Establishment and validation of a calibration curve for dicentric chromosome induced by 6MV X-ray.

Radiation during radiotherapy and nuclear accidents is currently one of the biggest concerns for the international community. Biological dosimetry examines the amount of damage caused by radiation at the cellular level by quantifying a radiation biomarker. In particular, the dicentric chromosome assay is a biodosimetric technique that can quantify radiation damage by correlating radiation dose exposure with the frequency of dicentric chromosomes in the peripheral lymphocytes extracted from exposed individuals. This study aims to present of the reference dose-response calibration curve for biodosimetry laboratory of Mashhad University of Medical Sciences (north-east of Iran). In all, 40 samples of peripheral blood from four healthy volunteers were irradiated at doses of 0-5 Gray in a customised water phantom using a 6 MV X-rays at dose rate of 2 Gy/min from a linear accelerator. The irradiated samples were cultured and analysed according to the International Atomic Energy Agency Cytogenetic Dosimetry Protocol (2011) with some modifications. Linear-quadratic model curve fitting and further statistical analysis were done using Chromosome Aberration Calculation Software Version 2.0 and Dose Estimate (Version 5.2). The curve equation obtained was ${Y}_{dic}=0.0533{D}^2+0.0231D+0.0001$ and was in the range of other studies. Validation of the calibration curve was done by estimating the dose of blind samples.

The role of microRNA-induced apoptosis in diverse radioresistant cancers.

Resistance to cancer radiotherapy is one of the biggest concerns for success in treating and preventing recurrent disease. Malignant tumors may develop when they block genetic mutations associated with apoptosis or abnormal expression of apoptosis; Tumor treatment may induce the expression of apoptosis-related genes to promote tumor cell apoptosis. MicroRNAs have been shown to contribute to forecasting prognosis, distinguishing between cancer subtypes, and affecting treatment outcomes in cancer. Constraining these miRNAs may be an attractive treatment strategy to help overcome radiation resistance. The delivery of these future treatments is still challenging due to the excess downstream targets that each miRNA can control. Understanding the role of miRNAs brings us one step closer to attaining patient treatment and improving patient outcomes. This review summarized the current information on the role of microRNA-induced apoptosis in determining the radiosensitivity of various cancers.

Regulation of XPA could play a role in inhibition of radiation-induced bystander effects in QU-DB cells at high doses.

INTRODUCTION: Radiation-induced bystander effects (RIBE) is the radiobiological effects detected in nonirradiated cells that have received signals from neighboring irradiated cells. In some studies, there are observations that RIBE unexpectedly reduces at high doses. In this study, the expression of two selected apoptotic and repair genes and their possible role in the formation of this unexpected reduction is examined. MATERIALS AND METHODS: The QU-DB cells were irradiated with gamma rays of a60 Co teletherapy unit at doses of 2, 4, 6, and 8 Gy. One hour following irradiation, their culture media were transferred to bystander cells to induced RIBE. After 24 h incubation, the RNA of cells was isolated and cDNA synthesized. Expression levels of BAX, XPA, and XPA/BAX ratio were examined by relative quantitative reverse transcription-polymerase chain reaction. RESULTS: In target cells, up-regulation of both genes was observed at all doses. In bystander cells, at the low dose (2 Gy), the expression of BAX was more than XPA; at 4 Gy, the ratio was balanced. A significant correlation was found between the XPA/BAX ratio and the dose, at high doses pattern of gene expression dominated by DNA repair gene. CONCLUSION: Gene expression profile was distinctive in bystander cells compared to target cells. The observed linear increasing of the ratio of XPA/BAX could support the hypothesis that the DNA repair system is stimulated and causes a reduction in RIBE at high doses.

Accompanying photocytotoxic activity of gold nanoechinus and zinc phthalocyanine on cancerous cell lines.

BACKGROUND: Near-infrared triggered photodynamic therapy (NIR-PDT) has been introduced as a relatively deep tumor treatment modality. The gold Nanoechinus (Au NE) is a rare type of nanostructures that act as a transducer to change NIR wavelength to ultraviolet (UV) and visible lights. During the photodynamic process, Au nanoechinus (Au NE) converts the irradiation of 980 nm to 674 nm which is absorbed by Zn(II) Phthalocyanine tetrasulfonic acid (ZnPcS). In this study the cooperation effect of Au NE and ZnPcS in PDT on MCF7 and Hela cells was investigated. METHODS: Cytotoxicity and phototoxicity of the composition having different concentrations of Au NE and ZnPcS upon irradiation of 980 nm NIR light were evaluated against MCF7 and Hela cells after two different incubation times and irradiating with two different power densities of laser. RESULTS: Among different experimental groups, in MCF7 cells, which were incubated for 48 h with 50 µg/mL Au NE+2µM ZnPcS and were treated by 980 nm laser with a power density of 200 mW cm-2 for 15 and 30 min, 48 and 38% cell viability were recorded. No appreciable result was observed due to PDT of Hela cells. CONCLUSIONS: Comparing to other PDT modalities against MCF7 cells, NIR-PDT procedure suggested in this study with the synergistic effect of Au NE and ZnPcS could be a secure promising modality in the treatment of deep-seated tumors. Carefully increasing the power density and ambient temperature, to the extent of skin tolerance threshold value, seems to be efficient in the treatment of Hela cells.

