Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease

Abstract

To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma.

Expression of Fucosyltransferase 8 Is Associated with an Unfavorable Clinical Outcome in Non-Small Cell Lung Cancers

“…The upregulation of FUT8 has been observed in several types of malignancy, including liver, ovarian, thyroid, and colorectal cancers [15,16,17,18]. In thyroid papillary carcinomas, high expression of FUT8 is linked to tumor size and lymph node metastasis [15].…”

“…Many studies show that alterations in asparagine-linked oligosaccharides of tumor cells are associated with carcinogenesis, invasion, and metastasis [10,11,12]. Among 13 fucosyltransferases known to be encoded by the human genome, fucosyltransferase 8 (FUT8) is the only enzyme to catalyze the transfer of a fucosyl moiety from guanosine diphosphate (GDP)-fucose to the innermost GlcNAc residue of hybrid and complex asparagine-linked oligosaccharides in glycoprotein via α1,6 linkage to form core fucosylation, which is frequently observed in malignant transformation [13,14,15,16,17,18]. Increased FUT8 activity is certainly an important factor in the regulation of fucosylation, although other factors may be involved in its regulation, such as the synthesis of GDP- L -fucose (GDP- L -Fuc), the substrate for FUT8.…”