RUAN CESAR APARECIDO PIMENTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
10 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.
- 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.
- Validation of a New Low-Cost, Methanol-Based Fixative for Cervical Cytology and Human Papillomavirus Detection(2018) LEITE, Katia Ramos Moreira; SILVA, Thais; NAUM, Bruna; CANAVEZ, Flavio; CANAVEZ, Juliana; PIMENTA, Ruan; REIS, Sabrina; CAMARA-LOPES, Luiz HeraldoObjective: To test the performance of a new fixative for pap smear collection for liquid-based cervical cytology, CellPreserv (R) and compare it with the commercially available, PreservCyt (R) used in the diagnosis and detection of human papillomavirus (HPV). Methods: Seven hundred twenty five women participated in this study after signing an informed consent. The specimens were collected using a traditional device, agitated in PBS, and equally divided in both fixatives. The slides were prepared routinely, stained by Papanicolaou, examined blindly by 2 cytologists, and reviewed by one cytopathologist. To search for HPV, 1,000 mu L from each fixative was taken and processed by polymerase chain reaction. Results: Considering the adequacy of samples, both fixatives had similar results - 0.33 and 0.32% of the cases unsatisfactory for PreservCyt (R) and CellPreserv (R), respectively. Considering the 701 satisfactory cases and comparing the new fixative to the traditional fixative, there was 99.3% concordance between both. The results regarding the HPV detection was 100% concordant between the 2 fixatives. Conclusion: The new methanol-based fixative, CellPreserv (R), is cheaper and equally efficient for treating cervical cancer screening and for HPV detection, and can be safely used by the health system prevailing in low-income countries. (C) 2018 S. Karger AG, Basel
- Treating metastatic prostate cancer with microRNA-145(2018) ISCAIFE, Alexandre; REIS, Sabrina Thalita; MORAIS, Denis Reis; VIANA, Nayara Izabel; SILVA, Iran Amorim da; PIMENTA, Ruan; BORDINI, Andre; DIP, Nelson; SROUGI, Miguel; LEITE, Katia Ramos MoreiraProstate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa.
- HPV Genotype Prevalence and Success of Vaccination to Prevent Cervical Cancer(2020) LEITE, Katia Ramos Moreira; PIMENTA, Ruan; CANAVEZ, Juliana; CANAVEZ, Flavio; SOUZA, Fernando R. de; VARA, Ligia; ESTIVALLET, Carmen; CAMARA-LOPES, Luiz HeraldoBackground:Nearly 500,000 new cases of cervical cancer are estimated annually worldwide. Three vaccines are currently licensed to prevent cervical cancer. The success of vaccination depends mainly on the prevalence of HPV genotypes, and many cases of HPV infection have been diagnosed after vaccination. Our aim was to search for HPV genotyping in cervical samples to verify the proportion of women that remain susceptible to infection even after vaccination.Methods:21,017 liquid-based cervical (LBC) specimens were received for cytology and HPV detection from 2015 to 2018. Before slide preparations for cytology, a 1,000-mu L aliquot was taken from the LBC fixative and subjected to automated DNA extraction and multiplex PCR followed by capillary electrophoresis to detect and classify HPV.Results:HPV was detected in 895 (4.3%) specimens. The most prevalent genotype was HPV-16, followed by HPV-58 and HPV-66. A total of 258 (28.8%) cases were positive for high-risk (HR)-HPV types (66, 59, 39, 56, 30, 35, 53, 51, 68, 82, and 70) that are not covered by the HPV vaccines.Conclusion:A significant proportion of HPV types detected in cytological specimens are representative of HR-HPV not covered by the available vaccines. The health system should be aware of the considerable percentage of women who are not being immunized and will continue to need cervical cancer screening.
- Hypothesis: The triad androgen receptor, zinc finger proteins and telomeres modulates the global gene expression pattern during prostate cancer progression(2021) SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; PIMENTA, Ruan; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, MiguelCurrently, the biggest challenge for prostate cancer (PCa) is to understand the mechanism by which the disease acquires the castration-resistant phenotype and progresses to a fatal disease. PCa has a high genetic heterogeneity, and cannot be separated into well-defined molecular subtypes. Despite this, there is consensus about the role of the androgen receptor (AR) in all stages of the disease, including the transition to the castration-resistant phenotype. Since AR is a transcription factor, we investigated the possibility of PCa presenting a pattern of global gene expression during disease progression. By analyzing the TCGA and CCLE datasets, we were able to find a pattern of waves of genes being expressed during each stage of disease progression. This phenomenon suggests the existence of a mechanism that globally regulates gene expression, being AR, telomeres, and zinc finger proteins (ZNF), three important players. The AR modulates the telomere biology, and its transcription is regulated by ZNF. Recently, a study suggested that the telomere length might influence the expression of ZNF. Thus, we hypothesized that changes in the triad AR, telomeres, and ZNF control gene expression during the progression of PCa.
- Downregulation of miR-29b is associated with Peyronie's disease(2022) SANTOS, Vinicius Genuino dos; SANTOS, Gabriel Arantes dos; NETO, Cristovao Barbosa; VIANA, Nayara Izabel; PIMENTA, Ruan; GUIMARAES, Vanessa Ribeiro; CANDIDO, Patricia; ROMAO, Poliana; CAMARGO, Juliana A. de; LEITE, Katia Ramos Moreira; SROUGI, Miguel; CURY, Jose; NAHAS, William C.; REIS, Sabrina ThalitaBackground: Peyronie's disease (PD) is characterized by the formation of fibrous plaque in tunica albuginea, causing several problems in patients. The etiology of this disease is not fully understood, and there are few effective treatments. To better understand the molecular pathways of PD, we studied miR-29b, a microRNA that could be involved with this illness. MicroRNAs are endogenous molecules that act by inhibiting messenger RNA. MiR-29b regulates 11 of 20 collagen genes and the TGF-beta 1 gene, which are related to PD progression. Methods: We compared miR-29b expression in 11 patients with PD and 14 patients without PD (control group). For the patients with PD, we utilized samples from the fibrous plaque (n = 9), from the tunica albuginea (n = 11), and from the corpus cavernosum (n = 8). For the control group, we utilized samples from the tunica albuginea (n = 14) and from the corpus cavernosum (n = 10). MiR-29b expression was determined by q-PCR. Results: We found a downregulation of miR-29b in the fibrous plaque, tunica albuginea and corpus cavernosum of patients with PD in comparison with the control group (p = 0.0484, p = 0.0025, and p = 0.0016, respectively). Conclusion: Although our study has a small sample, we showed for the first time an evidence that the downregulation of miR-29b is associated with PD.