Correlation of plasma osteoprotegerin (OPG) and receptor activator of the nuclear factor κB ligand (RANKL) levels with clinical risk factors in patients with advanced carotid atherosclerosis.

BACKGROUND: Osteoprotegerin (OPG) is considered to be a crucial regulatory mediator of bone metabolism by acting as a decoy receptor of the receptor activator of nuclear factor κB ligand (RANKL). OPG and RANKL have further become the subject of intense interest for their potential role in cardiovascular disease. The present study aimed to assess the clinical implication of plasma OPG and RANKL levels in patients with advanced carotid atherosclerosis. MATERIAL/METHODS: Plasma OPG and RANKL concentrations measured by solid-phase enzyme-linked immunosorbent assay (ELISA) were correlated with medical history, risk factors and medication intake in 131 patients who underwent carotid endarterectomy for vascular repair. RESULTS: Plasma OPG concentrations were associated with patients' age (p=0.0258), homocysteine levels (p<0.00001), eGFR (p=0.0254), history of diabetes (p=0.0324), statins therapy (p=0.0044), hyperlipidemia (p=0.0407), smoking (p=0.0226) and CAD (p=0.0377). Plasma RANKL concentrations were associated with patients' age (p=0.0191), homocysteine levels (p<0.00001), history of smoking (p=0.0185) and statins therapy (p=0.0004). Diabetes, CAD, smoking status, statins therapy and homocysteine were identified as independent predictors of OPG concentrations (p=0.0157, p=0.0030, p=0.0249, p=0.0047 and p=0.0072, respectively), whereas smoking showed an independent effect for RANKL (p=0.0010). CONCLUSIONS: The present data reinforce the clinical utility of OPG in carotid atherosclerosis, whereas the clinical implication of RANKL seems uncertain.

Coxsackievirus and adenovirus receptor expression in human endometrial adenocarcinoma: possible clinical implications.

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications.