High-density polyethylene (HDPE)-incorporated boron carbide and boric acid nanoparticles as a nanoshield of photoneutrons from medical linear accelerators.

PURPOSE: The current study aimed to investigate boron carbide and boric acid nanoparticles (NPs) as absorbents for thermal neutrons and high-density polyethylene (HDPE) as a substrate and neutron moderator for fast neutrons. The goal was to assess the performance of boron carbide and boric acid NPs based on HDPE as a nanoshield of photoneutrons from medical linear accelerators. MATERIALS AND METHODS: This study was conducted in two parts of simulation and practice. The Monte Carlo (MC) simulation involved modeling and verification of the single-layer, double-layer, and combined nanoshields by selecting nanomaterials and substrates and, finally, calculating the macroscopic cross-sections. The practical part involved manufacturing nanoshields based on the simulation results and evaluating the manufactured nanocomposites via experimental measurements. RESULTS: MC simulation results with an uncertainty of less than 1% showed that for the monolayer samples, the best result belonged to boron carbide at a concentration of 10% and a macroscopic cross-section of 0.933 cm-1. At a concentration of 20%, the highest value among the double-layer samples was 0.936 cm-1 and for the combined samples, this value was 0.928 cm-1. Boron carbide single-layer nanocomposites at a 10% concentration, as well as the bilayer nanoshield of 10% boron carbide and 20% boric acid performed well; however, the best performance belonged to the nanoshield with a macroscopic cross-section of 0.960 and the combination containing 5% boron carbide and 10% boric acid. CONCLUSIONS: The research suggests that utilizing boron carbide and boric acid nanoshields in combination with HDPE holds promise as a viable approach to protecting from the photoneutrons. Further exploration of these nanocomposite shields and their practical applications is warranted, with the potential to yield significant advancements in radiation therapy safety and efficacy.

Comparing Geant4 physics models for proton-induced dose deposition and radiolysis enhancement from a gold nanoparticle.

Gold nanoparticles (GNPs) are materials that make the tumor cells more radiosensitive when irradiated with ionizing radiation. The present study aimed to evaluate the impact of different physical interaction models on the dose calculations and radiochemical results around the GNP. By applying the Geant4 Monte Carlo (MC) toolkit, a single 50-nm GNP was simulated, which was immersed in a water phantom and irradiated with 5, 50, and 150 MeV proton beams. The present work assessed various parameters including the secondary electron spectra, secondary photon spectra, radial dose distribution (RDD), dose enhancement factor (DEF), and radiochemical yields around the GNP. The results with an acceptable statistical uncertainty of less than 1% indicated that low-energy electrons deriving from the ionization process formed a significant part of the total number of secondary particles generated in the presence of GNP; the Penelope model produced a larger number of these electrons by a factor of about 30%. Discrepancies of the secondary electron spectrum between Livermore and Penelope were more obvious at energies of less than 1 keV and reached the factor of about 30% at energies between 250 eV and 1 keV. The RDDs for Livermore and Penelope models were very similar with small variations within the first 6 nm from NP surface by a factor of 10%. In addition, neither the G-value nor the REF was affected by the choice of physical interaction models with the same energy cut-off. This work illustrated the similarity of the Livermore and Penelope models (within 15%) available in Geant4 for future simulation studies of GNP enhanced proton therapy with physical, physicochemical, and chemical mechanisms.

Inhibitory effects of gallic acid on the activity of exosomal secretory pathway in breast cancer cell lines: A possible anticancer impact.

