Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
NPJ Vaccines ; 8(1): 15, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36781862

RESUMEN

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

2.
Cancer Metastasis Rev ; 37(4): 779-790, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30203108

RESUMEN

Lung cancer is the leading cause of cancer mortality around the world. The lack of detailed understanding of the cellular and molecular mechanisms participating in the lung tumor progression restrains the development of efficient treatments. Recently, by using state-of-the-art technologies, including in vivo sophisticated Cre/loxP technologies in combination with lung tumor models, it was revealed that osteoblasts activate neutrophils that promote tumor growth in the lung. Strikingly, genetic ablation of osteoblasts abolished lung tumor progression via interruption of SiglecFhigh-expressing neutrophils supply to the tumor microenvironment. Interestingly, SiglecFhigh neutrophil signature was associated with worse lung adenocarcinoma patients outcome. This study identifies novel cellular targets for lung cancer treatment. Here, we summarize and evaluate recent advances in our understanding of lung tumor microenvironment.


Asunto(s)
Comunicación Celular/fisiología , Neoplasias Pulmonares/patología , Neutrófilos/patología , Osteoblastos/patología , Animales , Humanos , Microambiente Tumoral
3.
Angiogenesis ; 21(4): 667-675, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29761249

RESUMEN

Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Glioblastoma/tratamiento farmacológico , Pericitos/metabolismo , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Animales , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Glioblastoma/metabolismo , Glioblastoma/patología , Ratones , Pericitos/patología , Piperidinas , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Cancer Res ; 78(11): 2779-2786, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29789421

RESUMEN

The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion. Strikingly, genetic inactivation of KLF4 in pericytes inhibits pulmonary pericyte expansion and decreases metastasis in the lung. Here, we summarize and evaluate recent advances in the understanding of pericyte contribution to premetastatic niche formation. Cancer Res; 78(11); 2779-86. ©2018 AACR.


Asunto(s)
Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Pericitos/patología , Animales , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología
5.
Int J Biochem Cell Biol ; 99: 109-113, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29627438

RESUMEN

Fibrosis following injury leads to aberrant regeneration and incomplete functional recovery of skeletal muscle, but the lack of detailed knowledge about the cellular and molecular mechanisms involved hampers the design of effective treatments. Using state-of-the-art technologies, Murray et al. (2017) found that perivascular PDGFRß-expressing cells generate fibrotic cells in the skeletal muscle. Strikingly, genetic deletion of αv integrins from perivascular PDGFRß-expressing cells significantly inhibited skeletal muscle fibrosis without affecting muscle vascularization or regeneration. In addition, the authors showed that a small molecule inhibitor of αv integrins, CWHM 12, attenuates skeletal muscle fibrosis. From a drug-development perspective, this study identifies a new cellular and molecular target to treat skeletal muscle fibrosis.


Asunto(s)
Fibrosis/prevención & control , Integrina alfaV/química , Integrina alfaV/metabolismo , Músculo Esquelético/patología , Pericitos/patología , Animales , Fibrosis/metabolismo , Fibrosis/patología , Humanos , Músculo Esquelético/metabolismo , Pericitos/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo
6.
Cancer Med ; 7(4): 1232-1239, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29479841

RESUMEN

Glioblastoma multiforme is the most common and aggressive primary brain tumor, with an extremely poor prognosis. The lack of detailed knowledge about the cellular and molecular mechanisms involved in glioblastoma development restricts the design of efficient therapies. A recent study using state-of-art technologies explores the role of pericytes in the glioblastoma microenvironment. Glioblastoma-activated pericytes develop an immunosuppressive phenotype, reducing T-cell activation through the induction of an anti-inflammatory response. Strikingly, pericytes support glioblastoma growth in vitro and in vivo. Here, we describe succinctly the results and implications of the findings reported in pericytes' and glioblastomas' biology. The emerging knowledge from this study will be essential for the treatment of brain tumors.


