Comparative Study of Extremely Low-Frequency Electromagnetic Field, Radiation, and Temozolomide Administration in Spheroid and Monolayer Forms of the Glioblastoma Cell Line (T98).

BACKGROUND: Glioblastoma is the most common primary malignant tumor of the central nervous system. The patient's median survival rate is 13.5 months, so it is necessary to explore new therapeutic approaches. OBJECTIVE: Extremely low-frequency electromagnetic field (EMF) has been explored as a noninvasive cancer treatment. This study applied the EMF with previous conventional chemoradiotherapy for glioblastoma. METHODS: In this study, we evaluated the cytotoxic effects of EMF (50 Hz, 100 G), temozolomide (TMZ), and radiation (Rad) on gene expression of T98 glioma cell lines in monolayer and spheroid cell cultures. RESULTS: Treatment with Rad and EMF significantly increased apoptosis-related gene expression compared to the control group in monolayers and spheroids (p<0.001). The expression of apoptotic-related genes in monolayers was higher than the similar spheroid groups (p<0.001). We found that treatment with TMZ and EMF could increase the gene expression of the autophagy cascade markers compared to the control group (p<0.001). Autophagy-related gene expression in spheroids was higher than in the similar monolayer group (p<0.001). We demonstrated that coadministration of EMF, TMZ, and Rad significantly reduced cell cycle and drug resistance gene expression in monolayers and spheroids (p<0.001) compared to the control group. CONCLUSION: The combinational use of TMZ, Rad and, EMF showed the highest antitumor activity by inducing apoptosis and autophagy signaling pathways and inhibiting cell cycle and drug resistance gene expression. Furthermore, EMF increased TMZ or radiation efficiency.

Radioprotective Effect of Zinc Nanoparticles on Ionizing Radiation-induced Nephrotoxicity in Mice.

INTRODUCTION: Ionizing radiation (IR) causes oxidative stress in kidneys and subsequently disrupts renal function. The use of green synthesized zinc nanoparticles (Zn NPs) with antioxidant properties may reduce the damage caused by IR. METHODS: Thirty-six mice were kept in a standard situation and divided into 6 groups: 1: Control; 2-4: receiving 5 mg/kg, 10 mg/kg, and 25 mg/kg of Zn NPs with IR; 5: receiving 5 mg/kg of ZnSO4 with IR; and 6: IR. After 15 days, half of the animals in each group were sacrificed and their blood samples isolated to evaluate the plasma urea and creatinine levels. The kidneys were kept for evaluating the glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels; on 21st day, the rest of the animals were sacrificed and their kidneys removed for histological assessments. RESULTS: IR decreased GSH content, increased MDA level, and reduced SOD and CAT activity. On the other hand, Zn NPs at 10 and 25 mg/kg doses increased GSH, decreased MDA, and enhanced SOD and CAT activities. Zn NPs treatment at 10 and 25 mg/kg doses decreased the plasma urea and creatinine levels induced by IR. Moreover, Zn NPs significantly decreased the level of urea and creatinine in irradiated mice in comparison with IR alone (p < 0.05). The main histopathological results were tubular and glomerular atrophy and interstitial fibrosis in irradiated mice, while tubular degeneration and atrophy were less frequent in Zn NPs + IR group than in IR group alone. CONCLUSION: Zn NPs treatment, especially at 25 mg/kg dose, attenuates the side effect of IR on kidneys through reducing oxidative stress factors, biochemical, and histopathological changes.

Ferulago angulata as a Good Radioprotector Against Genotoxicity.

INTRODUCTION: Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells are exposed to ionizing radiation, they generate free radicals and reactive oxygen species that can cause damage in DNA, which leads to cellular dysfunction or even cell death. However, it is necessary to identify new radioprotective agents to protect normal cells. Ferulago angulata (F. angulata), a medicinal plant, can be used as a new radioprotective agent. PURPOSE: In this study, the radioprotective effect of F. angulata was evaluated against genotoxicity and oxidative stress induced by ionizing radiation in human blood lymphocytes. METHODS: The antioxidant activity of F. angulata was assayed using FRAP and DPPH methods. Then, the human blood samples were incubated with F. angulata at different concentrations (25, 50, 100, and 200 µM) and subsequently exposed to IR at a dose of 2Gy. The radioprotective effect of F. angulata on the exposed cells was assessed by the micronucleus (MN) method. Also, biomarkers of oxidative stress in the exposed cells were evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) methods. RESULTS: Our findings showed that F. angulata reduced the frequency of MN induced by IR in exposed cells. At a 200 µM concentration of F. angulata, the maximum reduction in the frequency of MN (63.11%) was observed that demonstrated a high degree of radioprotection. Afterward, pretreatment at 200 µM concentration of F. angulata inhibited oxidative stress in irradiated lymphocytes, leading to a reduction in MN frequency and MDA levels while SOD activity was enhanced in the exposed cells. CONCLUSION: F. angulata as a natural radioprotective agent can protect normal cells against reactive oxygen species and genetic damage induced by IR.

Radioprotective Potential of Sulindac Sulfide to Prevent DNA Damage Due to Ionizing Radiation.

