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
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Innate immunity and HPV: friends or foes(2018) NUNES, Rafaella Almeida Lima; MORALE, Mirian Galliote; SILVA, Gabriela Avila Fernandes; VILLA, Luisa Lina; TERMINI, LaraMost human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.
- Oxidative stress: therapeutic approaches for cervical cancer treatment(2018) SILVA, Gabriela Avila Fernandes; NUNES, Rafaella Almeida Lima; MORALE, Mirian Galliote; BOCCARDO, Enrique; AGUAYO, Francisco; TERMINI, LaraOBJECTIVES: Oxidative stress results from an imbalance between the generation and elimination of oxidant species. This condition may result in DNA, RNA and protein damage, leading to the accumulation of genetic alterations that can favor malignant transformation. Persistent infection with high-risk human papillomavirus types is associated with inflammatory responses and reactive oxygen species production. In this context, oxidative stress, chronic inflammation and high-risk human papillomavirus can act in a synergistic manner. To counteract the harmful effects of oxidant species, protective molecules, known as antioxidant defenses, are produced by cells to maintain redox homeostasis. In recent years, the use of natural antioxidants as therapeutic strategies for cancer treatment has attracted the attention of the scientific community. This review discusses specific molecules and mechanisms that can act against or together with oxidative stress, presenting alternatives for cervical cancer prevention and treatment.
- Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo(2019) PRATI, Bruna; ABJAUDE, Walason da Silva; TERMINI, Lara; MORALE, Mirian; HERBSTER, Suellen; LONGATTO-FILHO, Adhemar; NUNES, Rafaella Almeida Lima; CAMACHO, Lizeth Carolina Cordoba; RABELO-SANTOS, Silvia Helena; ZEFERINO, Luiz Carlos; AGUAYO, Francisco; BOCCARDO, EnriqueAlterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identified 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly affects tumor cells clonogenic and anchorage independent growth potential. We showed that this effect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression.
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, LaraconferenceObject 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- 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.
- High Expression of SOD2 Protein Is a Strong Prognostic Factor for Stage IIIB Squamous Cell Cervical Carcinoma(2021) TALARICO, Maria Cecilia Ramiro; NUNES, Rafaella Almeida Lima; SILVA, Gabriela Avila Fernandes; COSTA, Larissa Bastos Eloy da; CARDOSO, Marcella Regina; ESTEVES, Sergio Carlos Barros; SARIAN, Luis Otavio Zanatta; ZEFERINO, Luiz Carlos; TERMINI, LaraHigh superoxide dismutase 2 (SOD2) expression is associated with a poor prognosis at many cancer sites, the presence of metastases, and more advanced cervical cancer. This study aims to determine whether SOD2 protein expression is associated with the prognosis of stage IIIB cervical carcinoma. Methods: sixty-three patients with stage IIIB squamous cell cervical carcinoma were included. The evaluation of SOD2 expression by immunohistochemistry was based on a positive cell ratio score and the staining intensity score. Taking disease recurrence and death as endpoints, receiver operating characteristic curves were used to discriminate between high and low SOD2 expression. Results: high SOD2 expression was associated with recurrence (p = 0.001), distant recurrence (p = 0.002), and death (p = 0.005). A multivariate analysis showed that patients with high SOD2 expression had a threefold increased risk for recurrence (HR = 3.16; 1.33-7.51) and death (HR = 2.98; 1.20-7.40) compared with patients who had low SOD2 expression. Patients with high SOD2 expression had shorter disease-free survival (p = 0.001) and overall survival (p = 0.003) than patients with low SOD2 expression. Conclusion: high SOD2 expression is a strong prognostic factor for stage IIIB squamous cell carcinoma of the cervix and could be used as a prognostic marker in women with cervical carcinoma.