scholarly journals Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 31
Author(s):  
Samuel E. Weinberg ◽  
Le Yu Sun ◽  
Allison L. Yang ◽  
Jie Liao ◽  
Guang Yu Yang
Keyword(s):  
Inositol Phosphates ◽  
Human Cancer ◽  
Energy Transduction ◽  
Nutritional Deficiencies ◽  
Increased Risk ◽  
Rna Export ◽  
Inflammatory Bowel ◽  
And Function ◽  
Biologic Function ◽  
Atp Regeneration

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn’s disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.

Endothelial and Cardiac Dysfunction in Inflammatory Bowel Diseases: Does Treatment Modify the Inflammatory Load on Arterial and Cardiac Structure and Function?

2019 ◽  
Vol 18 (1) ◽  
pp. 27-37
Author(s):  
Charilaos Triantafyllou ◽  
Maria Nikolaou ◽  
Ignatios Ikonomidis ◽  
Giorgos Bamias ◽  
Ioannis Papaconstantinou
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Gastrointestinal Physiology ◽  
Research Perspectives ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Cardiac Structure And Function ◽  
And Function

Inflammatory bowel diseases (IBD), largely represented by Crohn’s disease (CD) and ulcerative colitis (UC), alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process. These diseases can lead to significant arterial endothelial dysfunction. There is also evidence linking IBD with a modification of cardiac structure and function. A growing body of research has associated IBD with an acceleration of arterial stiffness and atherosclerosis and an increased risk of cardiovascular (CV) morbidity and mortality. The focus of this review is two-fold. Firstly, the literature on IBD in relation to CV dysfunction was evaluated (mainly based on 25 relevant surveys carried out between 2005 and 2018). The vast majority of these studies support a significant association of IBD with a deterioration in CV function. Secondly, the literature available regarding the effect of IBD treatment on CV dysfunction was considered based on studies published between 2007 and 2018. This literature search suggests that IBD treatment may have the potential to ameliorate CV dysfunction resulting in CV benefits. This review will analyse the literature as well as consider emerging research perspectives regarding how IBD treatment could improve CV dysfunction.

scholarly journals Development of an Inflammation-Associated Colorectal Cancer Model and Its Application for Research on Carcinogenesis and Chemoprevention

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Takuji Tanaka
Keyword(s):  
Colorectal Cancer ◽  
Large Bowel ◽  
Human Cancer ◽  
Colon Carcinogenesis ◽  
Human Colorectal Cancer ◽  
Immune System Dysfunction ◽  
Molecular Events ◽  
Increased Risk ◽  
Intestinal Immune System ◽  
Inflammatory Bowel

Chronic inflammation is a well-recognized risk factor for development of human cancer in several tissues, including large bowel. Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer development. Several molecular events involved in chronic inflammatory process may contribute to multistep carcinogenesis of human colorectal cancer in the inflamed colon. They include overproduction of reactive oxygen and nitrogen species, overproduction and upregulation of productions and enzymes of arachidonic acid biosynthesis pathway and cytokines, and intestinal immune system dysfunction. In this paper, I will describe several methods to induce colorectal neoplasm in the inflamed colon. First, I will introduce a protocol of a novel inflammation-associated colon carcinogenesis in mice. In addition, powerful tumor-promotion/progression activity of dextran sodium sulfate in the large bowel ofApcMin/+mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned.