Introduction: Breast cancer cells produce exosomes that promote tumorigenesis. The anticancer properties of gallic acid have been reported. However, the mechanism underlying its anticancer effect on the exosomal secretory pathway is still unclear. We investigated the effect of gallic acid on exosome biogenesis in breast cancer cell lines. Methods: The cytotoxic effect of gallic acid on MCF-10a, MCF-7, and MDA-MD-231 cells was measured by MTT assay after 48 hours treatment. Expression of miRNAs including miRNA-21, -155, and 182 as well as exosomal genes such as Rab27a, b, Rab11, Alix, and CD63; along with HSP-70 (autophagy gene), was determined using Q-PCR. The subcellular distribution of it was monitored by flow cytometry analysis. Isolated exosomes were characterized by transmission and scanning electron microscopes and flow cytometry. Acetylcholinesterase activity is used to measure the number of exosomes in supernatants. In addition, autophagy markers including LC3 and P62 were measured by ELISA. Results: Data showed that gallic acid was cytotoxic to cells (P < 0.05). Gallic acid modulated expression of miRNAs and down-regulated transcript levels of exosomal genes and up-regulated the HSP-70 gene in three cell lines (P < 0.05). The surface CD63/total CD63 ratio as well as acetylcholinesterase activity decreased in treated cells (P < 0.05). The protein level of LC3 was increased in three cell lines, while the expression of P62 increased in MCF-7 and MDA-MB-231 cancer cell lines. Conclusion: Together, gallic acid decreased the activity of the exosomal secretory pathway in breast cancer cell lines, providing evidence for its anti-cancer effects.

Radiation dose and cancer risks from radiation exposure during abdominopelvic computed tomography (CT) scans: comparison of diagnostic and radiotherapy treatment planning CT scans.

In the present study, radiation doses and cancer risks resulting from abdominopelvic radiotherapy planning computed tomography (RP-CT) and abdominopelvic diagnostic CT (DG-CT) examinations are compared. Two groups of patients who underwent abdominopelvic CT scans with RP-CT (n = 50) and DG-CT (n = 50) voluntarily participated in this study. The two groups of patients had approximately similar demographic features including mass, height, body mass index, sex, and age. Radiation dose parameters included CTDIvol, dose-length product, scan length, effective tube current, and pitch factor, all taken from the CT scanner console. The ImPACT software was used to calculate the patient-specific radiation doses. The risks of cancer incidence and mortality were estimated based on the BEIR VII report of the US National Research Council. In the RP-CT group, the mean ± standard deviation of cancer incidence risk for all cancers, leukemia, and all solid cancers was 621.58 ± 214.76, 101.59 ± 27.15, and 516.60 ± 189.01 cancers per 100,000 individuals, respectively, for male patients. For female patients, the corresponding risks were 742.71 ± 292.35, 74.26 ± 20.26, and 667.03 ± 275.67 cancers per 100,000 individuals, respectively. In contrast, for DG-CT cancer incidence risks were 470.22 ± 170.07, 78.23 ± 18.22, and 390.25 ± 152.82 cancers per 100,000 individuals for male patients, while they were 638.65 ± 232.93, 62.14 ± 13.74, and 575.73 ± 221.21 cancers per 100,000 individuals for female patients. Cancer incidence and mortality risks were greater for RP-CT than for DG-CT scans. It is concluded that the various protocols of abdominopelvic CT scans, especially the RP-CT scans, should be optimized with respect to the radiation doses associated with these scans.

Prediction of Breast Cancer Survival by Machine Learning Methods: An Application of Multiple Imputation.

BACKGROUND: The low breast cancer survival rates in less developed countries are critical. The machine learning techniques predict cancers survival with high accuracy. Missing data are the most important limitation for using the highest potential of these techniques to predict cancers survival. Multiple imputation (MI) was implemented and analyzed in detail to impute the missing data of a breast cancer dataset. METHODS: The dataset was from The Omid Treatment and Research Center Urmia, Iran between Jan 2006 and Dec 2012 and had information from 856 women. The algorithms such as C5 and repeated incremental pruning to produce error reduction were applied on the imputed versions of the original dataset and the non-imputed dataset to predict and extract clinical rules, respectively. RESULTS: The findings showed the performance of C5 in all the evaluation criteria including accuracy (84.42%), sensitivity (92.21%), specificity (64%), Kappa statistic (59.06%), and the area under the receiver operator characteristic (ROC) curve (0.84), was improved after imputation. CONCLUSION: The dataset of the present study met the requirements for using the multiple imputation method. The extracted rules after the application of MI were more comprehensive and contained knowledge that is more clinical. However, the clinical value of the extracted rules after filling in the missing data did not noticeably increase.

Bystander effects induced by electron beam-irradiated MCF-7 cells: a potential mechanism of therapy resistance.

