Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

[Acoustic neuroma in children without association with neurofibromatosis. Report of 2 cases]. / Neurinoma do acústico em crianças sem associação com neurofibromatose. Relato de dois casos.

Acoustic schwannoma is the most common tumor of the cerebellopontine angle in adults and is rarely found in children without neurofibromatosis. In the literature there are 18 children under the age of 16 with such tumor. Two female patients with age of 9 and 15 years old with acoustic schwannoma without neurofibromatosis are related. Progressive deafness followed by signs and symptoms of a posterior fossa tumor were the initial complaint of both, as well as of the other related cases and in adulthood.

Biocompatibility of Optibond and XR-Bond adhesive systems in nonhuman primate teeth.

This study evaluated the histologic responses of two different adhesive systems on the teeth of seven healthy adult monkeys. Class V cavities in 128 teeth were observed at 7,21 to 27, and 90 to 97 days. Statistical data showed no significant differences in pulp inflammation between the Optibond (Kerr), XR-Bond (Kerr), and IRM (Caulk) groups in pulps at the three time intervals. Some odontoblastic disruption and inflammation was seen in pulps restored with XR-Primer at the three time intervals. Pulp healing was similar in teeth treated with both direct-capped Optibond and calcium hydroxide, and there was no significant increase in pulpal inflammation with time. No abscesses or necrotic pulps were seen in any teeth. Optibond and XR-Bond adhesive systems are biologically acceptable in nonhuman primate pulp tissues.

Biocompatability of compomer restorative systems on nonexposed dental pulps of primate teeth.

This study evaluated the histologic response of total-etched and nonetched compomer restored cavity preparations. One hundred fifteen class 5 cavity preparations were placed in the teeth of four healthy adult monkeys at 7, 27, and 90 days. A 37% H3PO4 was applied for 10 seconds and rinsed in total-etched preparations. No statistical differences were seen in inflammatory reactions among total-etched or nonetched compomers at 7, 27, and 90 days. There were no statistical differences in inflammatory cell responses among all compomer systems in regard to time intervals. Pulpal responses of compomers were greater than IRM at each time period. Pulp responses were associated with stained bacteria in 32 of 89 compomer teeth. No necrotic pulps were seen in any teeth. Statistical data show a positive correlation (P < 0.05) between bacterial presence and pulpal inflammation. IRM pulps showed no inflammation or bacterial staining. Compomers are biologically compatible with pulp tissues when bacteria are excluded.

Biocompatibility of various dental materials: pulp healing with a surface seal.

Class V cavities with mechanical exposures were prepared in 178 teeth of seven monkeys to observe the temporal healing of exposed pulps in direct contact with various dental materials, with or without a biologic seal of zinc-oxide eugenol cement against microleakage. Thirty pulps were direct capped as calcium hydroxide controls. The remaining 148 exposures were direct capped, 41 with silicate, 39 with zinc phosphate, 33 with amalgam, and 35 with an auto-cured composite. Sixty-four were restored to their cavosurface margin with their respective material and 84 were sealed to the covosurface margin with zinc-oxide eugenol cement. Tissues were obtained by perfusion fixation at intervals of 35, 21, 14, 10, 5, and 3 days, and then processed and evaluated. The results of this study demonstrated that exposed dental pulps possess an inherent healing capacity, allowing cell reorganization and dentin bridge formation when adequately sealed with zinc-oxide eugenol cement to prevent bacterial microleakage.

Evaluating the antagonistic wear of restorative materials when placed against human enamel.

Several clinical and laboratory studies have reported data on the nature of tooth wear against restorative materials (that is, amalgam, gold, glass ceramic and various composite resin systems). Several antagonistic substrates are known to cause various in vitro wear rates when placed in opposition to enamel. In this study, the authors evaluated 10 commercially available posterior composite resin systems and a gold alloy control. The findings showed that posterior composite resins containing zirconium silicate or quartz fillers caused greater antagonistic enamel wear than did microfilled or barium silicate-filled composite resins.

Tunnel defects in dentin bridges: their formation following direct pulp capping.

This study was conducted to observe the formation and nature of tunnel defects in dentin bridges, assess the nature of the associated soft tissue elements, and note the relationship of pulp inflammation and necrosis associated with these defects. A total of 235 teeth with class 5 cavity preparation exposures were randomly distributed throughout the dentitions of 14 adult rhesus monkeys. Each pulp was exposed and left open to the oral microflora at one of four time intervals, flushed with saline, debrided, capped with one of two hard-set calcium hydroxide medicaments [Ca(OH)2 (Dycal or Life)] and restored with a dispersed-phase amalgam alloy. Observation times were 14 days, 5 weeks, and 1 and 2 years. A total of 192 dentin bridges formed against the Ca(OH)2 medicaments Life or Dycal in 235 pulp-capped teeth. Considering all four capping periods, 89% of all dentin bridges contained tunnel defects (172 of 192). Forty-one percent (78) of the 192 dentin bridges were associated with recurring pulp inflammation or necrosis and were always associated with the presence of inflammatory cells and stained bacterial profiles. This study demonstrates that a statistically significant number of dentin bridges contain multiple tunnel defects, most of which appear to remain patent. These patent tunnels fail to provide a hermetic seal to the underlying pulp against recurring infection due to microleakage. Most Ca(OH)2 medicaments have been reported to disintegrate and wash out after 6 months, leaving a void underneath the restoration and thereby a pathway for bacterial infection. This study reemphasizes the need to employ biologically relevant measures that will provide a long-term clinical seal against microleakage following direct pulp capping with Ca(OH)2 medicaments alone.

Biocompatibility of dental adhesives.

This article provides biological and technological information to support routine use of new cohesive bonding systems with definitive restorations. With these systems, clinicians may expect many advantages over the more traditional water soluble base and liner systems. Hybridization of vital dentin will prevent postoperative hypersensitivity under restorations and completely seal the tooth-restoration interface to prevent bacterial infection of the underlying substrate, ultimately reducing recurrent caries underneath the hybridized restoration.