PAULO FRANCISCO RAMOS MARGARIDO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina - Docente
SCGINEC-62, Hospital Universitário
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
SCGINEC-62, Hospital Universitário
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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bookPart Sangramento uterino anormal na adolescência - conceito, classificação e manejo sindrômico(2021) MARGARIDO, Paulo Francisco Ramos; OLIVEIRA, Vanessa Heinrich Barbosa de; ALMEIDA, José Alcione Macedo- 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 multicenter, randomized trial comparing pelvic organ prolapse surgical treatment with native tissue and synthetic mesh: A 5-year follow-up study(2020) SILVEIRA, Simone dos Reis B. da; AUGE, Antomio P. F.; JARMY-DIBELLA, Zsuzsanna I. K.; MARGARIDO, Paulo F. R.; CARRAMAO, Silvia; RODRIGUES, Claudinei Alves; DOUMOUCHTSIS, Stergios K.; BARACAT, Edmund Chada; HADDAD, Jorge MilhemIntroduction The aim of this study was to compare long-term outcomes in patients who underwent either native tissue repair or monofilament macroporous polypropylene mesh. Methods This multicenter, randomized trial included-at the end of 5 years follow-up-122 women with severe pelvic organ prolapse, who were randomly assigned to undergo surgical treatment using native tissue repair (native tissue group, n = 59) or synthetic mesh repair (mesh group, n = 63). Cure criterion was when pelvic organ prolapse-quantification (POP-Q) point was <= 0. Quality of life was assessed using the prolapse quality-of-life questionnaire and sexual function with the quality of sexual function. Results Groups were homogeneous preoperatively with the exception of the previous pelvic surgery variable, which was higher in mesh (P = .019). Cure rate was significantly better for mesh group in the anterior compartment (P = .002) and in the combination of all compartments (P = .001). Native tissue group was significantly better when there was prolapse in the posterior and apical compartment (P = .031). In the quality of life analysis, mesh group showed a significant improvement compared with native tissue group (P = .004). Complications were significantly higher in mesh and recurrence in native tissue. Regarding the reoperation rate, there was no difference between groups, but native tissue had a higher reoperation rate due to recurrence (P = .031). Conclusions Outcomes in women with severe POP were better with mesh use than native tissue repair, both in the anterior compartment and in the multicompartmental prolapse after 5-year follow-up. Complications were more common in the mesh group and recurrences were more frequent in the native tissue group.
bookPart Anticoncepção e doenças tromboembólicas(2016) MARGARIDO, Paulo Francisco Ramos; MELO, Nilson Roberto de- Abnormal uterine bleeding and chronic iron deficiency Number 11-December 2022(2022) BARROS, Venina Viana de; HASE, Eliane Azeka; SALAZAR, Cristiano Caetano; IGAI, Ana Maria Kondo; ORSI, Fernanda Andrade; MARGARIDO, Paulo Francisco Ramos
- 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.
article 6 Citação(ões) na Scopus Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study(2011) MARGARIDO, P. F. R.; BAGNOLI, V. R.; FONSECA, A. Maggio da; MACIEL, G. A. R.; SOARES JR., J. M.; D'AMICO, E. A.; BARACAT, E. C.Objective: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17 beta estradiol. Methods: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the a angle), clot tensile strength (MA and G), global index of coagulation (Cl) and fibrinolysis (LY30) and fibrinogen levels. Results: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. Conclusions: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in FIT women.- Human Adipose Tissue Derived Pericytes Increase Life Span in Utrn(tm1Ked) Dmd(mdx)/J Mice(2014) VALADARES, M. C.; GOMES, J. P.; CASTELLO, G.; ASSONI, A.; PELLATI, M.; BUENO, C.; CORSELLI, M.; SILVA, H.; BARTOLINI, P.; VAINZOF, M.; MARGARIDO, P. F.; BARACAT, E.; PEAULT, B.; ZATZ, M.Duchenne muscular dystrophy (DMD) is still an untreatable lethal X-linked disorder, which affects 1 in 3500 male births. It is caused by the absence of muscle dystrophin due to mutations in the dystrophin gene. The potential regenerative capacity as well as immune privileged properties of mesenchymal Stem Cells (MSC) has been under investigation for many years in an attempt to treat DMD. One of the questions to be addressed is whether stem cells from distinct sources have comparable clinical effects when injected in murine or canine muscular dystrophy animal models. Many studies comparing different stem cells from various sources were reported but these cells were obtained from different donors and thus with different genetic backgrounds. Here we investigated whether human pericytes obtained from 4 different tissues (muscle, adipose tissue, fallopian tube and endometrium) from the same donor have a similar clinical impact when injected in double mutant Utrn(tm1Ked) Dmd(mdx)/J mice, a clinically relevant model for DMD. After a weekly regimen of intraperitoneal injections of 106 cells per 8 weeks we evaluated the motor ability as well as the life span of the treated mice as compared to controls. Our experiment showed that only adipose tissue derived pericytes are able to increase significantly (39 days on average) the life span of affected mice. Microarray analysis showed an inhibition of the interferon pathway by adipose derived pericytes. Our results suggest that the clinical benefit associated with intraperitoneal injections of these adult stem cells is related to immune modulation rather than tissue regeneration.
- Referral gynecological ambulatory clinic: principal diagnosis and distribution in health services(2018) SILVA, Adna Thaysa Marcial da; MENEZES, Camila Lohmann; SANTOS, Edige Felipe de Sousa; MARGARIDO, Paulo Francisco Ramos; SOARES JR., Jose Maria; BARACAT, Edmund Chada; ABREU, Luiz Carlos de; SORPRESO, Isabel Cristina EspositoBackground: The association between gynecological diagnoses and their distribution in the health sectors provides benefits in the field of women's health promotion and in medical and interdisciplinary education, along with rationalization according to level of care complexity. Thus, the objective is analyze the clinical-demographic characteristics, main diagnoses in gynecological ambulatory care, and their distribution in health services. Method: This is a research project of retrospective audit study design with a chart review of data from 428 women treated at University Ambulatory Clinic of Women's Health, the facility in gynecology and training for Family and Community Medical Residents, Sao Paulo, Brazil, from 2012 to 2014. Clinical and demographic information, gynecological diagnoses (International Classification of Diseases), and distribution of health services (primary, secondary, and tertiary) were described. Results: The female patients present non-inflammatory disorders of the female genital tract (81.07%, n = 347) and diseases of the urinary system (22.66%, n = 97) among the gynecological diagnoses. The chances of having benign breast disease and non-inflammatory disorders of the female genital tract during the reproductive period corresponds to being 3.61 (CI 1.00-16.29) and 2.56 times (CI 1.58-4.16) higher, respectively, than during the non-reproductive period. The noninflammatory disorders of the female genital tract (93.33%, n = 28) are most related to the tertiary sector. The distribution in health services was the following: 71.30% (n = 305) in the primary sector, 21.70% (n = 93) in the secondary sector and 7% (n = 30) in the tertiary sector. Conclusion: The studied women presented non-inflammatory disorders of the female genital tract and diseases of the urinary system as determined by gynecological diagnoses. Low-assistance complexity followed in most cases.