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Sample records for radiation-induced rectal toxicity

  1. Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

    SciTech Connect

    Prior, Phillip; Devisetty, Kiran; Tarima, Sergey S.; Lawton, Colleen A.F.; Semenenko, Vladimir A.

    2012-05-01

    Purpose: To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. Methods and Materials: A data survey was performed to identify the published reports on the dose-response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. Results: A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose-response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and {>=}36 months did not reveal significant differences (p {>=} .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. Conclusions: The proposed approach is feasible and allows for more systematic use of published dose-response data to estimate the complication risks for the individual patient.

  2. Management of radiation-induced rectal bleeding.

    PubMed

    Laterza, Liboria; Cecinato, Paolo; Guido, Alessandra; Mussetto, Alessandro; Fuccio, Lorenzo

    2013-11-01

    Pelvic radiation disease is one of the major complication after radiotherapy for pelvic cancers. The most commonly reported symptom is rectal bleeding which affects patients' quality of life. Therapeutic strategies for rectal bleeding are generally ignored and include medical, endoscopic, and hyperbaric oxygen treatments. Most cases of radiation-induced bleeding are mild and self-limiting, and treatment is normally not indicated. In cases of clinically significant bleeding (i.e. anaemia), medical therapies, including stool softeners, sucralfate enemas, and metronidazole, should be considered as first-line treatment options. In cases of failure, endoscopic therapy, mainly represented by argon plasma coagulation and hyperbaric oxygen treatments, are valid and complementary second-line treatment strategies. Although current treatment options are not always supported by high-quality studies, patients should be reassured that treatment options exist and success is achieved in most cases if the patient is referred to a dedicated centre.

  3. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients.

    PubMed

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Llontop, Pedro; Gutierrez, Dominga; Ceballos, Daniel; Méndez, Charlin; Rovira, Gloria; Suarez, Gerardo; Rey-Baltar, Dolores; Garcia-Cabrera, Laura; Martínez-Sánchez, Gregorio; Fiuza, Dolores

    2015-01-01

    Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52-119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7-14) g/dL to 13 (10-15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation.

  4. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients

    PubMed Central

    Clavo, Bernardino; Santana-Rodriguez, Norberto; Llontop, Pedro; Gutierrez, Dominga; Ceballos, Daniel; Méndez, Charlin; Rovira, Gloria; Suarez, Gerardo; Rey-Baltar, Dolores; Garcia-Cabrera, Laura; Martínez-Sánchez, Gregorio; Fiuza, Dolores

    2015-01-01

    Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52–119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7–14) g/dL to 13 (10–15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation. PMID:26357522

  5. The radiation-induced changes in rectal mucosa: Hyperfractionated vs. hypofractionated preoperative radiation for rectal cancer

    SciTech Connect

    Starzewski, Jacek J.; Pajak, Jacek T.; Pawelczyk, Iwona; Lange, Dariusz; Golka, Dariusz . E-mail: dargolka@wp.pl; Brzeziska, Monika; Lorenc, Zbigniew

    2006-03-01

    Purpose: The purpose of the study was the qualitative and quantitative evaluation of acute radiation-induced rectal changes in patients who underwent preoperative radiotherapy according to two different irradiation protocols. Patients and Methods: Sixty-eight patients with rectal adenocarcinoma underwent preoperative radiotherapy; 44 and 24 patients underwent hyperfractionated and hypofractionated protocol, respectively. Fifteen patients treated with surgery alone served as a control group. Five basic histopathologic features (meganucleosis, inflammatory infiltrations, eosinophils, mucus secretion, and erosions) and two additional features (mitotic figures and architectural glandular abnormalities) of radiation-induced changes were qualified and quantified. Results: Acute radiation-induced reactions were found in 66 patients. The most common were eosinophilic and plasma-cell inflammatory infiltrations (65 patients), erosions, and decreased mucus secretion (54 patients). Meganucleosis and mitotic figures were more common in patients who underwent hyperfractionated radiotherapy. The least common were the glandular architectural distortions, especially in patients treated with hypofractionated radiotherapy. Statistically significant differences in morphologic parameters studied between groups treated with different irradiation protocols were found. Conclusion: The system of assessment is a valuable tool in the evaluation of radiation-induced changes in the rectal mucosa. A greater intensity of regenerative changes was found in patients treated with hyperfractionated radiotherapy.

  6. Efficacy of hyperbaric oxygen therapy in patients with radiation-induced rectal ulcers: A report of five cases.

    PubMed

    Yoshimizu, Shoichi; Chino, Akiko; Miyamoto, Yuji; Tagao, Fuyuki; Iwasaki, Susumu; Ide, Daisuke; Tamegai, Yoshiro; Igarashi, Masahiro; Saito, Shoichi; Fujisaki, Junko

    2017-03-28

    For decades, hyperbaric oxygen therapy has been considered a treatment option in patients with chronic radiation-induced proctitis after pelvic radiation therapy. Refractory cases of chronic radiation-induced proctitis include ulceration, stenosis, and intestinal fistulas with perforation. Appropriate treatment needs to be administered. In this study, we assessed the efficacy of hyperbaric oxygen therapy in five patients with radiation-induced rectal ulcers. Significant improvement and complete ulcer resolution was observed in all treated patients; no side effects were reported. Hyperbaric oxygen therapy has a low toxicity profile and appears to be highly effective in patients with radiation-induced rectal ulcers. However, hyperbaric oxygen therapy alone failed to improve telangiectasia and easy bleeding in four of five patients; these patients were further treated with argon plasma coagulation. Although hyperbaric oxygen therapy may be effective in healing patients with ulcers, it seems inadequate in cases that easy bleeding. Altogether, these data suggest that combination therapy with hyperbaric oxygen therapy and argon plasma coagulation may be an effective and safe treatment strategy in patients with radiation-induced rectal ulcers. This article is protected by copyright. All rights reserved.

  7. Using dose-surface maps to predict radiation-induced rectal bleeding: a neural network approach

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

    2009-09-01

    The incidence of late-toxicities after radiotherapy can be modelled based on the dose delivered to the organ under consideration. Most predictive models reduce the dose distribution to a set of dose-volume parameters and do not take the spatial distribution of the dose into account. The aim of this study was to develop a classifier predicting radiation-induced rectal bleeding using all available information on the dose to the rectal wall. The dose was projected on a two-dimensional dose-surface map (DSM) by virtual rectum-unfolding. These DSMs were used as inputs for a classification method based on locally connected neural networks. In contrast to fully connected conventional neural nets, locally connected nets take the topology of the input into account. In order to train the nets, data from 329 patients from the RT01 trial (ISRCTN 47772397) were split into ten roughly equal parts. By using nine of these parts as a training set and the remaining part as an independent test set, a ten-fold cross-validation was performed. Ensemble learning was used and 250 nets were built from randomly selected patients from the training set. Out of these 250 nets, an ensemble of expert nets was chosen. The performances of the full ensemble and of the expert ensemble were quantified by using receiver-operator-characteristic (ROC) curves. In order to quantify the predictive power of the shape, ensembles of fully connected conventional neural nets based on dose-surface histograms (DSHs) were generated and their performances were quantified. The expert ensembles performed better than or equally as well as the full ensembles. The area under the ROC curve for the DSM-based expert ensemble was 0.64. The area under the ROC curve for the DSH-based expert ensemble equalled 0.59. This difference in performance indicates that not only volumetric, but also morphological aspects of the dose distribution are correlated to rectal bleeding after radiotherapy. Thus, the shape of the dose

  8. Faecal microbiota transplantation protects against radiation-induced toxicity.

    PubMed

    Cui, Ming; Xiao, Huiwen; Li, Yuan; Zhou, Lixin; Zhao, Shuyi; Luo, Dan; Zheng, Qisheng; Dong, Jiali; Zhao, Yu; Zhang, Xin; Zhang, Junling; Lu, Lu; Wang, Haichao; Fan, Saijun

    2017-04-01

    Severe radiation exposure may cause acute radiation syndrome, a possibly fatal condition requiring effective therapy. Gut microbiota can be manipulated to fight against many diseases. We explored whether intestinal microbe transplantation could alleviate radiation-induced toxicity. High-throughput sequencing showed that gastrointestinal bacterial community composition differed between male and female mice and was associated with susceptibility to radiation toxicity. Faecal microbiota transplantation (FMT) increased the survival rate of irradiated animals, elevated peripheral white blood cell counts and improved gastrointestinal tract function and intestinal epithelial integrity in irradiated male and female mice. FMT preserved the intestinal bacterial composition and retained mRNA and long non-coding RNA expression profiles of host small intestines in a sex-specific fashion. Despite promoting angiogenesis, sex-matched FMT did not accelerate the proliferation of cancer cells in vivo FMT might serve as a therapeutic to mitigate radiation-induced toxicity and improve the prognosis of tumour patients after radiotherapy.

  9. Management of late radiation-induced rectal injury after treatment of carcinoma of the uterus

    SciTech Connect

    Allen-Mersh, T.G.; Wilson, E.J.; Hope-Stone, H.F.; Mann, C.V.

    1987-06-01

    Sixty-one of 1418 (4.3 per cent) patients treated with radiation for carcinoma of the uterus from 1963 to 1983 had significant radiation-induced complications of the intestine develop which required a surgical opinion considering further management. Ninety-three per cent of these complications involved the rectum. Florid proctitis resolved within two years of onset in 33 per cent of the patients who were managed conservatively while 22 per cent of the patients died of disseminated disease within the same time period. Surgical treatment was eventually necessary in 39 per cent of the patients who were initially treated conservatively for radiation induced proctitis. Rectal excision with coloanal sleeve anastomosis produced a satisfactory result in eight of 11 patients with severe radiation injury involving the rectum. The incidence of radiation-induced and malignant rectovaginal fistula were similar (1 per cent), but disease-induced symptoms tended to occur earlier after primary treatment (a median of eight months) compared with radiation-induced symptoms (a median of 16 months).

  10. Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate

    SciTech Connect

    Kochhar, R.; Patel, F.; Dhar, A.; Sharma, S.C.; Ayyagari, S.; Aggarwal, R.; Goenka, M.K.; Gupta, B.D.; Mehta, S.K. )

    1991-01-01

    In a prospective study, 37 consecutive patients with radiation-induced proctosigmoiditis were randomized to receive a four-week course of either 3.0 g oral sulfasalazine plus 20 mg twice daily rectal prednisolone enemas (group I, N = 18) or 2.0 g twice daily rectal sucralfate enemas plus oral placebo (group II, N = 19). The two groups were comparable with respect to demographic features, duration of symptoms, and clinical and endoscopic staging of the disease. Fifteen patients in group I and 17 in group II completed the trial. At four weeks, both groups showed significant clinical improvement (P less than 0.01 for group I and P less than 0.001 for group II) and endoscopic healing (P less than 0.01 for group I and P less than 0.001 for group II). When the two groups were compared, sucralfate enemas showed a significantly better response as assessed clinically (P less than 0.05), although endoscopically the response was not statistically different (P greater than 0.05). We conclude that both treatment regimens are effective in the management of radiation proctitis. Sucralfate enemas give a better clinical response, are tolerated better, and because of the lower cost should be the preferred mode of short-term treatment.

  11. Radiation Dose-Volume Effects in Radiation-Induced Rectal Injury

    SciTech Connect

    Michalski, Jeff M.; Gay, Hiram; Jackson, Andrew; Tucker, Susan L.; Deasy, Joseph O.

    2010-03-01

    The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving >=60Gy is consistently associated with the risk of Grade >=2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04-0.14); m = 0.13 (0.10-0.17); and TD{sub 50} = 76.9 (73.7-80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions.

  12. Intrarectal application of amifostine for the prevention of radiation-induced rectal injury.

    PubMed

    Ben-Josef, Edgar; Han, Sue; Tobi, Martin; Vargas, Barbara J; Stamos, Beth; Kelly, Laura; Biggar, Sandra; Kaplan, Irving

    2002-01-01

    Clinically symptomatic late injury to the rectal wall occurs in about one third of patients with prostate cancer treated with external beam irradiation. Reducing the physical dose to the anterior rectal wall without a similar reduction in the posterior peripheral zone is difficult because of the proximity of these structures. Based on our previous observations that intrarectal application of amifostine resulted in very high concentrations of amifostine and its active metabolite WR-1065 in the rectal wall of Copenhagen rats, the authors initiated a phase I clinical trial in 1998. Twenty-nine patients with localized prostate cancer were accrued. Eligibility criteria included histologically confirmed adenocarcinoma, a Karnofsky performance status of > or =70, and no pelvic lymphadenopathy or distant metastases. The total dose to the prostate was 70.2 Gy (20 patients) and 73.8 Gy (9 patients). Therapy was delivered using a 4-field axial technique and 3-dimensional conformal planning. Amifostine was administered intrarectally as an aqueous solution 30 minutes before irradiation on the first 15 days of therapy. Amifostine dose was escalated, in cohorts, from 500 mg to 2,500 mg. Toxicity was evaluated using the Radiation Therapy Oncology Group late morbidity scale. All patients completed therapy with no amifostine-related toxicity at any dose level. The application was feasible and well tolerated. With a median follow-up time of 21 months, 9 patients (33%) had rectal bleeding (8 grade 1, 1 grade 2). Four patients (14%) had symptoms suggestive of radiation injury, which proved to be secondary to nonrelated processes. These included preexisting nonspecific proctitis (1 patient), diverticular disease of the sigmoid colon, rectal polyp (1 patient), and ulcerative colitis (1 patient). Symptoms developed significantly more often in patients receiving 500 to 1,000 mg than in patients receiving 1,500 to 2,500 mg amifostine (7 of 14 [50%] versus 2 of 13 [15%]; P =.0325, 1-sided

  13. Clinical and dosimetric factors of radiation-induced esophageal injury: Radiation-induced esophageal toxicity

    PubMed Central

    Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

    2005-01-01

    AIM: To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). METHODS: We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT. PMID:15849822

  14. Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy.

    PubMed

    Kawamoto, Aya; Tanaka, Koji; Saigusa, Susumu; Toiyama, Yuji; Morimoto, Yuhki; Fujikawa, Hiroyuki; Iwata, Takashi; Matsushita, Kohei; Yokoe, Takeshi; Yasuda, Hiromi; Inoue, Yasuhiro; Miki, Chikao; Kusunoki, Masato

    2012-03-01

    CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P<0.01). CD133 was associated with distant recurrence after CRT followed by surgery (P<0.05). Patients with elevated CD133 in residual cancer cells showed poor disease-free survival (P<0.05). No significant association between post-CRT CD44 and clinical outcome was found. The in vitro study showed that CD133 protein was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells. CD44 protein was decreased after irradiation. CD133, but not CD44, was increased in radiation-resistant surviving colon cancer cells. Post-CRT CD133 in residual cancer cells may predict metachronous distant recurrence and poor survival of rectal cancer patients after CRT.

  15. Mechanisms of radiation-induced brain toxicity and implications for future clinical trials.

    PubMed

    Kim, Jae Ho; Brown, Stephen L; Jenrow, Kenneth A; Ryu, Samuel

    2008-05-01

    Radiation therapy is widely used in the treatment of primary malignant brain tumors and metastatic tumors of the brain with either curative or palliative intent. The limitation of cancer radiation therapy does not derive from the inability to ablate tumor, but rather to do so without excessively damaging the patient. Among the varieties of radiation-induced brain toxicities, it is the late delayed effects that lead to severe and irreversible neurological consequences. Following radiation exposure, late delayed effects within the CNS have been attributable to both parenchymal and vascular damage involving oligodendrocytes, neural progenitors, and endothelial cells. These reflect a dynamic process involving radiation-induced death of target cells and subsequent secondary reactive neuroinflammatory processes that are believed to lead to selective cell loss, tissue damage, and functional deficits. The progressive, late delayed damage to the brain after high-dose radiation is thought to be caused by radiation-induced long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines. Experimental studies suggest that radiation-induced brain injury can be successfully mitigated and treated with several well established drugs in wide clinical use which exert their effects by blocking pro-inflammatory cytokines and reactive oxygen species. This review highlights preclinical and early clinical data that are translatable for future clinical trials.

  16. Dosimetric Predictors of Radiation-Induced Vaginal Stenosis After Pelvic Radiation Therapy for Rectal and Anal Cancer.

    PubMed

    Son, Christina H; Law, Ethel; Oh, Jung Hun; Apte, Aditya P; Yang, T Jonathan; Riedel, Elyn; Wu, Abraham J; Deasy, Joseph O; Goodman, Karyn A

    2015-07-01

    Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D) in dilator size before and after RT was recorded. Those with D ≤-1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = -1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Sodium Tanshinone IIA Sulfonate Prevents Radiation-Induced Toxicity in H9c2 Cardiomyocytes

    PubMed Central

    Zhang, Wenjing; Li, Rui; Wang, Yaya; Zhu, Mengwen; Wang, Bowen; Li, Yanling; Li, Dongyun

    2017-01-01

    The present study was designed to elucidate the key parameters associated with X-ray radiation induced oxidative stress and the effects of STS on X-ray-induced toxicity in H9c2 cardiomyocytes. Cytotoxicity of STS and radiation was assessed by MTT. Antioxidant activity was evaluated by SOD and MDA. Apoptosis was measured by the flow cytometry, Hoechst 33258, clonogenic survival assay, and western blot. It was found that the cell viability of H9c2 cells exposed to X-ray radiation was significantly decreased in a dose-dependent manner and was associated with cell cycle arrest at the G0/G1 phase as well as apoptosis. STS treatment significantly reversed the morphological changes, attenuated radiation-induced apoptosis, and improved the antioxidant activity in the H9c2 cells. STS significantly increased the Bcl-2 and Bcl-2/Bax levels and decreased the Bax and caspase-3 levels, compared with the cells treated with radiation alone. STS treatment also resulted in a significant increase in p38-MAPK activation. STS could protect the cells from X-ray-induced cell cycle arrest, oxidative stress, and apoptosis. Therefore, we suggest the STS could be useful for the treatment of radiation-induced cardiovascular injury. PMID:28386289

  18. Fatal hepatic and renal toxicity as a complication of trabectedin therapy for radiation-induced sarcoma.

    PubMed

    Pick, Amy M; Nystrom, Kelly K

    2010-12-01

    Trabectedin therapy was prescribed for a patient with radiation-induced sarcoma. Two doses of trabectedin were given before therapy was discontinued with the patient experiencing renal and liver failure. Despite discontinuing trabectedin the patient continued to experience increases in liver transaminases, bilirubin, blood urea nitrogen, and serum creatinine. Hemodialysis was initiated with no improvement. With all other causes being ruled out, trabectedin likely caused hepatic and renal failure leading to death in this patient. Recent literature suggests that patients may benefit from prophylactic dexamethasone as a means of reducing hepatic toxicity.

  19. PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2

    PubMed Central

    Taniguchi, Cullen M.; Miao, Yu Rebecca; Diep, Anh N.; Wu, Colleen; Rankin, Erinn B.; Atwood, Todd F.; Xing, Lei; Giaccia, Amato J.

    2014-01-01

    Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD isoforms by the small molecule dimethyloxyallylglycine (DMOG) increases HIF expression, improves epithelial integrity, reduces apoptosis, and increases intestinal angiogenesis, all of which are essential for radioprotection. HIF2, but not HIF1, is both necessary and sufficient to prevent radiation-induced GI toxicity and death. Increased VEGF expression contributes to the protective effects of HIF2, since inhibition of VEGF function reversed the radioprotection and radiomitigation afforded by DMOG. Additionally, mortality is reduced from abdominal or total body irradiation even when DMOG is given 24 hours after exposure. Thus, prolyl hydroxylase inhibition represents a new treatment strategy to protect against and mitigate GI toxicity from both therapeutic radiation and potentially lethal radiation exposures. PMID:24828078

  20. PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2.

    PubMed

    Taniguchi, Cullen M; Miao, Yu Rebecca; Diep, Anh N; Wu, Colleen; Rankin, Erinn B; Atwood, Todd F; Xing, Lei; Giaccia, Amato J

    2014-05-14

    Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD (prolyl hydroxylase domain) isoforms by the small-molecule dimethyloxallyl glycine (DMOG) increases hypoxia-inducible factor (HIF) expression, improves epithelial integrity, reduces apoptosis, and increases intestinal angiogenesis, all of which are essential for radioprotection. HIF2, but not HIF1, is both necessary and sufficient to prevent radiation-induced GI toxicity and death. Increased vascular endothelial growth factor (VEGF) expression contributes to the protective effects of HIF2, because inhibition of VEGF function reversed the radioprotection and radiomitigation afforded by DMOG. Additionally, mortality from abdominal or total body irradiation was reduced even when DMOG was given 24 hours after exposure. Thus, prolyl hydroxylase inhibition represents a treatment strategy to protect against and mitigate GI toxicity from both therapeutic radiation and potentially lethal radiation exposures.

  1. Radiation-Induced Lymphocyte Apoptosis to Predict Radiation Therapy Late Toxicity in Prostate Cancer Patients

    SciTech Connect

    Schnarr, Kara; Boreham, Douglas; Sathya, Jinka; Julian, Jim; Dayes, Ian S.

    2009-08-01

    Purpose: To examine a potential correlation between the in vitro apoptotic response of lymphocytes to radiation and the risk of developing late gastrointestinal (GI)/genitourinary (GU) toxicity from radiotherapy for prostate cancer. Methods and Materials: Prostate cancer patients formerly enrolled in a randomized study were tested for radiosensitivity by using a radiation-induced lymphocyte apoptosis assay. Apoptosis was measured using flow cytometry-based Annexin-FITC/7AAD and DiOC{sub 6}/7AAD assays in subpopulations of lymphocytes (total lymphocytes, CD4+, CD8+ and CD4-/CD8-) after exposure to an in vitro dose of 0, 2, 4, or 8 Gy. Results: Patients with late toxicity after radiotherapy showed lower lymphocyte apoptotic responses to 8 Gy than patients who had not developed late toxicity (p = 0.01). All patients with late toxicity had apoptosis levels that were at or below the group mean. The negative predictive value in both apoptosis assays ranged from 95% to 100%, with sensitivity values of 83% to 100%. Apoptosis at lower dose points and in lymphocyte subpopulations had a weaker correlation with the occurrence of late toxicity. Conclusions: Lymphocyte apoptosis after 8 Gy of radiation has the potential to predict which patients will be spared late toxicity after radiation therapy. Further research should be performed to identify the specific subset of lymphocytes that correlates with late toxicity, followed by a corresponding prospective study.

  2. Nomogram to predict rectal toxicity following prostate cancer radiotherapy

    PubMed Central

    Delobel, Jean-Bernard; Ospina, Juan David; Beckendorf, Véronique; Chira, Ciprian; Zhu, Jian; Bossi, Alberto; Messai, Taha; Acosta, Oscar; Castelli, Joël; de Crevoisier, Renaud

    2017-01-01

    Background To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. Methods In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. Results Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3–0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0–1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1–10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3–0.8, p<0.01). Based on these three parameters, a nomogram was generated. Conclusions Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique. PMID:28640871

  3. Dosimetric Predictors of Radiation-Induced Vaginal Stenosis After Pelvic Radiation Therapy for Rectal and Anal Cancer

    SciTech Connect

    Son, Christina H.; Law, Ethel; Oh, Jung Hun; Apte, Aditya P.; Yang, T. Jonathan; Riedel, Elyn; Wu, Abraham J.; Deasy, Joseph O.; Goodman, Karyn A.

    2015-07-01

    Purpose: Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. Methods and Materials: We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D) in dilator size before and after RT was recorded. Those with D ≤−1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. Results: The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = −1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Conclusions: Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.

  4. Quantitative Ultrasonic Evaluation of Radiation-Induced Late Tissue Toxicity: Pilot Study of Breast Cancer Radiotherapy

    SciTech Connect

    Liu Tian; Zhou Jun; Yoshida, Emi J.; Woodhouse, Shermian A.; Schiff, Peter B.; Wang, Tony J.C.; Lu Zhengfeng; Pile-Spellman, Eliza; Zhang Pengpeng; Kutcher, Gerald J.

    2010-11-01

    Purpose: To investigate the use of advanced ultrasonic imaging to quantitatively evaluate normal-tissue toxicity in breast-cancer radiation treatment. Methods and Materials: Eighteen breast cancer patients who received radiation treatment were enrolled in an institutional review board-approved clinical study. Radiotherapy involved a radiation dose of 50.0 to 50.4 Gy delivered to the entire breast, followed by an electron boost of 10.0 to 16.0 Gy delivered to the tumor bed. Patients underwent scanning with ultrasound during follow-up, which ranged from 6 to 94 months (median, 22 months) postradiotherapy. Conventional ultrasound images and radio-frequency (RF) echo signals were acquired from treated and untreated breasts. Three ultrasound parameters, namely, skin thickness, Pearson coefficient, and spectral midband fit, were computed from RF signals to measure radiation-induced changes in dermis, hypodermis, and subcutaneous tissue, respectively. Ultrasound parameter values of the treated breast were compared with those of the untreated breast. Ultrasound findings were compared with clinical assessment using Radiation Therapy Oncology Group (RTOG) late-toxicity scores. Results: Significant changes were observed in ultrasonic parameter values of the treated vs. untreated breasts. Average skin thickness increased by 27.3%, from 2.05 {+-} 0.22mm to 2.61 {+-} 0.52mm; Pearson coefficient decreased by 31.7%, from 0.41 {+-} 0.07 to 0.28 {+-} 0.05; and midband fit increased by 94.6%, from -0.92 {+-} 7.35 dB to 0.87 {+-} 6.70 dB. Ultrasound evaluations were consistent with RTOG scores. Conclusions: Quantitative ultrasound provides a noninvasive, objective means of assessing radiation-induced changes to the skin and subcutaneous tissue. This imaging tool will become increasingly valuable as we continue to improve radiation therapy technique.

  5. Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies.

    PubMed

    Wu, Cheng-Chia; Wuu, Yen-Ruh; Yanagihara, Theodore; Jani, Ashish; Xanthopoulos, Eric P; Tiwari, Akhil; Wright, Jason D; Burke, William M; Hou, June Y; Tergas, Ana I; Deutsch, Israel

    2017-09-01

    Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior

  6. Ability of radiation therapists to assess radiation-induced skin toxicity.

    PubMed

    Acharya, Urvi; Cox, Jennifer; Rinks, Marianne; Gaur, Pankaj; Back, Michael

    2013-06-01

    Radiation therapy has seen enhancement of the radiation therapist (RT) role, with RTs and nurses performing duties that were traditionally in the radiation oncologist's (RO) domain. This study aimed to assess whether RTs can consistently grade radiation-induced skin toxicity and their concordance with the gradings given by ROs. Digital photographs of skin reactions were taken at weeks 1, 3 and 6 of radiotherapy on nine patients with breast cancer. The randomly ordered photographs were reviewed once by eight ROs and four RO registrars and on two occasions separated by 6 weeks by 17 RTs. All graded the skin toxicities using the revised Radiation Therapy Oncology Group system. No significant difference was seen between the median scores of the RTs at the first scoring session and the RO/Registrar group. The RTs at both measurement times showed greater inter-rater reliability than the RO/Registrars (W = 0.6866, time 1 and 0.6981 time 2, vs. 0.6517), with the experienced RTs the most consistent (W = 0.7078). The RTs also showed high intra-rater reliability (rho = 0.8461, P < 0.0010). These results from RTs with no specific preparation indicate that experienced RTs could assess breast cancer skin toxicity as part of their role. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  7. The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity.

    PubMed

    Adhikari, Manish; Arora, Rajesh

    2016-06-01

    The main focus of this study is evaluation of radioprotective efficacy of silymarin, a flavonolignan, against γ-radiation-induced damage to hematological, vital organs (liver and intestine), and immune system. Survival studies revealed that silymarin (administered orally for 3 days) provided maximum protection (67%) at 70 mg/kg body weight (b.wt.) against lethal 9 Gy γ-irradiation (dose reduction factor = 1.27). The study revealed significant (p < 0.05) changes in levels of catalase (12.57 ± 2.58 to 30.24 ± 4.89 units), glutathione peroxidase (6.23 ± 2.95 to 13.26 ± 1.36 µg of reduced glutathione consumed/min/mg protein), glutathione reductase (0.25 ± 5.6 to 11.65 ± 2.83 pM NADPH consumed/min/mg protein), and superoxide dismutase (11.74 ± 0.2 to 16.09 ± 3.47 SOD U/mg of protein) activity at 30th day. Silymarin pretreated irradiated group exhibited increased proliferation in erythrocyte count (1.76 ± 0.41 × 10(6) to 9.25 ± 0.24 × 10(6) ), hemoglobin (2.15 ± 0.48g/dL to 14.77 ± 0.25g/dL), hematocrit (4.55 ± 0.24% to 37.22 ± 0.21%), and total leucocyte count (1.4 ± 0.15 × 10(6) to 8.31 ± 0.47 × 10(6) ) as compared with radiation control group on 15th day. An increase in CD4:CD8 ratio was witnessed (0.2-1%) at 30th day time interval using flow cytometry. Silymarin also countered radiation-induced decrease (p < 0.05) in regulatory T-cells (Tregs ) (11.23% in radiation group at 7th day versus 0.1% in pretreated silymarin irradiated group at 15th day). The results of this study indicate that flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity and might prove useful in management of nuclear and radiological emergencies. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 641-654, 2016.

  8. Prophylaxis and management of acute radiation-induced skin toxicity: a survey of practice across Europe and the USA.

    PubMed

    O'Donovan, A; Coleman, M; Harris, R; Herst, P

    2015-05-01

    Radiation-induced toxicity is a common adverse side effect of radiation therapy. Previous studies have demonstrated a lack of evidence to support common skincare advice for radiotherapy patients. The aim of the current study was to investigate the management of radiation-induced skin toxicity across Europe and the USA. Where previous surveys have focused on national practice or treatment of specific sites, the current study aimed to gain a broader representation of skincare practice. An anonymous online survey investigating various aspects of radiotherapy skincare management was distributed to departments across Europe and the USA (n = 181/737 responded i.e. 25%). The UK was excluded as a similar survey was carried out in 2011. The results highlight the lack of consistency in both the prevention and management of radiation-induced skin toxicity. Recommended products are often not based on evidence-based practice. Examples include the continued use of aqueous cream and gentian violet, as well as the recommendations on washing restrictions during treatment. To our knowledge, this is the most extensive survey to date on the current management of radiation-induced skin toxicity. This study highlights significant disparities between clinical practice and research-based evidence published in recent systematic reviews and guidelines. Ongoing large prospective randomised trials are urgently needed. © 2014 John Wiley & Sons Ltd.

  9. Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats.

    PubMed

    Mansour, Heba H; Hafez, Hafez F; Fahmy, Nadia M; Hanafi, Nemat

    2008-02-01

    The present study was designed to evaluate the radioprotective effect of N- acetylcysteine (NAC) on gamma-radiation induced toxicity in hepatic tissue in rat. The cellular changes were estimated using malondialdehyde (MDA, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), reduced glutathione (GSH), and total nitrate/nitrite (NO(x)) as markers of hepatic oxidative stress in rats following gamma-irradiation. The DNA damage was determined by agarose gel electrophoresis. To achieve the ultimate goal of this study, 40 adult rats were randomly divided into 4 groups of 10 animals each. Group I was injected intraperitoneally with saline solution for 7 consecutive days and served as control group. Group II was irradiated with a single dose of 6Gy gamma-radiation. Group III was daily injected with NAC (1g/kg, i.p.) for 7 consecutive days. Group IV received a daily i.p. injection of NAC (1g/kg, i.p.) for 7 consecutive days and 1h after the last dose, rats were irradiated with a single dose (6Gy) gamma-radiation. The animals were sacrificed after 24h. DNA damage was observed in tissue after total body irradiation with a single dose of 6Gy. Malondialdehyde and total nitrate/nitrite were increased significantly whereas the levels of GSH and antioxidant enzymes were significantly decreased in gamma-irradiated group. Pretreatment with NAC showed a significant decrease in the levels of MDA, NO(x) and DNA damage. The antioxidant enzymes increased significantly along with the levels of GSH. Moreover, histopathological examination of liver tissues confirmed the biochemical data. Thus, our results show that pretreatment with N-acetylcysteine offers protection against gamma-radiation induced cellular damage.

