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1.
Anticancer Res ; 21(4B): 3001-4, 2001.
Article in English | MEDLINE | ID: mdl-11712801

ABSTRACT

BACKGROUND: The aim of this study was to analyse the influence of cigarette smoking on bladder carcinomas. PATIENTS AND METHODS: 98 cases of bladder cancers were examined by single strand conformation polymorphism analysis of exons 5 to 9, followed by DNA direct sequencing. RESULTS: The incidence of p53 gene mutations was not significantly influenced by habitual smoking. However, the p53 mutation spectrum of current smokers differed significantly from the pattern for non-smokers and ex-smokers. Differences between the two populations included multiple mutations in the current-smokers and an absence in non- and ex-smokers (p<0.01), with the predominance of G:C to A:T transitions at CpG sites in non-smokers (60.0%) in comparison with current smokers (7.6%) (p<0.02). Moreover, G:C to T:A and G:C to C:G transversions were found solely in current smokers. CONCLUSION: It would appear that, in current-smokers, the spectrum of p53 gene mutations is related to tobacco-smoke carcinogens and that the habit of smoking increases the extent of DNA damage.


Subject(s)
Carcinoma, Transitional Cell/genetics , DNA, Neoplasm/genetics , Genes, p53 , Point Mutation , Smoking/adverse effects , Urinary Bladder Neoplasms/genetics , Aged , Carcinogens/adverse effects , Carcinoma, Transitional Cell/etiology , CpG Islands , DNA Mutational Analysis , Exons/genetics , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Smoke/analysis , Smoking/genetics , Smoking Cessation , Urinary Bladder Neoplasms/etiology
2.
J Steroid Biochem Mol Biol ; 78(4): 343-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11717004

ABSTRACT

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor whose expression is induced by the cAMP-dependent signalling pathway in several cell types, and by estrogens in some human breast cancer cells. Here, we investigated the cross-talk between estrogens and cAMP/PKA-dependent signalling pathway in human breast cancer MCF-7 cells. The results show that, in the absence of any CRE and ERE, forskolin induces whereas estrogens have no effect on VEGF promoter. Moreover, estrogens, through estrogen receptors, partly inhibit the forskolin-induced VEGF promoter in MCF-7 human breast cancer cells. Therefore, in breast cancers, estrogens could partly inhibit the effect of ligand-activated G protein-coupled receptors on VEGF expression.


Subject(s)
Adenocarcinoma/pathology , Breast Neoplasms/pathology , Colforsin/antagonists & inhibitors , Endothelial Growth Factors/genetics , Estradiol/pharmacology , Gene Expression Regulation/drug effects , Lymphokines/genetics , Promoter Regions, Genetic , Adenocarcinoma/genetics , Base Sequence , Breast Neoplasms/genetics , Colforsin/pharmacology , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , DNA Primers , Humans , Ligands , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
3.
J Urol ; 162(4): 1496-501, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10492244

ABSTRACT

PURPOSE: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.


Subject(s)
Carcinoma, Transitional Cell/chemistry , Gene Expression Regulation, Neoplastic/genetics , Tumor Suppressor Protein p53/analysis , Urinary Bladder Neoplasms/chemistry , Aged , Female , Genes, p53/genetics , Humans , Immunohistochemistry , Male , Mutation , Sequence Analysis, DNA
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