The effect of UV radiation in the presence of TiO2-NPs on Leishmania major promastigotes.

BACKGROUND: Cutaneous leishmaniasis is a parasitic disease, which is difficult to treat due to high drug resistance and adverse side effects. Photodynamic therapy by ultraviolet radiation using materials with high photocatalytic features like titanium dioxide nanoparticles (TiO2-NPs) is an emerging treatment for this disease. In this study, TiO2-NPs with ultraviolet (UV) radiation were administered as photodynamic therapy against Leishmania Major (LM) promastigotes. METHODS: Two forms of TiO2 viz. including Anatase and Rutile were administered in two UV ranges< UVA and UVB for different time periods (30 and 60 min). Finally, 24 and 48 h after incubation, the MTS test was performed and cell survival percentage was calculated. RESULTS: The mean size of Anatase and Rutile-NPs is approximately 32.5 and 50.9 nm respectively by DLS and FE-SEM, and crystal phase is emphasized by XRD. The combined treatment of LM with TiO2-NPs and UV has significant effects on LM promastigotes, which vary depending on NP and UV types. The synergistic effect was anticipated in the groups irradiated by UV-B in the presence of Rutile NPs. CONCLUSION: The combined treatment with UV- radiation and TiO2-NPs can be effective in killing the promastigotes of Leishmania major. The proper concentration of NPs and the type of UV-radiation must be taken into consideration. The results suggest improved treatment methods, after proper in vivo studies.

microRNAs: Potential glioblastoma radiosensitizer by targeting radiation-related molecular pathways.

Glioblastoma (GBM) is the most lethal type of primary brain tumor. Currently, even with optimal and multimodal cancer therapies, the survival rate of GBM patients remains poor. One reason for inadequate response of GBM tumors to radiotherapy is radioresistance (RR). Thus, there is a critical need for new insights about GBM treatment to increase the chance of treatment. microRNAs (miRNAs) are important regulatory molecules that can effectively control GBM radiosensitivity (RS) by affecting radiation-related signal transduction pathways such as apoptosis, proliferation, DNA repair and cell cycle regulation. miRNAs provide new clinical perspectives for developing effective GBM treatments. A growing body of literature has demonstrated that GBM RS can be modified by modulating the expression of miRNAs such as miR-7, miR-10b, miR-124, miR-128, miR-320, miR-21, miR-203, and miR-153. This paper highlights the miRNAs and the underlying molecular mechanisms that are involved in the RS of GBM. Besides highlighting the role of miRNAs in different signaling pathways, we explain the mechanisms that affect RS of GBM for modulating radiation response at the clinical level.

Dual Function of Gold Nanoparticles in Synergism with Mitoxantrone and Microwave Hyperthermia Against Melanoma Cells

Background: This study was performed to evaluate any synergetic effects of mitoxantrone (MX) and gold nanoparticles (GNPs) as dual therapeutic approach, along with microwave (MW) hyperthermia for melanoma cancer. Methods: Various tests were performed on the DFW melanoma cell line in the presence of MX and different concentrations of GNPs, with and without MW irradiation. MTT [3-(4,5-dimethylthiazol­2-yl)-2,5-iphenyltetrazolium bromide] assays were conducted to evaluate the effectiveness of the used therapeutic methods in terms of cell survival. Relative lethal synergism (RLS) was calculated as the ratio of cell death following hyperthermia in the presence of a treatment agent to that after applying hyperthermia in the absence of the same treatment agent. Results: Results showed MX and GNPs under MW irradiation to provide maximum cell death (P < 0.001 compared to the other groups). The mean RLS for MW hyperthermia along with the MX-GNP combination was 4.14, whereas in the absence of GNP the value for MX chemotherapy was 0.94. Conclusion: MX chemotherapy in the presence of different concentrations of GNP did not alter cell survival as compared to in its absence.

Silver nanoparticles and electroporation: Their combinational effect on Leishmania major.

Leishmaniasis is an emerging and uncontrolled disease. The use of routine drugs has been limited due to proven side effects and drug resistance. Interestingly, novel approaches such as nanotechnology have been applied as a therapeutic modality. Silver nanoparticles have shown antileishmanial effects but because of their nonspecific and toxic effects on normal cells, their use has been limited. On the other hand, it has been demonstrated that electric pulses induce electropores on cell membranes resulting in higher entrance of certain molecules into cells. There is a hypothesis proposing that use of electroporation and silver nanoparticles simultaneously can induce greater accumulation of particles in infected cells, besides higher toxicity. In this study, after applying electric pulses with different concentrations of silver nanoparticles (SNPs), cell survival rate was determined by standard viability assays. On the basis of these data, 2 µg/ml of SNPs and 700 V/cm with 100 µs duration of electroporation were selected as the non-lethal condition. Promastigotes and infected macrophage cells received both treatments and the survival percentage and Infection Index were calculated. In parasites and cells receiving both treatments, higher toxicity was observed in comparison to each treatment given individually, showing a synergic effect on promastigotes. Therefore, application of electric pulses could overcome limitations in using the antileishmanial properties of silver nanoparticles.