2,594 research outputs found
Hormonal regulation of mammary gland stem cells: differential role of progesterone receptor isoforms
No full textEn esta tesis se plantearon distintas estrategias para estudiar el papel de las isoformas del receptor de progesterona sobre la población de células madre de la glándula mamaria normal y tumoral. Para ello se utilizaron dos modelos: ratones transgénicos que sobre expresan la isoforma A (PR A) o B (PR B) del receptor de progesterona (PR), y la línea celular de cáncer de mama humano, T47D, y sus derivados T47D YA y T47D YB que expresan PR A y PR B respectivamente. Demostramos que tanto las glándulas mamarias de ratones transgénicos, como células de cáncer de mama humano T47D que sobre expresan PR B presentan mayor porcentaje de células positivas para marcadores de células madre. En los ratones, la ovariectomía llevó a una disminución en el porcentaje de células progenitoras luminales tanto en glándulas mamarias de ratones wild type como de transgénicos PR A, sin afectar a la población madre/progenitora basal. Por otra parte, ensayos con los anti estrógenos Fulvestran y Tamoxifeno demostraron que las células que sobre expresan PR B presentan resistencia a ambos tratamientos, mientras que aquellas con un incremento en la expresión de PR A son sensibles a los mismos. En el modelo tumoral la expresión de PR B se asoció a un fenotipo más maligno evaluado por la formación de mamoesferas de mayor tamaño, más irregulares, con mayor capacidad clonogénica y resistentes a terapias endocrinas. Los resultados obtenidos en este trabajo revelan que el balance adecuado en la expresión de las isoformas del PR es indispensable para mantener la homeostasis de la población de células madre mamarias, y que impacta también a esta población celular en el contexto tumoral. En particular, PR B jugaría un papel fundamental, indicando la relevancia de conocer si hay alteraciones en las cantidades relativas de PR A y PR B como factor de riesgo, o pronóstico al momento de una biopsia o decisión sobre una eventual terapia endocrina.In this thesis different strategies were proposed to study the role of progesterone receptor isoforms on the population of stem cells of the normal and tumor mammary gland. For this, two models were used: transgenic mice that overexpress the A (PR A) or B (PR B) isoforms of the progesterone receptor (PR), and the human breast cancer cell line, T47D, and its derivatives T47D YA and T47D YB expressing PR A and PR B respectively. We show that both the mammary glands of transgenic mice and T47D human breast cancer cells that overexpress PR B present a higher percentage of cells positive for stem cell markers. In mice, ovariectomy led to a decrease in the percentage of luminal progenitor cells in both mammary glands of wild type and transgenic PR A mice, without affecting the basal progenitor/stem cell population. On the other hand, the antiestrogens Fulvestran and Tamoxifen demonstrated that the cells that over-express PR B present resistance to both treatments, while those with an increase in the expression of PR A are sensitive to them. In the tumor model, the expression of PR B was associated with a more malignant phenotype evaluated by the formation of irregular mammospheres of larger size, with greater clonogenic capacity and resistant to endocrine therapies. The results obtained in this work reveal that the adequate balance in the expression of PR isoforms is essential to maintain the homeostasis of the mammary stem cell population, and that it also impacts this cell population in tumor contexts. In particular, PR B would play a fundamental role, indicating the relevance of knowing if there are alterations in the relative amounts of PR A and PR B as a risk factor, or prognostic factor, at the time of a biopsy or decision on an eventual endocrine therapy.Fil: Recouvreux, María Sol. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Hormonal regulation of mammary gland stem cells: differential role of progesterone receptor isoforms
No full textEn esta tesis se plantearon distintas estrategias para estudiar el papel de las isoformas del receptor de progesterona sobre la población de células madre de la glándula mamaria normal y tumoral. Para ello se utilizaron dos modelos: ratones transgénicos que sobre expresan la isoforma A (PR A) o B (PR B) del receptor de progesterona (PR), y la línea celular de cáncer de mama humano, T47D, y sus derivados T47D YA y T47D YB que expresan PR A y PR B respectivamente. Demostramos que tanto las glándulas mamarias de ratones transgénicos, como células de cáncer de mama humano T47D que sobre expresan PR B presentan mayor porcentaje de células positivas para marcadores de células madre. En los ratones, la ovariectomía llevó a una disminución en el porcentaje de células progenitoras luminales tanto en glándulas mamarias de ratones wild type como de transgénicos PR A, sin afectar a la población madre/progenitora basal. Por otra parte, ensayos con los anti estrógenos Fulvestran