PURPOSE: The distinct direct and non-targeting effects of electron beam radiation on MCF-7 cells remain obscure. We aimed to investigate the effect of electron beam irradiation (EBI) and conditioned media (CM) of the irradiated MCF-7 cells on MCF-7 cells. The cytotoxic effects of CM from irradiated MCF-7 cells on the mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs) were also examined. METHODS: Cell viability and apoptosis were assayed via MTT and flow cytometry analysis, respectively. The production of ROS (reactive oxygen species) was evaluated by the chemical fluorometric method, while the amount of extracellular vesicles was detected via acetylcholinesterase activity assay. Expression of genes involved in apoptosis, including caspase-3, -8, -9, and stemness such as Sox-2 and Oct-4, were calculated through qPCR. The wound healing rate of cells was monitored via in vitro scratch assay. RESULTS: Compared to the control group, EBI groups showed decreased cell viability but increased apoptosis and ROS as well as acetylcholinesterase activity dose-dependently (P < 0.05). Concurrently with increasing the dose of the electron beam, the transcript levels of apoptotic genes (caspase-3, -8, -9) and stemness-related genes (Sox-2 and Oct-4) were up-regulated following EBI. The wound healing rate of irradiated MCF-7 cells increased dose-dependently (P < 0.05). Similar results were observed after treatment with CM from irradiated MCF-7 cells. Additionally, CM from irradiated MCF-7 cells decreased the viability of MCF-7 cells, mesenchymal stem cells, and HUVECs (P < 0.05). CONCLUSION: MCF-7 cells treated with an electron beam and CMs from irradiated MCF-7 cells exhibit an up-regulation in both genes involved in the apoptosis pathway and stemness. As a result, EBI can affect apoptosis and stemness in MCF-7 cells in direct and bystander manners. However, specific signaling pathways require careful evaluation to provide an understanding of the mechanisms involved in the EBI-induced alternation in tumor cell dynamics.

Design and fabrication of a Nano-based neutron shield for fast neutrons from medical linear accelerators in radiation therapy.

BACKGROUND: Photo-neutrons are produced at the head of the medical linear accelerators (linac) by the interaction of high-energy photons, and patients receive a whole-body-absorbed dose from these neutrons. The current study aimed to find an efficient shielding material for fast neutrons. METHODS: Nanoparticles (NPs) of Fe3O4 and B4C were applied in a matrix of silicone resin to design a proper shield against fast neutrons produced by the 18 MeV photon beam of a Varian 2100 C/D linac. Neutron macroscopic cross-sections for three types of samples were calculated by the Monte Carlo (MC) method and experimentally measured for neutrons of an Am-Be source. The designed shields in different concentrations were tested by MCNPX MC code, and the proper concentration was chosen for the experimental test. A shield was designed with two layers, including nano-iron oxide and a layer of nano-boron carbide for eliminating fast neutrons. RESULTS: MC simulation results with uncertainty less than 1% showed that for discrete energies and 50% nanomaterial concentration, the macroscopic cross-sections for iron oxide and boron carbide at the energy of 1 MeV were 0.36 cm- 1 and 0.32 cm- 1, respectively. For 30% nanomaterial concentration, the calculated macroscopic cross-sections for iron oxide and boron carbide shields for Am-Be spectrum equaled 0.12 cm- 1 and 0.15 cm- 1, respectively, while they are 0.15 cm- 1 and 0.18 cm- 1 for the linac spectrum. In the experiment with the Am-Be spectrum, the macroscopic cross-sections for 30% nanomaterial concentration were 0.17 ± 0.01 cm- 1 for iron oxide and 0.21 ± 0.02 cm- 1 for boron carbide. The measured transmission factors for 30% nanomaterial concentration with the Am-Be spectrum were 0.71 ± 0.01, 0.66 ± 0.02, and 0.62 ± 0.01 for the iron oxide, boron carbide, and double-layer shields, respectively. In addition, these values were 0.74, 0.69, and 0.67, respectively, for MC simulation for the linac spectrum at the same concentration and thickness of 2 cm. CONCLUSION: Results achieved from MC simulation and experimental tests were in a satisfactory agreement. The difference between MC and measurements was in the range of 10%. Our results demonstrated that the designed double-layer shield has a superior macroscopic cross-section compared with two single-layer nanoshields and more efficiently eliminates fast photo-neutrons.