  10. A PPAR-gamma agonist protects from radiation-induced intestinal toxicity

    PubMed Central

    Sottili, Mariangela; Gerini, Chiara; Desideri, Isacco; Bastida, Cinzia; Pallotta, Stefania; Castiglione, Francesca; Bonomo, Pierluigi; Meattini, Icro; Greto, Daniela; Cappelli, Sabrina; Di Brina, Lucia; Loi, Mauro; Biti, Giampaolo; Livi, Lorenzo

    2016-01-01

    Objective Because of its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-neoplastic properties, the PPAR-γ agonist rosiglitazone is an interesting drug for investigating for use in the prevention and treatment of radiation-induced intestinal damage. We aimed to evaluate the radioprotective effect of rosiglitazone in a murine model of acute intestinal damage, assessing whether radioprotection is selective for normal tissues or also occurs in tumour cells. Methods Mice were total-body irradiated (12 Gy), with or without rosiglitazone (5 mg/kg/day). After 24 and 72 hours, mice were sacrificed and the jejunum was collected. HT-29 human colon cancer cells were irradiated with a single dose of 2 (1000 cells), 4 (1500 cells) or 6 (2000 cells) Gy, with or without adding rosiglitazone (20 µM) 1 hour before irradiation. HT-29-xenografted CD1 mice were irradiated (16 Gy) with or without rosiglitazone; tumour volumes were measured for 33 days. Results Rosiglitazone markedly reduced histological signs of altered bowel structures, that is, villi shortening, submucosal thickening, necrotic changes in crypts, oedema, apoptosis, and inflammatory infiltrate induced by irradiation. Rosiglitazone significantly decreased p-NF-kB p65 phosphorylation and TGFβ protein expression at 24 and 72 hours post-irradiation and significantly decreased gene expression of Collagen1, Mmp13, Tnfα and Bax at 24 hours and p53 at 72 hours post-irradiation. Rosiglitazone reduced HT-29 clonogenic survival, but only produced a slight reduction of xenograft tumour growth. Conclusion Rosiglitazone exerts a protective effect on normal tissues and reduces alterations in bowel structures and inflammation in a radiation-induced bowel toxicity model, without interfering with the radiation effect on HT-29 cancer cells. PPAR-γ agonists should be further investigated for their application in abdominal and pelvic irradiation. PMID:28344789

  11. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice

    PubMed Central

    Schüler, Emil; Larsson, Maria; Parris, Toshima Z.; Johansson, Martin E.; Helou, Khalil; Forssell-Aronsson, Eva

    2015-01-01

    The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity. Methods C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys). At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a) global transcriptional variations in kidney tissues, (b) morphological changes in the kidneys, (c) changes in white and red blood cell count as well as blood levels of urea, and (d) changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy. Results In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months. Conclusion Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm

  12. Poor Baseline Pulmonary Function May Not Increase the Risk of Radiation-Induced Lung Toxicity

    SciTech Connect

    Wang, Jingbo; Cao, Jianzhong; Yuan, Shuanghu; Arenberg, Douglas; Stanton, Paul; Tatro, Daniel; Ten Haken, Randall K.; Kong, Feng-Ming

    2013-03-01

    Purpose: Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). Methods and Materials: NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary disease (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. Results: There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). Conclusions: Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.

  13. Prospective evaluation of radiation-induced skin toxicity in a race/ethnically diverse breast cancer population.

    PubMed

    Wright, Jean L; Takita, Cristiane; Reis, Isildinha M; Zhao, Wei; Lee, Eunkyung; Nelson, Omar L; Hu, Jennifer J

    2016-03-01

    We evaluated predictors of radiation-induced skin toxicity in a prospective study of a tri-racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation-induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non-Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0-1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty-one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER-positive/PR-negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventionally fractionated regimens (OR = 3.25; 95%CI = 1.76, 6.01) were significantly associated with higher skin toxicity grade after adjustment for age, race, ethnicity, ER status, and breast volume. B MI specifically predicted for moist desquamation, but not degree of erythema. In this racially and ethnically diverse cohort of breast cancer patients receiving radiation to the intact breast, risk factors including BMI, disease stage, and conventionally fractionated radiation predicted for higher skin toxicity grade, whereas age, race, ethnicity, and breast volume did not. BMI specifically predicted for moist desquamation, suggesting that preventive measures to address this particular outcome should be investigated. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. The preventive effect of vitamin D3 on radiation-induced hair toxicity in a rat model.

    PubMed

    Baltalarli, Bahar; Bir, Ferda; Demirkan, Neşe; Abban, Gülçin

    2006-02-28

    Our aim is to investigate the protective effect of vitamin D3 especially from radiation-induced hair toxicity. A model of skin radiation injury was developed and a single fraction of 20 Gy Gamma irradiation was applied to the right dorsal skin of fourteen rats. All animals were randomly divided into 2 groups: Group I: irradiation alone (n = 7) and Group II: irradiation and 0.2 microg vitamin D3 given IM (n = 7). Fifty days after post-irradiation rats were sacrificed. The outcomes were evaluated on the basis of histopathological findings and immunohistochemical staining for Vitamin D receptor (VDR) in skin and hair follicles. The number of hair follicles in the radiation field for the group of animals irradiated without pretreatment was significantly lower than outside of the irradiated area (p = 0.016) as it is expected. Contrarily the number of hair follicles did not show significant difference in the pretreated group between the irradiated field and outside of the fields (p = 0,14). Skin of the vitamin D3 pretreated group demonstrated stronger immunoreactivity for VDR compared to irradiation alone group. These results indicate that administration of vitamin D3 may protect hair follicles from radiation toxicity. Further clinical trials should be conducted to prove the preventive effect of vitamin D3 as well as dosing and timing of the agent on radiation-induced alopecia.

  15. Radiation induced secretion of surfactant from cell cultures of type II pneumocytes: an in vitro model of radiation toxicity

    SciTech Connect

    Shapiro, D.L.; Finkelstein, J.N.; Rubin, P.; Penney, D.P.; Siemann, D.W.

    1984-03-01

    The pathogenesis of pneumonitis and fibrosis secondary to lung irradiation is incompletely understood. The role of the type II alveolar epithelial pneumocyte in these processes has been under investigation. The type II pneumocyte has been shown in vivo to respond to radiation induced injury with release of pulmonary surfactant. The effect of irradiation on cell cultures of type II pneumocytes was studied to determine if this could be reproduced in vitro. Type II pneumocytes were found to release surfactant material with a threshold of radiation dose between 1000 and 1500 rad. This is similar to the dosage range over which the same effect has been demonstrated in vivo. Experimental results support the concept that the release of surfactant is not due to either cell disruption or non-specific release of phospholipid from cell membranes. Irradiation appears to trigger membrane receptor mediated surfactant release. In addition, irradiation abolishes the ability of cells to subsequently respond to a physiologic agonist, suggesting radiation induced damage to the secretory mechanism. These studies establish that surfactant release in response to irradiation in vivo is a direct effect on type II pneumocytes. Cell cultures of type II pneumocytes can serve as a laboratory model of lung cell radiation toxicity.

  16. Racial Variations in Radiation-Induced Skin Toxicity Severity: Data From a Prospective Cohort Receiving Postmastectomy Radiation

    SciTech Connect

    Wright, Jean L.; Takita, Cristiane; Reis, Isildinha M.; Zhao, Wei; Lee, Eunkyung; Hu, Jennifer J.

    2014-10-01

    Purpose: Radiation-induced skin toxicity is one of the most symptomatic side effects of postmastectomy radiation therapy (PMRT). We sought to determine whether the severity of acute skin toxicity was greater in black patients in a prospective cohort receiving PMRT and to identify other predictors of more severe skin toxicity. Methods and Materials: We evaluated the first 110 patients in an ongoing prospective study assessing radiation-induced skin toxicity in patients receiving PMRT. We recorded patient demographics, body mass index (BMI), and disease and treatment characteristics. Logistic regression analyses were conducted to evaluate the effect of potential predictors on the risk of skin toxicity. Results: A total of 23.6% respondents self-identified as black, 5.5% as non-Hispanic white, 69.1% as Hispanic white, and 1.8% as other; 57% were postmenopausal, and 70.9% had BMI of >25. Median chest wall dose was 50 Gy, and mastectomy scar dose was 60 Gy. Most patients, 95.5%, were treated with a 0.5-cm bolus throughout treatment. There were no significant differences in patient characteristics in black versus non-black patients. At RT completion, moist desquamation was more common in black patients (73.1% vs 47.6%, respectively, P=.023), in postmenopausal patients (63.5% vs 40.4%, respectively, P=.016), and in those with BMI of ≥25 (60.3% vs 37.5%, respectively, P=.030). On multivariate analysis, the effects of black race (odds ratio [OR] = 7.46, P=.031), BMI ≥25 (OR = 2.95, P=.043) and postmenopausal status (OR = 8.26, P=.004) remained significant risk factors for moist desquamation. Conclusions: In this prospectively followed, racially diverse cohort of breast cancer patients receiving PMRT delivered in a uniform fashion, including the routine use of chest wall boost and bolus, black race, higher BMI, and postmenopausal status emerged as significant predictors of moist desquamation. There was a high frequency of moist desquamation, particularly in those

  17. Racial variations in radiation-induced skin toxicity severity: data from a prospective cohort receiving postmastectomy radiation.

    PubMed

    Wright, Jean L; Takita, Cristiane; Reis, Isildinha M; Zhao, Wei; Lee, Eunkyung; Hu, Jennifer J

    2014-10-01

    Radiation-induced skin toxicity is one of the most symptomatic side effects of postmastectomy radiation therapy (PMRT). We sought to determine whether the severity of acute skin toxicity was greater in black patients in a prospective cohort receiving PMRT and to identify other predictors of more severe skin toxicity. We evaluated the first 110 patients in an ongoing prospective study assessing radiation-induced skin toxicity in patients receiving PMRT. We recorded patient demographics, body mass index (BMI), and disease and treatment characteristics. Logistic regression analyses were conducted to evaluate the effect of potential predictors on the risk of skin toxicity. A total of 23.6% respondents self-identified as black, 5.5% as non-Hispanic white, 69.1% as Hispanic white, and 1.8% as other; 57% were postmenopausal, and 70.9% had BMI of >25. Median chest wall dose was 50 Gy, and mastectomy scar dose was 60 Gy. Most patients, 95.5%, were treated with a 0.5-cm bolus throughout treatment. There were no significant differences in patient characteristics in black versus non-black patients. At RT completion, moist desquamation was more common in black patients (73.1% vs 47.6%, respectively, P=.023), in postmenopausal patients (63.5% vs 40.4%, respectively, P=.016), and in those with BMI of ≥25 (60.3% vs 37.5%, respectively, P=.030). On multivariate analysis, the effects of black race (odds ratio [OR] = 7.46, P=.031), BMI ≥25 (OR = 2.95, P=.043) and postmenopausal status (OR = 8.26, P=.004) remained significant risk factors for moist desquamation. In this prospectively followed, racially diverse cohort of breast cancer patients receiving PMRT delivered in a uniform fashion, including the routine use of chest wall boost and bolus, black race, higher BMI, and postmenopausal status emerged as significant predictors of moist desquamation. There was a high frequency of moist desquamation, particularly in those patients with elevated risk. Continued study of patient

  18. The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats

    SciTech Connect

    Chen Liguang; Brizel, David M.; Rabbani, Zahid N.; Samulski, Thaddeus V.; Farrell, Catherine L.; Larrier, Nicole; Anscher, Mitchell S.; Vujaskovic, Zeljko . E-mail: vujas@radonc.duke.edu

    2004-12-01

    Purpose: Radiation-induced lung toxicity is a significant dose-limiting side effect of radiotherapy for thoracic tumors. Recombinant human keratinocyte growth factor (rHuKGF) has been shown to be a mitogen for type II pneumocytes. The purpose of this study was to determine whether rHuKGF prevents or ameliorates the severity of late lung damage from fractionated irradiation in a rat model. Methods and materials: Female Fisher 344 rats were irradiated to the right hemithorax with a dose of 40 Gy/5 fractions/5 days. rHuKGF at dose of 5 mg/kg or 15 mg/kg was given via a single intravenous injection 10 min after the last fraction of irradiation. Animals were followed for 6 months after irradiation. Results: The breathing rate increased beginning at 6 weeks and reached a peak at 14 weeks after irradiation. The average breathing frequencies in the irradiated groups with rHuKGF (5 mg/kg and 15 mg/kg) treatment were significantly lower than that in the group receiving radiation without rHuKGF (116.5 {+-} 1.0 and 115.2 {+-} 0.8 vs 123.5 {+-} 1.2 breaths/min, p < 0.01). The severity of lung fibrosis and the level of immunoreactivity of integrin {alpha}v{beta}6, TGF{beta}1, type II TGF{beta} receptor, Smad3, and phosphorylated Smad2/3 were significantly decreased only in the group receiving irradiation plus high-dose rHuKGF treatment compared with irradiation plus vehicle group, suggesting a dose response for the effect of rHuKGF. Conclusions: This study is the first to demonstrate that rHuKGF treatment immediately after irradiation protects against late radiation-induced pulmonary toxicity. These results suggest that restoration of the integrity of the pulmonary epithelium via rHuKGF stimulation may downregulate the TGF-{beta}-mediated fibrosis pathway. These data also support the use of rHuKGF in a clinical trial designed to prevent radiation-induced lung injury.

  19. Quantifying cell migration distance as a contributing factor to the development of rectal toxicity after prostate radiotherapy

    SciTech Connect

    Munbodh, Reshma; Jackson, Andrew

    2014-02-15

    Purpose: Spatial information is usually neglected in mathematical models of radiation-induced toxicity. In the presence of inhomogeneous dose distributions produced by intensity modulated radiation therapy (IMRT) and volumetric arc therapy, this may be a limitation. We present a model to quantify the spatial characteristics of the dose distribution on the rectum through the quantification of the distribution of distances between dose points on the surface of the rectum in three-dimensions. The method allows us to evaluate the hypothesis that distances between lower and higher dose regions on the rectum influence radiation damage repair due to the migration of normal cells into damaged areas, and consequently, the development of radiation-induced toxicity in patients treated with radiation for prostate cancer. Methods: We present a method to compute distances between dose points on the surface of the rectum in three dimensions (3D) and to generate distance maps representing the distances between specific dose regions on the rectum. We introduce the concept of the distance dose surface histogram (DDSH), which is computed from the distance maps. The DDSH is a 2D histogram of rectum area on a grid defined by pairwise combinations of dose and distance. Each bin in the DDSH quantifies the area of the rectum exposed to a given dose and at a given distance from other another dose region on the rectum. By summing across the columns and rows of the DDSH, we can generate the dose surface histogram (DSH) and distance surface histogram (DiSH) for a particular dose region. The DiSH is a marginal histogram showing the distribution of distances for the dose points in a specific dose region from another region. We computed the DDSH, DiSH, and DSH for 33 patients treated with IMRT for prostate cancer, nine of whom developed late Grade 2 or higher late rectal toxicity. Results: We show how even though the total area of the rectum exposed to a given dose may be the same for different

  20. Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

    PubMed Central

    Chin, Lee; Korpela, Elina; Kim, Anthony; Yohan, Darren; Niu, Carolyn; Wilson, Brian C.; Liu, Stanley K.

    2016-01-01

    Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting. PMID:27284926

  1. Non-dosimetric risk factors for radiation-induced lung toxicity

    PubMed Central

    Kong, Feng-Ming (Spring); Wang, Shulian

    2015-01-01

    The decision to administer a radical course of radiotherapy is largely influenced by the dose-volume metrics of the treatment plan, but what are the patient related and other factors that may independently increase the risk of radiation lung toxicity? Poor pulmonary function has been regarded as a risk factor and relative contraindication for patients having radical radiotherapy, but recent evidence suggests that patients with poor spirometry may tolerate conventional or high dose radiotherapy as well as, if not better than, patients with normal function. However, caution may need to be exercised in patients with underlying interstitial pulmonary fibrosis. Further there is emerging evidence of molecular markers of increased risk of toxicity. This review will discuss patient related and risk factors other than dosimetry for radiation lung toxicity. PMID:25771414

  2. Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Ippolito, Edy; Massaccesi, Mariangela; Digesu, Cinzia; Deodato, Francesco; Macchia, Gabriella; Pirozzi, Giuseppe Antonio; Cilla, Savino; Cuscuna, Daniele; Di Lallo, Alessandra; Mattiucci, Gian Carlo; Mantini, Giovanna; Pacelli, Fabio; Valentini, Vincenzo; Cellini, Numa; Ingrosso, Marcello; Morganti, Alessio Giuseppe

    2012-06-01

    Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Methods and Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade {>=}2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade {>=}2 clinical rectal late toxicity was higher in patients with grade {>=}2 (32% vs. 15 %, p = 0.02) or grade {>=}3 VRS telangiectasia (47% vs. 17%, p {<=} 0.01) and an overall VRS score of {>=}2 (31% vs. 16 %, p = 0.04) or {>=}3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

  3. ROC curves and evaluation of radiation-induced pulmonary toxicity in breast cancer

    SciTech Connect

    Lind, Pehr A. . E-mail: Pehr.Lind@Karolinska.se; Wennberg, Berit M.Sc.; Gagliardi, Giovanna; Rosfors, Stefan; Blom-Goldman, Ulla; Lidestahl, Anders; Svane, Gunilla

    2006-03-01

    Purpose: To study clinical, radiologic, and physiologic pulmonary toxicity in 128 women after adjuvant radiotherapy (RT) for breast cancer in relation to dosimetric factors. Methods and Material: The patients underwent pulmonary function testing before and 5 months post-RT. Similarly, computer tomography of the chest was repeated 4 months post-RT and changes were scored with a semiquantitative system. Clinical symptoms were registered and scored according to Common Toxicity Criteria. All patients underwent three-dimensional dose planning, and the ipsilateral lung volume receiving {>=}13 Gy (V13), V20, and V30 were calculated. Multiple logistic or regression analyses were used for multivariate modeling. The relation between the dosimetric factors and side effects was also analyzed with receiver operating characteristic (ROC) curves. Results: V20 was, according to multivariate modeling, the most important variable for the occurrence of the three studied side effects (p < 0.01). Age was also related to symptomatic and radiologic pneumonitis. Reduced pre-RT functional level was more common in patients developing symptomatic toxicity. The ROC areas for symptomatic pneumonitis in relation to V13, V20, and V30 were 0.69, 0.69, and 0.67, and for radiologic pneumonitis 0.85, 0.85, and 0.81. Conclusions: Our results support the use of three-dimensional planning aimed at minimizing the percent of incidentally irradiated lung volume to reduce pulmonary toxicity. Age was also correlated with post-RT side effects. According to ROC analysis, V20 could well predict the risk for radiologic pneumonitis for the studied semiquantitative model.

  4. Late Rectal Toxicity on RTOG 94-06: Analysis Using a Mixture Lyman Model

    SciTech Connect

    Tucker, Susan L.; Dong Lei; Bosch, Walter R.; Michalski, Jeff; Winter, Kathryn; Mohan, Radhe; Purdy, James A.; Kuban, Deborah; Lee, Andrew K.; Cheung, M. Rex; Thames, Howard D.; Cox, James D.

    2010-11-15

    Purpose: To estimate the parameters of the Lyman normal-tissue complication probability model using censored time-to-event data for Grade {>=}2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group 94-06, a dose-escalation trial designed to determine the maximum tolerated dose for three-dimensional conformal radiotherapy of prostate cancer. Methods and Materials: The Lyman normal-tissue complication probability model was fitted to data from 1,010 of the 1,084 patients accrued on Radiation Therapy Oncology Group 94-06 using an approach that accounts for censored observations. Separate fits were obtained using dose-volume histograms for whole rectum and dose-wall histograms for rectal wall. Results: With a median follow-up of 7.2 years, the crude incidence of Grade {>=}2 late rectal toxicity was 15% (n = 148). The parameters of the Lyman model fitted to dose-volume histograms data, with 95% profile-likelihood confidence intervals, were TD{sub 50} = 79.1 Gy (75.3 Gy, 84.3 Gy), m = 0.146 (0.107, 0.225), and n = 0.077 (0.041, 0.156). The fit based on dose-wall histogram data was not significantly different. Patients with cardiovascular disease had a significantly higher incidence of late rectal toxicity (p = 0.015), corresponding to a dose-modifying factor of 5.3%. No significant association with late rectal toxicity was found for diabetes, hypertension, rectal volume, rectal length, neoadjuvant hormone therapy, or prescribed dose per fraction (1.8 Gy vs. 2 Gy). Conclusions: These results, based on a large cohort of patients from a multi-institutional trial, are expected to be widely representative of the ability of the Lyman model to describe the long-term risk of Grade {>=}2 late rectal toxicity after three-dimensional conformal radiotherapy of prostate cancer.

  5. Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

    SciTech Connect

    Foro, Palmira; Algara, Manuel; Lozano, Joan; Rodriguez, Nuria; Sanz, Xavier; Torres, Erica; Carles, Joan; Reig, Anna; Membrive, Ismael; Quera, Jaume; Fernandez-Velilla, Enric; Pera, Oscar; Lacruz, Marti; Bellosillo, Beatriz

    2014-04-01

    Purpose: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. Methods and Materials: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. Results: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). Conclusions: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of

  6. Relationship between radiation-induced apoptosis of T lymphocytes and chronic toxicity in patients with prostate cancer treated by radiation therapy: a prospective study.

    PubMed

    Foro, Palmira; Algara, Manuel; Lozano, Joan; Rodriguez, Nuria; Sanz, Xavier; Torres, Erica; Carles, Joan; Reig, Anna; Membrive, Ismael; Quera, Jaume; Fernandez-Velilla, Enric; Pera, Oscar; Lacruz, Marti; Bellosillo, Beatriz

    2014-04-01

    To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of CD8+ T lymphocytes was associated with overall survival

  7. Modulation of radiation-induced organs toxicity by cremophor-el in experimental animals.

    PubMed

    Ramadan, L A; Shouman, S A; Sayed-Ahmed, M M; El-Habit, O H

    2001-02-01

    Pharmacological and cytogenetic evaluations of the protective effects of polyethoxylated castor oil cremophor-EL (cremophor) against hepato, renal and bone marrow toxicity induced by gamma irradiation in normal rats were carried out. A single dose of irradiation (6 Gy) caused hepatic and renal damage manifested biochemically as an elevation in levels of serum alanine and aspartate aminotransferase as well as an increase in blood urea. Cremophor administration at a dose level of 50 microl kg-1 intravenously 1 day before exposure to irradiation (6 Gy) protected the liver and kidney as indicated by the recovery of levels of hepatic aminotransferase, urea and lipid profiles to normal values. Gamma irradiation of male rats caused a decrease in reduced glutathione and an increase in the oxidized form in rat-liver homogenate. A highly significant increase in the incidence of micronucleated normochromatic erythrocytes and micronucleated polychromatic erythrocytes was observed after irradiation exposure. The induced genotoxicity in the bone marrow cells was corrected by pretreatment with cremophor. The findings of this study suggest that cremophor pretreatment can potentially be used clinically to prevent irradiation-induced hepato, renal and bone marrow toxicity without interference with its cytotoxic activity.

  8. Mathematical Model for Evaluating Incidence of Acute Rectal Toxicity During Conventional or Hypofractionated Radiotherapy Courses for Prostate Cancer

    SciTech Connect

    Strigari, Lidia Arcangeli, Giorgio; Arcangeli, Stefano; Benassi, Marcello

    2009-04-01

    Purpose: To describe the radiation-induced acute rectal toxicity (ART) using a modified Lyman-Kutcher-Burman normal tissue complication probability model and parameters set, taking into account the overall treatment time. Methods and Materials: A total of 160 patients underwent three-dimensional conformal radiotherapy to the prostate and seminal vesicles and were randomized to receive 80 Gy in 40 fractions within 8 weeks (Group A) or 62 Gy in 20 fractions within 5 weeks, 4 d/wk (Group B). An additional 52 patients (Group C) underwent intensity-modulated radiotherapy with a hypofractionation schedule consisting of 56 Gy, delivered in 16 fractions (4/wk) of 3.5 Gy. Patients were followed for ART weekly during treatment. The overall treatment time, rectal dose-volume histograms, and ART status, defined as Radiation Therapy Oncology Group Grade 2 or greater gastrointestinal toxicity, were used to determine the modified Lyman-Kutcher-Burman model parameters. The m and n values were obtained from the cohort, and the tolerance doses for 50% complication probability for uniform irradiation [TD{sub 50}(1){sub k}] were obtained for each fractionation schedule indicated with k. Results: Of 212 patients treated with localized prostate radiotherapy, 65 developed Grade for {>=}1 week during treatment. The m and n value was 0.17 and 0.08, respectively. The TD{sub 50}(1){sub k} parameter was 79, 62.5, and 53 Gy, respectively for Group A, B, and C. Conclusion: The optimized modified Lyman-Kutcher-Burman normal tissue complication probability model allowed us to describe the ART data from conventional and hypofractionated regimens, using the dose-volume histograms and overall treatment time. This model could prove useful in designing hypofractionation schedules to reduce the incidence of ART.

  9. Toxic leukoencephalopathies, including drug, medication, environmental, and radiation-induced encephalopathic syndromes.

    PubMed

    Rimkus, Carolina de Medeiros; Andrade, Celi Santos; Leite, Claudia da Costa; McKinney, Alexander M; Lucato, Leandro Tavares

    2014-04-01

    Toxic leukoencephalopathies can be secondary to the exposure to a wide variety of exogenous agents, including cranial irradiation, chemotherapy, antiepileptic agents, drugs of abuse, and environmental toxins. There is no typical clinical picture, and patients can present with a wide array of signs and symptoms. Involvement of white matter is a key finding in this scenario, although in some circumstances other high metabolic areas of the central nervous system can also be affected. Magnetic resonance (MR) imaging usually discloses bilateral and symmetric white matter areas of hyperintense signal on T2-weighted and fluid-attenuated inversion recovery images, and signs of restricted diffusion are associated in the acute stage. In most cases, the changes are reversible, especially with prompt recognition of the disease and discontinuation of the noxious agent. Either the MR or clinical features may be similar to several nontoxic entities, such as demyelinating diseases, leukodystrophies, hepatic encephalopathy, vascular disease, hypoxic-ischemic states, and others. A high index of suspicion should be maintained whenever a patient presents recent onset of neurologic deficit, searching the risk of exposure to a neurotoxic agent. Getting to know the most frequent MR appearances and mechanisms of action of causative agents may help to make an early diagnosis and begin therapy, improving outcome. In this review, some of the most important causes of leukoencephalopathies are presented; as well as other 2 related conditions: strokelike migraine attacks after radiation therapy syndrome and reversible splenial lesions. © 2013 Published by Elsevier Inc.

  10. Random forests to predict rectal toxicity following prostate cancer radiation therapy.

    PubMed

    Ospina, Juan D; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C; Simon, Antoine; Acosta, Oscar; de Crevoisier, Renaud

    2014-08-01

    To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    SciTech Connect

    Ospina, Juan D.; Zhu, Jian; Chira, Ciprian; Bossi, Alberto; Delobel, Jean B.; Beckendorf, Véronique; Dubray, Bernard; Lagrange, Jean-Léon; Correa, Juan C.; and others

    2014-08-01

    Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models.

  12. Hyperbaric oxygen therapy for late radiation-induced tissue toxicity: prospectively patient-reported outcome measures in breast cancer patients.

    PubMed

    Teguh, David N; Bol Raap, René; Struikmans, Henk; Verhoef, Cees; Koppert, Linetta B; Koole, Arne; Huang, Yadi; van Hulst, Rob A

    2016-09-29

    This study examines patient reported outcome measures of women undergoing hyperbaric oxygen treatment (HBOT) after breast-conserving therapy. Included were 57 women treated with HBOT for late radiation-induced tissue toxicity (LRITT) referred in the period January 2014-December 2015. HBOT consisted of (on average) 47 sessions. In total, 80 min of 100 % O2 was administered under increased pressure of 2.4 ATA. Quality of life was assessed before and after treatment using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23, and a NRS pain score. Fifty-seven women were available for evaluation before and after treatment. Before HBOT, patients had severe complaints of pain in the arm/shoulder (46 %), swollen arm/hand (14 %), difficulty to raise arm or move it sideways (45 %), pain in the area of the affected breast (67 %), swollen area of the affected breast (45 %), oversensitivity of the affected breast (54 %), and skin problems on/in the area of the affected breast (32 %); post HBOT, severe complaints were still experienced in 17, 7, 22, 15, 13, 15, and 11 % of the women, respectively. Differences were all significant. The NRS pain score improved at least 1 point (range 0-10) in 81 % of the patients (p < 0.05). In these breast cancer patients treated with HBOT for LRITT, the patient-reported outcomes were positive and improvements were observed. HBOT was a well-tolerated treatment for LRITT and its side-effects were both minimal and reversible.

  13. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  14. Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.

    PubMed

    Osti, Mattia F; Nicosia, Luca; Agolli, Linda; Gentile, Giovanna; Falco, Teresa; Bracci, Stefano; Di Nardo, Francesco; Minniti, Giuseppe; De Sanctis, Vitaliana; Valeriani, Maurizio; Maglio, Marianna; Borro, Marina; Simmaco, Maurizio; Enrici, Riccardo M

    2015-03-24

    To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.

  15. Radiation-Induced Thymidine Phosphorylase Upregulation in Rectal Cancer Is Mediated by Tumor-Associated Macrophages by Monocyte Chemoattractant Protein-1 From Cancer Cells

    SciTech Connect

    Kim, Tae-Dong; Li Ge; Song, Kyoung-Sub; Kim, Jin-Man; Kim, Jun-Sang; Kim, Jong-Seok; Yun, Eun-Jin; Park, Jong-Il; Park, Hae-Duck; Hwang, Byung-Doo; Lim, Kyu Yoon, Wan-Hee

    2009-03-01

    Purpose: The mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues. Methods and Materials: TP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells. Results: Expression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody. Conclusions: Use of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues.

  16. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  17. Repeated Autologous Bone Marrow-Derived Mesenchymal Stem Cell Injections Improve Radiation-Induced Proctitis in Pigs

    PubMed Central

    Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-01-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

  18. Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs.

    PubMed

    Linard, Christine; Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-11-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage.

  19. Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim; Litzenberg, Dale; Jackson, William; Johnson, Skyler; Albrecht-Unger, Liesel; Donaghy, Alex; Phelps, Laura; Blas, Kevin; Halverson, Schuyler; Marsh, Robin; Olson, Karin; Feng, Felix Y.

