NOELY PAULA CRISTINA LORENZI
Projetos de Pesquisa
Unidades Organizacionais
SCGINEC-62, Hospital Universitário
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
15 resultados
Resultados de Busca
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- B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses(2018) ROSSETTI, Renata Ariza Marques; LORENZI, Noely Paula Cristina; YOKOCHI, Kaori; ROSA, Maria Beatriz Sartor de Faria; BENEVIDES, Luciana; MARGARIDO, Paulo Francisco Ramos; BARACAT, Edmund Chada; CARVALHO, Jesus Paula; VILLA, Luisa Lina; LEPIQUE, Ana PaulaImmune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80(+)CD86(+) population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1(-/-) recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.
- Lactate secreted by cervical cancer cells modulates macrophage phenotype(2019) STONE, Simone Cardozo; ROSSETTI, Renata Ariza Marques; ALVAREZ, Karla Lucia Fernandez; CARVALHO, Jesus Paula; MARGARIDO, Paulo Francisco Ramos; BARACAT, Edmund Chada; TACLA, Maricy; BOCCARDO, Enrique; YOKOCHI, Kaori; LORENZI, Noely Paula; LEPIQUE, Ana PaulaCervical cancer continues to be a public health problem in developing countries. Previous studies have shown that cervical cancer cells display markers of aerobic glycolysis, indicating that these tumors are likely to secrete lactate. Mostly, lactate is recognized as a molecule capable of suppressing immune responses, through inhibition of T cells, M phi s, and dendritic cells. We and others have previously shown that M phi s are frequent cells infiltrating cervical cancers with the ability to inhibit antitumor immune responses and promote tumor growth through angiogenesis. Here, we have tested the hypothesis that lactate, secreted by cervical cancer cells, can modulate M phi phenotype. First, we showed higher lactate plasma concentrations in patients with increasing cervical lesion grades, with maximum concentration in the plasma of cancer patients, which supported our hypothesis. We then inhibited lactate production in tumor cell spheroids established from cervical cancer derived cell lines, using the lactate dehydrogenase inhibitor, oxamate, prior to co-culture with monocytes. Lactate mediated part of the crosstalk between tumor cells and M phi s, promoting secretion of IL-1, IL-10, IL-6, and up-regulation of hypoxia induced factor-1 expression, and down-regulation of p65-NFB phosphorylation in M phi s. We also showed that M phi s from co-cultures treated with oxamate were better inducers of T cell activation. Of note, experiments performed with inhibition of the monocarboxylate transporters rendered similar results. Our data confirms the hypothesis that lactate, secreted by cervical tumor cells, influences the phenotype of tumor M phi s, promoting a suppressive phenotype.
- A positive HPV test with positive p16/Ki-67 double staining in self-sampled vaginal material is an accurate tool to detect women at risk for cervical cancer(2022) LORENZI, Noely P. C.; TERMINI, Lara; FERREIRA-FILHO, Edson S.; NUNES, Rafaella A. L.; SILVA, Gabriela A. F.; LEPIQUE, Ana P.; LONGATTO-FILHO, Adhemar; TACLA, Maricy; BARACAT, Edmund C.; VILLA, Luisa L.; SOARES-JUNIOR, Jose M.BACKGROUND: The development of efficient strategies for managing high-risk human papillomavirus (HR-HPV)-positive women is a major challenge when human papillomavirus-based primary screening is being performed. The objectives of this study were to evaluate the comparative effectiveness of HR-HPV testing based on self-collection (SC) and HR-HPV testing based on collection by a health professional (HP) and to assess the potential usefulness of HR-HPV testing combined with testing with the biomarkers p16/Ki-67, alpha-mannosidase, and superoxide dismutase 2 (SOD2). METHODS: This was a cross-sectional study of 232 women admitted for colposcopy because of an abnormal Papanicolaou smear. The collected material underwent liquid-based cytology, HR-HPV detection, and immunocytochemical testing (p16/Ki-67, alpha-mannosidase, and SOD2). The gold standard was the histopathological result; the positive reference was CIN2+. RESULTS: The overall accuracy of HR-HPV testing was 76.6%; the results for the SC group (78.1%) and the HP group (75.2%) were similar. The positive predictive values (HP, 76.5%; SC, 80.0%), the negative predictive values (HP, 66.7%; SC, 64.3%), the positive likelihood values (HP, 1.35; SC, 1.36), and the negative likelihood values (HP, 0.21; SC, 0.19) were also similar. p16/Ki-67 showed higher sensitivity than the other 2 biomarkers: 78.1% versus 45.8% for alpha-mannosidase and 44.5% for SOD2. The specificities of the biomarkers were equivalent: 71.4% for p16/Ki-67, 77.8% for alpha-mannosidase, and 71.2% for SOD2. In the HP group, accuracy also leaned more heavily toward the final score (using alpha-mannosidase and SOD2) without statistical significance (80.8% vs 77.9%). The contrast with the SC group yielded the same level of accuracy. CONCLUSIONS: SC, when associated with testing with biomarkers, is as accurate as collection by HPs in the detection of women at risk for cervical cancer.
