6 NOVEL BRD4 INHIBITORS BLOCK THE PATHOLOGICAL ACTIVATION OF BRD4-NFκB SIGNALING AND SUPPRESS COLONIC INFLAMMATION IN IBD MOUSE MODELS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S7-S7
Author(s):  
Zhiqing Liu ◽  
Gabriela Uribe ◽  
Yi Li ◽  
Wang Pingyuan ◽  
Haiying Chen ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Critical Role ◽  
Neoplastic Transformation ◽  
Mucosal Inflammation ◽  
Gene Expressions ◽  
Colon Tissue ◽  
Colonic Inflammation ◽  
Brd4 Inhibition

Abstract Ulcerative Colitis (UC) and Crohn’s Disease (CD) are two major types of inflammatory bowel disease (IBD), with recurrent symptoms and significant morbidity. Long-term persistence of chronic inflammation in IBD is among the major factors contributing to neoplastic transformation and development of colitis-associated colorectal cancer. There is a lack of efficient medications for IBD, due to either limited efficacy or side effects. Antibodies against TNFα are effective therapies; however, they are expensive, and up to 40% of patients are non-responders. Thus, improved therapy with higher efficacy, enhanced safety and better patient affordability is urgently needed. The master regulator of innate immune response NFκB plays a critical role in the initiation and chronicity of IBD mucosal inflammation. We demonstrated that bromodomain-containing protein 4 (BRD4), an epigenetic reader, is required for stabilization of NFκB binding on the promoters of inflammatory genes, activation of RNA polymerase II, and histone H3 Lys122 acetylation (H3K122ac) to permit high levels of inflammatory gene expressions by sentinel epithelial cells and stromal fibroblasts. Our data using human IBD patient samples suggest that BRD4 activation is critical to the initiation of colonic inflammation. We have successfully identified highly potent and specific BRD4 inhibitors, demonstrating that inhibition of BRD4 suppresses expression of inflammatory cytokines TNFα, IL-6, IL-17A, and IL-8. Administration of our lead inhibitors (ZL0454 & ZL0420) significantly reduces initiation of the mucosal inflammation in both dextran sulfate sodium (DSS)-induced and Cbir1 T cell transfer colitis models in vivo, but with low toxicity and much safer than the generic NFκB/IKK inhibitor BMS345541. The levels of NFkB and BRD4 activation were also compared using immunofluorescence staining of NFkB/RelA translocation, phospho-Ser276 RelA formation, and induction of the BRD4 marker H3K122Ac. The BRD4 inhibitors reduced DSS-induced NFkB-BRD4 activation in colon tissue, demonstrating the target specificity in vivo. Our data suggest that BRD4 activation is critical to the initiation of the colonic inflammation during IBD. BRD4 inhibition disrupts its interactions with acetylated histone lysine residues, thereby blocking the pathological activation of the BRD4-NFκB signaling and suppressing colonic inflammation. Therefore, inhibition of the BRD4 activation is an attractive target for the development of novel IBD therapy and in prevention of CAC. Using our novel BRD4 inhibitors, we will further seek to evaluate the effect of long-term BRD4 inhibition on UC-induced neoplastic transformation and development of CAC. Funding support: Crohn’s & Colitis Foundation Entrepreneurial Investing (EI) Initiative award and a research fellowship award from the Crohn’s & Colitis Foundation of America.

Stimulation of the Supportive Function of Marrow Stromal Cells by Anticancer Agents: Critical Role of Marrow Macrophages.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4252-4252
Author(s):  
Kensuke Ohta ◽  
Hirohisa Nakamae ◽  
Ki-Ryang Koh ◽  
Kiyotaka Nakaie ◽  
Hong-Zhang Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Stromal Cells ◽  
Critical Role ◽  
Marrow Stromal Cells ◽  
Gene Expressions ◽  
Gene Response