    2013-04-01

    Purpose: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval (CI), 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

  20. Radiation-induced Vulvar Angiokeratoma Along with Other Late Radiation Toxicities after Carcinoma Cervix: A Rare Case Report

    PubMed Central

    Bhandari, Virendra; Naik, Ayush; Gupta, K L; Kausar, Mehlam

    2016-01-01

    Angiokeratoma including vulvar angiokeratoma is a very rare complication of radiation. Exact incidence is still unknown, we report a case that developed radiation-induced angiokeratoma of skin in the vulvar region along with other late radiation sequelae in the form of bone fracture, new bone formation, bone marrow widening, muscle hypertrophy, and subcutaneous fibrosis, 18 years after radiotherapy to the pelvic region for the treatment of carcinoma cervix. All these late radiation sequel are rare to be seen in a single patient, and none of the case reports could be found in the world literature. PMID:27057045

  1. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    PubMed Central

    Acosta, Oscar; Drean, Gael; Ospina, Juan David; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; De Crevoisier, Renaud

    2013-01-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80Gy to the prostate by IMRT. Within the patients presenting bleeding, a significant dose excess (6Gy on average, p<0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step. PMID:23528429

  2. Toward Restored Bowel Health in Rectal Cancer Survivors.

    PubMed

    Steineck, Gunnar; Schmidt, Heike; Alevronta, Eleftheria; Sjöberg, Fei; Bull, Cecilia Magdalena; Vordermark, Dirk

    2016-07-01

    As technology gets better and better, and as clinical research provides more and more knowledge, we can extend our ambition to cure patients from cancer with restored physical health among the survivors. This increased ambition requires attention to grade 1 toxicity that decreases quality of life. It forces us to document the details of grade 1 toxicity and improve our understanding of the mechanisms. Long-term toxicity scores, or adverse events as documented during clinical trials, may be regarded as symptoms or signs of underlying survivorship diseases. However, we lack a survivorship nosology for rectal cancer survivors. Primarily focusing on radiation-induced side effects, we highlight some important observations concerning late toxicity among rectal cancer survivors. With that and other data, we searched for a preliminary survivorship-disease nosology for rectal cancer survivors. We disentangled the following survivorship diseases among rectal cancer survivors: low anterior resection syndrome, radiation-induced anal sphincter dysfunction, gut wall inflammation and fibrosis, blood discharge, excessive gas discharge, excessive mucus discharge, constipation, bacterial overgrowth, and aberrant anatomical structures. The suggested survivorship nosology may form the basis for new instruments capturing long-term symptoms (patient-reported outcomes) and professional-reported signs. For some of the diseases, we can search for animal models. As an end result, the suggested survivorship nosology may accelerate our understanding on how to prevent, ameliorate, or eliminate manifestations of treatment-induced diseases among rectal cancer survivors.

  3. Semiquinone derivative isolated from Bacillus sp. INM-1 protects cellular antioxidant enzymes from γ-radiation-induced renal toxicity.

    PubMed

    Mishra, S; Reddy, D S K; Jamwal, V S; Bansal, D D; Patel, D D; Malhotra, P; Gupta, A K; Singh, P K; Jawed, S; Kumar, Raj

    2013-07-01

    This study was focused to evaluate protection of indigenous antioxidant system of mice against gamma radiation-induced oxidative stress using a semiquinone (SQGD)-rich fraction isolated from Bacillus sp. INM-1. Male C57bl/6 mice were administered SQGD (50 mg/kgb.w.i.p.) 2 h before irradiation (10 Gy) and modulation in antioxidant enzymes activities was estimated at different time intervals and compared with irradiated mice which were not pretreated by SQGD. Compared to untreated controls, SQGD pretreatment significantly (p < 0.05) accelerates superoxide dismutase, catalase, GSH, and glutathione-S-transferase activities. Similarly, significant (p < 0.05) increase in the expression of superoxide dismutase, catalase, GSH, and glutathione-S-transferase was observed in irradiated mice pretreated by SQGD, compared to only irradiated groups. Total antioxidant status equivalent to trolox was estimated in renal tissue of the mice after SQGD administration. Significant ABTS(+) radical formation was observed in H2O2-treated kidney homogenate, due to oxidative stress in the tissue. However, significant decrease in the levels of ABTS(+) radical was observed in kidney homogenate of the mice pretreated with SQGD. Therefore, it can be concluded that SQGD neutralizes oxidative stress by induction of antioxidant enzymes activities and thus improved total antioxidant status in cellular system and hence contributes to radioprotection.

  4. Radiation-Induced Cardiac Toxicity After Therapy for Breast Cancer: Interaction Between Treatment Era and Follow-Up Duration

    SciTech Connect

    Demirci, Senem; Nam, Jiho; Hubbs, Jessica L.; Nguyen, Thu; Marks, Lawrence B.

    2009-03-15

    Purpose: Cardiac toxicity after breast radiotherapy (RT) has been widely described in 'older' RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more 'modern' RT trials have shown less cardiac toxicity. The comparisons between the 'older' and 'modern' trials are confounded by the longer follow-up time in the 'older' trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT. Methods and Materials: The published data were surveyed using PubMed to identify studies using 'breast cancer,' 'irradiation/radiotherapy,' 'cardiac/heart,' and 'toxicity/morbidity/mortality' in a keyword search. Relevant data were extracted from the identified trials. The trials were defined as 'older' (patient accrual start year before 1980) and 'modern' (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up. Results: We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically {<=}10 years and did not report an excess toxicity risk. The modern studies lacked longer follow-up. Conclusion: Additional follow-up is needed to ensure that modern methods effectively reduce cardiac toxicity. Continued diligence to minimize cardiac exposure remains prudent.

  5. USE OF FRACTIONAL DOSE-VOLUME HISTOGRAMS TO MODEL RISK OF ACUTE RECTAL TOXICITY AMONG PATIENTS TREATED ON RTOG 94-06

    PubMed Central

    Tucker, Susan L.; Michalski, Jeff M.; Bosch, Walter R.; Mohan, Radhe; Dong, Lei; Winter, Kathryn; Purdy, James A.; Cox, James D.

    2012-01-01

    Background and Purpose For toxicities occurring during the course of radiotherapy, it is conceptually inaccurate to perform normal-tissue complication probability analyses using the complete dose-volume histogram. The goal of this study was to analyze acute rectal toxicity using a novel approach in which the fit of the Lyman-Kutcher-Burman (LKB) model is based on the fractional rectal dose-volume histogram (DVH). Materials and Methods Grade ≥2 acute rectal toxicity was analyzed in 509 patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06. These patients had no field reductions or treatment-plan revisions during therapy, allowing the fractional rectal DVH to be estimated from the complete rectal DVH based on the total number of dose fractions delivered. Results The majority of patients experiencing Grade ≥2 acute rectal toxicity did so before completion of radiotherapy (70/80=88%). Acute rectal toxicity depends on fractional mean rectal dose, with no significant improvement in the LKB model fit when the volume parameter differs from n=1. The incidence of toxicity was significantly lower for patients who received hormone therapy (P=0.024). Conclusions Variations in fractional mean dose explain the differences in incidence of acute rectal toxicity, with no detectable effect seen here for differences in numbers of dose fractions delivered. PMID:22673726

  6. Quantitative monitoring of radiation induced skin toxicities in nude mice using optical biomarkers measured from diffuse optical reflectance spectroscopy

    PubMed Central

    Yohan, Darren; Kim, Anthony; Korpela, Elina; Liu, Stanley; Niu, Carolyn; Wilson, Brian C; Chin, Lee CL

    2014-01-01

    Monitoring the onset of erythema following external beam radiation therapy has the potential to offer a means of managing skin toxicities via biological targeted agents – prior to full progression. However, current skin toxicity scoring systems are subjective and provide at best a qualitative evaluation. Here, we investigate the potential of diffuse optical spectroscopy (DOS) to provide quantitative metrics for scoring skin toxicity. A DOS fiberoptic reflectance probe was used to collect white light spectra at two probing depths using two short fixed source-collector pairs with optical probing depths sensitive to the skin surface. The acquired spectra were fit to a diffusion theory model of light transport in tissue to extract optical biomarkers (hemoglobin concentration, oxygen saturation, scattering power and slope) from superficial skin layers of nude mice, which were subjected to erythema inducing doses of ionizing radiation. A statistically significant increase in oxygenated hemoglobin (p < 0.0016) was found in the skin post-irradiation – confirming previous reports. More interesting, we observed for the first time that the spectral scattering parameters, A (p = 0.026) and k (p = 0.011), were an indicator of erythema at day 6 and could potentially serve as an early detection optical biomarker of skin toxicity. Our data suggests that reflectance DOS may be employed to provide quantitative assessment of skin toxicities following curative doses of external beam radiation. PMID:24876997

  7. Quantitative monitoring of radiation induced skin toxicities in nude mice using optical biomarkers measured from diffuse optical reflectance spectroscopy.

    PubMed

    Yohan, Darren; Kim, Anthony; Korpela, Elina; Liu, Stanley; Niu, Carolyn; Wilson, Brian C; Chin, Lee Cl

    2014-05-01

    Monitoring the onset of erythema following external beam radiation therapy has the potential to offer a means of managing skin toxicities via biological targeted agents - prior to full progression. However, current skin toxicity scoring systems are subjective and provide at best a qualitative evaluation. Here, we investigate the potential of diffuse optical spectroscopy (DOS) to provide quantitative metrics for scoring skin toxicity. A DOS fiberoptic reflectance probe was used to collect white light spectra at two probing depths using two short fixed source-collector pairs with optical probing depths sensitive to the skin surface. The acquired spectra were fit to a diffusion theory model of light transport in tissue to extract optical biomarkers (hemoglobin concentration, oxygen saturation, scattering power and slope) from superficial skin layers of nude mice, which were subjected to erythema inducing doses of ionizing radiation. A statistically significant increase in oxygenated hemoglobin (p < 0.0016) was found in the skin post-irradiation - confirming previous reports. More interesting, we observed for the first time that the spectral scattering parameters, A (p = 0.026) and k (p = 0.011), were an indicator of erythema at day 6 and could potentially serve as an early detection optical biomarker of skin toxicity. Our data suggests that reflectance DOS may be employed to provide quantitative assessment of skin toxicities following curative doses of external beam radiation.

  8. Rectal temperature changes and oxygen toxicity in dogs treated in a monoplace chamber.

    PubMed

    Shmalberg, Justin; Davies, Wendy; Lopez, Stacy; Shmalberg, Danielle; Zilberschtein, Jose

    2015-01-01

    Hyperbaric oxygen treatments are increasingly administered to pet dogs, using veterinary-specific monoplace chambers. The basic physiologic responses, chamber performance and oxygen toxicity rates have not yet been evaluated in dogs in a clinical setting. As a result, a series of consecutive 45-minute, 2-atmospheres absolute (atm abs) hyperbaric treatments with 100% oxygen were evaluated in a veterinary rehabilitation center (n = 285). 65 dogs with a mean body weight of 21 ± 15 kg (1.4-71 kg) were treated with an average of four sessions each. The mean rectal temperature of canine patients decreased 0.07 degrees C (0.1 degrees F) during treatments (p = 0.04). Intra-chamber temperature and humidity both increased: +1.0 degrees C (1.7 degrees F, p < 0.0001) and +5.7% (p < 0.0001), respectively. The mean maximal oxygen concentration measured before depressurization of the veterinary-specific commercial chamber was 98.0 ± 0.9%. No strong correlations (r > 0.75) were identified between body weights, body condition scores, maximal oxygen concentrations, starting or ending rectal temperature, chamber humidity and chamber temperature. Oxygen toxicity was not observed during the observational period. Patients were most commonly treated for intervertebral disc disease (n = 16 dogs) and extensive traumatic wounds (n = 10 dogs), which represented a large number of the total study sessions (19% and 16%, respectively).

  9. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    SciTech Connect

    Stenmark, Matthew H.; Cai Xuwei; Shedden, Kerby; Hayman, James A.; Yuan Shuanghu; Ritter, Timothy; Ten Haken, Randall K.; Lawrence, Theodore S.; Kong Fengming

    2012-10-01

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1{beta}), IL-6, IL-8, tumor necrosis factor alpha (TNF-{alpha}), and transforming growth factor beta1 (TGF-{beta}1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ss1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ss1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

  10. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy.

    PubMed

    Acosta, Oscar; Drean, Gael; Ospina, Juan D; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-21

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

  11. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Acosta, Oscar; Drean, Gael; Ospina, Juan D.; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

  12. Semiquinone fraction isolated from Bacillus sp. INM-1 protects hepatic tissues against γ-radiation induced toxicity.

    PubMed

    Mishra, Saurabh; Bansal, Deen Dayal; Malhotra, Poonam; K Reddy, D Sudheer; Jamwal, Vishawdeep S; Patel, Dev Dutt; Gupta, Ashutosh Kumar; Singh, Praveen Kumar; Javed, Saleem; Kumar, Raj

    2014-12-01

    Present study was focused on evaluation of a semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 for its ability against γ radiation induced oxidative stress in irradiated mice. Animals were divided into four group, i.e., (i) untreated control mice; (ii) SQGD treated (50 mg/kg b. wt. i.p.) mice; (iii) irradiated (10 Gy) mice; and (iv) irradiated mice which were pre-treated (-2 h) with SQGD (50 mg/kg b. wt. i.p.). Following treatment, liver homogenates of the treated mice were subjected to endogenous antioxidant enzymes estimation. Result indicated that SQGD pre-treatment, significantly (P < 0.05) induced superoxide dismutase (SOD) (19.84 ± 2.18% at 72 h), catalase (CAT) (26.47 ± 3.11% at 12 h), glutathione (33.81 ± 1.99% at 24 h), and glutathione-S-transferase (24.40 ± 2.65% at 6 h) activities in the liver of mice as compared with untreated control. Significant (P < 0.05) induction in SOD (50.04 ± 5.59% at 12 h), CAT (62.22 ± 7.50 at 72 h), glutathione (42.92 ± 2.28% at 24 h), and glutathione-S-transferase (46.65 ± 3.25 at 12 h) was observed in irradiated mice which were pre-treated with SQGD compared with only irradiated mice. Further, significant induction in ABTS(+) radicals (directly proportional to decrease mM Trolox equivalent) was observed in liver homogenate of H2 O2 treated mice which were found to be significantly inhibited in H2 O2 treated mice pre-treated with SQGD. Thus, it can be concluded that SQGD treatment neutralizes oxidative stress caused by irradiation not only by enhancing endogenous antioxidant enzymes but also by improving total antioxidant status of cellular system and thus cumulative effect of the phenomenon may contributes to radioprotection.

  13. Simple Factors Associated with Radiation-Induced Lung Toxicity after Stereotactic Body Radiation Therapy of the Thorax: A Pooled Analysis of 88 Studies

    PubMed Central

    Zhao, Jing; Yorke, Ellen D.; Li, Ling; Kavanagh, Brian D.; Li, X. Allen; Das, Shiva; Miften, Moyed; Rimner, Andreas; Campbell, Jeffrey; Xue, Jinyu; Jackson, Andrew; Grimm, Jimm; Milano, Michael T.; Kong, Feng-Ming (Spring)

    2017-01-01

    Purpose To study the risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) of the thorax. Methods Published studies on lung toxicity in patients with early stage non-small cell lung cancer (NSCLC) or metastatic lung tumors treated with SBRT were pooled and analyzed. The primary endpoint was RILT including pneumonitis and fibrosis. Data of RILT and risk factors were extracted from each study, and rates of grade 2-5 (G2+) and grade 3-5 (G3+) RILT were computed. Patient, tumor and dosimetric factors were analyzed for their correlation with RILT. Results Eighty-eight studies (7752 patients), that reported RILT incidence, were eligible. The pooled rates of G2+ and G3+ RILT from all 88 studies were 9.1% (95% CI: 7.15-11.4) and 1.8% (95% CI: 1.3-2.5), respectively. The median of median tumor sizes was 2.3 (range 1.4-4.1) cm. Among the factors analyzed, older patient age (P= 0.044) and larger tumor size (the greatest diameter) were significantly correlated with higher rates of G2+ (P= 0.049) and G3+ RILT (P= 0.001). Patients with stage IA vs. stage IB NSCLC had significantly lower risks of G2+ RILT (8.3% vs 17.1%, OR= 0.43, 95% CI: 0.29-0.64, P<0.0001). Among studies that provided detailed dosimetric data, the pooled analysis demonstrated a significantly higher mean lung dose (MLD) (P= 0.027) and V20 (P= 0.019) in patients with G2+ RILT comparing to that of grade 0-1 RILT. Conclusions The overall rate of RILT is relatively low after thoracic SBRT. Older age and larger tumor size are significant adverse risk factors for RILT. Lung dosimetry, specifically lung V20 and MLD also significantly affect RILT risk. Summary Risk factors for radiation-induced lung toxicity (RILT) after stereotactic body radiotherapy (SBRT) were analyzed from 88 published studies (7752 patients). The overall rate of RILT is relatively low after thoracic SBRT. Adverse risk factors for RILT after SBRT include older age, larger tumor size and greater lung

  14. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  15. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines.

    PubMed

    Okunieff, Paul; Xu, Jianhua; Hu, Dongping; Liu, Weimin; Zhang, Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L; Ding, Ivan

    2006-07-01

    To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-alpha, and lymphotoxin-beta) or fibrogenic cytokines (transforming growth factor [TGF]-beta) during the same acute and chronic phases. Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-alpha, and lymphotoxin-beta) and the fibrogenic cytokine, TGF-beta, in cutaneous tissues at 21 days postradiation. Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  16. Validation of Normal Tissue Complication Probability Predictions in Individual Patient: Late Rectal Toxicity

    SciTech Connect

    Semenenko, Vladimir A.; Tarima, Sergey S.; Devisetty, Kiran; Pelizzari, Charles A.; Liauw, Stanley L.

    2013-03-15

    Purpose: To perform validation of risk predictions for late rectal toxicity (LRT) in prostate cancer obtained using a new approach to synthesize published normal tissue complication data. Methods and Materials: A published study survey was performed to identify the dose-response relationships for LRT derived from nonoverlapping patient populations. To avoid mixing models based on different symptoms, the emphasis was placed on rectal bleeding. The selected models were used to compute the risk estimates of grade 2+ and grade 3+ LRT for an independent validation cohort composed of 269 prostate cancer patients with known toxicity outcomes. Risk estimates from single studies were combined to produce consolidated risk estimates. An agreement between the actuarial toxicity incidence 3 years after radiation therapy completion and single-study or consolidated risk estimates was evaluated using the concordance correlation coefficient. Goodness of fit for the consolidated risk estimates was assessed using the Hosmer-Lemeshow test. Results: A total of 16 studies of grade 2+ and 5 studies of grade 3+ LRT met the inclusion criteria. The consolidated risk estimates of grade 2+ and 3+ LRT were constructed using 3 studies each. For grade 2+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.537 compared with 0.431 for the best-fit single study. For grade 3+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.477 compared with 0.448 for the best-fit single study. No evidence was found for a lack of fit for the consolidated risk estimates using the Hosmer-Lemeshow test (P=.531 and P=.397 for grade 2+ and 3+ LRT, respectively). Conclusions: In a large cohort of prostate cancer patients, selected sets of consolidated risk estimates were found to be more accurate predictors of LRT than risk estimates derived from any single study.

  17. Polysaccharide protein complex isolated from mushroom Phellinus rimosus (berk.) Pilat alleviates γ radiation-induced toxicity in mice.

    PubMed

    Joseph, Jini; Smina, Thozhuthum Parambil Pathmanabhan; Janardhanan, Kainoor Krishnankutty

    2011-06-01

    Ionizing radiations generate reactive oxygen species in irradiated tissue that induces several pathophysiological changes in the body. Radiotherapy induced toxicity is a major dose-limiting factor in anticancer treatments. Radioprotective agents are of significant importance in medical, industrial, environmental, military, and space applications. Radioprotective effect of polysaccharide protein complex (PPC-Pr) isolated from mushroom, Phellinus rimosus, was evaluated in Swiss albino mice. PPC-Pr (5 and 10 mg/kg bwt, i.p.) significantly increased leukocyte count, bone marrow cellularity, glutathione content, and activities of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase in blood as well as intestinal mucosa when compared with the irradiated control group. Histopathological observation of intestinal jejunal mucosa revealed the tissue protective effects of PPC-Pr. Further radioprotective activity of PPC-Pr was in a dose-dependent manner. The findings suggest potential radioprotective efficacy of PPC-Pr.

  18. Evaluation of UV radiation-induced toxicity and biophysical changes in various skin cells with photo-shielding molecules.

    PubMed

    Bennet, Devasier; Kim, Sanghyo

    2015-09-21

    Ultraviolet radiation (UVR) triggers many complex events in different types of skin cells, including benign, malignant and normal cells. Chromophores present in these cells play a crucial role in various cellular processes. Unprecedented methods are required for the real-time monitoring of changes in an in vitro model exposed to intermittent mild and intense UVR to determine the mechanisms underlying cell degeneration and the effects of unexpected toxic, agonist and antagonist agents. This study reports the analytical application of a whole cell-based sensor platform for examining the biophysical effects of UVR. We used human keratinocyte, melanocyte and fibroblast cell lines to determine the normal, pathological and protective roles of UVR. In addition, we examined the real-time morphological, biophysical and biomechanical changes associated with cell degeneration induced by UVR at 254 and 365 nm. Information on UVR-induced changes in the cytoskeleton ultrastructure, cellular integrity, cell spreading area, actin microfilament distribution inflammation, microtubule damage, membrane damage, rupture and death was characterized by examining the loss or increase in biophysical and biomechanical properties of these cells. All cells exposed to UVR at 254 and 365 nm showed a significant increase in surface roughness and stiffness in a time-dependent manner. UVR-induced toxicity in differently pigmented skin cells was compared with that in cells pretreated with melanin, keratin and basic fibroblast growth factor to analyze the shielding efficiency of these agents. Melanin exerted a significant shielding effect compared to the other two agents. The biophysical and biomechanical information obtained in this study could advance our understanding of the UVR-induced degeneration process, and help in developing new interventions strategies.

  19. Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy.

    PubMed

    Wedlake, Linda; Shaw, Clare; McNair, Helen; Lalji, Amyn; Mohammed, Kabir; Klopper, Tanya; Allan, Lindsey; Tait, Diana; Hawkins, Maria; Somaiah, Navita; Lalondrelle, Susan; Taylor, Alexandra; VanAs, Nicholas; Stewart, Alexandra; Essapen, Sharadah; Gage, Heather; Whelan, Kevin; Andreyev, H Jervoise N

    2017-09-01

    Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P < 0.001). The difference between groups in the change in IBDQ-B scores between the start and nadir was not significant (P = 0.093). However, the change in score between the start and end of radiotherapy was smaller in the high-fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal

  20. Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

    SciTech Connect

    Peeters, Stephanie T.H.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Koper, Peter C.M.

    2006-03-15

    Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.

  1. Mercury toxicity in the shark (Squalus acanthias) rectal gland: apical CFTR chloride channels are inhibited by mercuric chloride.

    PubMed

    Ratner, Martha A; Decker, Sarah E; Aller, Stephen G; Weber, Gerhard; Forrest, John N

    2006-03-01

    In the shark rectal gland, basolateral membrane proteins have been suggested as targets for mercury. To examine the membrane polarity of mercury toxicity, we performed experiments in three preparations: isolated perfused rectal glands, primary monolayer cultures of rectal gland epithelial cells, and Xenopus oocytes expressing the shark cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. In perfused rectal glands we observed: (1) a dose-dependent inhibition by mercury of forskolin/3-isobutyl-1-methylxanthine (IBMX)-stimulated chloride secretion; (2) inhibition was maximal when mercury was added before stimulation with forskolin/IBMX; (3) dithiothrietol (DTT) and glutathione (GSH) completely prevented inhibition of chloride secretion. Short-circuit current (Isc) measurements in monolayers of rectal gland epithelial cells were performed to examine the membrane polarity of this effect. Mercuric chloride inhibited Isc more potently when applied to the solution bathing the apical vs. the basolateral membrane (23 +/- 5% and 68 +/- 5% inhibition at 1 and 10 microM HgCl2 in the apical solution vs. 2 +/- 0.9% and 14 +/- 5% in the basolateral solution). This inhibition was prevented by pre-treatment with apical DTT or GSH; however, only the permeant reducing agent DTT reversed mercury inhibition when added after exposure. When the shark rectal gland CFTR channel was expressed in Xenopus oocytes and chloride conductance was measured by two-electrode voltage clamping, we found that 1 microM HgCl2 inhibited forskolin/IBMX conductance by 69.2 +/- 2.0%. We conclude that in the shark rectal gland, mercury inhibits chloride secretion by interacting with the apical membrane and that CFTR is the likely site of this action.

  2. TU-G-BRA-08: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Hybrid PET-MRI Imaging of Acute Radiation Induced Cardiac Toxicity

    SciTech Connect

    El-Sherif, O; Xhaferllari, I; Gaede, S; Sykes, J; Butler, J; Wisenberg, G; Prato, F

    2015-06-15

    Purpose: To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irradiation, and 1 month post cardiac irradiation using a hybrid PET- MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess acute changes in myocardial perfusion and inflammation. Myocardial perfusion imaging was performed using N13-ammonia tracer followed by a dynamic PET acquisition scan. A compartmental tracer kinetic model was used for absolute perfusion quantification. Myocardial inflammation imaging was performed using F18-fluorodeoxyglucose (FDG) tracer. The standard uptake value (SUV) over a region encompassing the whole heart was used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). Results: The delivered dose (mean ± standard deviation) to heart was 1.8±0.2 Gy. Reductions in myocardial stress perfusion relative to baseline were observed in 2 of the 5 animals 1 month post radiation. A global inflammatory response 1 month post radiation was observed in 4 of the 5 animals. The calculated SUV at 1 month post radiation was significantly higher (p=0.05) than the baseline SUV. Conclusion: Low doses of cardiac irradiation (< 2 Gy) may lead to myocardial perfusion defects and a global inflammatory response that can be detectable as early as 1 month post irradiation

  3. To Find a Better Dosimetric Parameter in the Predicting of Radiation-Induced Lung Toxicity Individually: Ventilation, Perfusion or CT based

    PubMed Central

    Xiao, Lin-Lin; Yang, Guoren; Chen, Jinhu; Wang, Xiaohui; Wu, Qingwei; Huo, Zongwei; Yu, Qingxi; Yu, Jinming; Yuan, Shuanghu

    2017-01-01

    This study aimed to find a better dosimetric parameter in predicting of radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) individually: ventilation(V), perfusion (Q) or computerized tomography (CT) based. V/Q single-photon emission computerized tomography (SPECT) was performed within 1 week prior to radiotherapy (RT). All V/Q imaging data was integrated into RT planning system, generating functional parameters based on V/Q SPECT. Fifty-seven NSCLC patients were enrolled in this prospective study. Fifteen (26.3%) patients underwent grade ≥2 RILT, the remaining forty-two (73.7%) patients didn’t. Q-MLD, Q-V20, V-MLD, V-V20 of functional parameters correlated more significantly with the occurrence of RILT compared to V20, MLD of anatomical parameters (r = 0.630; r = 0.644; r = 0.617; r = 0.651 vs. r = 0.424; r = 0.520 p < 0.05, respectively). In patients with chronic obstructive pulmonary diseases (COPD), V functional parameters reflected significant advantage in predicting RILT; while in patients without COPD, Q functional parameters reflected significant advantage. Analogous results were existed in fractimal analysis of global pulmonary function test (PFT). In patients with central-type NSCLC, V parameters were better than Q parameters; while in patients with peripheral-type NSCLC, the results were inverse. Therefore, this study demonstrated that choosing a suitable dosimetric parameter individually can help us predict RILT accurately. PMID:28294159

  4. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy

    SciTech Connect

    Kim, Tae Hyun; Kim, Dae Yong . E-mail: radiopia@ncc.re.kr; Park, Joong-Won; Kim, Seong Hoon; Choi, Joon-Il; Kim, Hyun Beom; Lee, Woo Jin; Park, Sang Jae; Hong, Eun Kyung; Kim, Chang-Min

    2007-01-01

    Purpose: To identify the dose-volumetric parameters associated with the risk of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Methods and Materials: A total of 105 hepatocellular carcinoma patients underwent three-dimensional conformal radiotherapy (total dose range, 44-58.5 Gy; median, 54). RIHT was scored within 4 months of completing three-dimensional conformal radiotherapy. The dose-volume parameters analyzed were the gross tumor volume; normal liver volume; total liver volume; radiation dose; mean dose to the normal liver; percentage of the normal liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; percentage of the total liver volume receiving {>=}20, {>=}25, {>=}30, {>=}35, and {>=}40 Gy; and the normal tissue complication probability. Results: Of the 105 patients, Grade 1 RIHT was observed in 21 (20.0%), Grade 2 in 7 (6.7%), Grade 3 in 5 (4.8%), and Grade 4 in 1 (1.0%) patient. No fatal Grade 5 RIHT developed. On multivariate analysis for predicting Grade 2 or worse RIHT, the total liver volume receiving {>=}30 Gy was the only significant parameter (p < 0.001). Grade 2 or worse RIHT was observed in only 2 (2.4%) of 85 patients with a total liver volume receiving 30 Gy of {<=}60% and in 11 (55.0%) of 20 patients with >60% (p < 0.001). Conclusion: The total liver volume receiving {>=}30 Gy appears to be a useful dose-volumetric parameter for predicting the risk of RIHT. This volume should be limited to {<=}60% whenever possible to minimize the risk of Grade 2 or worse RIHT.

  5. Reducing the probability of radiation-induced hepatic toxicity by changing the treatment modality from helical tomotherapy to fixed-beam intensity-modulated radiotherapy

    PubMed Central

    Song, Jin Ho; Son, Seok Hyun; Kay, Chul Seung; Jang, Hong Seok

    2015-01-01

    Purpose To estimate and compare the risk of radiation-induced hepatic toxicity (RIHT) in helical tomotherapy and fixed-beam intensity-modulated radiotherapy (IMRT) for the treatment of hepatocellular carcinoma (HCC). Materials and Methods Twenty patients with unresectable HCC treated with tomotherapy were selected. We performed tomotherapy re-planning to reduce the non-target normal liver volume receiving a dose of more than 15 Gy (NTNL-V15Gy), and we created a fixed-beam IMRT plan (FB-P). We compared the dosimetric results as well as the estimated probability of RIHT among the tomotherapy initial plan (T-IP), the tomotherapy re-plan (T-RP), and the FB-P. Results Comparing the T-RP and FB-P, the homogeneity index was 0.11 better with the T-RP. However, the mean NTNL-V15Gy was 6.3% lower with the FB-P. These differences result in a decline in the probability of RIHT from 0.216 in the T-RP to 0.115 in the FB-P. In patients whose NTNL-V15Gy was higher than 43.2% with the T-RP, the probability of RIHT markedly reduced from 0.533 to 0.274. Conclusions By changing the treatment modality from tomotherapy to fixed-beam IMRT, we could reduce the liver dose and the probability of RIHT without scarifying the target coverage, especially in patients whose liver dose is high. PMID:26376679

  6. Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumour and dosimetric parameters and radical and postoperative radiation therapy.

