Geraldo Barroso Cavalcanti

Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I.

T-cell leukemia/lymphoma (T-c LL) associated with prior infection with HTLV-I is rarely described in children. We present herein, the clinical, morphological, and virologic features of T-c LL, which occurred in eight pediatric cases with similar features of ATLL described in adults. There were three girls and five boys with age ranging from 2 to 18 years. Lymphoadenopathy, hepatosplenomegaly and marked skin lesions were presented in all cases. Five patients had hypercalcemia. The diagnostic criteria of T-c LL were based on both morphological and immunophenotypical analyses characterized by T-cell markers positively. Seven cases were cCD3+, CD4/CD25+, whereas CD1a and TdT were negative in all cases tested. HTLV-I antibodies were detected in all cases. HTLV-I provirus integration of at least one provirus was seen in all cases tested by molecular analysis. Mother-to-child transmission of HTLV-I was demonstrated in six cases. Interestingly, a homozygous deletion in p16 gene locus was observed in all four cases studied, while exons 7 and 8 of p53 were deleted in one child. The deletion of the p16(INK4A)/p14(ARF) or mutation of p53, key regulatory protein of cell cycle checkpoint in G1/S progression, found in five of the eight pediatric patients suggests that in these cases genetic lesions associated with HTLV-I infection may predispose for an early onset of leukemia.

Coexpression of p53 protein and MDR functional phenotype in leukemias: the predominant association in chronic myeloid leukemia.

One of the best characterized resistance mechanisms of leukemias is multidrug resistance (MDR) mediated by P‐glycoprotein (Pgp) and multidrug‐resistant related protein (MRP). In addition to Pgp and MRP, p53 mutation or inactivation might play a relevant role in therapeutic failure. Some studies have demonstrated that Pgp and MRP may be activated in association with overexpression of mutant or inactivated p53 protein. The aim of this study was to investigate the association between p53 expression and MDR functional phenotype analyzed by flow cytometry (FCM).

Analysis of HFE Genes C282Y, H63D, and S65D in Patients With Hyperferritinemia From Northeastern Brazil

Hereditary hemochromatosis (HH) is a genetic disease caused by the high absorption and deposition of iron in several organs. This accumulation results in several clinical complications such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders, and skin darkening. The H63D and C282Y mutations are well defined in the HH etiology. The objective of this article is identification of the H63D and C282Y mutations in the HFE protein gene and the frequency assessment of these mutations in patients with persistent increase of serum ferritin in patients from Natal City from state of Rio Grande do Norte, located in northeastern Brazil.

Immunohistochemical expression of p16, Ki-67 and p53 in cervical lesions – A systematic review

This study evaluated the immunohistochemical (IHC) expression of p16, p53 and Ki-67 in precancerous lesions and in cervical cancer (CC). Identification and review of publications assessing IHC expression in cervical intraepithelial neoplasia (CIN) and CC until February 15, 2017. Systematic review of studies in women with and without cervical lesions in order to evaluate whether there is overexpression of these biomarkers. A total of 28 publications met the criteria which included 6005 patients. The analysis showed that there is higher IHC expression of these biomarkers associated with the more severe lesions. Nineteen out of 22 evaluated studies have shown that there is a higher p16 expression in more severe lesions (CC), while in p53 expression only 4 out of the 9 studies showed a higher expression among more severe cases. Regarding the Ki-67 expression, it was observed that 9 out of 14 studies showed higher expression in more severe lesions. A complete absence of or just minimal IHC expression was observed in the normal cervical epithelium, whilst a significant increase in the expression of these biomarkers was detected according to the severity of lesions. Results suggest that these biomarkers can be considered useful tools for discriminating between the stages of the progressive cervical disease.

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

p53 is a cell cycle checkpoint control protein that assesses DNA damage and acts as a transcription factor regulating genes, which control cell growth, DNA repair, and apoptosis. p53 mutations have been found in a wide variety of different cancers including flow cytometric assessment of p53 protein expression using anti‐p53 monoclonal antibodies. We studied p53 protein expression by flow cytometry (FC) assay in 223 blood and/or bone marrow samples from 72 patients with chronic myeloid leukemia (CML): 54 in chronic phase (CML‐CP), 7 in accelerated phase (CML‐AP), and 11 in blastic phase (CML‐BP); 64 patients with chronic lymphoid leukemia (CLL): (34 at diagnosis, 21 in previously treated, and 9 with Richters syndrome); 44 patients with acute lymphoid leukemia (ALL): 36 at diagnosis and 8 in relapse; and 43 acute myeloid leukemia (AML): 27 de novo, 7 in relapse, and 9 secondary. p53 protein expression was observed in 64 of 223 patients samples: 14/64 (21.9%) CLL, 13/44 (29.5%) ALL, 19/43 (44.2%) AML, and 17/72 (23.6%) CML. Highest levels were detected in the advanced phases of CLL, ALL, and CML. In addition, in patients with AML, high levels of p53 expression were detected in secondary and relapse disease and also in de novo AML cases. Our results demonstrated that p53 expression levels are strongly associated with advanced disease. On the basis of these results, we concluded that FC can be a reliable approach to study p53 protein expression in leukemic patients.

MC3T3‐E1 Cells Behavior on Surfaces Bombarded by Argon Ions in Planar Cathode Discharge

To evaluate the effect of topography in nanoscale, titanium surfaces were bombarded by argon ions (a chemically inert gas), in an atmosphere of plasma. The effects of surface parameters on morphology, adhesion, proliferation, and MC3T3-E1 preosteoblasts differentiation were analyzed. Nontreated (smooth) surfaces were used as a control. The levels of average roughness (Ra) observed in bombarded and smooth titanium surfaces were of 95 and 14 nm, respectively. The wettability increased on treated surfaces. The number of attached cells (30 and 60 min) was significantly higher on the bombarded surface. The cell proliferation after 3 and 7 days was also significantly higher on the ion-bombarded surface. In addition, the ALP activity and expression of osteocalcin were higher in cells grown on the treated surface. The results showed that bombardment with argon ions increased the roughness and the wettability of the Ti surface, promoting a significant increase in the adhesion, proliferation, and differentiation of preosteoblasts.