RESUMO
BACKGROUND: Immune checkpoint blocker (ICB) therapy has shown survival benefits for some patients with cancer. Nevertheless, many individuals remain refractory or acquire resistance to treatment, motivating the exploration of complementary immunotherapies. Accordingly, cancer vaccines offer an attractive alternative. Optimal delivery of multiple tumor-associated antigens combined with potent adjuvants seems to be crucial for vaccine effectiveness. METHODS: Here, a prototype for a generic melanoma vaccine, named TRIMELVax, was tested using B16F10 mouse melanoma model. This vaccine is made of heat shock-treated tumor cell lysates combined with the Concholepas concholepas hemocyanin as adjuvant. RESULTS: While B16F10 lysate provides appropriate melanoma-associated antigens, both a generic human melanoma cell lysate and hemocyanin adjuvant contributes with danger signals promoting conventional dendritic type 1 cells (cDC1), activation, phagocytosis and effective antigen cross-presentation. TRIMELVax inhibited tumor growth and increased mice survival, inducing cellular and humoral immune responses. Furthermore, this vaccine generated an increased frequency of intratumor cDC1s but not conventional type 2 dendritic cells (cDC2s). Augmented infiltration of CD3+, CD4+ and CD8+ T cells was also observed, compared with anti-programmed cell death protein 1 (PD-1) monotherapy, while TRIMELVax/anti-PD-1 combination generated higher tumor infiltration of CD4+ T cells. Moreover, TRIMELVax promoted an augmented proportion of PD-1lo CD8+ T cells in tumors, a phenotype associated with prototypic effector cells required for tumor growth control, preventing dysfunctional T-cell accumulation. CONCLUSIONS: The therapeutic vaccine TRIMELVax efficiently controls the weakly immunogenic and aggressive B16F10 melanoma tumor growth, prolonging tumor-bearing mice survival even in the absence of ICB. The strong immunogenicity shown by TRIMELVax encourages clinical studies in patients with melanoma.
Assuntos
Vacinas Anticâncer/imunologia , Imunoterapia/métodos , Melanoma Experimental/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NODRESUMO
Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4+ and CD8+ T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8+ T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches.
Assuntos
Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Neoplasias da Vesícula Biliar/terapia , Animais , Antígenos de Neoplasias/imunologia , Biomarcadores , Vacinas Anticâncer/efeitos adversos , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/imunologia , Neoplasias da Vesícula Biliar/metabolismo , Regulação da Expressão Gênica , Resposta ao Choque Térmico , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Los lentes de contacto esclerales han mantenido un pequeño pero valioso lugar entre los lentes de contacto en la práctica clínica. Es evidente que, debido a la poca instrucción del lente escleral, no se le hadado una alta prioridad en el ámbito profesional, lo que conlleva a que muchos profesionales no tengan una comprensión de sus ventajas intrínsecas y, en consecuencia, rara vez se prescribe o recomienda su uso. Este tipo de lentes rígidos gas permeables desempeñan un papel importante y no se valoran suficientemente en el tratamiento de enfermedades corneales, así como su beneficio para la rehabilitación visual de ectasias, astigmatismos irregulares y en la terapia de la enfermedad de la superficie ocular.
Scleral contact lenses lenses have maintained a small but uniquely valuable place within the contact lenses in clinical practice. It is obvious that due to poorly educated scleral lens has not been given a high priority in the professional field which implies that many professionals do not have an understanding of their intrinsic merits and therefore rarely prescribedor recommended for use. This type of rigid gaspermeable lenses performs an important role and its underrated in the treatment of corneal diseases and their performance for the rehabilitation of visual ecstasies, irregular astigmatism, and therapy of disease of the ocular surface.
Assuntos
Lentes de Contato , ReabilitaçãoRESUMO
Es de real importancia realizar cambios que nos conlleven a mejorar las condiciones de nuestra vida y nuestra profesión. Por lo tanto es imprescindible crear, proponer y por supuesto llevar a cabo nuestras mejores ideas y oportunidades que el mundo actual nos ofrece. Es fundamental conocer a nuestro país para tratar de aportar de algún modo desde nuestro campo profesional un cimiento más para construir entre todos una gran pirámide de triunfadores empresarios, apoyados por las nuevas instituciones creadoras e impulsadoras de pequeñas y mediana empresas.