Asunto(s)
Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Glioblastoma/inmunología , Glioblastoma/patología , Inmunomodulación , Pericitos/inmunología , Animales , Biomarcadores , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Humanos , Tolerancia Inmunológica , Pericitos/metabolismo , Fenotipo , Transducción de Señal , Escape del Tumor/inmunología , Microambiente Tumoral/inmunología
7.
J Cell Physiol ; 233(8): 5523-5529, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29215724

RESUMEN

Multiple sclerosis is a highly prevalent chronic demyelinating disease of the central nervous system. Remyelination is the major therapeutic goal for this disorder. The lack of detailed knowledge about the cellular and molecular mechanisms involved in myelination restricts the design of effective treatments. A recent study by using [De La Fuente et al. (2017) Cell Reports, 20(8): 1755-1764] by using state-of-the-art techniques, including pericyte-deficient mice in combination with induced demyelination, reveal that pericytes participate in central nervous system regeneration. Strikingly, pericytes presence is essential for oligodendrocyte progenitors differentiation and myelin formation during remyelination in the brain. The emerging knowledge from this research will be important for the treatment of multiple sclerosis.


Asunto(s)
Sistema Nervioso Central/fisiología , Vaina de Mielina/fisiología , Pericitos/citología , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Enfermedades Desmielinizantes/fisiopatología , Ratones , Esclerosis Múltiple/fisiopatología , Regeneración Nerviosa/fisiología , Oligodendroglía/citología
8.
Cytometry A ; 93(2): 167-171, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29236351

RESUMEN

Adipocyte infiltration in the bone marrow follows chemotherapy or irradiation. Previous studies indicate that bone marrow fat cells inhibit hematopoietic stem cell function. Recently, Zhou et al. (2017) using state-of-the-art techniques, including sophisticated Cre/loxP technologies, confocal microscopy, in vivo lineage-tracing, flow cytometry, and bone marrow transplantation, reveal that adipocytes promote hematopoietic recovery after irradiation. This study challenges the current view of adipocytes as negative regulators of the hematopoietic stem cells niche, and reopens the discussion about adipocytes' roles in the bone marrow. Strikingly, genetic deletion of stem cell factor specifically from adipocytes leads to deficiency in hematopoietic stem cells, and reduces animal survival after myeloablation, The emerging knowledge from this research will be important for the treatment of multiple hematologic disorders. © 2017 International Society for Advancement of Cytometry.


Asunto(s)
Adipocitos/fisiología , Células de la Médula Ósea/fisiología , Trasplante de Médula Ósea , Adipocitos/trasplante , Animales , Médula Ósea/fisiología , Trasplante de Médula Ósea/tendencias , Células Madre Hematopoyéticas/fisiología , Humanos
9.
Cell Mol Neurobiol ; 38(4): 777-782, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-28894964

RESUMEN

Pericytes are defined by their anatomical location encircling blood vessels' walls with their long projections. The exact embryonic sources of cerebral pericytes remain poorly understood, especially because of their recently revealed diversity. Yamamoto et al. (Sci Rep 7(1):3855, 2017) using state-of-the-art techniques, including several transgenic mice models, reveal that a subpopulation of brain pericytes are derived from phagocytic macrophages during vascular development. This work highlights a new possible ancestor of brain pericytes. The emerging knowledge from this research may provide new approaches for the treatment of several neurodevelopmental disorders in the future.


Asunto(s)
Encéfalo/patología , Macrófagos/patología , Trastornos del Neurodesarrollo/patología , Pericitos/patología , Animales , Encéfalo/irrigación sanguínea , Humanos , Ratones Transgénicos , Trastornos del Neurodesarrollo/diagnóstico
11.
Cell Cycle ; 16(21): 2018-2022, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28976809

RESUMEN

Bone marrow fibrosis is a reactive process, and a central pathological feature of primary myelofibrosis. Revealing the origin of fibroblastic cells in the bone marrow is crucial, as these cells are considered an ideal, and essential target for anti-fibrotic therapy. In 2 recent studies, Decker et al. (2017) and Schneider et al. (2017), by using state-of-the-art techniques including in vivo lineage-tracing, provide evidence that leptin receptor (LepR)-expressing and Gli1-expressing cells are responsible for fibrotic tissue deposition in the bone marrow. However, what is the relationship between these 2 bone marrow cell populations, and what are their relative contributions to bone marrow fibrosis remain unclear. From a drug development perspective, these works bring new cellular targets for bone marrow fibrosis.


