Early T1-T2 stage p16+ oropharyngeal tumours. Role of upfront transoral robotic surgery in de-escalation treatment strategies. A review of the current literature.

Human papillomavirus is responsible of approximately 70% oropharyngeal tumours and is related with more favourable outcomes. It has led to an increasing interest for de-escalation treatment strategies such as Trans Oral Robotic Surgery (TORS). A literature review was performed searching for the role of TORS as de-escalation modality of treatment in patients with p16 positive oropharyngeal squamous cell carcinoma (OPSCC). Special attention was paid to the potential advantage offered by TORS in reducing adjuvant radiation therapy. Six questions were formulated. 67 studies were selected. Several trials analysing the role of upfront TORS to treat early stage p16+ OPSCC and the possibility of reducing the adjuvant radiotherapy were founded. A lot of studies based on the experience of single centres show promising results. Nevertheless to date no definitive data can be extrapolated. The continued investigation of this line of de-escalation therapy with randomized prospective clinical trials is needed.

La sanidad Militar Española. Su devenir histórico / The spanish Military Health Services. Its historic outcome

No disponible

No disponible

Agonistic anti-Fas antibodies induce glomerular cell apoptosis in mice in vivo.

Recent studies suggest that apoptotic cell death regulates the cell complement in glomerular diseases. However, little is-known about the factors that promote glomerular cell apoptosis. Activation of the Fas receptor by the Fas ligand or agonistic antibodies triggers apoptosis in some cell types that express Fas. Cultured human mesangial cell are among the cells that undergo apoptosis upon Fas activation, but it is unclear whether mesangial cells are sensitive to death induced by Fas in vivo. We have now explored the role of Fas in experimental glomerular injury. Murine mesangial cells in culture express fas and undergo apoptosis when stimulated with the Jo2 agonistic anti-Fas mAb. A fas mRNA transcript is present in normal murine kidney and freshly isolated glomeruli. Balb-c mice developed hematuria and proteinuria within 24 hours of the intraperitoneal injection of 10 micrograms Jo2 anti-Fas mAb. In addition to liver cell apoptosis, glomerular cell apoptosis and mesangial cell depletion were evident in the kidney at three hours and more pronounced at 24 hours. Glomerular and liver injury were not prevented by decomplementation. These data suggest that Fas activation in vivo by specific antibodies induces glomerular and mesangial cell apoptosis in mice.

Anti-Fas antibodies induce cytolysis and apoptosis in cultured human mesangial cells.

Death of renal cells often occurs during the acute and resolution phases of some forms of glomerulonephritis. The apoptotic Fas protein belongs to a recently described family of cytokine receptors with similarities to tumor necrosis factor (TNF) receptors, and may contribute to the necrobiology of renal cells. Fas transduces a signal for apoptosis in sensitive cells after binding by specific antibodies or following contact with natural Fas ligand. We have studied Fas in cultured human mesangial cells. Cytoflurography demonstrated Fas expression on the surface of human mesangial cells that was increased by stimulation with interferon gamma (IFN gamma). Agonistic anti-human Fas antibodies were cytotoxic to these cells. Cytotoxicity was time- and dose-dependent, and was modulated by pre-stimulation of the mesangial cells with IFN gamma and/or by co-treatment with actinomycin-D. Mesangial cell death following exposure to anti-Fas antibodies has features consistent with apoptosis, such as internucleosomal DNA fragmentation, nuclear shrinkage and condensation, and decreased DNA content. These data suggest that Fas and its ligand could play a mechanistic role in human glomerular cell injury.