4 research outputs found
Nanoparticle formulations for new cytostatic agents against glioblastomas
No full textMany highly active antitumour agents are currently not employable for the systemic chemotherapy of brain tumours since their entrance into the brain is blocked by the BBB. Obviously, the development of a strategy allowing effective delivery of these agents across the BBB would enormously extend the potential of the systemic chemotherapy. Chemotherapy of rat glioblastoma using nanoparticle-bound doxorubicin Doxorubicin bound to polysorbate-coated nanoparticles had been previously shown to significantly enhance survival in the orthotopic rat 101/8 glioblastoma model. The objective of this study was to investigate the therapeutic effects of this formulation by morphometric, histological and immunohistological methods. The 101/8 glioblastoma was implanted intracranially into the male Wistar rats. The animals were randomly divided into 3 groups; one group served as untreated control (n = 20). The second group received doxorubicin in solution (Dox-sol, n = 18), and the third group received doxorubicin bound to PBCA nanoparticles coated with PS 80 (Dox-NP + PS 80, n = 18). The treatment regimen was 3 × 1.5 mg/kg on days 2, 5, and 8 after tumor implantation. The formulations were injected into the tail vein. The untreated control animals were sacrificed on days 6, 8, 10, 12, and 14 after the implantation. The animals that had received chemotherapy were sacrificed on day 10, 14 and 18 after the implantation. The brains were investigated by morphometrical, histochemical, and immunohistochemical methods such as the measurement of the tumor size, proliferation of tumor cells, vessel density, expression of glial fibrillary acidic protein (GFAP), expression of vascular endothelial growth factor (VEGF), incidence and dimension of necrosis, and microvascular proliferation. Tumours showed signs of malignancy including invasion to brain tissue and brisk mitotic activity. The tumor proliferation remained stable at high levels throughout the host survival time. Overall, the tumor showed a reproducible growth pattern and temporal development that is comparable to human glioblastoma. Furthermore, the 101/8 glioblastoma had infiltrated diffusely the surrounding host brain at the edge of the solid tumor mass showed no signs of encapsulation. Thus the 101/8 glioblastoma fulfills the most criteria for an adequate glioma model and can be qualified as a reliable model. ...Viele hochaktive Zytostatika sind zurzeit für die systematische chemotherapeutische Anwendung nicht einsetzbar, weil ihr Eintritt ins Gehirn durch die Blut-Hirn-Schranke (BHS) blockiert wird. Die Entwicklung einer Möglichkeit zum Transport dieser Stoffe über diese Schranke würde das Potenzial einer systemischen Chemotherapie bedeutend erhöhen. Chemotherapie von Glioblastomen mit Doxorobicin beladenen Nanopartikeln In früheren Studien wurde gezeigt, dass die Überlebenszeiten von Ratten mit ins Gehirn transplantierten 101/8 Glioblastomen durch mit Polysorbat 80 überzogenen Doxorubicin-Nanopartikel signifikant verlängert werden können. Ziel der vorliegenden Studie war es, die Effizienz dieser Doxorubicin-beladenen Nanopartikel mit morphometrischen, histologischen und immunohistologischen Methoden zu untersuchen, um so die Tiere weniger zu belasten als das in Letalitätsstudien erfolgt. Das 101/8 Glioblastom wurde dazu intrakranial männlichen Wistar-Ratten implantiert. Die Ratten wurden randomisiert in drei Gruppen geteilt: die erste Gruppe erhielt keine Behandlung (Kontrolle, n = 20), die zweite Gruppe wurde mit Doxorubicin-Lösung (Dox-sol, n = 18) und die dritte Gruppe mit Polysorbat 80-überzogenen Doxorubicin-Nanopartikeln (Dox-NP + PS 80, n = 18) behandelt. ..
PLAY AND PLAYSCRIPT: DRAMATIC STRUCTURE IN SIX VOLTAIREAN TRAGEDIES (FRANCE)
No full textKnown primarily as a playwright by his contemporaries, today Voltaire the dramatist is generally dismissed as inferior. This fact led to the hypothesis that for their dramatic value as theatre to surface, his texts must be considered as playscripts bound for completion in performance rather than as finite literary works. Therefore, six representative tragedies were chosen, Adela(\u27)ide du Guesclin (1734), Zulime (1740), Semiramis (1748), L\u27Orphelin de la Chine (1755), Tancrede (1760), and Le Triumvirat (1764). The plays were evaluated through analysis of dramatic structure in relationship to dramatic effectiveness. First, after extensive study of the playscript, a unifying principle was proposed to which all subsequent interpretive decisions were referred in order to ensure unity and consistency. Next, the dramatic structure was examined with a view toward answering four fundamental questions: (1) What structures are used to promote audience involvement and disengagement? (2) How might the actor enhance or detract from audience response? (3) What is specifically tragic about the dramatic structure he employed? (4) How do the nontraditional endings fit into this basic tragic structure? Assuming that the author\u27s goal is to interest an audience through manipulation of dramatic structure, the creation of sympathetic characters, suspense generated as to a situation\u27s outcome, and varying tempo, intensity, and levels of knowledge constitute the means to this end. Close playscript analysis reveals the importance of the actor\u27s contribution to dramatic effectiveness. The works\u27 tragic tone derives from the type of situation explored. Voltaire preferred personal rather than universal dilemmas--man against man or man against society, and, often, the hero is able to overcome the obstacle confronting him, allowing the tragedy to end happily. Overall dramatic structure shows marked variation and experimentation in the elaboration of plot and in the devices employed to provoke spectator response. These include the use of a late point of attack; progression, repetition, and juxtaposition of events; a balanced act structure; and action-filled entr\u27actes. All the essentially theatrical elements which contribute to performance--actors/physical properties/audience--combine with tragic tests structured to evoke maximum audience response to produce interesting, involving plays
