13 research outputs found
Enterocolitis necrotizante en reciĂ©n nacidos ingresados en el Servicio de NeonatologĂa del Hospital Escuela "Carlos Roberto Huembes" en el perĂodo comprendido de Enero 2011 a Diciembre 2013
La enterocolitis necrotizante en el reciĂ©n nacido presenta un amplio espectro de manifestaciones clĂnicas, caracterizándose principalmente por la trĂada de distensiĂłn abdominal, sangramiento gastrointestinal y neumatosis intestinal. A pesar del avance en el cuidado intensivo neonatal, persiste como una enfermedad grave, que afecta habitualmente al reciĂ©n nacido pretĂ©rmino, especialmente de muy bajo peso
Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation.
The TP53 tumor suppressor gene is the most frequent target for genetic alterations in human cancer. TP53 gene alterations may result in the gain of oncogenic functions such as neoangiogenesis and resistance to therapy. The TP53 germ line mutation c.659A>C (p.Y220S) was identified in stored DNA from related patients with Li-Fraumeni syndrome (LFS) who died after developing clinically aggressive tumors. All of the patients were treated with protocols that included doxorubicin hydrochloride (DX) as a pivotal drug. To define the in vitro mutational phenotype of this germ line mutation, we used murine fibroblasts explanted from wild-type (wt) and p53 knockout (KO) mice from the same littermate. p53Y220S and p53R175H fibroblasts, obtained from p53KO fibroblasts transfected with expression vectors encoding the human Y220S and R175H p53 mutants, respectively, exhibited resistance to DX treatment. Moreover, p53Y220S fibroblasts exhibited angiogenetic properties, and after DX treatment, p53Y220S failed to translocate into the nucleus and showed an increase in its cytosolic levels. DX treatment does not influence p53 distribution within the nuclear and cytosolic compartments in p53R175H fibroblasts. Peroxiredoxin II (Prx II), a protein that is involved in eliminating reactive oxygen species (ROS), showed increased expression intensity in p53Y220S fibroblasts after DX treatment, as observed by two-dimensional electrophoresis analysis. Moreover, Thioredoxin (Trx), a protein that cooperates with Prx II, is overexpressed in p53Y220S mutants under basal conditions. These data suggest a relationship between the presence of the p53Y220S mutation and enhanced levels of Prx II and Trx in mutant fibroblasts. Since one of the mechanisms of the DX antitumor effect has been ascribed to production of ROS, future studies will evaluate the involvement of PrxII and Trx in the chemoresistance of p53Y220S fibroblasts to DX
Nxf and Fbxo33: novel seizure-responsive genes in mice
The definitive version is available at www.blackwell-synergy.comMuch is understood about the response of the brain to seizure but little is known in relation to the underlying molecular mechanisms involved. We used microarray technology to investigate the complex genetic response of the brain to generalized seizure. For this investigation a seizure-specific mouse brain cDNA library was generated and spotted onto microarray slides with the aim of increasing the likelihood of identifying novel genes responsive to seizure. Microarray analysis was performed on mouse hippocampus 1 h after generalized seizure pharmacologically induced by pentylenetetrazol (PTZ). Using the custom microarray slides, six genes were identified as being up-regulated in this seizure model and results were validated by real-time PCR. Four of the seizure-responsive genes had previously-reported roles in apoptosis, proliferation or differentiation of neural cells. Two of the genes were novel and in situ hybridization analysis demonstrated heightened mRNA expression in the hippocampus 1 h following generalized convulsive seizure, in a pattern which is typical for other activity-dependant genes expressed in this structure. In addition to being up-regulated postseizure, the genes described in this paper appear to be expressed normally in the adult hippocampus and during development.Warren D. Flood, Robert W. Moyer, Anna Tsykin, Grant R. Sutherland, Simon A. Kobla
Positively selected enhancer elements endow osteosarcoma cells with metastatic competence
Thrombosis and Hemostasi
Views of parents regarding human papillomavirus vaccination: A systematic review and meta-ethnographic synthesis of qualitative literature
Therapeutic Potential of Directed Tyrosine Kinase Inhibitor Therapy in Sarcomas
Background
Sarcomas are rare mesenchymally derived tumors for which there are limited treatment options. This paper discusses the current therapeutic potential of directed tyrosine kinase inhibitors (TKIs) in sarcoma.
Methods
The authors review antibody-based strategies and small molecular inhibitors of TKIs, with specific emphasis placed on the potential use of these targeted agents as therapeutic options for the treatment of sarcomas that are not gastrointestinal stromal tumors.
Results
Many TKs have been shown to be mutated or overexpressed in human sarcoma tumors and cell lines and may serve as potential targets for promising new sarcoma therapies. Furthermore, the novel mechanism of targeting TKs may complement the antitumor activity of existing sarcoma treatment options.
Conclusions
TKIs such as imatinib, sunitinib, and sorefanib are promising new therapeutic options for the management of patients with soft tissue sarcoma