RUAN CESAR APARECIDO PIMENTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
34 resultados
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- 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.
- Prognostic value of TERF1 expression in prostate cancer(2021) SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; PIMENTA, Ruan; GUIMARAES, Vanessa Ribeiro; CAMARGO, Juliana Alves de; ROMAO, Poliana; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, MiguelBackground: Telomere dysfunction is one of the hallmarks of cancer and is crucial to prostate carcinogenesis. TERF1 is a gene essential to telomere maintenance, and its dysfunction has already been associates with several cancers. TERF1 is a target of miR-155, and this microRNA can inhibit its expression and promotes carcinogenesis in breast cancer. We aim to analyze TERF1, in gene and mRNA level, involvement in prostate cancer progression. Results: Alterations in TERF1 DNA were evaluated using datasets of primary tumor and castration-resistant tumors (CRPC) deposited in cBioportal. The expression of TERF1 mRNA levels was assessed utilizing TCGA datasets, clinical specimens, and metastatic prostate cancer cell lines (LNCaP, DU145, and PC3). Six percent of localized prostate cancer presents alterations in TERF1 (the majority of that was amplifications). In the CRPC cohort, 26% of samples had TERF1 amplification. Patients with TERF1 alterations had the worst overall survival only on localized cancer cohort (p = 0.0027). In the TCGA cohort, mRNA levels of TERF1 were downregulated in comparison with normal tissue (p = 0.0013) and upregulated in tumors that invade lymph nodes (p = 0.0059). The upregulation of TERF1 is also associated with worst overall survival (p = 0.0028) and disease-free survival (p = 0.0023). There is a positive correlation between TERF1 and androgen receptor expression in cancer tissue (r = 0.53, p < 0.00001) but not on normal tissue (r = - 0.16, p = 0.12). In the clinical specimens, there is no detectable expression of TERF1 and upregulation of miR-155 (p = 0.0348). In cell lines, TERF1 expression was higher in LNCaP and was progressively lower in DU145 and PC3 (p = 0.0327) with no differences in miR-155 expression. Conclusion: Amplification/upregulation of TERF1 was associated with the worst prognostic in localized prostate cancer. Our results corroborate that miR-155 regulates TERF1 expression in prostate cancer. TERF1 has the potential to become a biomarker in prostate cancer.
- Can we use Ki67 expression to predict prostate cancer aggressiveness?(2022) MAIA, RONALDO; SANTOS, GABRIEL ARANTES DOS; REIS, SABRINA; VIANA, NAYARA I; PIMENTA, RUAN; GUIMARÃES, VANESSA R; RECUERO, SAULO; ROMÃO, POLIANA; LEITE, KATIA RAMOS MOREIRA; SROUGI, MIGUEL; PASSEROTTI, CARLO CARMARGOABSTRACT Introduction: specialists have an urge for biomarkers that can discriminate indolent prostate cancer from aggressive tumors. Ki67 is a proliferation marker, and its expression is associated with the aggressiveness of several cancers. Objective: analyze the expression of Ki67 in prostate cancer samples correlating with the aggressiveness of the disease. Methods: Ki67 mRNA levels were determined utilizing data from a TCGA cohort (Tumor(n)=492 and control(n)=52). The protein expression was determined on 94 biopsies from patients by immunohistochemical assay. Results: in mRNA, the Ki67 upregulation is associated with cancer tissue (p<0.0001) and worst disease-free survival (p=0.035). The protein upregulation is associated with increase of the ISUP score (p<0.0001), cancer stage (p=0.05), biochemical recurrence (p=0.0006) and metastasis (p<0.0001). We also show a positive correlation between Ki67 expression and ISUP score (r=0.5112, p<0.0001) and disease risk stratification (r=0.3388, p=0.0009). Ki67 expression is a factor independently associated with biochemical recurrence (p=0.002) and metastasis (p<0.0001). Finally, the patients with high Ki67expression shows better survival regarding biochemical recurrence (p=0.008) and metastasis (p=0.056). Patients with high Ki67 expression are 2.62 times more likely to develop biochemical recurrence (p=0.036). Conclusion: Ki67 upregulation is associated with prostate cancer aggressiveness.
- Single nucleotide polymorphism analysis in interstitial cystitis/painful bladder syndrome(2019) CASSAO, Valter D.; REIS, Sabrina T.; PIMENTA, Ruan; LUCON, Marcos; LEITE, Katia R. M.; SROUGI, Miguel; BRUSCHINI, HomeroIntroduction Interstitial Cystitis (IC) is a chronic condition diagnosed based on the presence of symptoms, such as suprapubic/pelvic pain, pressure or discomfort in association with urgency and increased urinary frequency. Confusable diseases must be excluded. However, there is no objective test or marker to establish the presence of the disease. Diagnosis and patient management is often difficult, given the poor understanding of IC pathogenesis and its unknown etiology and genetics. As an attempt to find biomarkers related to IC, we assessed the association between 20 selected single nucleotide polymorphism (SNPs) with IC and pain severity. Objectives To assess the presence of SNPs in IC patients' blood samples and correlate them with the disease and chronic pain condition. Methods A case-control study was conducted. We selected 34 female patients with IC diagnosed according to NIDDK criteria and 23 patients in the control group (previously healthy women with only stress urinary incontinence). IC patients were allocated into two groups according to reported chronic pain severity. We selected the following SNPs for analysis: rs1800871, rs1800872, rs1800896, rs1800471, rs1800629, rs361525, rs1800497, rs6311, rs6277, rs6276, rs6313, rs2835859, rs11127292, rs2243248, rs6887695, rs3212227, rs1799971, rs12579350, rs3813034, and rs6746030. Genotyping was performed by real- time PCR (qPCR). Results The polymorphic allele of SNP rs11127292 exhibited a higher frequency in subjects with IC than in controls (p: 0.01). The polymorphic allele of SNP rs6311 was more frequent in patients with severe pain (p:0.03). The frequency of the wild-type allele of SNP rs1799971 was higher in patients with mild to moderate pain (p:0.04). Conclusion The results indicated differences in SNP frequency among subjects, suggesting that SNPs could serve either as a marker of IC or as a marker of pain severity in IC patients. The study showed promising results regarding IC and polymorphism associations. These associations have not been previously reported.
- 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, EduardoThe 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.
- 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 ThalitaBackground: 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.
- 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.
- 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.
- 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
- 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.