Focal adhesion molecules as potential target of lead toxicity in NRK-52E cell line

AbstractIn this study, we investigated the influence of inorganic lead (Pb(II)), an environmental pollutant having nephrotoxic action, on the focal adhesion (FA) organization of a rat kidney epithelial cell line (NRK-52E). In particular, we evaluated the effects of the metal on the recruitment of paxillin, focal adhesion kinase, vinculin and cytoskeleton proteins at the FAs complexes. We provided evidences that, in proliferating NRK-52E cell cultures, low concentrations of Pb(II) affect the cell adhesive ability and stimulate the disassembly of FAs, thus inhibiting the integrin-activated signalling. These effects appeared to be strictly associated to the Pb-induced arrest of cell cycle at G0/G1 phase also proved in this cell line

Re-evaluating Adjuvant Breast Cancer Trials: Assessing Hormone Receptor Status by Immunohistochemical Versus Extraction Assays

Background: Tumor levels of steroid hormone receptors, a factor used to select adjuvant treatment for early-stage breast cancer, are currently determined with immunohistochemical assays. These assays have a discordance of 10%-30% with previously used extraction assays. We assessed the concordance and predictive value of hormone receptor status as determined by immunohistochemical and extraction assays on specimens from International Breast Cancer Study Group Trials VIII and IX. These trials predominantly used extraction assays and compared adjuvant chemoendocrine therapy with endocrine therapy alone among pre- and postmenopausal patients with lymph node-negative breast cancer. Trial conclusions were that combination therapy provided a benefit to pre- and postmenopausal patients with estrogen receptor (ER)-negative tumors but not to ER-positive postmenopausal patients. ER-positive premenopausal patients required further study. Methods: Tumor specimens from 571 premenopausal and 976 postmenopausal patients on which extraction assays had determined ER and progesterone receptor (PgR) levels before randomization from October 1, 1988, through October 1, 1999, were re-evaluated with an immunohistochemical assay in a central pathology laboratory. The endpoint was disease-free survival. Hazard ratios of recurrence or death for treatment comparisons were estimated with Cox proportional hazards regression models, and discriminatory ability was evaluated with the c index. All statistical tests were two-sided. Results: Concordance of hormone receptor status determined by both assays ranged from 74% (κ = 0.48) for PgR among postmenopausal patients to 88% (κ = 0.66) for ER in postmenopausal patients. Hazard ratio estimates were similar for the association between disease-free survival and ER status (among all patients) or PgR status (among postmenopausal patients) as determined by the two methods. However, among premenopausal patients treated with endocrine therapy alone, the discriminatory ability of PgR status as determined by immunohistochemical assay was statistically significantly better (c index = 0.60 versus 0.51; P = .003) than that determined by extraction assay, and so immunohistochemically determined PgR status could predict disease-free survival. Conclusions: Trial conclusions in which ER status (for all patients) or PgR status (for postmenopausal patients) was determined by immunohistochemical assay supported those determined by extraction assays. However, among premenopausal patients, trial conclusions drawn from PgR status differed—immunohistochemically determined PgR status could predict response to endocrine therapy, unlike that determined by the extraction assa

Human Papillomavirus DNA and p16 Gene inSquamous Cell Lung Carcinoma

AIM: To investigate the presence of human papillomavirus (HPV) DNA in squamous cell carcinoma (SCC) of the lung, and to examine the protein expression and genomic status of p16 and their correlation. MATERIALS AND METHODS: Fifty cases of surgically removed primary lung SCC were analyzed. HPV detection was performed by Polymerase Chain Reaction (PCR) of L1 region and E6/E7 region of high-risk viral genotype. p16 protein and gene analysis were carried out by immunohistochemistry and Fluorescence In Situ Hybridization (FISH), respectively. RESULTS: HPV DNA was found in two out of 50 cases (4%, p>0.05). In five cases, p16 protein expression was positive. The data showed that in 45/50 cases (90%, p<0.05) HPV DNA and p16 were both negative, in 2/50 cases (4%) both were positive, and in 3/50 (6%) cases, HPV DNA was negative and p16 positive. FISH analysis for p16 gene showed aneusomia of chromosome 9 with or without loss of p16 gene in all cases (100%, p<0.05). CONCLUSION: Our study shows that in pulmonary SCC, there is no association between the presence of HPV DNA and the expression of p16 protein. Furthermore, the loss of the p16 gene and the instability of chromosome 9 were frequently found in HPV DNA-negative cases