Browsing by Author "Monteiro, C."
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- Complete pathological response (pCR) in gastroesophageal cancer: Correlation with metabolic responsePublication . Cabral, Francisco; Cruz, A.; Casaca, R.; Monteiro, C.; Ramos, P.; Pedro, C.; Brandão, F.; Fonseca, R.; Ratão, P.; Saldado, L.; Pinto, Iola; Abecasis, N.Purpose. - Neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with resectable esophageal or esophagogastric junctional (GEJ) (Siewert I) cancer is associated with long term overall survival benefits. Up to one third of all patients submitted to nCRT present pathological complete response (pCR). F-18-fluorodeoxyglucose positron emission tomography with CT (F-18-FDG PET-CT) is an important tool for assessing treatment response. Purpose was to assess retrospectively the power of F-18-FDG PET-CT in predicting pCR to evaluate the feasibility of a "watch and wait" approach. Patients and methods. - Retrospective analysis of a prospective database with esophageal or GEJ submitted to pre-operative chemoradiation. Pre and pos treatment F-18-FDG PET-CT were reviewed and classified using visual assessment and PERCIST criteria and the values of maximum standard uptake value were also recorded. Patients were classified as pCR or non-PCR. F-18-FDG PET-CT and pathological findings were compared against each other. Results. - Forty-three patients were included. The median age was 67 years and 90.7% were male. All patients underwent preoperative CRT and were evaluated with F-18-FDG PET-CT pre and post treatment. Transthoracic surgery was performed in all patients. Histological type was adenocarcinoma in 37% and squamous cell carcinoma in 58%. pCR was achieved in 56% of cases. Visual assessment of F-18-FDG PET-CT showed overall sensitivity 57.9%, specificity 62.5% and PERCIST criteria had 100% sensibility and 16.7% specificity. Conclusions. - F-18-FDG PET-CT is not an ideal predictor of pCR but if we use the PERCIST criteria we will have a high sensitivity and negative predictive value, avoiding false negative scans. (C) 2020 Societe francaise de radiotherapie oncologique (SFRO).
- Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological typesPublication . Malta-Vacas, Joana; Aires, C.; Costa, P.; Conde, A. R.; Ramos, S.; Martins, A. P.; Monteiro, C.; Brito, MiguelBackground: There are now several lines of evidence to suggest that protein synthesis and translation factors are involved in the regulation of cell proliferation and cancer development. Aims: To investigate gene expression patterns of eukaryotic releasing factor 3 (eRF3) in gastric cancer. Methods: RNA was prepared from 25 gastric tumour biopsies and adjacent non-neoplastic mucosa. Real time TaqMan reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the relative gene expression levels. DNA was isolated from tumour and normal tissues and gene dosage was determined by a quantitative real time PCR using SYBR Green dye. Results: Different histological types of gastric tumours were analysed and nine of the 25 tumours revealed eRF3/GSPT1 overexpression; moreover, eight of the 12 intestinal type carcinomas analysed overexpressed the gene, whereas eRF3/GSPT1 was overexpressed in only one of the 10 diffuse type carcinomas (Kruskal-Wallis Test; p , 0.05). No correlation was found between ploidy and transcript expression levels of eRF3/GSPT1. Overexpression of eRF3/GSPT1 was not associated with increased translation rates because the upregulation of eRF3/GSPT1 did not correlate with increased eRF1 levels. Conclusions: Overexpression of eRF3/GSPT1 in intestinal type gastric tumours may lead to an increase in the translation efficiency of specific oncogenic transcripts. Alternatively, eRF3/GSPT1 may be involved in tumorigenesis as a result of its non-translational roles, namely (dis)regulating the cell cycle, apoptosis, or transcription.
- Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibilityPublication . Brito, Miguel; Malta-Vacas, Joana; Carmona, Bruno; Aires, C.; Costa, P.; Martins, A. P.; Ramos, S.; Conde, A. R.; Monteiro, C.Gastric cancer remains a major cause of death in the developed countries, and a large percentage is still genetically unexplained. Because of their major role in cell survival, mutations in translation factors and altered expression of these genes have been associated with cancer development. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation, cytoskeleton organization, and apoptosis. The aim of this study was to evaluate eRF3/GSPT1 gene as a potential genetic susceptibility associated locus for gastric cancer, analyzing a stable GGC expansion in exon 1 encoding a polyglycine tract in the N-terminal domain of the protein. DNA was obtained from 139 patients with gastric cancer and from 100 individuals of a healthy control population. The GGC expansion was amplified by PCR and the number of repeats determined by genotyping in an automatic sequencer. There are five known alleles encoding from 8 to 12 glycines. The most common allele encodes 10 glycines. The 12-Gly allele was detected exclusively in the cancer patients (allelic frequency = 5%). Regardless of the genotype, patients with the 12-Gly allele had a 20-fold increased risk for gastric cancer. We also detected a single-base alteration in the gene (G274T) although no correlation with cancer development has been found. Thus, our results show that the GGC expansion may have a potential role in regulating eRF3/GSPT1 expression and/or changing the protein function that can lead to gastric cancer development.