The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

Protective role of hesperetin in sorafenib-induced hepato- and neurotoxicity in mice via modulating apoptotic pathways and mitochondrial reprogramming.

INTRODUCTION: Sorafenib, an FDA-approved standard chemotherapy for advanced hepatocellular carcinoma, is associated with numerous adverse effects that significantly impact patients' physiological well-being. Consequently, identifying agents that mitigate these side effects while enhancing efficacy is crucial. Hesperetin, a flavone present in fruits and vegetables, possesses antioxidant, anti-inflammatory, and anti-cancer properties. This study aimed to investigate the hepatotoxic and neurotoxic effects of sorafenib and the potential protective role of hesperetin. MATERIALS AND METHODS: Swiss albino mice were orally administered sorafenib (100 mg/kg) alone or in combination with hesperetin (50 mg/kg) over 21 days. Behavioral assessments for anxiety and depressive-like behaviors were conducted. Additionally, evaluations encompassed apoptotic activity, mitochondrial integrity, liver enzyme levels, proliferation rates, and histopathological changes. RESULTS: Combining hesperetin with sorafenib showed improvements in behavioral alterations, liver damage, brain mitochondrial dysfunction, and liver apoptosis compared to the sorafenib-only group in mice. CONCLUSION: Hesperetin exhibits potential as an adjunct to sorafenib, mitigating its side effects by attenuating its toxicity, enhancing efficacy, and potentially reducing the occurrence of sorafenib-induced resistance through the downregulation of hepatocyte growth factor levels.

Diagnostic utility of the combined use of HNF4A and GATA3 in distinction between primary and metastatic breast and gastric carcinomas.

Sometimes the distinction between gastric adenocarcinomas and breast carcinomas can be challenging. Hepatocyte nuclear factor 4-alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of the present work was to evaluate the role of the combined use of HNF4A and GATA3 as immunohistochemical markers in distinction between primary and metastatic breast and gastric carcinomas. This retrospective study was conducted on (81) cases divided into four groups of cohorts: primary BC (cohort I, n = 25), primary GC (cohort II, n = 23), and metastases derived from both types of tumors designated as metastasis derived from BC (cohort III-A, n = 17) and metastasis derived from GC (cohort III-B, n = 16). We performed immunohistochemistry analysis of HNF4A and GATA3 in all (81) cases. HNF4A expression was seen in 22 of 23 primary gastric adenocarcinomas and was absent in all 25 primary breast carcinomas (sensitivity 95.7%, specificity 100%). HNF4A was seen in 15 of 16 metastatic gastric adenocarcinomas and was absent in all 17 metastatic breast carcinomas (sensitivity 93.8%, specificity 100%). GATA3 showed 92 and 88% sensitivity, and 95.7 and 100% specificity for primary breast carcinomas and metastatic breast carcinomas, respectively. Our data confirmed the potential utility of HNF4A as a diagnostic marker and can be used as an adjunct to GATA3 as an immunohistochemical panel to differentiate between breast and gastric carcinomas.