NAYARA IZABEL VIANA MOURA

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LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: WILLIAM CARLOS NAHAS ×

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Agora exibindo 1 - 10 de 27
  • article 1 Citação(ões) na Scopus
    Gene expression profile of renal cell carcinomas after neoadjuvant treatment with sunitinib: new pathways revealed
    (2017) DZIK, Carlos; REIS, Sabrina T.; VIANA, Nayara I.; BRITO, Glauber; PALOPPI, Isis; NAHAS, Willian; SROUGI, Miguel; LEITE, Katia R. M.
    Background: In renal cell carcinoma (RCC) of the clear cell type, inactivity of the VHL gene induces overexpression of HIF1 alpha and its targets, the tyrosine kinase receptors, promoting RCC development and progression. The discovery of tyrosine kinase inhibitors (TKIs) changed the treatment of these tumors. Other molecular pathways involved in the TKI mechanisms of action have not been described in the literature. The aim of our study was to elucidate alternative mechanisms of action of sunitinib in tumor tissue after neoadjuvant treatment of RCC. Methods: The gene expression profile was accessed using microarray (Affymetrix Human Genome U133 Plus 2.0 platform) and frozen RCC tissues collected from 5 patients with locally advanced non-metastatic tumors who underwent nephrectomy after being treated with 2 cycles of neoadjuvant sunitinib. The results were compared with matched controls comprising 6 patients with no neoadjuvant intervention. Results: There was underexpression of the majority of genes after sunitinib treatment. The lower expression levels of IGFBP1, CCL20, CXCL6 and FGB were confirmed by qRT-PCR in all cases. The downregulation of gene expression leads us to search for methylation as a mechanism of action of the TKI. IGFBP1 was shown to be methylated by methylation-sensitive high-resolution melting technique. Conclusions: The ultimate genetic effects of sunitinib may explain its actions as an antitumor drug that apparently suppresses the expression of important genes related to cell survival, adhesion, invasion and immunomodulation. The methylation of gene promoters was shown to be part of the mechanism of action of this class of drugs.
  • article 2 Citação(ões) na Scopus
    Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families
    (2019) REIS, Sabrina T.; LEITE, Katia R. M.; MARCHINI, Giovanni S.; GUIMARAES, Ronaldo M.; VIANA, Nayara I.; PIMENTA, Ruan C. A.; TORRICELLI, Fabio C.; DANILOVIC, Alexandre; VICENTINI, Fabio Carvalho; NAHAS, William Carlos; SROUGI, Miguel; MAZZUCCHI, Eduardo
    The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome-Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan (R) SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0-fold (P = 0.036). Pre-B-cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3-fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild-type homozygote genotype had overexpression of PBX1. There is a 3-fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.
  • article 17 Citação(ões) na Scopus
    Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics
    (2017) OLIVEIRA, Rita de Cassia; IVANOVIC, Renato Fidelis; LEITE, Katia Ramos Moreira; VIANA, Nayara Izabel; PIMENTA, Ruan Cesar Aparecido; PONTES JUNIOR, Jose; GUIMARAES, Vanessa Ribeiro; MORAIS, Denis Reis; ABE, Daniel Kanda; NESRALLAH, Adriano Joao; SROUGI, Miguel; NAHAS, William; REIS, Sabrina Thalita
    Background: Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC. Methods: The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-alpha, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion. Results: miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression was associated with Fuhrman's low grade (p = 0.03). Conclusions: Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia.
  • article 0 Citação(ões) na Scopus
    Physical activity effects on bladder dysfunction in an obese and insulin-resistant murine model
    (2021) OLIVEIRA, Andre Matos de; FONSECA, Fernando Mello Froes; REIS, Sabrina Thalita; VIANA, Nayara Izabel; OLIVEIRA, Edilamar Menezes; LEIRIA, Luiz Osorio; LEITE, Katia Ramos Moreira; NAHAS, William Carlos; SROUGI, Miguel; ANTUNES, Alberto Azoubel
    Objective: To investigate the role of physical activity in functional and molecular bladder alterations in an obese and insulin-resistant murine model. Methods: Wistar rats were randomized into 1. physical activity and standard diet; 2. physical activity and high-fat diet; 3. no physical activity and standard diet; and 4. no physical activity and high-fat diet. Groups 1 and 2 were subjected to a 10-week swimming protocol. Urodynamic study (UDS) was performed, and the expression of genes in the bladder tissue related to the insulin pathway (IRS1/IRS2/PI3K/AKT/eNOS) was assessed using quantitative real-time polymerase chain reaction. Results; Groups 1 and 2 presented lower body weight gains than groups 3 (213.89 +/- 13.77 vs 261.63 +/- 34.20 grams (g), p = 0.04) and 4 (209.84 +/- 27.40 vs 257.57 +/- 32.95 g, p = 0.04), respectively. Group 4 had higher insulin level (6.05 +/- 1.79 vs 4.14 +/- 1.14 ng/ml, p = 0.038) and higher homeostasis model assessment of insulin resistance (HOMA-IR) index (1.95 +/- 0.73 vs 1.09 +/- 0.37, p = 0.006) than group 1. On UDS, group 4 had greater number of micturition (13.6 +/- 4.21 vs 6.0 +/- 1.82, p = 0.04), higher postvoid pressure (8.06 +/- 2.24 vs 5.08 +/- 1.23, p = 0.04), lower capacity (0.29 +/- 0.18 vs 0.91 +/- 0.41 ml, p = 0.008), and lower bladder compliance (0.027 +/- 0.014 vs 0.091 +/- 0.034 ml/mmHg, p = 0.016) versus group 1. High-fat diet was related to an underexpression throughout insulin signaling pathway, and physical activity was related to an overexpression of the pathway. Conclusions: The insulin signaling pathway may be involved in the pathogenesis of bladder dysfunction related to a high-fat diet. Physical activity may help to prevent bladder disfunction induced by a high-fat diet through the insulin pathway.
