Browsing by Author "Lacerda, J"
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- Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein LevelsPublication . Gomes, AM; Soares, M; Ribeiro, P; Caldas, J; Póvoa, V; Martins, L; Melão, A; Serra-Caetano, A; Botelho de Sousa, A; Lacerda, J; Barata, JAdult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.
- Cúpulas Acetabulares em Próteses Totais da Anca Não Cimentadas (Dez Anos de Experiência)Publication . Andrade da Fonseca, L; Ricciardi, L; Chambel da Fonseca, J; Lacerda, JOs autores apresentam um estudo baseado na revisão clínica e radiográfica das artroplastias da anca não cimentadas, efectuadas no Serviço entre 1981 e 1991. Foram revistos 295 casos, em doentes com idades compreendidas entre os vinte e sete e os setenta e quatro anos, sendo a coxartrose a patologia que mais frequentemente levou à intervenção cirúrgica. Da análise realizada concluímos: 1 - As cúpulas em titânio (Ti - A1 - Va) revestidas com hidroxiapatite, de forma semi-esférica, são preferíveis às cúpulas tronco-elipso-cónicas; 2 - As próteses auto-roscantes têm uma melhor fixação primária quando comparadas com as roscadas; 3 - É útil a fixação das cúpulas acetabulares com parafusos, usando-se neste momento no Serviço acetábulos auto-roscantes, que também podem ser aparafusados, permitindo uma melhor fixação secundária.
- The Use of Free Fibula-Flexor Hallucis Longus Osteomuscular Flap for Calcaneal Reconstruction After Partial Calcanectomy for the Chronic Osteomyelitis: a Case ReportPublication . Mata-Ribeiro, L; Casal, D; Amaral Ferreira, J; Sá Costa, D; Lacerda, JINTRODUCTION: Calcaneal osteomyelitis poses a tough challenge for any reconstructive surgeon. The eradication of the infection and the reconstruction of the defect are the main goals of treatment. PRESENTATION OF CASE: We present the case of a 53-year-old male with chronic calcaneal osteomyelitis. The patient was submitted to several bone and soft tissue debridements and twice the application of gentamicin/sulfate implants at the wound bed with no success. He was then submitted to a partial calcanectomy followed by obliteration of the bone defect (4.5 × 2 × 1.5 cm) with a free vascularized fibula-flexor hallucis longus osteomuscular flap (bone dimension:4.5 × 1.5 × 1.2 cm; muscle size: 4 × 1.5 × 0.5 cm). The flap remained viable, and the post-operative period was uneventful. Bone incorporation was evident nine months after the surgery with no signs of recurrent infection or avascular necrosis. Final follow up, at one year, showed an excellent functional result. The patient was able to ambulate without assistance and referred occasional minimal foot pain. Donor site morbidity was minimal. CONCLUSION: The authors believe that this osteomuscular flap may be a valuable option to reconstruct calcaneal defects after chronic osteomyelitis.