    PubMed

    Martínez-Arribas, C M; González-San Segundo, C; Cuesta-Álvaro, P; Calvo-Manuel, F A

    2017-06-15

    To determine rectal and urinary toxicity after external beam radiation therapy (EBRT), assessing the results of patients who undergo radical or postoperative therapy for prostate cancer (pancreatic cancer) and their correlation with potential risk factors. A total of 333 patients were treated with EBRT. Of these, 285 underwent radical therapy and 48 underwent postoperative therapy (39 cases of rescue and 9 of adjuvant therapy). We collected clinical, tumour and dosimetric variable to correlate with toxicity parameters. We developed decision trees based on the degree of statistical significance. The rate of severe acute toxicity, both urinary and rectal, was 5.4% and 1.5%, respectively. The rate of chronic toxicity was 4.5% and 2.7%, respectively. Twenty-seven patients presented haematuria, and 9 presented haemorrhagic rectitis. Twenty-five patients (7.5%) presented permanent limiting sequela. The patients with lower urinary tract symptoms prior to the radiation therapy presented poorer tolerance, with greater acute bladder toxicity (P=0.041). In terms of acute rectal toxicity, 63% of the patients with mean rectal doses >45Gy and anticoagulant/antiplatelet therapy developed mild toxicity compared with 37% of the patients with mean rectal doses <45 Gy and without anticoagulant therapy. We were unable to establish predictors of chronic toxicity in the multivariate analysis. The long-term sequelae were greater in the patients who underwent urological operations prior to the radiation therapy and who were undergoing anticoagulant therapy. The tolerance to EBRT was good, and severe toxicity was uncommon. Baseline urinary symptoms constitute the predictor that most influenced the acute urinary toxicity. Rectal toxicity is related to the mean rectal dose and with anticoagulant/antiplatelet therapy. There were no significant differences in severe toxicity between radical versus postoperative radiation therapy. Copyright © 2017 AEU. Publicado por Elsevier España, S

  7. Systematic Review of Radiation Therapy Toxicity Reporting in Randomized Controlled Trials of Rectal Cancer: A Comparison of Patient-Reported Outcomes and Clinician Toxicity Reporting

    SciTech Connect

    Gilbert, Alexandra; Ziegler, Lucy; Martland, Maisie; Davidson, Susan; Efficace, Fabio; Sebag-Montefiore, David; Velikova, Galina

    2015-07-01

    The use of multimodal treatments for rectal cancer has improved cancer-related outcomes but makes monitoring toxicity challenging. Optimizing future radiation therapy regimens requires collection and publication of detailed toxicity data. This review evaluated the quality of toxicity information provided in randomized controlled trials (RCTs) of radiation therapy in rectal cancer and focused on the difference between clinician-reported and patient-reported toxicity. Medline, EMBASE, and the Cochrane Library were searched (January 1995-July 2013) for RCTs reporting late toxicity in patients treated with regimens including preoperative (chemo)radiation therapy. Data on toxicity measures and information on toxicity reported were extracted using Quantitative Analyses of Normal Tissue Effects in the Clinic recommendations. International Society for Quality of Life Research standards on patient-reported outcomes (PROs) were used to evaluate the quality of patient-reported toxicity. Twenty-one RCT publications met inclusion criteria out of 4144 articles screened. All PRO studies reported higher rates of toxicity symptoms than clinician-reported studies and reported on a wider range and milder symptoms. No clinician-reported study published data on sexual dysfunction. Of the clinician-reported studies, 55% grouped toxicity data related to an organ system together (eg “Bowel”), and 45% presented data only on more-severe (grade ≥3) toxicity. In comparison, all toxicity grades were reported in 79% of PRO publications, and all studies (100%) presented individual symptom toxicity data (eg bowel urgency). However, PRO reporting quality was variable. Only 43% of PRO studies presented baseline data, 28% did not use any psychometrically validated instruments, and only 29% of studies described statistical methods for managing missing data. Analysis of these trials highlights the lack of reporting standards for adverse events and reveals the differences between clinician and

  8. Low interrater reliability in grading of rectal bleeding using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity scales: a survey of radiation oncologists.

    PubMed

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T; DeWeese, Theodore L; Song, Daniel Y

    2014-12-01

    To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both reporting and interpretation. Copyright © 2014 Elsevier

  9. Radiation-induced bowel injury: the impact of radiotherapy on survivorship after treatment for gynaecological cancers

    PubMed Central

    Kuku, S; Fragkos, C; McCormack, M; Forbes, A

    2013-01-01

    Background: The number of women surviving cancer who live with symptoms of bowel toxicity affecting their quality of life continues to rise. In this retrospective study, we sought to describe and analyse the presenting clinical features in our cohort, and evaluate possible predictors of severity and chronicity in women with radiation-induced bowel injury after treatment for cervical and endometrial cancers. Methods: Review of records of 541 women treated within the North London Gynaecological Cancer Network between 2003 and 2010 with radiotherapy with or without chemotherapy for cervical and endometrial cancer identified 152 women who reported significant new bowel symptoms after pelvic radiation. Results: Factor analysis showed that the 14 most common and important presenting symptoms could be ‘clustered' into 3 groups with predictive significance for chronicity and severity of disease. Median follow-up for all patients was 60 months. Univariate analysis showed increasing age, smoking, extended field radiation, cervical cancer treatment and the need for surgical intervention to be significant predictors for severity of ongoing disease at last follow-up. On multivariate analysis, only age, cancer type (cervix) and symptom combinations/‘cluster' of (bloating, flatulence, urgency, rectal bleeding and per-rectal mucus) were found to be significant predictors of disease severity. Fifteen (19%) women in the cervical cancer group had radiation-induced bowel injury requiring surgical intervention compared with five (6.7%) in the endometrial cancer group. Conclusion: Women with cervical cancer are younger and appear to suffer more severe symptoms of late bowel toxicity, whereas women treated for endometrial cancer suffer milder more chronic disease. The impact of radiation-induced bowel injury and the effect on cancer survivorship warrants further research into investigation of predictors of severe late toxicity. There is a need for prospective trials to aid early

  10. Radiation-induced gliomas

    PubMed Central

    Prasad, Gautam; Haas-Kogan, Daphne A.

    2013-01-01

    Radiation-induced gliomas represent a relatively rare but well-characterized entity in the neuro-oncologic literature. Extensive retrospective cohort data in pediatric populations after therapeutic intracranial radiation show a clearly increased risk in glioma incidence that is both patient age- and radiation dose/volume-dependent. Data in adults are more limited but show heightened risk in certain groups exposed to radiation. In both populations, there is no evidence linking increased risk associated with routine exposure to diagnostic radiation. At the molecular level, recent studies have found distinct genetic differences between radiation-induced gliomas and their spontaneously-occurring counterparts. Clinically, there is understandable reluctance on the part of clinicians to re-treat patients due to concern for cumulative neurotoxicity. However, available data suggest that aggressive intervention can lead to improved outcomes in patients with radiation-induced gliomas. PMID:19831840

  11. Radiation-induced pneumothorax

    SciTech Connect

    Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

    1983-01-01

    Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis.

  12. Radiation-Induced Bioradicals

    NASA Astrophysics Data System (ADS)

    Mondelaers, Win; Lahorte, Philippe

    This chapter is part one of a review in which the production and application of radiation-induced bioradicals is discussed. Bioradicals play a pivotal role in the complex chain of processes starting with the absorption of radiation in biological materials and ending with the radiation-induced biological after-effects. The general aspects of the four consecutive stages (physical, physicochemical, chemical and biological) are discussed from an interdisciplinary point of view. The close relationship between radiation dose and track structure, induced DNA damage and cell survival or killing is treated in detail. The repair mechanisms that cells employ, to insure DNA stability following irradiation, are described. Because of their great biomedical importance tumour suppressor genes involved in radiation-induced DNA repair and in checkpoint activation will be treated briefly, together with the molecular genetics of radiosensitivity. Part two of this review will deal with modern theoretical methods and experimental instrumentation for quantitative studies in this research field. Also an extensive overview of the applications of radiation-induced bioradicals will be given. A comprehensive list of references allows further exploration of this research field, characterised in the last decade by a substantial advance, both in fundamental knowledge and in range of applications.

  13. Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

    SciTech Connect

    Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella; McKibben, Brian T.; Henderson, Randal H.; Bryant, Curtis; Nichols, Romaine C.; Mendenhall, William M.; Li, Zuofeng; Su, Zhong; Morris, Christopher G.; Mendenhall, Nancy P.

    2015-01-01

    Purpose: Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials: A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. Results: Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT, accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. Conclusions: PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.

  14. Late rectal toxicity after image-based high-dose-rate interstitial brachytherapy for postoperative recurrent and/or residual cervical cancers: EQD2 predictors for Grade ≥II toxicity.

    PubMed

    Chopra, Supriya; Dora, Tapas; Engineer, Reena; Mechanery, Siji; Agarwal, Priyanka; Kannan, Sadhna; Ghadi, Yogesh; Swamidas, Jamema; Mahantshetty, Umesh; Shrivastava, Shyam Kishore

    2015-01-01

    To investigate the correlation of rectal dose volume metrics with late rectal toxicity after high-dose-rate pelvic interstitial brachytherapy. From October 2009 to November 2012, 50 patients with residual or recurrent cervical cancer were included. Patients received external radiation 50 Gy in 25 fractions over 5 weeks with weekly cisplatin. Rectum and rectal mucosal (RM) contours were delineated retrospectively. RM was defined as the outer surface of the flatus tube inserted at brachytherapy. The dose received by 0.1, 1, 2, 5 cc of rectum, RM, and sigmoid was recorded. Cumulative equivalent dose in 2 Gy (EQD2) for organs at risk was calculated assuming α/β of 3. Univariate analysis was performed to identify predictors of rectal toxicity. At a median follow-up of 34 months (12-51 months), Grade II and III late rectal toxicity was observed in 9 (18%) and 2 (4%) patients, respectively. On univariate analysis, rectal doses were not significant predictors; however, D 0.1-cc RM dose >72 Gy (p = 0.04), D 1-cc RM dose >65 Gy (p = 0.004), D 2-cc RM dose >62.3 Gy (p = 0.004), and D 5-cc RM dose >60 Gy (p = 0.007) correlated with Grade ≥II toxicity. On probit analysis, the estimated dose in EQD2 for a 10% and 20% risk of rectal toxicity was D 2-cc rectum of 55 and 66 Gy, and RM <55 and 63 Gy, respectively. Limiting 2-cc RM and rectal doses within the proposed thresholds can minimize Grade ≥II toxicity for gynecologic high-dose-rate interstitial brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  15. TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy

    PubMed Central

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Liang, Liping; Deng, Yun; Li, Guichao; Zhu, Ji; Wu, Yongxin; Fan, Ming; Deng, Weijuan; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Abstract Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process. We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients. We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152–19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123–17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069–15.966, and P = 0.04. Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings. PMID:26559268

  16. Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

    SciTech Connect

    Vavassori, Vittorio; Fiorino, Claudio . E-mail: fiorino.claudio@hsr.it; Rancati, Tiziana; Magli, Alessandro; Fellin, Gianni; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Valdagni, Riccardo

    2007-04-01

    Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132 patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for

  17. Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

    SciTech Connect

    Valdagni, Riccardo; Kattan, Michael W.; Rancati, Tiziana; Yu Changhong; Vavassori, Vittorio; Fellin, Giovanni; Cagna, Elena; Gabriele, Pietro; Mauro, Flora Anna; Baccolini, Micaela; Bianchi, Carla; Menegotti, Loris; Monti, Angelo F.; Stasi, Michele; Giganti, Maria Olga; and others

    2012-04-01

    Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.

  18. Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT (B-mode acquisition and targeting system) for prostate cancer.

    PubMed

    Bohrer, Markus; Schröder, Peter; Welzel, Grit; Wertz, Hansjörg; Lohr, Frank; Wenz, Frederik; Mai, Sabine Kathrin

    2008-12-01

    To evaluate the effect of image guided radiotherapy with stereotactic ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in conformal radiotherapy of prostate cancer. 42 sequential patients with prostate cancer undergoing radiotherapy before and after the introduction of BAT were included. Planning computed tomography (CT) was performed with empty rectum and moderately filled bladder. The planning target volume (PTV) included the prostate and seminal vesicles with a safety margin of 1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3 of the rectum circumference were included. Total dose was 66 Gy and a boost of 4 Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT group) an EPID (electronic portal imaging device) was performed once a week. Acute and late genito-urinary (GU) and rectal toxicity and PSA values were evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of toxicity was 3 years in the BAT group and 4 years in the NoBAT group. In the NoBAT group significant more rectal toxicity occurred, while in GU toxicity no difference was seen. Two patients in the NoBAT group showed late rectal toxicity grade 3, no toxicity>grade 2 occurred in the BAT group. There was no significant difference in PSA reduction between the groups. Without BAT significant more acute and a trend to more late rectal toxicity was found. With regard to dose escalation this aspect is currently evaluated with a larger number of patients using intensity-modulated radiotherapy (IMRT).

  19. Radiation-Induced Oral Mucositis

    PubMed Central

    Maria, Osama Muhammad; Eliopoulos, Nicoletta; Muanza, Thierry

    2017-01-01

    Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with head and neck cancers. This review will discuss RIOM definition, epidemiology, impact and side effects, pathogenesis, scoring scales, diagnosis, differential diagnosis, prevention, and treatment. PMID:28589080

  20. Radiation-Induced Oral Mucositis.

    PubMed

    Maria, Osama Muhammad; Eliopoulos, Nicoletta; Muanza, Thierry

    2017-01-01

    Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with head and neck cancers. This review will discuss RIOM definition, epidemiology, impact and side effects, pathogenesis, scoring scales, diagnosis, differential diagnosis, prevention, and treatment.

  1. Elevation of Plasma TGF-{beta}1 During Radiation Therapy Predicts Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer: A Combined Analysis From Beijing and Michigan

    SciTech Connect

    Zhao Lujun; Wang Luhua Ji Wei; Wang Xiaozhen; Zhu Xiangzhi; Hayman, James A.; Kalemkerian, Gregory P.; Yang Weizhi; Brenner, Dean; Lawrence, Theodore S.; Kong, F.-M.

    2009-08-01

    Purpose: To test whether radiation-induced elevations of transforming growth factor-{beta}1 (TGF-{beta}1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power. Methods and Materials: Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-{beta}1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was {>=} Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results: A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-{beta}1 ratio > 1 vs. 7.9% in patients with a TGF-{beta}1 ratio {<=} 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD {<=} 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-{beta}1 ratio {<=} 1 and MLD {<=} 20 Gy, 47.4% in those with a TGF-{beta}1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-{beta}1 ratio >1 and MLD > 20 Gy (p < 0.001). Conclusions: Radiation-induced elevation of plasma TGF-{beta}1 level during RT is predictive of RILT. The combination of TGF- {beta}1 and MLD may help stratify the patients for their risk of RILT.

  2. SU-D-BRB-02: Patient-Specific Rectal Toxicity Predictor Based Plan Quality Control for Prostate Stereotactic Body Radiation Therapy (SBRT)

    SciTech Connect

    Song, T; Zhou, L; Li, Y; Jiang, S; Gu, X

    2015-06-15

    Purpose: To develop a patient-specific rectal toxicity predictor guided plan quality control tool for prostate SBRT plans. Methods: For prostate SBRT cases, four segments of rectal walls including peri-prostatic anterior rectal wall, peri-prostatic lateral rectal walls, peri-prostatic posterior rectal wall and rectum superior to prostate are identified as organs at risk and the circumference of rectal wall receiving more than 39 Gy (CRW39) and 24 Gy (CRW24) are rectal toxicity predictors. In this new geometry-dosimetry model, a patient geometry descriptor, differential circumference of rectal wall (dCRW) is used as model input geometry parameters and plan dosimetric endpoints CRW39 and CRW24 are output dosimetric parameters. Linear models are built to correlate dCRW to both CRW39 and CRW24 and established with both a linear regression method and a modified bagging ensemble machine learning method. 27 SBRT prostate cases are retrospectively studied from a dose-escalated clinical trial research. 20 prescribed 50 Gy SBRT cases are recruited to train the model and the other rescaled 7 cases are used to evaluated model feasibility and accuracy. Results: Each solved linear coefficient sequence related to CRW39 or CRW24 is a one-dimensional decreasing function of the distance from the PTV boundary, indicating that the different locations of each rectal circumference have different contributions to each particular dosimetric endpoint. The fitting errors for those trained 20 prostate SBRT cases are small with mean values of 2.39%, 2.45% relative to the endpoint values for SBRT rectal toxicity predictor CRW39 and CRW24 respectively. 1 out of 7 evaluation plans is identified as poor quality plan. After re-planning, the CRW39 and CRW24 can be reduced by 3.34% and 3%, without sacrificing PTV coverage. Conclusion: The proposed patient geometry-plan toxicity predictor model for SBRT plans can be successfully applied to plan quality control for prostate SBRT cases.

  3. WE-EF-210-06: Ultrasound 2D Strain Measurement of Radiation-Induced Toxicity: Phantom and Ex Vivo Experiments

    SciTech Connect

    Liu, T; Torres, M; Rossi, P; Jani, A; Curran, W; Yang, X

    2015-06-15

    Purpose: Radiation-induced fibrosis is a common long-term complication affecting many patients following cancer radiotherapy. Standard clinical assessment of subcutaneous fibrosis is subjective and often limited to visual inspection and palpation. Ultrasound strain imaging describes the compressibility (elasticity) of biological tissues. This study’s purpose is to develop a quantitative ultrasound strain imaging that can consistently and accurately characterize radiation-induce fibrosis. Methods: In this study, we propose a 2D strain imaging method based on deformable image registration. A combined affine and B-spline transformation model is used to calculate the displacement of tissue between pre-stress and post-stress B-mode image sequences. The 2D displacement is estimated through a hybrid image similarity measure metric, which is a combination of the normalized mutual information (NMI) and normalized sum-of-squared-differences (NSSD). And 2D strain is obtained from the gradient of the local displacement. We conducted phantom experiments under various compressions and compared the performance of our proposed method with the standard cross-correlation (CC)- based method using the signal-to-noise (SNR) and contrast-to-noise (CNS) ratios. In addition, we conducted ex-vivo beef muscle experiment to further validate the proposed method. Results: For phantom study, the SNR and CNS values of the proposed method were significantly higher than those calculated from the CC-based method under different strains. The SNR and CNR increased by a factor of 1.9 and 2.7 comparing to the CC-based method. For the ex-vivo experiment, the CC-based method failed to work due to large deformation (6.7%), while our proposed method could accurately detect the stiffness change. Conclusion: We have developed a 2D strain imaging technique based on the deformable image registration, validated its accuracy and feasibility with phantom and ex-vivo data. This 2D ultrasound strain imaging

  4. Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

    SciTech Connect

    Ohashi, Toshio; Yorozu, Atsunori; Saito, Shiro; Tanaka, Nobumichi; Katayama, Norihisa; Kojima, Shinsuke; Maruo, Shinichiro; Kikuchi, Takashi; Dokiya, Takushi; Fukushima, Masanori; Yamanaka, Hidetoshi

    2015-09-01

    Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.

  5. Late toxicity and quality of life after definitive treatment of prostate cancer: redefining optimal rectal sparing constraints for intensity-modulated radiation therapy

    PubMed Central

    Chennupati, Sravana K; Pelizzari, Charles A; Kunnavakkam, Rangesh; Liauw, Stanley L

    2014-01-01

    The objective of this study was to assess late toxicity and quality of life (QOL) for patients receiving definitive intensity-modulated radiotherapy (IMRT) and image-guided radiation therapy (IGRT) with regard to normal tissue sparing objectives. Three hundred and seventy-two consecutive men treated with definitive IMRT for prostate adenocarcinoma. Toxicity was graded by CTC v3.0 genitourinary (GU) and gastrointestinal (GI) toxicity at each follow-up visit. Patient-reported QOL (EPIC-26) was prospectively collected for a subset of men. Dosimetric data for bladder and rectum were compared to toxicity and QOL global domain scores, specifically analyzing outcomes for men who met ideal rectal constraints (V70 <10%, V65 <20%, V40 <40%). The median age and prescription dose was 69 years and 76 Gy, respectively. Median follow-up was 47 months. At 4 years, freedom from Grade 2 (FFG2) GI toxicity was 92% and FFG2 GU toxicity was 76%. On univariate analysis, current smoking, larger bladder volume, and higher RT dose were associated with decreased FFG2 GU toxicity, while use of anticoagulation, increasing age, and not meeting ideal rectal constraints were associated with decreased FFG2 GI toxicity (all P ≤ 0.05). Bowel QOL remained stable over the 2-year follow-up period and was higher for patients who met ideal rectal constraints (P = 0.05). IMRT with IGRT is associated with low rates of severe toxicity and a high GI and GU QOL. The use of strict rectal constraints can further improve GI QOL and reduce GI toxicity. PMID:24803087

  6. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning

    SciTech Connect

    Tho, Lye Mun . E-mail: l.tho@beatson.gla.ac.uk; Glegg, Martin; Paterson, Jennifer; Yap, Christina; MacLeod, Alice; McCabe, Marie; McDonald, Alexander C.

    2006-10-01

    Purpose: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Methods and Materials: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V{sub 5}, V{sub 1}, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. Results: VSB correlated strongly with diarrheal severity at every dose level (p < 0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p {<=} 0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p = 0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p = 0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V{sub 5} and V{sub 15}. Conclusions: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further

  7. Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

    PubMed

    Caloglu, Murat; Yurut-Caloglu, Vuslat; Durmus-Altun, Gulay; Oz-Puyan, Fulya; Ustun, Funda; Cosar-Alas, Rusen; Saynak, Mert; Parlar, Sule; Turan, Fatma N; Uzal, Cem

    2009-05-01

    1. The aim of the present study was to compare the protective effects of L-carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2. Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., L-carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., L-carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3. The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (T(max)) and time from peak count to half count (T((1/2))) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T((1/2)) of the right kidney was 8 +/- 2 and 21 +/- 2 min, respectively. The T(max) values for

  8. Absolute volume of the rectum and AUC from rectal DVH between 25Gy and 50Gy predict acute gastrointestinal toxicity with IG-IMRT in prostate cancer.

    PubMed

    Mirjolet, Céline; Walker, Paul M; Gauthier, Mélanie; Dalban, Cécile; Naudy, Suzanne; Mazoyer, Frédéric; Martin, Etienne; Maingon, Philippe; Créhange, Gilles

    2016-11-04

    To determine whether dose/volume specific endpoints (DVSE) or Area under the rectal DVH curve (rAUC) better predict acute gastrointestinal (GI) toxicity in prostate cancer patients treated with IMRT in the era of daily image guidance (IG-IMRT). A set of DVSE was recorded from V25 to V75 (increments of 5Gy) (both in % and in cc) for 180 men. The rAUC was calculated for doses ranging between 25Gy and 50Gy (rAUC25-50). Univariate and multivariate logistic regressions were performed to determine the relationship between DVSE or rAUC25-50 and the appearance of any acute GI toxicity. The rates of acute grade 1 (G1), G2 and G3 GI toxicities were 53.3 %, 10.6 % and 1.1 %, respectively. No G4+ toxicity was observed. Rectal V25 to V75 expressed in % were not predictive of G ≥ 1 GI toxicity (p ≥ 0.12) whereas rectal V25 to V50 expressed in cc did correlate with GI toxicity G ≥ 1 (p ≤ 0.04). rAUC25-50 expressed in cc. Gy correlated significantly with the occurrence of any acute GI toxicity G ≥ 1 (p = 0.027). The absolute volume of the rectum between 25Gy and 50Gy and rAUC25-50 could significantly predict any acute rectal toxicity in prostate cancer patients treated with daily IG-IMRT.

  9. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    SciTech Connect

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    2014-04-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

  10. Radiation-Induced Bioradicals

    NASA Astrophysics Data System (ADS)

    Lahorte, Philippe; Mondelaers, Wim

    This chapter represents the second part of a review in which the production and application of radiation-induced radicals in biological matter are discussed. In part one the general aspects of the four stages (physical, physicochemical, chemical and biological) of interaction of radiation with matter in general and biological matter in particular, were discussed. Here an overview is presented of modem technologies and theoretical methods available for studying these radiation effects. The relevance is highlighted of electron paramagnetic resonance spectroscopy and quantum chemical calculations with respect to obtaining structural information on bioradicals, and a survey is given of the research studies in this field. We also discuss some basic aspects of modem accelerator technologies which can be used for creating radicals and we conclude with an overview of applications of radiation processing in biology and related fields such as biomedical and environmental engineering, food technology, medicine and pharmacy.

  11. Radiation Induced Oral Mucositis

    PubMed Central

    PS, Satheesh Kumar; Balan, Anita; Sankar, Arun; Bose, Tinky

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene PMID:20668585

  12. Radiation-induced esophagitis in lung cancer

    PubMed Central

    Baker, Sarah; Fairchild, Alysa

    2016-01-01

    Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed. PMID:28210168

  13. Ultrasound GLCM texture analysis of radiation-induced parotid-gland injury in head-and-neck cancer radiotherapy: An in vivo study of late toxicity

    PubMed Central

    Yang, Xiaofeng; Tridandapani, Srini; Beitler, Jonathan J.; Yu, David S.; Yoshida, Emi J.; Curran, Walter J.; Liu, Tian

    2012-01-01

    sonographic features were computed from the contoured region-of-interest. Results: The authors observed significant differences (p < 0.05) in all sonographic features between the normal and postradiotherapy parotid glands. The sonographic findings were consistent with the clinical observations of the ultrasound images: normal parotid glands exhibited homogeneous texture, while the postradiotherapy parotid glands exhibited heterogeneous echotexture (e.g., hyperechoic lines and spots), which likely represents fibrosis. Conclusions: The authors have demonstrated the feasibility of ultrasonic texture evaluation of parotid glands; and the sonographic features may serve as imaging signatures to assess radiation-induced parotid injury. PMID:22957638

  14. Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant

    SciTech Connect

    Schirmer, Markus Anton; Mergler, Caroline Patricia Nadine; Rave-Fraenk, Margret; Herrmann, Markus Karl; Hennies, Steffen; Gaedcke, Jochen; Conradi, Lena-Christin; Jo, Peter; Beissbarth, Tim; Hess, Clemens Friedrich; Becker, Heinz; Ghadimi, Michael; Brockmoeller, Juergen; Christiansen, Hans; Wolff, Hendrik Andreas

    2012-05-01

    Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions. Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade {>=}2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped. Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT. Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.

  15. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

    PubMed Central

    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their “M1/M2” activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased

  16. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients.

    PubMed

    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 m

  17. Radiation Induced Genomic Instability

    SciTech Connect

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  18. Quercetin inhibits radiation-induced skin fibrosis.

    PubMed

    Horton, Jason A; Li, Fei; Chung, Eun Joo; Hudak, Kathryn; White, Ayla; Krausz, Kristopher; Gonzalez, Frank; Citrin, Deborah

    2013-08-01

    Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.

  19. Quercetin Inhibits Radiation-Induced Skin Fibrosis

    PubMed Central

    Horton, Jason A.; Li, Fei; Chung, Eun Joo; Hudak, Kathryn; White, Ayla; Krausz, Kristopher; Gonzalez, Frank; Citrin, Deborah

    2013-01-01

    Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis. PMID:23819596

  20. A Preliminary Study on Racial Differences in HMOX1, NFE2L2 and TGFβ1 Gene Polymorphisms and Radiation Induced Late Normal Tissue Toxicity

    PubMed Central

    Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi; Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S.; Mikkelsen, Ross B.

    2015-01-01

    Purpose This study tests whether racial differences in genetic polymorphisms of four genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiotherapy and indicate potential therapeutic targets. Methods and Materials This prospective study examines genetic polymorphisms that modulate the expression of four genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3 and TGFβ1). DNA from blood samples of 179 patients (~80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were: 56% Caucasian, 43% African-American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared to those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later post-therapy, were also analyzed. Results Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African-American and Caucasian populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African-Americans but not Caucasians. A combined analysis of these polymorphisms revealed that >90% of African-American patients with late effects had at least one and 58% two or more of these minor alleles. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of

  1. A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

    SciTech Connect

    Alam, Asim; Mukhopadhyay, Nitai D.; Ning, Yi; Reshko, Leonid B.; Cardnell, Robert J.G.; Alam, Omair; Rabender, Christopher S.; Yakovlev, Vasily A.; Walker, Linda; Anscher, Mitchell S.; Mikkelsen, Ross B.

    2015-10-01

    Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the

  2. Multi-Institutional Phase II Study of Proton Beam Therapy for Organ-Confined Prostate Cancer Focusing on the Incidence of Late Rectal Toxicities

    SciTech Connect

    Nihei, Keiji; Ogino, Takashi; Onozawa, Masakatsu; Murayama, Shigeyuki; Fuji, Hiroshi; Murakami, Masao; Hishikawa, Yoshio

    2011-10-01

    Purpose: Proton beam therapy (PBT) is theoretically an excellent modality for external beam radiotherapy, providing an ideal dose distribution. However, it is not clear whether PBT for prostate cancer can clinically control toxicities. The purpose of the present study was to estimate prospectively the incidence of late rectal toxicities after PBT for organ-confined prostate cancer. Methods and Materials: The major eligibility criteria included clinical Stage T1-T2N0M0; initial prostate-specific antigen level of {<=}20 ng/mL and Gleason score {<=}7; no hormonal therapy or hormonal therapy within 12 months before registration; and written informed consent. The primary endpoint was the incidence of late Grade 2 or greater rectal toxicity at 2 years. Three institutions in Japan participated in the present study after institutional review board approval from each. PBT was delivered to a total dose of 74 GyE in 37 fractions. The patients were prospectively followed up to collect the data on toxicities using the National Cancer Institute-Common Toxicity Criteria, version 2.0. Results: Between 2004 and 2007, 151 patients were enrolled in the present study. Of the 151 patients, 75, 49, 9, 17, and 1 had Stage T1c, T2a, T2b, T2c, and T3a, respectively. The Gleason score was 4, 5, 6, and 7 in 5, 15, 80 and 51 patients, respectively. The initial prostate-specific antigen level was <10 or 10-20 ng/mL in 102 and 49 patients, respectively, and 42 patients had received hormonal therapy and 109 had not. The median follow-up period was 43.4 months. Acute Grade 2 rectal and bladder toxicity temporarily developed in 0.7% and 12%, respectively. Of the 147 patients who had been followed up for >2 years, the incidence of late Grade 2 or greater rectal and bladder toxicity was 2.0% (95% confidence interval, 0-4.3%) and 4.1% (95% confidence interval, 0.9-7.3%) at 2 years, respectively. Conclusion: The results of the present prospective study have revealed a valuable piece of evidence that

  3. Low inter-rater reliability in grading of rectal bleeding using NCI CTC and RTOG toxicity scales: a survey of radiation oncologists

    PubMed Central

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.; DeWeese, Theodore L.; Song, Danny Y.

    2014-01-01

    Purpose/Objective(s) Rectal bleeding is one of the most common toxicities following prostate radiotherapy (RT), and both NCI CTC and RTOG grading scales are frequently used to report outcomes. We measured concordance among genitourinary radiation oncologists in using these scales to grade rectal bleeding. Methods and Materials From 6/2013–1/2014, a web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes where patients received RT and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked if they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1–2 vs. high grades 3–4) was also assessed, using kappa statistic for multiple respondents. Results Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC=0.52, 95% CI 0.47–0.58) when using NCI CTC and fair using the RTOG scale (ICC=0.28, 95% CI 0.20–0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (p<0.0001). Using the dichotomous scale, we observed moderate agreement (kappa=0.42, 95% CI 0.40–0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (kappa=0.19, 95% CI 0.17–0.21). Conclusion Low inter-rater reliability was observed among radiation oncologists grading rectal bleeding using two common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability

  4. SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

    SciTech Connect

    Pokhrel, D; Sood, S; Badkul, R; Jiang, H; Saleh, H; Wang, F

    2015-06-15

    Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) with 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.

  5. Use of probiotics for prevention of radiation-induced diarrhea

    PubMed Central

    Delia, P; Sansotta, G; Donato, V; Frosina, P; Messina, G; De Renzis, C; Famularo, G

    2007-01-01

    AIM: To investigate the efficacy of a high-potency probiotic preparation on prevention of radiation-induced diarrhea in cancer patients. METHODS: This was a double-blind, placebo-controlled trial. Four hundred and ninety patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer were assigned to either the high-potency probiotic preparation VSL#3 (one sachet t.i.d.,) or placebo starting from the first day of radiation therapy. Efficacy endpoints were incidence and severity of radiation-induced diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication. RESULTS: More placebo patients had radiation-induced diarrhea than VSL#3 patients (124 of 239 patients, 51.8%, and 77 of 243 patients, 31.6%; P < 0.001) and more patients given placebo suffered grade 3 or 4 diarrhea compared with VSL#3 recipients (55.4% and 1.4%, P < 0.001). Daily bowel movements were 14.7 ± 6 and 5.1 ± 3 among placebo and VSL#3 recipients (P < 0.05), and the mean time to the use of loperamide was 86 ± 6 h for placebo patients and 122 ± 8 h for VSL#3 patients (P < 0.001). CONCLUSION: Probiotic lactic acid-producing bacteria are an easy, safe, and feasible approach to protect cancer patients against the risk of radiation-induced diarrhea. PMID:17352022

  6. Transperineal Injection of Hyaluronic Acid in Anterior Perirectal Fat to Decrease Rectal Toxicity From Radiation Delivered With Intensity Modulated Brachytherapy or EBRT for Prostate Cancer Patients

    SciTech Connect

    Prada, Pedro J. Fernandez, Jose; Martinez, Alvaro A.; Rua, Angeles de la; Gonzalez, Jose M.; Fernandez, Jose M.; Juan, German

    2007-09-01

    Purpose: Rectal toxicity remains a serious complication affecting quality of life for prostate cancer patients treated with radiotherapy. We began an investigational trial injecting hyaluronic acid (HA) in the perirectal fat to increase the distance between the prostate and the anterior rectal wall. This is the first report using HA injection in oncology. Methods and Materials: This is a trial of external beam radiation therapy with HDR brachytherapy boosts in prostate cancer. During the two high-dose-rate (HDR) fractions, thermoluminescent dosimeter dosimeters were placed in the urethra and in the rectum. Before the second HDR fraction, 3-7 mL (mean, 6 mL) of HA was injected under transrectal ultrasound guidance in the perirectal fat to systematically create a 1.5-cm space. Urethral and rectal HDR doses were calculated and measured. Computed tomography and magnetic resonance imaging were used to assess the stability of the new space. Results: Twenty-seven patients enrolled in the study. No toxicity was produced from the HA or the injection. In follow-up computed tomography and magnetic resonance imaging, the HA injection did not migrate or change in mass/shape for close to 1 year. The mean distance between rectum and prostate was 2.0 cm along the entire length of the prostate. The median measured rectal dose, when normalized to the median urethral dose, demonstrated a decrease in dose from 47.1% to 39.2% (p < 0.001) with or without injection. For an HDR boost dose of 1150 cGy, the rectum mean Dmax reduction was from 708 cGy to 507 cGy, p < 0.001, and the rectum mean Dmean drop was from 608 to 442 cGy, p < 0.001 post-HA injection. Conclusion: The new 2-cm distance derived from the HA injection significantly decreased rectal dose in HDR brachytherapy. Because of the several-month duration of stability, the same distance was maintained during the course of external beam radiation therapy.

