NAYARA IZABEL VIANA MOURA
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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- 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.
- Cholesterol Triggers Nuclear Co-Association of Androgen Receptor, p160 Steroid Coactivators, and p300/CBP-Associated Factor Leading to Androgenic Axis Transactivation in Castration-Resistant Prostate Cancer(2022) PIMENTA, R.; CAMARGO, J. A.; CANDIDO, P.; GHAZARIAN, V.; GONçALVES, G. L.; GUIMARãES, V. R.; ROMãO, P.; CHIOVATTO, C.; MIOSHI, C. M.; SANTOS, G. A. dos; SILVA, I. A.; BIRBRAIR, A.; SROUGI, M.; NAHAS, W. C.; LEITE, K. R.; VIANA, N. I.; REIS, S. T.Background/Aims: Cholesterol modulates intratumoral androgenic signaling in prostate cancer; however, the molecular mechanisms underlying these changes in castration-resistant prostate cancer (CRPC) are not fully elucidated. Herein, we investigated the effect of cholesterol on androgen receptor (AR) coactivators expression and tumorigenesis in vitro and in vivo. Methods: Herein, we monitored the expression of AR coactivators (SRC-1, 2, 3 and PCAF) genes in PC-3 cells exposed to 2µg/mL of cholesterol for 8 hours by qPCR. We also performed cell migration at 0, 8, 24, 48 and 72h and flow cytometry assays (viability, apoptosis, and cell cycle) after a 24h exposure. Immunofluorescence assay was performed to evaluate the protein expression of the AR coactivators. Additionally, in vivo experiments were conducted using 22 male NOD/SCID mice. Mice were fed a standard (Control) or hypercholesterolemic (HCOL) diet for 21 days and then subcutaneously implanted with PC-3 cells. The tumor volume was calculated every two days, and after four weeks, the tumors were resected, weighed, and the serum lipid profile was measured. We also measured the intratumoral lipid profile and AR coactivators gene and protein expression by qPCR and Western Blot, respectively. Intratumor testosterone and dihydrotestosterone (DHT) concentrations were determined using ELISA. Results: Cholesterol up-regulated the gene expression of coactivators SRC-1, SRC-2, SRC-3 and PCAF, increasing AR expression in PC-3 cells. Next, cholesterol-supplemented PC-3 cells exhibited increased cell migration and altered cell cycle phases, leading to changes in proliferation and reduced apoptosis. We found that SRC-1, SRC-2, SRC-3 and PCAF proteins co-localized in the nucleus of cholesterol-supplemented cells and co-associate with AR. In the in vivo model, the hypercholesterolemic (HCOL) group displayed higher serum total and intratumoral cholesterol levels, increased testosterone and dihydrotestosterone concentrations, and up-regulated AR coactivator expression. The tumor volume of the HCOL group was significantly higher than the control group. Conclusion: Our findings revealed that increased nuclear translocation of the coactivators leads to up-regulated AR gene and protein expression, potentially influencing tumor progression. Studies targeting cholesterol-modulated changes in AR coactivator expression may provide insights into the molecular mechanisms associated with the CRPC phenotype. © 2022 Cell Physiol Biochem Press GmbH & Co KG. All rights reserved.
- 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.
- Tgf-beta 1 expression as a biomarker of poor prognosis in prostate cancer(2011) REIS, Sabrina Thalita dos; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; SOUSA-CANAVEZ, Juliana Moreira de; ABE, Daniel Kanda; CRUZ, Jose Arnaldo Shiomi da; DALL'OGLIO, Marcos Francisco; CRIPPA, Alexandre; PASSEROTTI, Carlo Camargo; RIBEIRO-FILHO, Leopoldo A.; VIANA, Nayara Izabel; SROUGI, Miguel; LEITE, Katia Ramos MoreiraOBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-beta 1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-beta 1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of 11 patients with benign prostate hyperplasia. The expression levels of TGF-beta 1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-beta 1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-beta 1, a higher expression level was found in patients with Gleason scores >= 7 when compared to patients with Gleason scores <7 (p = 0.002). Among the 26 cases of TGF-beta 1 overexpression, 92.3% had poor prognostic features. CONCLUSIONS: TGF-beta 1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-beta 1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-beta 1 in prostate carcinogenesis.
- miR-29b enhances prostate cancer cell invasion independently of MMP-2 expression(2018) IVANOVIC, Renato F.; VIANA, Nayara I.; MORAIS, Denis R.; SILVA, Iran A.; LEITE, Katia R.; PONTES-JUNIOR, Jose; INOUE, Gustavo; NAHAS, William C.; SROUGI, Miguel; REIS, Sabrina T.Background: The ability to metastasize is one of the most important characteristics of neoplastic cells. An imbalance between the action of some matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs drives the invasion process. Some studies have suggested that MMP-2 is involved in metastasis, while other studies have reported that collagen production by cancer cells might also contribute to motility. However, decreased expression of microRNA-29b (miR-29b), which may control MMP-2 and collagen gene expression, has been shown in prostate cancer (PCa). The objectives of the present study were to clarify whether MMP-2 as well as collagens I and III (encoded by COL1A1 and COL3A1, respectively) are controlled by miR-29b and to determine whether metastasis is altered by this relationship. Methods: PCa DU145 and PC-3 cells were transfected with 100 mu L of OPTI-MEM I containing 100 nmol of miR-29b (or its inhibitor) along with 1.5 mu L of lipofectamine. Positive and negative controls were prepared using the same protocol. MMP-2, COL1A1 and COL3A1 messenger RNA (mRNA) levels were evaluated via real-time polymerase chain reaction (qRT-PCR). For qRT-PCR, 6 x 10(4) cells were used. Invasion studies were conducted with Matrigel assays, which simulate invasion of the extracellular matrix by neoplastic cells. After transfection of 3 x 10(4) cells, invasion was allowed to proceed for 48 h. Invasive cells were counted under an optical microscope. Each experiment was performed in triplicate. Results: MMP-2 mRNA was not expressed in DU145 cells after transfection with miR-29b. After transfection of cells with the miR-29b inhibitor, COL1A1 (p = 0.02) and COL3A1 (p = 0.06) mRNA expression was increased in DU145 cells, and a large number of transfected DU145 and PC3 cells invaded the Matrigel membrane. Conclusions: In vitro studies showed that reducing the amount of miR-29b may lead to higher PCa cell invasion via a process that is independent of MMP-2. Collagen expression, controlled by miR-29b, may facilitate this motility process. Thus, the present study suggests that collagen production plays an active role in metastasis control and restoration of miR-29b levels may decrease metastasis. Altogether, these findings support further exploration of drug therapy targeting this aspect of the metastasis circuit.
- Digital application developed to evaluate functional results following robot-assisted radical prostatectomy* App for prostate cancer(2020) FARIA, Leandro F.; REIS, Sabrina T.; LEITE, Katia R.; CRUZ, Jose Arnaldo Shiomi da; PIMENTA, Ruan; I, Nayara Viana; AMARAL, Gabriela Q.; SANTOS, Gabriel A. G. D.; ILIAS, Daniel; FAKHOURI, Felipe; XAVIER, Geraldo; SROUGI, Miguel; PASSEROTTI, Carlo CamargoIntroduction: Mobile applications (""apps"") developed for smartphones and tablets are increasingly used in healthcare, allowing remote patient support or promoting self-health care. Prostate cancer (PC) screening allows for early-stage PC diagnosis, resulting in high rates of curative procedures such as radical prostatectomy. The main complications following surgery are urinary incontinence and erectile dysfunction. However, the exact numbers related to these morbidities are often missing due to brief interviews during consultations in the medical office. Therefore, the aim of this study was to create an app to determine whether response rates to preand post-surgical PC questionnaires will increase. Methods: The app was built using the IONIC framework system and provided to patients through a prospective randomized study. We included 100 patients divided into two groups: 1. first group used the app (n = 50); and 2. second group responded via validated printed questionnaires (control group) (n = 50). All patients received discharge counseling to respond to the questionnaires 1, 3, 6 and 12 months after the procedure. The app group received verbal guidance on how monitoring would occur, received an SMS containing a username and password providing access to the system and received reminder alerts to respond to the questionnaires. Results: The new app is called UroHealth and is available for download in the Apple App Store or at www.urohealth.com.br . When we evaluated the response rates, we found that 42.9% of the patients answered the preoperative questionnaire in the app group, while 16% responded in the control group (p = 0.003). By the end of the follow-up, we found that 24.5% of the patients answered the questionnaire in the app group, while 4% responded in the control group (p = 0.003). Conclusion: This app enabled almost 6 times more patients to answer long-term follow-up questions after surgical procedures, providing high-quality information regarding morbidity related to treatment. Although our initial results indicate that this app may become a useful tool in obtaining more frequent and realistic answers, thus helping to improve surgical techniques, other ways of reaching the patient should be tested to achieve higher response rates.
- Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer(2015) LEITE, Katia R. M.; REIS, Sabrina T.; VIANA, Nayara; MORAIS, Denis R.; MOURA, Caio M.; SILVA, Iran A.; PONTES JR., Jose; KATZ, Betina; SROUGI, MiguelThe search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip (R) miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.
- Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model(2023) PIMENTA, Ruan; CAMARGO, Juliana A.; GONCALVES, Guilherme L.; GHAZARIAN, Vitoria; CANDIDO, Patricia; GUIMARAES, Vanessa R.; ROMAO, Poliana; CHIOVATTO, Caroline; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; NAHAS, William C.; LEITE, Katia R.; PESSOA, Ana Flavia Marcal; VIANA, Nayara I.; REIS, Sabrina T.BackgroundPreviously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia.Methods and resultsIn vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 & mu;g/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation.ConclusionOur results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.
- Robotically assisted laparoscopic radical prostatectomy induces lower tissue trauma than radical retropubic prostatectomy(2021) QUINTO, Denise; REIS, Sabrina T.; ZAMPOLLI, Lucca Juvele; PIMENTA, Ruan; GUIMARAES, Vanessa R.; VIANA, Nayara I.; SANTOS, Gabriel A. dos; GIMENEZ, Mario P.; LEITE, Katia R.; ZAMPOLLI, Hamilton; CRUZ, Jose Arnaldo S. da; SROUGI, Miguel; PASSEROTTI, Carlo C.To compare tissue trauma between Retropubic Radical Prostatectomy and Robotically Assisted Laparoscopic Radical Prostatectomy by inflammatory mediators. Serum samples from 40 patients submitted to RALP and 20 patients submitted to RRP were withdrawn at four different time points. The cytokines IL-4, IL-8, IL-6, IL-1B, IL-10 and TNF-alpha were detected using ELISA/Multiplex assays and xMAP-Luminex (R). With both techniques, IL-10 and IL-6 were higher in T4 than in T1-T3 (p = 0.001). IL-10 and IL-6 were higher in T4 in open surgery than in robotic surgery (p = 0.000 andp = 0.001, respectively). Compared with both groups, IL-6 and IL-10 were higher in T4 in open surgery than in robotic surgery. Thus, we can postulate that RALP causes less tissue trauma than classical RRP, as indicated by the more limited increase in inflammatory mediators such as IL-6 and IL-10.
- Correlation between chromosome 9p21 locus deletion and prognosis in clinically localized prostate cancer(2017) BARROS, Erika Aparecida Felix de; PONTES-JUNIOR, Jose; REIS, Sabrina Thalita; LIMA, Amanda Eunice Ramos; SOUZA, Isida C.; SALGUEIRO, Jose Lucas; FONTES, Douglas; DELLE, Humberto; COELHO, Rafael Ferreira; VIANA, Nayara Izabel; LEITE, Katia Ramos Moreira; NAHAS, William C.; SROUGI, MiguelBackground: Some studies have reported that deletions at chromosome arm 9p occur frequently and represent a critical step in carcinogenesis of some neoplasms. Our aim was to evaluate the deletion of locus 9p21 and chromosomes 3, 7 and 17 in localized prostate cancer (PC) and correlate these alterations with prognostic factors and biochemical recurrence after surgery. Methods: We retrospectively evaluated surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Biochemical recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and the mean postoperative follow-up was 123 months. The deletions were evaluated using fluorescence in situ hybridization with centromeric and locus-specific probes in a tissue microarray containing 2 samples from each patient. We correlated the occurrence of any deletion with pathological stage, Gleason score, ISUP grade group, PSA and biochemical recurrence. Results: We observed a loss of any probe in only 8 patients (7.2%). The most common deletion was the loss of locus 9p21, which occurred in 6.4% of cases. Deletions of chromosomes 3, 7 and 17 were observed in 2.3%, 1.2% and 1.8% patients, respectively. There was no correlation between chromosome loss and Gleason score, ISUP, PSA or stage. Biochemical recurrence occurred in 83% cases involving 9p21 deletions. Loss of 9p21 locus was significantly associated with time to recurrence (p = 0.038). Conclusions: We found low rates of deletion in chromosomes 3, 7 and 17 and 9p21 locus. We observed that 9p21 locus deletion was associated with worse prognosis in localized PC treated by radical prostatectomy.