Long-term changes of prostacyclin secretion in radiation-induced myelopathy

Background: We have previously reported the short-term changes in prostacyclin profile after irradiation of rat cervical cord. Aim: Present research investigated the long-term changes of prostacyclin content. Materials/Methods: Wistar rats in groups of five were irradiated with doses of 2, 4, 6, 15, 25, 30Gy and a single group of 25 with 35Gy X-rays. After 26 and 39 weeks, prostacyclin content was quantified by 6-keto-prostaglandin-F1α (prostacyclin stabilized metabolite) . Specimens were stained routinely for histological studies. Results: The 50 latent period and effective dose were 14.86±1.16 weeks and 25.66±0.54Gy (p<0.0001), respectively. Average ratios of 6-keto-PG-F1α for doses of 2-30Gy were between 78.33-12.93 and 79.48-99.96 for 26 and 39 weeks, respectively. Prostacyclin level after 35Gy shows approximately a 7:1 ratio in comparison to the control group (p<0.002). Histopathological changes in glial and vascular tissues were diagnosed and scored. Prostacyclin bimodal profile was observed. Conclusions: Radiation can cause complex fluctuations of prostacyclin in association with marked histopathological changes

High-dose-rate 192Ir brachytherapy dose verification: A phantom study

Background: The high-dose-rate (HDR) brachytherapy might be an effective tool for palliation of dysphagia. Because of some concerns about adverse effects due to absorbed radiation dose, it is important to estimate absorbed dose in risky organs during this treatment. Objectives: This study aimed to measure the absorbed dose in the parotid, thyroid, and submandibular gland, eye, trachea, spinal cord, and manubrium of sternum in brachytherapy in an anthropomorphic phantom. Materials and Methods: To measure radiation dose, eye, parotid, thyroid, and submandibular gland, spine, and sternum, an anthropomorphic phantom was considered with applicators to set thermoluminescence dosimeters (TLDs). A specific target volume of about 23 cm3 in the upper thoracic esophagus was considered as target, and phantom planned computed tomography (CT) for HDR brachytherapy, then with a micro-Selectron HDR (192Ir) remote after-loading unit. Results: Absorbed doses were measured with calibrated TLDs and were expressed in centi-Gray (cGy). In regions far from target (� 16 cm) such as submandibular, parotid and thyroid glands, mean measured dose ranged from 1.65 to 5.5 cGy. In closer regions (� 16 cm), the absorbed dose might be as high as 113 cGy. Conclusions: Our study showed similar depth and surface doses; in closer regions, the surface and depth doses differed significantly due to the role of primary radiation that had imposed a high-dose gradient and difference between the plan and measurement, which was more severe because of simplifications in tissue inhomogeneity, considered in TPS relative to phantom. © 2015, Iranian Journal of Cancer Prevention

Determining lymphocyte radiosensitivity of healthy individuals and prostate cancer patients using premature chromosome condensation

Background and purpose: Cytogenetic tests are used to assess the individual�s radiosensitivity and the potential to develop cancerous diseases. Our aim was to assess the radiosensitivity of patients with prostate cancer and healthy individuals based on Premature Chromosome Condensation (PCC). Materials and methods: 3.5 ml blood was collected from peripheral veins of 10 healthy individuals and 10 patients with prostate cancer and put into 7 sterile microtubes. All samples, except the controls, were irradiated to 6MV beams of a Siemens LINAC at different doses (0.25, 0.5, 1, 2, 4 and 6 Gy). Chemical PCC test was performed on each sample and the prepared slides were scored. The Kruskal-Wallis non-parametric ANOVA and Mann-Whitney statistical tests were used to compare the chromosomal aberrations resulted from different dose levels in each group (healthy/cancerous), and identical doses resulted from the two groups, respectively. Results: There was a significant correlation between irradiation dose (for doses �0.5 Gy) and the rings in both of the healthy and prostate cancer patients indicating an increase in the number of rings with dose escalation (P<0.05). Comparing healthy individuals and cancerous patients revealed no significant difference in their ring number at the same level of radiation doses (P= 0.784). Conclusion: In theory, PCC test should be capable of determining more chromosomal aberrations than dicentric test, so, if the FISH test is used simultaneously, we might be able to score dicentrics and other fragments. By these, it may also be possible to better differentiate the radiosensitivity of healthy individuals and prostate cancer patients. © 2016, Mazandaran University of Medical Sciences. All rights reserved

