VANESSA RIBEIRO GUIMARAES SCHREITER

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LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina

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  • article 4 Citação(ões) na Scopus
    Prognostic value of TERF1 expression in prostate cancer
    (2021) SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; PIMENTA, Ruan; GUIMARAES, Vanessa Ribeiro; CAMARGO, Juliana Alves de; ROMAO, Poliana; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, Miguel
    Background: Telomere dysfunction is one of the hallmarks of cancer and is crucial to prostate carcinogenesis. TERF1 is a gene essential to telomere maintenance, and its dysfunction has already been associates with several cancers. TERF1 is a target of miR-155, and this microRNA can inhibit its expression and promotes carcinogenesis in breast cancer. We aim to analyze TERF1, in gene and mRNA level, involvement in prostate cancer progression. Results: Alterations in TERF1 DNA were evaluated using datasets of primary tumor and castration-resistant tumors (CRPC) deposited in cBioportal. The expression of TERF1 mRNA levels was assessed utilizing TCGA datasets, clinical specimens, and metastatic prostate cancer cell lines (LNCaP, DU145, and PC3). Six percent of localized prostate cancer presents alterations in TERF1 (the majority of that was amplifications). In the CRPC cohort, 26% of samples had TERF1 amplification. Patients with TERF1 alterations had the worst overall survival only on localized cancer cohort (p = 0.0027). In the TCGA cohort, mRNA levels of TERF1 were downregulated in comparison with normal tissue (p = 0.0013) and upregulated in tumors that invade lymph nodes (p = 0.0059). The upregulation of TERF1 is also associated with worst overall survival (p = 0.0028) and disease-free survival (p = 0.0023). There is a positive correlation between TERF1 and androgen receptor expression in cancer tissue (r = 0.53, p < 0.00001) but not on normal tissue (r = - 0.16, p = 0.12). In the clinical specimens, there is no detectable expression of TERF1 and upregulation of miR-155 (p = 0.0348). In cell lines, TERF1 expression was higher in LNCaP and was progressively lower in DU145 and PC3 (p = 0.0327) with no differences in miR-155 expression. Conclusion: Amplification/upregulation of TERF1 was associated with the worst prognostic in localized prostate cancer. Our results corroborate that miR-155 regulates TERF1 expression in prostate cancer. TERF1 has the potential to become a biomarker in prostate cancer.
  • article 4 Citação(ões) na Scopus
    Can we use Ki67 expression to predict prostate cancer aggressiveness?
    (2022) MAIA, RONALDO; SANTOS, GABRIEL ARANTES DOS; REIS, SABRINA; VIANA, NAYARA I; PIMENTA, RUAN; GUIMARÃES, VANESSA R; RECUERO, SAULO; ROMÃO, POLIANA; LEITE, KATIA RAMOS MOREIRA; SROUGI, MIGUEL; PASSEROTTI, CARLO CARMARGO
    ABSTRACT Introduction: specialists have an urge for biomarkers that can discriminate indolent prostate cancer from aggressive tumors. Ki67 is a proliferation marker, and its expression is associated with the aggressiveness of several cancers. Objective: analyze the expression of Ki67 in prostate cancer samples correlating with the aggressiveness of the disease. Methods: Ki67 mRNA levels were determined utilizing data from a TCGA cohort (Tumor(n)=492 and control(n)=52). The protein expression was determined on 94 biopsies from patients by immunohistochemical assay. Results: in mRNA, the Ki67 upregulation is associated with cancer tissue (p<0.0001) and worst disease-free survival (p=0.035). The protein upregulation is associated with increase of the ISUP score (p<0.0001), cancer stage (p=0.05), biochemical recurrence (p=0.0006) and metastasis (p<0.0001). We also show a positive correlation between Ki67 expression and ISUP score (r=0.5112, p<0.0001) and disease risk stratification (r=0.3388, p=0.0009). Ki67 expression is a factor independently associated with biochemical recurrence (p=0.002) and metastasis (p<0.0001). Finally, the patients with high Ki67expression shows better survival regarding biochemical recurrence (p=0.008) and metastasis (p=0.056). Patients with high Ki67 expression are 2.62 times more likely to develop biochemical recurrence (p=0.036). Conclusion: Ki67 upregulation is associated with prostate cancer aggressiveness.
  • article 17 Citação(ões) na Scopus
    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 Thalita
    Background: 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.
  • article 12 Citação(ões) na Scopus
    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 Moreira
    Introduction 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.
