Browsing by Author "Melo, JB"
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- Early detection and personalized treatment in oral cancer: the impact of omics approachesPublication . Ribeiro, IP; Barroso, L; Marques, F; Melo, JB; Carreira, IMBACKGROUND: Oral cancer is one of the most common malignant lesions of the head and neck. This cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades. Moreover, the incidence of oral HPV-positive tumors is rising, especially in young people. This oral neoplasm develops through numerous molecular imbalances that affect key genes and signaling pathways; however, the molecular mechanisms involved in the pathogenesis and progression of oral tumors are still to be fully determined. In order to improve the quality of life and long-term survival rate of these patients, it is vital to establish accurate biomarkers that help in the early diagnosis, prognosis and development of target treatments. Such biomarkers may possibly allow for selection of patients that will benefit from each therapy modality, helping in the optimization of intensity and sequence of the treatments in order to decrease side effects and improve survival. CONCLUSION: In this review we discuss the current knowledge of oral cancer and the potential role of omics approaches to identify molecular biomarkers in the improvement of early diagnosis, treatment and prognosis. The pursuit to improve the quality of life and decrease mortality rates of the oral patients needs to be centralized on the identification of critical genes in oral carcinogenesis. Understanding the molecular biology of oral cancer is vital for search new therapies, being the molecular-targeted therapies the most promising treatment for these patients.
- Interstitial 287 kb deletion of 4p16.3 including FGFRL1 gene associated with language impairment and overgrowthPublication . Matoso, E; Ramos, F; Ferrão, J; Pires, LM; Mascarenhas, A; Melo, JB; Carreira, IMWe report a male patient with developmental delay carrying an interstitial 4p16.3 deletion of 287 kb, disclosed by oligo array-CGH and inherited from his father with a similar but milder phenotype. This deletion is distal to the Wolf-Hirschhorn syndrome critical regions, but includes the FGFRL1 gene proposed to be a plausible candidate for part of the craniofacial characteristics of Wolf-Hirschhorn syndrome patients. However, the proband lacks the typical facial appearance of the syndrome, but exhibits overgrowth, dysfunction of temporomandibular articulation and a bicuspid aortic valve. Given the pattern of expression of the fibroblast growth factor receptor-like 1 and its involvement in bone and cartilage formation as well as in heart valve morphogenesis, we discuss the impact of its haploinsufficiency in the phenotype.
- Mitochondrial Alterations in Fibroblasts of Early Stage Bipolar Disorder PatientsPublication . Marques, AP; Resende, R; Silva, DF; Batista, M; Pereira, D; Wildenberg, B; Morais, S; Macedo, A; Pais, C; Melo, JB; Madeira, N; Pereira, CFThis study aims to evaluate whether mitochondrial changes occur in the early stages of bipolar disorder (BD). Using fibroblasts derived from BD patients and matched controls, the levels of proteins involved in mitochondrial biogenesis and dynamics (fission and fusion) were evaluated by Western Blot analysis. Mitochondrial membrane potential (MMP) was studied using the fluorescent probe TMRE. Mitochondrial morphology was analyzed with the probe Mitotracker Green and mitophagy was evaluated by quantifying the co-localization of HSP60 (mitochondria marker) and LC3B (autophagosome marker) by immunofluorescence. Furthermore, the activity of the mitochondrial respiratory chain and the glycolytic capacity of controls and BD patients-derived cells were also studied using the Seahorse technology. BD patient-derived fibroblasts exhibit fragmented mitochondria concomitantly with changes in mitochondrial dynamics and biogenesis in comparison with controls. Moreover, a decrease in the MMP and increased mitophagy was observed in fibroblasts obtained from BD patients when compared with control cells. Impaired energetic metabolism due to inhibition of the mitochondrial electron transport chain (ETC) and subsequent ATP depletion, associated with glycolysis stimulation, was also a feature of BD fibroblasts. Overall, these results support the fact that mitochondrial disturbance is an early event implicated in BD pathophysiology that might trigger neuronal changes and modification of brain circuitry.
- Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31 --> qter) detected in an autistic boyPublication . Carreira, IM; Melo, JB; Rodrigues, C; Backx, L; Vermeesch, J; Weise, A; Kosyakova, N; Oliveira, G; Matoso, EBACKGROUND: Inverted duplications (inv dup) of a terminal chromosome region are a particular subset of rearrangements that often results in partial tetrasomy or partial trisomy when accompanied by a deleted chromosome. Associated mosaicism could be the consequence of a post-zygotic event or could result from the correction of a trisomic conception. Tetrasomies of distal segments of the chromosome 3q are rare genetic events and their phenotypic manifestations are diverse. To our knowledge, there are only 12 cases reported with partial 3q tetrasomy. Generally, individuals with this genomic imbalance present mild to severe developmental delay, facial dysmorphisms and skin pigmentary disorders. RESULTS: We present the results of the molecular cytogenetic characterization of an unbalanced mosaic karyotype consisting of mos 46,XY,add(12)(p13.3) [56]/46,XY [44] in a previously described 11 years old autistic boy, re-evaluated at adult age. The employment of fluorescence in situ hybridization (FISH) and multicolor banding (MCB) techniques identified the extra material on 12p to be derived from chromosome 3, defining the additional material on 12p as an inv dup(3)(qter --> q26.3::q26.3 --> qter). Subsequently, array-based comparative genomic hybridization (aCGH) confirmed the breakpoint at 3q26.31, defining the extra material with a length of 24.92 Mb to be between 174.37 and 199.29 Mb. CONCLUSION: This is the thirteenth reported case of inversion-duplication 3q, being the first one described as an inv dup translocated onto a non-homologous chromosome. The mosaic terminal inv dup(3q) observed could be the result of two proposed alternative mechanisms. The most striking feature of this case is the autistic behavior of the proband, a characteristic not shared by any other patient with tetrasomy for 3q26.31 --> 3qter. The present work further illustrates the advantages of the use of an integrative cytogenetic strategy, composed both by conventional and molecular techniques, on providing powerful information for an accurate diagnosis. This report also highlights a chromosome region potentially involved in autistic disorders.