506 research outputs found
RANKL inhibitors for osteosarcoma treatment: hope and caution
Chen and collaborators propose RANKL blockade for the treatment and prevention of aggressive RANKL-overexpressing osteosarcoma (OS) in humans. Here we comment the main findings, putative applications and concerns.
OS is the most common primary bone cancer, which occurs primarily in children and adolescents, severely affecting survivors’ quality of life. Current treatment for newly diagnosed OS includes three main components: preoperative chemotherapy, surgical resection, and postoperative chemotherapy (1). This strategy has improved the outcome of patients with localized OS. However, patients with advanced, metastatic, and recurrent OSs continue to experience a quite poor prognosis. After aggressive treatment with both surgery and chemotherapy, the 5-year survival rate for OS patients with localized disease is about 65%, whereas it is less than 20% for patients with metastases. The use of adjuvant chemotherapy provides no survival advantage for patients with pulmonary metastases (2). So that, it is of particular importance to develop molecularly targeted therapy to treat patients with this metastatic bone malignancy, on the basis of in-depth understanding of signaling mechanisms involved in OS tumorigenesis
Rank ectopic expression in the presence of Neu and PyMT oncogenes alters mammary epithelial cell populations and their tumorigenic potential
Determination of the mammary epithelial cell that serves as the cell of origin for breast cancer is key to understand tumor heterogeneity and clinical management. In this study, we aimed to decipher whether Rank expression in the presence of PyMT and Neu oncogenes might affect the cell of origin of mammary gland tumors. We observed that Rank expression in PyMT+/- and Neu(+/-) mammary glands alters the basal and luminal mammary cell populations already in preneoplasic tissue, which may interfere with the tumor cell of origin restricting their tumorigenesis ability upon transplantation assays. In spite of this, Rank expression eventually promotes tumor aggressiveness once tumorigenesis is established
Management of bone health in solid tumours: From bisphosphonates to a monoclonal antibody
Patients with solid tumours are at risk of impaired bone health from metastases and cancer therapy-induced bone loss (CTIBL). We review medical management of bone health in patients with solid tumours over the past 30 years, from first-generation bisphosphonates to the receptor activator of nuclear factor kappa B ligand (RANKL)-targeted monoclonal antibody, denosumab. In the 1980s, first-generation bisphosphonates were shown to reduce the incidence of skeletal-related events (SREs) in patients with breast cancer. Subsequently, more potent second-and third-generation bisphosphonates were developed, particularly zoledronic add (ZA). Head-to-head studies showed that ZA was significantly more effective than pamidronate for reducing SREs in patients with breast and castrate-resistant prostate cancer (CRPC), becoming the standard of care for more than a decade. The RANKL inhibitor denosumab was licensed in 2010, and head-to-head studies and integrated analyses confirmed its superiority to ZA for preventing SREs, particularly in breast cancer and CRPC. Bisphosphonates and denosumab have also been investigated for prevention of CTIBL in patients receiving hormonal therapy for breast and prostate cancer, and denosumab is licensed in this indication. Despite advances in management of bone health, several issues remain, notably the optimal time to initiate therapy, duration of therapy, and dosing frequency, and how to avoid toxicity, particularly with long-term treatment. In summary, introduction of ZA and denosumab has protected patients with bone metastasis from serious bone complications and improved their quality of life. Ongoing research will hopefully guide the optimal use of these agents to help maintain bone health in patients with solid tumours
European Network of Breast Development and Cancer turned 10 years: a growing family of mammary gland researchers
The European Network for Breast Development and Cancer (ENBDC), a worldwide network (http://www.enbdc.org/), celebrated its tenth anniversary with a fantastic meeting last March 15-17, 2018 in Weggis with 76 attendees
Adaptación curricular por competencias como medida educativa inclusiva. Exposición de un caso con amplias dificultades de comunicación y lenguaje en Educación Infantil
La comunicación en el ser humano es la clave del aprendizaje, progreso y evolución social, por lo que
la carencia de la misma puede portear serias dificultades en el desarrollo psicológico, educativo y social
de los niños y niñas. En la etapa de Educación Infantil es cuando podemos detectar de forma temprana
