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
67 resultados
Resultados de Busca
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- Factors associated with HPV and other self-reported STI coinfections among sexually active Brazilian young adults: cross-sectional nationwide study(2019) KOPS, Natalia Luiza; BESSEL, Marina; HORVATH, Jaqueline Driemeyer Correia; DOMINGUES, Carla; SOUZA, Flavia Moreno Alves de; BENZAKEN, Adele Schwartz; PEREIRA, Gerson Fernando Mendes; MARANHAO, Ana Goretti Kalume; VILLA, Luisa Lina; MELLO, Barbara; WENDLAND, Eliana MarciaObjectives To analyse factors associated with genital human papillomavirus (HPV) and other self-reported sexually transmitted infection (STI) coinfections among women and men aged 16-25 years from Brazil. Design A cross-sectional, nationwide, multicentre study. Setting 119 primary healthcare centres between September 2016 and November 2017. Participants 6388 sexually active young adults were enrolled by trained health professionals. Primary outcome measure Genital HPV and other self-reported STI coinfections. Results Of 3512 participants with valid data for genital HPV and (STI)-positive status, 276 (9.60%, 95%61 7.82% to 11.36%) had HPV/STI coinfection. Among men, HPV/STI coinfection was more prevalent than HPV infection alone. Among HPV-positive participants, the percentage of subjects who reported having another STI was highest for gonorrhoea at 4.24% (95% CI 2.67% to 5.81%), followed by syphilis, herpes and HIV. Smoking, drug use and ever having a same-sex sexual experience were risk factors that were uniquely associated with HPV/STI coinfection compared with HPV infection alone. Conclusions The results identified a low prevalence of self-reported STIs, but in participants with at least one STI, the prevalence of HPV was high. These results reinforce the importance of implementing strategies to prevent risky behaviours among Brazilian young adults.
- HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS(2019) CABECA, Tatiane Karen; ABREU, Alice de Mello; ANDRETTE, Rafael; LINO, Vanesca de Souza; MORALE, Mirian Galliote; AGUAYO, Francisco; TERMINI, Lara; VILLA, Luisa Lina; LEPIQUE, Ana Paula; BOCCARDO, EnriquePersistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we characterized the response to the individual and combined action of the pro-inflammatory cytokines tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL) on HPV-transformed cells and human keratinocytes ectopically expressing E6 and E7 early proteins from different HPV types. We showed that keratinocytes expressing HPV early proteins exhibited global alterations in the expression of proteins involved in apoptosis regulation/execution, including TNF and TRAIL receptors. Besides, we provided evidence that TNF receptor 1 (TNFR1) was down-regulated and may be retained in the cytoplasm of keratinocytes expressing HPV16 oncoproteins. Finally, fluorescence analysis demonstrated that cytokine treatment induced the production and release of reactive oxygen and nitrogen species (ROS/RNS) in cells expressing HPV oncogenes. Alterations in ROS/RNS production and apoptosis regulatory factors expression in response to inflammatory mediators may favor the accumulation of genetic alterations in HPV-infected cells. Altogether, our results suggested that these events may contribute to lesion progression and cancer onset.
