KATIA RAMOS MOREIRA LEITE
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/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats(2017) TURCO, Marcelo Pitelli; SOUZA, Alex Balduino de; SOUSA, Isida de Campos; FRATINI, Paula; VERAS, Mariana Matera; RODRIGUES, Marcio Nogueira; BESSA JR., Jose de; BROLIO, Marina Pandolphi; LEITE, Katia Ramos Moreira; BRUSCHINI, Homero; SROUGI, Miguel; MIGLINO, Maria Angelica; GOMES, Cristiano MendesAimsInvestigate the effect of a novel cell-based therapy with skeletal muscle-derived mononuclear cells (SMDMCs) in a rat model of stress urinary incontinence. MethodsMale Wistar-Kyoto rats' hind limb muscles were enzymatically dissociated, and SMDMCs were isolated without needing expansion. The cell population was characterized. Twenty female rats underwent urethrolysis. One week later, 10 rats received periurethral injection of 10(6) cells (SMDMC group), and 10 rats received saline injections (Saline group). Ten rats underwent sham surgery (Sham group). Four weeks after injection, animals were euthanized and the urethra was removed. The incorporation of SMDMCs in the female urethra was evaluated with fluorescence in situ hybridization for the detection of Y-chromosomes. Hematoxylin and eosin, Masson's trichrome staining, and immunohistochemistry for actin and myosin were performed. The muscle/connective tissue, actin and myosin ratios were calculated. Morphological evaluation of the urethral diameters and fractional areas of the lumen, mucosa, and muscular layer was performed. ResultsSMDMCs population was consistent with the presence of muscle cells, muscle satellite cells, perivascular cells, muscle progenitor cells, and endothelial cells. SMDMCs were incorporated into the urethra. A significant decrease in the muscle/connective tissue ratio was observed in the Saline group compared with the SMDMC and Sham groups. The proportions of actin and myosin were significantly decreased in the Saline group. No differences were observed in the morphometric parameters. ConclusionsSDMSC were incorporated into the rat urethra and promoted histological recovery of the damaged urethral sphincter, resulting in decreased connective tissue deposition and increased muscle content.
- Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer(2012) REIS, Sabrina Thalita; LEITE, Katia Ramos M.; PIOVESAN, Luis Felipe; PONTES-JUNIOR, Jose; VIANA, Nayara Izabel; ABE, Daniel Kanda; CRIPPA, Alexandre; MOURA, Caio Martins; ADONIAS, Sanarelly Pires; SROUGI, Miguel; DALL'OGLIO, Marcos FranciscoBackground: 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, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.
- Prostate biopsy in patients with long-term use of indwelling bladder catheter: What is the rationale?(2012) ANTUNES, Alberto A.; BARBOSA, Joao Arthur B. A.; REIS, Sabrina T.; GUARIERO, Mary S.; FUKUSHIMA, Julia T.; DALL'OGLIO, Marcos F.; FREIRE, Geraldo de C.; LUCON, Antonio M.; LEITE, Katia R.; SROUGI, MiguelObjective: Acute urinary retention (AUR) is expected to occur in 2% to 39% men with benign prostatic hyperplasia. To date, no study has elucidated the effect of long-term use of indwelling bladder catheter on serum prostate specific antigen (PSA) levels and on the incidence of prostate cancer (CaP). The aim of the present study is to analyze the incidence of CaP in patients with long-term use of indwelling bladder catheter and determine some practice patterns on this issue. Materials and methods: The study comprised a retrospective analysis of data from 1,651 patients who had undergone transrectal ultrasound (TRUS)-guided prostate biopsy from July 2004 to June 2009. Among these patients, 198 (12%) were using an indwelling bladder catheter during the biopsy for at least 1 month. The incidence of CaP was recorded according to total PSA levels. Other variables such patient age, free/total PSA rate, PSA density, prostate volume, and duration of catheter use was also analyzed. Men with a digital rectal examination suspicious for cancer were not considered for analysis. Results: Median patient age was 71 years (37 to 89 years). Overall, 25% of patients presented a CaP diagnosis. CaP incidence according to the PSA levels was 0%, 18.9%, 24.5%, and 40.6% for patients with PSA <= 4.0, 4.1-10.0, 10.1-20.0, and >20.0 ng/ml, respectively. When prostate volume was analyzed together, we demonstrated that only 1 (2.4%) patient with PSA below 10.0 ng/ml and prostate volume >60 g had CaP. Median total PSA, PSA density, and prostate volume were statistically different between patients with and without CaP. Conclusions: Prostate biopsy should not be indicated for all patients with diagnosis of BPH and AUR who present an elevated PSA level. Patients with PSA below 10.0 ng/ml, and prostate volume >60 g should only undergo biopsy in selected cases. Patients with PSA >20.0 ng/ml and a prostate volume <= 60 g are at higher risk of CaP diagnosis.
