E18-2007-91 SIMULATIONS OF PROTON BEAM DEPTH-DOSE DISTRIBUTIONS

Rajcan M., Molokanov A. G., Mumot M. E18-2007-91 Simulations of Proton Beam Depth-Dose Distributions Proton beams are successfully used in radiotherapy. A correct modiˇcation of beam parameters enables to spare normal surrounding tissues from radiation action. Our work is focused on passive beam-shaping techniques, which are used to modify the proton beam properties. The beam passes through the scattering system, which consists of scattering materials, energy degraders, drift spaces and collimators. In order to model the proton beam transport through the scattering system, the new Monte Carlo (MC) computer code Track has been developed. The code Track can predict output proton beam parameters modulated by various system adjustments and helps to optimize them. It calculates a beam proˇle, creates beam emittance diagram at a speciˇed position of the system and predicts proton beam depthdose distribution in a water phantom. In addition it calculates beam losses on individual components. We present a physical model of the beam transport calculations and algorithm implemented in a code Track. We compared the Track code calculations of depth-dose distributions in water phantom with experimental data and with a set of MC calculations in the FLUKA code. The accuracy of simulation results and calculation time in Track code are observed

Measurements of Spatial Dose Distributions of Proton Beam with the Use of Radiochromic Films

A radiochromic film (RCF) is investigated for use in proton beam dosimetry in a water phantom. Investigations have been performed to measure the sensitivity of the RCF and its dependence on changing energy of the beam and on linear energy transfer (LET). Experiments were carried out with both unmodulated and modulated proton beams. The results show that the sensitivity of the RCF decreases with increasing LET and this effect increases errors of measurements for lower energies of the beam. Nevertheless, the radiochromic film seems to be an adequate detector for dosimetry in phantom measurements where high spatial resolution is required. The correction of the film sensitivity in the Bragg peak region is advisable

A novel Bim-BH3-derived Bcl-XL inhibitor

BH3-only members of the Bcl-2 family exert a fundamental role in apoptosis induction. This work focuses on the development of a novel peptidic molecule based on the BH3 domain of Bim. The antiapoptotic molecule Bcl-XL, involved in cancer development/ progression and tumour resistance to cytotoxic drugs, is a target for Bim. According to a rational study of the structural interactions between wt Bim-BH3 and Bcl-XL, we replaced specific residues of Bim-BH3 with natural and non-natural aminoacids and added an internalizing sequence, thus increasing dramatically the inhibitory activity of our modified Bim-BH3 peptide, called 072RB. Confocal microscopy and flow cytometry demonstrated cellular uptake and internalization of 072RB, followed by co-localization with mitochondria. Multiparameter flow cytometry demonstrated that the 072RB dose-dependent growth inhibition of leukaemia cell lines was due to apoptotic cell death. No effect was observed when cells were treated with the internalizing vector alone or a mutated control peptide (single aminoacid substitution L94A). Ex-vivo derived leukemic cells from acute myeloid leukaemia (AML) patients underwent cell death when cultured in vitro in the presence of 072RB. Conversely, no significant cytotoxic effect was observed when 072RB was administered to cultures of peripheral blood mononuclear cells, either resting or PHA-stimulated, and bone marrow cells of normal donors. Xenografts of human AML cells in NOD/SCID mice displayed a significant delay of leukemic cell growth upon treatment with 072RB administered intravenously (15 mg/Kg three times, 48 hours after tumour cell injection). Altogether, these observations support the therapeutic potentials of this novel BH3 mimetic