- Oral HPV prevalence assessment by Linear Array vs. SPF10 PCR-DEIA-LiPA(25) system in the HPV Infection in Men (HIM) study(2020) BETTAMPADI, Deepti; SIRAK, Bradley A.; FULP, William J.; ABRAHAMSEN, Martha; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; SALMERON, Jorge; ISAACS-SORIANO, Kimberly A.; BAGGIO, Maria L.; TRENADO, Manuel Quiterio; GIULIANO, Anna R.Introduction: Oral human papillomavirus (HPV) attributable oropharyngeal cancers are on the rise in many countries. Oral HPV infections among healthy individuals are commonly detected using oral gargle samples. However, the optimal method for HPV genotyping oral gargle specimens in research studies has not been previously evaluated. Materials and methods: Oral gargle samples from 1455 HPV Infection in Men (HIM) study participants were HPV genotyped using two different methods: Linear Array and the SPF10 PCR-DEIA-LiPA(25). The sensitivity of the two tests for detecting individual HPV types and grouped HPV types, high-risk HPV, low-risk HPV, grouped 4-HPV-vaccine types, and grouped 9-HPV-vaccine-types, and the degree of concordance between the two tests was assessed. We also examined whether socio-demographic-behavioral factors were associated with concordance between the two assays. Results: The sensitivity of SPF10 PCR-DEIA-LiPA(25) was higher than Linear Array, with the exception of HPV 70, for the detection of oral HPV. The prevalence ratio of SPF10 PCR-DEIA-LiPA(25) to Linear Array varied between 1.0 and 9.0 for individual HPV genotypes, excluding HPV 70, and between 3.8 and 4.4 for grouped 4-valent and 9-valent HPV vaccine types, respectively. There was no association between socio-demographic-behavioral factors and discordance in results between the two tests for oral HPV 16 detection. Discussion: SPF10 PCR-DEIA-LiPA(25) was more sensitive than Linear Array for detecting HPV in oral gargle samples. Given the growing importance of detecting oral HPV infection for research studies of oral HPV natural history and vaccine effectiveness evaluation, we recommend using methods with higher sensitivity such as SPF10 PCR-DEIA-LiPA(25) for detecting HPV in oral gargle samples.
- Co-infection of sexually transmitted pathogens and Human Papillomavirus in cervical samples of women of Brazil(2017) AMORIM, Aline Teixeira; MARQUES, Lucas Miranda; CAMPOS, Guilherme Barreto; LOBAO, Tassia Neves; LINO, Vanesca de Souza; CINTRA, Ricardo Cesar; ANDREOLI, Maria Antonieta; VILLA, Luisa Lina; BOCCARDO, Enrique; BRAGA JUNIOR, Antonio Carlos Ricardo; LOPEZ, Rossana Veronica Mendoza; SANTOS, Djanilson Barbosa dos; SOUZA, Gerson Maciel de; ROMANO, Carla Cristina; TIMENETSKY, JorgeBackground: Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, the aim of this study was to determine any association between the presence of microorganisms of gynecological importance, sexual behavior, clinical and demographical variables to the development and progress of cervical lesions. Methods: One hundred and thirty-two women between 14 and 78 years and living at Vitoria da Conquista, Bahia, Brazil, were included (62 individuals with cervical lesions and 70 without lesions). They answered a questionnaire to provide data for a socioeconomic and sexual activity profile. Samples of cervical swabs were collected and analyzed by PCR to detect genital microorganisms and HPV. Quantitative PCR was used to detect and quantify Ureaplasma urealyticum and Ureaplasma parvum. Univariate and multiple logistic regression were performed to measure the association with the cervical lesions, and an odds ratio (OR) with 95% confidence intervals (95% CI) were calculated. The Mann-Whitney U test was also used to compare the microorganism load in the case and control groups. The significance level was 5% in all hypotheses tested. Results: Cervical lesions were associated with: women in a stable sexual relationship (OR = 14.21, 95% CI = 3.67-55.018), positive PCR for HPV (OR = 16.81, 95% CI = 4.19-67.42), Trichomonas vaginalis (OR = 8.566, 95% CI = 2.04-35.94) and Gardnerella vaginalis (OR = 6.13, 95% CI = 1.53-24.61), adjusted by age and qPCR for U. parvum. U. parvum load showed a statistical difference between the case and control groups (p-value = 0.002). Conclusion: Variables such as stable relationship, HPV, T. vaginalis, G. vaginalis were associated with cervical lesions in epidemiological studies. U. parvum load was higher in woman with cervical lesions compared with women without lesions. Additional studies are needed to better understand the role of these factors in cervical lesion development.
