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Departamento de Hematologia
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Centro de Investigação de Patobiologia Molecular
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Serviço de Gastrenterologia
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Publication History View all

  • Pediatric Neurology 10/2013;
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    ABSTRACT: Higher-risk myelodysplastic syndromes (MDS) are aggressive disorders with rapid progression to AML and short survival. Azacitidine has shown unprecedented survival advantage in these patients but its treatment schedule involves daily hospital administrations for 7 days every 4 weeks. Due to patient and staffing constraints, we have treated 50 patients with a 5-day dose-intensified (500 mg/m(2) total monthly dose divided in 5 days) azacitidine schedule in our center. The regimen was well tolerated, with Grade 3/4 adverse events seen in 24 % patients and only two discontinuations due to toxicity. The response rate was similar to that reported with the 7-day schedule: 16 % complete remissions, 32 % partial remissions, and 62 % transfusion independence. The median survival was 19.2 months from diagnosis. In addition, this regimen reduced hospital visits by 28 % and drug use by 30 %. Our results demonstrate the safety and efficacy of a dose-intensified 5-day regimen.
    Annals of Hematology 04/2013;
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    ABSTRACT: CONTEXT: The BRAF V600E mutation is the most frequent genetic alteration in papillary thyroid carcinoma (PTC). In colorectal cancer, BRAF V600E was described to functionally cooperate with Rac1b, a hyperactive splice variant of the small GTPase Rac1, to sustain cell survival. This interplay has never been investigated in PTCs. OBJECTIVE: We aimed to analyze the expression of Rac1b in PTC and correlate its expression with BRAF V600E mutational status, histopathological features and clinical outcome. PATIENTS AND METHODS: 61 patients and 87 samples (61 PTCs, 26 normal thyroid tissues) were included. Patients were divided into two groups based on longitudinal evolution and final outcome. Rac1b expression levels were determined by quantitative RT-PCR and Western blotting. RESULTS: Rac1b was expressed in thyroid and overexpressed in 46% of PTCs. Neither Rac1b overexpression nor V600E mutation correlated with histopathological features classically associated with worse prognosis. Rac1b overexpression was significantly associated with both V600E mutation (P = 0.0008) and poor clinical outcome (P = 0.0029). Whereas BRAF V600E alone did not associate with patient outcome (P = 0.2865), the association of Rac1b overexpression with BRAF V600E was overrepresented in the group with poorer clinical outcome (P = 0.0044). CONCLUSIONS: Present results document, for the first time, expression of Rac1b in normal thyroid cells as well as overexpression in a subset of PTCs. Furthermore, they suggest a possible interplay between BRAF V600E and Rac1b contributing to poor clinical outcome. Future studies are needed to clarify the oncogenic potential of Rac1b in thyroid carcinogenesis.
    European Journal of Endocrinology 03/2013;


  • Address
    R. Prof. Lima Basto, 1099-023, Lisbon, Portugal
  • Head of Institution
    Francisco Ventura Ramos
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  • Phone
    +351 217229800
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Top publications last week by downloads

Acta Radiológica Portuguesa. 01/2009; Vol.XXI(81):53-61.
Acta Radiológica Portuguesa. 01/2009; Vol.XXI(81):27-35.

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