Asunto(s)
Células de la Médula Ósea/patología , Médula Ósea/patología , Fibroblastos/patología , Mielofibrosis Primaria/metabolismo , Receptores de Leptina/metabolismo , Animales , Disentimientos y Disputas , Humanos
12.
Neoplasia ; 19(11): 928-931, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28957694

RESUMEN

Prostate cancer cells metastasize to the bones, causing ectopic bone formation, which results in fractures and pain. The cellular mechanisms underlying new bone production are unknown. In a recent study, Lin and colleagues, by using state-of-the-art techniques, including prostate cancer mouse models in combination with sophisticated in vivo lineage-tracing technologies, revealed that endothelial cells form osteoblasts induced by prostate cancer metastasis in the bone. Strikingly, genetic deletion of osteorix protein from endothelial cells affected prostate cancer-induced osteogenesis in vivo. Deciphering the osteoblasts origin in the bone microenvironment may result in the development of promising new molecular targets for prostate cancer therapy.


Asunto(s)
Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Células Endoteliales/patología , Osteoblastos/patología , Osteogénesis/fisiología , Neoplasias de la Próstata/patología , Animales , Neoplasias Óseas/metabolismo , Células Endoteliales/metabolismo , Humanos , Masculino , Osteoblastos/metabolismo , Neoplasias de la Próstata/metabolismo , Microambiente Tumoral/fisiología
13.
Neuroscience ; 363: 62-65, 2017 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-28893649

RESUMEN

Niches are specialized microenvironments that regulate stem cells' activity. The neural stem cell (NSC) niche defines a zone in which NSCs are retained and produce new cells of the nervous system throughout life. Understanding the signaling mechanisms by which the niche controls the NSC fate is crucial for the success of clinical applications. In a recent study, Sato and colleagues, by using state-of-the-art techniques, including sophisticated in vivo lineage-tracing technologies, provide evidence that endothelial amyloid precursor protein (APP) is an important component of the NSC niche. Strikingly, depletion of APP increased NSC proliferation in the subventricular zone, indicating that endothelial cells negatively regulate NSCs' growth. The emerging knowledge from this research will be important for the treatment of several neurological diseases.


Asunto(s)
Células Madre Adultas , Células-Madre Neurales , Adulto , Encéfalo , Células Endoteliales , Humanos , Nicho de Células Madre
14.
Exp Hematol ; 54: 12-16, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28690072

RESUMEN

Bone marrow fibrosis is a critical component of primary myelofibrosis in which normal bone marrow tissue and blood-forming cells are gradually replaced with scar tissue. The specific cellular and molecular mechanisms that cause bone marrow fibrosis are not understood. A recent study using state-of-the-art techniques, including in vivo lineage tracing, provides evidence that Gli1+ cells are the cells responsible for fibrotic disease in the bone marrow. Strikingly, genetic depletion of Gli1+ cells rescues bone marrow failure and abolishes myelofibrosis. This work introduces a new central cellular target for bone marrow fibrosis. The knowledge that emerges from this research will be important for the treatment of several malignant and nonmalignant disorders.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Terapia Molecular Dirigida , Factor Plaquetario 4/genética , Mielofibrosis Primaria/tratamiento farmacológico , Piridinas/farmacología , Pirimidinas/farmacología , Proteína con Dedos de Zinc GLI1/genética , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Médula Ósea/patología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Proliferación Celular , Modelos Animales de Enfermedad , Expresión Génica , Humanos , Ratones , Ratones Transgénicos , Factor Plaquetario 4/metabolismo , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/metabolismo , Mielofibrosis Primaria/patología , Proteína con Dedos de Zinc GLI1/antagonistas & inhibidores , Proteína con Dedos de Zinc GLI1/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA