CARLO CAMARGO PASSEROTTI
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
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- 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.
- MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer(2011) REIS, Sabrina Thalita; PONTES-JUNIOR, Jose; ANTUNES, Alberto Azoubel; SOUSA-CANAVEZ, Juliana Moreira de; DALL'OGLIO, Marcos Francisco; PASSEROTTI, Carlo C.; ABE, Daniel Kanda; CRIPPA, Alexandre; CRUZ, Jose Arnaldo Shiomi da; TIMOSZCZUK, Luciana M. S.; SROUGI, Miguel; LEITE, Katia R. M.Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9 and its specific inhibitors, TIMP-1 and RECK, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome in prostate cancer (PC). Methods: MMP-9, TIMP-1, and RECK expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79 patients with clinically localized PC submitted to radical prostatectorny (RP). Frozen benign prostatic tissue from another 10 men with prostate cancer, also submitted to RP, was analyzed to determine if the profile of gene expression was maintained. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). Results: In the tumor samples, MMP-9 was overexpressed by 9.2 times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times, respectively). Overexpression of MMP-9 was significantly related to PSA levels above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9 was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and RECK, in contrast to their underexpression in tumor samples. Conclusion: Our results show that MMP-9 is overexpressed and its negative regulators are underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the carcinogenesis process. Additionally, we noticed a relationship between MMP-9 overexpression and increased levels of PSA, an important prognostic factor. In benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained because the expression of its negative regulators is preserved.
- MMP9 overexpression is associated with good surgical outcome in children with UPJO: Preliminary results(2016) REIS, Sabrina Thalita; LEITE, Katia R. M.; VIANA, Nayara Izabel; LOPES, Roberto Iglesias; MOURA, Caio Martins; IVANOVIC, Renato F.; MACHADO, Marcos; DENES, Francisco Tibor; GIRON, Amilcar; NAHAS, William Carlos; SROUGI, Miguel; PASSEROTTI, Carlo C.Background: Ureteropelvic junction obstruction (UPJO) diagnosed prenatally occurs in 1: 150 -1: 1200 pregnancies. Although many studies investigating the molecular changes of this obstructed segment have been performed, the underlying mechanisms are still unclear. The role of extracellular matrix (ECM) components remains controversial, and the investigations in the field of ECM changes, might help the better understanding of the pathogenesis of this common condition. The aim of the present study was to investigate for the first time in the literature whether MMP9 and its specific inhibitors, TIMP1 and RECK, are expressed in a reproducible, specific pattern in UPJ. Methods: UPJO specimens were obtained from 16 children at the time of dismembered pyeloplasty due to intrinsic UPJ stenosis. Expression levels of the three genes (MMP9, TIMP1 and RECK) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Then correlated the expression levels of the genes according to grade study population that was divided in 2 categories according to Society of Fetal Urology classification, grade 3 (moderate) and 4 (severe). For DTPA we subdivided the childrens in 2 groups, obstructive (T 1/2 more than 20 min) and partial obstructive (T 1/2 between 10 and 20 min) and success in a surgery was defined as decrease in T 1/ 2 to less than 20 min, absence of symptoms, improving renal function and decreasing dilatation on successive exams. Results: MMP9 was underexpressed and TIMP1 and RECK were overexpressed in children with obstructive DTPA but the differences were not statistically significant. Overexpression of MMP9 was higher among patients with severe grade of UPJ compared to those with moderate grade. Surprisingly expression levels of MMP-9 was three times higher in children who were successfully treated by surgery (n = 10) (p = 0.072), so those who were followed for at least 1 year after surgery and remained with improvement in renal function and decreasing dilation on intravenous urogram and TIMP-1 was underexpressed in 100 % of this cases (p = 0.00). Conclusions: We showed an increase in expression of MMP9 and a decrease in expression of TIMP1 in children who improving renal function and decreasing dilation after surgery. We believe that the higher expression of MMP9 in these cases can reflect an increase in degradation and remodeling process that could be used as a marker for surgical outcome.
- Testing for urinary hyaluronate improves detection and grading of transitional cell carcinoma(2011) PASSEROTTI, Carlo C.; SROUGI, Miguel; BOMFIM, Alexandre C.; MARTINS, Joao Roberto M.; LEITE, Katia R. M.; REIS, Sabrina T. dos; SAMPAIO, Lucia O.; ORTIZ, Valdemar; DIETRICH, Carl P.; NADER, Helena B.Objective: The purpose of this study is to establish a method for the diagnosis and grading of transitional cell carcinoma (TCC), which is responsible for 90% of bladder tumors, using a recently developed ultrasensitive assay for the measurement of hyaluronan (HA). Materials and methods: Urine samples were collected prior to surgery (cystoscopy, transurethral resection for bladder cancer (TURBT), and cystectomy) in 350 patients. After the procedure, pathologic examination revealed that 160 patients had TCC. HA was measured directly in the urine by a noncompetitive enzyme-linked immunosorbent assay (ELISA)-like fluorometric assay. Using the receiver operator characteristic curve (ROC), t-test, Dunn test, Kruskal-Wallis test, and Mann-Whitney test, we evaluated the differences between groups (those with TCC vs. those without TCC). Results: By analyzing the ROC curve, we chose a urinary HA cutoff value of 13.0 mu g/l for indicating risk of TCC. Using the value this of 13.0 mu g/l, we found that this test had an overall sensitivity of 82.3% and an overall specificity of 81.2%. The positive predictive value of this assay was 78.9%, the negative predictive negative value was 84.2%, and the predictive accuracy was 81.7%. Logistic regression analysis revealed that every 1 mu g/l increase in HA increased a patient's likelihood of having TCC by 3.9%. The sensitivity of this test to detect superficial tumors was 76.6%, whereas its sensitivity for detecting invasive tumors was 94.6%. The urinary HA excretion of patients with TCC, classified according to the TNM staging system and the World Health Organization (WHO) grading system, were compared, and a significant difference was observed between the HA levels of patients with superficial tumors compared with invasive tumors (P = 0.005) as well as between patients with low- vs. high-grade carcinomas (P < 0.001). Patients with urinary HA levels >35 mu g/l had a 4.63 times increased risk of having an aggressive, invasive, high grade tumor (P = 0.005). Conclusions: Our results support the postulate that urinary HA may be used as a tumor marker to aid in the diagnosis and grading of TCC. Additionally, more invasive tumors produce and release more HA in urine than superficial tumors, thus higher HA levels indicate more aggressive disease.