It is really important to carry out changes that involve us to improve living and professional conditions. For instance is essential to create, to propose and carried out all the best ideas and opportunities that the present world offered us. It is basic to know our country and give to people help, since our profession al field. Allow for to build among us, a big pyramid of winning businessmen supported by new creative institutions that drive the small and medium companies.
Assuntos
Saúde Ocupacional , Qualidade de VidaRESUMO
El ser humano fue diseñado para triunfar, cualquier ser humano tiene la capacidad de lograrlo, esto se alcanza si el individuo esta motivado, inicia la visualización de planes, si es positivo, constante, aprende a automotivarse y realiza cambios que conlleven al mejoramiento continuo. La gran mayoría de las personas adquieren las habilidades y talentos en su vida pero unas pocas logran explotar todo su potencial a través de la motivación, esta es la fuerza de voluntad que le permite a cada persona convertirse en un ser extraordinario y sin limites.
Assuntos
Optometria , Qualidade de VidaRESUMO
Se reporta que la orientación espacial durante la microcirugía, constituye un elemento indispensable. Se demuestra esta aplicación de la cirugía estereotáxica en el Centro Internacional de Restauración Neurológica (CIREN) de mayo de 1994 a febrero de 1998, al describir la realización de 65 intervenciones microquirúrgicas en condiciones estereotáxicas, a 62 pacientes con tumores cerebrales intracraneales. El proceder se dividió en 3 etapas: adquisición de la imagen, tomografía axial computadorizada, planificación quirúrgica, con sistema de planeamiento STASSIS y procederes microquirúrgicos, que incluyeron los sistemas estereotáxicos: Leksell, Micromar y Estereoflex. Del total, 27 de estos pacientes presentaron tumores gliales, 33 no gliales y sólo 2 lesiones no neoplásicas de localización y tamaño variados. Se realizaron 30 resecciones totales. La morbilidad quirúrgica fue mínima y no hubo mortalidad quirúrgica. Las principales ventajas del método son: localización exacta de la craneotomía, fácil orientación espacial, facilidad para distinguir los límites entre el tumor y el tejido sano. Se verificó la aplicabilidad del Estereoflex a la microcirugía cerebral(AU)
It is reported that spatial guidance during microsurgery is an essential element. This application of stereotaxic surgery is shown at the International Center of Neurological Restoration (CIREN, in Spanish) from May, 1994, to February, 1998, on describing the performance of 65 microsurgical procedures under stereotaxic conditions among 62 patients with cerebral intracranial tumors. The procedure was divided into 3 stages: image adquisition, CAT, surgical planning , with STASSIS planning system, and microsurgical procedures that included the Leksell, Micromar and Esteroflex stereotaxic systems. 27 of the total of patients presented glial tumors; 33, non-glial; and only 2 non-neoplastic lesions of diverse localization and size. 30 total resections were made. Surgical morbidity was minimum and there was no surgical mortality. The main advantages of this method are: exact localization of the craniotomy, easy spatial guidance, and the opportunity to distinguish the limits between the tumor and the sound tissue. The possibility to apply Esteroflex to cerebral microsurgery was demonstrated(AU)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/cirurgia , Tomografia Computadorizada por Raios X/métodos , Técnicas Estereotáxicas/efeitos adversos , Microcirurgia/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
El estudio de la masa del callo óseo transversal, en la evolución de una fractura u osteotomía, así como el conocimiento de la mineralización de dicha masa no son alcanzables por los métodos usuales de evaluación de la consolidación. Como un nuevo método, hemos estudiado ambos aspectos a partir del corte simple de la TAC, usando para precisar el sitio exacto el Topograma del Somaton-SF Siemens, y el mapa de las densidades Hounsfield de dicha sección, ploteado en foram de curvas. Para obtener los patrones de imágenes y confeccionar las curvas de mineralización que permitieron confiar los distintos tipos de consolidación fueron procesados 50 especímenes de callos de tibia de perros esteotomizados con variados tratamiento y estimulación del callo por corriente directa bipolar. Las características de la imágen de cad tipo de callo no expuestas, la mineralización es mostrada en las curvas de tratamientos por estabilización, distracción y compresión. Los indicaciones y contraindicaciones en la práctica clínica son ejemplificadas