  7. Late Patient-Reported Toxicity After Preoperative Radiotherapy or Chemoradiotherapy in Nonresectable Rectal Cancer: Results From a Randomized Phase III Study

    SciTech Connect

    Braendengen, Morten; Tveit, Kjell Magne; Bruheim, Kjersti; Cvancarova, Milada; Berglund, Ake; Glimelius, Bengt

    2011-11-15

    Purpose: Preoperative chemoradiotherapy (CRT) is superior to radiotherapy (RT) in locally advanced rectal cancer, but the survival gain is limited. Late toxicity is, therefore, important. The aim was to compare late bowel, urinary, and sexual functions after CRT or RT. Methods and Materials: Patients (N = 207) with nonresectable rectal cancer were randomized to preoperative CRT or RT (2 Gy Multiplication-Sign 25 {+-} 5-fluorouracil/leucovorin). Extended surgery was often required. Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), International Index of Erectile Function (IIEF), and sexual function -vaginal changes questionnaire (SVQ). Results: Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up, 78 (74%) responded. More patients in the CRT group had received a stoma (73% vs. 52%, p = 0.09). Most patients without a stoma (7 of 12 in CRT group and 9 of 16 in RT group) had incontinence for liquid stools or gas. No stoma and good anal function were seen in 5 patients (11%) in the CRT group and in 11 (30%) in the RT group (p = 0.046). Of 44 patients in the CRT group, 12 (28%) had had bowel obstruction compared with 5 of 33 (15%) in the RT group (p = 0.27). One-quarter of the patients reported urinary incontinence. The majority of men had severe erectile dysfunction. Few women reported sexual activity during the previous month. However, the majority did not have concerns about their sex life. Conclusions: Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer. There was a clear tendency for the problems to be more common after CRT than after RT.

  8. [{sup 18}F]fluorodeoxyglucose Uptake Patterns in Lung Before Radiotherapy Identify Areas More Susceptible to Radiation-Induced Lung Toxicity in Non-Small-Cell Lung Cancer Patients

    SciTech Connect

    Petit, Steven F.; Elmpt, Wouter J.C. van; Oberije, Cary J.G.; Vegt, Erik; Dingemans, Anne-Marie C.; Lambin, Philippe; Dekker, Andre L.A.J.; De Ruysscher, Dirk

    2011-11-01

    Purpose: Our hypothesis was that pretreatment inflammation in the lung makes pulmonary tissue more susceptible to radiation damage. The relationship between pretreatment [{sup 18}F]fluorodeoxyglucose ([{sup 18}F]FDG) uptake in the lungs (as a surrogate for inflammation) and the delivered radiation dose and radiation-induced lung toxicity (RILT) was investigated. Methods and Materials: We retrospectively studied a prospectively obtained cohort of 101 non-small-cell lung cancer patients treated with (chemo)radiation therapy (RT). [{sup 18}F]FDG-positron emission tomography-computed tomography (PET-CT) scans used for treatment planning were studied. Different parameters were used to describe [{sup 18}F]FDG uptake patterns in the lungs, excluding clinical target volumes, and the interaction with radiation dose. An increase in the dyspnea grade of 1 (Common Terminology Criteria for Adverse Events version 3.0) or more points compared to the pre-RT score was used as an endpoint for analysis of RILT. The effect of [{sup 18}F]FDG and CT-based variables, dose, and other patient or treatment characteristics that effected RILT was studied using logistic regression. Results: Increased lung density and pretreatment [{sup 18}F]FDG uptake were related to RILT after RT with univariable logistic regression. The 95th percentile of the [{sup 18}F]FDG uptake in the lungs remained significant in multivariable logistic regression (p = 0.016; odds ratio [OR] = 4.3), together with age (p = 0.029; OR = 1.06), and a pre-RT dyspnea score of {>=}1 (p = 0.005; OR = 0.20). Significant interaction effects were demonstrated among the 80th, 90th, and 95th percentiles and the relative lung volume receiving more than 2 and 5 Gy. Conclusions: The risk of RILT increased with the 95th percentile of the [{sup 18}F]FDG uptake in the lungs, excluding clinical tumor volume (OR = 4.3). The effect became more pronounced as the fraction of the 5%, 10%, and 20% highest standardized uptake value voxels that

  9. Radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Kronenberg, A.

    1994-01-01

    Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

  10. Radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Kronenberg, A.

    1994-01-01

    Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

  11. Low Interrater Reliability in Grading of Rectal Bleeding Using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity Scales: A Survey of Radiation Oncologists

    SciTech Connect

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.; DeWeese, Theodore L.; Song, Daniel Y.

    2014-12-01

    Purpose: To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. Methods and Materials: From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Results: Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Conclusion: Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both

  12. A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

    SciTech Connect

    Hille, Andrea . E-mail: ahille@med.uni-goettingen.de; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

    2005-12-01

    Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.

  13. Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

    PubMed

    Chung, Heeteak; Polf, Jerimy; Badiyan, Shahed; Biagioli, Matthew; Fernandez, Daniel; Latifi, Kujtim; Wilder, Richard; Mehta, Minesh; Chuong, Michael

    2017-01-01

    The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields. Dose volume histograms (DVH) were generated for the prostate, rectum, bladder, and right and left femoral heads. The normal tissue complication probability (NTCP) for ≥grade 2 rectal toxicity was calculated using the Lyman-Kutcher-Burman model and compared between patients with and without the rectal spacer. A significantly lower mean rectal DVH was achieved in patients with rectal spacer compared to those without. For LAT plans, the mean rectal V70 with and without rectal spacer was 4.19 and 13.5%, respectively. For LAO/RAO plans, the mean rectal V70 with and without rectal spacer was 5.07 and 13.5%, respectively. No significant differences were found in any rectal dosimetric parameters between the LAT and the LAO/RAO plans generated with the rectal spacers. We found that ≥ 9 mm space resulted in a significant decrease in NTCP modeled for ≥grade 2 rectal toxicity. Rectal spacers can significantly decrease modeled rectal dose and predicted ≥grade 2 rectal toxicity in prostate cancer patients treated in silico with PBS. A minimum of 9 mm separation between the prostate and anterior rectal wall yields the largest benefit.

  14. Radiation-induced cardiovascular effects

    NASA Astrophysics Data System (ADS)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

  15. The effect of tianeptine in the prevention of radiation-induced neurocognitive impairment.

    PubMed

    Akyurek, Serap; Senturk, Vesile; Oncu, Bedriye; Ozyigit, Gokhan; Yilmaz, Sercan; Gokce, Saban Cakir

    2008-12-01

    Radiation-induced neurocognitive impairment is an undesirable radiation-induced toxicity and a common health problem in patients with primary or metastatic brain tumor. It greatly impairs quality of life for long-term brain tumor survivors. Hippocampus is the most important brain structure for neurocognitive functions. It has been shown that radiation affects the hippocampal neurogenesis due to either induce the apoptosis or reduce the precursor cell proliferation in the hippocampus. Radiation-induced microglial inflammatory response is also negative regulator of neurogenesis. Tianeptine is a clinically effective antidepressant that induces neurogenesis. It has also been shown that tianeptine is able to reduce apoptosis and cytoprotective against the effects of proinflammatory cytokines in the hippocampus. Given the putative role of impaired hippocampal neurogenesis in radiation-induced neurocognitive impairment we think that tianeptine can be effective for preventing radiation-induced neurocognitive impairment by increasing hippocampal neurogenesis.

  16. Diazepam Rectal

    MedlinePlus

    Diazepam rectal gel is used in emergency situations to stop cluster seizures (episodes of increased seizure activity) in people who are ... Diazepam comes as a gel to instill rectally using a prefilled syringe with a special plastic tip. Follow the directions on your prescription label carefully, ...

  17. Radiation-induced bladder carcinoma

    SciTech Connect

    Uyama, T.; Nakamura, S.; Moriwaki, S.

    1981-01-01

    Two cases are presented of radiation-induced bladder carcinoma which followed prior irradiation for cervical carcinoma of the uterus. One was a sixty-eight-year-old woman with bladder carcinoma fourteen years after irradiation (total dose of 4,500 rad) for cervical carcinoma of the uterus. The other was a sixty-four-year-old woman with bladder carcinoma twenty-five years after irradiation with 150-K volt apparatus for cervical carcinoma of the uterus. From the late radiation change of the skin, it was estimated that the total dose of prior radiation might be 4,000 rad or more. Both had high-grade, high-stage transitional cell bladder carcinoma, and the former was with marked mucus-forming adenomatous metaplasia.

  18. Dose and volume impact on radiation-induced xerostomia.

    PubMed

    Marmiroli, Luca; Salvi, Giovanna; Caiazza, Adolfo; Di Rienzo, Luigi; Massaccesi, Mariangela; Murino, Paola; Macchia, Gabriella

    2005-01-01

    Radiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glands. Methods of measuring the salivary output are essentially represented by 99mTc-pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or unstimulated saliva. There are subjective and objective criteria of classification and grading of the secretion of saliva. Radiation-induced xerostomia, namely the residual salivary gland function is evidently associated with the mean dose absorbed. The salivary output tends to decrease after the end of radiotherapy. The partial dose-volume is substantially correlated with the mean dose to the whole gland. As for ipsilateral irradiation for head and neck cancer, conformal RT or IMRT allow to spare the contralateral parotid gland without increasing the risk of contralateral nodal recurrences. The monitoring system of late toxicity used by the authors is presented.

  19. A new CT-based method to quantify radiation-induced lung damage in patients.

    PubMed

    Ghobadi, Ghazaleh; Wiegman, Erwin M; Langendijk, Johannes A; Widder, Joachim; Coppes, Robert P; van Luijk, Peter

    2015-10-01

    A new method to assess radiation-induced lung toxicity (RILT) using CT-scans was developed. It is more sensitive in detecting damage and corresponds better to physician-rated radiation pneumonitis than routinely-used methods. Use of this method may improve lung toxicity assessment and thereby facilitate development of more accurate predictive models for RILT.

  20. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2017-06-13

    Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

  1. Treatment of Radiation-Induced Urethral Strictures.

    PubMed

    Hofer, Matthias D; Liu, Joceline S; Morey, Allen F

    2017-02-01

    Radiation therapy may result in urethral strictures from vascular damage. Most radiation-induced urethral strictures occur in the bulbomembranous junction, and urinary incontinence may result as a consequence of treatment. Radiation therapy may compromise reconstruction due to poor tissue healing and radionecrosis. Excision and primary anastomosis is the preferred urethroplasty technique for radiation-induced urethral stricture. Principles of posterior urethroplasty for trauma may be applied to the treatment of radiation-induced urethral strictures. Chronic management with suprapubic tube is an option based on patient comorbidities and preference.

  2. Radiation-induced moyamoya syndrome

    SciTech Connect

    Desai, Snehal S.; Paulino, Arnold C. . E-mail: apaulino@tmh.tmc.edu; Mai, Wei Y.; Teh, Bin S.

    2006-07-15

    Purpose: The moyamoya syndrome is an uncommon late complication after radiotherapy (RT). Methods and Materials: A PubMed search of English-language articles, with radiation, radiotherapy, and moyamoya syndrome used as search key words, yielded 33 articles from 1967 to 2002. Results: The series included 54 patients with a median age at initial RT of 3.8 years (range, 0.4 to 47). Age at RT was less than 5 years in 56.3%, 5 to 10 years in 22.9%, 11 to 20 years in 8.3%, 21 to 30 years in 6.3%, 31 to 40 years in 2.1%, and 41 to 50 years in 4.2%. Fourteen of 54 patients (25.9%) were diagnosed with neurofibromatosis type 1 (NF-1). The most common tumor treated with RT was low-grade glioma in 37 tumors (68.5%) of which 29 were optic-pathway glioma. The average RT dose was 46.5 Gy (range, 22-120 Gy). For NF-1-positive patients, the average RT dose was 46.5 Gy, and for NF-1-negative patients, it was 58.1 Gy. The median latent period for development of moyamoya syndrome was 40 months after RT (range, 4-240). Radiation-induced moyamoya syndrome occurred in 27.7% of patients by 2 years, 53.2% of patients by 4 years, 74.5% of patients by 6 years, and 95.7% of patients by 12 years after RT. Conclusions: Patients who received RT to the parasellar region at a young age (<5 years) are the most susceptible to moyamoya syndrome. The incidence for moyamoya syndrome continues to increase with time, with half of cases occurring within 4 years of RT and 95% of cases occurring within 12 years. Patients with NF-1 have a lower radiation-dose threshold for development of moyamoya syndrome.

  3. Radiation-induced accelerated coronary arteriosclerosis

    SciTech Connect

    Mittal, B.; Deutsch, M.; Thompson, M.; Dameshek, H.L.

    1986-07-01

    There is a paucity of information on radiation-induced coronary heart disease. A young patient with myocardial infarction following mediastinal irradiation is described. The role of radiotherapy and chemotherapy on the subsequent development of coronary heart disease is discussed.

  4. Radiation-induced sarcoma of the thyroid

    SciTech Connect

    Griem, K.L.; Robb, P.K.; Caldarelli, D.D.; Templeton, A.C. )

    1989-08-01

    A 23-year-old white man presented with a thyroid mass 12 years after receiving high-dose radiotherapy for a T2 and N1 lymphoepithelioma of the nasopharynx. Following subtotal thyroidectomy, a histopathologic examination revealed liposarcoma of the thyroid gland. The relationship between sarcomas and irradiation is described and Cahan and colleagues' criteria for radiation-induced sarcomas are reviewed. To our knowledge, we are presenting the first such case of a radiation-induced sarcoma of the thyroid gland.

  5. Modulation of Radiation-Induced Apoptosis by Thiolamines

    NASA Technical Reports Server (NTRS)

    Warters, R. L.; Roberts, J. C.; Wilmore, B. H.; Kelley, L. L.

    1997-01-01

    Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8-3 hybridoma after 60-minute (LD(sub50) = 4.5mM) or during a 20-hour (LD(sub50) = 0.15 mM) exposure. In contrast, a 20-hour exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50 percent apoptosis within 20 hours. Apoptosis was not induced by either a 60-minute or 20-hour exposure to 10 mM of the thiazolidime prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4mM for 15 minutes) or cysteine (10mM for 60 minutes) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 hours) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 minutes beginning 60 minutes after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 hours beginning 60 minutes after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.

  6. Modulation of Radiation-Induced Apoptosis by Thiolamines

    NASA Technical Reports Server (NTRS)

    Warters, R. L.; Roberts, J. C.; Wilmore, B. H.; Kelley, L. L.

    1997-01-01

    Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8-3 hybridoma after 60-minute (LD(sub50) = 4.5mM) or during a 20-hour (LD(sub50) = 0.15 mM) exposure. In contrast, a 20-hour exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50 percent apoptosis within 20 hours. Apoptosis was not induced by either a 60-minute or 20-hour exposure to 10 mM of the thiazolidime prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4mM for 15 minutes) or cysteine (10mM for 60 minutes) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 hours) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 minutes beginning 60 minutes after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 hours beginning 60 minutes after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.

  7. SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

    SciTech Connect

    Oh, J; Deasy, J; Kerns, S; Ostrer, H; Rosenstein, B

    2016-06-15

    Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation). To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques

  8. SU-D-204-03: Comparison of Patient Positioning Methods Through Modeling of Acute Rectal Toxicity in Intensity Modulated Radiation Therapy for Prostate Cancer. Does Quality of Data Matter More Than the Quantity?

    SciTech Connect

    Liu, X; Fatyga, M; Vora, S; Wong, W; Schild, S; Schild, M; Herman, M; Li, J; Wu, T

    2016-06-15

    Purpose: To determine if differences in patient positioning methods have an impact on the incidence and modeling of grade >=2 acute rectal toxicity in prostate cancer patients who were treated with Intensity Modulated Radiation Therapy (IMRT). Methods: We compared two databases of patients treated with radiation therapy for prostate cancer: a database of 79 patients who were treated with 7 field IMRT and daily image guided positioning based on implanted gold markers (IGRTdb), and a database of 302 patients who were treated with 5 field IMRT and daily positioning using a trans-abdominal ultrasound system (USdb). Complete planning dosimetry was available for IGRTdb patients while limited planning dosimetry, recorded at the time of planning, was available for USdb patients. We fit Lyman-Kutcher-Burman (LKB) model to IGRTdb only, and Univariate Logistic Regression (ULR) NTCP model to both databases. We perform Receiver Operating Characteristics analysis to determine the predictive power of NTCP models. Results: The incidence of grade >= 2 acute rectal toxicity in IGRTdb was 20%, while the incidence in USdb was 54%. Fits of both LKB and ULR models yielded predictive NTCP models for IGRTdb patients with Area Under the Curve (AUC) in the 0.63 – 0.67 range. Extrapolation of the ULR model from IGRTdb to planning dosimetry in USdb predicts that the incidence of acute rectal toxicity in USdb should not exceed 40%. Fits of the ULR model to the USdb do not yield predictive NTCP models and their AUC is consistent with AUC = 0.5. Conclusion: Accuracy of a patient positioning system affects clinically observed toxicity rates and the quality of NTCP models that can be derived from toxicity data. Poor correlation between planned and clinically delivered dosimetry may lead to erroneous or poorly performing NTCP models, even if the number of patients in a database is large.

  9. Rectal planning risk volume correlation with acute and late toxicity in 3-dimensional conformal radiation therapy for prostate cancer.

    PubMed

    Dias, R S; Giordani, A J; Souhami, L; Segreto, R A; Segreto, H R C

    2011-12-01

    The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications.This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0.The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade ≥ 2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p 5 0.011) and 40% (p 5 0.005) of the rectum volume and at 40% of the PRV (p 5 0.012). The dose at 25% of the rectum volume (p 5 0.033) and acute complications ≥ grade 2 (p 5 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence.

  10. PAI-1-Dependent Endothelial Cell Death Determines Severity of Radiation-Induced Intestinal Injury

    PubMed Central

    Abderrahmani, Rym; François, Agnes; Buard, Valerie; Tarlet, Georges; Blirando, Karl; Hneino, Mohammad; Vaurijoux, Aurelie; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

    2012-01-01

    Normal tissue toxicity still remains a dose-limiting factor in clinical radiation therapy. Recently, plasminogen activator inhibitor type 1 (SERPINE1/PAI-1) was reported as an essential mediator of late radiation-induced intestinal injury. However, it is not clear whether PAI-1 plays a role in acute radiation-induced intestinal damage and we hypothesized that PAI-1 may play a role in the endothelium radiosensitivity. In vivo, in a model of radiation enteropathy in PAI-1 −/− mice, apoptosis of radiosensitive compartments, epithelial and microvascular endothelium was quantified. In vitro, the role of PAI-1 in the radiation-induced endothelial cells (ECs) death was investigated. The level of apoptotic ECs is lower in PAI-1 −/− compared with Wt mice after irradiation. This is associated with a conserved microvascular density and consequently with a better mucosal integrity in PAI-1 −/− mice. In vitro, irradiation rapidly stimulates PAI-1 expression in ECs and radiation sensitivity is increased in ECs that stably overexpress PAI-1, whereas PAI-1 knockdown increases EC survival after irradiation. Moreover, ECs prepared from PAI-1 −/− mice are more resistant to radiation-induced cell death than Wt ECs and this is associated with activation of the Akt pathway. This study demonstrates that PAI-1 plays a key role in radiation-induced EC death in the intestine and suggests that this contributes strongly to the progression of radiation-induced intestinal injury. PMID:22563394

  11. Radiation-induced vaginal stenosis: current perspectives

    PubMed Central

    Morris, Lucinda; Do, Viet; Chard, Jennifer; Brand, Alison H

    2017-01-01

    Treatment of gynecological cancer commonly involves pelvic radiation therapy (RT) and/or brachytherapy. A commonly observed side effect of such treatment is radiation-induced vaginal stenosis (VS). This review analyzed the incidence, pathogenesis, clinical manifestation(s) and assessment and grading of radiation-induced VS. In addition, risk factors, prevention and treatment options and follow-up schedules are also discussed. The limited available literature on many of these aspects suggests that additional studies are required to more precisely determine the best management strategy of this prevalent group after RT. PMID:28496367

  12. Radiation-induced amorphization of intermetallic compounds

    NASA Astrophysics Data System (ADS)

    Lam, N. Q.; Sabochick, M. J.; Okamoto, P. R.

    1994-06-01

    In the present paper, important results of our recent computer simulation of radiation-induced amorphization in the ordered compounds CuTi and Cu4Ti3 are summarized. The energetic, structural, thermodynamic and mechanical responses of these intermetallics during chemical disordering, point-defect production and heating were simulated, using molecular dynamics and embedded-atom potentials. From the atomistic details obtained, the critical role of radiation-induced structural disorder in driving the crystalline-to-amorphous phase transformation is discussed.

  13. Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury

    PubMed Central

    Cotrim, Ana P.; Hyodo, Fuminori; Baum, Bruce J.; Krishna, Murali C.; Mitchell, James B.

    2010-01-01

    Radiation is used in the treatment of a broad range of malignancies. Exposure of normal tissue to radiation may result in both acute and chronic toxicities that can result in an inability to deliver the intended therapy, a range of symptoms, and a decrease in quality of life. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Herein, we review agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury. Few agents are approved for clinical use, but many new compounds show promising results in preclinical testing. PMID:20413641

  14. Radiation-induced lung injury

    SciTech Connect

    Rosiello, R.A.; Merrill, W.W. )

    1990-03-01

    The use of radiation therapy is limited by the occurrence of the potentially fatal clinical syndromes of radiation pneumonitis and fibrosis. Radiation pneumonitis usually becomes clinically apparent from 2 to 6 months after completion of radiation therapy. It is characterized by fever, cough, dyspnea, and alveolar infiltrates on chest roentgenogram and may be difficult to differentiate from infection or recurrent malignancy. The pathogenesis is uncertain, but appears to involve both direct lung tissue toxicity and an inflammatory response. The syndrome may resolve spontaneously or may progress to respiratory failure. Corticosteroids may be effective therapy if started early in the course of the disease. The time course for the development of radiation fibrosis is later than that for radiation pneumonitis. It is usually present by 1 year following irradiation, but may not become clinically apparent until 2 years after radiation therapy. It is characterized by the insidious onset of dyspnea on exertion. It most often is mild, but can progress to chronic respiratory failure. There is no known successful treatment for this condition. 51 references.

  15. Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

    SciTech Connect

    Pouliliou, Stamatia E.; Dimitriou, Thespis; Giatromanolaki, Alexandra; Papazoglou, Dimitrios; Pappa, Aglaia; Pistevou, Kyriaki

    2015-07-01

    Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2{sub [4h]}) and 24 hours (SF2{sub [24h]}) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2{sub (4h)} was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio{sub (30min)} (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio{sub (4h)}/γH2AX-ratio{sub (30min)}) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with

  16. Prevention and management of radiation-induced dermatitis, mucositis, and xerostomia.

    PubMed

    Radvansky, Lauren J; Pace, Makala B; Siddiqui, Asif

    2013-06-15

    Current strategies for preventing and managing radiation-induced dermatitis, mucositis, and xerostomia are reviewed, with an emphasis on pharmacologic interventions. Nearly two thirds of all patients with cancer receive radiation therapy during the course of treatment, frequently resulting in acute skin and mucosal toxicities. The severity of radiotherapy-associated toxicities varies according to multiple treatment- and patient-related factors (e.g., total radiation dose and dose fractionation schedule, volume of organ or tissue irradiated, use of concurrent versus sequential chemotherapy, comorbid conditions, functional performance status). Three major radiation toxicities encountered in clinical practice are (1) radiation dermatitis, typically managed with a variety of topical agents such as water-based moisturizing creams or lotions, topical steroids, antiinflammatory emulsions, and wound dressings, (2) radiation-induced oral mucositis, which can be managed through proper basic oral care practices, appropriate pain management, and the use of medicated mouthwashes and oral rinses and gels, and (3) radiation-induced xerostomia, which can be alleviated with saliva substitutes, moistening agents, and sialagogues. Pharmacists involved in the care of patients receiving radiotherapy can play an important role in optimizing symptom control, educating patients on self-care strategies, and adverse effect monitoring and reporting. Radiation-induced dermatitis, mucositis, and xerostomia can cause significant morbidity and diminished quality of life. Pharmacologic interventions for the prevention and treatment of these toxicities include topical agents for dermatitis; oral products, analgesics, and palifermin for mucositis; and amifostine, saliva substitutes, and pilocarpine for xerostomia.

  17. Factors that modify radiation-induced carcinogenesis.

    PubMed

    Kennedy, Ann R

    2009-11-01

    It is known that numerous factors can influence radiation carcinogenesis in animals; these factors include the specific characteristics of the radiation (radiation type and dose, dose-rate, dose-fractionation, dose distribution, etc.) as well as many other contributing elements that are not specific to the radiation exposure, such as animal genetic characteristics and age, the environment of the animal, dietary factors and whether specific modifying agents for radiation carcinogenesis have been utilized in the studies. This overview focuses on the modifying factors for radiation carcinogenesis, in both in vivo and in vitro systems, and includes a discussion of agents that enhance (e.g., promoting agents) or suppress (e.g., cancer preventive agents) radiation-induced carcinogenesis. The agents that enhance or suppress radiation carcinogenesis in experimental model systems have been shown to lead to effects equally as large as other known modifying factors for radiation-induced carcinogenesis (e.g., dose-rate, dose-fractionation, linear energy transfer). It is known that dietary factors play an important role in determining the yields of radiation-induced cancers in animal model systems, and it is likely that they also influence radiation-induced cancer risks in human populations.

  18. Molecular pathways: radiation-induced cognitive impairment.

    PubMed

    Greene-Schloesser, Dana; Moore, Elizabeth; Robbins, Mike E

    2013-05-01

    Each year, approximately 200,000 patients in the United States will receive partial- or whole-brain irradiation for the treatment of primary or metastatic brain cancer. Early and delayed radiation effects are transient and reversible with modern therapeutic standards; yet, late radiation effects (≥6 months postirradiation) remain a significant risk, resulting in progressive cognitive impairment. These risks include functional deficits in memory, attention, and executive function that severely affect the patient's quality of life. The mechanisms underlying radiation-induced cognitive impairment remain ill defined. Classically, radiation-induced alterations in vascular and neuroinflammatory glial cell clonogenic populations were hypothesized to be responsible for radiation-induced brain injury. Recently, preclinical studies have focused on the hippocampus, one of two sites of adult neurogenesis within the brain, which plays an important role in learning and memory. Radiation ablates hippocampal neurogenesis, alters neuronal function, and induces neuroinflammation. Neuronal stem cells implanted into the hippocampus prevent the decrease in neurogenesis and improve cognition after irradiation. Clinically prescribed drugs, including PPARα and PPARγ agonists, as well as RAS blockers, prevent radiation-induced neuroinflammation and cognitive impairment independent of improved neurogenesis. Translating these exciting findings to the clinic offers the promise of improving the quality of life of brain tumor patients who receive radiotherapy. ©2013 AACR.

  19. Inhibition of radiation-induced skin fibrosis with imatinib.

    PubMed

    Horton, Jason A; Chung, Eun Joo; Hudak, Kathryn E; Sowers, Anastasia; Thetford, Angela; White, Ayla O; Mitchell, James B; Citrin, Deborah E

    2013-03-01

    Dermal fibrosis is a disabling late toxicity of radiotherapy. Several lines of evidence suggest that overactive signaling via the Platelet-derived growth factor receptor-beta (PDGFR-β) and V-abl Abelson murine leukemia viral oncogene homolog 1 (cAbl) may be etiologic factors in the development of radiation-induced fibrosis. We tested the hypothesis that imatinib, a clinically available inhibitor of PDGFR-β, Mast/stem cell growth factor receptor (c-kit) and cAbl, would reduce the severity of dermal fibrosis in a murine model. The right hind legs of female C3H/HeN mice were exposed to 35 Gy of X-rays. Cohorts of mice were maintained on chow formulated with imatinib 0.5 mg/g or control chow for the duration of the experiment. Bilateral hind limb extension was measured serially to assess fibrotic contracture. Immunohistochemistry and biochemical assays were used to evaluate the levels of collagen and cytokines implicated in radiation-induced fibrosis. Imatinib treatment significantly reduced hind limb contracture and dermal thickness after irradiation. Immunohistochemical studies demonstrated a substantial reduction in PDGFR-β phosphorylation. We also observed reduced Transforming Growth factor-β (TGF-β) and collagen expression in irradiated skin of imatinib-treated mice, suggesting that imatinib may suppress the fibrotic process by interrupting cross-talk between these pathways. Taken together, these results support that imatinib may be a useful agent in the prevention and treatment of radiation-induced dermal fibrosis.

  20. [Quantification of radiation-induced genetic risk].

    PubMed

    Ehling, U H

    1987-05-01

    Associated with technical advances of our civilization is a radiation- and chemically-induced increase in the germ cell mutation rate in man. This would result in an increase in the frequency of genetic diseases and would be detrimental to future generations. It is the duty of our generation to keep this risk as low as possible. The estimation of the radiation-induced genetic risk of human populations is based on the extrapolation of results from animal experiments. Radiation-induced mutations are stochastic events. The probability of the event depends on the dose; the degree of the damage does not. The different methods to estimate the radiation-induced genetic risk will be discussed. The accuracy of the predicted results will be evaluated by a comparison with the observed incidence of dominant mutations in offspring born to radiation exposed survivors of the Hiroshima and Nagasaki atomic bombings. These methods will be used to predict the genetic damage from the fallout of the reactor accident at Chernobyl. For the exposure dose we used the upper limits of the mean effective life time equivalent dose from the fallout values in the Munich region. According to the direct method for the risk estimation we will expect for each 100 to 500 spontaneous dominant mutations one radiation-induced mutation in the first generation. With the indirect method we estimate a ratio of 100 dominant spontaneous mutations to one radiation-induced dominant mutation. The possibilities and the limitations of the different methods to estimate the genetic risk will be discussed. The discrepancy between the high safety standards for radiation protection and the low level of knowledge for the toxicological evaluation of chemical mutagens will be emphasized.

  1. [Quality radiotherapy in rectal cancer].