Breast cancer-derived exosomes: Tumor progression and therapeutic agents.

Tumor cells secrete extracellular vesicles (EVs) for intercellular communication. EVs by transporting different proteins, nucleic acids, and lipids contribute to affect target cell function and fate. EVs which originate directly from multivesicular bodies so-called exosomes have dramatically fascinated the attention of researchers owing to their pivotal roles in the tumorigenesis. Breast cancer, arising from milk-producing cells, is the most identified cancer among women and has become the leading cause of cancer-related death in women globally. Although different therapies are applied to eliminate breast tumor cells, however, the efficient therapy and survival rate of patients remain challenges. Growing evidence shows exosomes from breast cancer cells contribute to proliferation, metastasis, angiogenesis, chemoresistance, and also radioresistance and, thus carcinogenesis. Additionally, these exosomes may serve as a cancer treatment tool because they are a good candidate for cancer diagnosis (as biomarker) and therapy (as drug-carrier). Despite recent development in the biology of tumor-derived exosomes, the detailed mechanism of tumorigenesis, and exosome-based cancer-therapy remain still indefinable. Here, we discuss the key function of breast cancer-derived exosomes in tumorgenesis and shed light on the possible clinical application of these exosomes in breast cancer treatment.

Tumor-derived extracellular vesicles: insights into bystander effects of exosomes after irradiation.

This review article aims to address the kinetic of TDEs in cancer cells pre- and post-radiotherapy. Radiotherapy is traditionally used for the treatment of multiple cancer types; however, there is growing evidence to show that radiotherapy exerts NTEs on cells near to the irradiated cells. In tumor mass, irradiated cells can affect non-irradiated cells in different ways. Of note, exosomes are nano-scaled cell particles releasing from tumor cells and play key roles in survival, metastasis, and immunosuppression of tumor cells. Recent evidence indicated that irradiation has the potential to affect the dynamic of different signaling pathways such as exosome biogenesis. Indeed, exosomes act as intercellular mediators in various cell communication through transmitting bio-molecules. Due to their critical roles in cancer biology, exosomes are at the center of attention. TDEs contain an exclusive molecular signature that they may serve as tumor biomarker in the diagnosis of different cancers. Interestingly, radiotherapy and IR could also contribute to altering the dynamic of exosome secretion. Most probably, the content of exosomes in irradiated cells is different compared to exosomes originated from the non-irradiated BCs. Irradiated cells release exosomes with exclusive content that mediate NTEs in BCs. Considering variation in cell type, IR doses, and radio-resistance or radio-sensitivity of different cancers, there is, however, contradictions in the feature and activity of irradiated exosomes on neighboring cells.

The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer.

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.

Bystander effects of ionizing radiation: conditioned media from X-ray irradiated MCF-7 cells increases the angiogenic ability of endothelial cells.

BACKGROUND: Non-targeting effects of radiotherapy have become as clinical concern due to secondary tumorigenesis in the patients receiving radiotherapy. Radiotherapy also affects non-tumoral cells present in the tumor microenvironment and surrounding tissues. As such, the irradiated cells are thought to communicate the signals that promote secondary tumorigenesis by affecting the function and fate of non-irradiated cells in the vicinity including endothelial cells. This may include up-regulation of genes in irradiated cells, secretion of paracrine factors and induction of gene expression in surrounding non-irradiated cells, which favor cell survival and secondary tumorigenesis. In the current study, we aimed to investigate whether the conditioned media from X-ray irradiated MCF-7 cells contribute to induction of gene expression in human umbilical vein endothelial cells (HUVECs) in vitro and modulate their angiogenic capability and migration. METHODS: Following the co-culturing of X-ray irradiated MCF-7 media with HUVECs, the migration and wound healing rate of HUVECs was monitored using Transwell plate and scratch wound healing assay, respectively. The levels of angiogenic protein i.e. vascular endothelial growth factor (VEGF-A) in the conditioned media of MCF-7 cells was measured using ELISA. Additionally, we quantified mRNA levels of VEGFR-2, HSP-70, Ang-2, and Ang-1 genes in HUVECs by real time-PCR. Tubulogenesis capacity of endothelial cells was measured by growth factor reduced Matrigel matrix, whereas expression of CD34 (a marker of angiogenic tip cells) was detected by flow cytometry. RESULTS: Data showed that VEGF-A protein content of conditioned media of irradiated MCF-7 cells was increased (P < 0.05) with increase in dose. Data showed that irradiated conditioned media from MCF-7 cells, when incubated with HUVECs, significantly enhanced the cell migration and wound healing rate of HUVECs in a dose-dependent manner (P < 0.05). The mRNA levels of VEGFR-2, HSP-70, Ang-2, and Ang-1 were dose-dependently enhanced in HUVECs incubated with irradiated conditioned media (P < 0.05). Importantly, HUVECs treated with irradiated conditioned media showed a marked increase in the tube formation capability as well as in expression of CD34 marker (P < 0.05). CONCLUSIONS: Our findings indicate that conditioned media from irradiated MCF-7 cells induce angiogenic responses in endothelial cells in vitro, which could be due to transfer of overexpressed VEGF-A and possibly other factors secreted from irradiated MCF-7 cells to endothelial cells, and induction of intrinsic genes (VEGFR-2, HSP-70, Ang-2, and Ang-1) in endothelial cells. Video abstract.

