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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- Correlation of a microRNA expression profile and the prognosis of penile cancer: A prospective study using microarray data analysis(2018) FURUYA, Tatiane K.; MURTA, Claudio B.; PONTES JR., Jose; UNO, Miyuki; CARRASCO, Alexis; SICHERO, Laura C.; VILLA, Luisa L.; COELHO, Rafael F.; GUGLIELMETTI, Giuliano B.; CORDEIRO, Mauricio D.; LEITE, Katia R.; SROUGI, Miguel; CHAMMAS, Roger; NAHAS, William C.
conferenceObject GLUT1 Expression Is Related to Tumor Recurrence and Survival in Renal Cell Carcinoma Clear Cell Type(2017) LEITE, Katia R. M.; CARVALHO, Paulo A.; PINHEIRO, Celine M.; REIS, Sabrina T.; SROUGI, Miguel; NAHAS, William C.conferenceObject GLUT1 Expression Is Related to Tumor Recurrence and Survival in Renal Cell Carcinoma Clear Cell Type(2017) LEITE, Katia R. M.; CARVALHO, Paulo A.; PINHEIRO, Celme M.; REIS, Sabrina T.; SROUGI, Miguel; NAHAS, William C.- 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.
- 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.
- Histological Variants of Urothelial Carcinoma Predict No Response to Neoadjuvant Chemotherapy(2022) LEITE, Katia Ramos Moreira; BORGES, Leonardo Lima; RIBEIRO FILHO, Leopoldo; CHADE, Daher; COELHO, Rafael Ferreira; CORDEIRO, Mauricio; SROUGI, Miguel; NAHAS, Willian CarlosMicroabstract: This study shows that the presence of divergent histological differentiation and the immunexpression of CAIX in muscle invasive urothelial carcinoma, predicts no response to cisplatin based neoadjuvant chemotherapy. Background: Platinum-based neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIBC) has been adopted as a standard of care related to better survival outcomes. However, there is a considerable number of patients who do not respond, experiencing toxicity and delay in the surgical treatment. Our aim is to find biomarkers of response that could be easily adopted in the clinical practice. Methods: Between January 2009 and July 2016, 52 patients with MIBC were submitted to radical cystectomy after NAC. A tissue microarray containing 25 cases, who met the inclusion criteria was built for immunohistochemical analysis of Cytokeratins 5/6, 7, and 20, GATA3, Her2, EGFR, p63, p53, Carbonic-anhydrase IX (CAIX), MLH1, MSH2, MSH6, and PMS2. The surgery was performed in a mean time of 58.7 (+/- 21) days after the end of the NAC. Fisher's exact test was used to analyze the relationship between response (<= pT1) and histopathological and immunohistochemical results and Kaplan-Meier curves were designed for survival analysis. Results: Ten (40.0%) patients presented response to NAC. Histological variants of the urothelial carcinoma characterized by squamous, sarcomatous/rhabdoid, plasmacytoid, and micropapillary was present in 36.0% and none responded to NAC (P = .002). CAIX was expressed by 53.3% and none responded to NAC (P= .005). Lymph-node metastasis, divergent differentiation, and expression of cytokeratin 5/6 were related to short cancer specific survival. Conclusion: Histological variants and CAIX immune-expression are biomarkers of nonresponse to NAC of MIBC, and might be easily used in the clinical practice to select patients to be submitted to surgery upfront.
- Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families(2019) REIS, Sabrina T.; LEITE, Katia R. M.; MARCHINI, Giovanni S.; GUIMARAES, Ronaldo M.; VIANA, Nayara I.; PIMENTA, Ruan C. A.; TORRICELLI, Fabio C.; DANILOVIC, Alexandre; VICENTINI, Fabio Carvalho; NAHAS, William Carlos; SROUGI, Miguel; MAZZUCCHI, EduardoThe aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome-Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan (R) SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0-fold (P = 0.036). Pre-B-cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3-fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild-type homozygote genotype had overexpression of PBX1. There is a 3-fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.
- Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics(2017) OLIVEIRA, Rita de Cassia; IVANOVIC, Renato Fidelis; LEITE, Katia Ramos Moreira; VIANA, Nayara Izabel; PIMENTA, Ruan Cesar Aparecido; PONTES JUNIOR, Jose; GUIMARAES, Vanessa Ribeiro; MORAIS, Denis Reis; ABE, Daniel Kanda; NESRALLAH, Adriano Joao; SROUGI, Miguel; NAHAS, William; REIS, Sabrina ThalitaBackground: Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC. Methods: The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-alpha, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion. Results: miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression was associated with Fuhrman's low grade (p = 0.03). Conclusions: Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia.
conferenceObject DO THE REGULATION OF MATRIX METALLOPROTEINASES AND TISSUE INHIBITORS OF MATRIX METALLOPROTEINASES HAVE ANY ASSOCIATION WITH PEYRONIE'S DISEASE?(2020) NETO, Cristovao Barbosa; REIS, Sabrina T.; ARANTES, Gabriel; NASCIMENTO, Bruno; SAYAO, Rogerio; LEITE, Katia Ramos; SROUGI, Miguel; NAHAS, William; CURY, JoseconferenceObject Randomized phase II trial of neoadjuvant androgen deprivation therapy plus abiraterone and apalutamide for patients with high-risk localized prostate cancer: Pathologic response and PSMA imaging correlates.(2022) BASTOS, Diogo Assed; COELHO, Rafael; CARDILI, Leonardo; GALIZA, Felipe; ILARIO, Eder Nisi; VIANA, Ublio; MURTA, Claudio Bovolenta; GUGLIELMETTI, Giuliano; CORDEIRO, Mauricio; PONTES JR., Jose; MUNIZ, David Queiroz Borges; SILVA, Jamile Almeida; MOTA, Jose Mauricio; FREITAS, Guilherme Fialho De; LEITE, Katia Ramos Moreira; BUCHPIGUEL, Carlos Alberto; NAHAS, William Carlos