Anti-MADCAM therapy for ulcerative colitis

Picardo, Sherman; Panaccione, Remo

doi:10.1080/14712598.2020.1691520

Cited by 12 publications

(7 citation statements)

References 34 publications

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“…These results suggest that SHP647 may be a safe and e cacious therapeutic agent for UC treatment. Further study, however, is necessary to elucidate the long-term safety and effectiveness of PF-00547659 in the management of UC [41].…”

Section: Discussionmentioning

confidence: 99%

Network meta-analysis on efficacy and safety of different biologics for ulcerative colitis

Chu

Biao

Guo

et al. 2023

Preprint

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Background:Therapeutic options for ulcerative colitis (UC) have increased since the introduction of biologics a few decades ago. Due to the wide range of biologics available, physicians have difficulty in selecting biologics and do not know how to balance the best drug between clinical efficacy and safety. This study aimed to compare the efficacy and safety of biologics in treating ulcerative colitis. Methods: In this study, eight electronic databases (PubMed, Web of Science, Cochrane, Embase, Sinomed, China National Knowledge Infrastructure, Chongqing VIP Information, and WanFang Data) were searched to collect eligible studies without language restrictions. Retrieved 6 September 2022, from inception. All articles included in the mesh analysis are randomised controlled trials (RCTs). The inclusion of drugs for each outcome was ranked using a curved surface under cumulative ranking (SUCRA). Higher SUCRA scores were associated with better outcomes, whereas lower SUCRA scores were associated with better safety. This study has registered with PROSPERO, CRD42023389483. Results: A total of 25 RCTs, including 7595 patients, were included in this network meta-analysis. PF-00547659 ranked the highest in clinical remission among pure biologics (SUCRA 73.6%) and also ranked third in mucosal healing (SUCRA 74.1%), while adalimumab ranked highest in clinical response (SUCRA 94.9%). Infliximab ranked highest in endoscopy improvement (SUCRA 83.9%). BMS-936557 ranked second lowest in terms of adverse events (30.8% SUCRA) and severe adverse events (20.5% SUCRA). Conclusion: By indirect comparison, PF-00547659, adalimumab and infliximab were effective biological agents in UC patients. Further studies are required to evaluate their short- and long-term efficacy and safety.

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Section: Discussionmentioning

confidence: 99%

Network meta-analysis on efficacy and safety of different biologics for ulcerative colitis

Chu

Biao

Guo

et al. 2023

Preprint

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“…Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) belongs to the member of the immunoglobulin superfamily. It is an adhesion molecule selectively expressed on the surface of vascular endothelial cells of the intestinal mucosa and related lymphoid tissues, which mediates primarily the selective homing of lymphocytes to normal mucosa [ 31 ]. The adhesion mechanism of MAdCAM-1 plays an important role in the gut mucosal-associated lymphoimmune system.…”

Section: Discussionmentioning

confidence: 99%

The Experimental Exploration of TCM Theory “Treating the Same Disease with Different Approaches” on an Ulcerative Colitis Model

Kong

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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There is a relationship between lung injury and ulcerative colitis. Currently, traditional Chinese medicine (Huangqi Jiegeng (HQJGD) and Huangqi Huanglian decoctions (HQHLD)) is commonly used for UC-related lung injury; however, the mechanisms of these drugs remain unclear. In this study, UC models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 4 weeks. The pathological changes in the lung, intestine, liver, and kidney were observed; cytokines, chemokines, and adhesion molecules in lung tissue were detected in order to explore the immunological mechanism of UC-related lung injury and the intervention mechanism of traditional Chinese medicine in treating the lung and intestine in the immune-TNBS-ethanol rat model. Histology examinations demonstrated evident pathological changes in the lungs and intestines of the model groups. Furthermore, all groups treated with TCMs demonstrated reduced expressions of toll-like receptor 4, nuclear factor kappa-B, and macrophage migration inhibitory factor. Additionally, radioimmunoassay and immunohistochemistry showed tumor necrosis factor-α, interleukin-6, and 8 expression downregulation. The results showed that HQJGD and HQHLD could alleviate pulmonary inflammation in UC-related lung injury by obviously improving the pathology and fibrosis of the lung, inhibiting the positive feedback loop of MIF/NF-κB, and reducing lymphocyte homing to bronchial mucosa. This model revealed the immune mechanism of UC-related lung injury and the intervention mechanism of the Chinese medicine, which provided the rationale for treating ulcerative colitis clinically, so as to demonstrate the theory of “the lung and the large intestine being interior-exteriorly related” and “treating the same disease with different approaches.”

