Monte Carlo Simulation of Bony Heterogeneity Effects on Dose Profile for Small Irradiation Field in Radiotherapy

In the radiotherapy treatment planning of a lesion located in the head region with small field radiation beams, the heterogeneity corrections play an important role. In this work, we investigated the influence of a bony heterogeneity on dose profile inside a soft tissue phantom containing a bony material. PDD curves were obtained by simulation using the Monte Carlo code EGSnrc and employing Eclipse® treatment planning system algorithms (Batho, Modified Batho, Equivalent TAR and Anisotropic Analytic Algorithm) for a 15 MV photon beam and field sizes of 2×2 and 10×10 cm2. The Equivalent TAR method exhibited better agreement with Monte Carlo simulations for the 2×2 cm2 field size. The magnitude of the effect on PDD due to the bony heterogeneity for 1×1, 2×2 and 10×10 cm2 field sizes increases to 10, 5 and 3%, respectively

Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding

Peroxisome proliferator activated receptors (PPARs δ, α and γ) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328) in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design

Low-Resolution Molecular Models Reveal the Oligomeric State of the PPAR and the Conformational Organization of Its Domains in Solution

The peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid and carbohydrate metabolism, and are targets of drugs approved for human use. Whereas the crystallographic structure of the complex of full length PPARγ and RXRα is known, structural alterations induced by heterodimer formation and DNA contacts are not well understood. Herein, we report a small-angle X-ray scattering analysis of the oligomeric state of hPPARγ alone and in the presence of retinoid X receptor (RXR). The results reveal that, in contrast with other studied nuclear receptors, which predominantly form dimers in solution, hPPARγ remains in the monomeric form by itself but forms heterodimers with hRXRα. The low-resolution models of hPPARγ/RXRα complexes predict significant changes in opening angle between heterodimerization partners (LBD) and extended and asymmetric shape of the dimer (LBD-DBD) as compared with X-ray structure of the full-length receptor bound to DNA. These differences between our SAXS models and the high-resolution crystallographic structure might suggest that there are different conformations of functional heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange experiments reveal that the heterodimer binding to DNA promotes more compact and less solvent-accessible conformation of the receptor complex

Evaluation of the radiotherapy treatment planning in the presence of a magnetic valve tissue expander.

The combination of radiotherapy treatments and breast reconstruction, using temporary tissue expanders, generates several concerns due to the presence of a magnetic valve inside the radiation field. The objective of this work is to evaluate a radiotherapy treatment planning for a patient using a tissue expander. Isodose curve maps, obtained using radiochromic films, were compared to the ones calculated with two different dose calculation algorithms of the Eclipse radiotherapy Treatment Planning System (TPS), considering the presence or absence of the heterogeneity. The TPS calculation considering the presence of the heterogeneity shows changes around 5% in the isodose curves when they were compared with the calculation without heterogeneity correction. This calculation did not take in account the real density value of the heterogeneity. This limitation was quantified to be around 10% in comparison with the TPS calculation and experimental measurements using the radiochromic film. These results show that the magnetic valve should be taken in account in dose calculations of the TPS. With respect to the AAA and Pencil Beam Convolution algorithms, when the calculation is compared with the real distribution, AAA presents a distribution more similar to experimental dose distribution

Results for density and dimensional stability tests for some breast phantoms.

<p>Results for density and dimensional stability tests for some breast phantoms.</p

Dose x Depth Monte Carlo Simulations, comparing the two densities; black squares for 7.4g/cm³ and red circles for 5.0g/cm³.

<p>Dose x Depth Monte Carlo Simulations, comparing the two densities; black squares for 7.4g/cm³ and red circles for 5.0g/cm³.</p

Isodose crossplane calculated with (a) TPS and (b) measured with radiochromic film.

<p>Isodose crossplane calculated with (a) TPS and (b) measured with radiochromic film.</p

CT image showing artifacts due to the presence of the magnetic disk.

<p>CT image showing artifacts due to the presence of the magnetic disk.</p

Maps of isodose curves calculated with and without correction for two different algorithms, PBC and AAA.

<p>Maps of isodose curves calculated with and without correction for two different algorithms, PBC and AAA.</p