AOM intraperitoneally, followed by three DSS cycles...
December 23, 2019: Nutrients
Cong-Lin Liu, Guo-Ping Shi
CLCA1 is a member of the CLCA (calcium-activated chloride channel regulator) family and plays an essential role in goblet cell mucus production from the respiratory tract epithelium. CLCA1 also regulates Ca2+ -dependent Cl- transport that involves the channel protein transmembrane protein 16A (TMEM16A) and its accessary molecules. CLCA1 modulates epithelial cell chloride current and participates in the pathogenesis of mucus hypersecretory-associated respiratory and gastrointestinal diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, pneumonia, colon colitis, cystic fibrosis intestinal mucous disease, ulcerative colitis, and gastrointestinal parasitic infection...
November 2019: World Allergy Organization Journal
Taku Kobayashi, Akihito Uda, Eri Udagawa, Toshifumi Hibi
BACKGROUND AND AIMS: Patients with inflammatory bowel diseases may have higher incidences of non-melanoma skin cancers and non-Hodgkin lymphoma, potentially linked to underlying disease and treatments. This analysis assessed incidence rates of these malignancies in Japanese patients with ulcerative colitis or Crohn's disease, and their association with thiopurine and/or anti-tumor necrosis factor-α treatment, using data from a nationwide administrative database in Japan. METHODS: Patients diagnosed with inflammatory bowel disease without malignancy were identified from the Medical Data Vision database...
December 23, 2019: Journal of Crohn's & Colitis
Olga A Sukocheva, Hideki Furuya, Mei Li Ng, Markus Friedemann, Mario Menschikowski, Vadim V Tarasov, Vladimir N Chubarev, Sergey G Klochkov, Margarita E Neganova, Arduino A Mangoni, Gjumrakch Aliev, Anupam Bishayee
Inflammatory gastrointestinal (GI) diseases and malignancies are associated with growing morbidity and cancer-related mortality worldwide. GI tumor and inflammatory cells contain activated sphingolipid-metabolizing enzymes, including sphingosine kinase 1 (SphK1) and SphK2, that generate sphingosine-1-phosphate (S1P), a highly bioactive compound. Many inflammatory responses, including lymphocyte trafficking, are directed by circulatory S1P, present in high concentrations in both the plasma and the lymph of cancer patients...
December 18, 2019: Pharmacology & Therapeutics
Yu-Lin Xu, Cui-Ling Ding, Chun-Lin Qian, Zhong-Tian Qi, Wen Wang
Inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Although some studies reported the roles of Retinoid acid induced 16 (RAI16) in the tumorigenesis of hepatocellular carcinoma and PKA signaling, the roles of RAI16 in IBD and CRC are undressed. RAI16-/- mice were generated and the roles of RAI16 were addressed in dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS induced IBD or CAC mouse models, respectively...
December 20, 2019: Cell Death & Disease
Jae Gon Lee, Chang Soo Eun, Su Vin Jo, A-Reum Lee, Chan Hyuk Park, Dong Soo Han
It has been suggested that manipulation of gut microbiota using antibiotics can inhibit colitis-associated colorectal cancer (CAC) in a mouse model. We investigated whether timing of gut microbial manipulation using antibiotics affects colon tumorigenesis in the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model. CAC was induced in C57BL/6 mice by injection of 12.5 mg/kg AOM followed by three rounds of 1.7% DSS exposure. There were six groups based on timing of antibiotic administration. Colonic inflammation, proliferation, and tumorigenesis were evaluated after animal sacrifice...
2019: PloS One
Hamed Khalili, David Bergman, Bjorn Roelstraete, Kristin E Burke, Michael C Sachs, Olén O, Ludvigsson Jf
BACKGROUND & AIMS: Microscopic colitis is one of the most common causes of chronic diarrhea in older populations. We investigated all-cause and cause-specific mortality in patients with microscopic colitis. METHODS: We conducted a nationwide cohort study of all cases of microscopic colitis (n=14,333) diagnosed from 1990 through 2017 in Sweden. Cases of microscopic colitis were identified using SNOMED codes from gastrointestinal histopathology reports collected from Sweden's 28 pathology departments...
December 16, 2019: Clinical Gastroenterology and Hepatology
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