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The Oncologist Mar 2020As the use of immune checkpoint inhibitors for several different malignancies becomes more mainstream, their side-effect profile raises new challenges. In 2011, the Food... (Review)
Review
As the use of immune checkpoint inhibitors for several different malignancies becomes more mainstream, their side-effect profile raises new challenges. In 2011, the Food and Drug Administration approved the first checkpoint inhibitor for the treatment of advanced melanoma, and since then, checkpoint inhibitors have demonstrated efficacy in many other tumor types. Given the frequent use of immune checkpoint inhibitors in a wide range of cancers today, the diagnosis and management of their immune-mediated toxicities need special attention. One of the most common is immune-mediated colitis. Workup and management of immune-mediated colitis can be challenging and is the purpose of this review. KEY POINTS: Rate of immune mediated colitis differ from different kind of immune checkpoint inhibitor treatment. To work up immune-mediated colitis, tests to rule out infectious etiologies of diarrhea, colonoscopy and abdominal image will help to differentiate immune mediated colitis from colitis from other etiology. Patients with mild colitis can be managed with supportive therapies alone, but more severe cases may require immunomodulators such as steroid. Refractory cases may require tumor necrosis factor (TNF) inhibitors, such as infliximab in addition to steroid treatment.
Topics: Colitis; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Infliximab; Melanoma
PubMed: 32162824
DOI: 10.1634/theoncologist.2018-0304 -
Advanced Science (Weinheim,... Feb 2024Stanniocalcin-1 (STC1) is upregulated by inflammation and modulates oxidative stress-induced cell death. Herein, the function of STC1 in colitis and stress-induced...
Stanniocalcin-1 (STC1) is upregulated by inflammation and modulates oxidative stress-induced cell death. Herein, the function of STC1 in colitis and stress-induced parthanatos, a newly identified type of programmed necrotic cell death dependent on the activation of poly-ADP ribose polymerase-1 (PARP1) is investigated. Results show that STC1 expression is markedly increased in the inflamed colonic mucosa of Crohn's disease (CD) patients and chemically-induced mice colitis models. Evaluation of parthanatos severity and pro-inflammatory cytokine expression shows that intestinal-specific Stc1 knockout (Stc1 ) mice are resistant to dextran sulfate sodium (DSS)-induced colitis and exhibit lower disease severity. STC1-overexpressing cells show an increased degree of parthanatos and proinflammatory cytokine expression, whereas STC1-knockout cells show a decreased degree of parthanatos. Co-immunoprecipitation, mass spectrometry, and proteomic analyses indicate that STC1 interacts with PARP1, which activates the JNK pathway via PARP1-JNK interactions. Moreover, inhibition of PARP1 and JNK alleviates parthanatos and inflammatory injuries triggered by STC1 overexpression. Finally, following restoration of Stc1 and Parp1 expression by adeno-associated viruses, and overexpression of Stc1 and Parp1 aggravated DSS-induced colitis in Stc1 mice. In conclusion, STC1 mediates oxidative stress-associated parthanatos and aggravates inflammation via the STC1-PARP1-JNK interactions and subsequent JNK pathway activation in CD pathogenesis.
Topics: Animals; Humans; Mice; Apoptosis; Colitis; Cytokines; Glycoproteins; Inflammation; Poly (ADP-Ribose) Polymerase-1; Proteomics
PubMed: 38088577
DOI: 10.1002/advs.202304123 -
World Journal of Gastroenterology Jan 2016Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking... (Review)
Review
Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.
Topics: Animals; Colitis; Colon; Colonoscopy; Dextran Sulfate; Diagnostic Imaging; Diffusion of Innovation; Disease Models, Animal; Magnetic Resonance Imaging; Mice; Predictive Value of Tests; Time Factors; Tomography, X-Ray Computed; Ultrasonography
PubMed: 26811642
DOI: 10.3748/wjg.v22.i3.996 -
Alimentary Pharmacology & Therapeutics Jul 2012Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities. (Review)
Review
BACKGROUND
Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities.
AIM
To compare pathoanatomical findings, clinical presentations, risk factors, course of diseases and response to treatment in CC and LC to establish whether they could be subtypes of the same disease, microscopic colitis (MC).
METHODS
The MEDLINE was searched for CC, LC and MC, and clinical studies of >20 patients were included. Pooled results with 95% confidence intervals were calculated based on the number of patients.
