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1.
Ecancermedicalscience ; 15: 1312, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35047063

RESUMO

BACKGROUND: The role of the molecular tumour board (MTB) is to recommend personalised therapy for patients with cancer beyond standard-of-care treatment. A comprehensive molecular analysis of the tumour in a molecular pathology laboratory is important for all targeted therapies approaches. Here we report the 1-year experience of the Instituto Alexander Fleming Molecular Tumour Board. PATIENTS AND METHODS: The MTB of the Instituto Alexander Fleming was launched in December 2019 in a monthly meeting. In each interactive monthly session, five cases were presented and discussed by the members. These cases were referred by the treating oncologists. The MTB recommendations were sent to each physician individually, and to the rest of the meeting participants. This was discussed with the patients/families by the treating oncologist. The final decision to choose therapy was left to the treating physicians. Of the 32 patients presented at MTB, 28 (87.5%) had potentially actionable alterations and only 4 (12.5%) had no actionable mutation. Six (19%) patients received a local regulatory agency approved drug recommendation, nine (28%) patients received an off-label approval treatment recommendation and three (9%) patients did not receive the treatment due to access and reimbursement of the drug. CONCLUSION: In most of the cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. Molecular-guided extended personalised patient care is effective for a small but clinically significant proportion of patients in challenging clinical situations. We believe that the implementation of a MTB is feasible in the Latin America (LATAM) region.

2.
Invest Ophthalmol Vis Sci ; 44(5): 2252-9, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12714668

RESUMO

PURPOSE: In a recent study, it was demonstrated that docosahexaenoic acid (DHA) promotes the survival of retinal photoreceptors in vitro, delaying apoptosis. However, lipid enrichment in DHA is known to contribute to retina vulnerability to oxidative stress. In this study, the effect of oxidative damage on rat retina neurons in vitro and whether DHA enhances or diminishes this damage were investigated. METHODS: Rat retina neurons in 3-day cultures, with or without DHA, were treated with the oxidant paraquat. After 24 hours, apoptosis, mitochondrial membrane integrity, and Bcl-2 and Bax expression were immunocytochemically determined. RESULTS: Paraquat induced apoptosis in amacrine and photoreceptor neurons, major neuronal types in the culture. Neuronal apoptosis was accompanied by mitochondrial membrane depolarization, an increase in the amount of photoreceptors expressing Bax, and a decrease in those expressing Bcl-2. Addition of DHA reduced photoreceptor apoptosis by almost half, simultaneously preserving their mitochondrial membrane integrity. DHA blocked the paraquat-induced increase in Bax expression and remarkably upregulated Bcl-2 expression. Glia-derived neurotrophic factor, a photoreceptor trophic factor, only slightly increased Bcl-2 expression and did not protect photoreceptors from oxidative damage. Similarly, other fatty acids tested did not prevent photoreceptor apoptosis. CONCLUSIONS: These results show that oxidative damage induces apoptosis in retinal neurons during their early development in culture and suggest that the loss of mitochondrial membrane integrity is crucial in the apoptotic death of these cells. DHA activates intracellular mechanisms that prevent this loss and by modulating the levels of pro- and antiapoptotic proteins of the Bcl-2 family selectively protect photoreceptors from oxidative stress.


Assuntos
Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Herbicidas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Células Fotorreceptoras de Vertebrados/citologia , Animais , Técnicas de Cultura de Células , Sobrevivência Celular , Potenciais da Membrana/fisiologia , Mitocôndrias/fisiologia , Fatores de Crescimento Neural/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Regulação para Cima , Proteína X Associada a bcl-2
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