Navegando por Autor "Louro, Iúri Drumond"

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ATM, BCL2, and TGFb gene polymorphisms as radiotherapy outcome biomarkers in head and neck squamous cell carcinoma patients
(Mary Ann Liebert, 2017-12) Agostini, Lidiane Pignaton; Stur, Elaine; Garcia, Fernanda M.; Ventorim, Diego P.; Reis, Raquel S. dos; Dettogni, Raquel S.; Santos, Eldamária V. W. dos; Peterle, Gabriela T.; Maia, Lucas L.; Mendes, Suzanny O.; Carvalho, Marcos B. de; Tajara, Eloiza H.; Paula, Flavia de; Santos, Marcelo dos; Silva, Adriana M. A. da; Louro, Iúri Drumond
Aims: Polymorphisms in cell cycle genes are considered prognostic as radiosensitivity markers in patients with head and neck squamous cell carcinoma. Therefore, we aimed to investigate the relationship of ATM 5557G>A, ATM IVS62 + 60G>A, TP53 215G>C, BCL2-938C>A, TGFb-509C>T, and TGFb 29C>T with radiotherapy response. Materials and Methods: Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in 210 patients with oral cavity/oropharyngeal carcinoma and 101 patients with laryngeal tumors. Results: In irradiated oral cavity/oropharyngeal tumors, the ATM IVS62 + 60G>A AA genotype significantly increased local recurrence risk (odds ratio [OR] = 4.43; confidence interval [CI] = 1.22–16.13) and the BCL2- 938C>A C allele and the TGFb-509C>T T allele were associated with worse disease-specific survival (hazar dratio [HR] = 0.46; CI = 0.24–0.90 and HR = 2.20; CI = 1.12–4.29, respectively). In irradiated laryngeal carcinoma, the TGFb 29C>T C allele was associated with increased local recurrence risk (OR = 0.09; CI = 0.02–0.53), death rate (OR = 0.18; CI = 0.04–0.86), and worse local disease-free and disease-specific survival rates (HR = 0.13; CI = 0.03–0.59 and HR = 0.21; CI = 0.07–0.60, respectively), while the BCL2-938C>A C allele was related to a worse disease-specific survival (HR = 0.32; CI = 0.12–0.83). Discussion: These results can help individualize treatment according to a patient’s genetic markers. We demonstrated that ATM IVS62 + 60G>A, TGFb 29C>T, TGFb-509C>T, and BCL2-938C>A can function as biomarkers of tumor radiosensitivity, being candidates for a predictive genetic profile of radiotherapy response
HIF-1alpha expression profile in intratumoral and peritumoral inflammatory cells as a prognostic marker for squamous cell carcinoma of the oral cavity
(Public Library of Science, 2014-01-09) Mendes, Suzanny Oliveira; Santos, Marcelo dos; Peterle, Gabriela Tonini; Maia, Lucas de Lima; Stur, Elaine; Agostini, Lidiane Pignaton; Carvalho, Marcos Brasilino de; Tajara, Eloiza Helena; Louro, Iúri Drumond; Trivilin, Leonardo Oliveira; Silva-Conforti, Adriana Madeira Álvares da
The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker
JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma
(Public Library of Science, 2018-03-28) Maia, Lucas de Lima; Peterle, Gabriela Tonini; Santos, Marcelo dos; Trivilin, Leonardo Oliveira; Mendes, Suzanny Oliveira; Oliveira, Mayara Mota de; Santos, Joaquim Gasparini dos; Stur, Elaine; Agostini, Lidiane Pignaton; Couto, Cinthia Vidal Monteiro da Silva; Dalbo, Juliana; Assis, Arícia Leone Evangelista Monteiro de; Archanjo, Anderson Barros; Mercante, Ana Maria Da Cunha; Lopez, Rossana Veronica Mendoza; Nunes, Fábio Daumas; Carvalho, Marcos Brasilino de; Tajara, Eloiza Helena; Louro, Iúri Drumond; Álvares-da-Silva, Adriana Madeira
Aims: Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types. Methods and results: We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffinembedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk. Conclusion: JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets
PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma
(John Wiley and Sons, 2018-05) Peterle, Gabriela Tonini; Maia, Lucas Lima; Trivilin, Leonardo Oliveira; Oliveira, Mayara Mota de; Santos, Joaquim Gasparini dos; Mendes, Suzanny Oliveira; Stur, Elaine; Agostini, Lidiane Pignaton; Rocha, Lília Alves; Moysés, Raquel Ajub; Cury, Patrícia Maluf; Nunes, Fábio Daumas; Louro, Iúri Drumond; Santos, Marcelo dos; Silva, Adriana Madeira Alvares da
Background: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. Materials and Methods: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. Results: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). Conclusion: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients
Polymorphisms in methylenetetrahydrofolate reductase and cystathionine beta-synthase in oral cancer - a case-control study in southeastern Brazilians
(Elsevier, 2016) Barbosa, Andressa; Santos, Marcelo dos; Podestá, José Roberto Vasconcelos de; Gouvêa, Sônia Alves; Zeidler, Sandra Ventorin Von; Louro, Iúri Drumond; Cordeiro-Silva, Melissa de Freitas
Introduction: Oral squamous cell carcinoma (OSCC) is a serious public health problem, due to its high mortality rate and worldwide rising incidence. OSCC susceptibility is mediated by interactions between genetic and environmental factors. Studies suggest that genetic variants encoding enzymes involved in folate metabolism may modulate OSCC risk by altering DNA synthesis/repair and methylation process. Objective: The goals of this study were to evaluate the association of three genotypic polymorphism (MTHFR C677T, MTHFR A1298C and CBS 844ins68) and oral cancer risk in southeastern Brazilians and evaluate the interactions between polymorphisms and clinical histopathological parameters. Methods: This case-control study included 101 cases and 102 controls in the state of Espírito Santo, Brazil. MTHFR genotyping was done by PCR-RFLP (polymerase chain reaction --- restriction fragment length polymorphism) and CBS genotyping by PCR (polymerase chain reaction) analysis
Single nucleotide polymorphisms in immune system genes and their association with clinical symptoms persistence in dengue-infected persons
(Elsevier, 2015) Dettogni, Raquel Spinassé; Tristão-Sá, Ricardo; Santos, Marcelo dos; Silva, Franciane Figueiredo da; Louro, Iúri Drumond
This study was undertaken to determine the prevalence of dengue clinical symptom persistence during 60 days of disease follow up, in patients of Espírito Santo state (ES)-Brazil and to evaluate the relation of single nucleotide polymorphisms (SNPs) in FccRIIa, CD209, VDR, TNF-a, IL-4, IL-6 and IFN-c genes with symptom persistence. During 2012–2013, 96 blood samples from individuals diagnosed with symptomatic dengue were collected. Clinical symptom persistence in 60 days of follow-up was assessed by a clinical and epidemiological questionnaire filled in 4 interviews. SNP genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). In two months of monitoring the dengue infection, we observed that symptoms persisted in 38.5% (37/96) of dengue patients at the end of the first month (D30) and in 11.5% (11/96) of dengue patients at the end of the second month (D60). Our results show an association between FccRIIa, TNF-a and IL-6 gene SNPs and symptom persistence and an association trend with CD209, IL-4 and IFN-c gene SNPs. Our findings may increase the knowledge on the pathophysiological mechanisms of persistent symptoms of infection with the dengue virus (DENV) and thus help the clinical management of patients

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Navegando por Autor "Louro, Iúri Drumond"