Activity and Expression Pattern of NF-κB/P65 in Peripheral Blood from Hepatocellular Carcinoma Patients - Link to Hypoxia Inducible Factor -1α

Gaballah, Hanaa Hibishy; Zakaria, Soha S.; Ismail, Saber A.

doi:10.7314/apjcp.2014.15.16.6911

Cited by 10 publications

(4 citation statements)

References 45 publications

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“…This is supported by the recent study of Gaballah et al which provided evidence that active NF-κB signaling has a major contribution to the molecular pathogenesis of human hepatocellular carcinoma. They also concluded that, the association between NF-κB activity and expression levels with the bad prognostic parameters for HCC potentiates their value as prognostic markers to predict treatment outcome, metastasis or recurrence (Gaballah et al, 2014). Luedde and Schwabe (2011) proposed that NF-ĸB acts as a central link between hepatic injury, fibrosis and HCC, and that it may represent a target for the prevention or treatment of liver fibrosis and HCC.…”

Section: Discussionmentioning

confidence: 99%

Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma

Ismail¹,

Mayah²,

Battia³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-ĸB) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-ĸB) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-ĸB and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-ĸB) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-ĸB and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-ĸB) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

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Section: Discussionmentioning

confidence: 99%

Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma

Ismail¹,

Mayah²,

Battia³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…192 During anti-angiogenic treatments and especially after hypoxia-promoting interventions such as transarterial chemoembolization, monitoring hypoxia by quantification of HIF-1a levels in the blood could be helpful to adjust the drug dose. [194][195][196] Anti-VEGF/VEGFR treatments lead to the development of resistance through several mechanisms, such as upregulation of VEGF or other pro-angiogenic factors, which could be targeted in combination therapies with VEGF, including ephrins, placental growth factor, FGFR, p38, and angiopoietin. 193,[197][198][199][200] In preclinical models, targeting angiopoietin 2 (Ang2) + VEGF and VEGF + PDGF had better vessel-normalization effects at lower doses than VEGF alone.…”

Section: Mkismentioning

confidence: 99%

The therapeutic landscape of hepatocellular carcinoma

Gallage

García‐Beccaria

Szydlowska

et al. 2021

Med

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The liver is endowed with an amazing regenerative capacity that allows it to withstand an enormous amount of damage. Nevertheless, it is precisely this highly regenerative capacity that renders it susceptible to dysplasia and liver cancer. Liver cancer is not only one of the most common cancers but also one of the deadliest. Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for up to 70%-90% of all cases, but treatment options for advanced stages remain scarce. Therefore, a great deal of effort has gone into identifying early diagnostic markers as well as novel therapies, both local and systemic, for the treatment of this deadly disease. In this review, we aim to shed light into the current therapeutic landscape of HCC with an emphasis on the available treatments, ranging from surgical and local-ablative therapy for early and intermediate stages of the disease to systemic therapies for advanced cancer treatments. We will also address the molecular mechanisms and limitations of currently available systemic therapies and the causes of treatment resistance and finally summarize the emerging future avenues and novel concepts that are promising.

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“…oxygen-sensitive alpha subunit (HIF-α) and a constitutive beta subunit (HIF-β). Both subunits are heterodimeric, facilitating both oxygen delivery and adaptation to oxygen deprivation (Gaballah et al, 2014). HIF-1α is a transcription factor that binds to hypoxia responsive element (HRE), which in turn enhances the transcription of hypoxia-responsive genes.…”

mentioning

confidence: 99%

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

Shafik¹,

Mohamed²,

Bedder³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background:The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-1 α (HIF-1α), with the inflammatory markers nuclear factor kappa B/p65 (NF-κB /P65) and interleukin-1 beta (IL-1β) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-κB /P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-1α and IL-1β were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma (1.47±0.31 and 184.98±18.18, respectively) compared to low grade carcinoma (1.21±0.32 and 171.76±7.58, respectively) and controls (0.70±0.02 and 65.34±6.41, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-1α and IL-1β as well as NF-κB /P65 DNA binding activity were significantly higher in high grade breast carcinoma (148.54±14.20, 0.79±0.03 and 247.13±44.35 respectively) than their values in low grade carcinoma ( 139.14±5.83, 0.34±0.02 and 184.23±37.75, respectively) and controls (33.95±3.11, 0.11±0.02 and 7.83±0.92, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-1α could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-1β and NF-κB/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

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Activity and Expression Pattern of NF-κB/P65 in Peripheral Blood from Hepatocellular Carcinoma Patients - Link to Hypoxia Inducible Factor -1α

Cited by 10 publications

References 45 publications

Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma

Plasma Nuclear Factor Kappa B and Serum Peroxiredoxin 3 in Early Diagnosis of Hepatocellular Carcinoma

The therapeutic landscape of hepatocellular carcinoma

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

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