Introduction: The ionizing radiation exposure of the normal cell causes damage to DNA, which leads to cell dysfunction or even cell death. However, it is necessary to identify new radio protectives in order to protect normal cells. Sulindac sulfide (SS) is a metabolite of sulindac (a non-steroidal anti-inflammatory drug) known as a cyclooxygenase inhibitor. Free radicals and reactive oxygen species are generated in the IR-exposed cells. Also, the induced inflammation process causes damage in DNA. PURPOSE: In this research, the radioprotective effect of SS was investigated against genotoxicity and lipid peroxidation induced by ionizing radiation in the human blood lymphocytes. METHODS: In this study, the human blood samples were pretreated with SS at different concentrations (10, 25, 50, 100 and 250 µM) and then were exposed to IR at a dose of 1.5 Gy. The micronucleus (MN) assay was used to indicate the radioprotective effects of SS on exposed cells. Total antioxidant activity of the SS was measured by using FRAP and DPPH assay. Also, the malondialdehyde (MDA) levels and the activity of superoxide dismutase (SOD) on the exposed cells were evaluated. RESULTS: It was found that SS decreased the percentage of MN induced by IR in exposed cells. Maximum reduction in the frequency of MN was observed at 250 µM of SS (87%) that provides the highest degree of protection against IR. On the other hand, pretreatment at 250 µM of SS inhibited IR-induced oxidative stress, which led to a decrease in the MN frequencies and MDA levels, while SOD activity showed an increase in the exposed cells. CONCLUSION: It could be concluded that SS as a good radioprotective agent protects the human normal cells against the oxidative stress and genetic damage induced by IR.

Interpretation of In-air Output Ratio of Wedged Fields in Different Measurement Conditions.

BACKGROUND: The collimator scatter factor (Sc) is one of the most important parameters in monitor unit (MU) calculation. There are several factors that impact Sc values, including head structures, backscatter in dose monitoring chambers, and wedges. The objective of this study was to investigate the variation of Sc with different buildup cap materials, wall thickness of buildup caps, source-to-chamber distances (SCDs), ionization chambers, and wedge angles in 6 MV photon beam. METHODS: In this study, copper and Perspex buildup caps were made with two different thicknesses for each buildup cap. Measurements were performed on an Elekta Compact medical linear accelerator (6 MV) using RK dosimeter with a sensitive volume of 0.120 cm3 and Farmer-type ion chamber with a sensitive volume of 0.65 cm3. In all measurements, buildup caps and ionization chambers were positioned such as to stand vertically to the beam central axis. It was also investigated the effect of internal wedge with different angles (30° and 60°) different SCDs on Sc. RESULTS: It was found in large field sizes, Sc values in Perspex buildup cap were higher than copper. Different SCDs and type of ion chamber and wall thickness of buildup caps had no significant influence on Sc values. The presence of wedge influenced Sc values significantly. Variation of Sc in wedged fields compared to open fields had a maximum deviation of 0.9% and 6.8% in 30° and 60° wedge angles, respectively. CONCLUSION: It was found that the presence of wedges had a significant influence on Sc and increases with wedge angles. As such, it should be taken into account in manual MU calculations.

Effect of Material and Wall Thickness Buildup Caps on the Head Scatter Factor Measurements in Irregular Fields Shielded by Cerrobend.

The head scatter factor (Sc ) is important to measurements radiation beam and beam modeling of treatment planning systems used for advanced radiation therapy techniques. This study aimed to investigate the design of a miniphantom to measurement variations in collimator Sc in the presence of shielding blocks for shaping the beam using different field sizes. Copper, Brass, and Perspex buildup caps were designed and fabricated locally as material with three different thicknesses for buildup caps (miniphantoms). Measurements were performed on an Elekta Compact medical linear accelerator (6 MV) in Shafa Kerman Hospital, Iran. The Farmer-type ion chamber FG65-P (Scanditronix, Wellhofer) was used for all measurements. To measure the Sc , miniphantom was positioned in a stand vertical to the beam central axis. The data indicate that the Sc measurements using different buildup cap materials and thicknesses in 5 × 10, 7.5 × 7.5, and two 10 × 10 cm Cerrobend shield blocks ranged 0.98 to 1.00, 1.04 to 1.05, and 1.04 to 1.06, respectively. Also, it was observed that by increasing the block shield area from 50 cm2 to both 56.25 and 100 cm2, the Sc increased in all situations. Results showed that using Brass compared to Perspex and Copper has less uncertainty due to its simple preparation and cutting which is useful to measurement of variations in collimator Sc and shaping the photon beam.

Assessment of a 2D electronic portal imaging devices-based dosimetry algorithm for pretreatment and in-vivo midplane dose verification.

BACKGROUND: The use of electronic portal imaging devices (EPIDs) is a method for the dosimetric verification of radiotherapy plans, both pretreatment and in vivo. The aim of this study is to test a 2D EPID-based dosimetry algorithm for dose verification of some plans inside a homogenous and anthropomorphic phantom and in vivo as well. MATERIALS AND METHODS: Dose distributions were reconstructed from EPID images using a 2D EPID dosimetry algorithm inside a homogenous slab phantom for a simple 10 × 10 cm2 box technique, 3D conformal (prostate, head-and-neck, and lung), and intensity-modulated radiation therapy (IMRT) prostate plans inside an anthropomorphic (Alderson) phantom and in the patients (one fraction in vivo) for 3D conformal plans (prostate, head-and-neck and lung). RESULTS: The planned and EPID dose difference at the isocenter, on an average, was 1.7% for pretreatment verification and less than 3% for all in vivo plans, except for head-and-neck, which was 3.6%. The mean γ values for a seven-field prostate IMRT plan delivered to the Alderson phantom varied from 0.28 to 0.65. For 3D conformal plans applied for the Alderson phantom, all γ1% values were within the tolerance level for all plans and in both anteroposterior and posteroanterior (AP-PA) beams. CONCLUSION: The 2D EPID-based dosimetry algorithm provides an accurate method to verify the dose of a simple 10 × 10 cm2 field, in two dimensions, inside a homogenous slab phantom and an IMRT prostate plan, as well as in 3D conformal plans (prostate, head-and-neck, and lung plans) applied using an anthropomorphic phantom and in vivo. However, further investigation to improve the 2D EPID dosimetry algorithm for a head-and-neck case, is necessary.