RESULTS
An abnormal number of intraepithelial lymphocytes are found in 45% (40-50%) with CC, and an abnormal subepithelial collagen band in 16% (13-20%) with LC suggesting a histological overlap. The incidence of CC and LC has increased in parallel. Mean age (CC 63 years; LC 60 years) and clinical presentation are indistinguishable, and females are predominant in CC (77%; 75-79%) as well as LC (68%; 66-70%). Risk factors such as nonsteroid anti-inflammatory drugs consumption CC 39% (36-42%); LC 32% (29-35%) are similar and prevalence of concomitant autoimmune diseases such as coeliac disease (CC 5%; CI: 4-6% and LC 7%; CI: 6-9%) do not differ. Bile acid diarrhoea is highly prevalent in CC (41%; 37-45%) and LC (29%; 24-34%). The effect of budesonide is identical.
CONCLUSIONS
CC and LC could be considered histological subtypes of the same disease, MC. To facilitate recruitment to clinical trials, all MC patients could be included in future trials and stratified for subtypes.
Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Diagnosis, Differential; Humans
PubMed: 22670660
DOI: 10.1111/j.1365-2036.2012.05166.x -
Canadian Family Physician Medecin de... Nov 2003To describe microscopic colitis (MC) and a stepwise approach to its diagnosis and management. (Review)
Review
OBJECTIVE
To describe microscopic colitis (MC) and a stepwise approach to its diagnosis and management.
QUALITY OF EVIDENCE
MEDLINE was searched from January 1996 to August 2002. Controlled trials were sought, but due to their relative rarity, most articles cited are well designed retrospective studies and reviews.
MAIN MESSAGE
Microscopic colitis in both its collagenous and lymphocytic forms is a relatively common and important cause of diarrhea in middle-aged and elderly patients. It usually presents as chronic watery diarrhea. Results of endoscopic and radiologic examinations are normal; specific histologic findings are seen on colonic biopsy. Once the diagnosis is confirmed, we suggest a stepwise approach to therapy. First-line therapies include antidiarrheal agents; second-line include bismuth subsalicylates and budesonide; third-line include cholestyramine and 5-aminosalicylic acid agents. When patients fail to respond to these therapies, oral corticosteroids or immune modulatory therapy should be considered. For severe unresponsive cases, colectomy is the last resort.
CONCLUSION
Microscopic colitis is an important cause of chronic diarrhea. Once the diagnosis is confirmed, a stepwise approach to treatment is suggested.
Topics: Adrenal Cortex Hormones; Adult; Age Factors; Aged; Antidiarrheals; Biopsy; Chronic Disease; Colitis; Colonoscopy; Diagnosis, Differential; Diarrhea; Humans; Middle Aged
PubMed: 14649986
DOI: No ID Found -
European Review For Medical and... Jul 2020To explore the effects of IFNG-AS1 and ANRIL on intestinal epithelial cells and their relationship with colitis.
OBJECTIVE
To explore the effects of IFNG-AS1 and ANRIL on intestinal epithelial cells and their relationship with colitis.
PATIENTS AND METHODS
From May 2017 to May 2019, 118 colitis patients admitted to our hospital were selected as the research group (RG), and 124 healthy controls were selected as the control group (CG). In addition, the normal intestinal epithelial cells HIEC and HIEC-6 were purchased to detect the IFNG-AS1 and ANRIL in the peripheral blood of patients in the two groups, and the effects of IFNG-AS1 and ANRIL on the intestinal epithelial cells were analyzed.
RESULTS
IFNG-AS1 and ANRIL were highly expressed in colitis (p<0.050), and their combined detection had good diagnostic value for the occurrence of colitis and complications (p<0.050). In intestinal epithelial cells transfected with IFNG-AS1 and ANRIL, it was found that inhibition of IFNG-AS1 and ANRIL remarkably increased the proliferation and decreased the apoptosis of intestinal epithelial cells (p<0.050).
CONCLUSIONS
IFNG-AS1 and ANRIL are highly expressed in colitis, and inhibiting their expression can promote the proliferation of intestinal epithelial cells and reduce apoptosis, which may be potential therapeutic targets for Crohn's colitis in the future.
Topics: Adult; Apoptosis; Case-Control Studies; Cell Line; Cell Proliferation; Colitis; Female; Gene Expression Regulation; Humans; Intestinal Mucosa; Male; Middle Aged; RNA, Long Noncoding
PubMed: 32706073
DOI: 10.26355/eurrev_202007_21901 -
World Journal of Gastroenterology Aug 2023Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates...
BACKGROUND
Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC.
AIM
To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice.
METHODS
A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing.
RESULTS
The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of decreased, and became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of . Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with included Aqp4, Clca4a, Dpm, Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 ( > 0.9, < 0.01).
CONCLUSION
FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. bear great therapeutic potential for colitis.
Topics: Animals; Mice; Colitis; Colitis, Ulcerative; Disease Models, Animal; Fecal Microbiota Transplantation; Signal Transduction; Toll-Like Receptor 4
PubMed: 37662857
DOI: 10.3748/wjg.v29.i30.4657 -
Journal of Innate Immunity 2022Inflammatory mediator S100A9 is dramatically elevated in ulcerative colitis and correlates with disease severity. S100A9 is a potential molecule to target for the...
BACKGROUND AND AIMS
Inflammatory mediator S100A9 is dramatically elevated in ulcerative colitis and correlates with disease severity. S100A9 is a potential molecule to target for the treatment of colitis, but to date, there is no effective targeting method. The aim of this study was to develop a safe and effective nano-delivery system targeting S100A9 and to evaluate its therapeutic efficacy in ulcerative colitis mouse model.
METHODS
We designed an oral nano-delivery system using poly (lactic acid-glycolic acid) (PLGA)-loaded S100A9 inhibitor tasquinimod to synthesize PLGA-TAS nanoparticles. TLR4-overexpressing macrophage membranes (MMs) were used to wrap the nanoparticles to make MM-PLGA-TAS, which allowed the nanoparticles to acquire the ability to specifically enrich the colitis region.
RESULTS
MM-PLGA-TAS was endocytosed by inflammatory phenotype RAW264.7 cells in vitro and can efficiently enrich in inflamed mouse colitis tissue in vivo. A chemically induced ulcerative colitis mouse model was used to evaluate the therapeutic effect of oral MM-PLGA-TAS. MM-PLGA-TAS significantly alleviated the symptoms of ulcerative colitis, and mechanically, MM-PLGA-TAS achieved immunomodulatory and suppressive effects by reducing S100a9 and other cytokines in the colitis region.
CONCLUSION
We describe a convenient, orally targeted colitis drug delivery system that cures the disease in ulcerative colitis mice. This system substantially increases drug accumulation in inflamed colonic tissue, reduces the risk of systemic exposure, and is a promising therapeutic approach against ulcerative colitis.
Topics: Animals; Biomimetics; Colitis; Colitis, Ulcerative; Drug Carriers; Macrophages; Mice; Nanoparticles
PubMed: 34724662
DOI: 10.1159/000519363 -
Cellular and Molecular Gastroenterology... 2023Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to...
BACKGROUND & AIMS
Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to ameliorate 2 chronic inflammatory states, namely, metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter.
METHODS
Mice were fed grain-based chow, which is naturally rich in fiber or compositionally defined diets enriched with semi-purified fibers. Mice were studied basally and in models of chemical-induced and T-cell transfer colitis.
RESULTS
Relative to all diets tested, mice consuming psyllium-enriched compositionally defined diets were markedly protected against both dextran sulfate sodium- and T-cell transfer-induced colitis, as revealed by clinical-type, histopathologic, morphologic, and immunologic parameters. Such protection associated with stark basal changes in the gut microbiome but was independent of fermentation and, moreover, maintained in mice harboring a minimal microbiota (ie, Altered Schaedler Flora). Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acids (BA) secretion, suggesting that psyllium's known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated level of fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA sequestrant cholestyramine, increased serum BA levels. Moreover, the use of BA mimetics that activate the farnesoid X receptor (FXR), as well as the use of FXR-knockout mice, suggested that activation of FXR plays a central role in psyllium's protection against colitis.
CONCLUSIONS
Psyllium protects against colitis via altering BA metabolism resulting in activation of FXR, which suppresses pro-inflammatory signaling.
Topics: Mice; Animals; Psyllium; Bile Acids and Salts; Health Promotion; Colitis; Inflammation; Mice, Knockout
PubMed: 36828279
DOI: 10.1016/j.jcmgh.2023.02.007 -
Revista Espanola de Enfermedades... Jul 2011Apart from inflammatory bowel diseases (IBD), there are several other form of colitis that may resemble macroscopically IBD, entering the differential diagnosis. These... (Review)
Review
Apart from inflammatory bowel diseases (IBD), there are several other form of colitis that may resemble macroscopically IBD, entering the differential diagnosis. These forms are represented by infectious colitis, ischemic colitis, pseudomembranous colitis, colitis related to diverticular disease, colitis related to mucosal prolapse, drug colitis, allergic colitis, and microscopic colitis. However, to distinguish between these forms is not always easy, and it frequently requires a strict interrelationship between the pathologist and the gastroenterologist. Here we discuss the more frequent forms of non- inflammatory bowel diseases colitides, trying to give useful hints for helping the clinician to better understand the extent to which the pathologist is called to give a definitive response in the differential diagnosis of these entities.
Topics: Colitis; Colitis, Collagenous; Colitis, Ischemic; Diagnosis, Differential; Diverticulitis, Colonic; Enterocolitis, Pseudomembranous; Humans; Hypersensitivity; Infections; Intestinal Mucosa
PubMed: 21770683
DOI: 10.4321/s1130-01082011000700006