Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma

El-Baky, Reham M Abd; Hetta, Helal F; Koneru, Gopala; Ammar, Marwa; Shafik, Engy A; Mohareb, Dina A; El‐Masry, Muhammad Abbas; Ramadan, Haidi Karam‐Allah; Rahma, Mohamed Zakaria Abu; Fawzy, Michael Atef; Fathy, Moustafa

doi:10.1007/s12026-020-09126-8

Cited by 20 publications

(16 citation statements)

References 45 publications

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“…Hepatocellular carcinoma (HCC) the fourth most common cause of cancer-related death worldwide; >80% of HCC cases occur in low-resource and middle-resource countries, particularly in Eastern Asia and sub-Saharan Africa, where medical and social care resources are often constrained [1]. One of the common risk factors for HCC is chronic hepatitis B and chronic hepatitis C (CHC) infection [2][3][4]. In areas with a high endemicity of HCV, like in Egypt, a rising trend of HCC will be expected [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

et al. 2020

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Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.

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Section: Introductionmentioning

confidence: 99%

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

et al. 2020

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“…[19][20][21][22][23][24][25][26] Advanced hepatocellular carcinoma is a challenging disease with different epidemiology and risk factors based on demographics worldwide. 27,28 There was no universal approved drug for systemic treatment of advanced HCC until the approval of sorafenib. As sorafenib showed short overall survival benefit and modest response, clinical trials have been ongoing in that field.…”

Section: Discussionmentioning

confidence: 99%

<p>Cytotoxic Chemotherapy as an Alternative for Systemic Treatment of Advanced Hepatocellular Carcinoma in Developing Countries</p>

Abouelezz¹,

Khanapara²,

Batiha³

et al. 2020

CMAR

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Systemic therapy options nowadays for advanced hepatocellular carcinoma (HCC) are either immunotherapy with immune checkpoint inhibitors or targeted therapy. As the incidence of liver cancer is much higher in developing countries, these new medications are not readily accessible for most of the patients. Cytotoxic chemotherapy agents are more available and affordable in developing countries. We are trying to explore the effectiveness of the newer cytotoxic agents in the systematic treatment for advanced HCC. This is a systematic review of all randomized controlled trials since 1997 that utilized systemic cytotoxic chemotherapy agents in the systemic treatment for advanced HCC using Scopus, PubMed, and Cochrane library up to February 2020. Six randomized trials were found. Different drugs and dosages were used, so it was statistically inappropriate to conduct a meta-analysis. No Phase III trial showed statistically significant overall survival (OS) benefit for cytotoxic chemotherapy, except subgroup analysis of Chinese patients in one study who had leucovorin, fluorouracil, and oxaliplatin (FOLFOX) regimen. There was no significant progression-free survival (PFS) or response rate in the Phase II trials. There are not enough data to infer the actual benefits of systemic cytotoxic chemotherapy in advanced HCC. However, oxaliplatin-based regimens may give feasible results. Health systems with limited access to targeted therapy and immunotherapy agents may use oxaliplatin-based regimens in clinical trials for advanced HCC. These results should be confirmed in multiple future randomized clinical trials.

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“…However, when the triggering factors are not contained, inflammation can be associated with a dysregulation of the normal physiological processes, and the escalated response can cause serious chronic inflammatory disorders [ 1 , 2 , 3 , 4 ]. Inflammation can contribute to the pathogenesis of arthritis, stroke, cancer, neurodegenerative, and cardiovascular diseases [ 5 , 6 , 7 , 8 , 9 ]. Prostaglandins (PGs) are key regulators in the generation of the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

A New EGFR Inhibitor from Ficus benghalensis Exerted Potential Anti-Inflammatory Activity via Akt/PI3K Pathway Inhibition

Alaaeldin

Hassan

Abdel-Rahman

et al. 2022

CIMB

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Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysis. Furthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition.

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Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma

Cited by 20 publications

References 45 publications

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

<p>Cytotoxic Chemotherapy as an Alternative for Systemic Treatment of Advanced Hepatocellular Carcinoma in Developing Countries</p>

A New EGFR Inhibitor from Ficus benghalensis Exerted Potential Anti-Inflammatory Activity via Akt/PI3K Pathway Inhibition

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