The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer

More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). In contrast, most of the spontaneous, chemically or MMTV induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate (MPA) to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent, metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependency, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discussthe relevance of this model in comparison with other currently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Helguero, Luisa A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Soldati, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bottino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Wargon, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Molinolo, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Public Health Service. National Institute Of Health; Estados Unido

Kinetics and mechanism of the electrochemical oxidation of nitrite ion dissolved as sodium nitrite in dimethylsulphoxide solutions on platinum electrodes

The kinetics of the electrochemical oxidation of NO2− ion dissolved in DMSO has been studied on Pt electrodes at temperature ranging from 25 to 44°C, by means of potentiostatic E/I curves and by relaxation techniques. The oxidation reaction is explained in terms of a consecutive reaction scheme which involves, as rate-determining step, nitrite-ion discharge on an adsorbed intermediate at the reaction interface, the latter apparently obeying a Langmuir isotherm.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Does Chinese research hinge on US co-authors? Evidence from the China initiative

Launched in November 2018 by the Trump administration, the China Initiative was meant to "protect US intellectual property and technologies against Chinese Economic Espionage". In practice, it made administrative procedures more complicated and funding less accessible for collaborative projects between Chinese and US researchers. In this paper we use information from the Scopus database to analyze how the China Initiative shock affected the volume, quality and direction of Chinese research. We find a negative effect of the Initiative on the average quality of both the publications and the co-authors of Chinese researchers with prior US collaborations. Moreover, this negative effect has been stronger for Chinese researchers with higher research productivity and/or who worked on US-dominated fields and/or topics prior to the shock. Finally, we find that Chinese researchers with prior US collaborations reallocated away from US coauthors after the shock and also towards more basic research

Kinetics of the cathodic discharge of ammonium ion dissolved in dimethylsulfoxide on platinum

The cathodic discharge of ammonium ion dissolved in DMSO solution on platinum electrodes in the temperature range from 25 to 44 °C yields ammonia and hydrogen at the ratio 2 : 1. The kinetics of the reaction was studied both under stationary and non-stationary conditions and reveals an influence of the treatment of the electrode surface. The kinetic parameters were interpreted with a reaction mechanism involving the participation of adsorption competition between either solvent or impurity molecules and hydrogen atoms, assuming the recombination of these adatoms is rate determining.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Novel, low cost, highly effective, handmade steroid pellets for experimental studies

The basic component of SilasticH glue (Dow Corning) used to prepare SilasticH pellets is polydimethylsiloxane. This compound is also present in other commercial adhesives such as FASTIXH (Akapol SA) that are available in any store for that category. In the present study we developed low cost, easy to prepare handmade steroid pellets (HMSP) by mixing 17bestradiol, progesterone or other synthetic steroids with FASTIXH adhesive. We assessed serum levels of 17b-estradiol, progesterone, prolactin and luteinizing hormone in ovariectomized mice treated for 24 and 48 h or 7, 14 and 28 days with 20 mg or 5 mg of 17b-estradiol or 5 mg progesterone HMSP. We found a time dependent and significant increase in the levels of both natural hormones, and a downregulation of serum luteinizing hormone levels, while both 17b-estradiol doses increased serum prolactin. Uterine weights at sacrifice and histological examination of the uteri and the mammary glands correlated with estrogen or progestin action. Finally, we evaluated the biological effects of HMSP compared to commercial pellets or daily injections in the stimulation or inhibition of hormone dependent mammary tumor growth, and found that HMSP were as effective as the other methods of hormone administration. These data show that HMSP represent a useful, low cost, easily accessible method for administering steroids to miceFil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Wargon, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Molinolo, Alfredo. National Institutes of Health. National Institute of Dental and Craniofacial Research; Estados UnidosFil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

Multidrug resistance protein 4/ ATP binding cassette transporter 4: a new potential therapeutic target for acute myeloid leukemia

Less than a third of adults patients with acute myeloid leukemia (AML) are cured by current treatments, emphasizing the need for new approaches to therapy. We previously demonstrated that besides playing a role in drug-resistant leukemia cell lines, multidrug resistance protein 4 (MRP4/ABCC4) regulates leukemia cell proliferation and differentiation through the endogenous MRP4/ABCC4 substrate, cAMP. Here, we studied the role of MRP4/ABCC4 in tumor progression in a mouse xenograft model and in leukemic stem cells (LSCs) differentiation. We found a decrease in the mitotic index and an increase in the apoptotic index associated with the inhibition of tumor growth when mice were treated with rolipram (PDE4 inhibitor) and/or probenecid (MRPs inhibitor). Genetic silencing and pharmacologic inhibition of MRP4 reduced tumor growth. Furthermore, MRP4 knockdown induced cell cycle arrest and apoptosis in vivo. Interestingly, when LSC population was isolated, we observed that increased cAMP levels and MRP4/ABCC4 blockade resulted in LSCs differentiation. Taken together, our findings show that MRP4/ABCC4 has a relevant role in tumor growth and apoptosis and in the eradication of LSCs, providing the basis for a novel promising target in AML therapy.Fil: Copsel, Sabrina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Beyrath, Julien. Radboud Universiteit Nijmegen; Países BajosFil: Wargon, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Cany, Jeannette. Radboud Universiteit Nijmegen; Países BajosFil: Russel, Frans G. M.. Radboud Universiteit Nijmegen; Países BajosFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Association of Over-The-Counter Pharmaceutical Sales with Influenza-Like-Illnesses to Patient Volume in an Urgent Care Setting

We studied the association between OTC pharmaceutical sales and volume of patients with influenza-like-illnesses (ILI) at an urgent care center over one year. OTC pharmaceutical sales explain 36% of the variance in the patient volume, and each standard deviation increase is associated with 4.7 more patient visits to the urgent care center (p<0.0001). Cross-correlation function analysis demonstrated that OTC pharmaceutical sales are significantly associated with patient volume during non-flu season (p<0.0001), but only the sales of cough and cold (p<0.0001) and thermometer (p<0.0001) categories were significant during flu season with a lag of two and one days, respectively. Our study is the first study to demonstrate and measure the relationship between OTC pharmaceutical sales and urgent care center patient volume, and presents strong evidence that OTC sales predict urgent care center patient volume year round. © 2013 Liu et al

A comparison of multivariate and univariate time series approaches to modelling and forecasting emergency department demand in Western Australia

Objective: To develop multivariate vector-ARMA (VARMA) forecast models for predicting emergency department (ED) demand in Western Australia (WA) and compare them to the benchmark univariate autoregressive moving average (ARMA) and Winters’ models. Methods: Seven-year monthly WA state-wide public hospital ED presentation data from 2006/07 to 2012/13 were modelled. Graphical and VARMA modelling methods were used for descriptive analysis and model fitting. The VARMA models were compared to the benchmark univariate ARMA and Winters’ models to determine their accuracy to predict ED demand. The best models were evaluated by using error correction methods for accuracy. Results: Descriptive analysis of all the dependent variables showed an increasing pattern of ED use with seasonal trends over time. The VARMA models provided a more precise and accurate forecast with smaller confidence intervals and better measures of accuracy in predicting ED demand in WA than the ARMA and Winters’ method. Conclusion: VARMA models are a reliable forecasting method to predict ED demand for strategic planning and resource allocation. While the ARMA models are a closely competing alternative, they under-estimated future ED demand