A New Diagnostic Method for Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma Based on Serum Metallothionein, Copper, and Zinc Levels

Metallothionein Expression Is Suppressed in Primary Human Hepatocellular Carcinomas and Is Mediated through Inactivation of CCAAT/Enhancer Binding Protein α by Phosphatidylinositol 3-Kinase Signaling Cascade

“…The relative lack of MT expression in primary HCC is consistent with similar observations on hepatocellular, colorectal, and papillary thyroid carcinomas (38)(39)(40). Histochemical analysis has shown that MT expression is significantly reduced even in the serum of patients with HCCs and liver adenocarcinomas and MT level correlates inversely with tumor grade in HCC (41,42). Based on these observations, it is tempting to conclude that the reduced level or absence of MTs can be potential biomarker for HCCs.…”

An Improved Diagnostic Method for Chronic Hepatic Disorder: Analyses of Metallothionein Isoforms and Trace Metals in the Liver of Patients with Hepatocellular Carcinoma as Determined by Capillary Zone Electrophoresis and Inductively Coupled Plasma-Mass Spectrometry

“…[15][16][17] The serum Cu/Zn ratio in the patients with different hepatic diseases has been confirmed to be significantly higher than that of patients without hepatic disorders (Ctrl). [18][19][20] However, during our study, some patients with congestive heart failure, diabetes mellitus, and hypertension exhibited markedly high Cu/Zn ratio, indicating that the ratio could not be considered selective for diagnosing the diseases. On the other hand, we also reported that Cu concentrations in the human liver cytosol increased with the development of HCC.…”

“…On the other hand, we also reported that Cu concentrations in the human liver cytosol increased with the development of HCC. [18][19][20] The increase in Cu concentrations in the hepatic tissues were due to the distribution of Cu in MT rather than in superoxide dismutase (SOD) in the hepatic tissues.21) Based on these observations, we attempted to determine whether monitoring of MT isomers and metal concentrations in human liver is a better approach for diagnosing human liver disorder.It is well known that MT occurs in several isoforms, 22) among which MT-1 and MT-2 are induced in most organs by specific stimuli such as exposure to toxic metals and glucocorticoids. 23) Although the biological functions and physiological role of MT are not yet known, based on the results of the analysis of hepatic MT-1 and MT-2 in LEC rats we recently proposed that MT-1 is related to the metabolism or detoxification of toxic metals such as cadmium, and, MT-2 is responsible for the homeostasis of essential metals such as Cu.…”

“…On the other hand, we also reported that Cu concentrations in the human liver cytosol increased with the development of HCC. [18][19][20] The increase in Cu concentrations in the hepatic tissues were due to the distribution of Cu in MT rather than in superoxide dismutase (SOD) in the hepatic tissues. 21) Based on these observations, we attempted to determine whether monitoring of MT isomers and metal concentrations in human liver is a better approach for diagnosing human liver disorder.…”

Plasma concentrations of zinc, copper, interleukin-6 and interferon-γ, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C

“…In contrast, serum copper levels are significantly elevated in patients with cirrhosis and hepatocellular carcinoma compared with patients with chronic hepatitis and healthy control subjects. Zinc concentration is reduced in all three patient groups compared with control subjects (16).…”