  • article 7 Citação(ões) na Scopus
    Pan-cancer analysis reveals that CTC1-STN1-TEN1 (CST) complex may have a key position in oncology
    (2022) SANTOS, Gabriel Arantes dos; VIANA, Nayara I.; PIMENTA, Ruan; CAMARGO, Juliana Alves de; GUIMARAES, Vanessa R.; ROMAO, Poliana; CANDIDO, Patricia; GHAZARIAN, Vitoria; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, Miguel
    Telomere dysfunction is one of the hallmarks of cancer, which puts telomere-associated genes in a prominent position in oncology. The CTC1-STN1-TEN1 (CST) complex is vital for telomere maintenance and participates in several steps of DNA metabolism, such as repair and replication, essential functions for malignant cells. Despite this, little is known about these genes in cancer biology. Here, using bioinformatics tools, we performed a study in 33 cancer types and over 10,0 0 0 TCGA samples analyzing the role of the CST complex in cancer. We obtained the somatic landscape and gene expression patterns of each of the subunits of the complex studied. Furthermore, we show that CST is important for genetic stability and nucleic acid metabolism in cancer. We identify possible interactors, transcription factors, and microRNAs associated with CST and two drugs that may disrupt their pathways. In addition, we show that CST gene expression is associated with cancer survival and recurrence in several tumor types. Finally, we show negative and positive correlations between immune checkpoint genes and CST in different types of cancer. With this work, we corroborate the importance of these genes in cancer biology and open perspectives for their use in other works in the field.
  • article 32 Citação(ões) na Scopus
    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.
  • article 3 Citação(ões) na Scopus
    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.
  • article 1 Citação(ões) na Scopus
    Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study
    (2022) INOUE, Gustavo N. C.; PIMENTA, Ruan; CAMARGO, Juliana A.; I, Nayara Viana; GUIMARAES, Vanessa R.; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R. M.; REIS, Sabrina T.
    Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines. Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia. Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group. Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery. Institutional protocol number: Animal Ethics Committee 1332/2019.
  • article 13 Citação(ões) na Scopus
    Shorter leukocyte telomere length is associated with severity of COVID-19 infection.
    (2021) SANTOS, Gabriel Arantes dos; PIMENTA, Ruan; I, Nayara Viana; GUIMARAES, Vanessa R.; ROMAO, Poliana; CANDIDO, Patricia; CAMARGO, Juliana A. de; HATANAKA, Dina M.; QUEIROZ, Paula G. S.; TERUYA, Alexandre; LEITE, Katia R. M.; SROUGI, Victor; SROUGI, Miguel; REIS, Sabrina T.
    The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by QPCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology.
  • article 24 Citação(ões) na Scopus
    MiR-200c-3p expression may be associated with worsening of the clinical course of patients with COVID-19
    (2021) PIMENTA, Ruan; I, Nayara Viana; SANTOS, Gabriel A. dos; CANDIDO, Patricia; GUIMARAES, Vanessa R.; ROMAO, Poliana; SILVA, Iran A.; CAMARGO, Juliana A. de; HATANAKA, Dina M.; QUEIROZ, Paula G. S.; TERUYA, Alexandre; ECHENIQUE, Leandro; BESEN, Bruno A. M. P.; LEITE, Katia R. M.; SROUGI, Victor; SROUGI, Miguel; REIS, Sabrina T.
    COVID-19 represents a public health emergency, whose mechanism of which is not fully understood. It is speculated that microRNAs may play a crucial role in host cells after infection by SARS-CoV-2. Thus, our study aimed to analyze the expression of miR-200c-3p in saliva samples from patients with COVID-19. One handred eleven samples from patients with COVID-19 were divided into 4 groups. Group I: 39 patients negative for Covid-19; Group II: 37 positive and symptomatic patients, with no indication of hospitalization; Group III: 21 patients with respiratory disorders (hospitalized); Group W: 14 patients with severe conditions (oxygen therapy). The expression levels of miR-200c-3p were determined using qPCR. We found greater expression of miR-200c-3p in patients in group W (p<0.0001), and also verified that patients aged >= 42 years had a higher expression of this miR (p=0.013). Logistic regression analysis revealed that the expression of miR-200c-3p and systemic arterial hypertension are factors independently associated with patients in group IV (p<0.0001). Our results suggest that miR-200c-3p is a predictor of severity independent of COVID-19 risk factors, which could represent a way of screening patients affected by SARS-CoV-2.