  • article 12 Citação(ões) na Scopus
    Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer
    (2015) REIS, Sabrina Thalita dos; VIANA, Nayara Izabel; ISCAIFE, Alexandre; PONTES-JUNIOR, Jose; DIP, Nelson; ANTUNES, Alberto Azoubel; GUIMARAES, Vanessa Ribeiro; SANTANA, Isaque; NAHAS, William Carlos; SROUGI, Miguel; LEITE, Katia Ramos Moreira
    Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
  • article 1 Citação(ões) na Scopus
    Nomograms using a small panel of genes for predicting the diagnosis and aggressiveness of prostate cancer
    (2020) LEITE, Katia R. M.; ORTEGA, Fabio L.; DAMIANI, Lucas P.; GUIMARAES, Vanessa; VIANA, Nayara; SILVA, Iran A.; REIS, Sabrina T.; PIMENTA, Ruan; ADONIAS, Sanarelly P.; CHAMMAS, Cristina; SROUGI, Miguel; NAHAS, Willian
  • article 5 Citação(ões) na Scopus
    Role of Genetic Polymorphisms in the Development and Prognosis of Sporadic and Familial Prostate Cancer
    (2016) REIS, Sabrina T.; VIANA, Nayara I.; LEITE, Katia R. M.; DIOGENES, Erico; ANTUNES, Alberto A.; ISCAIFE, Alexandre; NESRALLAH, Adriano J.; PASSEROTTI, Carlo C.; SROUGI, Victor; PONTES-JUNIOR, Jose; SALLES, Mary Ellen; NAHAS, William C.; SROUGI, Miguel
    Backgrounds Our aim was to evaluate the role of 20 genetic polymorphisms in the development and prognosis of sporadic and familial PC. A case-control study of 185 patients who underwent radical prostatectomy from 1997 to 2011. These patients were divided into two groups based on their family history. Gleason grade, PSA value and pathological TNM 2002 stage were used as prognostic factors. Blood samples from 70 men without PC were used as controls. The SNPs were genotyped using a TaqMan SNP Genotyping Assay Kit. Results Considering susceptibility, the polymorphic allele in the SNP rs2660753 on chromosome 3 was significantly more prevalent in controls (p = 0.01). For familial clustering, the polymorphic homozygote genotype of the SNP rs7931342 was five times more frequent in patients with familial PC compared to sporadic PC (p = 0.01). Regarding the SNP 1447295, the polymorphic homozygote genotype was more prevalent in patients with organ-confined PC (p = 0.05), and most importantly, the polymorphic allele occurred more frequently in patients without biochemical recurrence (p = 0.01). Kaplan-Meier analysis showed a median biochemical recurrence free survival of 124.2 compared to 85.6 months for patients with the wild-type allele (p = 0.007). Conclusion Our findings provide the evidence for the association of 20 recently highlighted SNPs and their susceptibility, familial clustering, staging, Gleason score and biochemical recurrence of PC. We believe that the association between these SNPs and PC may contribute to the development of alternative tools that can facilitate the early detection and prognosis of this disease.
  • article 3 Citação(ões) na Scopus
    Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer
    (2023) PIMENTA, Ruan; MIOSHI, Carolina Mie; GONCALVES, Guilherme L.; CANDIDO, Patricia; CAMARGO, Juliana A.; GUIMARAES, Vanessa R.; CHIOVATTO, Caroline; GHAZARIAN, Vitoria; ROMAO, Poliana; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; VIANA, Nayara I.; REIS, Sabrina T.
    MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 mu g weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.
  • article 2 Citação(ões) na Scopus
    Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study
    (2022) INOUE, Gustavo N. C.; PIMENTA, Ruan; CAMARGO, Juliana A.; I, Nayara Viana; GUIMARAES, Vanessa R.; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R. M.; REIS, Sabrina T.
    Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines. Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia. Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group. Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery. Institutional protocol number: Animal Ethics Committee 1332/2019.
  • conferenceObject
    SNP RS17383719 IN THE PBX1 GENE IS ASSOCIATED WITH CYSTINURIA
    (2017) REIS, Sabrina; GUIMARAES, Ronaldo; VIANA, Nayara; LEITE, Katia; MARCHINI, Giovanni; TORRICELLI, Fabio; NAHAS, William; SROUGI, Miguel; MAZZUCCHI, Eduardo