Abstract Anticancer agents used for the treatment of hematological malignancies are known to cause long-term toxicities to the structure and function of bone marrow microenvironment. These obbservations are based predominantly on the in vivo experiments with anticancer drug-treated mice and also on the clinical features of the patients who survived after inhtensive chemotherapies. In the present study, in order to evaluate immediate gene response of human marrow stromal cells to anticancer drugs, we tested with real-time PCR for the expression of various cytokine mRNAs from the stromal cells treated with anticancer drugs. Contrary to our expectation, we found that treatment of stromal cells with cytarabine (Ara-C; 0.1–100 μmol) for 3 to 14 days significantly and dose-dependently enhances the expression of mRNAs of stem cell factor (SCF) and leukemia inhibitory factor (LIF) while downregulates interleukin-6 (IL-6) mRNA. On the other hand, carboplatin (0.1–100 μmol) up-regulated only SCF mRNA and adriamycin (0.001–1 μmol) did not affect these gene expressions (n=6). In order to determine the responsive cell elements of stromal cells for these novel responses to Ara-C, mRNAs were independently quantified after separating CD14 positive macrophages and CD45 negative mesenchymal cells from Ara-C-treated stromal cells (n=6). In this additional experiments, we found that the above-mentioned changes in gene expression by Ara-C were provoked predominantly in the stromal macrophage fraction. Based on these observations, we treated the stromal cells established from 6 patients with AML and 11 with non-leukemic subjects with Ara-C for 2 weeks, followed by washing 3-times to eliminate Ara-C. Allogenic CD34 positive cells were then recharged and supportive functions of the stromal cells were evaluated with standard 2-stage long-term cultures. Indeed, the results showed that transient treatment with Ara-C significantly and dose-dependently upregulates supporting function of premature hematopoietic cells in non-leukemic and, although to the less extent, in leukemic stromal cells. These novel short-term stimulatory effects of Ara-C to marrow microenvironment may provide new explanations for some clinical events such as mechanism of rapid recovery of normal hematopoiesis and stem cell mobilization observed several days after completion of intensive chemotherapy to acute leukemia. In addfition, the pattern of gene response of stromal cells induced by Ara-C is of biologically great interest since it is quite different from the already known gene response of human stromal cells provoked by IL-1.

scholarly journals A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1019 ◽  
Author(s):  
Nur Zuliani Ramli ◽  
Mohamad Fairuz Yahaya ◽  
Ikuo Tooyama ◽  
Hanafi Ahmad Damanhuri
Keyword(s):  
Oxidative Stress ◽  
Natural Antioxidants ◽  
Green Tea Polyphenols ◽  
Food Sources ◽  
Gene Expressions ◽  
Neuroprotective Effects ◽  
Antioxidative Effects

Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption.

scholarly journals DEVELOPMENT OF SMALL MOLECULE EPIGENETIC THERAPEUTICS FOR INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S35-S36
Author(s):  
Yi Li ◽  
Gabriela Uribe ◽  
Wang Pingyuan ◽  
Haiying Chen ◽  
Zhiqing Liu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Animal Models ◽  
Epithelial Cells ◽  
Rna Polymerase Ii ◽  
Small Molecule ◽  
Bowel Disease ◽  
Mononuclear Cells ◽  
Mucosal Inflammation ◽  
Colonic Inflammation ◽  
Inflammatory Bowel

