A Systematic Review of Factors That Contribute to Hepatosplenic T-Cell Lymphoma in Patients With Inflammatory Bowel Disease

Kotlyar, David; Osterman, Mark T.; Diamond, Robert H.; Porter, David L.; Błoński, Wojciech; Wasik, Mariusz A.; Sampat, Sami; Mendizábal, Manuel; Lin, Ming V.; Lichtenstein, Gary R.

doi:10.1016/j.cgh.2010.09.016

Cited by 423 publications

(271 citation statements)

References 37 publications

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“…19 However, early use of therapeutic antibodies, typically combined with immunomodulators to promote mucosal healing may also lead to increased risk of toxicity, infections and the rare risk of hepatosplenic T-cell lymphoma in young men. [20][21][22] While current therapeutic approaches reduce disease activity and improve symptoms, the degree to which sustained mucosal healing has been achieved has been disappointing in randomized-controlled trials in both ulcerative colitis and Crohn's disease. 23 A number of key limitations still exist with current therapeutic options.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Hydroxylases as therapeutic targets in inflammatory bowel disease

Cummins

Doherty

Taylor

2013

Laboratory Investigation

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Inflammatory bowel disease (IBD) is a common and debilitating clinical disorder comprising ulcerative colitis and Crohn's disease. IBD occurs when inappropriate immunological activity in the intestinal mucosa results in epithelial barrier dysfunction leading to exposure of the mucosal immune system to luminal antigenic material. This in turn results in the cycles of inflammation and further barrier dysfunction which underlie disease progression. Although significant therapeutic advances have been made over the last decade, current immunosuppressive and anti-inflammatory treatments for IBD have significant limitations due to lack of treatment response in some patients and adverse effects, including increased risk of infection and malignancy. Recent studies using experimental models of IBD have identified that intracellular hydroxylases, a group of enzymes responsible for oxygen sensing and activation of adaptive transcriptional responses to hypoxia may represent a new class of therapeutic targets in IBD. Hydroxylase inhibitors are effective in ameliorating symptoms of colitis at least in part through the promotion of intestinal epithelial barrier function. The mechanism of this protection is due to activation of hypoxia-sensitive transcription factors, including the hypoxiainducible factor (HIF) and nuclear factor kappa-B (NF-kB), which activate specific epithelial barrier-protective transcriptional programs. In this review, the mechanism(s) of action and the therapeutic potential of small molecule hydroxylase inhibitors for the treatment of IBD will be discussed.

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Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Hydroxylases as therapeutic targets in inflammatory bowel disease

Cummins

Doherty

Taylor

2013

Laboratory Investigation

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“…Die Tatsache, dass der Antikörper Ipilimumab, der den endogenen Kostimulationshemmer CTLA-4 blockiert, Antitumoreffekte zeigt [12] Bei (v. a. jungen männlichen) CEDPatienten treten unter der Kombination von Anti-TNF-Antikörpern mit Azathioprin hepatosplenische T-Zell-Lymphome deutlich häufiger, aber noch immer sehr selten auf [16]. Diese sonst extrem seltenen Lymphome haben bislang leider eine extrem schlechte Prognose.…”

Section: Cd28-antagonist Abatacept: Hemmung Der T-zell-aktivierungunclassified

Einfluss der Therapie auf das Krebsrisiko bei rheumatoider Arthritis

2016

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Anschließend wird die zunehmende Proliferation der initiierten Tumorzellen im Rahmen der Tumorpromotion nicht nur durch klassische Wachstumsfaktoren, sondern auch durch proinflammatorische Zytokine beeinflusst. So konnte z. B. für Tumornekrosefaktor-α (TNF-α), Interleukin-6 (IL-6) und IL-22 ein direkter proliferationsfördernder und antiapoptotischer Effekt auf Tumorzellen nachgewiesen werden [9].Diese Effekte werden in den Tumorzellen durch die Aktivierung von Signalwegen vermittelt, die den Zellzyklus direkt beeinflussen oder durch Transkriptionsfaktoren wie NF-κB ("nuclear factor ,kappa-light-chain-enhancer' of activated B cells") oder STAT3 ("signal transducer and activator of transcription 3") zu einer Veränderung der Genexpression führen. Diese veränderte Genexpression kann wiederum zu einer Veränderung der Zellfunktion mit Entwicklung eines malignen Phänotyps führen.In diesem Zusammenhang ist einerseits interessant, dass sich die Signalwege von Wachstumsfaktoren und Zytokinen zumindest teilweise überlappen. Andererseits stellen Mutationen bestimmter Signalmoleküle, wie z. B. von STAT3 (dem wichtigsten Signaltransduktionsmolekül von IL-6), selbst onkogene Mutationen dar. Zeitschrift für Rheumatologie 1 · 2016Hier steht eine Anzeige. K

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“…Of particular, concern is the development of a hepatosplenic T-cell lymphoma (HSTCL), which predominately affects men less than 35 years of age on AZA and anti-TNF. HSTCL is almost uniformly fatal [13,14]. Third, combination therapy including early IS and anti-TNF use is more costly than either agent alone.…”

Section: Use Of Concurrent Is During Anti-tnf Treatmentmentioning

confidence: 99%

Which patients with inflammatory bowel disease should receive combination therapy?

Cross

2015

Expert Review of Gastroenterology & Hepatology

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A Systematic Review of Factors That Contribute to Hepatosplenic T-Cell Lymphoma in Patients With Inflammatory Bowel Disease

Cited by 423 publications

References 37 publications

Hydroxylases as therapeutic targets in inflammatory bowel disease

Hydroxylases as therapeutic targets in inflammatory bowel disease

Einfluss der Therapie auf das Krebsrisiko bei rheumatoider Arthritis

Which patients with inflammatory bowel disease should receive combination therapy?

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