Dysplastic Lesions in Inflammatory Bowel Disease: Molecular Pathogenesis to Morphology

2013 ◽  
Vol 137 (3) ◽  
pp. 338-350 ◽  
Author(s):  
Kristina A. Matkowskyj ◽  
Zongming E. Chen ◽  
M. Sambasiva Rao ◽  
Guang-Yu Yang
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Human Cancer ◽  
Significant Risk ◽  
Molecular Pathogenesis ◽  
Field Cancerization ◽  
Molecular Events ◽  
Increased Risk ◽  
Inflammatory Bowel

Context.—Inflammatory bowel disease (IBD) is a long-standing chronic active inflammatory process in the bowel with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic active inflammatory processes contribute to multistage progression of human cancer development, including reactive oxygen and nitrogen species, aberrant arachidonic acid metabolites and cytokines/growth factors, and immune dysfunction. These molecular events in IBD lead to genetic abnormality and promote aberrant cell proliferation, which further lead to epithelial changes encompassing a broad spectrum from inflammation-induced hyperplasia to dysplasia. Objective.—To review the (1) epidemiologic and molecular pathogenesis of the risk for colorectal cancer in IBD, (2) morphologic characterization, biomarker(s), and classification of dysplastic lesions, and (3) clinical management of dysplastic lesions arising in IBD. Data Sources.—The different IBD-related dysplastic lesions are illustrated by using morphology in conjunction with molecular pathways, and the “field cancerization” theory and its potential significance are discussed with a review of the literature. Conclusions.—Patients with IBD are at increased risk of developing colorectal cancer. The risk of developing carcinoma is related to the extent/duration/activity of the patient's disease. There is no consensus regarding the extent of carcinoma risk associated with IBD; however, all would agree that patients with IBD represent a group at significant risk for developing carcinoma and as such, warrant adequate surveillance and prevention. With better screening modalities and detection/characterization of dysplastic lesions, IBD-associated serrated lesions, and “field cancerization,” we will improve our understanding of and approach to risk stratification.

scholarly journals Inflammatory Bowel Diseases and Sarcopenia: The Role of Inflammation and Gut Microbiota in the Development of Muscle Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Maria Nardone ◽  
Roberto de Sire ◽  
Valentina Petito ◽  
Anna Testa ◽  
Guido Villani ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Adverse Outcomes ◽  
Low Grade ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
And Function ◽  
Host Metabolism ◽  
Low Grade Inflammation

Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.

A Mucin-Specific Protease Enables Molecular and Functional Analysis of Human Cancer-Associated Mucins

2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
High Resolution Mass Spectrometry ◽  
Human Cancer ◽  
Glycosylation Sites ◽  
Bacterial Protease ◽  
Specific Protease ◽  
To Come ◽  
And Function

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>

Thrombosis in IBD in the Era of JAK Inhibition

2020 ◽  
Vol 22 (1) ◽  
pp. 126-136
Author(s):  
Virginia Solitano ◽  
Gionata Fiorino ◽  
Ferdinando D’Amico ◽  
Laurent Peyrin-Biroulet ◽  
Silvio Danese
Keyword(s):  
Small Molecules ◽  
Arterial Thrombosis ◽  
Protective Role ◽  
Jak Inhibitors ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Thrombotic Complications ◽  
Inflammatory Bowel ◽  
Inflammatory Effect

: Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis. The interaction between inflammation and coagulation has been extensively studied. It is well-known that some drugs can influence the haemostatic system, but several concerns on the association between therapies and increased risk of thrombosis remain open. While biologics seem to have a protective role against thrombosis via their anti-inflammatory effect, some concerns about an increased risk of thrombosis with JAK inhibitors have been raised. We conducted a literature review to assess the association between biologics/small molecules and venous/arterial thrombotic complications. An increased risk of venous and arterial thrombosis was found in patients treated with corticosteroids, whereas anti-TNF were considered protective agents. No thromboembolic adverse event was reported with vedolizumab and ustekinumab. In addition, thromboembolic events rarely occurred in patients with ulcerative colitis (UC) after therapy with tofacitinib. The overall risk of both venous and arterial thrombosis was not increased based on the available evidence. Finally, in the era of JAK inhibitors, treatment should be individualized by evaluating the pre-existing potential thrombotic risk balanced with the intrinsic risk of the medication used.

37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Hamad Medical Corporation ◽  
Inflammatory Bowel ◽  
Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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