ISABELA BARBOSA FIRIGATO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
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- Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder(2021) CASTALDELLI-MAIA, Joao M.; MALBERGIER, Andre; OLIVEIRA, Adriana B. P. de; AMARAL, Ricardo A.; NEGRAO, Andre B.; GONCALVES, Priscila D.; VENTRIGLIO, Antonio; BERARDIS, Domenico de; ANTONIO, Juliana de; FIRIGATO, Isabela; GATTAS, Gilka J. F.; GONCALVES, Fernanda de ToledoBackground: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.
bookPart Carcinogênese(2022) FIRIGATO, Isabela Barbosa; SICHERO, Laura- Circulating sTREM-1 as a predictive biomarker of pediatric multisystemic inflammatory syndrome (MIS-C)(2023) GONCALVES, Guilherme S.; CORREA-SILVA, Simone; ZHENG, Yingying; AVELAR, Isabela; MONTENEGRO, Marilia M.; FERREIRA, Arthur E. F.; BAIN, Vera; FINK, Thais T.; SUGUITA, Priscila; ASTLEY, Camilla; LINDOSO, Livia; MARTINS, Fernanda; MATSUO, Olivia M.; FERREIRA, Juliana C. O. A.; FIRIGATO, Isabela; GONCALVES, Fernanda de Toledo; PEREIRA, Maria Fernanda B.; SILVA, Clovis Artur A. da; CARNEIRO-SAMPAIO, Magda; MARQUES, Heloisa H. S.; PALMEIRA, PatriciaThe exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group); 54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64-317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-alpha concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions.
- Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk(2022) FIRIGATO, Isabela; LOPEZ, Rossana V. M.; CURIONI, Otavio A.; ANTONIO, Juliana De; GATTAS, Gilka Figaro; GONCALVES, Fernanda de ToledoBackground: Genetic alterations of oral squamous cell carcinoma (OSCC) allow the understanding of the oral carcinogenesis and the identification of molecular biomarkers that aid the early diagnosis of the disease. The copy number variation (CNV) of GSTM1 and GSTT1 are promising targets because these two genes codify enzymes that perform the inactivation of tobacco carcinogens, which are the main risk factor of OSCC. However, the different levels of - detoxification mechanism in relation to each copy of the genes are unknown. Therefore, this study aimed to investigate the possible association of the CNV of GSTM1 and GSTT1 with the risk of development of OSCC. Methods: A total of 234 OSCC patients and 422 patients without any cancer diagnoses were recruited from Heli acute accent opolis Hospital from 2000 to 2011. The CNV was determined by TaqMan real-time PCR and the CopyCaller software. Odds ratio (OR) and 95% confidence interval (95% CI) values were calculated by Multiple Logistic Regression. Results: Most OSCC patients reported they continued smoking high amounts of cigarettes despite the tumor diagnosis. The CNV of GSTM1 varied from zero to two copies and the analysis revealed that two copies of GSTM1 decreased by 53% the OSCC risk (OR 0.47; 95% CI 0.24-0.92) and the risk of the tumor was modified according to the interaction of the CNV of GSTM1 and the cigarette smoking consumption, which for the amount of 40 packs-year of cigarettes the OSCC risk diminished progressively according to the increase of copies of GSTM1. Although the GSTT1 gene varied from zero to three copies, none of them were associated with the tumor risk. Conclusion: The findings suggest that the CNV of GSTM1 might be applied as a tool for the surveillance of patients and the early detection of OSCC.
- Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain(2023) GONCALVES, Fernanda de Toledo; PACHECO-BARRIOS, Kevin; REBELLO-SANCHEZ, Ingrid; CASTELO-BRANCO, Luis; MELO, Paulo S. de; PARENTE, Joao; CARDENAS-ROJAS, Alejandra; FIRIGATO, Isabela; PESSOTTO, Anne Victorio; IMAMURA, Marta; SIMIS, Marcel; BATTISTELLA, Linamara; FREGNI, FelipeBackground/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global dis-ability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analy-ses to compare carriers versus non-carriers in terms of clinical and neurophysiological character-istics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabili-tation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intra-cortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and corti-cal inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population. (c) 2022 The Authors.
