SABRINA THALITA DOS REIS FARIA
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
11 resultados
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Agora exibindo 1 - 10 de 11
- 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.
- 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.
- 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.
- 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.
- Evaluating TIMP-2 and IGFBP-7 as a predictive tool for kidney injury in ureteropelvic junction obstruction(2022) MELLO, Marcos Figueiredo; BESSA JUNIOR, Jose de; REIS, Sabrina T.; KONDO, Enzo Yagi; YU, Luis; DENES, Francisco Tibor; LOPES, Roberto IglesiasA major challenge in the management of ureteropelvic junction obstruction (UPJO) is the selection of patients who would benefit from surgical treatment. Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) indicate renal cell stress and are associated with cell cycle arrest. The [TIMP-2] [IGFBP7] ratio (Nephrocheck (R)) has been recently applied in patients in intensive care units patients to predict the development of acute kidney injury. In this study, we evaluated the performance of these biomarkers performance to distinguishing obstructive hydronephrosis (HN) from non-obstructive HN. Materials and Methods: Consecutive patients with UPJO were enrolled in this study. Urinary [TIMP-2] [IGFBP7] and clinical characteristics (hydronephrosis grade, differential renal function, and drainage half-time) were measured in the following groups: 26 children with obstructive HN at initial diagnosis (group IA) and after six months of dismembered pyeloplasty (group 1B); 22 children with non-obstructive HN (group 2), and 26 children without any urinary tract condition, as the control group (group 3). Results: Comparing the initial samples, [TIMP-2] [IGFBP7] had higher levels in the HN groups and lower levels in the control group; however, no difference was observed between the HN groups (obstructive vs. non-obstructive). After six months of followup, patients who underwent dismembered pyeloplasty showed stability in the urinary concentration of [TIMP-2] [IGFBP7]. All patients with [TIMP-2] [IGFBP7] higher than 1.0 (ng/mL)(2)/1000 had diffuse cortical atrophy on ultrasonography. Conclusions: We showed that urinary levels of urinary [TIMP-2] [IGFBP7] are higher in children with HN than controls. Nephrocheck (R) is not reliable in predicting the need for surgical intervention for pediatric patients with UPJO.
- Indoleamine 2,3-Dioxygenase-1 Expression is Changed During Bladder Cancer Cell Invasion(2022) SANTOS, Hellen Joyce Sousa Pereira; MATHEUS, Luiz Henrique Gomes; SILVA, Aline; DALMAZZO, Stephanie Vanin; SANTOS, Andressa Assuncao; SANTOS, Leticia Rafaela Alves Rubens; SOUZA, Diego Mota; REIS, Sabrina Thalita; NASCIMENTO, Ivan Pereira; DELLE, HumbertoThe severity of the bladder carcinoma (BC) is directly linked to cell invasion and metastasis. Indoleamine 2,3-dioxygenase-1 (IDO-1) is an INF-gamma-induced immunomodulating enzyme that has been linked to the cancer cell invasiveness. Because IDO1 is variable among the tumors, we analyzed its expression in the BC invasion using BC mice models and cell culture. MB49 cells were orthotopically or ectopically inoculated in C57Bl6 mice to evaluate IDO1 by immunohistochemistry. For in vitro experiments, expression of IDO1 and INF-gamma was evaluated in grade-1 (RT4) and in grade-3 (T24) BC cell lines. Invading and non-invading T24 cells were separated using the Matrigel/Transwell system, of which total RNA was extracted immediately or after 2 weeks of subculture. Finally, IDO1 was silenced in T24 cells to verify its role on cell invasiveness. In both animal models, IDO1 was differentially expressed between non-invading and invading cells. In cell culture, T24 cells expressed more IDO1 than RT4 cells, independently of the INF-gamma expression. IDO1 was differentially expressed between non-invading and invading T24 cells, a difference that was lost by long-time subculture. IDO1 silencing resulted in diminished cell invasiveness. In conclusion, IDO1 expression is changed during bladder carcinoma invasion, playing an important role in this process.