y Tamoxifeno demostraron que las células que sobre expresan PR B presentan resistencia a ambos tratamientos, mientras que aquellas con un incremento en la expresión de PR A son sensibles a los mismos. En el modelo tumoral la expresión de PR B se asoció a un fenotipo más maligno evaluado por la formación de mamoesferas de mayor tamaño, más irregulares, con mayor capacidad clonogénica y resistentes a terapias endocrinas. Los resultados obtenidos en este trabajo revelan que el balance adecuado en la expresión de las isoformas del PR es indispensable para mantener la homeostasis de la población de células madre mamarias, y que impacta también a esta población celular en el contexto tumoral. En particular, PR B jugaría un papel fundamental, indicando la relevancia de conocer si hay alteraciones en las cantidades relativas de PR A y PR B como factor de riesgo, o pronóstico al momento de una biopsia o decisión sobre una eventual terapia endocrina.In this thesis different strategies were proposed to study the role of progesterone receptor isoforms on the population of stem cells of the normal and tumor mammary gland. For this, two models were used: transgenic mice that overexpress the A (PR A) or B (PR B) isoforms of the progesterone receptor (PR), and the human breast cancer cell line, T47D, and its derivatives T47D YA and T47D YB expressing PR A and PR B respectively. We show that both the mammary glands of transgenic mice and T47D human breast cancer cells that overexpress PR B present a higher percentage of cells positive for stem cell markers. In mice, ovariectomy led to a decrease in the percentage of luminal progenitor cells in both mammary glands of wild type and transgenic PR A mice, without affecting the basal progenitor/stem cell population. On the other hand, the antiestrogens Fulvestran and Tamoxifen demonstrated that the cells that over-express PR B present resistance to both treatments, while those with an increase in the expression of PR A are sensitive to them. In the tumor model, the expression of PR B was associated with a more malignant phenotype evaluated by the formation of irregular mammospheres of larger size, with greater clonogenic capacity and resistant to endocrine therapies. The results obtained in this work reveal that the adequate balance in the expression of PR isoforms is essential to maintain the homeostasis of the mammary stem cell population, and that it also impacts this cell population in tumor contexts. In particular, PR B would play a fundamental role, indicating the relevance of knowing if there are alterations in the relative amounts of PR A and PR B as a risk factor, or prognostic factor, at the time of a biopsy or decision on an eventual endocrine therapy.Fil: Recouvreux, María Sol. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
The hyperplastic phenotype in PR-A and PR-B transgenic mice: lessons on the role of estrogen and progesterone receptors in the mouse mammary gland and breast cancer.
No full textProgesterone receptor (PR) belongs to the superfamily of steroid receptors and mediates the action of progesterone in its target tissues. In the mammary gland, in particular, PR expression is restricted to the luminal epithelial cell compartment. The generation of estrogen receptor-a (ER) and PR knockout mice allowed the specific characterization of the roles of each of these in mammary gland development: ER is critical for ductal morphogenesis, whereas PR has a key role in lobuloalveolar differentiation. To further study the role PR isoforms have in mammary gland biology, transgenic mice overexpressing either the ?A? (PR-A) or the ?B? (PR-B) isoforms of PR were generated. Overexpression ofthe A isoform of PR led to increased side branching, multilayered ducts, loss of basement membrane integrity, and alterations in matrix metalloproteinase activation in the mammary gland. Moreover, levels of TGFb1 and p21 were diminished and those of cyclin D1 increased. Interestingly, the phenotype was counteracted by antiestrogens, suggesting that ER is essential for the manifestation of the hyperplasias. Mice overexpressing the B isoform of PR had limited ductal growth but retained the ability to differentiate during pregnancy. Levels of latent and active TGFb1 were increased compared to PR-A transgenics.
The phenotypes of these transgenic mice are further discussed in the context of the impact of progesterone on mammary stem cells and breast cancer. We conclude that an adequate balance between the A and B isoforms of PR is critical for tissue homeostasis. Future work to further understand the biology of PR in breast biology will hopefully lead to new and effective preventive and therapeutic alternatives for patients.Fil: Sampayo, Rocío Guadalupe. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Recouvreux, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Simian, Marina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin
Microenvironment and endocrine resistance in breast cancer: Friend or foe?
No full textBreast cancer affects one in eight women around the world. Seventy five percent of these patients have tumors that are estrogen receptor positive and as a consequence receive endocrine therapy. However, about one third eventually develop resistance and cancer reappears. In the last decade our vision of cancer has evolved to consider it more of a tissuerelated disease than a cell-centered one. This editorial argues that we are only starting to understand the role the tumor microenvironment plays in therapy resistance in breast cancer. The development of new therapeutic strategies that target the microenvironment will come when we clearly understand this extremely complicated scenario. As such, and as a scientific community, we have extremely challenging work ahead. We share our views regarding these matters.Fil: Recouvreux, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Sampayo, Rocío Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Díaz Bessone, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Simian, Marina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
The Development of Nanostructured TiO2 Sol-Gel Derived Coatings – the Influence of Substrate Preparation Method and Post Treatment of Coatings
No full textThe analysis of literature data and experimental results obtained by the Author of the report clearly showed that further researches shall be devoted to the surface preparation method and characterization of the substrate obtained to check the dependency of morphological features whether they are characteristics of sol or substrates
RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes
No full textAbstract Runx1 participation in epithelial mammary cells is still under review. Emerging data indicates that Runx1 could be relevant for breast tumor promotion. However, to date no studies have specifically evaluated the functional contribution of Runx1 to control gene expression in mammary epithelial tumor cells. It has been described that Runx1 activity is defined by protein context interaction. Interestingly, Foxp3 is a breast tumor suppressor gene. Here we show that endogenous Runx1 and Foxp3 physically interact in normal mammary cells and this interaction blocks Runx1 transcriptional activity. Furthermore we demonstrate that Runx1 is able to bind to R-spondin 3 (RSPO3) and Gap Junction protein Alpha 1 (GJA1) promoters. This binding upregulates Rspo3 oncogene expression and downregulates GJA1 tumor suppressor gene expression in a Foxp3-dependent manner. Moreover, reduced Runx1 transcriptional activity decreases tumor cell migration properties. Collectively, these data provide evidence of a new mechanism for breast tumor gene expression regulation, in which Runx1 and Foxp3 physically interact to control mammary epithelial cell gene expression fate. Our work suggests for the first time that Runx1 could be involved in breast tumor progression depending on Foxp3 availability.Fil: Recouvreux, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Echeverria, Pablo Christian. Universidad de Ginebra; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rocha Viegas, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Castilla, Lucio Hernán. University Of Massachussets. Medical School; Estados UnidosFil: Schere Levy, Carolina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Tocci, Johanna Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Rubinstein, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin
Sol Grossbard papers 1919
No full textA typescript written while serving in the Signal Corps with the U.S. Expeditionary Forces in Siberia, 1918-1919. It is a critique of the attitudes and policies of the Allies towards Russia and its various political groups which led to the Allies' intervention in Siberia in 1918, and how these shared Russian attitudes toward each of the Allies and contributed to the final outcome of the Allies' venture in Russia. The author also presents his views as to what steps the U.S. should have taken to have enabled a stable democratic Russian government to have evolve
Scrutinizing the importance of surface chemistry versus surface roughness for aluminium / sol-gel film adhesion
No full textThe sol-gel synthesis process is a versatile method used to produce a wide diversity of materials and is being increasingly used as a surface modification method to alter porosity, wettability, catalytic activity, biocompatibility and corrosion performance of underlying substrates. Silane sol–gel films deposited on aluminium and aluminium alloys have been widely studied as chemical conversion coatings and as coupling agent between the substrate and organic layers. This study set out to investigate the effect of the surface chemical treatment prior to sol-gel application on the interfacial adhesion properties of a hybrid sol-gel film. Different surface pre-treatments, including two abrasive treatments and three chemical surface pre-treatments were used and their effect on surface chemistry and surface roughness was assessed. Surfaces were characterized by scanning electron microscopy, x-ray photoelectron spectroscopy, roughness measurements and static contact angles. Cerium nitrate loaded hybrid sol-gel films were deposited and adhesion on commercially pure aluminium was evaluated using pull-off testing. Statistical analysis revealed that, although highest adhesion values were obtained on rougher surfaces, the strongest correlation exists between the surface hydroxyl fraction and adhesion strength.Team Arjan MolTeam Yaiza Gonzalez Garci
From past research experiences looking to the future of sol–gel
No full textAbstract: Based on the outline of the conference that the author held in St. Petersburg for the conferment of the Life Achievement Award, some important steps in the evolution of science and sol–gel technology are revisited through examples taken from his research experiences. The goal is to reconsider what has been done in the past in light of what has been learned in the meantime. Some topics are still current and probably deserve further and more in-depth research, and new ideas for future work may be suggested. Driven by the interest of finding new materials and new fields of application, the sol–gel has evolved from the first studies on simple glass and glass–ceramic systems, to more sophisticated and complex organic–inorganic systems, multifunctional materials, and nanocomposites. [Figure not available: see fulltext.]
Sol–gel one-pot synthesis in soft conditions of mesoporous silica materials ready for drug delivery system
No full textThe present work reveals a new and simple strategy, a one-step sol–gel procedure, to encapsulate a low water-soluble drug in silica mesostructured microparticles and to improve its release in physiological media. The synthesis of these new materials is based on the efficient solubilisation of a poorly water-soluble drug in surfactant micelles (Tween 80, a pharmaceutical excipient) which act as template for the silica network. A strict control of the sol–gel process and the parameters procedure in soft conditions (concentration, pH, temperature) was applied to reach the solubilisation limit of the drug in the micellar solution so as to optimise its encapsulation. Even if this one-pot procedure could appear limited by the low drug loading, it could provide an interesting alternative for the formulation of many recent highly active but very poorly soluble drugs.Nanostructured MaterialsApplied Science
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