• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2613-2617
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• 2015

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.103-115
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• 2014

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6441-6446
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• 2012

Background: Radiation therapy plays an important role in lung carcinoma treatment. However, the incidence of symptomatic radiation-induced lung injury is high. This study aimed to evaluate radioprotective effects of flavonoids extracted from Astragalus complanatus and mechanisms of action against radiation damage. Methods: Alteration in antioxidant status and levles of several cytokines were investigated in BABL/C mice treated with 4 mg/kg b.wt. flavonoids after exposure to 10Gy thoracic radiation. Results: Serum levels of SOD in the flavonoids+radiation group were significantly higher compared to the radiation control group, while TGF-${\beta}1$ and IL-6 were lower. Mice in the radiation control group displayed more severe lung damage compared with the flavonoids+radiation group. The expression of TGF-${\beta}1$ and TNF-${\alpha}$ in the radiation control group was markedly increased in alveolar epithelial cells and macrophages of the alveolar septum. Conclusions: From the results of the present study, flavonoids could be excellent candidates as protective agents against radiation-induced lung injury.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2405-2425
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• 2014

Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex-vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (${\leq}5Gy$) to the whole body or high doses (12-13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury.

• Radiation Oncology Journal
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• v.1 no.1
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• pp.103-109
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• 1983

47 out of 56 cases of intact uterine cervix cancer treated by radiation at the Hanyang University Hospital were followed 18 months or more after treatment. (7 patients died before 18 months, 2 cases lost to follow-up). Age distribution reveal 5 cases in 30's, 18 cases in 40's, 17 cases in 50's, 7 cases in 60's. Histologically, all cases were squamous cell type except one case of adenocarcinoma. 1. 45 cases were treated by combined external Co-60 irradiation and intracavitary irradiation by Cs-137 small sources. 1 case was treated by external irradiation only, and 1 case by intracavitary only. 2. Rectal injuries were observed in 13 cased (27.6%), 4 cases in Grade 1, 8 cased in Grade 2 and 1 cases in Grade 3 which needed surgical management. 3. Average intervals of rectal injury following treatment was 9.2 months varying from 5 to 15 months. 4. Relation between rectal injury and point A dose reveal 6 cases between 7000-7999 rad and 6 cases between 8000-8999 rad and 1 case above 9000 rad. Even though there is no direct relation between point A dose and rectal injury, it is expected that rectal injury increases as point A dose increase. 5. In the normal condition, rectal injury can't be attributed to one major cause. Radiation dose, small source distribution, general condition of patients, local anatomy of the individual patient, history of PID and previous surgery, all play complex roles.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.37-46
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• 1998

It has been known that $\gamma$-irradiation usually induces cell death in regenerating stem cell in normal tissues like skin, intestine and hematopoietic organ. The experiment were carried out to evaluate the early response of radiation injury in radiosensitive and intermediate radiosensitive tissues in feeding and starving rats with the doses of 3.5 and 7.0 Gy. The results of the study showed that the histological phenomenon was apoptosis in the doses of the radiation as the early response of tissue injury. Apoptosis were showed organ-specific and cellular specific responses suggesting that the selection of apoptosis be exactly focused on highly renewal organs and cells. It was interesting that the rats starved for 72 hours prior to irradiation induced less apoptosis in liver than fed rats. As for cellular responses it appeared that apoptotic cells were mostly distributed in ductal or periportal cells in liver of feeding rats unlikely in liver of Starving rots which showed no difference in zonal distribution. In salivary gland apoptotic cells in fed rats were highly induced in intercalating and ductal cell population than in acinar cell population although unlikely in starved rats. This study showed the value of apoptosis using the detection system of TUNEL for evaluating cellular damage after radiation injury and the diminished effect of starvation on cell damage after ionizing irradiation.

• Archives of Plastic Surgery
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• v.45 no.5
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• pp.403-410
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• 2018

Background Radiation-induced skin injury is a dose-limiting complication of radiotherapy. To investigate this problem and to develop a framework for making decisions on treatment and dose prescription, a murine model of radiation-induced skin injury was developed. Methods The dorsal skin of the mice was isolated, and irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were followed for 12 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy samples were obtained and subjected to a histological analysis, immunostaining against transforming growth factor beta (TGF-${\beta}$), and Western blotting with Wnt-3 and ${\beta}$-catenin. Increases in the levels of TGF-${\beta}$, Wnt, and ${\beta}$-catenin were detected after irradiation. Results All tested radiation doses caused progressive dermal thickening and fibrosis. The cause of this process, however, may not be radiation alone, as the natural course of wound healing may elicit a similar response. The latent appearance of molecular and histological markers that induce fibrosis in the 15 Gy group without causing apparent gross skin injuries indicates that 15 Gy is an appropriate dose for characterizing the effects of chronic irradiation alone. Thus, this model best mimics the patterns of injury that occur in human subjects. Conclusions This animal model can be used to elucidate the gross and molecular changes that occur in radiation-induced skin injury and provides an effective platform for studying this adverse effect without complicating the process of wound healing.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4763-4767
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• 2012

