Serum Cell Death Biomarker Mirrors Liver Cancer Regression after Transarterial Chemoembolisation

Böck, Barbara C.; Hasdemir, D.; Wandrer, Franziska; Rodt, Thomas; Manns, MP; Schulze‐Osthoff, Klaus; Bantel, Heike

doi:10.1055/s-0036-1597493

Cited by 2 publications

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“…Immunohistochemical detection of activated caspase-3 was performed in paraffin-embedded liver sections as described 34,35 . Briefly, liver sections were incubated with an antibody against activated caspase-3 (Cell Signaling, Danvers, MA, USA) for one hour following antigen retrieval and blocking of endogenous peroxidase.…”

Section: Analyses Of Blood and Liver Tissue Samplesmentioning

confidence: 99%

TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) shows an increasing prevalence and is associated with the development of liver fibrosis and cirrhosis as the major risk factors of liver-related mortality in this disease. The therapeutic possibilities are limited and restricted to life style intervention, since specific drugs for NAFLD are unavailable so far. TNFα has been implicated as a major pathogenic driver of NAFLD. TNFα-mediated liver injury occurs mainly via TNF-receptor-1 (TNFR1) signaling, whereas TNFR2 mediates protective pathways. In this study, we analyzed the therapeutic effects of a novel antibody, which selectively inhibits TNFR1 while retaining protective TNFR2 signaling in a high-fat diet (HFD) mouse model of NAFLD. Mice were fed with HFD for 32 weeks and treated with anti-TNFR1-antibody or controlantibody for the last 8 weeks. We then investigated the mechanisms of TNFR1 inhibition on liver steatosis, inflammatory liver injury, insulin resistance and fibrosis. Compared to control-antibody treatment, TNFR1 inhibition significantly reduced liver steatosis and triglyceride content, which was accompanied by reduced expression and activation of the transcription factor SREBP1 and downstream target genes of lipogenesis. Furthermore, inhibition of TNFR1 resulted in reduced activation of the MAP kinase MKK7 and its downstream target JNK, which was associated with significant improvement of insulin resistance. Apoptotic liver injury, NAFLD activity and alanine aminotransferase (ALT) levels, as well as liver fibrosis significantly decreased by anti-TNFR1 compared to control-antibody treatment. Thus, our results suggest selective TNFR1 inhibition as a promising approach for NAFLD treatment.

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Section: Analyses Of Blood and Liver Tissue Samplesmentioning

confidence: 99%

TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice

et al. 2020

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“…4 The work of Bock et al, which focuses on response after initiation of TACE, complements other studies aimed at identifying serum biomarkers that might predict response to TACE before such therapy is initiated. 5,6 While the results of Bock et al 1 suggest that CK-18 may track reliably with HCC regression, their results should be considered preliminary until more extensive analyses can be performed. CK-18, a marker of hepatocyte apoptosis, is useful to predict the presence of chronic liver injury, inflammatory activity in chronic hepatitis B virus infection, degree of liver fibrosis, presence of nonalcoholic steatohepatitis, and poor prognosis in liver cirrhosis.…”

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confidence: 99%

“…SIRS, We read with interest the recent article by Bock et al 1 evaluating serum levels of cytokeratin-18 (CK-18) as a non-invasive index of the response of patients with hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). This work is timely and important because the efficacy of TACE remains controversial, 2 and clinical outcomes can vary substantially because of factors related to HCC and the TACE procedure itself.…”

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confidence: 99%

“…7 Moreover, baseline serum levels of CK-18 are higher in HCC patients when compared to patients with liver cirrhosis. 1 Bock et al compared CK-18 levels between patients who showed, or did not show, HCC regression after TACE. While CK-18 levels did differ significantly between these groups, so did alpha-fetoprotein levels, which have been shown to predict prognosis of patients with HCC.…”

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confidence: 99%

“…SIRS, We thank He et al for their interest in our report and their letter to the Editor that addresses the prognostic value of TACE-induced cytokeratin-18 (CK-18) fragments in sera of hepatocellular carcinoma (HCC) patients. 1,2 Increased levels of caspase-cleaved CK-18 fragments mirror hepatocyte apoptosis and can be detected in a variety of liver diseases. 3 The utility of this cell death biomarker for monitoring treatment response has already been shown for other epithelial tumours.…”

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confidence: 99%

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Letter: cytokeratin‐18 as a biomarker of hepatocellular carcinoma regression after transarterial chemoembolization

et al. 2016

Aliment Pharmacol Ther

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While high-HBV DNA levels have been associated with higher HCC recurrence rates, 5 it is still unclear as to which patients would benefit the most from anti-viral therapy in this setting, the optimal treatment duration and optimal cut-off for HBV DNA levels. We agree that further research is necessary given the large burden of chronic liver disease, especially in Asia, and the evolving modalities of curative HCC treatment. ACKNOWLEDGEMENTThe authors' declarations of personal and financial interests are unchanged from those in the original article.

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Serum Cell Death Biomarker Mirrors Liver Cancer Regression after Transarterial Chemoembolisation

Cited by 2 publications

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TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice

TNF-Receptor-1 inhibition reduces liver steatosis, hepatocellular injury and fibrosis in NAFLD mice

Letter: cytokeratin‐18 as a biomarker of hepatocellular carcinoma regression after transarterial chemoembolization

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