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1دورية أكاديمية
المؤلفون: Catania, C., Sotiropoulos, I., Silva, R., Onofri, C., Breen, K. C., Sousa, Nuno, Almeida, O. F. X.
مصطلحات موضوعية: Amyloid beta-Protein Precursor, Analysis of Variance, Animals, Behavior, Animal, Disease Models, Emotions, Glucocorticoids, Hippocampus, Male, Memory, Prefrontal Cortex, Rats, Wistar, Space Perception, Stress, Psychological, Alzheimer’s disease, Amyloid precursor protein, Amyloid-b, Anxiety, Amyloid-β, Science & Technology
الوصف: Observations of elevated basal cortisol levels in Alzheimer's disease (AD) patients prompted the hypothesis that stress and glucocorticoids (GC) may contribute to the development and/or maintenance of AD. Consistent with that hypothesis, we show that stress and GC provoke misprocessing of amyloid precursor peptide in the rat hippocampus and prefrontal cortex, resulting in increased levels of the peptide C-terminal fragment 99 (C99), whose further proteolytic cleavage results in the generation of amyloid-beta (Abeta). We also show that exogenous Abeta can reproduce the effects of stress and GC on C99 production and that a history of stress strikingly potentiates the C99-inducing effects of Abeta and GC. Previous work has indicated a role for Abeta in disruption of synaptic function and cognitive behaviors, and AD patients reportedly show signs of heightened anxiety. Here, behavioral analysis revealed that like stress and GC, Abeta administration causes spatial memory deficits that are exacerbated by stress and GC; additionally, Abeta, stress and GC induced a state of hyperanxiety. Given that the intrinsic properties of C99 and Abeta include neuroendangerment and behavioral impairment, our findings suggest a causal role for stress and GC in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy can have a cumulative impact on the course of AD development and progression. ; CC and IS were supported by stipends from the Max Planck Society and EU Marie Curie Training Fellowships (at University College London, UK). The collaboration between the German and Portuguese laboratories was supported through the German–Portuguese Luso-Alemas Program (DAAD/GRICES). This study was conducted within the framework of the EU-supported integrated project ‘CRESCENDO’ (Contract FP6-018652).
وصف الملف: application/pdf
العلاقة: DAAD/GRICES; FP6-018652; https://www.nature.com/articles/4002101Test; http://hdl.handle.net/1822/64301Test
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2دورية أكاديمية
المؤلفون: Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., Stalla, G.K., Renner, U.
المصدر: J. Endocrinol. 2006;191(1):249-261
مصطلحات موضوعية: cyclin D1, messenger RNA, neuropilin 1, phosphatidylinositol 3 kinase, placental growth factor, protein bcl 2, vasculotropin A, vasculotropin receptor, vasculotropin receptor 1, vasculotropin receptor 2, adult, aged, animal cell, article, cell proliferation, controlled study, endocrine cell, endothelium cell, epithelium tumor, female, gene expression, human, human cell, human tissue, hypophysis adenoma, immunohistochemistry, in situ hybridization, male, nonhuman, nucleotide sequence
الوصف: As for any solid tumour, pituitary adenoma expansion is dependent on neovascularization through angiogenesis. In this process, vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) may play an outstanding role. The intention of this work was to study the expression/localization and possible function of VEGF receptors in pituitary adenomas. VEGF receptor mRNA and protein expression was studied by in situ hybridization, immunohistochemistry and RT-PCR in 6 normal human pituitaries, 39 human pituitary adenomas and 4 rodent pituitary adenoma cell lines. VEGFR-1 expressing somatotroph MtT-S cells were used as a model to study the role of VEGF on cell proliferation and to elucidate the underlying mechanism of action. In normal pituitaries, VEGFR-1 was detected in endocrine cells, whereas VEGFR-2 and NRP-1 were exclusively expressed in endothelial cells. In pituitary tumours, a heterogeneous VEGFR expression pattern was observed by IHC. VEGFR-1, VEGFR-2 and NRP-1 were detected in 24, 18 and 17 adenomas respectively. In the adenomas, VEGFR-1 was expressed in epithelial tumour cells and VEGFR-2/NRP-1 in vessel endothelial cells. Functional studies in VEGFR-1-positive MtT-S cells showed that the ligands of VIEGFR-1 significantly stimulated cell proliferation. This effect was mediated through the phosphatidylinositol-3-kinase-signalling pathway and involves induction of cyclin D1 and Bcl-2. Based on our results, we speculate that the ligands of VEGF receptors, such as VEGF-A and placenta growth factor, not only play a role in angiogenesis in pituitary adenomas, but also affect the growth of pituitary tumour cells through VEGFR-1. © 2006 Society for Endocrinology.
وصف الملف: application/pdf
العلاقة: http://hdl.handle.net/20.500.12110/paper_00220795_v191_n1_p249_OnofriTest; http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=dTest&c=artiaex&d=paper_00220795_v191_n1_p249_Onofri_oai
الإتاحة: https://doi.org/20.500.12110/paper_00220795_v191_n1_p249_OnofriTest
https://hdl.handle.net/20.500.12110/paper_00220795_v191_n1_p249_OnofriTest
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=dTest&c=artiaex&d=paper_00220795_v191_n1_p249_Onofri_oai -
3دورية أكاديمية
المؤلفون: Onofri, C., Carbia Nagashima, A., Schaaf, L., Feirer, M., Lohrer, P., Stummer, W., Berner, S., Chervin, A., Goldberg, V., Stalla, G.K., Renner, U., Arzt, E.
مصطلحات موضوعية: Estrogens, Interleukin-6, Lactotroph/lactosomatotroph adenomas, Vascular endothelial growth factor, estradiol, interleukin 6, vasculotropin, adult, article, clinical article, cytokine production, female, hormonal regulation, human, human tissue, hypophysis adenoma, male, neuroendocrinology, priority journal, protein expression, Enzyme-Linked Immunosorbent Assay, Humans, Middle Aged, Pituitary Neoplasms, Prolactinoma, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A
الوصف: Estrogens are considered to be critically involved in lactotroph and lactosomatotroph pituitary tumor development. In addition to direct effects, estradiol-induced tumor formation may involve alterations in growth factor and cytokine production. We have studied whether estradiol stimulates the production of the angiogenic vascular endothelial growth factor and the potential tumor progression factor interleukin-6 in 5 lactotroph (LA) and 5 lactosomatotroph (LSA) human pituitary adenoma cell cultures. All tumors secreted heterogenous basal amounts of VEGF (18.0 ± 1.4 to 425 ± 26 pg/ml per 24h) and IL-6 (18.1 ± 1.5 to 604 ± 17 pg/ml per 24h). Estradiol (100nM) significantly enhanced VEGF release in all LA and LSA cell cultures (47 to 168% above basal). IL-6 secretion was stimulated in 3 out of 5 LA and in all LSA cell cultures (31 to 287% above basal). In cell cultures obtained from tumors from which sufficient cells could be isolated, a dose-dependent effect of estradiol (1 to 100 nM) on VEGF and IL-6 production was observed. Stimulation of IL-6 and/or VEGF secretion by estradiol in the majority of human lactotroph and lactosomatotroph adenoma cell cultures studied, suggests that estrogens may contribute to adenoma expansion through the stimulation of these auto-/paracrine-acting adenoma progression factors. ; Fil:Carbia Nagashima, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
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4دورية أكاديمية
المؤلفون: Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., Stalla, G.K., Renner, U.
مصطلحات موضوعية: cyclin D1, messenger RNA, neuropilin 1, phosphatidylinositol 3 kinase, placental growth factor, protein bcl 2, vasculotropin A, vasculotropin receptor, vasculotropin receptor 1, vasculotropin receptor 2, adult, aged, animal cell, article, cell proliferation, controlled study, endocrine cell, endothelium cell, epithelium tumor, female, gene expression, human, human cell, human tissue, hypophysis adenoma, immunohistochemistry, in situ hybridization, male, nonhuman, nucleotide sequence
الوصف: As for any solid tumour, pituitary adenoma expansion is dependent on neovascularization through angiogenesis. In this process, vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) may play an outstanding role. The intention of this work was to study the expression/localization and possible function of VEGF receptors in pituitary adenomas. VEGF receptor mRNA and protein expression was studied by in situ hybridization, immunohistochemistry and RT-PCR in 6 normal human pituitaries, 39 human pituitary adenomas and 4 rodent pituitary adenoma cell lines. VEGFR-1 expressing somatotroph MtT-S cells were used as a model to study the role of VEGF on cell proliferation and to elucidate the underlying mechanism of action. In normal pituitaries, VEGFR-1 was detected in endocrine cells, whereas VEGFR-2 and NRP-1 were exclusively expressed in endothelial cells. In pituitary tumours, a heterogeneous VEGFR expression pattern was observed by IHC. VEGFR-1, VEGFR-2 and NRP-1 were detected in 24, 18 and 17 adenomas respectively. In the adenomas, VEGFR-1 was expressed in epithelial tumour cells and VEGFR-2/NRP-1 in vessel endothelial cells. Functional studies in VEGFR-1-positive MtT-S cells showed that the ligands of VIEGFR-1 significantly stimulated cell proliferation. This effect was mediated through the phosphatidylinositol-3-kinase-signalling pathway and involves induction of cyclin D1 and Bcl-2. Based on our results, we speculate that the ligands of VEGF receptors, such as VEGF-A and placenta growth factor, not only play a role in angiogenesis in pituitary adenomas, but also affect the growth of pituitary tumour cells through VEGFR-1. © 2006 Society for Endocrinology.
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