scholarly journals The Role of HSP70, CD34 and Ki 67 Expression in Liver Cirrhosis and Hepatocellular Carcinoma, Immunohistochemical Study

2018 ◽  
Vol 10 (1) ◽  
pp. 91-101
Author(s):  
Sayed Abdel Raheem, ◽  
Abdel Naby Saied ◽  
Emadeldin Mater
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Immunohistochemical Study ◽  
Ki 67

scholarly journals Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2560
Author(s):  
Luis G. Guijarro ◽  
Patricia Sanmartin-Salinas ◽  
Eva Pérez-Cuevas ◽  
M. Val Toledo-Lobo ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Cellular Polarity ◽  
Ki 67 ◽  
Tissue Samples ◽  
Vitro Analysis ◽  
Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

Dantrolene Potentiates the Antineoplastic Effect of Sorafenib in Hepatocellular Carcinoma via Targeting Ca+2/PI3K Signaling Pathway

2021 ◽  
Vol 14 ◽  
Author(s):  
Sherin Zakaria ◽  
Abeer Ansary ◽  
Nabil M. Abdel-Hamid ◽  
Mamdouh M. ElShishtawy
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cyclin D1 ◽  
Antineoplastic Agent ◽  
Inhibitory Effect ◽  
Pi3k Pathway ◽  
Ki 67 ◽  
Antineoplastic Effect ◽  
Pi3k Signaling Pathway ◽  
Proliferation And Metastasis

Background: Hepatocellular carcinoma (HCC) is the 6th prevalent cancer and the 4th leading cause of cancer related deaths all over the world. A major challenge for sorafenib, the standard chemotherapeutic agent in HCC treatment, is the chemo-resistance. Objective: This study was conducted to evaluate the role of dantrolene as a possible antineoplastic agent in HCC, and in chemo-sensitization of sorafenib via targeting Ca+2/PI3K pathway. Methods: HCC was induced in rats using a single dose of diethyl nitrosamine (DENA) (200 mg/kg, ip), followed by phenobarbital sodium (0.05%) in drinking water for 18 weeks. At the end of 18th week, rats were allocated into 4 groups (10 rats/each), one group was left without treatment (DENA group) and the other three groups were treated with either sorafenib, dantrolene, or their combination for further 4 weeks. One day after last injection, serum and liver tissues were collected. Liver tissue p53, VEGF, MMP-9, Cyclin D1, PI3K, and, serum AFP were assessed using immunoassay. Hepatic and serum Ca+2 were also computed. Furthermore, Ki67 was assessed immunohistochemically. Results: Dantrolene exhibited synergistic effect when used in combination with sorafenib compared to either drug alone (p <0.05) through decreasing p53, VEGF, MMP-9, Cyclin D1, and Ki-67. In addition, dantrolene was evidenced to have an inhibitory effect on Ca+2/PI3K pathway that mediates its antineoplastic action when used alone or in combination with sorafenib. Conclusion: Dantrolene exerted antineoplastic effect as well as augmented sorafenib antineoplastic activity via intervention of Ca+2/PI3K pathway, manifested by ameliorating angiogenesis, apoptosis, proliferation and metastasis.

scholarly journals Role of CD8 Cytotoxic T Lymphocytes in Hepatocellular Carcinoma: An Immunohistochemical Study

2019 ◽  
Vol 87 (12) ◽  
pp. 4061-4069
Author(s):  
ASMAA G. ABDOU, M.D.; HALA S. EL-REBEY, M.D. ◽  
NANIS S. HOLAH, M.D.; MERVAT S. SULTAN, M.D. ◽  
SHYMAA H. IBRAHIM, M.Sc.
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Immunohistochemical Study

scholarly journals The Role of IL-35 in the Pathophysiological Processes of Liver Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuang Hu ◽  
Pan-pan Lian ◽  
Ying Hu ◽  
Xing-yu Zhu ◽  
Shao-wei Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Liver Diseases ◽  
T Regulatory Cells ◽  
Liver Inflammation ◽  
Regulatory Cells ◽  
Anti Inflammatory ◽  
Lipid Metabolic Disorder ◽  
Environmental Attack

It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.

Diagnostic Role of Blood Tumor Markers in Predicting Hepatocellular Carcinoma in Liver Cirrhosis Patients Undergoing Liver Transplantation

2016 ◽  
Vol 21 ◽  
pp. 660-667 ◽  
Author(s):  
Younghwan Kim ◽  
Yo-Han Park ◽  
Shin Hwang ◽  
Ki-Hun Kim ◽  
Chul-Soo Ahn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Cirrhosis ◽  
Tumor Markers ◽  
Diagnostic Role

scholarly journals The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma

2012 ◽  
Vol 12 (11) ◽  
Author(s):  
Olfat Hammam ◽  
Ola Mahmoud ◽  
Manal Zahran ◽  
Sohair Aly ◽  
Karim Hosny ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Fas Ligand ◽  
Ligand System

scholarly journals Role of bile acids in the prediction of hepatocellular carcinoma in HCV-induced liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashraf Khalil ◽  
Azza Elsheashaey ◽  
Eman Abdelsameea ◽  
Manar Obada ◽  
F. F. Mohamed Bayomy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Bile Acids ◽  
Organic Molecules ◽  
Roc Curves ◽  
Chronic Liver ◽  
Control Group ◽  
Serum Bile Acid ◽  
And Control

Abstract Background Bile acids are essential organic molecules synthesized from cholesterol in the liver and regarded as indicators of hepatobiliary impairment; however, their role in the pathogenesis of hepatocellular carcinoma (HCC) is still unclear. The study aimed to examine the feasibility of bile acids in distinguishing HCC from post hepatitis C virus liver cirrhosis. A UPLC/MS was used to measure 14 bile acids in patients with noncirrhotic HCV disease (n = 50), cirrhotic HCV disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50). Results The progression of liver cirrhosis to HCC was associated with a significant increase in serum bile acids compared to the normal or the noncirrhotic HCV disease (p < 0.05). The fold changes in bile acids concentrations showed a trend that HCC > cirrhotic HCV disease > noncirrhotic HCV disease. Four conjugated acids GCA, GCDCA, GUDCA, and TCDCA steadily increased across the different groups. ROC curves analysis revealed that these bile acids discriminated noncirrhotic liver patients from HCC (AUC 0.850–0.963), with a weaker potential to distinguish chronic liver cirrhosis from HCC (AUC 0.414–0.638). Conclusion The level of serum bile acid was associated primarily with liver cirrhosis, with little value in predicting the progress of chronic liver cirrhotic disease into hepatocellular carcinoma.

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