bookPart Herpes genital na infância e na adolescência(2021) ROA, Cristiane Lima; LORENZI, Noely Paula Cristina; AGUIAR, Lana Maria de; ALMEIDA, José Alcione MacedobookPart Vulvovaginite na adolescência(2021) ALMEIDA, José Alcione Macedo; ROA, Cristiane Lima; FUKAZAWA, Eiko Ines; LORENZI, Noely Paula Cristina- A New Brazilian Device for Cervical Cancer Screening: Acceptability and Accuracy of Self-sampling(2023) LICHTENFELS, Martina; LORENZI, Noely Paula Cristina; TACLA, Maricy; YOKOCHI, Kaori; FRUSTOCKL, Flavia; SILVA, Camila Alves; SILVA, Andre Luiz da; TERMINI, Lara; FARIAS, Caroline BrunettoObjective To evaluate the accuracy and patient acceptability toward self-sampling using a new device - SelfCervix (R) - for detecting HPV-DNA.Methods A total of 73 women aged 25-65 who underwent regular cervical cancer screening from March to October 2016 were included. Women performed self-sampling followed by a physician-sampling, and the samples were analyzed for HPV-DNA. After that, patients were surveyed about their acceptability of self-sampling.Results HPV-DNA detection rate of self-sampling presented high accuracy and was similar to physician-collection. Sixty-four (87.7%) patients answered the acceptability survey. Most patients (89%) considered the self-sampling comfortable, and 82.5% preferred self-sampling to physician-sampling. The reasons cited were time-saving and convenience. Fifty-one (79.7%) reported that they would recommend self-sampling.Conclusion Self-sampling using the new Brazilian device SelfCervix (R) is not inferior in HPV-DNA detection rate compared with physician-collection, and patients are supportive of the method. Therefore, it might be an option to reach under-screened populations in Brazil.
bookPart Sífilis na infância e na adolescência(2021) LORENZI, Noely Paula Cristina; ROA, Cristiane Lima; AGUIAR, Lana Maria de; ALMEIDA, José Alcione Macedo- RELATION BETWEEN Candida SPECIES ISOLATED FROM VAGINAL MUCOSA AND LESIONS CAUSED BY HIGH-RISK HUMAN PAPILLOMAVIRUS FOR CERVICAL CANCER(2021) SOUZA, A. C. de; PAULA, C. R.; RUIZ, L. da Silva; MARGARIDO, P. F. R.; AULER, M. E.; LORENZI, N. P. C.; MOREIRA, D.; SANTOS, R. L. O. dos; TACLA, M.; MICHEL-CROSATO, E.; DOMANESCHI, C.This study characterized and related yeasts of the genus Candida isolated from vaginal mucous membranes of women with lesions caused by high-risk human Papillomavirus (HPV) for cervical cancer. Forty-two women treated at the Lower Genital Tract Pathology Clinic of the University of São Paulo Medical School Hospital of Clinics were examined, with 30 high-grade (G1) uterine lesions with a mean age of 36.5 years ± 11. 1 and 12 with low grade (G2) uterine lesions with a mean age of 34.7 years ± 15.5. Clinical conditions and laboratory data on HPV were collected from patients’ medical records; the socio-demographic data obtained from an appropriate questionnaire. For the study of association between the variables, Odds Ratio analysis was used from the STATA 13.1 program. Patients G1 had a higher prevalence for diabetes and the results indicated 27% prevalence of Candida spp. in vaginal mucosa, in G2 this was 33% in vaginal mucosa. Among the species found in vaginal mucosa of patients, Candida albicans was the most isolated with 88%, followed by C. tropicalis (8%) and C. glabrata (4%). The strains of C. albicans isolated from mucosa presented sensitivity to all antifungal agents tested, unlike the C. tropicalis strain isolated in G2 in vaginal mucosa, which presented a resistance profile to fluconazole. Thus, monitoring and supervision through clinical and laboratory testing of HPV patients is important, reinforcing the need for care, treatment and prevention of HPV-related infections and Candida spp. © 2021 Brazilian Society of Parasitology. All rights reserved.
- Microbiome and Cervical Cancer(2021) CASTANHEIRA, Cristina Paula; SALLAS, Mayara Luciana; NUNES, Rafaella Almeida Lima; LORENZI, Noely Paula Cristina; TERMINI, LaraPersistent infection with some types of mucosal human papillomavirus (HPV) is the etiological factor for the development of cervical cancer and its precursor lesions. Besides, several cofactors are known to play a role in cervical disease onset and progression either by favoring or by preventing HPV infection and persistence. The microbiome of a healthy female genital tract is characterized by the presence of 1 or few varieties of lactobacilli. However, high-throughput studies addressing the bacterial diversity and abundance in the female genital tract have shown that several factors, including hormonal levels, hygiene habits, and sexually transmitted diseases may disrupt the natural balance, favoring the outgrowth of some groups of bacteria, which in turn may favor some pathological states. Recently, the vaginal microbiome has emerged as a new variable that could greatly influence the natural history of HPV infections and their clinical impact. In this context, changes in the vaginal microbiome have been detected in women infected with HPV and women with HPV-associated lesions and cancer. However, the role of specific bacteria groups in the development/progression or prevention/regression of HPV-associated pathologies is not well understood. In this review we summarize the current knowledge concerning changes in vaginal microbiome and cervical disease. We discuss the potential functional interplay between specific bacterial groups and HPV infection outcomes.
bookPart Infecção pelo HPV na vagina e no colo uterino de adolescentes(2021) LORENZI, Noely Paula Cristina; ROA, Cristiane Lima; AGUIAR, Lana Maria de; ALMEIDA, José Alcione Macedo