article 13 Citação(ões) na Scopus Socioeconomic status is an independent predictor of biochemical recurrence among patients with prostate cancer who undergo radical prostatectomy(2011) SROUGI, Victor; ANTUNES, Alberto A.; REIS, Sabrina T.; DALL'OGLIO, Marcos F.; NESRALLAH, Adriano J.; LEITE, Ktia R. M.; SROUGI, MiguelPurpose: Socioeconomic status (SES) may influence cancer characteristics and behavior in several aspects. We analyzed PCa characteristics and behavior among low income uninsured men, and compare them to high income patients with health insurance in a developing country. Materials and Methods: A retrospective case-control study was performed on 934 patients with clinically localized PCa who underwent radical prostatectomy between March, 1999 and July, 2009. Patients were divided in two groups, according to their SES. In group 1 (n=380), all had low income, low educational levels and couldn't afford medical insurance. In group 2 (n=554), all had higher income, higher education and had medical insurance. Results: Patients from group 1 were older, had higher Gleason scores, higher rates of seminal vesicle and bladder neck involvement. The Kaplan Meier disease-free survival curve demonstrated that after a follow-up of four years, about 50% of uninsured patients had biochemical recurrence, versus 21% of insured patients (Log rank test: p < 0.001). A multivariate Cox regression analysis for the risk of disease recurrence demonstrated that only PSA levels, Gleason score, seminal vesicle involvement and SES were statistically significant variables. Patients with a low SES presented 1.8 times the risk of recurrence as compared to patients with a high SES. Conclusions: Patients with low SES were older, presented more aggressive PCa characteristics and a high rate of disease recurrence. A low SES constituted an independent predictor for disease recurrence.- Gene expression profile of renal cell carcinomas after neoadjuvant treatment with sunitinib: new pathways revealed(2017) DZIK, Carlos; REIS, Sabrina T.; VIANA, Nayara I.; BRITO, Glauber; PALOPPI, Isis; NAHAS, Willian; SROUGI, Miguel; LEITE, Katia R. M.Background: In renal cell carcinoma (RCC) of the clear cell type, inactivity of the VHL gene induces overexpression of HIF1 alpha and its targets, the tyrosine kinase receptors, promoting RCC development and progression. The discovery of tyrosine kinase inhibitors (TKIs) changed the treatment of these tumors. Other molecular pathways involved in the TKI mechanisms of action have not been described in the literature. The aim of our study was to elucidate alternative mechanisms of action of sunitinib in tumor tissue after neoadjuvant treatment of RCC. Methods: The gene expression profile was accessed using microarray (Affymetrix Human Genome U133 Plus 2.0 platform) and frozen RCC tissues collected from 5 patients with locally advanced non-metastatic tumors who underwent nephrectomy after being treated with 2 cycles of neoadjuvant sunitinib. The results were compared with matched controls comprising 6 patients with no neoadjuvant intervention. Results: There was underexpression of the majority of genes after sunitinib treatment. The lower expression levels of IGFBP1, CCL20, CXCL6 and FGB were confirmed by qRT-PCR in all cases. The downregulation of gene expression leads us to search for methylation as a mechanism of action of the TKI. IGFBP1 was shown to be methylated by methylation-sensitive high-resolution melting technique. Conclusions: The ultimate genetic effects of sunitinib may explain its actions as an antitumor drug that apparently suppresses the expression of important genes related to cell survival, adhesion, invasion and immunomodulation. The methylation of gene promoters was shown to be part of the mechanism of action of this class of drugs.
- 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.
- Involvement of the central nervous system in neuroblastomas: A potential direct pathway(2020) ODONE-FILHO, Vicente; CRISTOFANI, Lilian Maria; MALUF, Paulo Taufi; ALMEIDA, Maria Tereza Assis; HALLEY, Nathalia; VINCE, Carolina Sgarioni Camargo; AZAMBUJA, Alessandra Milani Prandini de; BRUMATTI, Melina; LUBRAICO, Priscilla; LOPES, Luiz Heraldo Arouche da Camara; LEITE, Katia Ramos Moreira; SILVA, Joao Luis Fernandes; PLESE, Jose Pindaro Pereira; WELTMAN, EduardoAlthough frequently disseminated to other anatomical sites, neuroblastoma (NB) is rarely reported as involving the central nervous system (CNS), which may reflect insufficient research in poorly controlled systemic disease. Here we demonstrate the involvement of the CNS in patients with NB over 18 months of age at diagnosis of extensive systemic disease. Meningeal metastases were observed even in the presence of complete systemic control. Although no improvement in patient's survival was observed, radiotherapy was effective in preventing CNS recurrence after observation of actual or previous dural disease. In conclusion, this study uncovered the uncommon pathologic involvement of the CNS in children with advanced NB and underscores the meningeal surface as a potential pathway for this to occur.
- Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model(2011) WATANABE, Fabio T.; CHADE, Daher C.; REIS, Sabrina T.; PIANTINO, Camila; OGLIO, Marcos Francisco Dall'; SROUGI, Miguel; LEITE, Katia R. M.OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six-to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.
- Detecting and grading prostate cancer in radical prostatectomy specimens through deep learning techniques(2021) MELO, Petronio Augusto de Souza; ESTIVALLET, Carmen Liane Neubarth; SROUGI, Miguel; NAHAS, William Carlos; LEITE, Katia Ramos MoreiraOBJECTIVES: This study aims to evaluate the ability of deep learning algorithms to detect and grade prostate cancer (PCa) in radical prostatectomy specimens. METHODS: We selected 12 whole-slide images of radical prostatectomy specimens. These images were divided into patches, and then, analyzed and annotated. The annotated areas were categorized as follows: stroma, normal glands, and Gleason patterns 3, 4, and 5. Two analyses were performed: i) a categorical image classification method that labels each image as benign or as Gleason 3, Gleason 4, or Gleason 5, and ii) a scanning method in which distinct areas representative of benign and different Gleason patterns are delineated and labeled separately by a pathologist. The Inception v3 Convolutional Neural Network architecture was used in categorical model training, and a Mask Region-based Convolutional Neural Network was used to train the scanning method. After training, we selected three new whole-slide images that were not used during the training to evaluate the model as our test dataset. The analysis results of the images using deep learning algorithms were compared with those obtained by the pathologists. RESULTS: In the categorical classification method, the trained model obtained a validation accuracy of 94.1% during training; however, the concordance with our expert uropathologists in the test dataset was only 44%. With the image-scanning method, our model demonstrated a validation accuracy of 91.2%. When the test images were used, the concordance between the deep learning method and uropathologists was 89%. CONCLUSION: Deep learning algorithms have a high potential for use in the diagnosis and grading of PCa. Scanning methods are likely to be superior to simple classification methods.
- Histologic Abnormalities in Non-neoplastic Renal Parenchyma and the Risk of Chronic Kidney Disease Following Radical Nephrectomy(2017) BRANDINA, Ricardo; LEITE, Katia Ramos Moreira; GREGORIO, Emerson Pereira; FERNANDES, Karen Barros Parron; SROUGI, MiguelOBJECTIVE To assess the association of histopathological parameters in non-neoplastic renal parenchyma with the development of new-onset chronic kidney disease (CKD) after radical nephrectomy. PATIENTS AND METHODS Data were extracted from 222 patients who underwent radical nephrectomy. The Modification of Diet in Renal Disease formula was used. The study end point was development of CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m(2). A renal pathologist assessed three histologic features in the non-neoplastic parenchyma, namely global glomerulosclerosis (GS), arteriosclerosis (AS), and interstitial fibrosis (IF). For GS assessment, the percent of affected glomeruli was determined. AS was graded and divided into three groups, namely 1-0%-25%, 2-26%-50%, and 3-greater than 50%. IF was evaluated as absent or present. RESULTS After a mean follow-up of 49.06 months, the mean eGFR rate decrease was 26.5% after radical nephrectomy. Almost half of the patients (53.8%) developed CKD. For each 2.5% increase in GS, each point increase in Charlson comorbidity index (CCI), and each 10-year increase in patient's age, the eGFR decreased 28%, 33%, and 39%, respectively (P < .05). In a univariate analysis, age, CCI, GS, AS, IF, hypertension, and diabetes mellitus were associated with new-onset CKD after radical nephrectomy (P < .05). After multivariate logistic regression, CCI, GS, and baseline eGFR were associated with new-onset CKD after radical nephrectomy. CONCLUSION Histopathological evaluation of non-neoplastic renal parenchyma in patients who undergo radical nephrectomy can be used to predict the development of new-onset CKD. UROLOGY 100: 158-162, 2017. (c) 2016 Elsevier Inc.