Skin dose distributions between Stanford and rotational techniques in total skin electron therapy (TSET).

PURPOSE: Total skin electron therapy (TSET) has proven to be one of the most effective treatments for advanced-stage cutaneous T-cell lymphoma. Two most used techniques are the Stanford six-field and rotational techniques. This study compares patient skin dose distributions as a function of depth between these two techniques. METHODS: The EGSnrc system was used to simulate electron beams and calculate patient dose distributions. The calculations assumed the same patient standing on a platform, and the patient's different postures were ignored for the Stanford technique in the comparison of dose distributions. The skin doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms (DVH). The comparisons were performed in three realistic clinical settings in which dual-field were used for patients treated at extended distances of 316 and 500 cm, and a single field was used at 700 cm. In all cases the realistic patient treatment beam delivery geometry was simulated. RESULTS: Although small dose differences were observed in some local areas, no clinically significant differences were found in the patient 3D dose distributions between the Stanford and rotational techniques. Virtually the same DVH curves between two the techniques were observed for mean dose to skin depth of 0-5, 5-10, and 10-15 mm from the skin surface, respectively. It is found that the skin depth dose coverage is 2 mm shallower for patient treatment at 500 cm compared to at 316 cm due to the additional air attenuation. However, very similar dose coverage and uniformity can be achieved at these two different extended treatment distances by adjusting the thickness of acrylic scatter plate. Adequate thickness of a scattering plate improves the skin dose uniformity. CONCLUSION: Both the Stanford and rotational techniques deliver very similar skin dose coverage in DVH plots, and only small differences are seen in local areas. It is worth to emphasize that the DVH is a graphical representation of the distribution of dose within a structure, and it does not contain spatial information. Therefore, comparison of entire skin dose using DVH may mask some variations at different locations of the surface area. In addition, the comparison did not consider different patient postures of the Stanford technique. Including the different patient postures in the calculation may affect the result of doses to the limbs.

Cherenkov imaging for Total Skin Electron Therapy - an evaluation of dose uniformity.

Total Skin Electron Therapy (TSET) utilizes high-energy electrons to treat cancers on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high-energy electron beam and tissue. Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real-time using a time-gated intensified camera system. Each patient was monitored during TSET by in-vivo detectors (IVD) as well as Scintillators. Patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. A rigorous methodology for converting Cherenkov intensity to surface dose as products of correction factors, including camera vignette correction factor, incident radiation correction factor, and tissue optical properties correction factor. A comprehensive study has been carried out by inspecting various positions on the patients such as vertex, chest, perineum, shins, and foot relative to the umbilicus point (the prescription point).

Monte Carlo (MC) study of dose distribution and Cherenkov imaging in total skin electron therapy (TSET) with TOPAS.

Malignant tissues can be effectively treated by Total Skin Electron Therapy (TSET) over the entire body surface using 6 MeV electron beams. During the radiation treatment, Cherenkov photons are emitted from the patient's skin, and can potentially be used for in-vivo imaging of the radiation dose distribution. A Monte Carlo (MC) simulation toolkit TOPAS is used to study the generation and propagation of Cherenkov photons that are generated from the interaction of electron radiation with human tissues, and to understand the relationship between the dose distributions and the Cherenkov photon distributions. Validation of MC simulations with experiments are performed at 100 SSD and 500 SSD, and simulations of a patient phantom in realistic clinical treatment setups have been done. These simulations with TOPAS show that the emitted Cherenkov distributions at phantom surfaces closely follow their corresponding dose distributions.

A Toll-like receptor 9-mediated pathway stimulates perilipin 3 (TIP47) expression and induces lipid accumulation in macrophages.

Excessive accumulation of lipids in macrophages results in formation of foam cells and is a hallmark of atherosclerosis. The PAT family of proteins has been implicated in this process, but details of their involvement in foam cell formation have not been fully elucidated. One of dominant members of the PAT proteins, perilipin 3 (TIP47), is likely to be involved in such a regulatory mechanism. In this study, we demonstrated that the Toll-like receptor 9 (TLR9)-mediated pathway stimulates perilipin 3 expression and accumulation of lipids, especially triglycerides, in macrophages. Oligodeoxynucleotide (ODN) 1826, a ligand of TLR9, significantly enhanced perilipin 3 expression in RAW264.7 cells, and chloroquine, a TLR9 inhibitor, almost completely inhibited ODN1826-induced perilipin 3 expression. The inhibitors of c-jun NH2-terminal kinase and PI 3-kinase suppressed the level of perilipin 3 mRNA induced by ODN1826. ODN1826 induced the expression of IL-1α and IFNß, both of which increased perilipin 3 expression. Antibodies against these cytokines suppressed the ODN1826-induced perilipin 3 mRNA levels. These results suggest that the expression of perilipin 3 in macrophages is in part regulated through the TLR9-mediated mechanism. Furthermore, ODN1826 increased intracellular lipid accumulation in the presence of oxLDL, which was reduced by perilipin 3 siRNA. Perilipin 3 expression was not stimulated by oxLDL. Depletion of perilipin 3 by siRNA specifically reduced triglyceride content in the cells but not cholesterol content, indicating that perilipin 3 is involved mainly in triglyceride accumulation. In conclusion, the TLR9-mediated pathway facilitates foam cell formation in part through increased expression of perilipin 3.

L-arginine attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells.

OBJECTIVE: Endothelial dysfunction is a key event in the onset and progression of atherosclerosis associated with diabetes. Increasing cell senescence may lead to endothelial dysfunction and contribute to vascular complications. Therefore, we aimed to elucidate the possible role and mechanism of L-arginine in preventing cell senescence induced by high glucose. METHODS: HUVECs were respectively cultured under normal control glucose (5.5mM), high glucose (33mM), co-incubation with L-arginine (800microM)and high glucose, and senescence was identified by beta-galactosidase staining, change of cell cycle and telomerase activity. Akt and eNOS activity was analyzed by western blot. RESULTS: High glucose significantly increased number of beta-galactosidase-positive stained cells, inhibited telomerase activity, increased proportion of cells in the G(0)/G(1) phase and reduced proportion in the S phase, and decreased NO synthesis. L-arginine significantly attenuated these senescent alterations. Furthermore, high glucose induced a decrease in Akt and eNOS activity, and L-arginine prevented the decrease in activity. The PI3K inhibitor LY294002 or eNOS inhibitor L-NAME attenuated anti-senescence effect of L-arginine. CONCLUSION: L-arginine may have an anti-senescence effect via the PI3K/Akt pathway in HUVECs exposed to high glucose and it might be a therapeutic agent for diabetic vascular complications.