P.131 Superoxide dismutase in hepatocellular carcinoma affects patient prognosis

Lin, Ming-Tsan; Liaw, Koung-Yi; Lee, Po-Huang; Chien, Shiuh‐Shen; Tsai, Jir-Shiong; Lin-Shiaut, Shoei-Yn

doi:10.1016/s0261-5614(98)80287-2

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extra neuronal phenotypes are also striking, in particular the well-known susceptibility to hepatocellular carcinoma, a feature that also manifests in the human population; there is a positive correlation between SOD1 activity and postoperative hepatocellular carcinoma survival time, as well as low levels of SOD1 and severity of hepatocellular carcinoma (Elchuri et al , 2005; Takahashi et al , 2002; Casaril et al , 1994; Liaw et al , 1997; Lin et al , 2001). Other non-neuronal features include impaired endothelial-dependent relaxation, thinning of the skin, osteoporosis and female infertility (Supplementary Box 1).…”

Section: Sod1−/− Mice Have Neuromuscular Neuronal and Extra-neuronalmentioning

confidence: 99%

Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

Saccon

Bunton-Stasyshyn

Fisher

et al. 2013

Brain

262

235

View full text Add to dashboard Cite

Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a—still unknown—toxic gain of function, and the possibility that loss of function plays a role in amyotrophic lateral sclerosis pathogenesis was abandoned. Although loss of function is not causative for amyotrophic lateral sclerosis, here we re-examine two decades of evidence regarding whether loss of function may play a modifying role in SOD1–amyotrophic lateral sclerosis. From analysing published data from patients with SOD1–amyotrophic lateral sclerosis, we find a marked loss of SOD1 enzyme activity arising from almost all mutations. We continue to examine functional data from all Sod1 knockout mice and we find obvious detrimental effects within the nervous system with, interestingly, some specificity for the motor system. Here, we bring together historical and recent experimental findings to conclude that there is a possibility that SOD1 loss of function may play a modifying role in amyotrophic lateral sclerosis. This likelihood has implications for some current therapies aimed at knocking down the level of mutant protein in patients with SOD1–amyotrophic lateral sclerosis. Finally, the wide-ranging phenotypes that result from loss of function indicate that SOD1 gene sequences should be screened in diseases other than amyotrophic lateral sclerosis.

show abstract

Section: Sod1−/− Mice Have Neuromuscular Neuronal and Extra-neuronalmentioning

confidence: 99%

Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

Saccon

Bunton-Stasyshyn

Fisher

et al. 2013

Brain

262

235

View full text Add to dashboard Cite

show abstract

“…The role of ROS in hepatocarcinogenesis is supported by an electron paramagnetic resonance study on patients with chronic hepatitis and at different stages of malignant transformation (Valgimigli et al, 2002). Several clinical studies with patients at different stages of HCC showed a strong correlation between low levels of SOD and the severity of HCC (Huang and Wu, 1990;Inagaki et al, 1992;Casaril et al, 1994;Liaw et al, 1997), and SOD activities in tumors and surrounding normal tissues have been found to correlate positively with postsurgery survival time in HCC patients (Lin et al, 2001). In addition, overexpression of CuZnSOD in the HCC cell line HepG2 has been shown to suppress cell growth in vitro and to reduce tumor mass in vivo (Bai et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

et al. 2004

View full text Add to dashboard Cite

Mice deficient in CuZn superoxide dismutase (CuZn-SOD) showed no overt abnormalities during development and early adulthood, but had a reduced lifespan and increased incidence of neoplastic changes in the liver. Greater than 70% of Sod1À/À mice developed liver nodules that were either nodular hyperplasia or hepatocellular carcinoma (HCC). Cross-sectional studies with livers collected from Sod1À/À and age-matched þ / þ controls revealed extensive oxidative damage in the cytoplasm and, to a lesser extent, in the nucleus and mitochondria from as early as 3 months of age. A marked reduction in cytosolic aconitase, increased levels of 8-oxo dG and F2-isoprostanes, and a moderate reduction in glutathione peroxidase activities and porin levels were observed in all age groups of Sod1À/À mice examined. There were also age-related reductions in Mn superoxide dismutase activities and carbonic anhydrase III. Parallel to the biochemical changes, there were progressive increases in the DNA repair enzyme APEX1, the cell cycle control proteins cyclin D1 and D3, and the hepatocyte growth factor receptor Met. Increased cell proliferation in the presence of persistent oxidative damage to macromolecules likely contributes to hepatocarcinogenesis later in life.

show abstract

“…SOD is a metalloenzyme that protects cells from oxygen-free radicals. Notably, a decrease in SOD level was reported to be related to the survival rate of HCC patients, 201,202 suggesting that SOD can be used as a prognostic marker of HCC. Using conventional methods, the down-regulation of enoyl-CoA hydratase was also demonstrated in HBV-associated diseases and HCC.…”

Section: Serological Markersmentioning

confidence: 99%

The Molecular Diagnosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Wong

Chan²,

Chan³

et al. 2006

Critical Reviews in Clinical Laboratory Sciences

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC) worldwide. The pathogenesis of HBV-associated HCC has been studied extensively, and molecular changes during malignant transformation have been identified. It has been proposed that the insertion of HBV DNA into the human genome results in chromosomal instability and inactivation of tumor suppressor genes. Transactivation of oncogenes, inactivation of tumor suppressor genes, and alteration of the cell cycle by HBV proteins are also involved in the progression of hepatocellular carcinogenesis. Traditional clinical examinations of HCC, such as biopsy, computer tomography, ultrasonic imaging, and detection of such biomarkers as a-fetoprotein, are currently the "gold standard" in diagnosis. These tests diagnose HCC only in the late stages of disease. This limitation has greatly reduced the chance of survival of HCC patients. To resolve this problem, new biomarkers that can diagnose HCC in earlier stages are necessary. Based on recent molecular studies of the effects of HBV on cellular transformation, differentially expressed biomarkers of HBV infection have been elucidated. With the analyses of the HBV replication profile, the viral load (HBV DNA levels) of patients, and the viral protein expression, the severity of hepatitis in the preneoplastic stages can be assessed. In the future, with the molecular profiles identified by genomic and proteomic approaches, stage-specific biomarkers should be identified to monitor the progression and prognosis of HCC.

show abstract

P.131 Superoxide dismutase in hepatocellular carcinoma affects patient prognosis

Cited by 4 publications

References 0 publications

Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life

The Molecular Diagnosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Contact Info

Product

Resources

About