LAURA CRISTINA SICHERO VETTORAZZO
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
62 resultados
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- 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.
- Human papillomavirus type 57 in generalized verrucosis without immunodeficiency(2013) ARAUJO, Fernanda Mendes; GON, Airton dos Santos; SICHERO, Laura; SIMAO SOBRINHO, Joao
- Human papillomavirus type 18 E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state(2020) HOCHMANN, Jimena; PARIETTI, Felipe; MARTINEZ, Jennyfer; LOPEZ, Ana C.; CARRENO, Mara; QUIJANO, Celia; BOCCARDO, Enrique; SICHERO, Laura; MOLLER, Matias N.; MIRAZO, Santiago; ARBIZA, JuanBACKGROUND High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins (E5, E6, and E7) that possess a high transformation potential in culture cells when transduced simultaneously. In the present study, we analysed how these oncoproteins cooperate to boost key cancer cell features such as uncontrolled cell proliferation, invasion potential, and cellular redox state imbalance. Oxidative stress is known to contribute to the carcinogenic process, as reactive oxygen species (ROS) constitute a potentially harmful by-product of many cellular reactions, and an efficient clearance mechanism is therefore required. Cells infected with HR-HPVs can adapt to oxidative stress conditions by upregulating the formation of endogenous antioxidants such as catalase, glutathione (GSH), and peroxiredoxin (PRX). OBJECTIVES The primary aim of this work was to study how these oncoproteins cooperate to promote the development of certain cancer cell features such as uncontrolled cell proliferation, invasion potential, and oxidative stress that are known to aid in the carcinogenic process. METHODS To perform this study, we generated three different HaCaT cell lines using retroviral transduction that stably expressed combinations of HPV-18 oncogenes that included HaCaT E5-18, HaCaT E6/E7-18, and HaCaT E5/E6/E7-18. FINDINGS Our results revealed a statistically significant increment in cell viability as measured by MTT assay, cell proliferation, and invasion assays in the cell line containing the three viral oncogenes. Additionally, we observed that cells expressing HPV-18 E5/E6/E7 exhibited a decrease in catalase activity and a significant augmentation of GSII and PRX1 levels relative to those of E5, E6/E7, and HaCaT cells. MAIN CONCLUSIONS This study demonstrates for the first time that HPV-18 E5, E6, and E7 oncoproteins can cooperate to enhance malignant transformation.
- Cutaneous human papillomayirus types detected on the surface of male external genital lesions: A case series within the HPV Infection in Men Study(2013) CAMPBELL, Christine M. Pierce; MESSINA, Jane L.; STOLER, Mark H.; JUKIC, Drazen M.; TOMMASINO, Massimo; GHEIT, Tarik; ROLLISON, Dana E.; SICHERO, Laura; SIRAK, Bradley A.; INGLES, Donna J.; ABRAHAMSEN, Martha; LU, Beibei; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.Background: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta []-HPV in male genital skin or external genital lesions (EGLs) Objectives: To examine cutaneous beta-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. Study design: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Results: beta-HPV DNA was detected on 61.1% of all EGLs, with types 38(16.7%), 5(15.3%), and 12(12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of beta-HPV types detected on condylomas. Most beta-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. Conclusions: EGLs and the normal genital skin of men harbor a large number of beta-HPV types; however, it appears that beta-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.
- Role of microRNAs in a panel of human cervical cancer cell lines(2020) CAUSIN, R. L.; NUNES, M. R.; SILVA, L. S. da; FREITAS, A. J. A. de; CARVALHO, A. C.; SICHERO, L. C.; VILLA, L. L.; SILVA, V. A. O.; REIS, R. M. V.; MARQUES, M. M. C.
- The contribution of Latin American research to HPV epidemiology and natural history knowledge(2020) SICHERO, L.; PICCONI, M. A.; VILLA, L. L.Our aim was to review the major contributions of studies conducted in different Latin American (LA) countries to the field of human papillomavirus (HPV) epidemiology, natural history, risk of disease, and prevention strategies, mainly in the uterine cervix. Although cytological screening is established in several countries in LA, incidence and mortality rates from cervical cancer (CC) are still extremely high. Finally, data from large cohort studies conducted in LA countries provided seminal data to propose primary and secondary prevention modalities: the HPV vaccine has been introduced in the national immunization programs of several LA countries and multiple screening experiences using HPV testing are under evaluation in the region.
- Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study(2016) CAMPBELL, Christine M. Pierce; GHEIT, Tarik; TOMMASINO, Massimo; LIN, Hui-Yi; TORRES, B. Nelson; MESSINA, Jane L.; STOLER, Mark H.; ROLLISON, Dana E.; SIRAK, Bradley A.; ABRAHAMSEN, Martha; SILVA, Roberto J. Carvalho da; SICHERO, Laura; VILLA, Luisa L.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.Background: Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. Methods: In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. Results: While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Conclusions: Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. (C) 2016 Published by Elsevier Inc.
- Epidemiology and biology of cutaneous human papillomavirus(2018) NUNES, Emily M.; TALPE-NUNES, Valeria; SICHERO, LauraCutaneous human papillomaviruses (HPVs) include beta- and gamma-HPVs, in addition to a small fraction of alpha-HPVs. beta-HPVs were first isolated from patients with the rare genetic disorder Epidermodysplasia verruciformis, and they are associated with the development of nonmelanoma skin cancer at sun-exposed skin sites in these individuals. Organ transplant recipients also have greater susceptibility to beta-HPV infection of the skin and an increased risk of developing nonmelanoma skin cancer. In both immunosuppressed and immunocompromised individuals, cutaneous HPVs are ubiquitously disseminated throughout healthy skin and may be an intrinsic part of the commensal flora. Functional analysis of E6 and E7 proteins of specific cutaneous HPVs has provided a mechanistic comprehension of how these viruses may induce carcinogenesis. Nevertheless, additional research is crucial to better understand the pathological implications of the broad distribution of these HPVs.
- E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes(2021) NUNES, Emily Montosa; TALPE-NUNES, Valeria; SOBRINHO, Joao Simao; FERREIRA, Silvaneide; LINO, Vanesca de Souza; TERMINI, Lara; SILVA, Gabriela Avila Fernandes; BOCCARDO, Enrique; VILLA, Luisa Lina; SICHERO, LauraIt is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants' functions, the few studies reported focus on E6, and none were performed using natural host cells. Here, we immortalized primary human keratinocytes (PHKs) with E6/E7 of HPV-18 A1 and B1 sublineages and functionally characterized these cells. PHK18A1 reached immortalization significantly faster than PHK18B1 and formed a higher number of colonies in monolayer and 3D cultures. Moreover, PHK18A1 showed greater invasion ability and higher resistance to apoptosis induced by actinomycin-D. Nevertheless, no differences were observed regarding morphology, proliferation after immortalization, migration, or epithelial development in raft cultures. Noteworthy, our study highlights qualitative differences among HPV-18 A1 and B1 immortalized PHKs: in contrast to PHK18A1, which formed more compact colonies and spheroids of firmly grouped cells and tended to invade and migrate as clustered cells, morphologically, PHK18B1 colonies and spheroids were looser, and migration and invasion of single cells were observed. Although these observations may be relevant for the association of these variants with cervical cancer of different histological subtypes, further studies are warranted to elucidate the mechanisms behind these findings.
- Broad HPV distribution in the genital region of men from the HPV infection in men (HIM) study(2013) SICHERO, Laura; CAMPBELL, Christine M. Pierce; FERREIRA, Silvaneide; SOBRINHO, Joao S.; BAGGIO, Maria Luiza; GALAN, Lenice; SILVA, Roberto C.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; VILLA, Luisa L.The HPV infection in men (HIM) study examines the natural history of genital HPV infection in men. Genotyping methods used in this study identify 37 alpha-HPV types; however, the viral type could not be identified in approximately 22% of male genital specimens that were HPV PCR positive. Our aim was to genotype HPV-unclassified specimens by sequencing PGMY09/11, GP5+/6+ or FAP59/64 PCR products. Using this approach we were able to detect 86 unique HPV types among 508 of 931 specimens analyzed. We report for the first time the presence of a broad range of alpha-, beta- and gamma-HPV at the male genitals.