Tumor-derived extracellular vesicles: reliable tools for Cancer diagnosis and clinical applications.

BACKGROUND: Studies have recently revealed that almost every type of cells including tumor cells abundantly release small vesicles known as extracellular vesicles (EVs) into the extracellular milieu. EVs carry a repertoire of biological molecules including nucleic acids, proteins, lipids, and carbohydrates and transport their cargo between cells in the vicinity as well as distantly located cells and hence act as messengers of intercellular communication. In this review, we aimed to discuss the tumor-derived exosome biology and the pivotal roles of exosomes in cancer diagnosis and treatment. METHODS: In the present review study, the authors studied several articles over the past two decades published on the kinetics of EVs in tumor environment as well as on the application of these vesicles in cancer diagnosis and therapy. RESULTS: A growing body of evidence indicates that nucleic acids such as microRNAs (miRNAs) transferring by EVs participate to create a conducive tumor environment. As EV-associated miRNAs are tissue-specific and present in most biological fluids, they hold great potential for clinical application in cancer early diagnosis, prognosis, and treatment response. Furthermore, exosomes can serve as drug delivery vehicles transferring miRNAs as well as therapeutic agents to target cells. These nano-vesicles exhibit ideal properties in comparison with the synthetic carriers that attracted scientist's attention in the field of nanotechnology medicine. Scientists have employed different strategies to build exosomes-based drug delivery system. In general, two methods (direct engineering and indirect engineering) are being utilized to produce artificial exosomes. Para-clinical data have confirmed the beneficial effects of engineering exosomes in cancer therapy. CONCLUSION: Exosomal miRNAs hold great promise for clinical application in early diagnosis and treatment of cancers. In addition, in spite of enthusiastic results obtained by engineered exosomes, however, there is an increasing concern over the use of optimal methods for engineering exosomes and the safety of engineered exosomes in clinical trials is still unclear.

Ionizing Radiation Increases the Activity of Exosomal Secretory Pathway in MCF-7 Human Breast Cancer Cells: A Possible Way to Communicate Resistance against Radiotherapy.

Radiation therapy, which applies high-energy rays, to eradicate tumor cells, is considered an essential therapy for the patients with breast cancer. Most tumor cells secrete exosomes, which are involved in cell-to-cell communication in tumor tissue and contribute therapeutic resistance and promote tumor aggressiveness. Here, we investigated the effect of clinically applicable doses of X-ray irradiation (2, 4, 6, 8, 10 Gy) on the dynamics of the exosomes' activity in MCF-7 breast cancer cells. Survival and apoptosis rate of cells against X-ray doses was examined using MTT and flow cytometry assays, respectively. Whereas, the levels of reactive oxygen species (ROS) in the X-ray-treated cells were detected by fluorometric method. The mRNA levels of vital genes involved in exosome biogenesis and secretion including Alix, Rab11, Rab27a, Rab27b, TSPA8, and CD63 were measured by real-time PCR. The protein level of CD63 was examined by Western blotting. Additionally, exosomes were characterized by monitoring acetylcholinesterase activity, transmission electron microscopy, size determination, and zeta potential. The result showed that in comparison with control group cell survival and the percentage of apoptotic cells as well as amount of ROS dose-dependently decreased and increased in irradiated cells respectively (p < 0.05). The expression level of genes including Alix, Rab27a, Rab27b, TSPA8, and CD63 as well as the protein level of CD63 upraised according to an increase in X-ray dose (p < 0.05). We found that concurrent with an increasing dose of X-ray, the acetylcholinesterase activity, size, and zeta-potential values of exosomes from irradiated cells increased (p < 0.05). Data suggest X-ray could activate exosome biogenesis and secretion in MCF-7 cells in a dose-dependent way, suggesting the therapeutic response of cells via ROS and exosome activity.