Abstract Long-term persistence of chronic inflammation in inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) is among the major factors contributing to neoplastic transformation and the development of colitis-associated colorectal cancer. There exists a lack of efficient medications for IBD, primarily due to emergence of resistance or side effects. Antibodies against tumor necrosis factor-α (anti-TNFα) are effective therapies in the armamentarium; however, up to 40% of patients become resistant to this therapy. Thus, target-based improved therapy with higher efficacy and enhanced safety profile is urgently needed to fill these gaps. We have demonstrated that bromodomain-containing protein 4 (BRD4), an epigenetic regulator, is required for stabilization of NFkB binding on the promoters of inflammatory genes, activation of RNA polymerase II, and histone H3 Lys122 acetylation (H3K122ac) to permit high levels of inflammatory gene expressions in sentinel immune cells, epithelial cells, and fibroblasts. Our compelling data using human IBD patient samples suggest that BRD4 activation is coincident with the initiation of colonic inflammation. Inhibition of the BRD4 activation is an attractive target for the development of superior therapeutics for IBD, especially for anti-TNFα-resistant patients. We have successfully identified proprietary highly potent and specific BRD4 inhibitors (patent WO 2018/112037 A1) with direct binding modes validated by the solved co-complex crystal structures. We observed that our lead compounds exhibit low toxicity both in vitro and in vivo. Therapeutic administration of our lead inhibitors ZL0516 and ZL0590 significantly reduces mucosal inflammation in several animal models of IBD and restores tissue architecture. Our data show that inhibition of BRD4 results in a decrease of key inflammatory cytokines associated with pathological responses in IBD such as TNFα, IL-6, IL-17A, and IL-1β expression in human colonic epithelial cells and peripheral blood mononuclear cells as well as several animal models of IBD colitis. Collectively, our data suggest that BRD4 activation is critical to the initiation of human colonic inflammation during IBD. BRD4 inhibition disrupts its protein-protein interactions with acetylated histone lysine residues, thereby blocking the pathological activation of the BRD4-NFκB signaling and suppressing colonic inflammation. Thus, BRD4 represents a unique drug target, and novel BRD4 inhibitors ZL0516 and ZL0590 have been identified as promising drug candidates towards the development of small molecule epigenetic therapeutics for the treatment of IBD and its chronic sequelae. Funding support: Crohn’s & Colitis Foundation Entrepreneurial Investing (EI) Initiative award, Litwin IBD Pioneers Program, and a research fellowship award from the Crohn’s & Colitis Foundation of America.

scholarly journals Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Lei Lei ◽  
Jianan Zhang ◽  
Eric A. Decker ◽  
Guodong Zhang
Keyword(s):  
Colorectal Cancer ◽  
Lipid Peroxidation ◽  
Critical Role ◽  
Redox Stress ◽  
Colonic Inflammation ◽  
Colon Tumorigenesis ◽  
Inflammatory Bowel

Redox stress is a common feature of gut disorders such as colonic inflammation (inflammatory bowel disease or IBD) and colorectal cancer (CRC). This leads to increased colonic formation of lipid-derived electrophiles (LDEs) such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE). Recent research by us and others support that treatment with LDEs increases the severity of colitis and exacerbates the development of colon tumorigenesis in vitro and in vivo, supporting a critical role of these compounds in the pathogenesis of IBD and CRC. In this review, we will discuss the effects and mechanisms of LDEs on development of IBD and CRC and lifestyle factors, which could potentially affect tissue levels of LDEs to regulate IBD and CRC development.

scholarly journals Redundant Role of Tissue-Selective TAFII105 in B Lymphocytes

2002 ◽  
Vol 22 (18) ◽  
pp. 6564-6572 ◽  
Author(s):  
Richard N. Freiman ◽  
Shane R. Albright ◽  
Leslie E. Chu ◽  
Shuang Zheng ◽  
Hong-Erh Liang ◽  
...  
Keyword(s):  
B Cells ◽  
Rna Polymerase Ii ◽  
B Lymphocyte ◽  
Critical Role ◽  
Central Component ◽  
Related Factors ◽  
Tissue Specific ◽  
Regulated Gene Expression

ABSTRACT Regulated gene expression is a complex process achieved through the function of multiple protein factors acting in concert at a given promoter. The transcription factor TFIID is a central component of the machinery regulating mRNA synthesis by RNA polymerase II. This large multiprotein complex is composed of the TATA box binding protein (TBP) and several TBP-associated factors (TAFIIs). The recent discovery of multiple TBP-related factors and tissue-specific TAFIIs suggests the existence of specialized TFIID complexes that likely play a critical role in regulating transcription in a gene- and tissue-specific manner. The tissue-selective factor TAFII105 was originally identified as a component of TFIID derived from a human B-cell line. In this report we demonstrate the specific induction of TAFII105 in cultured B cells in response to bacterial lipopolysaccharide (LPS). To examine the in vivo role of TAFII105, we have generated TAFII105-null mice by homologous recombination. Here we show that B-lymphocyte development is largely unaffected by the absence of TAFII105. TAFII105-null B cells can proliferate in response to LPS, produce relatively normal levels of resting antibodies, and can mount an immune response by producing antigen-specific antibodies in response to immunization. Taken together, we conclude that the function of TAFII105 in B cells is likely redundant with the function of other TAFII105-related cellular proteins.

