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- The sex bias of cancerPublication . Costa, Ana Raquel; Cruz, Inês; Oliveira, Mariana Lança de; Gonçalves, Isabel; Cascalheira, José; Santos, CeciliaIn cancers of hormone-dependent organs like women breast and reproductive organs, endometrium and ovaries, and men’s prostate and testicular cancer, the roles of sex hormones and deregulation of hormone axes are well-documented. More strikingly, epidemiological data highlights significant differences between sexes in the incidence of various cancers in non-reproductive organs, where the role of sex hormones has been less studied. In an era when personalised medicine is gaining recognition, understanding molecular, cellular and biological differences between men and women is timely for developing more appropriate therapeutic interventions according to gender. In this review we show that sex hormones also shape much of the deregulated cellular and molecular pathways leading to cell proliferation and cancer in nonreproductive organs.
- Triiodothyronine modulates neuronal plasticity mechanisms to enhance functional outcome after strokePublication . Talhada, Daniela; Feiteiro, Joana; Costa, Ana Raquel; Talhada, Tiago; Cairrão, Elisa; Wieloch, Tadeusz; Englund, Elisabet; Santos, Cecilia Reis; Gonçalves, Isabel; Ruscher, KarstenThe development of new therapeutic approaches for stroke patients requires a detailed understanding of the mechanisms that enhance recovery of lost neurological functions. The efficacy to enhance homeostatic mechanisms during the first weeks after stroke will influence functional outcome. Thyroid hormones (TH) are essential regulators of neuronal plasticity, however, their role in recovery related mechanisms of neuronal plasticity after stroke remains unknown. This study addresses important findings of 3,5,3'-triiodo-L-thyronine (T3) in the regulation of homeostatic mechanisms that adjust excitability - inhibition ratio in the post-ischemic brain. This is valid during the first 2 weeks after experimental stroke induced by photothrombosis (PT) and in cultured neurons subjected to an in vitro model of acute cerebral ischemia. In the human post-stroke brain, we assessed the expression pattern of TH receptors (TR) protein levels, important for mediating T3 actions.Our results show that T3 modulates several plasticity mechanisms that may operate on different temporal and spatial scales as compensatory mechanisms to assure appropriate synaptic neurotransmission. We have shown in vivo that long-term administration of T3 after PT significantly (1) enhances lost sensorimotor function; (2) increases levels of synaptotagmin 1&2 and levels of the post-synaptic GluR2 subunit in AMPA receptors in the peri-infarct area; (3) increases dendritic spine density in the peri-infarct and contralateral region and (4) decreases tonic GABAergic signaling in the peri-infarct area by a reduced number of parvalbumin+ / c-fos+ neurons and glutamic acid decarboxylase 65/67 levels. In addition, we have shown that T3 modulates in vitro neuron membrane properties with the balance of inward glutamate ligand-gated channels currents and decreases synaptotagmin levels in conditions of deprived oxygen and glucose. Interestingly, we found increased levels of TRβ1 in the infarct core of post-mortem human stroke patients, which mediate T3 actions. Summarizing, our data identify T3 as a potential key therapeutic agent to enhance recovery of lost neurological functions after ischemic stroke.