- Lung function, blood markers and genetic polymorphisms differences, between subjects exposed and not to silica(2019) LOMBARDI, Elisa; GONCALVES, Fernanda; FIRIGATO, Isabela; TERRA-FILHO, Mario; PRADO, Gustavo; SANTOS, Ubiratan
- Polymorphisms of CHRNA3 and CHRNA5: Head and neck cancer and cigarette consumption intensity in a Brazilian population(2019) SILVA, Mariana R.; GATTAS, Gilka J. F.; ANTONIO, Juliana De; FIRIGATO, Isabela; CURIONI, Otavio A.; GONCALVES, Fernanda de ToledoBackground: Cigarette consumption has been identified as the main non-etiological factor in head and neck cancer (HNC) development. One of the main compounds in cigarettes is nicotine, which binds directly to nicotine acetylcholine receptors (nAchRs) in the body, which are encoded by different genes of the CHRNA family. Polymorphisms in some of these genes have been studied in relation to the risk of HNC and cigarette consumption intensity. The aim of this study was to evaluate whether there were associations between the CHRNA3 (rs578776) and CHRNA5 (rs16969968) polymorphisms and HNC risk and between the polymorphisms and the intensity of cigarette consumption. Methods: A total of 1,067 individuals from Heliopolis Hospital in Sao Paulo were investigated, including 619 patients with HNC and 448 patients without diagnosed tumors. All participants answered a questionnaire about sociodemographic information and cigarette consumption data. The polymorphisms were determined by TaqMan genotyping by real-time PCR. Results: The polymorphisms studied, rs578776 (CHRNA3) and rs16969968 (CHRNA5), did not have an association with HNC risk, but the rs16969968 homozygous genotype was associated with increased cigarette consumption intensity (OR 1.93, 95% CI 1.05-3.58). Conclusion: The polymorphism CHRNA5 can be considered an indirect risk factor for neoplasms in these Brazilian samples when cigarette consumption increased.
- How many copies of GSTM1 and GSTT1 are associated with head and neck cancer risk?(2019) FIRIGATO, Isabela; GONCALVES, Fernanda de Toledo; ANTONIO, Juliana De; CURIONI, Otavio Alberto; SILVA, Mariana Rocha; GATTAS, Gilka Jorge FigaroPurpose: GSTM1 and GSTT1 present a polymorphism that can drive complete gene deletions. The current methodology can powerfully determine GSTM1 and GSTT1 copy number variations (CNVs), which may clarify the real contribution of each gene copies to the cellular detoxification process and tumour risk. However, only analysing the presence/absence of these genes yielded controversial results for several disorders, including cancer. Because head and neck cancer (HNC) is becoming a serious global health problem, this study determined the CNVs of GSTM1 and GSTT1 in an HNC case-control population and investigated the possible association between gene copy numbers and tumour risk. Methods: CNV was evaluated by (Ct) 2(-Delta Delta Ct) qPCR methodology in 619 HNC patients and 448 patients with no tumour diagnosis. Results: The genes copy number range was 0-3. The CNV of GSTM1 and GSTT1 frequencies were similar between the cases and control. Thus, none copy of GSTM1 and GSTT1 were associated with HNC risk. Notwithstanding, one copy of both genes had higher frequencies among individuals who carried GSTM1 and GSTT1. Conclusions: One copy number of GSTM1 and GSTT1 presented a higher frequency among carrier genes, but the CNV of GSTM1 and GSTT1 was not associated with HNC risk.
- The copy number variation of GSTM1 as a promising prognostic factor of oral squamous cell carcinoma(2022) FIRIGATO, Isabela; LOPEZ, Rossana V. M.; CURIONI, Otavio A.; ANTONIO, Juliana De; GATTAS, Gilka J. F.; GONCALVES, Fernanda de ToledoObjective. The aim of this study was to investigate whether the copy number variation (CNV) of GSTM1 and GSTT1 is related to the occurrence of oral squamous cell carcinoma (OSCC) relapses, along the overall and progression-free survival of patients. Study Design. A total of 234 OSCC patients were recruited from the Heliopolis hospital and they were distributed among 4 groups according to the occurrence of OSCC relapses. Fisher exact test, odds ratio (OR), and 95% CI were determined to investigate the chances of OSCC progression. The overall and progression-free survival were analyzed by the Kaplan-Meier and Cox regression methods. Results. The CNV of GSTM1 analysis showed that one copy of the gene was associated with reduced chances of OSCC recurrences (OR 0.45; 95% CI 0.25-0.81) and decreased the risk of tumor progression (HR 0.50; 95% CI 0.33-0.75). Furthermore, one copy of GSTM1 was related to a better overall survival rate (HR 0.63; 95% CI 0.0.44-0.91). Regarding the CNV of GSTT1, no copies were associated with the chances of OSCC relapses, the overall survival, or the progression-free survival. Conclusions. The CNV of GSTM1 may be applied to predict OSCC relapses and aid the treatment management, which might improve the survival rates of patients.