ABSTRACT
Histone deacetylase inhibitors (HDIs) are valuable drugs in breast cancer where estrogen receptor alpha (ER alpha) can be silenced by epigenetic modifications. We report the effect of the clinically available HDI, valproic acid (VPA), on ER alpha expression and function in ER-negative breast cancer cells, MDA-MB-231. VPA induced ER alpha mRNA and protein, while did not modify ER beta. In VPA-treated cells, we also observed: (1) a correct transcriptional response to estradiol after transfection with the luciferase gene under the control of an estrogen-responsive minimal promoter (ERE-TKluc); (2) increased expression of the ER-related transcription factor FoxA1; (3) estradiol-induced up-regulation of several estrogen-regulated genes (e.g. pS2, progesterone receptor); (4) inhibitory effect of tamoxifen on cell growth. In conclusion, the HDI VPA, inducing ER alpha and FoxA1, confers to MDA-MB 231 cells an estrogen-sensitive "phenotype", restoring their sensitivity to antiestrogen therapy.
Subject(s)
Breast Neoplasms , Cell Line, Tumor/drug effects , Enzyme Inhibitors/pharmacology , Estrogen Receptor Modulators , Estrogen Receptor alpha/metabolism , Valproic Acid/pharmacology , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Proliferation/drug effects , Estradiol/metabolism , Estradiol/pharmacology , Estrogen Antagonists/pharmacology , Estrogen Receptor Modulators/metabolism , Estrogen Receptor Modulators/therapeutic use , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Hepatocyte Nuclear Factor 3-alpha/genetics , Hepatocyte Nuclear Factor 3-alpha/metabolism , Humans , Tamoxifen/pharmacology , Transcription, Genetic/drug effectsABSTRACT
Tritium present in the environment gradually decreased in the last decades and nowadays it has reached extremely low activity concentrations. The purpose of the present work is the implementation of a tritium enrichment system in water samples using electrolytic techniques and pure nickel and iron electrodes. In the present work a mean tritium enrichment factor of 13.0 +/- 3.2 was obtained. This result should allow to reach a minimum detectable activity of tritium in water samples of about 1 tritium unit (TU) or less. The present enrichment system necessitates further adjustments and improvements, such as a cooling system in order to reduce the tritium losses due to evaporation.
Subject(s)
Electrochemistry/methods , Radiometry/methods , Tritium/analysis , Tritium/chemistry , Water Pollutants, Radioactive/analysis , Water Pollutants, Radioactive/chemistry , Water/chemistry , Radiation DosageABSTRACT
In this study the air gamma dose rate map of Piemonte, a region in the North-West of Italy, was produced from gamma spectrometry soil data. Soil samples collected in 110 different sites of Piemonte were analysed with Hyperpure Germanium (HPGe) detectors (30% relative efficiency), which allow the evaluation of the activity concentrations of natural radionuclides and (137)Cs. Then, using the available mathematical models, the gamma absorbed dose rate in air due to radionuclides was calculated. The contribution of the cosmic radiation to the total absorbed dose rate, which depend on the site altitude was also evaluated and added to the soil contribution. Finally, the map of the whole region was obtained by fitting the dose rate values of the different sites with kriging algorithms.
Subject(s)
Gamma Rays , Radiation Monitoring/methods , Radiometry/methods , Risk Assessment/methods , Soil Pollutants, Radioactive/analysis , Spectrometry, Gamma/methods , Topography, Medical/methods , Algorithms , Italy , Radiation Dosage , Radioisotopes/analysis , Risk FactorsABSTRACT
The possibility of using conventional analysis, such as gamma spectrometry and alpha spectrometry, for the detection of traces of depleted uranium (DU) in environmental samples has been investigated. The expected values have been compared with the experimental results obtained by using mollusc samples gathered in the Adriatic Sea. The analysis has shown that it is possible to detect DU. if the percentage composition is about 20% depleted uranium and 80% natural uranium, for a sample containing 10 Bq x kg(-1) of 238U. The possibility of extending this approach to samples with any given uranium concentration is investigated.
Subject(s)
Soil Pollutants, Radioactive/analysis , Uranium/analysis , Water Supply/analysis , Environmental Monitoring/methods , Humans , Reproducibility of Results , Scintillation Counting , Sensitivity and Specificity , Spectrometry, Gamma , Warfare , YugoslaviaSubject(s)
Art Therapy/methods , Child Psychiatry/methods , Disabled Children/psychology , Play Therapy/methods , Psychiatric Nursing/methods , Child , Creativity , Female , Humans , MaleABSTRACT
PIP: 2 models are proposed for the microsimulation of the family and analysis of family structure and life cycle. These models were devised primarily for teaching purposes. The families are composed of 3 generations (parents, grandparents, children). Cohabitation is not considered. The 1st model is governed by a transition mechanism based on the rules of a Markov multidimensional, nonhonogeneous chain. The 2nd model is based on stochastic point processes. Input data comprise annual mortality probability according to 1) sex, 2) age, 3) civil status, 4) annual probability of 1st marriage, 5) age combinations between the spouses, and 6) the probability of having 1, 2, or 3 children at 6 months intervals from the previous event (marriage or birth of nth child). The applications of the 1st model are presented using 2 mortality and fertility hypotheses (high and low) and a nuptiality hypothesis (West European nature). The various features of family composition are analyzed according to the duration of a couple's marriage and the age of the individual, as well as the characteristic features of the individual and family life cycle given these 2 demographic conditions.^ieng
