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
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- 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.
- Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils(2017) ALVAREZ, Karla Lucia Fernandez; BELDI, Mariana; SARMANHO, Fabiane; ROSSETTI, Renata Ariza Marques; SILVEIRA, Caio Raony Farina; MOTA, Giana Rabello; ANDREOLI, Maria Antonieta; CARUSO, Eliana Dias de Carvalho; KAMILLOS, Marcia Ferreira; SOUZA, Ana Marta; MASTROCALLA, Haydee; CLAVIJO-SALOMON, Maria Alejandra; BARBUTO, Jose Alexandre Marzagao; LORENZI, Noely Paula; LONGATTO-FILHO, Adhemar; BARACAT, Edmund; LOPEZ, Rossana Veronica Mendoza; VILLA, Luisa Lina; TACLA, Maricy; LEPIQUE, Ana PaulaCervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.
- The acceptability of vaginal smear self-collection for screening for cervical cancer: a systematic review(2017) BRAZ, Natalia Serrano Doratioto Faria; LORENZI, Noely Paula Cristina; SORPRESO, Isabel Cristina Esposito; AGUIAR, Lana Maria de; BARACAT, Edmund Chada; SOARES-JUNIOR, Jose MariaCervical cancer is a major cause of death in adult women. However, many women do not undergo cervical cancer screening for the following reasons: fear, shame, physical limitations, cultural or religious considerations and lack of access to health care services. Self-collected vaginal smears maybe an alternative means of including more women in cervical cancer screening programs. The objective of this systematic review was to evaluate the acceptability of vaginal smear self-collection for cervical cancer screening. We selected articles from PubMed, the Cochrane Library and Embase that were published between January 1995 and April 2016. Studies written in English, French, Italian, Portuguese or Spanish that involved women between 18 and 69 years of age who had engaged in sexual intercourse were included in this review. The review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Nineteen studies were ultimately evaluated in this review. Most of the included studies (n=17) demonstrated that the self-collection method exhibited outstanding acceptability among women with respect to cervical cancer screening, and only two studies indicated that self-collection exhibited low acceptability among women in this context. The acceptability of self-collection was determined subjectively (without standardized questionnaires) in 10 studies (53%) and via structured and validated questionnaires in the remaining studies. The results of our review suggest that the self-collection method is well-accepted and may therefore encourage greater participation in cervical cancer screening programs. However, additional studies are required to verify these results.
- Age-related acceptability of vaginal self-sampling in cervical cancer screening at two university hospitals: a pilot cross-sectional study(2019) LORENZ, Noely Paula Cristina; TERMINI, Lara; LONGATTO FILHO, Adhemar; TACLA, Maricy; AGUIAR, Lana Maria de; BELDI, Mariana Carmezim; FERREIRA-FILHO, Edson Santos; BARACAT, Edmund Chada; SOARES-JUNIOR, Jose MariaBackground: To determine whether age is a barrier against acceptability of cervicovaginal self-sampling in screening for cervical cancer at two gynecology outpatient clinics. Methods: This is a cross-sectional study involving 116 women over 21 years of age with an abnormal Pap smear. Clinical and laboratorial data were recorded in electronic files. Women received detailed self-collection instructions. After the self-sampling procedure (Evalyn Brush (R)), women were instructed to answer a questionnaire about vaginal self-sampling acceptability that consisted of seven multiple-choice items. The participants were divided into three age brackets: 21 to 29 years, 30 to 49 years, and 50 years and over. Chi-square, Fischer exact, Kolmogorov-Smirnov and Kruskal-Wallis tests were used. Results: The analysis of the participants' perception of the procedure stratified according to age groups showed a decline in the fear of hurting oneself during the procedure as age increased. Most participants reported that it was very easy to understand how to use the self-sampling brush and that it was easy to use it. Most of them were neither embarrassed nor afraid of getting hurt during the procedure. The majority preferred self-sampling to collection by a healthcare professional. The main reason was practicality: the possibility of choosing the place and time for sampling. Conclusions: The participating women found self-collection simple to understand and easy to accept regardless of age. The younger women indicated more fear and discomfort in self-sampling, which points to the need for attraction strategies that are more appealing to the younger generations.
- Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer(2020) ROSSETTI, Renata A. M.; SILVA-JUNIOR, Ildefonso A. da; RODRIGUEZ, Gretel R; ALVAREZ, Karla L. F.; STONE, Simone C.; CIPELLI, Marcella; SILVEIRA, Caio R. F.; BELDI, Mariana Carmezim; MOTA, Giana R.; MARGARIDO, Paulo F. R.; BARACAT, Edmund C.; UNO, Miyuki; VILLA, Luisa L.; CARVALHO, Jesus P.; YOKOCHI, Kaori; ROSA, Maria Beatriz S. F.; LORENZI, Noely P.; LEPIQUE, Ana PaulaCervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NF kappa B, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NF kappa B decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NF kappa B partially reversed these effects. This study indicates that STAT3 and NF kappa B are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer.