Browsing by Author "Costa, S"
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- Association between functional EGF+61 polymorphism and glioma riskPublication . Costa, BM; Ferreira, P; Costa, S; Canedo, P; Oliveira, P; Silva, AI; Pardal, F; Suriano, G; Machado, JC; Lopes, JM; Reis, RMPURPOSE: Epidermal growth factor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61 in glioma susceptibility and prognosis. EXPERIMENTAL DESIGN: A case-control study involving 197 glioma patients and 570 controls was done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed. The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. RESULTS: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR, 1.32; 95% CI, 1.04-1.67), glioblastomas (OR, 1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR, 1.55; 95% CI, 1.07-2.23). The GG genotypes were associated with increased risk for gliomas (OR, 1.71; 95% CI, 1.07-2.73), glioblastomas (OR, 2.03; 95% CI, 1.02-4.05), and oligodendrogliomas (OR, 2.72; 95% CI, 1.18-6.28). In addition, the AG+GG genotypes were associated with higher risk for gliomas (OR, 1.52; 95% CI, 1.03-2.23) and oligodendrogliomas (OR, 2.80; 95% CI, 1.35-5.79). No significant association was observed between the EGF+61 polymorphism and glioblastoma or oligodendroglioma patients' overall survival. The luciferase reporter gene assay exhibited a significant increased promoter activity for the G variant compared with the reference A allele. CONCLUSIONS: These findings support the role of the EGF+61 polymorphism as a susceptibility factor for development of gliomas and show its implication on EGF promoter activity.
- Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosisPublication . Marques, H; Catarino, R; Domingues, N; Barros, E; Portela, C; Almeida, MI; Costa, S; Reis, RM; Medeiros, R; Longatto-Filho, AThe Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or β-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.
- Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosisPublication . Xavier-Magalhães, A; Oliveira, AI; Vieira de Castro, J; Pojo, M; Gonçalves, CS; Lourenço, T; Viana-Pereira, M; Costa, S; Linhares, P; Vaz, R; Nabiço, R; Amorim, J; Pinto, AA; Reis, RM; Costa, BMAbnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these HOTAIR SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.
- Eosinophilic EsophagitisPublication . Costa, S; Ferreira, M; Gonçalves, B; Gonçalves, R
- Frontal lobe lesion at brain CT as initial presentation of esophageal cancerPublication . Costa, S; Gonçalves, B; Cruz, M; Gonçalves, R
- Impact of EGFR genetic variants on glioma risk and patient outcomePublication . Costa, BM; Viana-Pereira, M; Fernandes, R; Costa, S; Linhares, P; Vaz, R; Pinheiro, C; Lima, J; Soares, P; Silva, A; Pardal, F; Amorim, J; Nabiço, R; Almeida, R; Alegria, C; Pires, MM; Pinheiro, C; Carvalho, E; Oliveira, P; Lopes, JM; Reis, RMBACKGROUND: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, -216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. METHODS: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. RESULTS: None of the EGFR -216G/T variants was significantly associated with glioma risk. The -191C/A genotype was associated with higher risk for glioma when the (CA)(n) alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)(n) cutoff points, only -191C/A genotype was consistently associated with improved survival of patients with glioblastoma. CONCLUSIONS: Our findings implicate EGFR -191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and suggest -191C/A as a prognostic marker in glioblastoma. IMPACT: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies
- Intragastric Penetration of the Connecting Tube After Laparoscopic Adjustable Gastric BandingPublication . Costa, S; Machado, A; Gonçalves, B; Costa, JM; Gonçalves, R
