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
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- 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.
- 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.
- 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.
- Oncogenic potential diverge among human papillomavirus type 16 natural variants(2012) SICHERO, Laura; SIMAO SOBRINHO, Joao; VILLA, Luisa LinaWe compared E6/E7 protein properties of three different HPV-16 variants: AA. E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.
article 13 Citação(ões) na Scopus Concordance of Beta-papillomavirus across anogenital and oral anatomic sites of men: The HIM Study(2017) NUNES, Emily M.; LOPEZ, Rossana V. M.; SUDENGA, Staci L.; GHEIT, Tarik; TOMMASINO, Massimo; BAGGIO, Maria L.; FERREIRA, Silvaneide; GALAN, Lenice; SILVA, Roberto C.; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; VILLA, Luisa L.; SICHERO, LauraWe evaluated the concordance between beta-HPVs detected in external genital skin, anal canal, and oral cavity specimens collected simultaneously from 717 men that were participating in the multinational HIM Study. Viral genotyping was performed using the Luminex technology. Species- and type-specific concordance was measured using kappa statistics for agreement. Overall, concordance of P-HPVs across sites was low and mainly observed among paired genital/anal canal samples. When grouped by species, solely beta-4 HPVs showed moderate concordance in genital/anal pairs (k = 0.457), which could be attributed to the substantial concordance of HPV-92 in men from Brazil and Mexico (k > 0.610). beta-HPV type concordance was higher in Mexico, where HPV-19 was consistently concordant in all anatomic site combinations. Our analysis indicates that type-specific concordance across sites is limited to few viral types; however, these infections seem to occur more often than would be expected by chance, suggesting that although rare, there is agreement among sites.- Diversity of beta-papillomavirus at anogenital and oral anatomic sites of men: The HIM Study(2016) NUNES, Emily Montosa; SUDENGA, Staci L.; GHEIT, Tarik; TOMMASINO, Massimo; BAGGIO, Maria Luiza; FERREIRA, Silvaneide; GALAN, Lenice; SILVA, Roberto C.; CAMPBELL, Christine M. Pierce; LAZCANO-PONCE, Eduardo; GIULIANO, Anna R.; VILLA, Luisa L.; SICHERO, LauraOur goal was to describe prevalence of P-HPVs at three anatomic sites among 717 men from Brazil, Mexico and US enrolled in the HPV Infection in Men (HIM) Study. beta-HPVs were genotyped using Luminex technology. Overall, 77.7%, 543% and 293% men were positive for any (beta-HPV at the genitals, anal canal, and oral cavity, respectively. Men from US and Brazil were significantly less likely to have beta-HPV at the anal canal than men from Mexico. Older men were more likely to have (beta-HPV at the anal canal compared to younger men. Prevalence of beta-HPV at the oral cavity was significantly associated with country of origin and age. Current smokers were significantly less likely to have beta-HPV in the oral cavity than men who never smoked. Lack of associations between beta-HPV and sexual behaviors may suggest other routes of contact such as autoinoculation which need to be explored further.
- The Asian-American variant of human papillomavirus type 16 exhibits higher activation of MAPK and PI3K/AKT signaling pathways, transformation, migration and invasion of primary human keratinocytes(2016) HOCHMANN, Jimena; SOBRINHO, Joao S.; VILLA, Luisa L.; SICHERO, LauraAsian-American (AA) HPV-16 variants are associated with higher risk of cancer. Abnormal activation of intracellular signaling play a critical role in cancer development and progression. Our aim was to elucidate mechanisms underlying the higher oncogenic potential attributed to AA variant. We evaluated activation of MAPK and PI3K/AKT pathways in primary human keratinocytes (PHKs) transduced with E6/E7 of three HPV-16 variants: E-P, AA, E-350G. Phenotypes examined included migration, anchorage independent growth and invasion. AA PHKs presented the highest levels of active proteins involved in all cascades analyzed: MAPK-ERK, MAPK-p38 and PI3K-AKT. AA PHKs were more efficient in promoting anchorage independent growth, and in stimulating cell migration and invasion. MEK1 inhibition decreased migration. The mesenchymal phenotype marker vimentin was increased in AA PHKs. Our results suggest that MEK1, ERK2, AKT2 hyperactivation influence cellular behavior by means of GSK-3b inactivation and EMT induction prompting AA immortalized PHKs to more efficiently surpass carcinogenesis steps.