Measurement of surface dose in external radiotherapy of brain frontal lobe: A study on patient and phantom

Introduction: Radiotherapy plays an important role in the treatment of most malignant and also benign primary CNS tumors. Radiotherapy affects both tumor cells and normal cells. The aim of this study was to determine the absorbed dose of radiation by the skin surfacing organs at risk (lens, parotid, thyroid and submandibular gland) during radiotherapy of tumors at the frontal lobe of the brain via direct measurement in patients and phantom. Materials and methods: There are two conventional techniques for external radiotherapy of patients with tumors of the right frontal lobe. These techniques were used to estimate the amount of surface dose absorption by organs at risk (lens of eye, parotid, thyroid, submandibular glands). Technique 1 was performed for 10 patients who referred to Reza Radiation Oncology Center. Technique 1 is the radiation of frontal field with an extension to the lateral field portion. Technique I and 2, which included radiation of one frontal field along with a bilateral field were performed for a phantom model with an anthropomorphic head and neck constructed from natural human bone with paraffin wax and NaCl as surrounding soft tissues. The surface dose for each organ was measured using TLD chips. Results: The measured radiation dose within all organs was within the safe limits in phantom and most patients, however, the surface dose were higher in patients in compare to phantom. In some patients, the right lens was not protected and therefore there would be some risk for cataracts. The findings provide estimation for probable complications along with frontal lobe radiotherapy. Conclusion: Our findings showed that regarding these two techniques, technique I impose less harm to normal tissue, since the right lobe of brain is only irradiated. Besides, the higher values of surface dose in patients compared to phantom might be due to larger tumor field in patients, because the tumor dimensions in phantom was considered 4 cm, while in some patients it was larger. © 2015, Singapore Medical Association. All rights reserved

Allopurinol mouthwash for prevention or alleviation radiotherapy induced oral mucositis: A randomized, placebo-controlled trial

Background and the purpose of the study: A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of an allopurinol mouthwash in prevention and alleviation of the oral radiotherapy induced mucositis. Methods: An allopurinol suspension mouthwash having proper physical stability at least for 6 weeks was prepared. A total of 24 patients with oral, nasopharynx or hypopharynx cancer were enrolled in the study. They were randomly allocated to receive either an allopurinol suspension or normal saline as placebo that were identical in appearance. Patients were instructed to use the suspension as a mouthwash 3 times a day for 3 minutes after beginning of each radiotherapy cycle. Patients were graded on the basis of severity of their own symptoms on a weekly basis by using WHO scale. Results: There were no differences in the severity of mucosits between the allopurinol and placebo-treated groups in first and second weeks of treatment (p =0.227, p = 0.121 respectively). In the third, fourth, fifth and sixth weeks, there were significant differences between two groups (p< 0.05 in each weeks separately). Major conclusion: Result of this study support the hypothesis that an allopurinol mouthwash may prevents or alleviate oral mucositis induced by radiotherapy

Differential miRNAs expression pattern of irradiated breast cancer cell lines is correlated with radiation sensitivity

Radiotherapy is a fundamental step in the treatment of breast cancer patients. The treatment efficiency is however reduced by the possible onset of radiation resistance. In order to develop the effective treatment approach, it is important to understand molecular basis of radiosensitivity in breast cancer. The purpose of the present study was to investigate different radiation response of breast cancer cell lines, and find out if this response may be related to change in the microRNAs expression profile. MDA-MB-231 and T47D cells were subjected to different doses of radiation, then MTT and clonogenic assays were performed to assess radiation sensitivity. Cytofluorometric and western blot analysis were performed to gain insight into cell cycle distribution and protein expression. MicroRNA sequencing and bioinformatics prediction methods were used to identify the difference in microRNAs expression between two breast cancer cells and the related genes and pathways. T47D cells were more sensitive to radiation respect to MDA-MB-231 cells as demonstrated by a remarkable G2 cell cycle arrest followed by a greater reduction in cell viability and colony forming ability. Accordingly, T47D cells showed higher increase in the phosphorylation of ATM, TP53 and CDK1 (markers of radiation response) and faster and more pronounced increase in RAD51 and γH2AX expression (markers of DNA damage), when compared to MDA-MB-231 cells. The two cell lines had different microRNAs expression profiles with a confirmed significant differential expression of miR-16-5p, which targets cell cycle related genes and predicts longer overall survival of breast cancer patients, as determined by bioinformatics analysis. These results suggest a possible role for miR-16-5p as radiation sensitizing microRNA and as prognostic/predictive biomarker in breast cancer. © 2020, The Author(s)

Cytotoxic effects of hyperthermia, chemotherapy (Navelbine) and radiation on glioma spheroids

Introduction: Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in humans. Current conventional treatment could not effectively increase the survival rate of patients who suffered from GBM. In clinical view, some experiments which can mimic in vivo conditions to evaluate anticancer agent effects on tumors are very useful. We can fairly reach to this goal using 3-dimentional spheroids rather than monolayer culture. The aim of this study was to determine the cytotoxicity caused by Navelbine, hyperthermia and radiation on glioma spheroids. Methods: The spheroid cells were separately or simultaneously treated with the doses of 7.5 μg/ml Navelbine for 50.3 h, irradiated with 2 Gy and incubated at 43 °C for 1 h. Comet and colony formation assays were applied to assess the DNA damages and survival rate of the cells. Results: In both comet and colony formation assays, cell damage in all treated groups was significantly higher in comparison with control group (P<0.05). Moreover, the synergistic effect of combined groups such as: hyperthermia and radiotherapy, Navelbine and radiotherapy and combination of Navelbine-hyperthermia-radiotherapy was observed. Conclusions: Combined agents with low concentration can cause a synergistic effect on treatment procedure and increased damages in multicellular spheroids. © 2016 Elsevier Ltd

Analysis of Radiomodulatory Effect of Low-Level Laser Irradiation by Clonogenic Survival Assay

Objective: The aim of this study was to investigate the radiomoulatory effects of low-level laser irradiation (LLLI) in normal and cancer cells exposed to ionizing X-ray radiation on clonogenic survival assay. Background data: LLLI does have radioprotective effects on normal tissue. LLLI can reduce the incidence of mucocutaneous complications of ionizing radiation. Few in vitro studies reported adaptive responses for LLLI to ionizing radiation in normal and cancer cells, particularly with respect to clonogenic cell survival assay. Methods: Normal NIH 3T3 cells and cancer HeLa cells were irradiated with 685 and 830 nm LLLI at different energy densities prior to ionizing X-ray radiation. The survival fraction was determined after ionizing radiation (0, 2, 4, and 6 Gy). The values of the linear (α) and quadratic (β) parameters were calculated based on the clonogenic survival curves. Results: Clonogenic radiation survival assay showed that the application of LLLI at 685 nm prior to ionizing radiation could significantly inhibit clonogenic growth of HeLa cells compared with unirradiated HeLa cells. LLLI could also significantly increase the α parameter of the linear quadratic (LQ) model. In contrast, application of LLLI at 830 nm could significantly protect NIH 3T3 cells against radiation and decreased α parameter. Conclusions: This study suggests that various physical parameters of LLLI can be diverse adaptive responses to ionizing radiation on normal and cancer cells. Copyright © 2015, Mary Ann Liebert, Inc

Epistasy search in population-based gene mapping using mutual information

Gene mapping intends to identify the causal genetic regions of a specific phenotype mostly a complex disease. These diseases are believed to have multiple contributing loci that are potentially unknown and often have subtle patterns making them hard to find. Shannon's mutual information figure is used as a criterion. Algorithms based on this criterion as presented and discussed. Furthermore, an algorithm is proposed to form relevance chains. The proposed algorithms are especially in favor of diseases having almost equally contributing regions known as being epistatic and is applied to both simulated and real data. AMD disease results are included. Some highly associated markers are found in AMD. C# source files for relevance-chains are freely available at https://www. sharemation. com/amanzour