RESUMEN
This study investigates the effects of mistletoe lectin-I (ML-I) on melanoma growth and spread in vivo. The human melanoma cell line MV3 was xenografted into severe combined immunodeficient mice and vehicle solution or purified ML-I was administered at 30, 150 and 500 ng per kg body weight (20 mice per group) daily. After 19 days, mice were killed, primary tumours (PTs) and lungs were dissected out, and tumour weights, number of lung metastases (LMs), number of tumour-infiltrating dendritic cells (DCs), and apoptosis rates in the melanoma cells and in the DCs were assessed. A 35% reduction of PT weight (P=0.03) and a 55% decrease in number of LMs (P=0.016) were evident for low-dose ML-I (30 ng kg(-1)) treatment but not for higher doses. Mistletoe lectin-I increased apoptosis rates in the melanoma cells of PTs at all doses, while no induction of apoptosis was noted in the LMs. Low-dose ML-I significantly increased the number of DCs infiltrating the PTs (P<0.0001) and protected DCs against apoptosis, while higher doses induced apoptosis in the DCs (P<0.01). Our results demonstrate that low-dose ML-I reduced melanoma growth and number of metastases in vivo, primarily due to immunomodulatory effects.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma Experimental/tratamiento farmacológico , Preparaciones de Plantas/administración & dosificación , Proteínas de Plantas/administración & dosificación , Proteínas Inactivadoras de Ribosomas Tipo 2/administración & dosificación , Toxinas Biológicas/administración & dosificación , Animales , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Células Dendríticas/patología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Linfocitos Infiltrantes de Tumor , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
BACKGROUND: Glycoconjugates, as detected by lectin histochemistry, have been implicated in metastasis formation in many neoplasias. However, no data concerning the three mistletoe lectins (MLs) and the spread of malignant melanoma have been published. MATERIALS AND METHODS: The binding status of ML-I, -II and -III was histochemically assessed in 100 malignant melanomas and correlated with metastasis in a 10 year follow-up period. Furthermore, the staining intensity of the three MLs, scored from negative (-) to very intense (+ + +), was evaluated. RESULTS: Kaplan-Meier analsis revealed that very intense binding (+ + +) of ML-I was positively-correlated with metastasis (p=0.044). CONCLUSION: Since ML-I is specific for galactose, high density galactose expression in malignant melanoma is a predictor of poor prognosis.
Asunto(s)
Antineoplásicos Fitogénicos/metabolismo , Lectinas/metabolismo , Melanoma/metabolismo , Preparaciones de Plantas , Proteínas de Plantas , Neoplasias Cutáneas/metabolismo , Toxinas Biológicas/metabolismo , Adyuvantes Inmunológicos/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/patología , Tablas de Vida , Masculino , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Proteínas Inactivadoras de Ribosomas Tipo 2 , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Toxinas Biológicas/farmacologíaRESUMEN
In view of th reported high prevalence of otitis media and mastoiditis in the present-day Indian inhabitants or Arizona, when an opportunity arose to examine the skulls of prehistoric Indians in the collection of the Arizona State Museum, University of Arizona, Tucson, Arizona, it was thought that determining the prevalence of mastoiditis in them might be helpful in the treatment and prevention of mastoid infections in the present-day population. Our findings are compared with those of two other studies of mastoiditis in prehistoric Indians in another area of the United States.