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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- Could the differences in the biochemistry of prostate carcinoma compared to benign prostate tissue biopsy fragments be evaluated through Raman spectroscopy?(2013) SILVEIRA JR., Landulfo; LEITE, Katia Ramos M.; SROUGI, Miguel; SILVEIRA, Fabricio L.; PACHECO, Marcos Tadeu T.; ZANGARO, Renato A.; PASQUALUCCI, Carlos A.It has been proposed a spectral model to evaluate the biochemical differences between prostate carcinoma and benign fragments using dispersive Raman spectroscopy. We have examined 51 prostate fragments from surgically removed PrCa; each fragment was snap-frozen and stored (-80 degrees C) prior spectral analysis. Raman spectrum was measured using a Raman spectrometer (830 nm excitation) coupled to a fiber-optic probe. Integration time and laser power were set to 50 s and 300 mW, respectively. It has been collected triplicate spectra from each fragment (total 153 spectra). Some samples exhibited a strong fluorescence, which was removed by a 7th order polynomial fitting. It has been developed a spectral model based on the least-squares fitting of the spectra of pure biochemicals (actin, collagen, elastin, carotene, glycogen, phosphatidylcholine, hemoglobin, and water) with the spectra of tissues, where the fitting parameters are the relative contribution of the compounds to the tissue spectrum. The spectra (600-1800 cm(-1) range) are dominated by bands of proteins; it has been found a small difference in the mean spectra of PrCa compared to the benign tissue, mainly in the 1000-1400 cm(-1) region, indicating similar biochemical constitution. The spectral fitting model revealed that elastin and phosphatidylcholine were increased in PrCa, whereas blood and water were reduced in malignant lesions (p < 0.05). A discrimination of PrCa from benign tissue using Mahalanobis distance applied to the contribution of elastin, hemoglobin and phosphatidylcholine resulted in sensitivity of 72% and specificity of 70%.
- The influence of interstitial cells of Cajal density in the outcomes of pyeloplasty in adults: A prospective analysis(2023) SROUGI, Victor; BANDEIRA, Rodolfo Anisio Santana de Torres; REIS, Sabrina Thalita; SANTOS, Gabriel Arantes dos; ANDRADE, Hiury da Silva; LEITE, Katia Ramos Moreira; HAMILTON-CHO, David; MITRE, Anuar Ibrahim; ARAP, Marco Antonio; SROUGI, Miguel; DUARTE, Ricardo JordaoPurpose: To evaluate if the density of interstitial cells of Cajal (ICC) in the ureteropelvic junction (UPJ) influences the outcomes of pyeloplasty in adults. Methods: Twenty-three patients with the diagnosis of ureteropelvic junction obstruction (UPJO) that underwent laparoscopic dismembered pyeloplasty were included. ICC density was measured using immunohistochemistry reaction for c-KIT expression in the resected UPJ segment. Pyeloplasty outcome was evaluated by patient self-report pain, urinary outflow using DTPA renogram and hydronephrosis assessment using ultrasound (US) at 12 months of follow-up. A logistic regression analysis was performed to assess the association of pyeloplasty outcomes and ICC density. Results: Low, moderate, and high ICC density were present in 17.4%, 30.4%, and 52.2% of the patients, respectively. Complete pain resolution was observed in 100%, 85.7%, and 75% of patients with low, moderate and high ICC density, respectively (p = 0.791). DTPA renogram improved in 75%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.739). Hydronephrosis improved in 25%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.032). Conclusions: Patients with high ICC density have a significant amelioration of hydronephrosis after pyeloplasty. However, ICC density is not associated with functional outcomes.
