RESUMEN
Beta-papillomaviruses (beta-HPV) have been linked to the development of skin cancer in humans. Because both E6 and E7 proteins from beta-HPV have been involved in the potential carcinogenicity of these viruses, we investigated their role on UVB-induced apoptosis in HaCaT cell line. HaCaT cells have been transduced with both E6/E7 using a retroviral system and treated with PRIMA-1. Apoptosis was assessed by flow cytometry to measure mitochondrial membrane potential and DNA fragmentation. HaCat keratinocytes transduced with both E6 and E7 genes of seven beta-HPV types (HPV5, HPV8, HPV14, HPV24, HPV36, HPV38 and HPV49) did not demonstrate any inhibition of UVB-induced apoptosis, even after p53 reactivation through PRIMA-1. Our data suggest that the expression of E6 and E7 exert different modulatory effects on UVB-induced apoptosis according to beta-HPV types and to the cellular genetic context.
Asunto(s)
Apoptosis/efectos de la radiación , Betapapillomavirus/patogenicidad , Queratinocitos/efectos de la radiación , Queratinocitos/virología , Proteínas Oncogénicas Virales/fisiología , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de los fármacos , Compuestos Aza/farmacología , Betapapillomavirus/fisiología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Línea Celular , Cocarcinogénesis , Humanos , Queratinocitos/patología , Neoplasias Cutáneas/etiología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/fisiologíaRESUMEN
Anogenital lesions induced by human papillomaviruses (HPV) are due to both high-risk HPV types involved in carcinogenesis of the cervix (and also, to a lesser extent, of the vulva, anus and vagina) and to low-risk HPV types that cause external genital warts in the perianal region, perineum, vulva and vagina (less often the cervix). Cervical cancer is thus virus-induced, and there is a continuum from intraepithelial lesions to invasive cancer. This offers the opportunity to screen cervical smears for cytological abnormalities or to detect high-risk HPV infection by molecular methods. Although the causal link between human genital papillomavirus infection and cervical neoplasia is well established, the role of beta-HPV in non melanoma skin cancers is unclear.
Asunto(s)
Enfermedad de Bowen/etiología , Carcinoma de Células Escamosas/etiología , Infecciones por Papillomavirus/complicaciones , Lesiones Precancerosas/etiología , Neoplasias Cutáneas/etiología , Neoplasias del Cuello Uterino/etiología , Adulto , Cuello del Útero/patología , Colposcopía , Femenino , Humanos , Lesiones Precancerosas/diagnóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/etiología , Displasia del Cuello del Útero/patologíaRESUMEN
Human papillomaviruses (HPV) are found in most human epithelia and some tumors. Most HPV strains associated with cutaneous lesions belong to three types, named alpha, beta and gamma. Although the causal link between genital human papillomavirus infection and cervical neoplasia is well established, the role of beta-HPV in non melanoma skin cancers is unclear. HPV mainly causes benign cutaneous lesions on the hands and soles. Genital HPV infection is the most common sexually transmitted infection. It is generally asymptomatic. The genitals can be infected by two low-risk HPV types (6 and 11), which are responsible for benign anogenital warts (condylomata acuminata). The implications of anogenital warts in children are highly controversial as regards sexual abuse. Treatments (chemical, physical or immunological) are lengthy, expensive, inconvenient and often painful. Recurrence is frequent because of HPV persistence in perilesional skin.
Asunto(s)
Infecciones por Papillomavirus , Adulto , Niño , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/terapia , Crioterapia , Legrado , Femenino , Humanos , Recién Nacido , Queratolíticos/administración & dosificación , Queratolíticos/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/cirugía , Infecciones por Papillomavirus/terapia , Infecciones por Papillomavirus/transmisión , Infecciones por Papillomavirus/virología , Enfermedades del Pene/diagnóstico , Enfermedades del Pene/terapia , Podofilino/administración & dosificación , Podofilino/uso terapéutico , Recurrencia , Factores de Tiempo , Enfermedades del Cuello del Útero/diagnóstico , Enfermedades del Cuello del Útero/terapia , Verrugas/diagnóstico , Verrugas/terapia , Verrugas/transmisiónRESUMEN
We report a case of a cervical intraepithelial neoplasia associated with epidermodysplasia verruciformis human papillomavirus (HPV) type 5 and HPV type 16 in a human immunodeficiency virus-infected patient. Furthermore, epidermodysplasia verruciformis-like cutaneous eruptions after initiation of highly active antiretroviral therapy has never been described as a manifestation of an immune restoration syndrome.
