Apoptosis in chronic viral hepatitis parallels histological activity: An immunohistochemical investigation using anti‐activated caspase‐3 and M30 Cytodeath antibody

McPartland, Jo; Guzail, M.; Kendall, C H; Pringle, James H.

doi:10.1111/j.0959-9673.2005.00411.x

Cited by 33 publications

(18 citation statements)

References 32 publications

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“…This M30 antibody was evaluated as feasible for use in detecting cells of eukaryotic origin undergoing apoptosis (18). Our data reveal for the first time that hepatobiliary diseases are associated with elevated serum CK-18.…”

Section: Discussionmentioning

confidence: 86%

Caspase‐cleaved cytokeratin 18 and 20 S proteasome in liver degeneration

Hetz

Höetzenecker

Hacker

et al. 2007

Clinical Laboratory Analysis

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Apoptosis of epithelial hepatocytes plays a pivotal role in acute as well as in chronic liver diseases. The cleavage of cytokeratin-18 (CK-18) by caspases is an early event in the apoptotic process. We therefore sought to investigate serum levels of CK-18 and 20S proteasome in patients with liver cirrhosis, primary graft dysfunction (PDF), and acute liver failure (ALF), and in healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the concentration of M30, a fragment of CK-18 cleaved at Asp396 (M30 neoantigen), and the concentration of 20S proteasome. Serum levels of the CK-18 neoepitope M30 were significantly increased in ALF, primary graft dysfunction, and liver cirrhosis vs. healthy controls (1,993.6+/-124.7 U/L, 2,238.1+/-235.9 U/L, and 673.6+/-86.5 U/L vs. 66.8+/-29.1 U/L, respectively, P<0.001). Similar results were detected with the evaluation of 20S proteasome (124,014.5+/-13,235.6 ng/mL, 76,993.2+/-15,720.1 ng/mL, and 2,395.9+/-1,098.2 ng/mL vs. 1,074.5+/-259.4 ng/mL, respectively; P<0.001). Detection of CK-18 neoepitope M30 and 20S proteasome may represent a novel marker of tracing apoptotic epithelium, respectively mirroring degenerative liver processes in affected patient population.

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Section: Discussionmentioning

confidence: 86%

Caspase‐cleaved cytokeratin 18 and 20 S proteasome in liver degeneration

Hetz

Höetzenecker

Hacker

et al. 2007

Clinical Laboratory Analysis

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“…Other groups also reported a M30 increase [15] and TRAIL upregulation [7] in HCC. TRAIL signaling in HCC is of particular interest and a loss of TRAIL receptors has recently been described to further decrease the survival of HCC patients [16].…”

Section: Discussionmentioning

confidence: 92%

Expression of Apoptosis- and Vitamin D Pathway-Related Genes in Hepatocellular Carcinoma

Fingas

Altınbaş²,

Schlattjan³

et al. 2013

Digestion

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Background/Aims: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and therapeutic options are scarce. As they might represent future targets for cancer therapy, the expression of apoptosis-related genes in HCC is of particular interest. In this pilot study, we further examined apoptosis-related genes in human HCC and also focused on vitamin D signaling as this might be a regulator of HCC cell apoptosis. Methods: We employed tumor tissue and serum samples from 62 HCC patients as well as 62 healthy controls for these studies. Tissue and serum specimens were analyzed by quantitative RT-PCR, immunohistochemistry and ELISA. Results: In HCC patients the apoptosis marker M30 was found to be elevated and several pro-apoptotic (TRAIL, FasL and FasR) as well as anti-apoptotic genes (Mcl-1 and Bcl-2) were simultaneously upregulated in tumor tissue and especially tumor-surrounding tissue as compared to healthy control livers. Moreover, vitamin D serum levels were decreased in HCC patients whereas vitamin D receptor mRNA expression was increased in tumor tissue and tumor-surrounding tissue as compared to healthy livers. Conclusions: In human HCC, M30 serum levels are elevated indicating an increased cell turnover. Modulation of the vitamin D pathway might be a supportive, pro-apoptotic HCC therapy.

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“…Apoptosis has been extensively demonstrated in a variety of viral infections outside the brain, including mononucleosis 44 and hepatitis B and C, 45,46 and is also well documented in several viral infections of the brain such as herpes encephalitis, 47,48 poliomyelitis, 49 rabies encephalitis, 50 West Nile encephalitis, 51 subacute sclerosing panencephalitis, 52 and particularly, AIDS encephalopathy. [53][54][55] However, there is a noticeable lack of evidence to support the occurrence of apoptosis in PML.…”

Section: Discussionmentioning

confidence: 99%