- Is age an independent factor for prostate cancer? A paired analysis(2017) CRUZ, J. A. S. Da; PASSEROTTI, C. C.; REIS, S. T. Dos; GUARIERO, M. E. S.; CAMPOS, O. D. De; LEITE, K. R. M.; SROUGI, M.Introduction: Prostate cancer is the most prevalent malignant neoplasia among men worldwide. Several prognostic factors, including Gleason's score, the measurement of serum prostate-specific antigen (PSA) and the evaluation of the percentage of fragments affected by cancer on prostate biopsy, have already been established. Age alone, however, has yet to be studied as a prognostic factor independently from other known factors. The aim of the present study was to compare the characteristics and the evolution of prostate cancer in different age groups using a paired analysis for patients with equivalent known prognostic factors. In addition, we aimed to determine the true impact of age on the prognosis of prostate cancer. Material and Methods: The data from 2,283 patients subjected to radical retropubic prostatectomy between 1998 and 2009 were reviewed. The patients were divided into three age groups: < 55 years old, between 56 and 65 and > 65 years old. Each patient was matched to another patient in the other groups who had the same PSA range (< 4.0, between 4.0 and 10.0 and > 10), Gleason score on the surgical specimen and prognostic range of positive fragments in the prostate biopsy (< 33%, between 34 and 50% and > 50%). After pairing, each group consisted of 215 patients, who were compared using the biochemical recurrence of the disease (PSA > 0.2), the interval for biochemical relapse, extra-capsular invasion and invasion of the seminal vesicles or the lymph nodes. RESULTS. No significant difference was observed between the groups regarding the frequency of relapses, interval of relapse, extra-capsular invasion and invasion of the seminal vesicles or lymph nodes. Discussion: None of the studied factors were affected by the age of the patients. Therefore, patients of different ages had tumors with similar characteristics and behaviors. Conclusion: When assessed separately, without the effects of the main prognostic factors, age does not appear to be an independent prognostic factor for prostate cancer. © 2015 S. Karger AG, Basel.
- Telomeric zinc-finger associated protein (TZAP) in cancer biology: friend or foe?(2021) SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; PIMENTA, Ruan; CAMARGO, Juliana Alves de; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, MiguelThe new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker.
- Brazilian Expert Consensus for NTRK Gene Fusion Testing in Solid Tumors(2023) MACEDO, Mariana Petaccia de; NASCIMENTO, Ellen Caroline Toledo; SOARES, Fernando Augusto; SANTINI, Fernando Costa; COSTA, Felipe D'Almeida; CUNHA, Isabela Werneck da; MUNHOZ, Rodrigo Ramella; MARCHI, Pedro De; JORGE, Thiago William Carnier; LEITE, Katia Ramos MoreiraOncogenic neurotrophic tropomyosin receptor kinase gene fusions occur in less than 1% of common cancers. These mutations have emerged as new biomarkers in cancer genomic profiling with the approval of selective drugs against tropomyosin receptor kinase fusion proteins. Nevertheless, the optimal pathways and diagnostic platforms for this biomarker's screening and genomic profiling have not been defined and remain a subject of debate. A panel of national experts in molecular cancer diagnosis and treatment was convened by videoconference and suggested topics to be addressed in the literature review. The authors proposed a testing algorithm for oncogenic neurotrophic tropomyosin receptor kinase gene fusion screening and diagnosis for the Brazilian health system. This review aims to discuss the latest literature evidence and international consensus on neurotrophic tropomyosin receptor kinase gene fusion diagnosis to devise clinical guidelines for testing this biomarker. We propose an algorithm in which testing for this biomarker should be requested to diagnose advanced metastatic tumors without known driver mutations. In this strategy, Immunohistochemistry should be used as a screening test followed by confirmatory next-generation sequencing in immunohistochemistry-positive cases.
- Interobserver reproducibility of cribriform cancer in prostate needle biopsies and validation of International Society of Urological Pathology criteria(2023) EGEVAD, Lars; DELAHUNT, Brett; ICZKOWSKI, Kenneth A.; KWAST, Theo van der; LEENDERS, Geert J. L. H. van; LEITE, Katia R. M.; PAN, Chin-Chen; SAMARATUNGA, Hemamali; TSUZUKI, Toyonori; MULLIQI, Nita; JI, Xiaoyi; OLSSON, Henrik; VALKONEN, Masi; RUUSUVUORI, Pekka; EKLUND, Martin; KARTASALO, KimmoAimsThere is strong evidence that cribriform morphology indicates a worse prognosis of prostatic adenocarcinoma. Our aim was to investigate its interobserver reproducibility in prostate needle biopsies. Methods and resultsA panel of nine prostate pathology experts from five continents independently reviewed 304 digitised biopsies for cribriform cancer according to recent International Society of Urological Pathology criteria. The biopsies were collected from a series of 702 biopsies that were reviewed by one of the panellists for enrichment of high-grade cancer and potentially cribriform structures. A 2/3 consensus diagnosis of cribriform and noncribriform cancer was reached in 90% (272/304) of the biopsies with a mean kappa value of 0.56 (95% confidence interval 0.52-0.61). The prevalence of consensus cribriform cancers was estimated to 4%, 12%, 21%, and 20% of Gleason scores 7 (3 + 4), 7 (4 + 3), 8, and 9-10, respectively. More than two cribriform structures per level or a largest cribriform mass with >= 9 lumina or a diameter of >= 0.5 mm predicted a consensus diagnosis of cribriform cancer in 88% (70/80), 84% (87/103), and 90% (56/62), respectively, and noncribriform cancer in 3% (2/80), 5% (5/103), and 2% (1/62), respectively (all P < 0.01). ConclusionCribriform prostate cancer was seen in a minority of needle biopsies with high-grade cancer. Stringent diagnostic criteria enabled the identification of cribriform patterns and the generation of a large set of consensus cases for standardisation.
