Response to commentary “Zinc is decreased in prostate cancer: an established relationship of prostate cancer!”

10.1007/s00775-010-0737-8Journal of Biological Inorganic Chemistry1619-13JJBC

Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells

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

Laboratory Reference Interval For Hemostatic Model Assessment Of Insulin Resistance Index (Homa-Ir) In Abuja Metropolis

No Abstract

Assessment of the renal status of pregnant women through biochemical parameters at various trimesters of pregnancy

No Abstrac

The Study Of Serum Prostate Specific Antigen And Phosphatase Isoenzymes Activity As Diagnostic Parameters In Patients With Prostate Cancer In Nigeria

Serum activities of Acid Phosphatase (ACP) and Prostatic Acid Phosphatase (PAP) are still employed in most hospitals in Nigeria for the diagnosis of prostate cancer, because of lack of resources for prostate specific antigen (PSA) assay. Serum PSA and activities of phosphatase isoenzymes ACP and PAP, Alkaline Phosphatase (ALP) and Heat stable Alkaline Phosphatase (HSAP) were studied in 71 apparently healthy male controls and 47 proven prostate cancer patients. There were statistically significant increases in the mean serum levels of PSA, PAP, ACP, ALP and HSAP in the prostate cancer patients compared to the controls (P<0.001). PSA level was increased above the cut-off level in 85.1% of patients, PAP in 66.0%, ACP in 57.5%, ALP in 34.0% and HSAP in 21.3% of cases. Serum levels of PSA, ACP and PAP were lower and of ALP and HSAP higher in patients with longer duration of the disease (P<0.05). The study confirms the relevance of PSA assay over ACP, PAP, ALP and HSAP in the diagnosis of prostate cancer patients. It highlights the need for the inclusion of PSA assay in hospitals for accurate diagnosis of prostatic carcinoma

Prostate Tissue Metal Levels and Prostate Cancer Recurrence in Smokers

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N =25) had significantly higher Cd (median ppb, p =0.03) and lower Zn (p =0.002) in non-neoplastic tissue than never-smokers (N =21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p =0.009, adjacent nonneoplastic tissue Cd/Pb, 6.36 vs. 1.02, p =0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p =0.039 and adjacent non-neoplastic, p =0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process