scholarly journals Transition out of HSC Dormancy By a Continuous Upregulation of Metabolism Is Controlled Via Dietary Vitamin A/ Retinoic Acid Signaling

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. LBA-4-LBA-4
Author(s):  
Nina Cabezas-Wallscheid ◽  
Florian Buettner ◽  
Daniel Klimmeck ◽  
Pia Sommerkamp ◽  
Luisa Ladel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Retinoic Acid ◽  
Vitamin A ◽  
Single Cell ◽  
Critical Role ◽  
Dietary Vitamin ◽  
Self Renewal

Abstract Long-term quiescence or dormancy preserves the genomic integrity as well as the long-term self-renewal and functional capacities of hematopoietic stem cells (HSCs) during homeostasis. In response to infections, inflammatory or chemotherapy induced stress, dormant HSCs (dHSCs) become reversibly activated and are critical for the re-establishment of homeostasis. In our previous work, we defined the molecular landscape of HSCs and its immediate progenitors by determining their DNA-methylome, RNA- transcriptome and their proteome (Cabezas-Wallscheid et al., Cell Stem Cell 2014). This revealed the vitamin A/retinoic acid (RA) signaling pathway to be molecularly predominantly enriched in HSCs. However, the functional relevance of dietary vitamin A for maintenance of HSCs remains uncertain. Moreover, the molecular identity of very rare dHSCs as well as the mechanism regulating their maintenance or the transition out and back into dormancy remains unknown. We now show by single-cell RNA-seq analysis of >300 dHSCs and active HSCs (aHSCs) that the molecular transition from the most inactive dHSCs cluster to the most active HSCs can be best described as a continuous stream-like process linked to a steadily increasing metabolic activation. These single cell derived data are not consistent with a binary switch model, but instead suggest that activation/ differentiation downstream of dHSCs occurs in a continuum without the generation of discrete progenitor cell types. During this process,protein synthesis is increased first, followed by the increase of cell cycle related components. We then measured the time to first division starting from either a dHSC or an aHSC for 285 SiCs by single cell live cell imaging. We found that aHSCs showed an average of 29.5±0.7 hours to enter mitosis, while dHSCs needed 40.8±1.3 hours. This pronounced difference (11.3 hours) between two initially non-cycling populations suggests that dHSCs reside in a deeper level of quiescence, namely dormancy, which is also consistent with the molecular data mentioned above. The association of delayed cell cycle entry with the extremely low biosynthetic activity defines the status of dormancy and distinguishes it from quiescence. Furthermore, based on the acquired expression signatures, we describe the first marker-based, non-label retaining mouse model to specify dHSCs (Gpr-EGFP). We show molecularly and functionally that HSC-Gpr-pos cells resemble dHSCs demonstrating that the Gpr-EGFP mouse line can now be used as a simple alternative approach to track dHSCs and thus circumvent time-consuming label-retaining assays. The Gpr-EGFP model now allows to closely follow cell cycle dynamics within the dHSC compartment. Importantly, the mechanism regulating maintenance and the transition out of dormancy remains unknown. Our data focusing specifically on the most primitive HSCs revealed a critical role for vitamin A/RA signaling in controlling the cell cycle plasticity of dHSCs. We now show by in vitro and in vivo experiments, that treatment with the RA agonist all-trans retinoic-acid (ATRA) preserves dHSCs and maintains critical properties of HSCs. This includes maintenance of long-term self-renewal, low proliferation associated with decreased levels of Cdk6, expression of key transcription factors (Hoxb4), reduced protein synthesis and low levels of reactive oxygen species (ROS) as well as low Myc protein levels. Indeed, in response to activation signals, the presence of ATRA prevents up-regulation of c-Myc protein in HSCs and the effects of ATRA or drug induced Myc inhibition result in similar consequences on HSCs. Moreover, ATRA not only represses ROS production, but also prevents HSCs from entering the cell cycle upon diverse stress stimuli (pIC, LPS, 5-FU) in vivo. Most of the studies on vitamin A deficit-associated immunodeficiency are dedicated to the impaired function of lymphocytes. Thus, we analyzed the consequences of a vitamin A deficient diet for dormant HSCs. Strikingly, we found that HSCs are progressively lost over time and dHSCs did not recover after pIC-mediated activation in the absence of vitamin A. Collectively, these data uncover a critical role of vitamin A/RA signaling for the re-establishment of the dormant HSC population after stress-mediated activation. Together, our results highlight a so far unrecognized impact of dietary vitamin A on the regulation of cell cycle mediated stem cell plasticity. Disclosures No relevant conflicts of interest to declare.

Flt3-Ligand Plays a Critical Role in Restoring Function of NOD Facilitating Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1186-1186
Author(s):  
Yiming Huang ◽  
Isabelle J. Fugier-Vivier ◽  
Thomas Miller ◽  
Mary J. Elliott ◽  
Michael K. Tanner ◽  
...  
Keyword(s):  
Plasmacytoid Dendritic Cell ◽  
Critical Role ◽  
Nod Mice ◽  
Flt3 Ligand ◽  
Hematopoietic Stem ◽  
Functionally Impaired ◽  
And Function

Abstract CD8+/TCR− facilitating cells (FC) enhance engraftment of purified hematopoietic stem cells (HSC) in syngeneic and allogeneic recipients. FC also induce the production of regulatory T cells (Treg) in vivo and in vitro. The B220+/CD11c+/CD11b− precursor plasmacytoid dendritic cell (p-preDC) subpopulation in FC (p-preDC FC) is critical to FC function. However, p-preDC FC are significantly less efficient in function compared to FC total. In this study, we evaluated the phenotype and function of FC from diabetes-prone nonobese diabetes (NOD) mice. We found that NOD FC contain subpopulations similar to those previously described in B6 FC, including p-preDC, CD19+, NK1.1+DX5+ and myeloid cells. P-preDC represent the major FC subpopulation in NOD mice. The CD19+, DX5+ and B220−/CD11c+/CD11b+ subpopulations were significantly decreased in NOD FC compared to those from B6 or NOR mice (Figure 1a; * = P< 0.05; ** = P< 0.007). To test the function of NOD FC, 500 HSC (c-Kit+/Sca-1+/Lin−) were sorted and transplanted with or without 30,000 FC into conditioned 950 cGy recipients. MHC-matched diabetes-resistant NOR mice were served as a control strain for NOD mice. 5 (31%) of 16 recipients of NOR HSC were engrafted and survived up to 130 days. 7 (70%) of 10 recipients of NOR HSC plus FC have long-term engraftment and survival over 130 days, indicating that the NOR FC significantly enhanced engraftment of NOR HSC compared to HSC alone. In striking contrast, NOD FC were functionally impaired and did not enhance HSC engraftment in NOD recipients as evidenced by similar engraftment of HSC with FC (31%, n = 13) compared to the HSC alone (24%, n = 17; P = 0.579). Notably, when NOD mice were treated with Flt3 ligand (FL; 10 μg/ subcutaneous/daily, 10 days), FC were expanded in peripheral blood (PB). The DX5+ and B220−/CD11c+/CD11b+ subpopulations were significantly increased (Figure 1b). The FL-PB FC significantly facilitate engraftment of allogeneic HSC in vivo in the NOD → B10 model (Figure 1c; P = 0.02). These data demonstrate that NOD FC exhibit significantly impaired function and FL plays an important role in regulation and development of FC function. We propose that the defective function of NOD FC is mechanistically due either to the abnormal activation status of the p-preDC FC population and/or the absence of collaborative subpopulations in FC such as NK FC. This hypothesis offers an attractive explanation for the mechanism of FC to enhance HSC engraftment and to induce tolerance. Studies are underway to evaluate the mechanism by which FC contribute to diabetes-pathogenesis and/or prevention. Figure Figure