estas dificultades comunicativas, por lo que la rápida prevención, diagnóstico e intervención de las mismas
facilitarán dar respuesta educativa de la manera más adecuada posible. En este trabajo, tratamos
de exponer un caso real de un niño con amplias dificultades de comunicación y lenguaje en Educación
Infantil y cómo la medida más adecuada para dar respuesta a sus necesidades especÃficas de apoyo
educativo es una adaptación curricular por competencias desde una perspectiva inclusiva, enfoque que
defiende una educación de calidad e igualitaria para todos, para lo cual la metodologÃa más idónea serÃa
el trabajo por proyectos
Una medida innovadora para la atención a la diversidad. La adaptación curricular por competencias
En la actualidad, las instituciones educativas se están adaptando a una nueva forma de diseñar y planificar
el currÃculo. Este proceso es lento y complejo, ya que después de haberse familiarizado con las
pautas establecidas por la anterior ley educativa, la nueva concepción del currÃculo implica una programación
basada en las competencias básicas. Asimismo, la atención a la diversidad del alumnado debe
seguir preservando el derecho a una educación de calidad, siguiendo las directrices de una filosofÃa
inclusiva, democrática y compensatoria. Teniendo en cuenta estas directrices, en este artÃculo exponemos
la adaptación curricular por competencias como medida de atención al alumnado que precisa
concreciones del currÃculo más significativas. Partimos del hecho de la necesidad de saber elaborar
programaciones didácticas por competencias y a partir de éstas concretizar la medida de atención educativa
a la que hacemos mención. En nuestra opinión, la adaptación curricular por competencias puede
favorecer el desarrollo integral del alumnado con necesidades especÃficas de apoyo educativo, empleando
una metodologÃa de trabajo por proyectos que permita desarrollar las competencia básicas, pues se
basa en un proceso de enseñanza y aprendizaje globalizado y experimental que permite un aprendizaje
más significativo para el alumno/a
El profesor creativo y el profesor que potencia la creatividad en el contexto universitario
Dentro del proceso de adaptación de los nuevos planes de estudio a los créditos E.C.T.S., se está exigiendo un tipo de docente que pueda dar respuesta a las expectativas de este urgido cambio europeo, entre ellas, planificar, orientar, tutorizar y formar a los estudiantes en conocimientos, estrategias, habilidades y destrezas. En este trabajo pretendemos, de un lado, dar a conocer la importancia de la creatividad como competencia en el contexto universitario y, de otro, reflejar la necesidad de potenciar esta capacidad en la figura del profesor universitario haciendo hincapié en las estrategias que debe de poner en marcha para potenciar la creatividad en el alumnado universitario
Normal telomere length and chromosomal end capping in poly(ADP-ribose) polymerase–deficient mice and primary cells despite increased chromosomal instability
Poly(ADP-ribose) polymerase (PARP)-1, a detector of single-strand breaks, plays a key role in the cellular response to DNA damage. PARP-1–deficient mice are hypersensitive to genotoxic agents and display genomic instability due to a DNA repair defect in the base excision repair pathway. A previous report suggested that PARP-1–deficient mice also had a severe telomeric dysfunction consisting of telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P. Hande, W.-M. Tong, P.M. Lansdorp, Z.-Q. Wang, and S.P. Jackson. 1999. Nat. Genet. 23:76–80). In contrast to that, and using a panoply of techniques, including quantitative telomeric (Q)-FISH, we did not find significant differences in telomere length between wild-type and PARP-1−/− littermate mice or PARP-1−/− primary cells. Similarly, there were no differences in the length of the G-strand overhang. Q-FISH and spectral karyotyping analyses of primary PARP-1−/− cells showed a frequency of 2 end-to-end fusions per 100 metaphases, much lower than that described previously (d'Adda di Fagagna et al., 1999). This low frequency of end-to-end fusions in PARP-1−/− primary cells is accordant with the absence of severe proliferative defects in PARP-1−/− mice. The results presented here indicate that PARP-1 does not play a major role in regulating telomere length or in telomeric end capping, and the chromosomal instability of PARP-1−/− primary cells can be explained by the repair defect associated to PARP-1 deficiency. Finally, no interaction between PARP-1 and the telomerase reverse transcriptase subunit, Tert, was found using the two-hybrid assay
Qualitative and quantitative characterization of exosomes secreted by rat hepatocytes
Comunicaciones a congreso
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