Molecular markers of hepatitis C virus-related hepatocellular carcinoma

Sultan, Ahmed; Hessien, Mohamed; S, Mahmoud el; As, Ibrahim; Za, Sherif

doi:10.4161/cbt.5.6.2674

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…It suggests that bcl-2 may have a role in development or progression of HCC in patients with chronic hepatitis C. It was not correlated with total viremia or AFP or ALT levels in all patient groups either infected with HCV or not. Our data indicated that total viremia is related to AFP and bilirubin serum level in patients with chronic hepatitis C. This finding correlates with the previous reports (Sultan et al, 2006) which stated that high viral load associated frequently with HCC in patients with HCV. A study by Sultan.…”

Section: Discussionsupporting

confidence: 92%

The Role of BCL-2 Oncoprotein in Hepatitis C-Related Hepatocellular Carcinoma

Ibrahim¹,

Muawia²,

El-Shahat³

et al. 2016

Research Journal of Applied Biotechnology

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Viral hepatitis has emerged as a major public health problem worldwide. There is increasing evidence that, several viral oncogenes such as core protein C virus (HCV) is playing a direct role in neoplastic transformation. The tumor development requires both increased proliferation and inhibition of apoptosis. There is increasing experimental evidence to suggest that bcl-2 plays a critical role in blocking apoptosis in cancer cells. In the present study we tried to explore the role of bcl-2 in development of viral hepatitis into hepatocellular carcinoma (HCC). Out of 105 participants; 50 patients were HCV positive infected patients, 30 HCC patients either infected with HCV (HCC/HCV) or not (HCC) and 25 healthy volunteers were also included. We determined the serum level of bcl-2, AFP and HCV-RNA viral load in patients and compared them with the other clinicopathological parameters. Increased serum bcl-2 level was showed in HCC/HCV infected patients more than HCV and controls (P=0.001) and more than HCC patients (P=0.018). A significant positive correlation between AFP and total load of viremia was elucidated (r=0.345, P=0.014) in the HCV infected patients who didn′t develop HCC. By analyzing the diagnostic performance of the studied parameters among the different groups. Bcl-2 was found to be a significant prognostic marker for the progression of HCC, as it represented two or more diagnostic values (Sensitivity 80 % , 70% and specificity 60%, 70% respectively).and (OR=6.0, 95% CI=1.74-20.59& OR=5.4 & 95% CI=1.75-16.88).These results make bcl-2 a candidate marker for HCC progression following HCV infection in Egyptian patients.

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Section: Discussionsupporting

confidence: 92%

The Role of BCL-2 Oncoprotein in Hepatitis C-Related Hepatocellular Carcinoma

Ibrahim¹,

Muawia²,

El-Shahat³

et al. 2016

Research Journal of Applied Biotechnology

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“…Currently, the conventional treatments for HCC, such as liver transplantation or resection [ 7 ], radiotherapy, and chemotherapy, have severe side effects. As drug resistance and adverse effects remain two critical hurdles [ 8 ], the necessity of beefing up the development of new anticancer agents has become apparent.…”

Section: Introductionmentioning

confidence: 99%

Manuka honey enhanced sensitivity of HepG2, hepatocellular carcinoma cells, for Doxorubicin and induced apoptosis through inhibition of Wnt/β-catenin and ERK1/2

et al. 2021

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Background Recently, there is increasing awareness focused on the identification of naturally occurring anticancer agents derived from natural products. Manuka honey (MH) has been recognized for its biological properties as antimicrobial, antioxidant, and anticancer properties. However, its antiproliferative mechanism in hepatocellular carcinoma is not investigated. The current study focused mainly on investigating the molecular mechanism and synergistic effect of anticancer properties of MH on Doxorubicin (DOX)-mediated apoptotic cell death, using two different p53 statuses (HepG2 and Hep3B) and one non-tumorigenic immortalized liver cell line. Results MH treatment showed a proliferative inhibitory effect on tested cells in a dose-dependent manner with IC50 concentration of (6.92 ± 0.005%) and (18.62 ± 0.07%) for HepG2 and Hep3B cells, respectively, and induced dramatic morphological changes of Hep-G2 cells, which considered as characteristics feature of apoptosis induction after 48 h of treatment. Our results showed that MH or combined treatments induced higher cytotoxicity in p53-wild type, HepG2, than in p53-null, Hep3B, cells. Cytotoxicity was not observed in normal liver cells. Furthermore, the synergistic effect of MH and Dox on apoptosis was evidenced by increased annexin-V-positive cells and Sub-G1 cells in both tested cell lines with a significant increase in the percentage of Hep-G2 cells at late apoptosis as confirmed by the flow cytometric analysis. Consistently, the proteolytic activities of caspase-3 and the degradation of poly (ADP-ribose) polymerase were also higher in the combined treatment which in turn accompanied by significant inhibitory effects of pERK1/2, mTOR, S6K, oncogenic β-catenin, and cyclin D1 after 48 h. In contrast, the MH or combined treatment-induced apoptosis was accompanied by significantly upregulated expression of proapoptotic Bax protein and downregulated expression of anti-apoptotic Bcl-2 protein after 48 h. Conclusions Our data showed a synergistic inhibitory effect of MH on DOX-mediated apoptotic cell death in HCC cells. To our knowledge, the present study provides the first report on the anticancer activity of MH and its combined treatment with DOX on HCC cell lines, introducing MH as a promising natural and nontoxic anticancer compound.

