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Currently, many challenges are associated with hepatocellular carcinoma (HCC) as the failure of early diagnosis, and the lack of effective therapy. This study aimed to investigate the possible role of tuftelin 1 (TUFT 1) in the early diagnosis of HCC and evaluate the potential contribution of the TUFT 1/Ca+2/phosphinositol 3 kinase (PI3K) pathway in dantrolene sodium (Dan) therapeutic outcomes. The study was performed on two sets of rats, the staging (30 rats) and treatment sets (80 rats). HCC was induced by a single dose of diethylnitrosamine (DENA). The hepatic content of TUFT 1 protein was assayed via western blot and immunohistochemistry (IHC), while PI3K, vascular endothelial growth factor (VEGF), Cyclin D1, and matrix‐metalloproteinase‐9 (MMP‐9) contents were assessed using enzyme‐linked immunosorbent assay. Hepatic and serum calcium were measured colorimetrically. Furthermore, the nuclear proliferation marker, (Ki‐67), (Kiel [Ki] where the antibody was produced in the University Department of Pathology and the original clone number is 67)—expression was assessed by IHC. TUFT 1/Ca+2/PI3K signaling pathway was progressively activated in the 3 studied stages of HCC with subsequent upregulation of angiogenesis, cell cycle, and metastasis. More interestingly, Dan led to TUFT 1/Ca+2/PI3K pathway disruption by diminution of the hepatic contents of TUFT 1, calcium, PI3K, VEGF, Cyclin D1, and MMP‐9 in a dose‐dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC. Moreover, Dan exerted an antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2/PI3K pathway. Significance statement: We investigated the role of tuftelin 1 (TUFT 1) TUFT 1/Ca+2/phosphinositol 3 kinase (PI3K) pathway in giagnosis, staging and dantrolene sodium (Dan) therapy. Hepatocellular carcinoma (HCC) was induced by diethylnitrosamine (DENA). TUFT 1/Ca+2/PI3K signaling pathway was progressively activated during stages of HCC with upregulation of angiogenesis, cell cycle, and metastasis. Dan led to TUFT 1/Ca+2/PI3K pathway disruption by depressing the hepatic contents of TUFT 1, calcium, PI3K, vascular endothelial growth factor, Cyclin D1, and metalloproteinase 9 in a dose‐dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC and Dan showed a promising antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2/PI3K pathway. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly fatal tumor which represents a major health problem worldwide. Due to asymptomatic nature of HCC, most patients present with the progressive stage of disease, so, unfortunately, there are no effective therapies. Existing techniques for HCC surveillance and diagnosis lack the required accuracy. Therefore, searching for new diagnostic and/or therapeutic tools could improve patient survival. This study aimed to estimate the diagnostic role of Dickkopf-1 (DKK1) and amphiregulin (AREG) and to find out their correlation with different clinicopathological parameters in HCC patients. Materials and Methods: Serum levels of DKK1 and AREG in 55 HCC patients, 20 cirrhotic patients, and 15 healthy subjects as control group were measured using the ELISA technique. Results: Both of DKK1 and AREG showed a significant increase in the HCC group compared to cirrhotic and healthy groups. DKK1 at a cutoff point of 8.92 ng/ml showed that the area under the curve (AUC) was 0.826 with 87.3% sensitivity and 82.9% specificity. DKK1 showed a significant correlation with tumor size, liver dysfunction, and poor performance status in HCC patients. AREG at a cutoff point of 8.74 pg/ml showed a sensitivity of 74.5% but low specificity (47.1%). AREG showed a significant correlation with portal vein thrombosis and tumor metastasis in HCC patients. Conclusion: Serum DKK1 could be a diagnostic biomarker for HCC. Both of DKK1 and AREG may play significant roles in tumor progression and may offer promising therapeutic targets in HCC patients. [ABSTRACT FROM AUTHOR]