- HPV infection and cervical neoplasia: associated risk factors(2015) RIBEIRO, Andrea Alves; COSTA, Maria Cecilia; ALVES, Rosane Ribeiro Figueiredo; VILLA, Luisa Lina; SADDI, Vera Aparecida; CARNEIRO, Megmar Aparecida dos Santos; ZEFERINO, Luiz Carlos; RABELO-SANTOS, Silvia HelenaBackground: Behavioral risks such as age at first sexual intercourse, number of sexual partners and partner's sexual behavior are associated with an increased risk of HPV infection, persistence of the infection and the development of neoplastic precursor lesions. The objective of this study was to evaluate the risk factors associated with HPV positivity and with a diagnosis of cervical neoplasia in women referred with an abnormal cervical smear. Methods: This study evaluated a series of 198 women referred with an abnormal cervical smear. Risk factors for HPV infection were investigated using a questionnaire. All cervical specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay. Results: The overall prevalence of HPV was 87 %. First sexual intercourse before 16 years of age was significantly associated with a positive HPV test (OR 4.41; 95 % CI: 1.20 - 19.33; p = 0.01). A significant association was also found between this risk factor and CIN 1 lesions or worse (OR 2.2; 95 % CI 0.94 - 5.08; p = 0.03). Conclusions: The age at which a woman begins to be sexually active is associated with HPV infection and with a diagnosis of cervical neoplasia.
- TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line(2022) MORALE, Mirian Galliote; TAMURA, Rodrigo Esaki; CINTRA, Ricardo; ARAUJO, Natalia Meneses; VILLA, Luisa LinaHuman Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidates for contributing to the development of HPV-induced tumors. Here, we studied the receptor TLR4 and the adaptor molecule SARM1 in HeLa cells, an HPV-positive cervical cancer cell line. Knocking out of these genes individually proved to be important for maintaining cell viability and proliferation. TLR4 knock out cells were more sensitive to cisplatin treatment, which was illustrated by an increased frequency of apoptotic cells. Furthermore, TLR4 and SARM1 modulated ROS production, which was induced by cell death in response to cisplatin. In conclusion, TLR4 and SARM1 are important for therapy resistance and cervical cancer cell viability and may be relevant clinical targets.
- Effectiveness of a universal vaccination program with an HPV quadrivalent vaccine in young Brazilian women(2021) WENDLAND, Eliana M.; KOPS, Natalia Luiza; BESSEL, Marina; COMERLATO, Juliana; MARANHAO, Ana Goretti Kalume; SOUZA, Flavia Moreno Alves; VILLA, Luisa Lina; PEREIRA, Gerson Fernando MendesWe examined human papillomavirus (HPV) vaccine effectiveness in a nationwide sample of women aged 16 to 25 years who utilized the public health system in Brazil. This was a cross-sectional, multicentric survey conducted between September 2016 and November 2017 (POP-Brazil Study). A total of 5,945 young adult women were recruited from 119 public primary care units from all 27 federative units of Brazil by trained health professionals. The participants participated in a face-to-face interview and provided biological samples for genital HPV analysis. HPV genotyping was performed using a Linear Array HPV genotyping test in a central laboratory. Sampling weights were applied to the data. Overall, 11.92% (95% CI 10.65, 13.20) of the participants reported having been vaccinated. The frequency of vaccination was highest in 16- to 17-year-old women, with a decreasing vaccination rate with increasing age, and vaccinated women were more likely to belong to the high socioeconomic status group. The use of a quadrivalent vaccine decreased the HPV types 6, 11, 16, and 18 by 56.78%, from 15.64% in unvaccinated women to 6.76% in vaccinated women (P < 0.01), even after adjustment for age. Those who received the vaccine had lower HPV 16 (2.34% in vaccinated vs 8.91% in unvaccinated, P < 0.01) and 6 rates (2.06% vs 5.77%, P < 0.01). Additionally, a higher rate of high-risk HPV types other than HPV 16 and 18 (40.47% in vaccinated vs 32.63% in unvaccinated, P < 0.01) was observed. In conclusion, the results of this study support the effectiveness of HPV vaccination in Brazil. Continuous surveillance must be assured to monitor the HPV infection rate in the vaccination era. (C) 2021 The Author(s).
- 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.