ALBERTO AZOUBEL ANTUNES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
8 resultados
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- Biochemical recurrence rates are similar for pT2-positive surgical margins and pT3a(2014) LEITE, Katia R. M.; HARTMANN, Carolina; REIS, Sabrina T.; VIANA, Nayara; DALL'OGLIO, Marcos F.; ST'ANNA, Alexandre C.; NESRALLAH, Adriano; NESRALLAH, Luciano; ANTUNES, Alberto A.; CAMARA-LOPES, Luiz H.; SROUGI, MiguelObjective: Histological details of positive surgical margins in radical prostatectomy specimens have been related to outcome after surgery in rare studies recently published. Our objective is to assess whether the status of surgical margins, the extent and the Gleason score of positive margins, and the extent of the extraprostatic extension are predictive of biochemical recurrence post-radical prostatectomy. Materials and Methods: Three hundred sixty-five radical prostatectomy specimens were analyzed. The length of the positive surgical margin and extraprostatic extension and the Gleason score of the margin were recorded. Statistical analyses examined the predictive value of these variables for biochemical recurrence. Results: 236 patients were stage pT2R0, 58 pT2R1, 25 pT3R0 and 46 pT3R1. Biochemical recurrence occurred in 11%, 31%, 20% and 45.7% of pT2R0, pT2R1, pT3R0 and pT3R1, respectively. The extent of the positive surgical margins and the Gleason score of the positive surgical margins were not associated with biochemical recurrence in univariate analysis in a mean follow up period of 35.9 months. In multivariate analyses, only the status of the surgical margins and the global Gleason score were associated with biochemical recurrence, with a risk of recurrence of 3.1 for positive surgical margins and of 3.8 for a Gleason score > 7. Conclusion: Positive surgical margin and the global Gleason score are significant risk factors for biochemical recurrence post-radical prostatectomy, regardless of the extent of the surgical margin, the extent of the extraprostatic extension, or the local Gleason score of the positive surgical margin or extraprostatic tissue. pT2R1 disease behaves as pT3R0 and should be treated similarly.
- Physical activity effects on bladder dysfunction in an obese and insulin-resistant murine model(2021) OLIVEIRA, Andre Matos de; FONSECA, Fernando Mello Froes; REIS, Sabrina Thalita; VIANA, Nayara Izabel; OLIVEIRA, Edilamar Menezes; LEIRIA, Luiz Osorio; LEITE, Katia Ramos Moreira; NAHAS, William Carlos; SROUGI, Miguel; ANTUNES, Alberto AzoubelObjective: To investigate the role of physical activity in functional and molecular bladder alterations in an obese and insulin-resistant murine model. Methods: Wistar rats were randomized into 1. physical activity and standard diet; 2. physical activity and high-fat diet; 3. no physical activity and standard diet; and 4. no physical activity and high-fat diet. Groups 1 and 2 were subjected to a 10-week swimming protocol. Urodynamic study (UDS) was performed, and the expression of genes in the bladder tissue related to the insulin pathway (IRS1/IRS2/PI3K/AKT/eNOS) was assessed using quantitative real-time polymerase chain reaction. Results; Groups 1 and 2 presented lower body weight gains than groups 3 (213.89 +/- 13.77 vs 261.63 +/- 34.20 grams (g), p = 0.04) and 4 (209.84 +/- 27.40 vs 257.57 +/- 32.95 g, p = 0.04), respectively. Group 4 had higher insulin level (6.05 +/- 1.79 vs 4.14 +/- 1.14 ng/ml, p = 0.038) and higher homeostasis model assessment of insulin resistance (HOMA-IR) index (1.95 +/- 0.73 vs 1.09 +/- 0.37, p = 0.006) than group 1. On UDS, group 4 had greater number of micturition (13.6 +/- 4.21 vs 6.0 +/- 1.82, p = 0.04), higher postvoid pressure (8.06 +/- 2.24 vs 5.08 +/- 1.23, p = 0.04), lower capacity (0.29 +/- 0.18 vs 0.91 +/- 0.41 ml, p = 0.008), and lower bladder compliance (0.027 +/- 0.014 vs 0.091 +/- 0.034 ml/mmHg, p = 0.016) versus group 1. High-fat diet was related to an underexpression throughout insulin signaling pathway, and physical activity was related to an overexpression of the pathway. Conclusions: The insulin signaling pathway may be involved in the pathogenesis of bladder dysfunction related to a high-fat diet. Physical activity may help to prevent bladder disfunction induced by a high-fat diet through the insulin pathway.
- Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer(2015) REIS, Sabrina Thalita dos; VIANA, Nayara Izabel; ISCAIFE, Alexandre; PONTES-JUNIOR, Jose; DIP, Nelson; ANTUNES, Alberto Azoubel; GUIMARAES, Vanessa Ribeiro; SANTANA, Isaque; NAHAS, William Carlos; SROUGI, Miguel; LEITE, Katia Ramos MoreiraIntroduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
- Role of Genetic Polymorphisms in the Development and Prognosis of Sporadic and Familial Prostate Cancer(2016) REIS, Sabrina T.; VIANA, Nayara I.; LEITE, Katia R. M.; DIOGENES, Erico; ANTUNES, Alberto A.; ISCAIFE, Alexandre; NESRALLAH, Adriano J.; PASSEROTTI, Carlo C.; SROUGI, Victor; PONTES-JUNIOR, Jose; SALLES, Mary Ellen; NAHAS, William C.; SROUGI, MiguelBackgrounds Our aim was to evaluate the role of 20 genetic polymorphisms in the development and prognosis of sporadic and familial PC. A case-control study of 185 patients who underwent radical prostatectomy from 1997 to 2011. These patients were divided into two groups based on their family history. Gleason grade, PSA value and pathological TNM 2002 stage were used as prognostic factors. Blood samples from 70 men without PC were used as controls. The SNPs were genotyped using a TaqMan SNP Genotyping Assay Kit. Results Considering susceptibility, the polymorphic allele in the SNP rs2660753 on chromosome 3 was significantly more prevalent in controls (p = 0.01). For familial clustering, the polymorphic homozygote genotype of the SNP rs7931342 was five times more frequent in patients with familial PC compared to sporadic PC (p = 0.01). Regarding the SNP 1447295, the polymorphic homozygote genotype was more prevalent in patients with organ-confined PC (p = 0.05), and most importantly, the polymorphic allele occurred more frequently in patients without biochemical recurrence (p = 0.01). Kaplan-Meier analysis showed a median biochemical recurrence free survival of 124.2 compared to 85.6 months for patients with the wild-type allele (p = 0.007). Conclusion Our findings provide the evidence for the association of 20 recently highlighted SNPs and their susceptibility, familial clustering, staging, Gleason score and biochemical recurrence of PC. We believe that the association between these SNPs and PC may contribute to the development of alternative tools that can facilitate the early detection and prognosis of this disease.
- Prima-1 induces apoptosis in bladder cancer cell lines by activating p53(2013) PIANTINO, Camila B.; REIS, Sabrina T.; VIANA, Nayara I.; SILVA, Iran A.; MORAIS, Denis R.; ANTUNES, Alberto A.; DIP, Nelson; SROUGI, Miguel; LEITE, Katia R.OBJECTIVES: Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines. METHOD: The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR). RESULTS: Prima-1 was able to reactivate p53 function in the T24 (p53 mt) bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner. CONCLUSION: Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.
- 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.
- Immune expression of E-cadherin and alpha, beta and gamma-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas(2012) REIS, Sabrina Thalita dos; LEITE, Katia Ramos Moreira; MOSCONI NETO, Alcides; PONTES JUNIOR, Jose; VIANA, Nayara Izabel; ANTUNES, Alberto Azoubel; DALL'OGLIO, Marcos Francisco; SROUGI, MiguelIntroduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and alpha-, beta- and gamma-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of a-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of a-catenin expression is related to tumor size in upper tract urothelial carcinomas.
- The role of single nucleotide polymorphisms of miRNAs 100 and 146a as prognostic factors for prostate cancer(2021) CAMARGO, Juliana Alves de; LOPES, Renan Eboli; FERREIRA, Gabriel Fernandes Dias; VIANA, Nayara Izabel; GUIMARAES, Vanessa; LEITE, Katia Ramos Moreira; NAHAS, William C.; SROUGI, Miguel; ANTUNES, Alberto A.; REIS, Sabrina T.Introduction: Prostate cancer has a high incidence in men and is the second cause of cancer death among americans male. microRNA (miR) is becoming a potential new prognostic factor for prostate cancer. Single nucleotide polymorphisms (SNPs) are common polymorphisms, characterized by a single exchange of nitrogen based in the DNA. This polymorphism is present in the miRs, altering their function. Objective: To evaluate the role of SNP rs1834306 of miR100 and rs2910164 of miR146a in the development and prognosis of prostate cancer. Methods: One hundred patients diagnosed with prostate cancer and 68 controls were selected. The identification of SNP was rated by quantitative polymerase chain reaction from blood samples, and the analysis was performed within the presence of SNP and the prognostic variables. Results: In the SNP rs1834306 (miR100), a smaller presence of the polymorphic homozygous genotype was identified in patients with PSA >10 ng/mL, (P=0.03); when evaluating only the presence of the polymorphic allele G (P=0.09) it was compared to the presence of the wild type allele A. Among the patients with prostate cancer, SNP rs2910164 (miR146A), the polymorphic allele was more frequent in patients with a Gleason score > 7 than in patients with a Gleason score <7, (P=0.043). In patients with prostate cancer, miR100 was overexpressed in those with pT3 staging compared to pT2 and among those who had biochemical recurrence (P = 0.004 and P = 0.011, respectively). Conclusions: SNP of miR146a acts as a poor prognostic factor (Gleason > 7), and the SNP of miR100 is linked to better prognostic data (PSA <10). MiR100 was overexpressed in prostate cancer with worse prognostic factors.