Using CuO nanoparticles and hyperthermia in radiotherapy of MCF-7 cell line: synergistic effect in cancer therapy.

The aim of this paper was examining the combined impacts of CuO nanoparticles (CuO NPs), hyperthermia (H), and irradiation (R) on an increment of MCF-7 cells. The MTT assay was employed to assess the antiproliferative effects of CuO NPs (25, 50, and 100 µg/ml), hyperthermia (41 °C for 1 h), and irradiation (200 cGy). Moreover, the perniciousness was estimated through the survival capability of cells, and apoptosis, ROS production, and levels of caspase-3, -8 and -9 proteins were determined. A significant (p < .01) decrease in proliferation index (0.124 ± 0.021), a significant (p < .01) increase in apoptosis (42% ± 1.54) of MCF7 cells, a significant (p < .03) increase in ROS formation (32.16 ± 1.9) and a significant (p < .01) increase in LDH release (33.28 ± 1.56) were recorded in the adjacency of MCF-7 cells by a combination of CuO NPs (100 µg/ml) and R + H compared to control and other treatments. The activities of caspase-3 (0.33 ± 0.014) and caspase-9 (0.389 ± 0.019) also increased significantly (p < .05). However, caspase-8 showed no significant changes in its activity (p = .065). Based on these observations, a combination of CuO NPs, hyperthermia, and irradiation could suppress the growth of MCF-7 cells and evoke cell apoptosis via mitochondrial membrane potential.

Modulating Survivin as a Radioresistant Factor, Caspase-3, and Apoptosis by Omega-3 Docosahexaenoic Acid Sensitizes Mutant-p53 Colorectal Cancer Cells to γ-Irradiation.

Mutant-p53 colorectal cancer (CRC) cells are often resistant to radiotherapy. Loss of suppressor activity of wt-p53 on survivin is responsible for the enhanced expression of survivin as a radioresistant factor in tumor cells. Yet, no survivin-modulating drug has been approved for clinical application in CRC. Thus, the search for safe compounds that modulate survivin expression and induce apoptosis irrespective of p53 status may potentiate the efficacy of radiotherapy in mutant-p53 CRC cells. Omega-3 docosahexaenoic acid (DHA) induces apoptosis in malignant cells without cytotoxicity in normal cells. However, little is known whether in vitro concentrations of DHA equal to the human plasma levels are able to modulate expression of survivin and sensitize mutant-p53 CRC cells to γ-irradiation. Radioresistant mutant-p53 HT-29 cells were pretreated with 50- and 100-µM DHA for 48-h before 2-, 4-, 6-, 8-, and 10-Gy of γ-irradiation. Thereafter, proliferation rates were measured after 6 d. HT-29 cells were also pretreated with 50- and 100-µM DHA for 4-h before 2- and 10-Gy of γ-irradiation after which, cell number, survivin expression, caspase-3 activation, apoptosis, and ED50 (γ-irradiation dose causing 50% growth inhibition) were evaluated. Pretreatment of HT-29 cells with 50- and 100-µM DHA for 48-h followed by 2- to 10-Gy of γ-irradiation induced a dose-dependent additive decrease in cell proliferation rate and ED50 values were decreased by 88%, 44%, 41%, and 27% for 500-, 1500-, 2500-, and 5000 cells per well pretreated with 100-µM DHA respectively. Pretreatment of 5 × 105 HT-29 cells per well with 100-µM DHA for 4-h followed by 2- or 10-Gy of irradiation resulted in 53% and 86% decreases in cell numbers, 2- and 5.1-fold activation in caspase-3 followed by 66% and 60% decreases in survivin mRNA levels respectively. DHA in combination with radiation increased total apoptotic rate 48-h post-treatment. DHA decreases survivin expression and induces caspase-3 activation irrespective of p53 status. Significant decreases in ED50 values at concentrations of DHA equal to human plasma levels, suggesting that DHA could be used as an attractive radiosensitizer agent in CRC patients with mutant-p53.

