Targeting p53/TRAIL/caspase-8 signaling by adiponectin reverses thioacetamide-induced hepatocellular carcinoma in rats.

Given the enormous impact of HCC on the patients' quality of life and healthcare economics, the current study was conducted to investigate the potential ability of adiponectin to reverse established HCC and to investigate the underlying mechanisms which control the chemotherapeutic and hepatoprotective effects. HCC was induced in Male Sprague Dawely rats by I.P. injection of thioacetamide(200 mg/kg) 3 times/week for 14 weeks.HCC development was confirmed by histopathological examination and assessment of serum levels of α-fetoprotein (AFP). Adiponectin was administered (5 µg/kg, I.P.) starting from week 13 of the experiment and for further 4 weeks. Adiponectinadministration revealed a significant antitumor activity with significant improvement in liver functions and oxidative status. Nevertheless, pathological features as cirrhosis, dysplastic changes, and tumoral nodules were significantly attenuated with significant enhancement in hepatic caspase-3 immunostaining. Mechanistically, adiponectin administration was associated with significant restoration of p53 activity; which increased by 133%, with a reduction in HCC-induced expression of-JNK which decreased by 53%as well as a significant enhancement of hepatic TRAIL and caspase-8 activities which increased by 27% and 20% respectively. In conclusion; Adiponectin can be proposed as a promising therapy for HCC. Adiponectin's tumoricidal activity can be partially mediated by blocking HCC-induced reduction in p53 expression as well as reactivation of TRAIL signaling and induction of apoptotic pathway providing more protection for the body against the tumor.

Significance of CEP78 and WDR62 gene expressions in differentiated thyroid carcinoma: Possible predictors of lateral lymph node metastasis.

OBJECTIVES: This study aimed at investigating the clinical significance of CEP78 and WDR62 in differentiated thyroid carcinoma (DTC). This study also aimed at finding predictors that help in detecting patients with DTC who have high risk for lateral lymph node metastasis (LNM). METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was performed to examine CEP78, and WDR62 mRNA expressions in 40 tissue specimens of DTC, and 40 goiter tissue specimens. Additionally, we reviewed clinical, ultrasound, laboratory, pathological data of patients to analyze the associations between these characteristics and lateral LNM. RESULTS: Our results demonstrated that relative CEP78 mRNA levels were significantly decreased in thyroid cancer tissues than goiter tissues (P = 0.002). ROC curve analysis confirmed the diagnostic value of CEP78 mRNA expression, providing an AUC equals to 0.698 (95% confidence intervals (CI), 0.583-0.813; P = 0.002). The relative WDR62 mRNA expression was not statistically different in DTC tissues and goiter tissues (P = 0.686). Furthermore, the DTC patients had been included to examine risk factors for lateral LNM. In multivariate analysis, the significant factors for predicting lateral LNM were low CEP78 mRNA expression (cut off value ≤0.54; P = 0.03; OR = 19.62; 95% CI, 1.3-296.23), central LNM (P = 0.011; OR = 33.6; 95% CI, 2.24-503.6) and calcifications (P = 0.023; OR = 27.187; 95% CI, 1.57-469.5). CONCLUSIONS: CEP78 can be used as a promising molecular biomarker for differentiation between DTC and goiter tissues, in addition it might serve as a predictor of lateral LNM in DTC along with central LNM and calcifications. Unlike CEP78, WDR62 mRNA expression was not statistically different in DTC and goiter.