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
46 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 46
- 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.
- 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.
- 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.
- Nucleotide and phylogenetic analysis of human papillomavirus types 6 and 11 isolated from recurrent respiratory papillomatosis in Brazil(2013) MATOS, Renata Prandini Adum de; SICHERO, Laura; MANSUR, Isabela Mazuco; BONFIM, Caroline Measso do; BITTAR, Cintia; NOGUEIRA, Rodrigo Lacerda; KUEPPER, Daniel Salgado; VALERA, Fabiana Cardoso Pereira; NOGUEIRA, Mauricio Lacerda; VILLA, Luisa Lina; CALMON, Marilia Freitas; RAHAL, PaulaThere are few studies about the distribution of natural molecular variants of low-risk HPVs. Our aim was to evaluate the E6 early gene variability among HPV-6 and HPV-11 isolates detected in recurrent respiratory papillomatosis (RRP) samples obtained in a cohort of Brazilian patients. We also performed a phylogenetic analysis in order to compare nucleotide sequences identified in our study with previously reported isolates from different anatomic sites (laryngeal papillomas, genital warts, cervical cancer and anal swabs) obtained from other parts of the world to determine the phylogenetic relationships of variants detected in Brazil. The complete coding region of the E6 gene of 25 samples was cloned and sequenced: 18 isolates of HPV-6 (72%) and 7 isolates of HPV-11 (28%). A total of four different HPV-6 genomic variants and two HPV-11 genomic variants was identified. It was not possible to correlate specific variants with disease severity. Phylogenetic trees for both HPV types were constructed enclosing both E6 sequences detected in our study and formerly published sequences. In both phylogenetic trees, the sequences from Brazil did not group together. We could not establish a geographical association between HPV-6 or HPV-11 variants, unlike HPV-16 and HPV-18.
- Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16(INK4a) status(2022) SICHERO, Laura; TAGLIABUE, Marta; MOTA, Giana; FERREIRA, Silvaneide; NUNES, Rafaella A. L.; CASTANEDA, Carlos Arturo; CASTILLO, Miluska; CORREA, Rita Mariel; PERDOMO, Sandra; RODRIGUEZ-URREGO, Paula A.; MATOS, Leandro Luongo; MOHSSEN, Ansarin; GHEIT, Tarik; TOMMASINO, Massimo; CHIOCCA, Susanna; VILLA, Luisa LinaBackground Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16(INK4a) in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru. Methods HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16(INK4a) immunohistochemistry. Results HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16(INK4a) positivity were observed among HPV positive OPC/OCC cases compared to LC cases. Conclusions Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.
- HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines(2016) CALMON, Marilia Freitas; SICHERO, Laura; BOCCARDO, Enrique; VILLA, Luisa Lina; RAHAL, PaulaAnnexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and 03 cells co-transduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis.