Navegando por Autor "Tajara, E. H."
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Artigo DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity(Fundação de Pesquisas de Ribeirão Preto, 2015-09-08) Santos, Marcelo dos; Maia, L. L.; Silva, C. V. M.; Peterle, G. T.; Mercante, A. M. C.; Nunes, F. D.; Carvalho, M. B.; Tajara, E. H.; Louro, I. D.; Silva-Conforti, A. M. A.Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastasesArtigo FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma(Fundação de Pesquisas de Ribeirão Preto, 2015-09-22) Peterle, G. T.; Santos, Marcelo dos; Mendes, S. O.; Carvalho-Neto, P. B.; Maia, L. L.; Stur, E.; Agostini, Lidiane Pignaton; Silva, C. V. M.; Trivilin, L. O.; Nunes, F. D.; Carvalho, M. B.; Tajara, E. H.; Louro, I. D.; Silva-Conforti, A. M. A.Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Diseasefree and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patientsArtigo Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer(Fundação de Pesquisas de Ribeirão Preto, 2015-11-24) Rodrigues, P. R. S.; Maia, L. L.; Santos, Marcelo dos; Peterle, G. T.; Alves, L. U.; Takamori, J. T.; Souza, R. P.; Barbosa, W. M.; Mercante, A. M. C.; Nunes, F. D.; Carvalho, M. B.; Tajara, E. H.; Louro, I. D.; Silva-Conforti, A. M. A.The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapiesArtigo MTHFR C677T and A1298C polymorphisms as predictors of radiotherapy response in head and neck squamous cell carcinoma(Fundação de Pesquisas de Ribeirão Preto, 2015-10-26) Anders, Q. S.; Stur, E.; Agostini, Lidiane Pignaton; Garcia, F. M.; Reis, R. S.; Santos, J. A.; Mendes, S. O.; Maia, L. L.; Peterle, G. T.; Stange, V.; Carvalho, M. B.; Tajara, E. H.; Santos, Marcelo dos; Silva-Conforti, A. M. A.; Louro, I. D.The C677T and A1298C polymorphisms in methylenetetrahydrofolate reductase (MTHFR), which regulates the release of active folate in the body, may have reduced activity. Given that folate participates in important intracellular pathways, such as nucleotide synthesis and biomolecule methylation, it seems plausible that patients with head and neck squamous cell carcinoma (HNSCC) may respond differently to radiotherapy treatments, based on genetic polymorphisms. Therefore, this study sought to understand the role of these polymorphisms in HNSCC patient radiotherapy response. Genotypes were detected by PCR-RFLP after extraction of DNA from peripheral blood lymphocytes. Survival curves were analyzed by the KaplanMeier model, and significant differences were analyzed by the Wilcoxon test. Response to radiotherapy in patients with laryngeal SCC was significantly associated with the MTHFR C677T polymorphism (P = 0.030). Indeed, the presence of at least one T allele decreases the mortality rate up to 3-fold. Therefore, we propose that MTHFR C677T may represent a putative biomarker for radiotherapy prognosis in laryngeal SCC patientsArtigo Prognostic significance of head and neck squamous cell carcinoma repair gene polymorphism(Fundação de Pesquisas de Ribeirão Preto, 2015-10-16) Stur, E.; Agostini, Lidiane Pignaton; Garcia, F. M.; Peterle, G. T.; Maia, L. L.; Mendes, S. O.; Anders, Q. S.; Reis, R. S.; Santos, J. A.; Ventorim, D. P.; Carvalho, M. B.; Tajara, E. H.; Santos, Marcelo dos; Paula, F.; Silva-Conforti, A. M. A.; Louro, I. D.The aims of this study were to analyze the polymorphisms XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPC Lys939Gln, ERCC1 Asn118Asn, and RAD51 -98G>C and to verify their influence on radiotherapy response and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). Peripheral blood DNA was extracted from 311 patients and analyzed by PCR-RFLP. Our results showed that in irradiated oral and oropharyngeal patients, the 939Gln allele increased 6-fold local disease relapse risk (OR = 6.04; CI = 1.47-24.88) and over 2-fold the earliness of relapse (HR = 2.63; CI = 1.04-6.70). As for the XRCC3 polymorphism, multivariate analysis showed that the 241Met allele increases over 33-fold local relapse risk (OR = 33.64; CI = 3.23-350.85), over 12-fold earliness of relapse (HR = 12.55; CI = 2.47-63.73) and over 3-fold earliness of death (HR = 3.04; CI = 1.08-8.61). For polymorphism RAD51 -98, multivariate analysis showed that allele C increases over 3-fold the risk of relapse (OR = 3.13; CI = 1.12-8.78) and over 2-fold the earliness of relapse (HR = 2.84; CI = 1.25-6.47). For polymorphism XRCC1 Arg399Gln, multivariate analysis showed that the 399Gln allele increased the risk of local disease relapse for irradiated oral and oropharyngeal patients (OR = 3.35; CI = 1.10-10.13) by over 3-fold. Based on these results, we suggest that these polymorphisms may be useful markers of prognosis in HNSCC