LARA TERMINI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses(2018) TERMINI, Lara; BOCCARDO, EnriqueIn vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.
- 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.
- Detection of human papillomaviruses and human polyomaviruses in immunosuppressed and immunocompetent individuals with actinic cheilitis: a case series(2019) PIMENTEL, D. R. Neto; NUNES, E. Montosa; TERMINI, L.; NUNES, R. Almeida Lima; LOPEZ, R. V. Mendoza; FERREIRA, S.; BOCCARDO, E.; PRADO, J. C. Mann; ENOKIHARA, M. M. S. S.; SICHERO, L.; TOMIMORI, J.
conferenceObject Study of superoxide dismutase-2 protein in HPV-mediated cell transformation.(2018) SILVA, Gabriela Avila Fernandes; NUNES, Rafaella Almeida Lima; BOCCARDO, Enrique; VILLA, Luisa Lina; TERMINI, Lara- Evaluation of Elafin Immunohistochemical Expression as Marker of Cervical Cancer Severity(2021) LONGATTO-FILHO, Adhemar; FREGNANI, Jose Humberto; COSTA, Allini Mafra da; ARAUJO-SOUZA, Patricia Savio de; SCAPULATEMPO-NETO, Cristovam; HERBSTER, Suellen; BOCCARDO, Enrique; TERMINI, LaraIntroduction: The main risk factor for the development of cervical cancer (CC) is persistent infection by human papillomavirus (HPV) oncogenic types. In order to persist, HPV exhibits a plethora of immune evasion mechanisms. PI3/Elafin (Peptidase Inhibitor 3) is an endogenous serine protease inhibitor involved in epithelial protection against pathogens. PI3/Elafin's role in CC is still poorly understood. Materials and Methods: In the present study, we addressed PI3/Elafin protein detection in 123 CC samples by immunohistochemistry and mRNA expression in several datasets available at Gene Expression Omnibus and The Cancer Genome Atlas platforms. Results: We observed that PI3/Elafin is consistently downregulated in CC samples when compared to normal tissue. Most of PI3/Elafin-positive samples exhibited this protein at the plasma membrane. Besides, high PI3/Elafin expression at the cellular membrane was more frequent in in situ stages I + II than in invasive cervical tumor stages III + IV. This indicates that PI3/Elafin expression is gradually lost during the CC progression. Of note, advanced stages of CC were more frequently associated with a more intense PI3/Elafin reaction in the nuclei and cytoplasm. Conclusion: Our results suggest that PI3/Elafin levels and subcellular localization may be used as a biomarker for CC severity.
conferenceObject SOD2 OVEREXPRESSION INDICATES POOR PROGNOSIS IN STAGE IIIB CERVICAL CANCER(2018) VALE, D.; TALARICO, M. C. Ramiro; TERMINI, L.; NUNES, R. Almeida Lima; SILVA, G. Avila Fertnandes; COSTA, L. Bastos Eloy da; ZEFERINO, L. C.conferenceObject Cytokine expression profile in keratinocytes transduced with HPV oncogenes(2018) NUNES, Rafaella Almeida Lima; SILVA, Gabriela Avila Fernandes; FERREIRA, Silvaneide Aparecida; SICHERO, Laura; VILLA, Luisa Lina; BOCCARDO, Enrique; TERMINI, Lara- Diacerein: A potential multi-target therapeutic drug for COVID-19(2020) OLIVEIRA, Pedro Goncalves de; TERMINI, Lara; DURIGON, Edison Luiz; LEPIQUE, Ana Paula; SPOSITO, Andrei C.; BOCCARDO, EnriqueSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-alpha, NF-kappa B and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-kappa B signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection.
- 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 Dano ao DNA, mecanismos de reparo e câncer(2022) PEREIRA, Gláucia Fernanda de Lima; TERMINI, Lara