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“…The interaction of MAdCAM-1-positive endothelial cells and intestinal-specific immune cells expressing α4β7 integrin promote the upregulation of immune cell migration to the intestinal mucosa (7). The increased MAdCAM-1positive vessels in UC mucosa causes colitis by enhancing the migration of immune cells into the intestinal tract (13). In colorectal carcinogenesis, several inflammatory All rights reserved.…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this this version posted December 20, 2022. ; https://doi.org/10.1101/2022.12.18.22283633 doi: medRxiv preprint 13 To clarify the molecular mechanism of the MAdCAM-1 antibody against tumours of the colitic cancer models, cap analysis of gene expression (CAGE) analysis was performed using tumours of the AOM/DSS mice from the IgG Ab and MAdCAM-1 Ab groups. Based on gene ontology (GO) analysis, the activity of cytokines, immune cells, angiogenesis, and proliferation was significantly downregulated in colitic tumours of the MAdCAM-1 Ab group compared to that in the IgG Ab group (Figure 7A).…”

Section: Madcam-1 Antibody Treatment Inhibits the Activation Of P-sta...mentioning

confidence: 99%

Targeting MAdCAM-1 can prevent colitic cancer progression by suppressing immune cell infiltration and inflammatory signals

Ozawa

Yokobori

Osone

et al. 2022

Preprint

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Chronic inflammation by infiltrating immune cells promotes colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) via activating inflammatory cytokine signalling (IL-6/p-STAT3 and TNFα/NF-κB). Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a cell adhesion molecule expressed on high endothelial venules that promote immune cell migration from the bloodstream to the gut. MAdCAM-1 targeting strategy is attracting attention as a novel therapeutic option for UC. However, the significance of MAdCAM-1-positive vessels in dysplasia/colitic cancers remains unclear. We conducted immunohistochemistry against MAdCAM-1, and immune cell markers in surgically resected samples from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC). Moreover, we used a colitic cancer model, azoxymethane (AOM)/dextran sodium sulphate (DSS) mouse, to evaluate whether anti-MAdCAM-1 blocking antibody can suppress colitic cancer progression. MAdCAM-1-positive vessel number and infiltrating CD8-, CD68-, and CD163-positive immune cell numbers were significantly higher in dysplasia/colitic cancer than in normal mucosa, SCRC, and UC mucosa. In the AOM/DSS mouse model, MAdCAM-1 antibody reduced the tumour number, tumour diameter, number of CD8-, CD68-, and CD163-positive immune cells, and IL-6/p-STAT3 and TNFα/NF-κB expression levels. Targeting MAdCAM-1 could be promising for inflammatory carcinogenesis, and tumour progression by regulating inflammation/immune cell infiltration in patients with UC. Keywords: colitic cancer, colitis-associated cancer, MAdCAM-1, AOM/DSS mouse, immune cells.

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Anti-MADCAM therapy for ulcerative colitis

Cited by 12 publications

References 34 publications

Network meta-analysis on efficacy and safety of different biologics for ulcerative colitis

Network meta-analysis on efficacy and safety of different biologics for ulcerative colitis

The Experimental Exploration of TCM Theory “Treating the Same Disease with Different Approaches” on an Ulcerative Colitis Model

Targeting MAdCAM-1 can prevent colitic cancer progression by suppressing immune cell infiltration and inflammatory signals

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