Immunomodulatory and anti-cancer potential of cloves (Syzygium aromaticum) bud extract and its phytogenic silver nanoparticles.

Clove plant (Syzygium aromaticum) is one of the Myrtaceae family. It's a common flavor in food and the traditional medicine. The study's objective was to ascertain whether the clove bud aqueous extract (CAE) and CAE + nanosilver have any biological effects on immune cells and HT-29 colon cancer cell line. Nanosilver was produced through green synthesis approach using CAE. Produced nanosilver was characterized via electron microscope (scanning, SEM) and ultraviolet-visible spectroscopy. CAE and CAE + nanosilver were examined for their active biomolecules using FTIR analysis, p53 contents using real-time PCR, apoptosis and cell cycle arrest power on HT-29 cancer cell line via flow cytometerty and immunomodulatory potential utilizing MTT assay. Results cleared that a spherical nanosilver with a diameter range of 53 nm was formed by CAE. There were several active biomolecules in CAE and CAE + nanosilver. CAE and CAE + nanosilver increased the p53 protein expression and apoptotic cell number in HT-29 colon cancer cells. CAE and CAE + nanosilver could arrest HT-29 cells at the phase G2/M. CAE and CAE + nanosilver stimulated quiescent and PHA-pre-treated splenic cells at higher concentrations, and CAE suppressed quiescent splenic cell when diluted. In conclusion, the safe edible Syzygium aromaticum plant can be utilized to make anti-tumor agent, essentially for colon tumor. As Syzygium aromaticum plant could stimulate immune cells, it can be used as immune-stimulatory agent that can help fight tumor and tumor development.

SU-E-T-576: Investigation of Combining Modulated Electron Beams with Intensity Modulated Photons for Radiation Therapy of Breast Cases.

PURPOSE: Modulated electron radiation therapy (MERT) can offer significant advantages for breast treatments over conventional radiotherapy in terms of sparing distal critical structures. While intensity modulated radiation therapy (IMRT) has the advantage of achieving better dose homogeneity inside the target combining both MERT and IMRT will be the ideal scenario. The Aim of the present study is to investigate the possibility of further improving breast radiation therapy using combined MERT/IMRT treatment technique. METHODS: Accurate modeling of a prototype motorized electron multileaf collimator was verified in a separate study. In this work treatment planning was performed by an in house Monte Carlo based inverse planning system. Dose deposition coefficients were calculated using MCPLAN and utilizing real patients CTs. Optimization is then conducted based on an equivalent uniform dose objective function. MERT and IMRT plans were created for different patients. RESULTS: The clinical beneficial outcome for MERT either alone or combined with IMRT was investigated based on isodose distributions and dose volume histograms. It is shown that MERT can give similar dose distributions as IMRT in some cases. For some cases, MERT could be advantageous whenever more skin dose was required. In some cases MERT can be identified as the best option. It was found that MERT compared to IMRT could introduce hot spots inside the target. However this was resolved in combined MERT/IMRT treatment. Dose uniformity can be restored with a reduction in the maximum lung and heart received dose. CONCLUSION: MERT can improve treatment plan quality for many breast patients. In some cases better results can be obtained with a combined MERT/IMRT treatment, where a homogeneous dose in the target can be achieved with an improvement in the DVH of critical structures. This work has been supported by a UICC American Cancer Society Beginning Investigators Fellowship funded by the American Cancer Society.

SU-E-T-441: A Feasibility Study to Replace Electron Cutouts with a Motorized Electron Multileaf Collimator.

PURPOSE: Fabrication of electron beam cutouts not only is a time consuming process but also involves the handling of cerrobend which is a toxic material. Hospital workers involved in cutout construction can actually be exposed to toxic fumes that are usually generated during the process. The aim of this work is to study the feasibility of replacing electron cutouts with our prototype motorized electron multileaf collimator (eMLC). METHODS: Electron beams collimated by an eMLC have very similar penumbra to those collimated by applicators and cutouts as we already demonstrated in a previous study. However undulation of the isodose curves is expected due to the finite size of the eMLC. This may be a problem when the field edge is close to critical structure. Thus ten different breast cases that were previously treated with an electron boost were selected from our database. An inhouse Monte Carlo based treatment planning system were used for dose calculation using the patients CTs. For each patient two plans were generated one with electron beams collimated using the applicator/cutout combination and the other plan with beams collimated only by the eMLC. Treatment plan quality was compared for each patient based on dose distribution and dose volume histogram. In order to determine the optimal position of the leaves, the impact of the different leaf positioning strategies were investigated. RESULTS: Results have shown that target coverage and critical structure sparing can be effectively achieved by electron beams collimated by eMLC. Preliminary results have shown that the out-of-field strategy is most conservative and would be the recommended method to define the actual leaf position for the eMLC defined field. CONCLUSION: The eMLC represents an effective time saving and pollution free device that can completely eliminate the need for patient specific cutouts. This work has been supported by a UICC American Cancer Society Beginning Investigators Fellowship funded by the American Cancer Society.

