NAYARA IZABEL VIANA MOURA
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
49 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 49
- 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.
- A novel supplement with yeast 6-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice(2021) NEHMI, Victor Abou; MURATA, Gilson Masahiro; MORAES, Ruan Carlos Macedo de; LIMA, Gabriely Cristina Alves; MIRANDA, Danielle Araujo De; RADLOFF, Katrin; COSTA, Raquel Galvao Figueredo; JESUS, Joyce de Cassia Rosa de; FREITAS, Jessica Alves De; VIANA, Nayara Izabel; PIMENTA, Ruan; LEITE, Katia Ramos Moreira; OTOCH, Jose Pinhata; PESSOA, Ana Flavia MarcalObjective: To evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast beta-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice. Methods: After an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice. Results: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-alpha, AMP-activated protein kinase-1 alpha, peroxisome proliferator-activated receptor c co-activator-1 alpha, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-kappa B kinase subunit a and p65 nuclear factor-kappa B expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic-pituitary-adrenal axis immune interface status, was found to be modulated by the supplement. Conclusion: We discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.
- The role of urinary KIM-1, NGAL, CA19-9 and beta 2-microglobulin in the assessment of ureteropelvic junction obstruction in adults(2017) MIRANDA, Eduardo P.; DUARTE, Ricardo J.; BESSA JR., Jose de; LOPES, Roberto I.; SROUGI, Victor; ANDRADE, Hiury S.; BANDEIRA, Rodolfo A. S. T.; ARAP, Marco A.; MITRE, Anuar I.; VIANA, Nayara I.; REIS, Sabrina T.; LEITE, Katia R. M.; SROUGI, MiguelPurpose: The objective of this study is to evaluate the diagnostic properties of urinary biomarkers in adults with ureteropelvic junction obstruction: KIM-1, NGAL, CA19-9, and beta 2-microglobulin. We also assessed urinary biomarker concentrations following pyeloplasty. Material and methods: We prospectively studied adults from December 2013 to February 2015. We included 47 patients with a mean age of 38.6 +/- 12.7 years. Each patient provided four samples of voided urine for biomarker measurement, one at pre-operative consultation and the others at 1, 3, and 6 months of post-operative follow-up. The control group consisted of 40 healthy individuals with no hydronephrosis on ultrasound evaluation. Results: KIM-1 had an area under the curve of 0.79 (95% CI 0.70-0.89), NGAL 0.71 (95% CI 0.61-0.83), CA19-9 0.70 (95% CI 0.60-0.81), and beta 2-microgloblin 0.61 (95% CI 0.50-0.73). KIM-1 was the most sensitive marker with a cut-off of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%), whereas CA19-9 was the most specific with a cut-off of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). Urinary concentrations of biomarkers decreased after pyeloplasty. Conclusions: The evaluation of urinary biomarkers is useful in adults undergoing pyeloplasty. KIM-1, NGAL, and CA19-9 were elevated and significantly decreased after surgery.
