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The Type II Pneumocyte
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
Freshly isolated type II cells from adult rat lung also synthesize four cytokeratins96 which, by electrophoretic mobilities and Western blot analysis, correspond to the same human cytokeratins. While in fully differentiated type II cells, cytokeratin 19 is predominant, in fetal immature epithelial cells it is synthesized at minimal levels. In contrast, cytokeratin 18 is largely expressed. When the undifferentiated epithelial cells are allowed to mature, either in utero or in vitro in appropriate conditions, they gradually develop the cytokeratin pattern of differentiated type II cells.96
Principles of Clinical Pathology
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Niraj K. Tripathi, Jacqueline M. Tarrant
Cytokeratin 18 (CK18) is a cytoskeletal protein found in epithelial tissue and associated with structural integrity of the cell. The full-length form is released from necrotic cells while a shorter fragment represents the caspase-cleaved (cc-CK18) product formed during apoptosis. Soluble CK18 is detected in human serum with immunoassays and these are applied to the diagnosis of patients with nonalcoholic steatohepatitis. In patients with suspected acetaminophen overdose, serum levels of CK18 total (M65 assay) and cc-CK18 (M30 assay) at hospital admission had good correlation with peak ALT and the liver functional marker, prothrombin time (Antoine et al. 2012; Antoine et al. 2013). These markers, CK18 and cc-CK18, provided better prediction of acetaminophen-related acute liver injury than ALT, especially in patients where ALT was within the normal range during the hospital visit and/or patients presenting within 8 h of overdose (Antoine et al. 2013). Furthermore, CK-18 was also prognostic in this context, with higher levels stratifying patients with a poor outcome. At the time of writing, there are no immunoassays available for rodent total and cc-CK18 and investigators have used laboratory-developed immunoprecipitation-LC-MS assay. In a mouse model of acetaminophen-induced toxicity, the apoptotic marker of CK18 transiently appeared early and the full length necrosis marker had a gradual increase over time. The pattern in CK18 corresponded with histologic and biochemical evidence of hepatocyte apoptosis and necrosis. This study demonstrated the value of CK18 as mechanistic biomarkers (Antoine et al. 2009).
Cell Differentiation and Heterogeneity in Spheroid Culture
Published in Rolf Bjerkvig, Spheroid Culture in Cancer Research, 2017
Ruth Knüchel, Robert M. Sutherland
In the more complex structure of tumor spheroids, examples of higher degrees of morphological differentiation, in comparison to monolayers, are numerous. Colon carcinoma spheroids from the cell line CO112 showed glandular formation with polar cells (Figure 1) and an eightfold increase in carcinoembryonic antigen (CEA) expression;23 nude mice xenograft tumors of the same cell line were similar in both respects. Surface cells of choriocarcinoma spheroids grown for more than 3 weeks became partly multinucleated, indicating additional trophoblast features.24 Similarly, enhanced expression of cytokeratin 18 was seen in the very flat surface cells of tumor spheroids of the moderately differentiated transitional cell line RT4.25 This cytokeratin is also expressed in the large surface cells of the normal transitional epithelium, called umbrella cells. Although these observations stress the importance of cell shape, correlation of spatial configuration and expression of bladder-tumor surface antigens could be demonstrated in another experiment in which two new transitional carcinoma-associated antigens, M344 and 19A211, were studied. The antigens showed a heterogeneous distribution in in vivo tumors, but were not found when the specific antibodies were applied to monolayer cultures of different transitional carcinoma cell lines. However, the antigen expression was high in spheroids and xenograft tumors of the same cell lines.26
Nonalcoholic fatty liver disease: use of diagnostic biomarkers and modalities in clinical practice
Published in Expert Review of Molecular Diagnostics, 2021
Saleh A Alqahtani, Jörn M Schattenberg
Several serum biomarkers have been examined and evaluated to assess NASH with unsatisfactory results. Cytokeratin 18 (CK18), is an intermediate filament protein found in hepatocytes that is released into the serum upon initiation of apoptosis and cleaved by caspase to yield CK18-M30 and CK18-M65 fragments. A meta-analysis combining 30 studies reported an AUC [95% CI] of 0.75 [0.69–0.82] for M30 and 0.82 [0.69–0.91] (M65) for NASH [54]. This decreased to 0.73 [0.57–0.85] (M30) for fibrotic NASH and 0.68 (M30) for significant (F2-4) fibrosis. Limitations include the lack of a specified cutoff inaccuracy, and different assay generation that have been used. A number of biomarker panels have included M30 together with other markers to improve the performance and reliability of diagnosing NASH. One such study, combining metabolic syndrome, ALT, and CK18 in morbidly obese patients, showed better performance with an AUROC of 0.88 than using only CK18, which had an AUROC value of 0.74 [55]. Another study reported that the triple combination of CK18, adiponectin, and interleukin (IL)-16 showed an AUROC of 0.90 with a sensitivity and specificity of 84.5% and 85.7%, respectively [56].Table 1
Lichens exerts an anti-proliferative effect on human breast and lung cancer cells through induction of apoptosis
Published in Drug and Chemical Toxicology, 2021
Sule Ozturk, Merve Erkisa, Seyhan Oran, Engin Ulukaya, Serap Celikler, Ferda Ari
Cytokeratin 18 (CK-18) is cleaved by specific caspases in apoptosis, followed by the occurrence of new CK-18 fragments (M30 antigens) whose concentrations are measured by an immunoassay kit (M30-Apoptosense ELISA kit, Peviva AB, Sweden). 10 000 cells were grown in a 96-well plate in 200 μl culture medium in triplicate and then treated for 72 h with 100 µg/ml of lichen extracts. As a positive control for cell death, paclitaxel (3.12 μM) was used because this agent is considered an appropriate apoptosis-inducer. Cells were exposed to 10% NP-40 for lysis for 10 min on a shaker at the end of the treatment. Wells were centrifuged at 2000 rpm for 10 s to remove the debris, followed by the placement of samples into wells that are coated with a mouse monoclonal antibody as a catcher. After cleansing the plate wells, M30 antibody that is horseradish peroxidase-conjugated was used for detection. An ELISA reader was used to read the absorbances at 450 nm (FLASH Scan S12, Eisfeld, Germany).
Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
Published in Gut Microbes, 2020
Luca Maccioni, Bei Gao, Sophie Leclercq, Boris Pirlot, Yves Horsmans, Philippe De Timary, Isabelle Leclercq, Derrick Fouts, Bernd Schnabl, Peter Stärkel
Cytokeratin 18 is released upon cell damage (necrosis, apoptosis) and has been considered as a liver-specific cell damage marker.32 Serum CK18-M65 increased significantly in AUD patients compared to healthy volunteers. When looking at the different clinical subgroups, high CK-M65 levels were found in AUD patients with progressive ALD but not in those with non-progressive forms of the disease (Figure 2). Receiver operating curve (ROC) analysis showed that serum CK18-M65 levels allowed to distinguish with high accuracy progressive ALD from the non-progressive forms of liver disease (AUROC = 0.8767; 95%CI: 0.7983–0.9551; p < .0001). We then identified the cutoff using the Youden’s statistics (416 U/L) with the best specificity and sensitivity profile (85.7% and 77.1%, respectively). Interestingly, CK18-M65 levels did not separate patients with steato-hepatitis from those with steato-fibrosis within the progressive ALD group (Supplementary Figure 1). Thus, CK18-M65 was associated with liver damage regardless of fibrosis.