Asunto(s)
Epidermodisplasia Verruciforme/diagnóstico , Infecciones por VIH , Papillomaviridae , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Diagnóstico Diferencial , Epidermodisplasia Verruciforme/virología , Femenino , Humanos , Huésped Inmunocomprometido , Papillomaviridae/clasificación , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/virologíaRESUMEN
Although previous studies have demonstrated the efficient modulatory effects of ultraviolet radiation B (UVB) on cutaneous graft-versus-host disease (GVHD), most animal research on GVHD has been performed in murine models of acute GVHD. Here, we studied the preventive effect of UVB radiation on the occurrence of chronic sclerodermatous (Scl) GVHD in a murine model. Scl GVHD was induced by transplanting lethally irradiated BALB/c mice with B10.D2 bone marrow and spleen cells. Recipient mice were exposed to UVB before or after bone marrow and spleen cell infusion. Histological and clinical evaluation of GVHD was performed, in association with the characterization of epidermal Langerhans cells. UVB irradiation of recipients after, and more remarkably before, transplantation induced a decrease of Scl GVHD severity associated with epidermal Langerhans cells depletion. We conclude that UVB irradiation of recipient before or after transplantation has a preventive effect on cutaneous Scl GVHD and may represent an effective strategy for prevention of Scl GVHD.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/patología , Transfusión de Linfocitos , Esclerodermia Limitada/radioterapia , Esclerodermia Limitada/cirugía , Trasplante Homólogo/inmunología , Trasplante Homólogo/patología , Rayos Ultravioleta , Animales , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Inmunohistoquímica , Células de Langerhans/patología , Células de Langerhans/efectos de la radiación , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Bazo/trasplanteRESUMEN
OBJECTIVES: Humoral and cellular immune responses are likely to play a key role for the clearance or persistence and progression of high risk (HR) HPV-associated cervical lesions. Although there are many studies describing the systemic T-cell responses to HPV16 and 18 proteins, few data are available regarding the cellular mucosal immune responses. We used immunohistochemistry to characterize populations of T-immune cells (CD4+, CD8+, CD45RO+) in HR-HPV-infected precancerous and cancerous lesions of the uterine cervix. METHODS: Four biopsies from normal cervix, 9 CIN1 which have regressed (rCIN), 5 CIN1 which have progressed (pCIN) to high grade lesions, 13 CIN3 and 11 invasive carcinomas were included. All dysplasias and carcinomas were HR-HPV-positive and low-risk-HPV-negative. They were stained with monoclonal antibodies specific for CD4, CD8 and CD45RO and examined by microscopy. STATISTICAL ANALYSIS: The Kruskal-Wallis test and the Siegel's and Castelan's method were used. RESULTS.: CD4+ cells predominated in regressing CIN1 both within the stroma and the epithelium with the highest CD4+/CD8+ ratio compared with pCIN1, CIN3 and invasive carcinoma. At the exception of CD45RO+ cells, T cells were detected with similar frequencies in both pCIN1 and CIN3. However, in 7 out of 10 CIN3, CD4+ and CD8+ cells were visible as organized lymphoid follicle structure. The CD8+ and CD45RO+ cells far exceeded the CD4+ cells in invasive cancers. CONCLUSIONS: Density and distribution of immune T cells depend on the malignant potential of HR-HPV lesions. These results suggest that the studied lymphocyte subsets have an important role to fulfil during the natural history of HR-HPV-associated lesions.