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“…Also, caspase‐7 has been found to be activated during HSV‐1, SARS‐CoV‐2, influenza and HCV mediated infections, thereby resulting in apoptosis 24–27 . Serum Bcl‐2 level was not significantly altered in any group of dengue patients of this study, which was also noted among HCV‐infected Chinese hamster ovary (CHO‐K1) cells and sera of HCV‐infected Egyptian patients 28,29 . However, earlier studies on febrile children < 24 months age, infected with common cold causing rhinovirus and respiratory syncytial virus also exhibited increased caspase 3/7 activity 30,31 …”

Section: Discussionmentioning

confidence: 52%

“…[24][25][26][27] Serum Bcl-2 level was not significantly altered in any group of dengue patients of this study, which was also noted among HCV-infected Chinese hamster ovary (CHO-K1) cells and sera of HCV-infected Egyptian patients. 28,29 However, earlier studies on febrile children < 24 months age, infected with common cold causing rhinovirus and respiratory syncytial virus also exhibited increased caspase 3/7 activity. 30,31 Significant increase in serum level of hepatic proteins (bilirubin, AST, ALT, and ALP) among SD patients indicated correlation of…”

Section: Discussionmentioning

confidence: 92%

Impact of apoptotic biomarkers for prognosis of dengue disease severity among eastern Indian patients

Sengupta,

Manna,

Saha

et al. 2023

Journal of Medical Virology

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Dengue virus (DENV) induced severe manifestations is a precursor for fatality among infected patients. Previous autopsy examinations of severe dengue (SD) patients reported presence of apoptotic cells in liver, brain, intestinal and lung tissues. Thus, serum‐level of major apoptotic proteins of dengue patients was evaluated in the current study, along with their biochemical parameters. Patients were categorized according to World Health Organization (WHO)‐defined classification. DENV‐infection was screened among 165 symptomatic patients by quantitative reverse transcription polymerase chain reaction, antidengue IgM, and IgG ELISA. Serum levels of apoptotic (Capase‐3,7,8, Bcl‐2 and FasL) and hepatic‐markers, lipid profile, hematological parameters of 78 dengue‐positive patients were determined by sandwich‐ELISA/immunoturbidimetry/auto‐analyzer. Significantly higher levels of caspase‐3,7,8 and FasL was detected among SD patients compared to those without warning (WOW) signs. Amongst biochemical parameters, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase serum concentrations significantly increased among severe patients. Principal component analysis followed by hierarchical clustering differentiated severe and with warning dengue patient groups from those WOW using caspase‐3,7,8 and FasL biomarkers—thus clearly distinguishing severe‐dengue group. Correlation analyses also established strong positive correlation between caspase‐3,7,8 and FasL. Thus, serum level of caspase‐3,7,8 and FasL during early stage of infection could be used as biomarkers for WHO‐defined dengue disease severity.

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Molecular markers of hepatitis C virus-related hepatocellular carcinoma

Cited by 5 publications

References 30 publications

The Role of BCL-2 Oncoprotein in Hepatitis C-Related Hepatocellular Carcinoma

The Role of BCL-2 Oncoprotein in Hepatitis C-Related Hepatocellular Carcinoma

Manuka honey enhanced sensitivity of HepG2, hepatocellular carcinoma cells, for Doxorubicin and induced apoptosis through inhibition of Wnt/β-catenin and ERK1/2

Impact of apoptotic biomarkers for prognosis of dengue disease severity among eastern Indian patients

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