- Learning curve of semi-rigid ureteroscopy for small calculi: how many cases are necessary?(2022) ILIAS, DANIEL; PASSEROTTI, CARLO CAMARGO; PONTES JUNIOR, JOSÉ; FAKHOURI, FELIPE; FARIA, SABRINA THALITA DOS REIS; MAXIMIANO, LINDA FERREIRA; OTOCH, JOSÉ PINHATA; DA-CRUZ, JOSE ARNALDO SHIOMIABSTRACT Introduction: semi-rigid ureteroscopy is the procedure of choice for the treatment of ureterolithiasis, but it requires a learning curve to be performed safely. Objective: To describe an estimate of the learning curve for performing semi-rigid ureterorenolithotripsy in patients with small-sized ureterolithiasis and to estimate the minimum number of procedures necessary to safely perform the surgical procedure. Methods: this is a prospective study evaluating the learning curve of a resident of urology in the first 60 semirigid ureteroscopies in patients with ureterolithiasis up to 1cm. The patients were divided into three groups: Group I one to twenty surgeries, Group II twenty one to forty surgeries and Group III forty one to sixty surgeries. The surgeries were recorded and analyzed by two urologists experienced in endourology. A qualitative analysis was performed based on a previously validated tool and a quantitative analysis. Results: all qualitative variables had significant variation between Groups I and II (p<0.001), and between Groups I and III (p<0.001). There was a difference in time to access the ureter, passage of a double J catheter and total operative time between Groups I and II (p<0.001) and Groups I and III (p<0.001). Conclusion: after 40 cases there seems to be little increase in both quantitative as well as qualitative evaluation in surgical performance for performing semi-rigid ureterolithotripsy safely in calculations up to 1cm.
- Uso da cetamina na depressão resistente ao tratamento: uma revisão sistemática(2022) DIAS, Isabela Karina Silva; SILVA, Juliano Kosuge da; GOMES JÚNIOR, Saulo Rogério; SANTOS, Thomas Henrique Neves dos; FARIA, Sabrina Thalita dos ReisABSTRACT Objective Ketamine presents itself as a promising alternative against treatment-resistant depression (TRD), however, the knowledge of its application as an antidepressant is still restricted. Therefore, the objective was to investigate its effectiveness in patients with TRD. Methods The literature search was carried out in the MedLine database. Inclusion criteria were: controlled and randomized clinical studies from the last five years and in English. We excluded articles that did not answer the PICO question and those with different sample size and study methodology, when compared to the tests that based this review. Results Considering a final sample of six articles, a better response to ketamine was observed (mainly in mood gain), when compared to conventional treatment against TRD. With its first infusion, at a dose of 0.5 mg/kg, it was possible to notice its antidepressant effects. The maintenance of these effects seems to be achieved with the administration of 0.5 mg/kg of the drug, three times a week. On the other hand, the reduction of such a dosage can diminish or cancel the effects. Conclusions The use of ketamine showed effective results improving the condition of TRD, with adverse effects of small severity and easy control. However, further studies, with larger samples and different methods, are needed, for a more consistent conclusion.
- Additional activation of the AR gene may be involved in the development of the castration resistance phenotype in prostate cancer(2022) ROMAO, P.; SOUZA, I. de Campos; SILVA, I; GUIMARAES, V. Ribeiro; CAMARGO, J. Alves de; SANTOS, G. A. dos; VIANA, N. Izabel; SROUGI, M.; LEITE, K. R. Moreira; REIS, S. T.; PIMENTA, R.Introduction: Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR. Materials and methods: To evaluate AR methylation, we performed a cytogenetic molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays. Results: In the qPCR assay, we found downregulation of AR in the PC-3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR. Conclusion: Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype.
- MicroRNA expression profiles in the progression of prostate cancer - From high-grade prostate intraepithelial neoplasia to metastasis (vol 31, pg 796, 2013(2022) LEITE, Katia R. M.; TOMIYAMA, Alberto; REIS, Sabrina T.; SOUSA-CANAVEZ, Juliana M.; SANUDO, Adriana; CAMARA-LOPES, Luiz H.; SROUGI, Miguel