{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:42:06Z","timestamp":1787668926013,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    Ulcerative colitis (UC) and Crohn\u2019s disease (CD) are two subtypes of chronic inflammatory bowel disease (IBD). Differential diagnosis remains a challenge. Anti-TNF\u03b1 treatment is an important treatment for IBD, yet resistance frequently occurs and cannot be predicted. Consequently, many patients receive ineffective therapy with potentially adverse effects. Novel assays are needed to improve diagnosis, and predict and monitor response to anti-TNF-\u03b1 compounds.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Design:<\/jats:bold>\n                    Signal transduction pathway (STP) technology was used to quantify activity of STPs (androgen and estrogen receptor, PI3K, MAPK, TGF\u03b2, Notch, Hedgehog, Wnt, NF\u03baB, JAK-STAT1\/2, and JAK-STAT3 pathways) in colon mucosa samples of CD and UC patients, based on transcriptome analysis. Previously described STP assay technology is based on computational inference of STP activity from mRNA levels of target genes of the STP transcription factor.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Results show that NF\u03baB, JAK-STAT3, Wnt, MAPK, and androgen receptor pathways were abnormally active in CD and UC. Colon and ileum-localized CD differed with respect to STP activity, the JAK-STAT1\/2 pathway being abnormally active in ileal CD. High activity of NF\u03baB, JAK-STAT3, and TGF\u03b2 pathways was associated with resistance to anti-TNF\u03b1 treatment in UC and colon-located CD, but not in ileal CD. Abnormal STP activity decreased with successful treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    We believe that measuring mucosal STP activity provides clinically relevant information to improve differential diagnosis of IBD and prediction of resistance to anti-TNF\u03b1 treatment in patients with colon-localized IBD, and provides new targets for treatment and overcoming anti-TNF\u03b1 resistance.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.1008976","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T15:28:45Z","timestamp":1665674925000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Improved diagnosis of inflammatory bowel disease and prediction and monitoring of response to anti-TNF alpha treatment based on measurement of signal transduction pathway activity"],"prefix":"10.3389","volume":"13","author":[{"given":"Wilbert","family":"Bouwman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Verhaegh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"van de Stolpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGF\u03b2 signalling pathway in disease","volume":"11","author":"Akhurst","year":"2012","journal-title":"Nat. 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