SU-E-T-450: An Evaluation Study of Dose Calculation Algorithms for Stereotactic Body Radiation Therapy in Heterogeneous Phantom.

PURPOSE: In Stereotactic body radiation therapy (SBRT) higher dose per fraction is delivered to patients and thus the need for an accurate dose computation is further elevated. However under such conditions of small field geometries, the electronic equilibrium can be lost, making it challenging for the dose-calculation algorithm to accurately predict the dose, especially in the presence of tissue heterogeneities. Thus the aim of this study is to evaluate the performance of the algorithms implemented in our treatment planning system. METHODS: In this study different phantoms were designed to model the lung with a small tumor volume of sizes that are usually encountered in SBRT. Solid water and cork slabs were used in constructing the phantom body. Perspex pieces of different diameters were created to be inserted in precut holes in the cork to simulate the tumor. The various dose calculation algorithms that are implemented in our CMS XIO planning system were then used for dose calculation inside the target. RESULTS: A significant discrepancies between maximum, minimum and mean dose for PTV was found between Clarkson, FFT Convolution, Fast superposition and superposition algorithms in dose calculation for the lung tumor. The FFT Convolution and Clarkson algorithms have higher calculated minimum dose than that predicted by the superposition and the fast superposition algorithm. A percentage difference as high as 62.5% was obtained between Clarkson and the superposition algorithm in the estimated minimum dose. A percentage difference up to 13.4% was obtained between the FFT Convolution and the superposition algorithm for the estimated maximum dose. Superposition and fast superposition showed little discrepancies for maximum, minimum and mean dose for the PTV. CONCLUSION: It is very critical to address the accuracy of dose computation for SBRT as a significant dose overestimation can occur inside the target due to the heterogeneous geometries.

Dosimetric verification of modulated electron radiotherapy delivered using a photon multileaf collimator for intact breasts.

Modulated electron radiotherapy (MERT) may potentially be an effective modality for the treatment of shallow tumors, but dose calculation accuracy and delivery efficiency challenges remain. The purpose of this work is to investigate the dose accuracy of MERT delivery using a photon multileaf collimator (pMLC) on a Siemens Primus accelerator. A Monte Carlo (MC)-based inverse treatment planning system was developed for the 3D treatment planning process. Phase space data of 6, 9, 12 and 15 MeV electron beams were commissioned and used as the input source for MC dose calculations. A treatment plan was performed based on the 3D CT data of a heterogeneous 'breast phantom' that mimics a breast cancer patient, and delivered with 22 segments, each associated with a particular energy and Monitor Unit value. Film and ion chamber dosimetry was carefully performed for the conversion from measurement reading to dose, and the results were employed for plan verification using the heterogeneous breast phantom and a solid water phantom. Dose comparisons between measurements and calculations showed agreement within 2% or 1 mm. We conclude that our in-house MC treatment planning system is capable of performing treatment planning and accurate dose calculations for MERT using the pMLC to deliver radiation therapy to the intact breast.

Autophagy in hepatocytes and erythropoietic cells isolated from the twenty-one day old rat embryo.

Liver cells of the twenty-one day old rat embryo are isolated by a modified method and autophagy is studied in them by electron microscopic morphology and morphometry. Immediately after isolation or 2.5 h incubation in nutrient-free medium, embryonic hepatocytes contain high amount of glycogen and only very few autophagic vacuoles. In contrast, all glycogen is lost and 15% of the cytoplasmic volume is occupied by late autophagic vacuoles in hepatocytes after 18 h in the same medium. Presence of 3-methyladenine in the latter case inhibits both the loss of glycogen and the appearance of autophagic vacuoles while enlarging the multivesicular body compartment. Our findings reveal major differences between isolated embryonic and adult hepatocytes concerning autophagy. Several types of autophagic vacuoles are described in the cell types of the erythropoietic cell lineage. This means that autophagy is an integral part of erythropoiesis not only in bone marrow, but also in embryonic liver that is investigated here for the first time from this point of view. The presence of unclosed isolation membranes and the predominance of early autophagic vacuoles in reticulocytes indicates that the molecular machinery of segregation is still active in this functionally and structurally highly reduced cell type.