conferenceObject Micro RNA 100, 145 and 373 in prostate cancer: From gene regulation to apoptosis(2014) ISCAIFE, A.; MORAIS, D. R.; REIS, S. T.; VIANA, N. I.; KATZ, B.; MOURA, C.; DIP, N.; SROUGI, M.; LEITE, K. R. MoreiraconferenceObject EXPRESSION PROFILE OF CD105 IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA (BPH): A NEW ANGIOGENIC MARKER(2013) BIOLO, Karlo; KIRIHARA, Ricardo; REIS, Sabrina T.; VIANA, Nayara I.; SAJOVIC, Paulo; ARAUJO, Luiz Henrique; LEITE, Katia R.; SROUGI, Miguel; ANTUNES, Alberto A.- MicroRNAs 143 and 145 may be involved in benign prostatic hyperplasia pathogenesis through regulation of target genes and proteins(2014) VIANA, Nayara I.; REIS, Sabrina T.; DIP, Nelson G.; MORAIS, Denis R.; MOURA, Caio M.; SILVA, Iran A.; KATZ, Betina; SROUGI, Miguel; LEITE, Katia R. M.; ANTUNES, Alberto A.Objectives: The aim of this study was to analyze the roles of miR-143 and miR-145, as well as the gene and protein expression of their targets (KRAS, ERK5, MAP3K3, and MAP4K4) in the pathogenesis of benign prostatic hyperplasia (BPH). Methods: We analyzed the specimens of 44 patients diagnosed with BPH who underwent surgical treatment. The control group consisted of prostate samples from 2 young patients who were organ donors. miRNAs and their target genes were assessed using real-time polymerase chain reaction (qRT-PCR), and protein levels were assessed by Western blotting. Results: miR-143 and miR-145 were overexpressed in, respectively, 62.5% and 73.8% of the cases. The ERK5 and MAP4K4 genes were underexpressed respectively in 59.4% and 100% of the BPH samples, whereas KRAS and MAP3K3 were overexpressed respectively in 79.4% and 61.5% of the samples. Increased protein expression was found for both KRAS (4,312.2 luminance/area) and MAP3K3 (7,461.7 luminance/area), while the ERK5 protein was more abundant in the samples from patients with prostate larger than 60 grams (p = 0.019). Conclusions: The overexpression of miR-143 and miR-145 in BPH samples suggests an association with the pathogenesis of the disease; additionally, the latter miRNA may act through the inhibition of MAP4K4. KRAS and MAP3K3 overexpression may also be associated with BPH pathogenesis. Further analyses are necessary to confirm these results.
- Telomeric zinc-finger associated protein (TZAP) in cancer biology: friend or foe?(2021) SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; PIMENTA, Ruan; CAMARGO, Juliana Alves de; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, MiguelThe new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker.
- The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior(2015) LEITE, Katia R. M.; MORAIS, Denis Reis; FLOREZ, Manuel Garcia; REIS, Sabrina T.; ISCAIFE, Alexandre; VIANA, Nayara; MOURA, Caio M.; SILVA, Iran A.; KATZ, Betina S.; PONTES JR., Jose; NESRALLAH, Adriano; SROUGI, MiguelBackground: The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. Methods: The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. Results: MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5 alpha-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5 alpha-dihydrotestosterone. Conclusion: Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.
- Pan-cancer analysis reveals that CTC1-STN1-TEN1 (CST) complex may have a key position in oncology(2022) SANTOS, Gabriel Arantes dos; VIANA, Nayara I.; PIMENTA, Ruan; CAMARGO, Juliana Alves de; GUIMARAES, Vanessa R.; ROMAO, Poliana; CANDIDO, Patricia; GHAZARIAN, Vitoria; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, MiguelTelomere dysfunction is one of the hallmarks of cancer, which puts telomere-associated genes in a prominent position in oncology. The CTC1-STN1-TEN1 (CST) complex is vital for telomere maintenance and participates in several steps of DNA metabolism, such as repair and replication, essential functions for malignant cells. Despite this, little is known about these genes in cancer biology. Here, using bioinformatics tools, we performed a study in 33 cancer types and over 10,0 0 0 TCGA samples analyzing the role of the CST complex in cancer. We obtained the somatic landscape and gene expression patterns of each of the subunits of the complex studied. Furthermore, we show that CST is important for genetic stability and nucleic acid metabolism in cancer. We identify possible interactors, transcription factors, and microRNAs associated with CST and two drugs that may disrupt their pathways. In addition, we show that CST gene expression is associated with cancer survival and recurrence in several tumor types. Finally, we show negative and positive correlations between immune checkpoint genes and CST in different types of cancer. With this work, we corroborate the importance of these genes in cancer biology and open perspectives for their use in other works in the field.
conferenceObject MICRO RNA 100 ROLE IN THE CONTROL OF GENES IN BLADDER CANCER CELL LINES(2013) MORAIS, Denis; REIS, Sabrina; VIANA, Nayara; MOURA, Caio; DIP, Nelson; FLOREZ, Manuel; SROUGI, Miguel; LEITE, Katia