Assessment of synergistic effect of combining hyperthermia with irradiation and calcium carbonate nanoparticles on proliferation of human breast adenocarcinoma cell line (MCF-7 cells).

The present study was undertaken to evaluate the synergistic effect of combining hyperthermia with irradiation and calcium carbonate nanoparticles (CC NPs) on proliferation of MCF-7 cells. The cells were randomly allocated to 19 groups: one negative control, three positive controls and 15 treatment groups. MCF-7 cells were treated with three concentrations of CC NPs (50, 100 and 150 µg/mL), gamma radiation (200 cGy), hyperthermia (41 °C for 1 h) and three concentrations of doxorubicin (200, 400 and 800 nm) and incubated at 37 °C for 24 h. Then the cell viability, the percentage of apoptosis and the levels of caspase-3, -8 and -9 proteins were measured. The results indicated that the combination group (150 µg/mL CC NPs + thermoradiotherapy) had a significant (p < .001) decrease in cell viability (48.65 ± 4.8%) and a significant (p < .001) increase in apoptosis percentage (45 ± 1.63%) of MCF-7 cells, as compared with the negative control and most of the other treatment groups. Moreover, a significant (p < .05) increase was observed in the activity of caspase-3 and caspase-9. Our findings revealed that CC NPs in combination with irradiation and hyperthermia could significantly reduce the cell viability and enhance the apoptosis of the MCF-7 breast cancer cells, the same as doxorubicin anti-cancer drug.

Estimation of lifetime attributable risks (LARs) of cancer associated with abdominopelvic radiotherapy treatment planning computed tomography (CT) simulations.

PURPOSE: The present study attempts to calculate organ-absorbed and effective doses for cancer patients to estimate the possible cancer induction and cancer mortality risks resulting from 64-slice abdominopelvic computed tomography (CT) simulations for radiotherapy treatment planning (RTTP). MATERIAL AND METHODS: A group of 70 patients, who underwent 64-slice abdominopelvic CT scan for RTTP, voluntarily participated in the present study. To calculate organ and effective doses in a standard phantom of 70 kg, the collected dosimetric parameters were used with the ImPACT CT Patient Dosimetry Calculator. Patient-specific organ dose and effective dose were calculated by applying related correction factors. For the estimation of lifetime attributable risks (LARs) of cancer incidence and cancer-related mortality, doses in radiosensitive organs were converted to risks based on the data published in Biological Effects of Ionizing Radiation VII (BEIR VII). RESULTS: The mean ± standard deviation (SD) of the effective dose for males and females were 13.87 ± 2.37 mSv (range: 9.25-18.82 mSv) and 13.04 ± 3.42 mSv (range: 6.99-18.37 mSv), respectively. The mean ± SD of LAR of cancer incidence was 35.34 ± 13.82 cases in males and 34.49 ± 9.63 cases in females per 100,000 persons. The LAR of cancer mortality had the mean ± SD value of 15.38 ± 4.25 and 16.72 ± 3.87 cases per 100,000 persons in males and females respectively. CONCLUSION: Increase in the LAR of cancer occurrence and mortality due to abdominopelvic treatment planning CT simulation is noticeable and should be considered.

Effects of gamma-low dose irradiation on skin flap survival in rats.