- Distinct urinary glycoprotein signatures in prostate cancer patients(2018) KAWAHARA, R.; ORTEGA, F.; ROSA-FERNANDES, L.; GUIMARãES, V.; QUINA, D.; NAHAS, W.; SCHWäMMLE, V.; SROUGI, M.; LEITE, K. R. M.; THAYSEN-ANDERSEN, M.; LARSEN, M. R.; PALMISANO, G.Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. Importantly, a panel of 56 intact N-glycopeptides perfectly discriminated PCa and BPH (ROC: AUC = 1). This study has generated a panel of intact glycopeptides that has a potential for PCa detection. © Kawahara et al.
- Main autopsyfindings of visceral involvement by fatal mpox in patients with AIDS: necrotising nodular pneumonia, nodular ulcerative colitis, and diffuse vasculopathy(2023) DUARTE-NETO, Amaro Nunes; GONCALVES, Ana Maria; ELIODORO, Raissa Heloisa de Araujo; MARTINS, Wilker Dias; CLARO, Ingra Morales; VALENCA, Ian Nunes; PAES, Vitor Ribeiro; TEIXEIRA, Ralcyon; SZTAJNBOK, Jaques; SILVA, Ivan Leonardo Avelino Franca e; LEITE, Luiz Antonio Ferreira; MALAQUE, Ceila Maria Sant'Ana; BORGES, Luciana Marques Sansao; GONZALEZ, Mario Peribanez; BARRA, Luiz Alberto Costa; PEREIRA JUNIOR, Luiz Carlos; MELLO, Claudia Figueiredo; QUEIROZ, Wladimir; ATOMYA, Angela Naomi; FERNEZLIAN, Sandra de Morais; ALVES, Venancio Avancini Ferreira; LEITE, Katia Ramos Moreira; FERREIRA, Cristiane Rubia; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; FARIA, Nuno R.; CORREA, Maria Cassia Jacinto Mendes; SABINO, Ester Cerdeira; SOTTO, Mirian Nacagami; DOLHNIKOFF, Marisa
- Could Raman spectroscopy discriminate the biochemical alterations among prostate carcinoma and benign prostate tissues? An in vitro study(2012) SILVEIRA JR., Landulfo; LEITE, Katia Ramos M.; SROUGI, Miguel; SILVEIRA, Fabricio L.; PACHECO, Marcos Tadeu T.; PASQUALUCCI, Carlos A.This work evaluated possible alterations in the Raman spectra of human prostate tissues in vitro, by developing a Principal Components Analysis algorithm for discriminating prostate carcinoma (PrCa) and benign prostate tissue. Raman spectrum was measured using a Raman spectrometer (830 nm) with a fiber Raman probe. Most of the samples exhibited a very strong background fluorescence, which was decreased by photobleaching the fragment during 5 min. and the remaining fluorescence was removed by polynomial filtering. The spectra of prostate in the fingerprint region are dominated by bands of proteins (mainly collagen, elastin, actin). By comparing the spectra of PrCa with the benign prostate tissue, we found a very small difference, indicating similar biochemical constitution of benign and malignant prostate tissue. Principal Components Analysis and Mahalanobis distance could discriminate the spectra of both benign and PrCa tissues with reasonable sensitivity and specificity.
- Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer(2023) PIMENTA, Ruan; MIOSHI, Carolina Mie; GONCALVES, Guilherme L.; CANDIDO, Patricia; CAMARGO, Juliana A.; GUIMARAES, Vanessa R.; CHIOVATTO, Caroline; GHAZARIAN, Vitoria; ROMAO, Poliana; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; VIANA, Nayara I.; REIS, Sabrina T.MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 mu g weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.