ORCID Profile
0000-0002-0097-6148
Current Organisations
North South University
,
Instituto de Investigação e Inovação em Saúde
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Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.UROLONC.2017.08.012
Abstract: To evaluate the potential of sialyl-Tn (STn), a cancer-associated glycan antigen present in membrane glycoproteins, to improve a recent molecular model for stratification and prognostication of advanced stage bladder tumors based on keratins (KRT14, 5, and 20) expression. In addition, determine the association between STn and disease dissemination based on the evaluation of circulating tumor cells (CTCs) and the metastasis, which is a critical matter to improve patient management. A retrospective series of 80 muscle-invasive primary bladder tumors and associated metastasis were screened for KRT14, 5, and 20 and STn by real-time polymerase chain reaction and immunohistochemistry. Peripheral blood was collected in a patients' subset, CTCs were isolated through a size-based microfluidic chip and screened for KRTs and STn. Basal-like lesions presented worse cancer-specific and disease-free survival compared to luminal tumors. STn antigen inclusion discriminated patients with worst survival in each subgroup (P = 0.047 for luminal P = 0.027 for basal-like tumors). STn expression in CTCs and distant metastasis was also demonstrated. This work reinforces the potential of the KRT-based model for bladder cancer management and the association of STn with aggressiveness, supporting its inclusion in predictive molecular models toward patient-tailored precision medicine. Moreover, we describe for the first time that CTCs and the metastasis present a basal phenotype and express the STn antigen, highlighting its link with disease dissemination. Future studies should focus on determining the biological and clinical significance of these observations in the context of liquid biopsies. Given the membrane nature of STn, highly specific targeted therapeutics may also be envisaged.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.NBT.2018.09.004
Abstract: Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes and distant metastases hold great potential for liquid biopsies by providing a molecular fingerprint for disease dissemination and its temporal evolution through the course of disease management. CTC enumeration, classically defined on the basis of surface expression of Epithelial Cell Adhesion Molecule (EpCAM) and absence of the pan-leukocyte marker CD45, has been shown to correlate with clinical outcome. However, existing approaches introduce bias into the subsets of captured CTCs, which may exclude biologically and clinically relevant subpopulations. Here we explore the overexpression of the membrane protein O-glycan sialyl-Tn (STn) antigen in advanced bladder and colorectal tumours, but not in blood cells, to propose a novel CTC isolation technology. Using a size-based microfluidic device, we show that the majority (>90%) of CTCs isolated from the blood of patients with metastatic bladder and colorectal cancers express the STn antigen, supporting a link with metastasis. STn
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.CLINTHERA.2010.07.007
Abstract: In Bangladesh, a number of generic oral formulations of esomeprazole are marketed. Study of the relative bioavailability of these generic formulations has yet to be conducted in a Bangladeshi population. The aims of this study were to assess the relative bioavailability and pharmacokinetic properties of 2 formulations (test and reference) of esomeprazole 40 mg. This open-label, randomized, 2-way crossover study was conducted in healthy Bangladeshi male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, as a single dose of esomeprazole 40 mg after a 12-hour overnight fast. A washout period of 1 week was maintained between treatments. Following oral administration, blood s les were collected at 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 7, 9, and 12 hour(s) after dosing and analyzed for esomeprazole concentrations using a validated HPLC method. Pharmacokinetic parameters, including C(max), AUC(0-12), and AUC(0-infinity), were determined with a non-compartmental method. The formulations were to be considered bioequivalent if the natural log (ln)-transformed ratios of the pharmacokinetic parameters were within the predetermined bioequivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement. The within- and between-group differences were examined using ANOVA. Tolerability was assessed by monitoring vital signs and conducting subject interviews regarding adverse events. Interviewers were not blinded to study design. A total of 24 nonsmoking, healthy, Bangladeshi male subjects (mean [SD] age, 22.8 [2.22] years [range, 20-29 years] weight, 64.7 [6.9] kg [range, 55-79 kg] height, 1.69 [0.05] m [range, 1.63-1.82 m] and body mass index, 22.39 [2.16] kg/m(2) [range, 18.99-27.34 kg/m(2)]) were enrolled. From serum data, the mean (SD) values for the test and reference products were as follows: 5.26 (1.57) and 5.54 (2.94) micromol/L for C(max) 2.53 (0.67) and 2.07 (0.65) hours for T(max) 15.74 (6.50) and 16.68 (6.77) micromol/L/h for AUC(0-12) and 17.15 (7.58) and 18.26 (7.31) micromol/L/h for AUC(0-infinity), respectively. The mean T(max) was found to be significantly different between the test and reference formulations (2.53 [0.67] vs 2.07 [0.65] hours, respectively P < 0.05). The point estimates (90% CI) for the test/reference ratios of the In-transformed AUC(0-infinity) and C(max) were 92.92% (84.02%-102.76%) and 102.36% (85.96%-121.90%), respectively, which were within the FDA-accepted limits for assuming bioequivalence. No adverse events were reported by the volunteers during the study. This single-dose study found that the test and reference formulations of esomeprazole 40 mg met the FDA regulatory criteria for assuming bioequivalence in these healthy, fasting Bangladeshi male volunteers. A significant difference was found in T(max) between the 2 formulations. Both formulations were well tolerated in the studied population.
Publisher: Springer Science and Business Media LLC
Date: 02-03-2012
DOI: 10.1007/S12011-012-9371-3
Abstract: The purpose of the present study was to evaluate the status of serum trace elements: zinc, copper, manganese, iron, calcium, and magnesium concentrations in obsessive-compulsive disorder patients. Forty-eight obsessive-compulsive disorder patients and 48 healthy volunteers were included in this study. Patients were recruited from Bangabandhu Sheikh Mujib Medical University by random s ling. Serum trace element concentrations were determined using flame atomic absorption spectroscopy (for zinc, copper, iron, calcium, and magnesium) as well as graphite furnace atomic absorption spectroscopy (for manganese). Data were analyzed using independent t test, Pearson's correlation analysis, regression analysis, and ANOVA. Statistical analysis of these data showed a definite pattern of variation among certain elements in patients with obsessive-compulsive disorder compared to controls. In patients' serum, zinc, iron, and magnesium concentrations decreased significantly (p<0.05) compared to the controls. Serum manganese and calcium concentrations were significantly higher (p<0.05) in patients compared to the controls. These data showed a definite imbalance in the interelement relations in obsessive-compulsive disorder patients compared to controls and therefore suggest a disturbance in the element homeostasis.
Publisher: MDPI AG
Date: 07-02-2021
DOI: 10.3390/IJMS22041664
Abstract: Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.BBAGEN.2015.12.016
Abstract: Terminal α2-3 and α2-6 sialylation of glycans precludes further chain elongation, leading to the biosynthesis of cancer relevant epitopes such as sialyl-Lewis X (SLe(X)). SLe(X) overexpression is associated with tumor aggressive phenotype and patients' poor prognosis. MKN45 gastric carcinoma cells transfected with the sialyltransferase ST3GAL4 were established as a model overexpressing sialylated terminal glycans. We have evaluated at the structural level the glycome and the sialoproteome of this gastric cancer cell line applying liquid chromatography and mass spectrometry. We further validated an identified target expression by proximity ligation assay in gastric tumors. Our results showed that ST3GAL4 overexpression leads to several glycosylation alterations, including reduced O-glycan extension and decreased bisected and increased branched N-glycans. A shift from α2-6 towards α2-3 linked sialylated N-glycans was also observed. Sialoproteomic analysis further identified 47 proteins with significantly increased sialylated N-glycans. These included integrins, insulin receptor, carcinoembryonic antigens and RON receptor tyrosine kinase, which are proteins known to be key players in malignancy. Further analysis of RON confirmed its modification with SLe(X) and the concomitant activation. SLe(X) and RON co-expression was validated in gastric tumors. The overexpression of ST3GAL4 interferes with the overall glycophenotype of cancer cells affecting a multitude of key proteins involved in malignancy. Aberrant glycosylation of the RON receptor was shown as an alternative mechanism of oncogenic activation. This study provides novel targets and points to an integrative tumor glycomic roteomic-profiling for gastric cancer patients' stratification. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
No related grants have been discovered for José Alexandre Ferreira.