N. Signals of growth factor receptors such
as EGFR activation Ras guanosine triphosphatase mediated the little FTase posttranslational modification for activity ben t CONFIRMS. FTase inhibitors inhibit the functions of Ras, including normal F Promotion of oncogenesis BMS-708163 and Strahlungsbest RESISTANCE. RTI not only directly the function of Ras, but. The effect of interrupting tyrosine kinase receptors that signal through Ras So although gliomas rarely contain mutated oncogenic forms of Ras, common genetic aberrations such as overexpression of EGFR are anf Llig for therapeutic targeting of FTI The exact mechanism of action of FTI remains uncertain as Ras mutation status is not always with the response of cells to FTI treatment also correlated Spreizk Body evidence that FTI activity T mediated in part by inhibition of farnesylation of other members of the Ras family how RhoB decreased this ambiguous bonds notwithstanding the treatment of gliomas in vitro results in FTI proliferation and apoptosis induction.
In addition, Glioma cells overexpressing EGFR hte increased sensitivity exposure RTI such treatment. The main purpose of the present study are promising results indicating that treatment with FTI sensitizes human cancer cells to irradiation, especially if they. Ras mutations or harboring a high activity T by Ras activation constitutive upstream signals These data MEK Signaling Pathway support the hypothesis that FTI is pr a selective action against BSG Sentieren compared to normal brain tissue and increased Hen tumor response to radiation.
Tipifarnib is a potent and selective, orally available, FTI nonpeptidomimetic durchl both phases Runs I and phase II metabolism in the liver A Phase I tipifarnib study of the Consortium has been carried out to p Pediatric brain tumors describe dose-limiting toxicity Th and maximum tolerated dose Sch the simultaneous oral administration of tipifarnib and radiation estimation for p diatrische patients nondisseminated diffuse intrinsic BSG intrinsic safety. This study provided the basis for a Phase II study of tipifarnib PBTC simultaneously and managed by radiation therapy in children with BSG. Materials and Methods The primary objectives of the study Re aim of the study was to determine the maximum tolerable Possible dose of tipifarnib administered protect fa beautiful It concomitant radiotherapy at p Nondisseminated pediatric patients, diffuse intrinsic BSG.
A secondary Res goal was the toxicity of th With tipifarnib treatment in combination with radiotherapy and more connected to describe. Another secondary Res target, which will be presented separately, it was the radiological changes Ver Tipifarnib in BSG with radiotherapy and MRI, spectroscopy, perfusion and diffusion imaging and PET characterize treated. Eligibility for Sick Children and over the years or less and recently new U diagnosed diffuse intrinsic BSG nondisseminated for this study. Other suitable criteria for assessment of Karnofsky performance score or Lansky performance, bone marrow function, and appropriate for a ad Quate renal and hepatic function. Patients again U before irradiation, chemotherapy or experimental anti-cancer agents, except for the stero Of, and the patient