Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently it has been shown that the expression of the immunoproteasome increased in proportion to the degree of chronic inflammation in both the liver cell cytoplasm and nuclei in liver biopsies from patients who had chronic active hepatitis or cirrhosis. In the present study, biopsies from patients with steatohepatitis, with or without Mallory-Denk body (MDB) formation, were studied by immunofluorescent staining. Normal liver showed colocalization of FAT10, LMP2, LMP7, and MECL-1 at the mitochondria. Only LMP2 and LMP7 were found in the cell nuclei. Liver biopsies from patients with steatohepatitis and MDB formation, and a case of hepatocellular carcinoma forming MDBs in the tumor cells, showed colocalization of FAT10 and ubiquitin with LMP2, LMP7 and MECL-1 within the MDB. This indicates involvement of the immunoproteasome in MDB formation in steatohepatitis cases and in a case of HCC forming MDBs. Prior studies have shown that the immunoproteasome was involved in drug-induced MDB formation using the same immunofluorescent colocalization approach as was used on these human liver biopsies. The increase in the immunoproteasome subunit proteins was made at the expense of the 26S proteasome. This indicates that the shift from the 26S to the immunoproteasome had occurred in the MDB positive hepatocytes.
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PMID:The immunoproteasome in steatohepatitis: its role in Mallory-Denk body formation. 2125 43

The most common type of liver cancer, hepatocellular carcinoma (HCC), affects over 500,000 people in the world. In the present study, liver tumor resections were used to prepare tissue arrays to examine the intensity of fluorescence of IHC stained stem cell markers in liver tissue from malignant HCC tumors and accompanying surrounding non-tumor liver. We hypothesized that a correlation exists between the fluorescence intensity of IHC stained HCC and surrounding non-tumor liver compared to liver tissue from a completely normal liver. 120 liver resection specimens (including four normal controls) were placed on a single slide to make a tissue array. They were examined by digitally quantifying the intensity of fluorescence using immuno-histochemically stained stem cell markers and protein quality control proteins. The stem cell markers were OCT3/4, Nanog, CD133, pEZH2, CD49F and SOX2. The protein quality control proteins were FAT10, UBA-6 and ubiquitin. The data collected was used to compare normal liver tissue with HCCs and parent liver tissue resected surgically using antibodies to stem cell markers and quality control protein markers. The measurements of the stem cell marker CD133 indicated an increase of fluorescence intensity for both the parent liver tissue and the HCC liver tissues. The other stem cell markers changed as follows: Nanog and OCT3/4 were decreased in both the HCCs and the parent livers; PEZH2 was reduced in the HCCs; SOX2 was increased in the parent livers compared to the controls; and CD49f was decreased in HCCs only. Protein quality control markers FAT10 and ubiquitin were downregulated in both the HCCs and the adjacent non-tumor tissue compared to the controls. UBA6 was increased in both the HCCs and the parent livers, and the levels were higher in the HCCs compared to the parent livers.
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PMID:Digital quantitation of HCC-associated stem cell markers and protein quality control factors using tissue arrays of human liver sections. 2521 10