Biomedical subjects

Maria Simon

Publications and source records attributed to Maria Simon.

5 recordsLinked to original sources

PubMed2006

Pharmacology of a new antidepressant: benefit of the implication of the melatonergic system.

The limitations of current antidepressant medications merit the exploration of alternative agents with novel antidepressant mechanisms of action. The established clinical finding that desynchronization of internal rhythms plays an important role in the pathophysiology of depressive disorders has stimulated the idea that resetting normal circadian rhythms may have antidepressant potential. Recent experiments using the novel melatonin receptor agonist and serotonin 2 (5-HT2c) receptor antagonist agomelatine (S20098; N[2-(7-methoxy-1-naphthyl)ethyl]- acetamide) revealed a notable chronobiotic activity and clear antidepressant-like effects in a variety of preclinical models. Binding studies performed in vitro proved that agomelatine is a high-affinity agonist at both the melatonin MT1 and MT2 receptor types. In addition, these studies revealed that agomelatine, in contrast to melatonin, blocks 5-HT2c receptors with significant affinity. Antagonism of 5-HT2c receptors is reported for various established antidepressant compounds. The antidepressant properties of agomelatine are thus based on its melatonergic actions and 5-HT2c receptor antagonism.

Acetamides↗

PubMed2005

Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia.

The beta-catenin protein is at the core of the canonical Wnt signalling pathway. Wnt stimulation leads to beta-catenin accumulation, nuclear translocation and interaction with T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors to regulate genes important for embryonic development and proliferation. Wnt/beta-catenin can promote stem cell self-renewal and is dysregulated in colon carcinoma. We have examined the role of the Wnt pathway in the development of acute myeloid leukaemia (AML) and find that the beta-catenin protein is readily detected in primary AML samples. Using transfection of a TCF/LEF reporter construct into primary AML cells and normal human progenitors, we find increased reporter activity in 16/25 leukaemia samples. Retrovirally mediated expression of a mutant active beta-catenin in normal progenitors preserves CD34 expression and impairs myelomonocytic differentiation. Activation of TCF/LEF signalling decreases factor withdrawal-induced apoptosis of normal progenitors. A significant proportion of AML cases show aberrant expression of components of the Wnt pathway including Wnt-1, Wnt-2b and LEF-1. These results provide evidence for the involvement of the Wnt/beta-catenin pathway in the pathogenesis of AML.

Acute Disease↗

PubMed2004

Distinct roles for the linker region tyrosines of Syk in FcepsilonRI signaling in primary mast cells.

Stimulation of FcepsilonRI, the high affinity IgE receptor of mast cells results in the rapid binding of the Syk tyrosine kinase to cytoplasmic domains of FcepsilonRI and to its subsequent activation. Syk plays an essential role in signal transduction from FcepsilonRI as shown by Syk-deficient mast cells, which are defective in receptor-induced degranulation, cytokine synthesis, and intracellular pathways. However the mechanism by which Syk activates these pathways remains unclear. Activation of Syk is associated with its phosphorylation on several tyrosine residues, including the linker tyrosines Tyr317, Tyr342, and Tyr346. These residues have been proposed to play important roles in the transduction of signals by binding to other signaling proteins. To test these hypotheses in primary murine mast cells, we used retroviral infection of Syk-deficient mast cells to generate cells expressing Syk proteins bearing mutations in the linker tyrosines. We show that Tyr342 and Tyr346 contribute positively to the function of Syk and have both overlapping as well as distinct functions. Mutations in either Tyr342 or Tyr346 alone had no effect on FcepsilonRI-induced degranulation or calcium flux, whereas mutation of both residues caused a significant reduction in both pathways. In contrast, phosphorylation of PLCgamma1, PLCgamma2, and Vav1 was strongly decreased by a mutation in Tyr342 alone, whereas phosphorylation of ERK and Akt was more dependent on Tyr346. Finally we show that Tyr317 functions as a negative regulatory site and that its mutation can partially compensate for the loss of both Tyr342 and Tyr346.

Animals↗

PubMedDate not supplied

[Evolution of pulmonary metastasis in osteosarcoma].

Osteosarcomas are tumors with a high aggressivity which gives early and frequent pulmonary metastasis. These patients have a poor prognosis. The reveal of prognosis factors and early detection of pulmonary relapse would influence the outcome of these patients. We performed a retrospective study at Oncology Institute from Cluj, observing 35 patients with osteosarcomas and pulmonary metastasis at the onset or in evolution. We tried to quantify some prognosis factors. We observed the predominance of male sex (20), from urban area (25), with age between 11-20 years (16 cases), with primary tumors localized more frequently at the limbs. Pulmonary metastasis were shown without free interval from the onset (12 patients), or in the first years (17 cases), more frequently with multiples locations (26 cases). 28 patients were submitted to surgical treatment for cure of primary tumor, 18 chemotherapy, and pulmonary metastasis resection in 5 cases only. The outcome under treatment was favorable in 4 cases only, compared with other studies. Early detection of pulmonary metastasis and aggressive therapy with augmentation of resection criteria for pulmonary metastasis would improve the prognosis of this patients.

Adolescent↗

PubMedDate not supplied

[Diagnostic difficulties in generalized tuberculosis--a case report].

Generalized tuberculosis (characterized by the presence in several organs of small tuberculous granulations surrounded by normal tissue) is becoming a more and more seldom disease, having an unpredictable evolution and prognosis. The diagnosis is often difficult. We present the case of a young woman, 29 years old, in which the diagnosis established in a late stage could have been fatal.

Adult↗