Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

Marra, Monica; Sordelli, I.; Lombardi, Angela; Lamberti, Monica; Tarantino, L.; Giudice, Aldo; Stiuso, Paola; Abbruzzese, Alberto; Sperlongano, Rossella; Accardo, Marina; Agresti, Massimo; Caraglia, Michele; Sperlongano, Pasquale

doi:10.1186/1479-5876-9-171

Cited by 207 publications

(158 citation statements)

References 148 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the variation on antioxidant gene expressions is a result of DNA damage and the alteration of cellular key processes which might not be directly related, as mentioned before, to antioxidant cell defense. The key role of ROS on the initiation stage of carcinogenesis, causing DNA damage, and interference to repair damaged DNA is indubitably recognized (Marra et al, 2011;Tasaki et al, 2014). Biochemical data concerning antioxidant biomarkers should provide early results before any cell or histology significant changes.…”

Section: Discussionmentioning

confidence: 99%

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Santos

Colaço

Costa

et al. 2014

Experimental and Toxicologic Pathology

View full text Add to dashboard Cite

Animal models, namely mice, have been used to study chemically induced carcinogenesis due to their similarity to the histological and genetic features of human patients. Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome. The high incidence of HCC might be related to expo-sure to known risk factors, including carcinogenic compounds, such as N-nitrosamines, which cause DNA damage. N-nitrosamines affect cell mitochondrial metabolism, disturbing the balance between reactive oxygen species (ROS) and antioxidants, causing oxidative stress and DNA damage, potentially leading to carcinogenesis. This work addresses the progressive histological changes in the liver of N-diethylnitrosamine (DEN)-exposed mice and its correlation with oxidative stress.Male ICR mice were randomly divided into five DEN-exposed and five matched control groups. DEN was IP administered, once a week, for eight consecutive weeks.2 Samples were taken 18 h after the last DEN injection (8 weeks post-exposure). The following sampling occurred at weeks 15th, 22nd, 29th and 36th after the first DEN injection. DEN resulted in early toxic lesions and, from week 29 onwards, in progressive proliferative lesions. Between 15 and 29 weeks, DEN-exposed animals showed significant changes in hepatic antioxidant (glutathione, glutathione reductase, and catalase) status (p < 0.05) compared with controls. These results point to an association between increased DEN-induced oxidative stress and the early histopathological alterations, suggesting that DEN disrupted the antioxidant defense mechanism, thereby triggering liver carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Santos

Colaço

Costa

et al. 2014

Experimental and Toxicologic Pathology

View full text Add to dashboard Cite

show abstract

“…Classical antioxidant genes related to cancer include superoxide dismutase (SOD), catalase, GST, glutathione peroxidase, peroxiredoxins (PRDXs), and thioredoxin (Trx) (Basu et al, 2011;Song et al, 2011;Marra et al, 2011). PRDX3 was identified as a member of the peroxiredoxin protein family (Prx), which acts as a cellular defense system against oxidative stress and whose catalytic activity and protein sequences are different from those of other antioxidants (Dietz et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

Shi¹,

Wu²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

show abstract

“…Till date Sorafenib is the well-known approved drug for the treatment of patients with unresectable HCC [50,51]. This multi kinase inhibitor targets serine/threonine kinases Raf/ERK as well as receptor tyrosine kinases VEGF receptor (VEGFR) and PDGF receptor (PDGFR) in HCC [52].…”

Section: Protective Role Of Puma In Non-malignant Cells: the Therapeumentioning

confidence: 99%

Context Dependent Role of P53 Up-Regulated Modulator of Apoptosis (Puma) During Liver Degeneration and Regeneration

Biswas¹

2016

JLRDT

View full text Add to dashboard Cite

Hepatocytes are susceptible to injury due to its contribution in xenobiotic metabolism including drugs and alcohol, fatty acid metabolism and enterohepatic circulation of bile acids and hepato tropic viruses. On the other hand regeneration of hepatocytes is well-studied phenomenon essential for maintenance of its volume during chronic liver injury as well as acute restoration of liver volume after resection. During chronic and acute insult of liver apoptosis and necrosis are the most widely documented forms of hepatocyte cell death. Experimental evidence also demonstrates that apoptosis and cell proliferation are closely linked and many proteins that can induce cell death are, in fact, components of the cell division cycle. Apoptosis is crucial for sustain tissue homeostasis and its circumvention is assumed as a hallmark of cancer. Conversely, there are several evidences also support the contribution of pro-apoptotic Bcl-2 family members in development of liver cancer. They also play vital role during liver regeneration induced by partial hepatectomy, a well characterized in vivo model of cell cycle progression. Here we discuss the context dependent role of specifically one BH3 only group of Bcl-2 family member, Puma during hepatic degeneration and regeneration. Up regulation and down regulation of this specific protein is vital for carcinogenesis as well as hepatic regeneration. The expression levels of Puma contributing to hepatocyte injuries, hepatic proliferation and progression of malignancies are also reflected in the context of potential therapeutic strategies.

show abstract

Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

Cited by 207 publications

References 148 publications

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

Context Dependent Role of P53 Up-Regulated Modulator of Apoptosis (Puma) During Liver Degeneration and Regeneration

Contact Info

Product

Resources

About