Carlos Sonnenschein

..Consequently, Systems Biology could be advantageously used both as a heuristic tool to guide "wet-experiments" and to refine hypotheses and test predictions...

..These disrupted interactions are hypothesized to be mediated by molecules, termed morphostats, which diffuse through the tissue to determine cell phenotype and maintain tissue architecture...

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..These results suggest that alterations in mammary gland phenotypes observed at puberty and adulthood in perinatally exposed mice have their origins in fetal development...

..Similar structures have also been observed following exposure to other estrogens. These results are further evidence that perinatal BPA exposure can alter the morphology of the rodent mammary gland in adulthood...

..In the present study, we developed 3-dimensional (3D) in vitro models to study breast cancer tissue organization and the role of the microenvironment in phenotypic determination...

..Furthermore, LuCAFs secreted soluble factors that induced HBECs to express genes associated with immune responses, apoptosis, mitosis, cell survival, differentiation and cancer...

..Future studies to assess the role of estrogen receptors as mediators of BPA action require estrogen receptor knock-out mice that were generated on a C57Bl6 background. The sensitivity of the C57Bl6 strain to estradiol and BPA is unknown...

..Our objective was to assess the histological changes in mammary glands of the female Wistar-Furth rat as a result of low dose exposure to N-nitrosomethylurea (NMU)...

..Thus, fetal bisphenol A exposure is sufficient to induce the development of preneoplastic and neoplastic lesions in the mammary gland in the absence of any additional treatment aimed at increasing tumor development...

..The development of fast and sensitive bioassays is central to the achievement of these three goals...

..Hence, both animal experiments and epidemiological data strengthen the hypothesis that foetal exposure to xenooestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years...

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..This non-monotonic dose-response in the mammary gland may reflect complex interactions, where estrogen can act on multiple targets either as an agonist or antagonist...

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..Perinatal exposure to low-doses of bisphenol A (BPA) results in alterations in the ovary, uterus, and mammary glands and in a sexually dimorphic region of the brain known to be important for estrous cyclicity...

..In addition, BPA-induced alterations that specifically affect hypothalamic-pituitary-gonadal axis function may further contribute to the anomalies observed at 3 mo of age, long after the cessation of BPA exposure...

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..These results suggest that proper collagen organization is necessary for epithelial morphogenesis to occur, and that biomechanical interactions between fibers and cells mediated duct formation, elongation and branching...

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..These models provide an excellent system to study tissue organization, epithelial morphogenesis, and breast carcinogenesis...

..We conclude that biochemical and biomechanical signals mediate the interaction between cells and matrix components and are necessary to induce tubulogenesis in vitro...

..Regardless, the data already amassed highlight the need for a public policy to reduce exposure to EDCs...

..It will promote the identification of similar and unique effects of different endocrine disruptors, and their inter-relationships...

..Thus, foetal BPA exposure was sufficient to induce the development of oestrogen-sensitive pre-neoplastic and neoplastic lesions in the mammary gland in the absence of any additional treatment aimed at increasing tumour incidence...

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..Our results suggest that the stroma is a crucial target of the carcinogen and that mutation in the Ha-ras-1 gene is neither necessary nor sufficient for tumor initiation...

..The merits of these competing theories are evaluated herein...

..Tap water was devoid of hormonal activity. We conclude that feedlot effluents contain sufficient levels of hormonally active agents to warrant further investigation of possible effects on aquatic ecosystem health...

..Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context...

..However, new theoretical concepts are needed in order to grapple with the apparent circular causality of complex biological phenomena in development and carcinogenesis...

..Herein, we argue that the differences between normal and cancerous states are instead identifiable at the tissue level of biological organization, and therefore, the search for identification of a cancer cell should be abandoned...

..These data suggest that AS3 is a mediator of the proliferative arrest in the normal rat prostate in situ and human prostate cell lines and that its expression is androgen-induced...

..The emerging field of endocrine disruptors promises to provide new insights into the mechanisms underlying the development of hormone-target organs and demonstrates that the environment plays important roles in the making of phenotypes...

..The results indicate that APRIN, in addition to its Pds5 similarity, has the features and localization of a hormone-induced chromatin regulator...

..Also, the present data suggest that the proposed mABP may be the recognition mechanism by which both HA and rHA inhibit MCF7 and T47D cell proliferation...

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..We suggest that future studies involving TSP analyses use quantitative and objective dosage standardization methods, such as those with quantitative cellular response or marker gene expression-based dosage criteria...

..Prenatal exposure to BPA has produced long-lasting and profound effects on rodent hormone-dependent tissues that are manifested 1-6 months after the end of exposure...

..Equally important, availability of the inhibitory we are purifying, will allow for testing of hypotheses now being proposed to explain the control of estrogen-sensitive cell proliferation...

..This inference is drawn based on the results of experiments described. The study of the mechanism of sex steroid action in adult rats is also proposed...

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