    PubMed

    Capirci, C; Amichetti, M; De Renzis, C

    2001-01-01

    The quality of radiotherapy significantly impacts on the results of treatment, in patients with rectal carcinoma, especially in terms of acute and late toxicity. Based on this assumption, the Italian Association of Radiation Oncology (AIRO) formulated a document aimed to define the standards of radiation treatment for rectal carcinomas. Two different levels of standard were described: a first level, considered as "minimal requirement", and a second level, considered as "optimal treatment". A retrospective evaluation, based on a questionnaire, revealed that in 1996, in most Italian Centers, patients affected by rectal carcinoma received radiation treatment within the first level of proposed standards. A subsequent analysis concerned the evaluation of the level of treatments applied in 2000. In this paper the radiotherapy standards proposed by the AIRO are described in the different phases of the radiation treatment.

  2. Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression.

    PubMed

    Klein, Diana; Steens, Jennifer; Wiesemann, Alina; Schulz, Florian; Kaschani, Farnusch; Röck, Katharina; Yamaguchi, Masahiro; Wirsdörfer, Florian; Kaiser, Markus; Fischer, Jens W; Stuschke, Martin; Jendrossek, Verena

    2017-04-10

    Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect to the vascular compartment remain elusive, and no causative radioprotective treatment is available to date. The importance of injury to EC for radiation-induced late toxicity in lungs after whole thorax irradiation (WTI) was investigated using a mouse model of radiation-induced pneumopathy. We show that WTI induces EC loss as long-term complication, which is accompanied by the development of fibrosis. Adoptive transfer of mesenchymal stem cells (MSCs) either derived from bone marrow or aorta (vascular wall-resident MSCs) in the early phase after irradiation limited the radiation-induced EC loss and fibrosis progression. Furthermore, MSC-derived culture supernatants rescued the radiation-induced reduction in viability and long-term survival of cultured lung EC. We further identified the antioxidant enzyme superoxide dismutase 1 (SOD1) as a MSC-secreted factor. Importantly, MSC treatment restored the radiation-induced reduction of SOD1 levels after WTI. A similar protective effect was achieved by using the SOD-mimetic EUK134, suggesting that MSC-derived SOD1 is involved in the protective action of MSC, presumably through paracrine signaling. In this study, we explored the therapeutic potential of MSC therapy to prevent radiation-induced EC loss (late effect) and identified the protective mechanisms of MSC action. Adoptive transfer of MSCs early after irradiation counteracts radiation-induced vascular damage and EC loss as late adverse effects. The high activity of vascular wall-derived MSCs for radioprotection may be due to their tissue-specific action. Antioxid. Redox Signal. 26, 563-582.

  3. Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

    PubMed Central

    Steens, Jennifer; Wiesemann, Alina; Schulz, Florian; Kaschani, Farnusch; Röck, Katharina; Yamaguchi, Masahiro; Wirsdörfer, Florian; Kaiser, Markus; Fischer, Jens W.; Stuschke, Martin; Jendrossek, Verena

    2017-01-01

    Abstract Aims: Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect to the vascular compartment remain elusive, and no causative radioprotective treatment is available to date. Results: The importance of injury to EC for radiation-induced late toxicity in lungs after whole thorax irradiation (WTI) was investigated using a mouse model of radiation-induced pneumopathy. We show that WTI induces EC loss as long-term complication, which is accompanied by the development of fibrosis. Adoptive transfer of mesenchymal stem cells (MSCs) either derived from bone marrow or aorta (vascular wall-resident MSCs) in the early phase after irradiation limited the radiation-induced EC loss and fibrosis progression. Furthermore, MSC-derived culture supernatants rescued the radiation-induced reduction in viability and long-term survival of cultured lung EC. We further identified the antioxidant enzyme superoxide dismutase 1 (SOD1) as a MSC-secreted factor. Importantly, MSC treatment restored the radiation-induced reduction of SOD1 levels after WTI. A similar protective effect was achieved by using the SOD-mimetic EUK134, suggesting that MSC-derived SOD1 is involved in the protective action of MSC, presumably through paracrine signaling. Innovation: In this study, we explored the therapeutic potential of MSC therapy to prevent radiation-induced EC loss (late effect) and identified the protective mechanisms of MSC action. Conclusions: Adoptive transfer of MSCs early after irradiation counteracts radiation-induced vascular damage and EC loss as late adverse effects. The high activity of vascular wall-derived MSCs for radioprotection may be due to their tissue-specific action. Antioxid. Redox Signal. 26, 563–582. PMID:27572073

  4. 3D ultrasound Nakagami imaging for radiation-induced vaginal fibrosis

    NASA Astrophysics Data System (ADS)

    Yang, Xiaofeng; Rossi, Peter; Shelton, Joseph; Bruner, Debrorah; Tridandapani, Srini; Liu, Tian

    2014-03-01

    Radiation-induced vaginal fibrosis is a debilitating side-effect affecting up to 80% of women receiving radiotherapy for their gynecological (GYN) malignancies. Despite the significant incidence and severity, little research has been conducted to identify the pathophysiologic changes of vaginal toxicity. In a previous study, we have demonstrated that ultrasound Nakagami shape and PDF parameters can be used to quantify radiation-induced vaginal toxicity. These Nakagami parameters are derived from the statistics of ultrasound backscattered signals to capture the physical properties (e.g., arrangement and distribution) of the biological tissues. In this paper, we propose to expand this Nakagami imaging concept from 2D to 3D to fully characterize radiation-induced changes to the vaginal wall within the radiation treatment field. A pilot study with 5 post-radiotherapy GYN patients was conducted using a clinical ultrasound scanner (6 MHz) with a mechanical stepper. A serial of 2D ultrasound images, with radio-frequency (RF) signals, were acquired at 1 mm step size. The 2D Nakagami shape and PDF parameters were calculated from the RF signal envelope with a sliding window, and then 3D Nakagami parameter images were generated from the parallel 2D images. This imaging method may be useful as we try to monitor radiation-induced vaginal injury, and address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

  5. Radiation-induced brain injury: A review

    PubMed Central

    Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

  6. Effects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis.

    PubMed

    Bickelhaupt, Sebastian; Erbel, Christian; Timke, Carmen; Wirkner, Ute; Dadrich, Monika; Flechsig, Paul; Tietz, Alexandra; Pföhler, Johanna; Gross, Wolfgang; Peschke, Peter; Hoeltgen, Line; Katus, Hugo A; Gröne, Hermann-Josef; Nicolay, Nils H; Saffrich, Rainer; Debus, Jürgen; Sternlicht, Mark D; Seeley, Todd W; Lipson, Kenneth E; Huber, Peter E

    2017-08-01

    Radiotherapy is a mainstay for the treatment of lung cancer that can induce pneumonitis or pulmonary fibrosis. The matricellular protein connective tissue growth factor (CTGF) is a central mediator of tissue remodeling. A radiation-induced mouse model of pulmonary fibrosis was used to determine if transient administration of a human antibody to CTGF (FG-3019) started at different times before or after 20 Gy thoracic irradiation reduced acute and chronic radiation toxicity. Mice (25 mice/group; 10 mice/group in a confirmation study) were examined by computed tomography, histology, gene expression changes, and for survival. In vitro experiments were performed to directly study the interaction of CTGF blockade and radiation. All statistical tests were two-sided. Administration of FG-3019 prevented (∼50%-80%) or reversed (∼50%) lung remodeling, improved lung function, improved mouse health, and rescued mice from lethal irradiation ( P < .01). Importantly, when antibody treatment was initiated at 16 weeks after thoracic irradiation, FG-3019 reversed established lung remodeling and restored lung function. CTGF blockade abrogated M2 polarized macrophage influx, normalized radiation-induced gene expression changes, and reduced myofibroblast abundance and Osteopontin expression. These results indicate that blocking CTGF attenuates radiation-induced pulmonary remodeling and can reverse the process after initiation. CTGF has a central role in radiation-induced fibrogenesis, and FG-3019 may benefit patients with radiation-induced pulmonary fibrosis or patients with other forms or origin of chronic fibrotic diseases.

  7. Radiation-induced meningiomas in pediatric patients

    SciTech Connect

    Moss, S.D.; Rockswold, G.L.; Chou, S.N.; Yock, D.; Berger, M.S.

    1988-04-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature.

  8. Bile acids in radiation-induced diarrhea

    SciTech Connect

    Arlow, F.L.; Dekovich, A.A.; Priest, R.J.; Beher, W.T.

    1987-10-01

    Radiation-induced bowel disease manifested by debilitating diarrhea is an unfortunate consequence of therapeutic irradiation for pelvic malignancies. Although the mechanism for this diarrhea is not well understood, many believe it is the result of damage to small bowel mucosa and subsequent bile acid malabsorption. Excess amounts of bile acids, especially the dihydroxy components, are known to induce water and electrolyte secretion and increase bowel motility. We have directly measured individual and total bile acids in the stool samples of 11 patients with radiation-induced diarrhea and have found bile acids elevated two to six times normal in eight of them. Our patients with diarrhea and increased bile acids in their stools had prompt improvement when given cholestyramine. They had fewer stools and returned to a more normal life-style.

  9. Radiation-induced meningiomas in pediatric patients.

    PubMed

    Moss, S D; Rockswold, G L; Chou, S N; Yock, D; Berger, M S

    1988-04-01

    Radiation-induced meningiomas rarely have latency periods short enough from the time of irradiation to the clinical presentation of the tumor to present in the pediatric patient. Three cases of radiation-induced intracranial meningiomas in pediatric patients are presented. The first involved a meningioma of the right frontal region in a 10-year-old boy 6 years after the resection and irradiation of a 4th ventricular medulloblastoma. Review of our pediatric tumor cases produced a second case of a left temporal fossa meningioma presenting in a 15-year-old boy with a history of irradiation for retinoblastoma at age 3 years and a third case of a right frontoparietal meningioma in a 15-year-old girl after irradiation for acute lymphoblastic leukemia. Only three cases of meningiomas presenting in the pediatric age group after radiation therapy to the head were detected in our review of the literature.

  10. Study of chemical and radiation induced carcinogenesis

    SciTech Connect

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  11. Radiation-induced heart disease in rats

    SciTech Connect

    Lauk, S.; Kiszel, Z.; Buschmann, J.; Trott, K.R.

    1985-04-01

    After local irradiation of the rat heart with X ray doses of over 10 Gy (single dose), animals developed symptoms of radiation-induced heart disease, which at higher doses would lead to fatal cardiac failure. The LD 50 at 1 year was between 15 Gy and 20 Gy. The pericardium and epicardium responded to irradiation with exudative pericarditis after 4 months. Focal myocardial damage was secondary to progressive capillary damage.

  12. Radiation induced fracture of the scapula

    SciTech Connect

    Riggs, J.H. III; Schultz, G.D.; Hanes, S.A. )

    1990-10-01

    A case of radiation induced osteonecrosis resulting in a fracture of the scapula in a 76-yr-old female patient with a history of breast carcinoma is presented. Diagnostic imaging, laboratory recommendations and clinical findings are discussed along with an algorithm for the safe management of patients with a history of cancer and musculoskeletal complaints. This case demonstrates the necessity of a thorough investigation of musculoskeletal complaints in patients with previous bone-seeking carcinomas.

  13. Imaging radiation-induced normal tissue injury.

    PubMed

    Robbins, Mike E; Brunso-Bechtold, Judy K; Peiffer, Ann M; Tsien, Christina I; Bailey, Janet E; Marks, Lawrence B

    2012-04-01

    Technological developments in radiation therapy and other cancer therapies have led to a progressive increase in five-year survival rates over the last few decades. Although acute effects have been largely minimized by both technical advances and medical interventions, late effects remain a concern. Indeed, the need to identify those individuals who will develop radiation-induced late effects, and to develop interventions to prevent or ameliorate these late effects is a critical area of radiobiology research. In the last two decades, preclinical studies have clearly established that late radiation injury can be prevented/ameliorated by pharmacological therapies aimed at modulating the cascade of events leading to the clinical expression of radiation-induced late effects. These insights have been accompanied by significant technological advances in imaging that are moving radiation oncology and normal tissue radiobiology from disciplines driven by anatomy and macrostructure to ones in which important quantitative functional, microstructural, and metabolic data can be noninvasively and serially determined. In the current article, we review use of positron emission tomography (PET), single photon emission tomography (SPECT), magnetic resonance (MR) imaging and MR spectroscopy to generate pathophysiological and functional data in the central nervous system, lung, and heart that offer the promise of, (1) identifying individuals who are at risk of developing radiation-induced late effects, and (2) monitoring the efficacy of interventions to prevent/ameliorate them.

  14. Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

    SciTech Connect

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C.

    2013-11-01

    Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays, were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.

  15. Selenoprotein P inhibits radiation-induced late reactive oxygen species accumulation and normal cell injury.

    PubMed

    Eckers, Jaimee C; Kalen, Amanda L; Xiao, Wusheng; Sarsour, Ehab H; Goswami, Prabhat C

    2013-11-01

    Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays, were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Radiation-induced injury of the esophagus

    SciTech Connect

    Lepke, R.A.; Libshitz, H.I.

    1983-08-01

    Forty patients with functional or morphologic esophageal abnormalities following radiotherapy were identified. Abnormalities included abnormal motility with and without mucosal edema, stricture, ulceration and pseudodiverticulum, and fistula. Abnormal motility occurred 4 to 12 weeks following radiotherapy alone and as early as 1 week after therapy when concomitant chemotherapy had been given. Strictures developed 4 to 8 months following completion of radiotherapy. Ulceration, pseudodiverticulum, and fistula formation did not develop in a uniform time frame. Radiation-induced esophageal injury is more frequent when radiotherapy and chemotherapy are combined than it is with radiotherapy alone.

  17. Radiation induced detwinning in nanotwinned Cu

    SciTech Connect

    Chen, Youxing; Wang, Haiyan; Kirk, Mark A.; Li, Meimei; Wang, Jian; Zhang, Xinghang

    2016-11-15

    Superior radiation tolerance has been experimentally examined in nanotwinned metals. The stability of nanotwinned structure under radiation is the key factor for advancing the application of nanotwinned metals for nuclear reactors. We thus performed in situ radiation tests for nanotwinned Cu with various twin thicknesses inside a transmission electron microscope. We found that there is a critical twin thickness (10 nm), below which, radiation induced detwinning is primarily accomplished through migration of incoherent twin boundaries. Lastly, detwinning is faster for thinner twins in this range, while thicker twins are more stable.

  18. A report on radiation-induced gliomas

    SciTech Connect

    Salvati, M.; Artico, M.; Caruso, R.; Rocchi, G.; Orlando, E.R.; Nucci, F. )

    1991-01-15

    Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.56 references.

  19. Silver clear nylon dressing is effective in preventing radiation-induced dermatitis in patients with lower gastrointestinal cancer: results from a phase III study.

    PubMed

    Niazi, Tamim M; Vuong, Te; Azoulay, Laurant; Marijnen, Corrie; Bujko, Kryzstof; Nasr, Elie; Lambert, Christine; Duclos, Marie; Faria, Sergio; David, Marc; Cummings, Bernard

    2012-11-01

    For patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients. A total of 42 rectal or anal canal cancer patients were randomized to either a SCND or standard skin care group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after treatment completion. In the control arm, sulfadiazine cream was applied at the time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on the last day, and two weeks after the treatment completion were scored by 10 blinded readers, who used the common toxicity scoring system for skin dermatitis. The radiation dose ranged from 50.4 to 59.4 Gy, and there were no differences between the 2 groups. On the last day of RT, when the most severe RID occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for the standard and 1.67 (SD, 1.2; P=.01) for the SCND arm. At 2 weeks after RT, the difference was 0.39 points in favor of SCND (P=.39). There was considerable intraclass correlation among the 10 observers. Silver clear nylon dressing is effective in reducing RID in patients with lower gastrointestinal cancer treated with combined chemotherapy and radiation treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Silver Clear Nylon Dressing is Effective in Preventing Radiation-Induced Dermatitis in Patients With Lower Gastrointestinal Cancer: Results From a Phase III Study

    SciTech Connect

    Niazi, Tamim M.; Vuong, Te; Azoulay, Laurant; Marijnen, Corrie; Bujko, Kryzstof; Nasr, Elie; Lambert, Christine; Duclos, Marie; Faria, Sergio; David, Marc; Cummings, Bernard

    2012-11-01

    Purpose: For patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients. Methods and Materials: A total of 42 rectal or anal canal cancer patients were randomized to either a SCND or standard skin care group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after treatment completion. In the control arm, sulfadiazine cream was applied at the time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on the last day, and two weeks after the treatment completion were scored by 10 blinded readers, who used the common toxicity scoring system for skin dermatitis. Results: The radiation dose ranged from 50.4 to 59.4 Gy, and there were no differences between the 2 groups. On the last day of RT, when the most severe RID occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for the standard and 1.67 (SD, 1.2; P=.01) for the SCND arm. At 2 weeks after RT, the difference was 0.39 points in favor of SCND (P=.39). There was considerable intraclass correlation among the 10 observers. Conclusions: Silver clear nylon dressing is effective in reducing RID in patients with lower gastrointestinal cancer treated with combined chemotherapy and radiation treatment.

  1. Digital rectal exam

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007069.htm Digital rectal exam To use the sharing features on this page, please enable JavaScript. A digital rectal exam is an examination of the lower ...

  2. Epigenetics in radiation-induced fibrosis.

    PubMed

    Weigel, C; Schmezer, P; Plass, C; Popanda, O

    2015-04-23

    Radiotherapy is a major cancer treatment option but dose-limiting side effects such as late-onset fibrosis in the irradiated tissue severely impair quality of life in cancer survivors. Efforts to explain radiation-induced fibrosis, for example, by genetic variation remained largely inconclusive. Recently published molecular analyses on radiation response and fibrogenesis showed a prominent role of epigenetic gene regulation. This review summarizes the current knowledge on epigenetic modifications in fibrotic disease and radiation response, and it points out the important role for epigenetic mechanisms such as DNA methylation, microRNAs and histone modifications in the development of this disease. The synopsis illustrates the complexity of radiation-induced fibrosis and reveals the need for investigations to further unravel its molecular mechanisms. Importantly, epigenetic changes are long-term determinants of gene expression and can therefore support those mechanisms that induce and perpetuate fibrogenesis even in the absence of the initial damaging stimulus. Future work must comprise the interconnection of acute radiation response and long-lasting epigenetic effects in order to assess their role in late-onset radiation fibrosis. An improved understanding of the underlying biology is fundamental to better comprehend the origin of this disease and to improve both preventive and therapeutic strategies.

  3. Radiation induced conductivity in space dielectric materials

    SciTech Connect

    Hanna, R.; Paulmier, T. Belhaj, M.; Dirassen, B.; Molinie, P.; Payan, D.; Balcon, N.

    2014-01-21

    The radiation-induced conductivity of some polymers was described mainly in literature by a competition between ionization, trapping/detrapping, and recombination processes or by radiation assisted ageing mechanisms. Our aim is to revise the effect of the aforementioned mechanisms on the complex evolution of Teflon{sup ®} FEP under space representative ionizing radiation. Through the definition of a new experimental protocol, revealing the effect of radiation dose and relaxation time, we have been able to demonstrate that the trapping/recombination model devised in this study agrees correctly with the observed experimental phenomenology at qualitative level and allows describing very well the evolution of radiation induced conductivity with irradiation time (or received radiation dose). According to this model, the complex behavior observed on Teflon{sup ®} FEP may be basically ascribed to the competition between electron/hole pairs generation and recombination: electrons are deeply trapped and act as recombination centers for free holes. Relaxation effects have been characterized through successive irradiations steps and have been again well described with the defined model at qualitative level: recombination centers created by the irradiation induce long term alteration on the electric properties, especially the effective bulk conductivity. One-month relaxation does not allow a complete recovery of the material initial charging behavior.

  4. Radiation induced conductivity in space dielectric materials

    NASA Astrophysics Data System (ADS)

    Hanna, R.; Paulmier, T.; Molinie, P.; Belhaj, M.; Dirassen, B.; Payan, D.; Balcon, N.

    2014-01-01

    The radiation-induced conductivity of some polymers was described mainly in literature by a competition between ionization, trapping/detrapping, and recombination processes or by radiation assisted ageing mechanisms. Our aim is to revise the effect of the aforementioned mechanisms on the complex evolution of Teflon® FEP under space representative ionizing radiation. Through the definition of a new experimental protocol, revealing the effect of radiation dose and relaxation time, we have been able to demonstrate that the trapping/recombination model devised in this study agrees correctly with the observed experimental phenomenology at qualitative level and allows describing very well the evolution of radiation induced conductivity with irradiation time (or received radiation dose). According to this model, the complex behavior observed on Teflon® FEP may be basically ascribed to the competition between electron/hole pairs generation and recombination: electrons are deeply trapped and act as recombination centers for free holes. Relaxation effects have been characterized through successive irradiations steps and have been again well described with the defined model at qualitative level: recombination centers created by the irradiation induce long term alteration on the electric properties, especially the effective bulk conductivity. One-month relaxation does not allow a complete recovery of the material initial charging behavior.

  5. Mouse models for radiation-induced cancers.

    PubMed

    Rivina, Leena; Davoren, Michael J; Schiestl, Robert H

    2016-09-01

    Potential ionising radiation exposure scenarios are varied, but all bring risks beyond the simple issues of short-term survival. Whether accidentally exposed to a single, whole-body dose in an act of terrorism or purposefully exposed to fractionated doses as part of a therapeutic regimen, radiation exposure carries the consequence of elevated cancer risk. The long-term impact of both intentional and unintentional exposure could potentially be mitigated by treatments specifically developed to limit the mutations and precancerous replication that ensue in the wake of irradiation The development of such agents would undoubtedly require a substantial degree of in vitro testing, but in order to accurately recapitulate the complex process of radiation-induced carcinogenesis, well-understood animal models are necessary. Inbred strains of the laboratory mouse, Mus musculus, present the most logical choice due to the high number of molecular and physiological similarities they share with humans. Their small size, high rate of breeding and fully sequenced genome further increase its value for use in cancer research. This chapter will review relevant m. musculus inbred and F1 hybrid animals of radiation-induced myeloid leukemia, thymic lymphoma, breast and lung cancers. Method of cancer induction and associated molecular pathologies will also be described for each model. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Effects of subdiaphragmatic vagotomy on the acquisition of a radiation-induced conditioned taste aversion

    SciTech Connect

    Hunt, W.A.; Rabin, B.M.; Lee, J.

    1987-01-01

    The effect of subdiaphragmatic vagotomy on the acquisition of a radiation-induced taste aversion was examined to assess the importance of the vagus nerve in transmitting information on the peripheral toxicity of radiation to the brain. Vagotomy had no effect on taste aversion learning, consistent with reports using other toxins. The data support the involvement of a blood-borne factor in the acquisition of taste aversion induced by ionizing radiation.

  7. Radiation-induced heart disease in lung cancer radiotherapy

    PubMed Central

    Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

    2016-01-01

    Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

  8. Role of neurotensin in radiation-induced hypothermia in rats

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H. )

    1991-05-01

    The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin.

  9. Extracellular Adenosine Production by ecto-5'-Nucleotidase (CD73) Enhances Radiation-Induced Lung Fibrosis.

    PubMed

    Wirsdörfer, Florian; de Leve, Simone; Cappuccini, Federica; Eldh, Therese; Meyer, Alina V; Gau, Eva; Thompson, Linda F; Chen, Ning-Yuan; Karmouty-Quintana, Harry; Fischer, Ute; Kasper, Michael; Klein, Diana; Ritchey, Jerry W; Blackburn, Michael R; Westendorf, Astrid M; Stuschke, Martin; Jendrossek, Verena

    2016-05-15

    Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment is available. In this study, we investigated the role of the extracellular adenosine as generated by the ecto-5'-nucleotidase CD73 in fibrosis development after thoracic irradiation. Exposure of wild-type C57BL/6 mice to a single dose (15 Gray) of whole thorax irradiation triggered a progressive increase in CD73 activity in the lung between 3 and 30 weeks postirradiation. In parallel, adenosine levels in bronchoalveolar lavage fluid (BALF) were increased by approximately 3-fold. Histologic evidence of lung fibrosis was observed by 25 weeks after irradiation. Conversely, CD73-deficient mice failed to accumulate adenosine in BALF and exhibited significantly less radiation-induced lung fibrosis (P < 0.010). Furthermore, treatment of wild-type mice with pegylated adenosine deaminase or CD73 antibodies also significantly reduced radiation-induced lung fibrosis. Taken together, our findings demonstrate that CD73 potentiates radiation-induced lung fibrosis, suggesting that existing pharmacologic strategies for modulating adenosine may be effective in limiting lung toxicities associated with the treatment of thoracic malignancies. Cancer Res; 76(10); 3045-56. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Inactivation of Kupffer Cells by Gadolinium Chloride Protects Murine Liver From Radiation-Induced Apoptosis

    SciTech Connect

    Du Shisuo; Qiang Min; Zeng Zhaochong; Ke Aiwu; Ji Yuan; Zhang Zhengyu; Zeng Haiying; Liu Zhongshan

    2010-03-15

    Purpose: To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis. Materials and Methods: A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining. Results: The expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3. Conclusion: Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage.

  11. Triptolide Mitigates Radiation-Induced Pulmonary Fibrosis.

    PubMed

    Yang, Shanmin; Zhang, Mei; Chen, Chun; Cao, Yongbin; Tian, Yeping; Guo, Yangsong; Zhang, Bingrong; Wang, Xiaohui; Yin, Liangjie; Zhang, Zhenhuan; O'Dell, Walter; Okunieff, Paul; Zhang, Lurong

    2015-11-01

    Triptolide (TPL) may mitigate radiation-induced late pulmonary side effects through its inhibition of global pro-inflammatory cytokines. In this study, we evaluated the effect of TPL in C57BL/6 mice, the animals were exposed to radiation with vehicle (15 Gy), radiation with TPL (0.25 mg/kg i.v., twice weekly for 1, 2 and 3 months), radiation and celecoxib (CLX) (30 mg/kg) and sham irradiation. Cultured supernatant of irradiated RAW 264.7 and MLE-15 cells and lung lysate in different groups were enzyme-linked immunosorbent assays at 33 h. Respiratory rate, pulmonary compliance and pulmonary density were measured at 5 months in all groups. The groups exposed to radiation with vehicle and radiation with TPL exhibited significant differences in respiratory rate and pulmonary compliance (480 ± 75/min vs. 378 ± 76/min; 0.6 ± 0.1 ml/cm H2O/p kg vs. 0.9 ± 0.2 ml/cm H2O/p kg). Seventeen cytokines were significantly reduced in the lung lysate of the radiation exposure with TPL group at 5 months compared to that of the radiation with vehicle group, including profibrotic cytokines implicated in pulmonary fibrosis, such as IL-1β, TGF- β1 and IL-13. The radiation exposure with TPL mice exhibited a 41% reduction of pulmonary density and a 25% reduction of hydroxyproline in the lung, compared to that of radiation with vehicle mice. The trichrome-stained area of fibrotic foci and pathological scaling in sections of the mice treated with radiation and TPL mice were significantly less than those of the radiation with vehicle-treated group. In addition, the radiation with TPL-treated mice exhibited a trend of improved survival rate compared to that of the radiation with vehicle-treated mice at 5 months (83% vs. 53%). Three radiation-induced profibrotic cytokines in the radiation with vehicle-treated group were significantly reduced by TPL treatment, and this partly contributed to the trend of improved survival rate and pulmonary density and function and the decreased severity of

  12. The potential clinical impact of probiotic treatment for the prevention and/or anti-inflammatory therapeutic effect against radiation induced intestinal mucositis. A review.

    PubMed

    Maria-Aggeliki, Kalogeridi S; Nikolaos, Kelekis L; Kyrias, George M; Vassilis, Kouloulias E

    2009-11-01

    Although pelvic radiotherapy, either alone or combined with chemotherapy, has proved to be successful in the treatment of patients with rectal, gynecological and urologic cancer, it is not devoid of side effects. Among patients receiving pelvic radiotherapy more than 70% develop acute inflammatory changes causing gastrointestinal symptoms during treatment. The most frequently reported symptom related to radiation-induced intestinal mucositis is diarrhea. Among nutritional interventions used to manage radiation-induced diarrhoea, probiotics has gained popularity. This term describes organisms and substances that improve microbial balance in the intestines. Although encouraging results have been obtained in clinical trials, the potential of oral probiotics to manage gastrointestinal symptoms needs further research. The article also outlines recent patents related to probiotics therapy to reduce radiation induced mocositis.

  13. Radiation-induced mutation at minisatellite loci

    SciTech Connect

    Dubrova, Y.E. |; Nesterov, V.N.; Krouchinsky, N.G.

    1997-10-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of {gamma}-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure {sup 137}Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed.

  14. Radiation-induced mutations and plant breeding

    SciTech Connect

    Naqvi, S.H.M.

    1985-01-01

    Ionizing radiation could cause genetic changes in an organism and could modify gene linkages. The induction of mutation through radiation is random and the probability of getting the desired genetic change is low but can be increased by manipulating different parameters such as dose rate, physical conditions under which the material has been irradiated, etc. Induced mutations have been used as a supplement to conventional plant breeding, particularly for creating genetic variability for specific characters such as improved plant structure, pest and disease resistance, and desired changes in maturity period; more than 200 varieties of crop plants have been developed by this technique. The Pakistan Atomic Energy Commission has used this technique fruitfully to evolve better germplasm in cotton, rice, chickpea, wheat and mungbean; some of the mutants have become popular commercial varieties. This paper describes some uses of radiation induced mutations and the results achieved in Pakistan so far.

  15. Transesophageal Echocardiography and Radiation-induced Damages

    PubMed Central

    Cottini, Marzia; Polizzi, Vincenzo; Pino, Paolo Giuseppe; Buffa, Vitaliano; Musumeci, Francesco

    2016-01-01

    The long-term sequelae of mantle therapy include, especially lung and cardiac disease but also involve the vessels and the organs in the neck and thorax (such as thyroid, aorta, and esophagus). We presented the case of 66-year-old female admitted for congestive heart failure in radiation-induced heart disease. The patient had undergone to massive radiotherapy 42 years ago for Hodgkin's disease (type 1A). Transesophageal echocardiography was performed unsuccessfully with difficulty because of the rigidity and impedance of esophageal walls. Our case is an extraordinary report of radiotherapy's latency effect as a result of dramatic changes in the structure of mediastinum, in particular in the esophagus, causing unavailability of a transesophageal echocardiogram. PMID:27867461

  16. Radiation induced carcinoma of the larynx

    SciTech Connect

    Amendola, B.E.; Amendola, M.A.; McClatchey, K.D.

    1985-07-01

    A squamous cell carcinoma presented in a 20 year old female nonsmoker three years after receiving a high dosage of radiation therapy to the base of the skull, face and entire neuroaxis and intense combination chemotherapy for a parameningeal rhabdomyosarcoma of the paranasal sinuses is reported. The larynx received a dose of about 3,500 rads over an eight week period. This dosage in conjunction with the associated intense chemotherapy regimen given to the patient may explain the appearance of a radiation induced tumor in an unusually short latent period. This certainly represents a risk in young patients in whom an aggressive combined approach is taken and the physician should be aware of.

  17. Epigallocatechin-3-gallate ameliorates radiation-induced acute skin damage in breast cancer patients undergoing adjuvant radiotherapy

    PubMed Central

    Zhu, Wanqi; Jia, Li; Chen, Guanxuan; Zhao, Hanxi; Sun, Xiaorong; Meng, Xiangjiao; Zhao, Xianguang; Xing, Ligang; Yu, Jinming; Zheng, Meizhu

    2016-01-01

    There are few effective treatment options for radiation-induced dermatitis in breast cancer patients. We conducted a single-arm trial to tested the hypothesis that topical epigallocatechin-3-gallate (EGCG) is effective against radiation-induced dermatitis in breast cancer patients undergoing radiotherapy. Forty-nine patients participated in this study. The patients underwent mastectomy followed by adjuvant radiotherapy. Topical EGCG was applied daily, starting when grade I dermatitis appeared and ending two weeks after radiotherapy. The maximum dermatitis observed during the EGCG treatment was as follows: Grade 1 toxicity, 71.4% (35 patients); grade 2 toxicity, 28.6% (14 patients); there were no patients with grade 3 or 4 toxicity. The majority of the radiation-induced dermatitis was observed 1 week after the end of radiotherapy. EGCG reduced the pain in 85.7% of patients, burning-feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6%. These findings suggest topical EGCG may be an effective treatment for radiation-induced dermatitis and has acceptable toxicity. PMID:27224910

  18. [Medical prevention and treatment of radiation-induced pulmonary complications].

