ABSTRACT
Toca 511 (vocimagene amiretrorepvec), an amphotropic retroviral replicating vector (RRV), can successfully and safely deliver a functional, optimized cytosine deaminase (CD) gene to tumors in orthotopic glioma models. This agent, in conjunction with subsequent oral extended-release 5-fluorocytosine (5-FC) (Toca FC), is currently under investigation in patients with recurrent high-grade glioma . Temozolomide (TMZ) with radiation is the most frequently used first-line treatment for patients with glioblastoma, the most common and aggressive form of primary brain cancer in adults. However, subsets of patients with certain genetic alterations do not respond well to TMZ treatment and the overall median survival for patients who respond remains modest, suggesting that combinatorial approaches may be necessary to significantly improve outcomes. We show that in vitro TMZ delays but does not prevent RRV spread, nor interfere with Toca 511+5-FC-mediated cell killing in glioma tumor cells, and in vivo there is no significant hematologic effect from the combination of 5-FC and the clinically relevant dose of TMZ. A synergistic long-term survival advantage is observed in mice bearing an orthotopic TMZ-sensitive glioma after Toca 511 administration followed by coadministration of TMZ and 5-FC. These results provide support for the investigation of this novel combination treatment strategy in patients with newly diagnosed malignant glioma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Brain Neoplasms/therapy , Cytosine Deaminase/genetics , Dacarbazine/analogs & derivatives , Flucytosine/pharmacology , Glioblastoma/therapy , Animals , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cytosine Deaminase/biosynthesis , Cytosine Deaminase/metabolism , Dacarbazine/administration & dosage , Dacarbazine/pharmacology , Drug Synergism , Female , Flucytosine/administration & dosage , Flucytosine/pharmacokinetics , Gene Expression , Gene Transfer Techniques , Genetic Vectors/genetics , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Mice , Mice, Nude , Retroviridae/genetics , Temozolomide , Xenograft Model Antitumor AssaysABSTRACT
En los cuadros severos de hidrosadenitis ( hidradenitis supurativa) axilar con un área infeccioso inflamatoria extendida y retracciones secundarias que limitan la capacidad funcional articular del hombro, la mejor solución pasa por el desbridamiento radical de todo el área afecta y su posterior cobertura con tejido de buena calidad. Los colgajos locales basados en perforantes torácico laterales y toracodorsales con distintos diseños y los derivados de la arteria circunfleja escapular con la Variante bilobulada escápulo - paraescapular para los casos extremos, ofrecen posibilidades locales de muy buena calidad para defectos de todas las dimensiones. Se presentan cinco casos de hidrosadenitis axilar mostrando las posibilidades de cobertura con los colgajos citados (AU)
Subject(s)
Adult , Female , Male , Humans , Hidradenitis/surgery , Axilla/surgery , Surgical Flaps/supply & distribution , Skin TransplantationABSTRACT
Tubular flaps, an early technique of reconstructive surgery, still are indicated for some diseases, such as post-traumatic helical reconstruction. In this disease, retroauricular skin is used to construct a bipedicled tube flap that later is transposed in various surgical stages to rebuild the missing structure. The procedure is ambulatory and carried out under local anesthesia in patients who are motivated to collaborate with this surgical approach.
Subject(s)
Ear, External/surgery , Surgery, Plastic , Animals , Humans , Surgical Flaps , Transplantation, AutologousABSTRACT
Problems in the reconstruction of full thickness burns of the sole of the foot are presented. After analysing the existing surgical possibilities for treating this injury, the good results obtained in the forefoot with radial forearm flaps are shown. The main virtues of this flap for treating plantar burns are its suppleness for adaptation to the different contours of the foot. This allows a functional recovery without losing the normal shape of the foot, making the use of prosthetic devices unnecessary.
