LUISA LINA VILLA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
21 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 21
- Correlation of a microRNA expression profile and the prognosis of penile cancer: A prospective study using microarray data analysis(2018) FURUYA, Tatiane K.; MURTA, Claudio B.; PONTES JR., Jose; UNO, Miyuki; CARRASCO, Alexis; SICHERO, Laura C.; VILLA, Luisa L.; COELHO, Rafael F.; GUGLIELMETTI, Giuliano B.; CORDEIRO, Mauricio D.; LEITE, Katia R.; SROUGI, Miguel; CHAMMAS, Roger; NAHAS, William C.
conferenceObject HPV-positive tumor cell lines exhibit major alterations in Toll-like receptor pathways and depend on HMGB1 expression(2018) MORALE, Mirian Galliote; ABJAUDE, Walason da Silva; SILVA, Aline Montenegro da; VILLA, Luisa Lina; BOCCARDO, Enrique- HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner(2018) RABACHINI, Tatiana; BOCCARDO, Enrique; ANDRADE, Rubiana; PEREZ, Katia Regina; NONOGAKI, Suely; CUCCOVIA, Iolanda Midea; VILLA, Luisa LinaBackground: Human Papillomavirus (HPV) infection is the main risk factor for the development and progression of cervical cancer. HPV-16 E6 and E7 expression is essential for induction and maintenance of the transformed phenotype. These oncoproteins interfere with the function of several intracellular proteins, including those controlling the PI3K/AKT/mTOR pathway in which Phospolipase D (PLD) and Phosphatidic acid (PA) play a critical role. Methods: PLD activity was measured in primary human keratinocytes transduced with retroviruses expressing HPV-16 E6, E7 or E7 mutants. The cytostatic effect of rapamycin, a well-known mTOR inhibitor with potential clinical applications, was evaluated in monolayer and organotypic cultures. Results: HPV-16 E7 expression in primary human keratinocytes leads to an increase in PLD expression and activity. Moreover, this activation is dependent on the ability of HPV-16 E7 to induce retinoblastoma protein (pRb) degradation. We also show that cells expressing HPV-16 E7 or silenced for pRb acquire resistance to the antiproliferative effect of rapamycin. Conclusion: This is the first indication that HPV oncoproteins can affect PLD activity. Since PA can interfere with the ability of rapamycin to bind mTOR, the use of combined strategies to target mTOR and PLD activity might be considered to treat HPV-related malignancies.
- 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.
- 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.
- Human papillomavirus (HPV) 16 E6 oncoprotein targets the Toll-like receptor pathway(2018) OLIVEIRA, Lucas Boeno; HAGA, Ismar R.; VILLA, Luisa LinaCervical cancer is one of the leading causes of death in women worldwide and is etiologically linked to human papillomavirus (HPV) infection. Viral early proteins E6 and E7 manipulate cellular functions to promote the virus life cycle and are essential to the cellular transformation process. The innate immune system plays a pivotal role in the natural history of HPV infection. Among the various proteins that mediate the innate immune response, Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and initiate the immune response. The objective of this study was to identify HPV E6 protein interaction partners in the TLR signalling pathway that may play a role in the immune response against HPV. Six TLR pathway proteins were shown to interact with HPV16 E6: myeloid differentiation primary response protein (MyD88), TIR domain-containing adapter molecule 1 (TRIF), interleukin-1 receptor-associated kinase-like (IRAK) 2, TNF receptor-associated factor (TRAF) 6, I-kappa B kinase beta (IKK beta) and I-kappa B kinase epsilon (IKK epsilon). The interaction site of IKK epsilon with E6 is located in the region containing the enzyme catalytic site, suggesting an influence of E6 on the activation of IKK epsilon target proteins. HPV16 E6 potentiated the activation of NF-kappa B by various TLR pathway members. These results suggest that HPV16 has the ability to interfere with components of the immune response, contributing to HPV carcinogenesis.
- Acquisition, Persistence, and Clearance of Human Papillomavirus Infection Among Male Virgins Residing in Brazil, Mexico, and the United States(2018) LIU, Zhiyue; NYITRAY, Alan G.; HWANG, Lu-Yu; SWARTZ, Michael D.; ABRAHAMSEN, Martha; LAZCANO-PONCE, Eduardo; VILLA, Luisa L.; GIULIANO, Anna R.Background. Little is known about the natural history of human papillomavirus (HPV) infection in male virgins. This study estimated the incidence and clearance of genital HPV infection and the factors associated with these measures among men who denied at baseline ever having penetrative sex. Methods. A cohort of 4123 men residing in Brazil, Mexico, and the United States were followed every 6 months for up to 10 visits. Genital exfoliated cells were collected and genotyped for 36 HPV types. Eighty-seven men were classified as virgins and included for analysis. Cox proportional hazards models identified factors associated with the incidence and clearance of genital HPV infection. Results. The incidence rates for any HPV infection among virgins who did and those who did not initiate sex during follow-up were 26.2 and 14.6 cases/1000 person-months, respectively. After penetrative sex initiation, 45.5% of men acquired HPV within 24 months. Younger age, current smoking, no recent female sex partners, and prevalent HPV infection were associated with high-risk HPV clearance. Conclusion. Virgins who did not initiate sex during follow-up still acquired HPV infection, possibly through nonpenetrative sexual contact. Further prospective cohort studies are needed to better understand factors associated with HPV acquisition and clearance in male virgins and recent nonvirgins.
conferenceObject Upregulation of IDO in bacterial vaginosis: Role in HPV coinfection.(2018) VENANCIO, Paloma Almeida; MARIA-ENGLER, Silvya Stuchi; CONSOLARO, Marcia Edilaine Lopes; VILLA, Luisa Lina; DERCHAIN, Sophie Francoise; CAMPA, Ana; DISCACCIATI, Michelle Garcia- Influence of Prior Knowledge of Human Papillomavirus Status on the Performance of Cytology Screening(2018) MARTINS, Toni Ricardo; LONGATTO-FILHO, Adhemar; COHEN, Diane; VISCONDI, Juliana Yukari Kodaira; FUZA, Luiz Mario; CURY, Lise; VILLA, Luisa Lina; LEVI, Jose Eduardo; ELUF-NETO, JoseObjectives: This study aimed to evaluate the influence of prior knowledge of human papillomavirus (HPV) status in cervical cytopathology readings. Methods: Participants comprised 2,376 women who underwent parallel cytology and HPV-DNA testing. Smears were read twice by the same team, first with previous knowledge of HPV-DNA status. Results: Overall, 239 (10.2%) smears had their cytology classification altered by the HPV-informed review. Cytology readings with prior knowledge of the HPV status revealed 10.5% of abnormal smears (atypical squamous cells of undetermined significance or higher), while without prior knowledge, this rate dropped to 7.6%. When HPV status was informed, a significant increase in all categories of altered smears was observed. Cytology with prior knowledge of HPV status detected more cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) compared with blinded: 86.7% vs 60.0%. Conclusions: Our data indicate that cytology interpreted with prior knowledge of the HPV status provides higher sensitivity for CIN 2+ lesions while marginally reducing the overall specificity compared with HPV status blinded cytology.
- Specific cell populations from the primary tumor invasive front and lymph nodes show protein signatures associated with local metastasis in head and neck cancer(2018) BUSSO-LOPES, Ariane F.; RIVERA, Cesar; MACEDO, Carolina C.; MELLO, Barbara P.; VILLA, Luisa L.; GONZALEZ-ARRIAGADA, Wilfredo A.; LEME, Adriana F. Paes
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