Aim of work The study was conducted for evaluation of the antitumor activity of SSTN 92-119 against HCC induced by thioacetamide in rats. Methods Sixty male Sprague-Dawley rats were randomized into four equal groups: Control, SSTN 92-119 , HCC, and HCC + SSTN 92-119 . Liver function tests were measured in serum. Liver homogenate was used for determination of: i) integrinαѴβ3 (ITGαѴβ3), insulin like growth factor-1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and alpha-fetoprotein (AFP) levels by ELISA, ii) syndecan-1 (CD-138), IGF-1R and VEGF genes expressions by qRT-PCR, iii) MDA, NO, GSH concentrations and SOD activity. Histopathological and immunohistochemical examination of liver tissue was performed. Results SSTN 92-119 decreased HCC-induced elevation in ALT, AST, ALP and GGT activities and reversed HCC-induced reduction in total protein and albumin concentrations significantly. SSTN 92-119 significantly elevated hepatic SOD and GSH and reduced both NO and MDA levels. Protein levels of ITGαѴβ3, IGF-1R, VEGF, FGF-2 and AFP were decreased in HCC- SSTN 92-119 group as well as gene expression of CD-138, IGF-1R and VEGF compared with HCC group. Conclusions SSTN 92-119 down regulates ITGαѴβ3 receptor and subsequently reduces the activation of angiogenic growth factors VEGF and FGF-2. Therefore, SSTN 92-119 is becoming a promising anti-integrin αѴβ3 that inhibits angiogenesis and proliferation in HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. In an attempt to understand some potential mechanisms of persistence and oncogenicity of Hepatitis C virus (HCV)-related HCC, microfibrillar-associated protein 4 (MFAP4), fibrotic indices and oxidative status biomarkers were assessed in the sera of 50 patients with HCV-associated HCC, 25 patients with HCV-related liver cirrhosis and 15 healthy individuals. Serum oxidized Coenzyme Q10 (CoQ10) and malondialdehyde showed significant elevation in HCC patients compared to the control group (p < 0.001), as well as cirrhotic patients (p < 0.05 and p < 0.001, respectively), while serum glutathione content and superoxide dismutase activity were significantly decreased in HCC patients compared to the control group (p < 0.001). Serum MFAP4, aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and Forns index showed significant increase in HCC patients compared to the control group (p < 0.001), while only APRI and FIB-4 were significantly different between HCC and cirrhotic patients (p < 0.05), with a sensitivity of 86% and 92%, respectively, at cut off ≥0.7 for APRI and ≥1.57 for FIB-4. Therefore, increasing oxidative stress and fibrosis might mediate HCV induced cirrhosis and HCC. APRI and FIB-4 may be used as a simple non-expensive formula for the screening of HCC rather than MFAP4. [ABSTRACT FROM AUTHOR]

Syndecan-1 is a trans-membrane heparan sulfate proteoglycan that localizes in epithelial cells and has been shown to be present in normal hepatocytes. It is thought to be involved in processes such as cell growth, differentiation and adhesion. However, the clinical data regarding syndecan-1 in patients with hepatocellular carcinoma (HCC) are scarce and controversial. Therefore, we need to evaluate the effects of HCC on the serum levels of syndecan-1. Thus, 40 patients with HCC and 31 patients with liver cirrhosis were physically examined. Blood samples were taken for measurements of routine markers (sGPT, sGOT, bilirubin, albumin, and a-fetoprotein), as well as serum levels of interleukin (IL)-6 and syndecan-1. Patients with liver cirrhosis showed significant increase in serum IL-6 as compared with HCC patients and the control subjects. Serum level of syndecan-1 was significantly increased in HCC patients as compared with the cirrhotic and control groups. In addition, significant positive correlations between syndecan-1 and serum levels of ALT, AST in HCC patients were found. Moreover, syndecan-1 increased significantly with increasing stage of Barcelona-Clinic Liver Cancer Group diagnostic and treatment strategy. In conclusion, the development of HCC is accompanied by a significant elevation in serum syndecan-1 levels. The increase in serum syndecan-1 may be linked with progression of HCC. [ABSTRACT FROM AUTHOR]