    PubMed

    Vallard, A; Rancoule, C; Le Floch, H; Guy, J-B; Espenel, S; Le Péchoux, C; Deutsch, É; Magné, N; Chargari, C

    2017-08-01

    Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  19. Radiation-induced osteosarcoma of the sphenoid bone

    SciTech Connect

    Tanaka, S.; Nishio, S.; Morioka, T.; Fukui, M.; Kitamura, K.; Hikita, K. )

    1989-10-01

    The case of a patient who developed osteosarcoma in the sphenoid bone 15 years after radiation therapy for a craniopharyngioma is reported. Radiation-induced osteosarcoma of the sphenoid bone has not been reported previously. Reported cases of radiation-induced osteosarcomas are reviewed.

  20. Preliminary results of a phase I/II study of sodium pentosanpolysulfate in the treatment of chronic radiation-induced proctitis

    SciTech Connect

    Grigsby, P.W.; Pilepich, M.V.; Parsons, C.L. )

    1990-02-01

    This is a report of a phase I/II study of 13 patients treated with sodium pentosanpolysulfate (PPS) for chronic radiation-induced proctitis. A complete response was obtained in 82%, a partial response occurred in 9%, and 9% failed to respond to therapy. No significant toxicity was observed. It is concluded that PPS is an effective treatment for chronic radiation-induced proctitis and a phase III randomized, double-blind study of PPS versus placebo is planned.

  1. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature

    PubMed Central

    Salvo, N.; Barnes, E.; van Draanen, J.; Stacey, E.; Mitera, G.; Breen, D.; Giotis, A.; Czarnota, G.; Pang, J.; De Angelis, C.

    2010-01-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus

  2. Radiation-induced complications in prostate cancer patients treated with radiotherapy

    SciTech Connect

    Azuddin, A. Yusof; Rahman, I. Abdul; Mohamed, F.; Siah, N. J.; Saadc, M.; Ismail, F.

    2014-09-03

    The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60{sub rectum}, rectal mean dose and NTCP{sub rectum} with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

  3. Radiation-induced complications in prostate cancer patients treated with radiotherapy

    NASA Astrophysics Data System (ADS)

    Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

    2014-09-01

    The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

  4. Nocifensive Behaviors in Mice with Radiation-Induced Oral Mucositis.

    PubMed

    Nolan, Michael W; Long, C Tyler; Marcus, Karen L; Sarmadi, Shayan; Roback, Donald M; Fukuyama, Tomoki; Baeumer, Wolfgang; Lascelles, B Duncan X

    2017-02-10

    Oral mucositis can result in significant dysphagia, and is the most common dose-limiting acute toxicity in head and neck cancer patients receiving chemoradiotherapy. There is a critical need to determine the cellular and molecular mechanisms that underlie radiotherapy-associated discomfort in patients with mucositis. The objective was to induce oral mucositis in mice, using a clinical linear accelerator, and to quantify resultant discomfort, and characterize peripheral sensitization. A clinical linear accelerator was used to deliver ionizing radiation to the oral cavity of mice. Mucositis severity scoring, and various behavioral assays were performed to quantify bouts of orofacial wiping and scratching, bite force, gnawing behavior and burrowing activity. Calcium imaging was performed on neurons of the trigeminal ganglia. Glossitis was induced with a single fraction of at least 27 Gy. Body weight decreased and subsequently returned to baseline, in concert with development and resolution of mucositis, which was worst at day 10 and 11 postirradiation, however was resolved within another 10 days. Neither bite force, nor gnawing behavior were measurably affected. However, burrowing activity was decreased, and both facial wiping and scratching were increased while mice had visible mucositis lesions. Sensory nerves of irradiated mice were more responsive to histamine, tumor necrosis factor alpha and capsaicin. Radiation-induced glossitis is associated with hyper-reactivity of sensory neurons in the trigeminal ganglia of mice, and is accompanied by several behaviors indicative of both itch and pain. These data validate an appropriate model for cancer treatment related discomfort in humans.

  5. Radiation-induced degradation of aqueous fluoranthene

    NASA Astrophysics Data System (ADS)

    Popov, Petar; Getoff, Nikola

    2005-01-01

    The radiation-induced degradation of fluoranthene (FA) in slightly alkaline aqueous solution was investigated in the presence of air as well as of N 2O. Depending on the starting FA-concentration the determined Gi(-FA) was 0.34 for 1×10 -5 mol/l FA upto 0.67 for 4.6×10 -5 mol/l FA. As major radiolytic products found by HPLC-analysis were: 9-fluorene carboxylic acid ( Gi =0.006), 9-fluorenone ( Gi=0.004) and fluorene ( Gi=0.002) in addition to a mixture of carboxylic acids and aldehydes. In the presence of N 2O (90% OH, 10% H) practically the same products were observed, however in this case the yield of the carboxylic acids was about 2-times higher than in solutions saturated with air, but 4-times less aldehydes, resp. For illustration of the rather complicated degradation process a probable reaction mechanism is presented.

  6. Radiation-induced segregation, hardening, and IASCC

    SciTech Connect

    Eason, E.D.; Nelson, E.E.

    1995-12-31

    Intergranular cracking has been discovered after extended radiation exposure in several boiling water reactor (BWR) internal components made of austenitic stainless steel and nickel-based alloys. There are fewer field observations of intergranular cracking in pressurized water reactors (PWR), but failures have occurred in bolts, springs, and fuel cladding. There is concern for other PWR components, some of which will receive greater radiation doses than BWR components during the plant lifetime. This paper presents the results of an investigation on the connection between radiation induced segregation, hardening and irradiation-assisted stress corrosion cracking (IASCC). A data base was developed containing the available data on austenitic stainless steel where the grain boundary composition was measured by Field Emission Gun-Scanning Transmission Election Microscopy (FEG-STEM), the stress corrosion susceptibility was measured by constant extension rate tests (CERT) in light water reactor environments, some estimate of irradiated strength was available and the irradiation was conducted in a power reactor. The data base was analyzed using advanced data analysis techniques, including tree-structured pattern recognition and transformation analysis codes. The most sensitive variables and optimal modeling forms were identified using these techniques, then preliminary models were calibrated using nonlinear least squares. The results suggest that more than one mechanism causes IASCC.

  7. Radiation-induced valvular heart disease.

    PubMed

    Gujral, Dorothy M; Lloyd, Guy; Bhattacharyya, Sanjeev

    2016-02-15

    Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Current concepts in rectal cancer.

    PubMed

    Fleshman, James W; Smallwood, Nathan

    2015-03-01

    The history of rectal cancer management informs current therapy and points us in the direction of future improvements. Multidisciplinary team management of rectal cancer will move us to personalized treatment for individuals with rectal cancer in all stages.

  9. Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

    PubMed Central

    Weiner, Joseph Paul; Wong, Andrew Thomas; Schwartz, David; Martinez, Manuel; Aytaman, Ayse; Schreiber, David

    2016-01-01

    Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting head-to-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient’s symptoms. For those cases that are clinically asymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases. PMID:27610010

  10. Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases

    PubMed Central

    Wang, Yingying; Boerma, Marjan; Zhou, Daohong

    2016-01-01

    Exposure to ionizing radiation induces not only apoptosis but also senescence. While the role of endothelial cell apoptosis in mediating radiation-induced acute tissue injury has been extensively studied, little is known about the role of endothelial cell senescence in the pathogenesis of radiation-induced late effects. Senescent endothelial cells exhibit decreased production of nitric oxide and expression of thrombomodulin, increased expression of adhesion molecules, elevated production of reactive oxygen species and inflammatory cytokines and an inability to proliferate and form capillary-like structures in vitro. These findings suggest that endothelial cell senescence can lead to endothelial dysfunction by dysregulation of vasodilation and hemostasis, induction of oxidative stress and inflammation and inhibition of angiogenesis, which can potentially contribute to radiation-induced late effects such as cardiovascular diseases (CVDs). In this article, we discuss the mechanisms by which radiation induces endothelial cell senescence, the roles of endothelial cell senescence in radiation-induced CVDs and potential strategies to prevent, mitigate and treat radiation-induced CVDs by targeting senescent endothelial cells. PMID:27387862

  11. Neoadjuvant Treatment in Rectal Cancer: Actual Status

    PubMed Central

    Garajová, Ingrid; Di Girolamo, Stefania; de Rosa, Francesco; Corbelli, Jody; Agostini, Valentina; Biasco, Guido; Brandi, Giovanni

    2011-01-01

    Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID:22295206

  12. Chemoradiation of rectal cancer.

    PubMed

    Arrazubi, V; Suárez, J; Novas, P; Pérez-Hoyos, M T; Vera, R; Martínez Del Prado, P

    2013-02-01

    The treatment of locally advanced rectal cancer is a challenge. Surgery, chemotherapy and radiotherapy comprise the multimodal therapy that is administered in most cases. Therefore, a multidisciplinary approach is required. Because this cancer has a high rate of local recurrence, efforts have been made to improve clinical outcomes while minimizing toxicity and maintaining quality of life. Thus, total mesorectal excision technique was developed as the standard surgery, and chemotherapy and radiotherapy have been established as neoadjuvant treatment. Both approaches reduce locoregional relapse. Two neoadjuvant treatments have emerged as standards of care: short-course radiotherapy and long-course chemoradiotherapy with fluoropyrimidines; however, long-course chemoradiotherapy might be more appropriate for low-lying neoplasias, bulky tumours or tumours with near-circumferential margins. If neoadjuvant treatment is not administered and locally advanced stage is demonstrated in surgical specimens, adjuvant chemoradiotherapy is recommended. The addition of chemotherapy to the treatment regimen confers a significant benefit. Adjuvant chemotherapy is widely accepted despite scarce evidence of its benefit. The optimal time for surgery after neoadjuvant therapy, the treatment of low-risk T3N0 neoplasms, the convenience of avoiding radiotherapy in some cases and tailoring treatment to pathological response have been recurrent subjects of debate that warrant more extensive research. Adding new drugs, changing the treatment sequence and selecting the treatment based on prognostic or predictive factors other than stage remain experimental.

  13. Radiation-Induced Alopecia after Endovascular Embolization under Fluoroscopy

    PubMed Central

    Ounsakul, Vipawee; Iamsumang, Wimolsiri

    2016-01-01

    Radiation-induced alopecia after fluoroscopically guided procedures is becoming more common due to an increasing use of endovascular procedures. It is characterized by geometric shapes of nonscarring alopecia related to the area of radiation. We report a case of a 46-year-old man presenting with asymptomatic, sharply demarcated rectangular, nonscarring alopecic patch on the occipital scalp following cerebral angiography with fistula embolization under fluoroscopy. His presentations were compatible with radiation-induced alopecia. Herein, we also report a novel scalp dermoscopic finding of blue-grey dots in a target pattern around yellow dots and follicles, which we detected in the lesion of radiation-induced alopecia. PMID:28074164

  14. Lipotransfer for radiation-induced skin fibrosis.

    PubMed

    Kumar, R; Griffin, M; Adigbli, G; Kalavrezos, N; Butler, P E M

    2016-07-01

    Radiation-induced fibrosis (RIF) is a late complication of radiotherapy that results in progressive functional and cosmetic impairment. Autologous fat has emerged as an option for soft tissue reconstruction. There are also sporadic reports suggesting regression of fibrosis following regional lipotransfer. This systematic review aimed to identify cellular mechanisms driving RIF, and the potential role of lipotransfer in attenuating these processes. PubMed, OVID and Google Scholar databases were searched to identify all original articles regarding lipotransfer for RIF. All articles describing irradiated fibroblast or myofibroblast behaviour were included. Data elucidating the mechanisms of RIF, role of lipotransfer in RIF and methods to quantify fibrosis were extracted. Ninety-eight studies met the inclusion criteria. A single, definitive model of RIF is yet to be established, but four cellular mechanisms were identified through in vitro studies. Twenty-one studies identified connective tissue growth factor and transforming growth factor β1 cytokines as drivers of fibrotic cascades. Hypoxia was demonstrated to propagate fibrogenesis in three studies. Oxidative stress from the release of reactive oxygen species and free radicals was also linked to RIF in 11 studies. Purified autologous fat grafts contain cellular and non-cellular properties that potentially interact with these processes. Six methods for quantifying fibrotic changes were evaluated including durometry, ultrasound shear wave elastography, thermography, dark field imaging, and laser Doppler and laser speckle flowmetry. Understanding how lipotransfer causes regression of RIF remains unclear; there are a number of new hypotheses for future research. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  15. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    SciTech Connect

    Rauch, Philipp J.; Park, Henry S.; Knisely, Jonathan P.S.; Chiang, Veronica L.; Vortmeyer, Alexander O.

    2012-05-01

    Purpose: Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy. Methods and Materials: We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively. Results: We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis. Conclusions: We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.

  16. Mouse models of radiation-induced cancers.

    PubMed

    Rivina, Leena; Schiestl, Robert

    2013-01-01

    Radiation-induced (RI) secondary cancers were not a major clinical concern even as little as 15 years ago. However, advances in cancer diagnostics, therapy, and supportive care have saved numerous lives and many former cancer patients are now living for 5, 10, 20, and more years beyond their initial diagnosis. The majority of these patients have received radiotherapy as a part of their treatment regimen and are now beginning to develop secondary cancers arising from normal tissue exposure to damaging effects of ionizing radiation. Because historically patients rarely survived past the extended latency periods inherent to these RI cancers, very little effort was channeled towards the research leading to the development of therapeutic agents intended to prevent or ameliorate oncogenic effects of normal tissue exposure to radiation. The number of RI cancers is expected to increase very rapidly in the near future, but the field of cancer biology might not be prepared to address important issues related to this phenomena. One such issue is the ability to accurately differentiate between primary tumors and de novo arising secondary tumors in the same patient. Another issue is the lack of therapeutic agents intended to reduce such cancers in the future. To address these issues, large-scale epidemiological studies must be supplemented with appropriate animal modeling studies. This work reviews relevant mouse (Mus musculus) models of inbred and F1 animals and methodologies of induction of most relevant radiation-associated cancers: leukemia, lymphoma, and lung and breast cancers. Where available, underlying molecular pathologies are included. © 2013 Elsevier Inc. All rights reserved.

  17. Protective effect of esculentoside A on radiation-induced dermatitis and fibrosis

    SciTech Connect

    Xiao Zhenyu; Su Ying; Yang Shanmin; Yin Liangjie; Wang Wei; Yi Yanghua; Fenton, Bruce M.; Zhang Lurong; Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu

    2006-07-01

    Purpose: To investigate the effect of esculentoside A (EsA) on radiation-induced cutaneous and fibrovascular toxicity and its possible molecular mechanisms, both in vivo and in vitro. Methods and Materials: Mice received drug intervention 18 hours before 30 Gy to the right hind leg. Alterations in several cytokines expressed in skin tissue 2 days after irradiation were determined by ELISA. Early skin toxicity was evaluated 3 to 4 weeks after irradiation by skin scoring, and both tissue contraction and expression of TGF-{beta}1 were determined for soft-tissue fibrosis 3 months after irradiation. In vitro, the effect of EsA on radiation-induced nitric oxide (NO) and cytokine production in different cell types was measured by application of 2, 4, and 8 Gy. Results: In vivo, EsA reduced levels of IL-1{alpha}, MCP-1, VEGF, and TGF-{beta}1 in cutaneous tissue and reduced soft-tissue toxicity. In vitro, EsA inhibited the IL-1{alpha} ordinarily produced after 4 Gy in A431 cells. In Raw264.7 cells, EsA reduced levels of IL-1{alpha}, IL-1{beta}, and NO production costimulated by radiation and lipopolysaccharide (LPS). In L-929 cells, EsA inhibited VEGF, TNF, and MCP-1 production at 2, 4, and 8 Gy. Conclusions: Esculentoside A protects soft tissues against radiation toxicity through inhibiting the production of several proinflammatory cytokines and inflammatory mediators in epithelial cells, macrophages, fibroblasts, and skin tissue.

  18. Influence of Rough Hair Coats and Steroidal Implants on Hair Growth, Rectal Temperatures, and Sweating by Steers Grazed on Toxic Tall Fescue During the Summer

    USDA-ARS?s Scientific Manuscript database

    Cattle grazing toxic tall fescue months [Schedonorus arundinaceus (Schreb.)] typically retain their rough hair coats into the summer, which can exacerbate heat stress induced by fescue toxicosis. Further, previous research has indicated that progesterone and estradiol implants may increase body tem...

  19. Radiation-induced endometriosis in Macaca mulatta

    SciTech Connect

    Fanton, J.W.; Golden, J.G. )

    1991-05-01

    Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.

  20. Pathogenesis and Prevention of Radiation-induced Myocardial Fibrosis

    PubMed

    Liu, Li Kun; Ouyang, Weiwei; Zhao, Xing; Su, Sheng Fa; Yang, Yan; Ding, Wen Jin; Luo, Da Xian; He, Zhi Xu; Lu, Bing

    2017-03-01

    Radiation therapy is one of the most important methods for the treatment of malignant tumors. However, in radiotherapy for thoracic tumors such as breast cancer, lung cancer, esophageal cancer, and mediastinal lymphoma, the heart, located in the mediastinum, is inevitably affected by the irradiation, leading to pericardial disease, myocardial fibrosis, coronary artery disease, valvular lesions, and cardiac conduction system injury, which are considered radiation-induced heart diseases. Delayed cardiac injury especially myocardial fibrosis is more prominent, and its incidence is as high as 20–80%. Myocardial fibrosis is the final stage of radiation-induced heart diseases, and it increases the stiffness of the myocardium and decreases myocardial systolic and diastolic function, resulting in myocardial electrical physiological disorder, arrhythmia, incomplete heart function, or even sudden death. This article reviews the pathogenesis and prevention of radiation-induced myocardial fibrosis for providing references for the prevention and treatment of radiation-induced myocardial fibrosis. Creative Commons Attribution License

  1. Radiation-induced charge trapping in bipolar base oxides

    SciTech Connect

    Fleetwood, D.M.; Riewe, L.C.; Witczak, Schrimpf, R.D.

    1996-03-01

    Capacitance-voltage and thermally stimulated current methods are used to investigate radiation induced charge trapping in bipolar base oxides. Results are compared with models of oxide and interface trap charge buildup at low electric fields.

  2. Rectal diverticulitis mimicking rectal carcinoma with intestinal obstruction: case report.

    PubMed

    Özçelik, Ümit; Bircan, Hüseyin Yüce; Eren, Eryiğit; Demiralay, Ebru; Işıklar, İclal; Demirağ, Alp; Moray, Gökhan

    2015-01-01

    Although diverticular disease of the colon is common, the occurrence of rectal diverticula is extremely rare with only sporadic reports in the literature since 1911. Symptomatic rectal diverticula are seen even less frequently, and surgical intervention is needed for only complicated cases. Here we report the case of a 63-year-old woman presenting with rectal diverticulitis mimicking rectal carcinoma with intestinal obstruction.

  3. Mitigation of whole-body gamma radiation-induced damages by Clerodendron infortunatum in mammalian organisms.

    PubMed

    Chacko, Tiju; Menon, Aditya; Majeed, Teeju; Nair, Sivaprabha V; John, Nithu Sara; Nair, Cherupally Krishnan Krishnan

    2016-11-17

    Several phytoceuticals and extracts of medicinal plants are reported to mitigate deleterious effects of ionizing radiation. The potential of hydro-alcoholic extract of Clerodendron infortunatum (CIE) for providing protection to mice exposed to gamma radiation was investigated. Oral administration of CIE bestowed a survival advantage to mice exposed to lethal doses of gamma radiation. Radiation-induced depletion of the total blood count and bone marrow cellularity were prevented by treatment with CIE. Damage to the cellular DNA (as was evident from the comet assay and the micronucleus index) was also found to be decreased upon CIE administration. Radiation-induced damages to intestinal crypt cells was also reduced by CIE. Studies on gene expression in intestinal cells revealed that there was a marked increase in the Bax/Bcl-2 ratio in mice exposed to whole-body 4 Gy gamma radiation, and that administration of CIE resulted in significant lowering of this ratio, suggestive of reduction of radiation-induced apoptosis. Also, in the intestinal tissue of irradiated animals, following CIE treatment, levels of expression of the DNA repair gene Atm were found to be elevated, and there was reduction in the expression of the inflammatory Cox-2 gene. Thus, our results suggest a beneficial use of Clerodendron infortunatum for mitigating radiation toxicity.

  4. Inhibition of CDK4/6 protects against radiation-induced intestinal injury in mice

    PubMed Central

    Wei, Liang; Leibowitz, Brian J.; Wang, Xinwei; Epperly, Michael; Greenberger, Joel; Zhang, Lin

    2016-01-01

    Radiotherapy causes dose-limiting toxicity and long-term complications in rapidly renewing tissues, including the gastrointestinal tract. Currently, there is no FDA-approved agent for the prevention or treatment of radiation-induced intestinal injury. In this study, we have shown that PD 0332991 (PD), an FDA-approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents radiation-induced lethal intestinal injury in mice. Treating mice with PD or a structurally distinct CDK4/6 inhibitor prior to radiation blocked proliferation and crypt apoptosis and improved crypt regeneration. PD treatment also enhanced LGR5+ stem cell survival and regeneration after radiation. PD was an on-target inhibitor of RB phosphorylation and blocked G1/S transition in the intestinal crypts. PD treatment strongly but reversibly inhibited radiation-induced p53 activation, which blocked p53-upregulated modulator of apoptosis–dependent (PUMA-dependent) apoptosis without affecting p21-dependent suppression of DNA damage accumulation, with a repair bias toward nonhomologous end joining. Further, deletion of PUMA synergized with PD treatment for even greater intestinal radioprotection. Our results demonstrate that the cell cycle critically regulates the DNA damage response and survival of intestinal stem cells and support the concept that pharmacological quiescence is a potentially highly effective and selective strategy for intestinal radioprotection. PMID:27701148

  5. Mint oil (Mentha spicata Linn.) offers behavioral radioprotection: a radiation-induced conditioned taste aversion study.

    PubMed

    Haksar, A; Sharma, A; Chawla, R; Kumar, Raj; Lahiri, S S; Islam, F; Arora, M P; Sharma, R K; Tripathi, R P; Arora, Rajesh

    2009-02-01

    Mentha spicata Linn. (mint), a herb well known for its gastroprotective properties in the traditional system of medicine has been shown to protect against radiation-induced lethality, and recently its constituents have been found to possess calcium channel antagonizing properties. The present study examined the behavioral radioprotective efficacy of mint oil (obtained from Mentha spicata), particularly in mitigating radiation-induced conditioned taste aversion (CTA), which has been proposed as a behavioral endpoint that is mediated by the toxic effects of gamma radiation on peripheral systems, primarily the gastrointestinal system in the Sprague-Dawley rat model. Intraperitoneal administration of Mentha spicata oil 10% (v/v), 1 h before 2 Gy gamma radiation, was found to render significant radioprotection against CTA (p < 0.05), by blocking the saccharin avoidance response within 5 post-treatment observational days, with the highest saccharin intake being observed on day 5. This finding clearly demonstrates that gastroprotective and calcium channel antagonizing properties of Mentha spicata can be effectively utilized in preventing radiation-induced behavioral changes. Copyright (c) 2008 John Wiley & Sons, Ltd.

  6. Radar detection of radiation-induced ionization in air

    DOEpatents

    Gopalsami, Nachappa; Heifetz, Alexander; Chien, Hual-Te; Liao, Shaolin; Koehl, Eugene R.; Raptis, Apostolos C.

    2015-07-21

    A millimeter wave measurement system has been developed for remote detection of airborne nuclear radiation, based on electromagnetic scattering from radiation-induced ionization in air. Specifically, methods of monitoring radiation-induced ionization of air have been investigated, and the ionized air has been identified as a source of millimeter wave radar reflection, which can be utilized to determine the size and strength of a radiation source.

  7. Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy

    NASA Astrophysics Data System (ADS)

    Bednarz, Bryan; Besemer, Abigail

    2017-09-01

    The use of radionuclide therapy in the clinical setting is expected to increase significantly over the next decade. There is an important need to understand the radiation-induced second cancer risk associated with these procedures. In this study the radiation-induced cancer risk in five radionuclide therapy patients was investigated. These patients underwent serial SPECT imaging scans following injection as part of a clinical trial testing the efficacy of a 131Iodine-labeled radiopharmaceutical. Using these datasets the committed absorbed doses to multiple sensitive structures were calculated using RAPID, which is a novel Monte Carlo-based 3D dosimetry platform developed for personalized dosimetry. The excess relative risk (ERR) for radiation-induced cancer in these structures was then derived from these dose estimates following the recommendations set forth in the BEIR VII report. The radiation-induced leukemia ERR was highest among all sites considered reaching a maximum value of approximately 4.5. The radiation-induced cancer risk in the kidneys, liver and spleen ranged between 0.3 and 1.3. The lifetime attributable risks (LARs) were also calculated, which ranged from 30 to 1700 cancers per 100,000 persons and were highest for leukemia and the liver for both males and females followed by radiation-induced spleen and kidney cancer. The risks associated with radionuclide therapy are similar to the risk associated with external beam radiation therapy.

  8. [Update in radiation-induced neoplasms: genetic studies].

    PubMed

    Chauveinc, Laurent; Lefevre, Sandrine; Malfoy, Bernard; Dutrillaux, Bernard

    2002-02-01

    Radiation induced tumors are a possible (very) late complications of radiotherapy. The evaluation of the risks of radiation-induced tumors has been presented in different epidemiological studies, with the evaluation of the relative risk for different tissues. But, the genetic studies are rare, and no global theory exists. Two cytogenetic profiles are described, one with translocations and one with genetic material losses, evoking two different genetic evolutions. Two questions are stated. What are the radiation-induced genetic mechanisms? Is it possible to differentiate the radiation-induced and spontaneous tumors with genetic approaches? With 37 cytogenetic cases, 12 analyzed in our laboratory, the radiation-induced tumors were characterized by genetic material losses. An anti-oncogenic evolution is probable. A new molecularly study confirm these results. Only thyroid tumors do not have this evolution. For tumors with simple karyotype, like meningioma, radiation-induced tumors seem to be more complex than spontaneous tumors. But for the others, the differentiation is impossible to be done with cytogenetic. The mechanism of the chromosomic material losses in unknown, but some hypothesis are discussed.

  9. Tristetraprolin mediates radiation-induced TNF-α production in lung macrophages.

    PubMed

    Ray, Dipankar; Shukla, Shirish; Allam, Uday Sankar; Helman, Abigail; Ramanand, Susmita Gurjar; Tran, Linda; Bassetti, Michael; Krishnamurthy, Pranathi Meda; Rumschlag, Matthew; Paulsen, Michelle; Sun, Lei; Shanley, Thomas P; Ljungman, Mats; Nyati, Mukesh K; Zhang, Ming; Lawrence, Theodore S

    2013-01-01

    The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages. For in vitro studies we irradiated (4 Gy) either a mouse lung macrophage cell line, MH-S or macrophages isolated from TTP knockout mice, and studied the effects of radiation on TTP and TNF-α levels. To study the in vivo relevance, mouse lungs were irradiated with a single dose (15 Gy) and assessed at varying times for TTP alterations. Irradiation of MH-S cells caused TTP to undergo an inhibitory phosphorylation at Ser-178 and proteasome-mediated degradation, which resulted in increased TNF-α mRNA stabilization and secretion. Similarly, MH-S cells treated with TTP siRNA or macrophages isolated from ttp (-/-) mice had higher basal levels of TNF-α, which was increased minimally after irradiation. Conversely, cells overexpressing TTP mutants defective in undergoing phosphorylation released significantly lower levels of TNF-α. Inhibition of p38, a known kinase for TTP, by either siRNA or a small molecule inhibitor abrogated radiation-induced TNF-α release by MH-S cells. Lung irradiation induced TTP(Ser178) phosphorylation and protein degradation and a simultaneous increase in TNF-α production in C57BL/6 mice starting 24 h post-radiation. In conclusion, irradiation of lung macrophages causes TTP inactivation via p38-mediated phosphorylation and proteasome-mediated degradation, leading to TNF-α production. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT.

  10. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis.

    PubMed

    Dadrich, Monika; Nicolay, Nils H; Flechsig, Paul; Bickelhaupt, Sebastian; Hoeltgen, Line; Roeder, Falk; Hauser, Kai; Tietz, Alexandra; Jenne, Jürgen; Lopez, Ramon; Roehrich, Manuel; Wirkner, Ute; Lahn, Michael; Huber, Peter E

    2016-05-01

    Background : Radiotherapy (RT) is a mainstay for the treatment of lung cancer, but the effective dose is often limited by the development of radiation-induced pneumonitis and pulmonary fibrosis. Transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF) play crucial roles in the development of these diseases, but the effects of dual growth factor inhibition on pulmonary fibrosis development remain unclear. Methods : C57BL/6 mice were treated with 20 Gy to the thorax to induce pulmonary fibrosis. PDGF receptor inhibitors SU9518 and SU14816 (imatinib) and TGFβ receptor inhibitor galunisertib were applied individually or in combinations after RT. Lung density and septal fibrosis were measured by high-resolution CT and MRI. Lung histology and gene expression analyses were performed and Osteopontin levels were studied. Results : Treatment with SU9518, SU14816 or galunisertib individually attenuated radiation-induced pulmonary inflammation and fibrosis and decreased radiological and histological signs of lung damage. Combining PDGF and TGFβ inhibitors showed to be feasible and safe in a mouse model, and dual inhibition significantly attenuated radiation-induced lung damage and extended mouse survival compared to blockage of either pathway alone. Gene expression analysis of irradiated lung tissue showed upregulation of PDGF and TGFβ-dependent signaling components by thoracic irradiation, and upregulation patterns show crosstalk between downstream mediators of the PDGF and TGFβ pathways. Conclusion : Combined small-molecule inhibition of PDGF and TGFβ signaling is a safe and effective treatment for radiation-induced pulmonary inflammation and fibrosis in mice and may offer a novel approach for treatment of fibrotic lung diseases in humans. Translational statement : RT is an effective treatment modality for cancer with limitations due to acute and chronic toxicities, where TGFβ and PDGF play a key role. Here, we show that a combined inhibition of

  11. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis

    PubMed Central

    Dadrich, Monika; Nicolay, Nils H.; Flechsig, Paul; Bickelhaupt, Sebastian; Hoeltgen, Line; Roeder, Falk; Hauser, Kai; Tietz, Alexandra; Jenne, Jürgen; Lopez, Ramon; Roehrich, Manuel; Wirkner, Ute; Lahn, Michael; Huber, Peter E.

