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Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Because of its increased incidence in the last decade and the estimated further increase in the next 2 decades, HCC is arousing great interest. In Europe and North America, it commonly develops on cirrhotic livers, and surveillance programs have therefore been suggested to identify early HCC, at a stage when it remains suitable for surgical therapy and has a better clinical outcome. The only serologic marker used in clinical practice is a-fetoprotein (a-FP), but its sensitivity is poor. In our study, 120 patients with HCC and 90 patients with liver cirrhosis were investigated. We report for the first time to our knowledge that as a marker of HCC, the squamous cell carcinoma (SCCA) antigen has high sensitivity (84.2%) but low specificity (48.9%). However, the combination of a-FP and SCCA yielded a correct serologic diagnosis in 90.83% of the HCC patients. A small percentage of patients remain undetected, likely because of the low specificity of SCCA. In conclusion, the combined use of a-FP and SCCA antigen represents a more powerful tool for the serologic detection of HCC. ' 2005 Wiley-Liss, Inc.Key words: SCCA; HCC; a-fetoprotein; diagnosis; cirrhosis Hepatocellular carcinoma (HCC) is becoming a major health problem worldwide as it represents the fifth most common cancer in the world and the third most common cause of cancer-related death. In Europe and the USA, the incidence rates of HCC have strongly increased in the last decade and will likely increase further in the upcoming 2 decades due to hepatitis C virus infection, 1,2 although there is some controversy as to whether it is directly responsible for liver cancer development. [3][4][5] In Western and North American countries, HCC commonly develops in cirrhotic livers whatever the etiology, so that liver cirrhosis by itself represents the strongest risk factor. 3,5,6 The clinical outcome and the prognosis of HCC are unsatisfactory, even if in developed countries a major improvement of treatment and survival has been achieved in patients with HCC at the initial stage. 7 Therefore, surveillance programs aimed at detecting early stage HCC have been recommended by the European Association for the Study of the Liver (EASL) as well as the Italian Association for the Study of the Liver (AISF). These programs are based on the use of ultrasound tomography and a-fetoprotein (a-FP). The reliability of imaging techniques has greatly improved in the last years but such diagnostic procedures are expensive and subject to interpretation. On the other hand, as the only diagnostic serologic test currently available in clinical practice, a-FP has too low a sensitivity and specificity; based on receiving operating characteristic (ROC) curve analysis, its sensitivity reaches only 60%. 8 It has been reported that the squamous cell carcinoma antigen (SCCA) is overexpressed in HCC tissues. 9 SCCA is a component of the high molecular weight serine protease inhibitors named serpins. 10 A different expressi...

In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.