Radiation pneumonitis and pulmonary fibrosis are the main complications with radiotherapy for thoracic neoplasms, directly limiting the efficient dose in clinical application and currently there are few medicines that effectively function as radioprotectants. However, a TLR5 agonist, CBLB502, was confirmed to have protective efficacy against hematopoietic and gastrointestinal radiation syndromes in mice and primates. This study points to a new direction for protection against thoracic radiation-induced pulmonary syndromes and skin injury by CBLB502. We utilized the TUNEL assay, pathological analysis and immunohistochemistry to obtain evidence thatCBLB502 could alleviate the occurrence of radiation pneumonitis and pulmonary fibrosis as well as radiation-induced skin injury. It may thus play a promising role in facilitating clinical radiotherapy of thoracic neoplasms.

• Journal of Radiation Protection and Research
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• v.42 no.4
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• pp.189-196
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• 2017

Background: The effects of radiation on tissues vary depending on the radiation type. In this study, a minipig model was used to compare the effects of ${\beta}$-rays from $^{166}Ho$ and ${\gamma}$-rays from $^{60}Co$ on the skin. Materials and Methods: In this study, the detrimental effects of ${\beta}$- and ${\gamma}$-irradiation on the skin were assessed in minipigs. The histopathological changes in the skin from 1 to 12 weeks after exposure to 50 Gy of either ${\beta}$- (using $^{166}Ho$ patches) or ${\gamma}$- (using $^{60}Co$) irradiation were assessed. Results and Discussion: The skin irradiated by ${\beta}$-rays was shown to exhibit more severe skin injury than that irradiated by ${\gamma}$-rays at 1-3 weeks post-exposure; however, while the skin lesions caused by ${\beta}$-rays recovered after 8 weeks, the ${\gamma}$-irradiated skin lesions were not repaired after this time. The observed histopathological changes corresponded with gross appearance scores. Seven days post-irradiation, apoptotic cells in the basal layer were detected more frequently in ${\beta}$-irradiated skin than in ${\gamma}$-irradiated skin. The basal cell density and skin thickness gradually decreased until 4 weeks after ${\gamma}$- and ${\beta}$- irradiation. In ${\beta}$-irradiated skin lesions, and the density and thickness increased sharply back to control levels by 6-9 weeks. However, this was not the case in ${\gamma}$-irradiated skin lesions. In ${\gamma}$-irradiated skin, cyclooxygenase-2 (COX-2) was shown to be expressed in the epidermis, endothelial cells of vessels, and fibroblasts, while ${\beta}$-irradiated lesions exhibited COX-2 expression that was mostly limited to the epidermis. Conclusion: In this study, ${\beta}$-rays were shown to induce more severe skin injury than ${\gamma}$-rays; however, the ${\beta}$-rays-induced injury was largely repaired over time, while the ${\gamma}$-rays-induced injury was not repaired and instead progressed to necrosis. These findings reveal the differential effects of ${\gamma}$- and ${\beta}$-irradiation on skin and demonstrate the use of minipigs as a beneficial experimental model for studying irradiation-induced skin damage.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4101-4105
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• 2012

Purpose: The degree of radiation injury to kidneys which are located within the limits of radiotherapy area is determined by the volume and the dose of radiation to which the organ is exposed. When the tolerance dose of the kidney is exceeded after a latent period of 6 months acute nephritis develops and after 18 months chronic nephritis ensues. Melatonin is known to prevent the oxidative injury of toxins and radiotherapy with its free radical scavenging capacity. Methods and Materials: In this study 8 weeks old 24 Sprague -Dawley rats were allocated into 4 groups: Control group; Radiotherapy group (20 Gy bilaterally in 5 fractions); Melatonin group (10 mg/kg intraperitoneally), and Melatonin+radiotherapy group (20 Gy Radiotherapy in 5 fractions+ melatonin 10 mg/kg intraperitoneally). After a follow-up period of 6 months BUN was determined in all groups. After rats were euthanized the kidneys were removed for histopathological examination under both light and electron microscopes. Results: After 6 months follow-up, both at light and electron microscopy levels, the rats in radiotherapy+melatonin group were significantly protected against the radiation injury comparing to radiotherapy group (p<0.05). Conclusion: It was shown in this experimental model that melatonin has protective effects against radiation injury to kidneys.