Long-Term Effects of In Vivo Administration of An Anti-VLA-4 Antibody (natalizumab) on Mobilization of Committed and Primitive Hematopoietic Progenitor Cells In Humans

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2264-2264
Author(s):  
Jorge Domenech ◽  
Julien Goustille ◽  
Maud Pallix ◽  
Zakia Bekhechi ◽  
Elfi Ducrocq ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Chronic Administration ◽  
Long Term Effects ◽  
Hematopoietic Stem ◽  
One Year ◽  
In Vivo Administration

Abstract Abstract 2264 The alpha4 beta1 integrin (VLA-4) exert a critical role on hematopoiesis by confining hematopoietic stem cells (HSC) and progenitor cells (HPC) within the niche. Previous preclinical studies have pointed out this role showing that HPCs can be mobilized by in vivo administration of a blocking anti-VLA-4 antibody (Ab) (Papayannopoulou et al, 1993). Very recently, two papers (Bonig et al, 2008; Zohren et al, 2008) have shown that such Ab exhibits a similar effect in humans for one month after treatment by natalizumab. In the present study, we have investigated long-term hematopoietic effects (up to 23 months) of repeated infusions of natalizumab in patients treated for multiple sclerosis (n=22). Seven patients have been explored sequentially (every month for one year) and 15 have been studied punctually (6 before and 9 after one year of treatment). We found that peripheral blood leukocytosis was consistently increased for one year in relation to lymphocytes, particularly to B lineage (by 3-fold). In parallel, an increase of circulating HPCs (CD34+ cells and total CFU) was observed and appeared more pronounced with levels above baseline values in all the patients studied (by 6-fold) while no increase of circulating mesenchymal stromal cells (CFU-F) was found. The increase was noted for both lymphoid (T and B lineages) and myeloid (granulo-monocyte, erythroid, and megakaryocyte) committed progenitor cells but also for primitive HPC (CD34+CD38- cells and CAFC). This effect was still found at long-term (up to two years of treatment) for both committed and primitive HPC. In conclusion, the HPC mobilizing effect of chronic administration of anti-VLA-4 Ab in humans involves all types of HPCs (lymphoid and myeloid, committed and primitive ones) and is not exhausted with time. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Magnifying Endoscopic Findings Can Predict Clinical Outcome during Long-Term Follow-Up of More Than 12 Months in Patients with Ulcerative Colitis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hajime Isomoto ◽  
Ryohei Uehara ◽  
Tomayoshi Hayashi ◽  
Junya Shiota ◽  
Kayoko Matsushima ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Narrow Band Imaging ◽  
Vital Staining ◽  
Mucosal Inflammation ◽  
Crypt Abscess ◽  
Long Term Follow Up ◽  
Microscopic Feature ◽  
Irregular Arrangement

Background and Aims. To explore the association of magnifying endoscopic (ME) findings with histopathology and relapse in ulcerative colitis (UC).Methods. Forty-six patients with UC underwent ME with narrow band imaging (NBI) and crystal violet staining and were followed for more than 12 months. ME findings with vital staining were classified into ME-A, regular arrangement of round to oval pits; ME-B, irregular arrangement with/without enlarged spaces between even pits; ME-C, irregular pits in size and shape with more irregular arrangement of pits; and ME-D, disrupted or disappeared pits. NBI-guided ME features of microvascular pattern (MVP) were divided into the MVP-regular and MVP-irregular type.Results. There were 5, 24, 10, and 7 cases of ME-A, ME-B, ME-C, and ME-D grade, respectively, while there were 21 and 25 of MVP-regular and MVP-irregular type, respectively. ME classifications were significantly associated with Matts endoscopic grade. ME classifications and MVP types were significantly associated with each pathognomonic microscopic feature of severe mucosal inflammation, crypt abscess, and goblet cell depletion. There were significant differences in the percentages of remission among ME classifications and between MVP types.Conclusion. ME findings can be predictive of relapse in UC and reliable forin vivohistopathological assessment.

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