- Prospective Observational Study on acute Appendicitis Worldwide (POSAW)Publication . Sartelli, M; Baiocchi, GL; Di Saverio, S; Ferrara, F; Labricciosa, FM; Ansaloni, L; Coccolini, F; Vijayan, D; Abbas, A; Abongwa, HK; Agboola, J; Ahmed, A; Akhmeteli, L; Akkapulu, N; Akkucuk, S; Altintoprak, F; Andreiev, AL; Anyfantakis, D; Atanasov, B; Bala, M; Balalis, D; Baraket, O; Bellanova, G; Beltran, M; Melo, RB; Bini, R; Bouliaris, K; Brunelli, D; Castillo, A; Catani, M; Che Jusoh, A; Chichom-Mefire, A; Cocorullo, G; Coimbra, R; Colak, E; Costa, S; Das, K; Delibegovic, S; Demetrashvili, Z; Di Carlo, I; Kiseleva, N; El Zalabany, T; Faro, M; Ferreira, M; Fraga, GP; Gachabayov, M; Ghnnam, WM; Giménez Maurel, T; Gkiokas, G; Gomes, CA; Griffiths, E; Guner, A; Gupta, S; Hecker, A; Hirano, ES; Hodonou, A; Hutan, M; Ioannidis, O; Isik, A; Ivakhov, G; Jain, S; Jokubauskas, M; Karamarkovic, A; Kauhanen, S; Kaushik, R; Kavalakat, A; Kenig, J; Khokha, V; Khor, D; Kim, D; Kim, JI; Kong, V; Lasithiotakis, K; Leão, P; Leon, M; Litvin, A; Lohsiriwat, V; López-Tomassetti Fernandez, E; Lostoridis, E; Maciel, J; Major, P; Dimova, A; Manatakis, D; Marinis, A; Martinez-Perez, A; Marwah, S; McFarlane, M; Mesina, C; Pędziwiatr, M; Michalopoulos, N; Misiakos, E; Mohamedahmed, A; Moldovanu, R; Montori, G; Mysore Narayana, R; Negoi, I; Nikolopoulos, I; Novelli, G; Novikovs, V; Olaoye, I; Omari, A; Ordoñez, CA; Ouadii, Mt; Ozkan, Z; Pal, A; Palini, GM; Partecke, LI; Pata, F; Pędziwiatr, M; Pereira Júnior, GA; Pintar, T; Pisarska, M; Ploneda-Valencia, CF; Pouggouras, K; Prabhu, V; Ramakrishnapillai, P; Regimbeau, JM; Reitz, M; Rios-Cruz, D; Saar, S; Sakakushev, B; Seretis, C; Sazhin, A; Shelat, V; Skrovina, M; Smirnov, D; Spyropoulos, C; Strzałka, M; Talving, P; Teixeira Gonsaga, RA; Theobald, G; Tomadze, G; Torba, M; Tranà, C; Ulrych, J; Uzunoğlu, MY; Vasilescu, A; Occhionorelli, S; Venara, A; Vereczkei, A; Vettoretto, N; Vlad, N; Walędziak, M; Yilmaz, TU; Yuan, KC; Yunfeng, C; Zilinskas, J; Grelpois, G; Catena, FBACKGROUND: Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments. METHODS: This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016-September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study. RESULTS: A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%. CONCLUSIONS: The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.
- The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung CancerPublication . de Mello, RA; Ferreira, M; Soares-Pires, F; Costa, S; Cunha, J; Oliveira, P; Hespanhol, V; Reis, RMINTRODUCTION: Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. MATERIALS AND METHODS: Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF -460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029. CONCLUSIONS: Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well.
- TP53 codon 72 polymorphism in susceptibility, overall survival, and adjuvant therapy response of gliomas.Publication . Lima-Ramos, V; Pacheco-Figueiredo, L; Costa, S; Pardal, F; Silva, A; Amorim, J; Lopes, JM; Reis, RMTP53 is a key tumor suppressor gene that encodes a transcriptional factor involved in several cellular mechanisms, including growth arrest, DNA repair, and induction of apoptosis. In addition to TP53 gene mutations, a common polymorphism, Arg72Pro, has been involved in the carcinogenesis process. The Pro72 variant has been associated with a slower induction of apoptosis and may influence the risk of cancer development. The role of Arg72Pro polymorphism in glioma susceptibility is poorly characterized. With the objective of analyzing the role of the TP53 Arg72Pro polymorphism in glioma risk, overall survival, and patient therapy response in a Portuguese population, we conducted a retrospective case-control study, including 171 patients with gliomas and 526 cancer-free individuals. The Arg72Pro genotype was assessed by the polymerase chain reaction-restriction fragment length polymorphism technique. No statistically significant differences were observed in the genotypic and allelic frequencies between glioma and control groups, and no statistically significant differences were observed with stratification of gliomas into distinct histological subtypes: astrocytic (n = 115), glioblastoma (n = 75), and oligodendroglial (n = 54) tumors. No significant association was observed between TP53 Arg72Pro and patient overall survival, but Kaplan-Meier analysis of glioma patients harboring the Pro72 allele showed a significantly longer survival with adjuvant therapy. In this first assessment of the role of TP53 Arg72Pro polymorphism in a large series of Portuguese glioma tumors, no association was observed with glioma susceptibility or overall survival, except for patients submitted to adjuvant therapy.