PURPOSE: Skin flap necrosis due to inadequate blood supply has remained a common postoperative problem in constructive surgery. As low-dose irradiation (LDI) has been shown to promote the wound-healing process, this study aims to investigate whether LDI could increase neovascularization and skin flap survival in rats. METHODS: McFarlane flaps were created in 21 male rats, which were divided into one control and two treatment groups (Ta and Tb). The treatment groups received a whole body single dose of 100cGy gamma ray irradiation before (Tb) and after (Ta) flap surgery. The flap survival area was evaluated after seven days. The skin samples were collected for histological analysis and determining the vascular endothelial growth factor (VEGF) using the immunohistochemical method. Serum malondialdehyde (MDA) was examined with the kit. RESULTS: The mean areas of flap survival were 56.7±3.24, 61.7±2.6, and 66.5±3.82 in the control, Tb, and Ta groups, respectively. There were significant differences between the Tb and Ta groups in comparison with the control group (P<0.05 and P<0.01, respectively). Compared with the control group (8.0±0.73), the mean numbers of the blood vessels in the Ta group (22±1.24) and the Tb group (14±1.29) were significantly higher (P<0.001 and P<0.01). Moreover, the mean numbers of the VEGF-positive cells in the Ta group (4.5±1.04) were significantly higher (P<0.05) than the control group (2.5±0.83). However, no significant differences in the MDA levels were observed among the groups. CONCLUSION: The findings of this study suggest that LDI has the potential to promote neovascularization to improve flap survival.

Acceleration of skin wound healing by low-dose indirect ionizing radiation in male rats.

A recent hypothesis has revealed that low-dose irradiation (LDI) with ionizing radiation might have a promoting effect on fracture healing. The aim of this study was to investigate the influence of direct (electron beam) and indirect (gamma-ray) low-dose ionizing irradiations on the wound healing process in male rats. In 72 male rats, a full-thickness wound was incised. The animals were randomly assigned to three groups, each with 24 rats. The first two groups were named IG-I and IG-II and respectively exposed to electron and gamma-radiations (75 cGy) immediately after the surgical procedure. The third group was considered as the control (CG) and remained untreated. Skin biopsies from the subgroups were collected on days 3, 7, 15, and 21 after the operation and evaluated using histological and biomechanical methods. Data were analyzed by one-way ANOVA, followed by Tukey's post hoc test using SPSS 20 software. Histological studies of tissues showed that the mean number of fibroblasts, macrophages, blood vessel sections, and neutrophils on the third and seventh days after the surgery in the gamma-treated group was higher than that in both other groups. In contrast, on day 21, the mean number of mentioned cells in the gamma-treated group was lower than in the other two groups. In addition, the mean maximum stress value was significantly greater in the gamma-treated group. Results of this study showed that gamma-ray irradiation is effective in the acceleration of wound healing.

Estimating cancer induction risk from abdominopelvic scanning with 6- and 16-slice computed tomography.

PURPOSE: The biological effects of ionizing radiation (BEIR VII) report estimates that the risk of getting cancer from radiation is increased by about a third from current regulation risk levels. The propose of this study was to estimate cancer induction risk from abdominopelvic computed tomography (CT) scanning of adult patients using 6- and 16-slice CT scanners. MATERIALS AND METHODS: A cross-sectional study on 200 patients with abdominopelvic CT scan in 6- and 16-slice scanners was conducted. The dose-length product (DLP) and volume CT Dose Index (CTDIvol) values from the scanners as well as the effective dose values from the ImPACT CT patient dosimetry calculator with the biological effects of ionizing radiation (BEIR VII) method were used to estimate the cancer induction risk. RESULTS: The mean (and standard deviation) values of CTDIvol and DLP were 6.9 (±1.07) mGy and 306.44 (± 60.57) mGy.cm for 6-slice, and 5.19 (±0.91) mGy and 219.7 (±49.31) mGy.cm for 16-slice scanner, respectively. The range of effective dose in the 6-slice scanner was 2.61-8.15 mSv and, in the 16-slice scanner, it was 1.47-4.72 mSv. The mean and standard deviation values of total cancer induction risk in abdominopelvic examinations were 0.136 ± 0.059% for men and 0.135 ± 0.063% for women in the 6-slice CT scanner. The values were 0.126 ± 0.051% for men and 0.127 ± 0.056% for women in the 16-slice scanner. CONCLUSIONS: The cancer induction risk of abdominopelvic scanning was noticeable. Therefore, radiation dose should be minimized by optimizing the protocols and applying appropriate methods.