    2016-01-01

    ABSTRACT Background: Radiotherapy (RT) is a mainstay for the treatment of lung cancer, but the effective dose is often limited by the development of radiation-induced pneumonitis and pulmonary fibrosis. Transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF) play crucial roles in the development of these diseases, but the effects of dual growth factor inhibition on pulmonary fibrosis development remain unclear. Methods: C57BL/6 mice were treated with 20 Gy to the thorax to induce pulmonary fibrosis. PDGF receptor inhibitors SU9518 and SU14816 (imatinib) and TGFβ receptor inhibitor galunisertib were applied individually or in combinations after RT. Lung density and septal fibrosis were measured by high-resolution CT and MRI. Lung histology and gene expression analyses were performed and Osteopontin levels were studied. Results: Treatment with SU9518, SU14816 or galunisertib individually attenuated radiation-induced pulmonary inflammation and fibrosis and decreased radiological and histological signs of lung damage. Combining PDGF and TGFβ inhibitors showed to be feasible and safe in a mouse model, and dual inhibition significantly attenuated radiation-induced lung damage and extended mouse survival compared to blockage of either pathway alone. Gene expression analysis of irradiated lung tissue showed upregulation of PDGF and TGFβ-dependent signaling components by thoracic irradiation, and upregulation patterns show crosstalk between downstream mediators of the PDGF and TGFβ pathways. Conclusion: Combined small-molecule inhibition of PDGF and TGFβ signaling is a safe and effective treatment for radiation-induced pulmonary inflammation and fibrosis in mice and may offer a novel approach for treatment of fibrotic lung diseases in humans. Translational statement: RT is an effective treatment modality for cancer with limitations due to acute and chronic toxicities, where TGFβ and PDGF play a key role. Here, we show that a combined

  12. Chronic radiation-induced dermatitis: challenges and solutions

    PubMed Central

    Spałek, Mateusz

    2016-01-01

    Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical

  13. [Radiation induced lung injuries secondary to radiotherapy for breast cancer].

    PubMed

    Toma, Claudia Lucia; Ciprut, Tudor; Bugarin, Svetlana; Roşca, Dorina; Bogdan, Miron Alexandru

    2011-01-01

    Modern radiotherapy decreased the number and severity of the effects of irradiation on the lung. Yet, the increased cancer incidence makes the related radiation injuries to remain actual, radiotherapy being frequently used in cancer treatment. Aim of the study consists in analysis of the radiological pattern of radiation induced lung disease due to radiotherapy for breast cancer. Sixty-eight female patients were evaluated for clinical and radiological suspicion of radiation pneumonitis after radiotherapy for breast cancer between 2001 and 2009 in "Marius Nasta" Institute of Pneumophtiziology, Bucharest. The following procedures were performed: medical history, physical examination, chest radiography and CT-scan (in a subgroup of 27 patients). Radiotherapy toxicity was evaluated based on the RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer) classification and radiological lesions based on Arriagada classification. Fifty patients (73.5%) were symptomatic (fever, dry cough, dyspnea, chest pain, fatigability), the other 18 were asymptomatic. Symptoms were mild to moderate corresponding to grade 1 (27 patients, 39.7%) or grade 2 (23 patients, 33.8%) according to RTOG/EORTC scale. All patients had radiological lesions: 25 patients (36.7%) had grade 2 lesions (linear opacities), 25 patients (36.7%) had grade 3 lesions (patchy opacities) and 18 patients (26.5%) had grade 4 lesions (dense opacities), according to Arriagada classification. Symptoms were more frequent in patients with extensive lesions on chest radiography. CT-scan, performed in 27 patients, showed more accurate images. Chest radiography remains the simplest method in screening for radiation pneumonitis and monitoring its outcome. Adverse effects secondary to radiotherapy are usually mild and self-limited, and the most difficult task remains the differential diagnosis with infections and cancer relapse.

  14. Chronic radiation-induced dermatitis: challenges and solutions.

    PubMed

    Spałek, Mateusz

    2016-01-01

    Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients' quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical

  15. Prevention of Gamma Radiation-Induced Mortality in Mice by the Isoflavone Genistein

    DTIC Science & Technology

    2005-01-01

    toxicity assessment of chronic dietary exposure to soy isoflavones in male rats , Reprod Toxicol 18: 605-611. [Grace 2002] M.B. Grace, C.B. McLeland...Prevention of Gamma Radiation-Induced Mortality in Mice by the Isoflavone Genistein M.R. Landauer, V. Srinivasan, M.B. Grace, C.M. Chang, V...of some types of cancer. The most plentiful isoflavone from soybeans is genistein (4’, 5, 7- trihydroxy-flavone). In the present study, the

  16. Rectal cancer: a review

    PubMed Central

    Fazeli, Mohammad Sadegh; Keramati, Mohammad Reza

    2015-01-01

    Rectal cancer is the second most common cancer in large intestine. The prevalence and the number of young patients diagnosed with rectal cancer have made it as one of the major health problems in the world. With regard to the improved access to and use of modern screening tools, a number of new cases are diagnosed each year. Considering the location of the rectum and its adjacent organs, management and treatment of rectal tumor is different from tumors located in other parts of the gastrointestinal tract or even the colon. In this article, we will review the current updates on rectal cancer including epidemiology, risk factors, clinical presentations, screening, and staging. Diagnostic methods and latest treatment modalities and approaches will also be discussed in detail. PMID:26034724

  17. A rectal neuroendocrine neoplasm.

    PubMed

    Varas Lorenzo, Modesto J; Muñoz Agel, Fernando

    2017-08-01

    The incidence of gastric and rectal carcinoids is increasing. This is probably due to endoscopic screening. The prognosis is primarily dependent upon tumor size, aggressiveness (pathology, Ki-67), metastatic disease and stage. However, neuroendocrine carcinoma usually behaves as an adenocarcinoma.

  18. Rectal imaging and cancer.

    PubMed

    Vining, D J

    1998-09-01

    Rectal imaging has evolved substantially during the past 25 years and now offers surgeons exquisite anatomic detail and physiologic information. Dynamic cystoproctography, helical computed tomography, endoscopic ultrasonography, endorectal magnetic resonance imaging, and immunoscintigraphy have become standards for the diagnosis of rectal disease, staging of neoplasia, and survey of therapeutic results. The indications, limitations, and relative costs of current imaging methods are reviewed, and advances in imaging technology that promise future benefits to colorectal surgeons are introduced.

  19. Radiation-induced myeloid leukemia in murine models

    PubMed Central

    2014-01-01

    The use of radiation therapy is a cornerstone of modern cancer treatment. The number of patients that undergo radiation as a part of their therapy regimen is only increasing every year, but this does not come without cost. As this number increases, so too does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards incidence reduction and treatment of these cancers. Development and efficacy testing of these agents requires not only extensive in vitro testing but also a set of reliable animal models to accurately recreate the complex situations of radiation-induced carcinogenesis. As radiation-induced leukemic progression often involves genomic changes such as rearrangements, deletions, and changes in methylation, the laboratory mouse Mus musculus, with its fully sequenced genome, is a powerful tool in cancer research. This fact, combined with the molecular and physiological similarities it shares with man and its small size and high rate of breeding in captivity, makes it the most relevant model to use in radiation-induced leukemia research. In this work, we review relevant M. musculus inbred and F1 hybrid animal models, as well as methods of induction of radiation-induced myeloid leukemia. Associated molecular pathologies are also included. PMID:25062865

  20. Radiation-induced myeloid leukemia in murine models.

    PubMed

    Rivina, Leena; Davoren, Michael; Schiestl, Robert H

    2014-07-25

    The use of radiation therapy is a cornerstone of modern cancer treatment. The number of patients that undergo radiation as a part of their therapy regimen is only increasing every year, but this does not come without cost. As this number increases, so too does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards incidence reduction and treatment of these cancers. Development and efficacy testing of these agents requires not only extensive in vitro testing but also a set of reliable animal models to accurately recreate the complex situations of radiation-induced carcinogenesis. As radiation-induced leukemic progression often involves genomic changes such as rearrangements, deletions, and changes in methylation, the laboratory mouse Mus musculus, with its fully sequenced genome, is a powerful tool in cancer research. This fact, combined with the molecular and physiological similarities it shares with man and its small size and high rate of breeding in captivity, makes it the most relevant model to use in radiation-induced leukemia research. In this work, we review relevant M. musculus inbred and F1 hybrid animal models, as well as methods of induction of radiation-induced myeloid leukemia. Associated molecular pathologies are also included.

  1. GUCY2C Signaling Opposes the Acute Radiation-Induced GI Syndrome.

    PubMed

    Li, Peng; Wuthrick, Evan; Rappaport, Jeff A; Kraft, Crystal; Lin, Jieru E; Marszalowicz, Glen; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Waldman, Scott A

    2017-09-15

    High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. Eliminating GUCY2C signaling exacerbated RIGS, amplifying radiation-induced mortality, weight loss, mucosal bleeding, debilitation, and intestinal dysfunction. Durable expression of GUCY2C, guanylin, and uroguanylin mRNA and protein by intestinal epithelial cells was preserved following lethal irradiation inducing RIGS. Oral delivery of the heat-stable enterotoxin (ST), an exogenous GUCY2C ligand, opposed RIGS, a process requiring p53 activation mediated by dissociation from MDM2. In turn, p53 activation prevented cell death by selectively limiting mitotic catastrophe, but not apoptosis. These studies reveal a role for the GUCY2C paracrine hormone axis as a novel compensatory mechanism opposing RIGS, and they highlight the potential of oral GUCY2C agonists (Linzess; Trulance) to prevent and treat RIGS in cancer therapy and nuclear disasters. Cancer Res; 77(18); 5095-106. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Potential prevention: Aloe vera mouthwash may reduce radiation-induced oral mucositis in head and neck cancer patients.

    PubMed

    Ahmadi, Amirhossein

    2012-08-01

    In recent years, more head and neck cancer patients have been treated with radiotherapy. Radiation-induced mucositis is a common and dose limiting toxicity of radiotherapy among patients with head and neck cancers. Patients undergoing radiation therapy for head and neck cancer are also at increased risk of developing oral candidiasis. A number of new agents applied locally or systemically to prevent or treat radiation-induced mucositis have been investigated, but there is no widely accepted prophylactic or effective treatment for mucositis. Topical Aloe vera is widely used for mild sunburn, frostbites, and scalding burns. Studies have reported the beneficial effects of Aloe gel for wound healing, mucous membrane protection, and treatment of oral ulcers, in addition to antiinflammatory, immunomudulation, antifungal, scavenging free radicals, increasing collagen formation and inhibiting collagenase. Herein the author postulates that oral Aloe vera mouthwash may not only prevent radiation-induced mucositis by its wound healing and antiinflammatory mechanism, but also may reduce oral candidiasis of patients undergoing head and neck radiotherapy due to its antifungal and immunomodulatory properties. Hence, Aloe vera mouthwash may provide an alternative agent for treating radiation-induced oral mucositis and candidiasis in patients with head and neck cancers.

  3. Extracellular adenosine production by ecto-5′-nucleotidase (CD73) enhances radiation-induced lung fibrosis

    PubMed Central

    Wirsdörfer, Florian; de Leve, Simone; Cappuccini, Federica; Eldh, Therese; Meyer, Alina V.; Gau, Eva; Thompson, Linda F.; Chen, Ning-Yuan; Karmouty-Quintana, Harry; Fischer, Ute; Kasper, Michael; Klein, Diana; Ritchey, Jerry W.; Blackburn, Michael R.; Westendorf, Astrid M.; Stuschke, Martin; Jendrossek, Verena

    2016-01-01

    Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment is available. In this study, we investigated the role of the extracellular adenosine as generated by the ecto-5'-nucleotidase CD73 in fibrosis development after thoracic irradiation. Exposure of wild-type C57BL/6 mice to a single dose (15 Gray) of whole thorax irradiation triggered a progressive increase in CD73 activity in the lung between 3 and 30 weeks post-irradiation. In parallel, adenosine levels in bronchoalveolar lavage fluid (BALF) were increased by approximately three-fold. Histological evidence of lung fibrosis was observed by 25 weeks after irradiation. Conversely, CD73-deficient mice failed to accumulate adenosine in BALF and exhibited significantly less radiation-induced lung fibrosis (P<0.010). Furthermore, treatment of wild-type mice with pegylated adenosine deaminase (PEG-ADA) or CD73 antibodies also significantly reduced radiation-induced lung fibrosis. Taken together, our findings demonstrate that CD73 potentiates radiation-induced lung fibrosis, suggesting that existing pharmacological strategies for modulating adenosine may be effective in limiting lung toxicities associated with the treatment of thoracic malignancies. PMID:26921334

  4. Hypopharyngeal carcinoma after radiation for tuberculosis: radiation-induced carcinoma.

    PubMed

    van der Putten, Lisa; de Bree, Remco; Kuik, Dirk J; Rietveld, Derek H F; Langendijk, Johannes A; Leemans, C René

    2010-09-01

    Radiation may cause radiation-induced cancers after a long latency period. In a group of 111 patients surgically treated for hypopharyngeal carcinoma, patients previously treated with radiotherapy for tuberculosis in the neck were compared to patients without previous radiotherapy. Seven patients (7.4%) underwent radiotherapy (median age 15 years) and developed a hypopharyngeal carcinoma (median age 70 years, median latency period 54.4 year). Considering this long latency period and the localisation in the previous radiation field these tumours can be classified as potentially radiation-induced carcinomas. Patients with potentially radiation-induced carcinomas were significantly older when the hypopharyngeal carcinoma was diagnosed (p=0.048), were more frequently females (p=0.05) and had a worse 5-year regional control rate (p=0.048). When radiotherapy is considered in young patients the risk of induction of tumours has to be kept in mind. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Panretinal photocoagulation for radiation-induced ocular ischemia

    SciTech Connect

    Augsburger, J.J.; Roth, S.E.; Magargal, L.E.; Shields, J.A.

    1987-08-01

    We present preliminary findings on the effectiveness of panretinal photocoagulation in preventing neovascular glaucoma in eyes with radiation-induced ocular ischemia. Our study group consisted of 20 patients who developed radiation-induced ocular ischemia following cobalt-60 plaque radiotherapy for a choroidal or ciliary body melanoma. Eleven of the 20 patients were treated by panretinal photocoagulation shortly after the diagnosis of ocular ischemia, but nine patients were left untreated. In this non-randomized study, the rate of development of neovascular glaucoma was significantly lower (p = 0.024) for the 11 photocoagulated patients than for the nine who were left untreated.

  6. The Mechanisms of Radiation-Induced Bystander Effect

    PubMed Central

    Najafi, M; Fardid, R; Hadadi, Gh; Fardid, M

    2014-01-01

    The radiation-induced bystander effect is the phenomenon which non-irradiated cells exhibit effects along with their different levels as a result of signals received from nearby irradiated cells. Responses of non-irradiated cells may include changes in process of translation, gene expression, cell proliferation, apoptosis and cells death. These changes are confirmed by results of some In-Vivo studies. Most well-known important factors affecting radiation-induced bystander effect include free radicals, immune system factors, expression changes of some genes involved in inflammation pathway and epigenetic factors. PMID:25599062

  7. [Symptoms, diagnosis and treatment of radiation-induced enteritis].

    PubMed

    Sinkó, Dániel; Baranyai, Zsolt; Nemeskéri, Csaba; Teknos, Dániel; Jósa, Valéria; Hegedus, László; Mayer, Arpád

    2010-09-05

    The number of radiotherapy in the treatment of malignant diseases is increasing worldwide. During the radiotherapy of tumors in the minor pelvis and abdomen intestinal inflammation of different degree may occur even if special attention is paid. Irradiation to the minor pelvis causes in half of the cases radiation induced acute enteritis, whereas in 25% chronic enteritis and colitis will develop. Chronic enteritis following radiotherapy raises a number of diagnostic and therapeutic problems that can be solved only with cooperation of different specialties. Authors present a short review regarding therapeutical options of radiation induced enteritis.

  8. Poor outcome in radiation-induced constrictive pericarditis

    SciTech Connect

    Karram, T.; Rinkevitch, D.; Markiewicz, W. )

    1993-01-15

    The purpose was to compare the outcome of patients with radiation-induced constrictive pericarditis versus patients with constiction due to another etiology. Twenty patients with constrictive pericarditis were seen during 1975-1986 at a single medical center. Six had radiation-induced constrictive pericarditis (Group A). The etiology was idiopathic in ten subjects and secondary to carcinomatous encasement, chronic renal failure, purulent infection and tuberculosis in one patient each (Group B, N = 14). Meang age was 53.4 [+-] 15.5 years. Extensive pericardiectomy was performed in 3/6 Group A and 13/14 Group B patients. All Group A patients died, 4 weeks - 11 years post-diagnosis (median = 10 months). Two Group A patients died suddenly, one died post-operatively of respiratory failure, another of pneumonia and two of recurrent carcinoma. Thirteen Group B patients are alive (median follow-up = 72 months). The only death in this group was due to metastatic cancer. The poor outcome with radiation-induced constriction is probably multi-factorial. Poor surgical outcome is to be expected in patients with evidence of recurrent tumor, high-dose irradiation, pulmonary fibrosis or associated radiation-induced myocardinal, valvular or coronary damage.

  9. Radiation-induced instability and its relation to radiation carcinogenesis

    NASA Technical Reports Server (NTRS)

    Ullrich, R. L.; Ponnaiya, B.

    1998-01-01

    PURPOSE: A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS: Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS: Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.

  10. Radiation-induced instability and its relation to radiation carcinogenesis

    NASA Technical Reports Server (NTRS)

    Ullrich, R. L.; Ponnaiya, B.

    1998-01-01

    PURPOSE: A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS: Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS: Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.

  11. Radiation-induced augmentation of the immune response

    SciTech Connect

    Anderson, R.E.; Lefkovits, I.; Troup, G.M.

    1980-01-01

    Radiation-induced augmentation of the immune response has been shown to occur both in vivo and in vitro. Evidence is presented to implicate injury to an extremely radiosensitive T cell in the expression of this phenomenon. Experiments are outlined which could be employed to support or reflect this hypothesis.

  12. Radiation-induced cognitive impairment-from bench to bedside

    PubMed Central

    Greene-Schloesser, Dana; Robbins, Mike E.

    2012-01-01

    Approximately 100 000 patients per year in the United States with primary and metastatic brain tumor survive long enough (>6 months) to develop radiation-induced brain injury. Before 1970, the human brain was thought to be radioresistant; the acute central nervous system (CNS) syndrome occurs after single doses of ≥30 Gy, and white matter necrosis can occur at fractionated doses of ≥60 Gy. Although white matter necrosis is uncommon with modern radiation therapy techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become increasingly important, having profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenic mechanisms involved in radiation-induced cognitive impairment. Although reductions in hippocampal neurogenesis and hippocampal-dependent cognitive function have been observed in rodent models, it is important to recognize that other brain regions are affected; non–hippocampal-dependent reductions in cognitive function occur. Neuroinflammation is viewed as playing a major role in radiation-induced cognitive impairment. During the past 5 years, several preclinical studies have demonstrated that interventional therapies aimed at modulating neuroinflammation can prevent/ameliorate radiation-induced cognitive impairment independent of changes in neurogenesis. Translating these exciting preclinical findings to the clinic offers the promise of improving the quality of life in patients with brain tumors who receive radiation therapy. PMID:23095829

  13. Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment.

    PubMed

    Guchelaar, H J; Vermes, A; Meerwaldt, J H

    1997-07-01

    Xerostomia, or oral dryness, is one of the most common complaints experienced by patients who have had radiotherapy of the oral cavity and neck region. The hallmarks of radiation-induced damage are acinar atrophy and chronic inflammation of the salivary glands. The early response, resulting in atrophy of the secretory cells without inflammation might be due to radiation-induced apoptosis. In contrast, the late response with inflammation could be a result of radiation-induced necrosis. The subjective complaint of a dry mouth appears to be poorly correlated with objective findings of salivary gland dysfunction. Xerostomia, with secondary symptoms of increased dental caries, difficulty in chewing, swallowing and speaking, and an increased incidence of oral candidiasis, can have a significant effect on the quality of life. At present there is no causal treatment for radiation-induced xerostomia. Temporary symptomatic relief can be offered by moistening agents and saliva substitutes, and is the only option for patients without residual salivary function. In patients with residual salivary function, oral administration of pilocarpine 5-10 mg three times a day is effective in increasing salivary flow and improving the symptoms of xerostomia, and this therapy should be considered as the treatment of choice. Effectiveness of sialogogue treatment requires residual salivary function, which emphasizes the potential benefit from sparing normal tissue during irradiation. The hypothesis concerning the existence of early apoptotic and late necrotic effects of irradiation on the salivary glands theoretically offers a way of achieving this goal.

  14. SPHINX Measurements of Radiation Induced Conductivity of Foam

    SciTech Connect

    Ballard, W.P.; Beutler, D.E.; Burt, M.; Dudley, K.J.; Stringer, T.A.

    1998-12-14

    Experiments on the SPHINX accelerator studying radiation-induced conductivity (RIC) in foam indicate that a field-exclusion boundary layer model better describes foam than a Maxwell-Garnett model that treats the conducting gas bubbles in the foam as modifying the dielectric constant. In both cases, wall attachment effects could be important but were neglected.

  15. Obstructive jaundice due to radiation-induced hepatic duct stricture

    SciTech Connect

    Chandrasekhara, K.L.; Iyer, S.K.

    1984-10-01

    A case of obstructive jaundice due to radiation-induced hepatic duct stricture is reported. The patient received postoperative radiation for left adrenal carcinoma, seven years prior to this admission. The sequelae of hepatobiliary radiation and their management are discussed briefly.

  16. Radiation-Induced Immune Modulation in Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    postulate that radiation-induced TNFR I probably acts as a “ brake ” on immunity. Because of the high risk of the proposed experiment and high...the rest of body shielded. Tumor diameters were measured in three mutually orthogonal dimensions at 2–3 day intervals with a vernier caliper and the

  17. Radiation-induced nonlinear optical response of quartz fibers

    NASA Astrophysics Data System (ADS)

    Plaksin, O. A.

    2006-10-01

    The intensity of radiation-induced luminescence and transient optical losses in KU-1 (Russia) and K-3 (Japan) quartz glass optical tibers irradiated in a fast pulsed fission reactor (a pulse duration of 80 μs and a neutron flux up to 7 × 1016 cm 2 s 2) has been measured in the visible range. The intensity of the fast luminescence component nonlinearly depends on the neutron flux. The luminescence intensity and the transient optical losses depend on the probe light intensity. Suppression of radiation-induced luminescence is observed at wavelengths that are longer or shorter than the probe light wavelength. Light probing leads to an increase in transient optical losses and a more rapid recovery of transparency. A model of two photon fluxes is proposed to analyze the relationship of the effects of suppression of radiation-induced luminescence and the increase in optical losses upon light probing. The effect of suppression of radiation-induced luminescence can be used to control the optical properties of fibers in radiation fields.

  18. Data acquisition system used in radiation induced electrical degradation experiments

    SciTech Connect

    White, D.P.

    1995-04-01

    Radiation induced electrical degradation (RIED) of ceramic materials has recently been reported and is the topic of much research at the present time. The object of this report is to describe the data acquisition system for an experiment designed to study RIED at the High Flux Beam Reactor (HFBR) at Brookhaven National Laboratory.

  19. Prevention of Radiation-Induced Breast Cancer by Amifostine

    DTIC Science & Technology

    2006-06-01

    acetylcysteine and captopril . 4 Task 2. To determine if post-irradiation amifostine treatment can reduce the frequency of radiation-induced ductal...similar to amifostine but more suited to oral administration such as WR- 3689, WR151327, N-acetylcysteine and captopril . The first task is to

  20. Prevention of Radiation-Induced Breast Cancer by Amifostine

    DTIC Science & Technology

    2009-01-01

    acetylcysteine and captopril . 4 Task 2. To determine if post-irradiation amifostine treatment can reduce the frequency of radiation-induced ductal...similar to amifostine but more suited to oral administration such as WR- 3689, WR151327, N-acetylcysteine and captopril . The first task is to

  1. Prevention of Radiation-Induced Breast Cancer by Amifostine

    DTIC Science & Technology

    2007-12-01

    and captopril . 4 Task 2. To determine if post-irradiation amifostine treatment can reduce the frequency of radiation-induced ductal dysplasia...amifostine but more suited to oral administration such as WR- 3689, WR151327, N-acetylcysteine and captopril . The first task is to determine if

  2. Radiation induces senescence and a bystander effect through metabolic alterations.

    PubMed

    Liao, E-C; Hsu, Y-T; Chuah, Q-Y; Lee, Y-J; Hu, J-Y; Huang, T-C; Yang, P-M; Chiu, S-J

    2014-05-22

    Cellular senescence is a state of irreversible growth arrest; however, the metabolic processes of senescent cells remain active. Our previous studies have shown that radiation induces senescence of human breast cancer cells that display low expression of securin, a protein involved in control of the metaphase-anaphase transition and anaphase onset. In this study, the protein expression profile of senescent cells was resolved by two-dimensional gel electrophoresis to investigate associated metabolic alterations. We found that radiation induced the expression and activation of glyceraldehyde-3-phosphate dehydrogenase that has an important role in glycolysis. The activity of lactate dehydrogenase A, which is involved in the conversion of pyruvate to lactate, the release of lactate and the acidification of the extracellular environment, was also induced. Inhibition of glycolysis by dichloroacetate attenuated radiation-induced senescence. In addition, radiation also induced activation of the 5'-adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor kappa B (NF-κB) pathways to promote senescence. We also found that radiation increased the expression of monocarboxylate transporter 1 (MCT1) that facilitates the export of lactate into the extracellular environment. Inhibition of glycolysis or the AMPK/NF-κB signalling pathways reduced MCT1 expression and rescued the acidification of the extracellular environment. Interestingly, these metabolic-altering signalling pathways were also involved in radiation-induced invasion of the surrounding, non-irradiated breast cancer and normal endothelial cells. Taken together, radiation can induce the senescence of human breast cancer cells through metabolic alterations.

  3. The effect of obesity on rectal dosimetry after permanent prostate brachytherapy.

    PubMed

    Patil, Nikhilesh; Crook, Juanita; Saibishkumar, Elantholi P; Aneja, Manipdip; Borg, Jette; Pond, Greg; Ma, Clement

    2009-01-01

    Men with higher body mass index (BMI) tend to have more fatty tissue in prostate-rectum interface, which may reduce the rectal wall dose by the inverse square law. We hypothesized that men with higher BMI will have a lower dose to the rectal wall and less rectal toxicity after permanent prostate implant. Prospectively collected data on rectal dosimetry/toxicity and BMI of 407 patients who underwent iodine-125 ((125)I) prostate implant were analyzed. Postimplant dosimetry used CT-MRI fusion on Day 30. Rectal wall was contoured on all slices where seeds were seen. The volume of rectal wall receiving the prescribed dose (RV(100) in cm(3)) and the dose to 1cc of rectal wall (RD(1cc)) were reported. Other factors evaluated for association with rectal dosimetry and toxicity included age, diabetes, hypertension, smoking, use of neoadjuvant hormones, T stage, baseline prostate volume, 1 month prostate edema, seed type and activity, and prostate dosimetry factors (the isodose enclosing 90% of the prostate volume [D(90)], the percentage of the prostate volume enclosed by the prescription [V(100)], and the percentage of the prostate volume enclosed by the 150% isodose [V(150)]). Rectal toxicity was reported as per Radiation Therapy Oncology Group criteria. BMIs ranged from 15.9 to 46.8 (mean+/-standard deviation [SD]: 27.8+/-4.2). The mean+/-SD values for RV(100) and RD(1cc) were 0.79+/-0.49cm(3) and 128.2+/-27.8Gy, respectively. There was a significant negative association of BMI with RV(100) (p=0.007) and RD(1cc) (p=0.01) on univariate analysis. The mean RV(100) and RD(1cc) for men with higher BMI (>27.8) were lower compared with their slimmer counterparts (0.70 vs. 0.86cm(3) and 123.4 vs. 132.4Gy, respectively). On multivariate analysis for RV(100) and RD(1cc), BMI remained significant (p-values 0.004 and 0.01, respectively) along with prostate volume and V(150), suggesting that anatomic factors are important in rectal dosimetry in prostate brachytherapy. Overall the

  4. Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury.

    PubMed

    Antonic, Vlado; Rabbani, Zahid N; Jackson, Isabel L; Vujaskovic, Zeljko

    2015-10-01

    The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation therapy (RT) mitigates development of pulmonary toxicity in rats. Female F344 rats (n = 60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT + 5 mg/kg bSOD; (3) RT + 15 mg/kg bSOD; (4) No RT; (5) sham RT + 5 mg/kg bSOD; and (6) sham RT + 15 mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 h post-radiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency, and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG(+), NOX4(+), nitrotyrosine(+), and 4HNE(+) cells), macrophage activation (ED1(+)), and expression of profibrotic transforming growth factor-β or TGF-β in irradiated tissue. Radiation led to an increase in all the evaluated parameters. Treatment with 15 mg/kg bSOD significantly decreased levels of all the evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance. The single application of bSOD (15 mg/kg) ameliorates radiation-induced lung injury through suppression of reactive oxygen species/reactive nitrogen species or ROS/RNS-dependent tissue damage.

  5. Risk and survival outcomes of radiation-induced CNS tumors.

    PubMed

    Lee, Jessica W; Wernicke, A Gabriella

    2016-08-01

    Patients treated with cranial radiation are at risk of developing secondary CNS tumors. Understanding the incidence, treatment, and long-term outcomes of radiation-induced CNS tumors plays a role in clinical decision-making and patient education. Additionally, as meningiomas and pituitary tumors have been detected at increasing rates across all ages and may potentially be treated with radiation, it is important to know and communicate the risk of secondary tumors in children and adults. After conducting an extensive literature search, we identified publications that report incidence and long-term outcomes of radiation-induced CNS tumors. We reviewed 14 studies in children, which reported that radiation confers a 7- to 10-fold increase in subsequent CNS tumors, with a 20-year cumulative incidence ranging from 1.03 to 28.9 %. The latency period for secondary tumors ranged from 5.5 to 30 years, with gliomas developing in 5-10 years and meningiomas developing around 15 years after radiation. We also reviewed seven studies in adults, where the two strongest studies showed no increased risk while the remaining studies found a higher risk compared to the general population. The latency period for secondary CNS tumors in adults ranged from 5 to 34 years. Treatment and long-term outcomes of radiation-induced CNS tumors have been documented in four case series, which did not conclusively demonstrate that secondary CNS tumors fared worse than primary CNS tumors. Radiation-induced CNS tumors remain a rare occurrence that should not by itself impede radiation treatment. Additional investigation is needed on the risk of radiation-induced tumors in adults and the long-term outcomes of these tumors.

  6. The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits

    PubMed Central

    Yang, Yunyi; Liu, Zi; Wang, Juan; Chai, Yanlan; Su, Jin; Shi, Fan; Wang, Jiquan; Che, Shao Min

    2016-01-01

    We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation–induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation group received 5.0 mL/kg saline. The rabbits were sacrificed at 4, 8, 12, and 16 weeks postradiation, and the rectal and ureteral tissues within the radiation areas were collected. The results showed that the morphology of rectal and ureteral tissues was changed by X-ray radiation. The degree of damage at 4, 8, and 12 weeks, but not at 16 weeks, postradiation was significantly different between the IFN-γ and conventional radiation groups. The expression of transforming growth factor beta 1 mRNA in the ureter and colorectal mucosa of the IFN-γ group was significantly lower than that in the conventional radiation group at 4, 8, 12, and 16 weeks postradiation, but it was still higher than that in the control group. There were significant differences in the expression of collagen III among the three groups. IFN-γ can inhibit the radiation-induced upregulation of transforming growth factor beta 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuate radiation-induced damage and fibrosis. PMID:27274263

  7. Rectal absorption of propylthiouracil.

    PubMed

    Bartle, W R; Walker, S E; Silverberg, J D

    1988-06-01

    The rectal absorption of propylthiouracil (PTU) was studied and compared to oral absorption in normal volunteers. Plasma levels of PTU after administration of suppositories of PTU base and PTU diethanolamine were significantly lower compared to the oral route. Elevated plasma reverse T3 levels were demonstrated after each treatment, however, suggesting a desirable therapeutic effect at this dosage level for all preparations.

  8. Endoglin haploinsufficiency reduces radiation-induced fibrosis and telangiectasia formation in mouse kidneys.

    PubMed

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S; Ten Dijke, Peter; Stewart, Fiona A

    2009-09-01

    Endoglin is a transforming growth factor beta (TGF-beta) co-receptor mainly expressed in dividing endothelial cells. It regulates cell proliferation and survival and is upregulated at sites of vessel repair. Mutations in endoglin have been linked to the vascular disease hereditary hemorrhagic telangiectasia (HHT). HHT patients display dilated capillaries (telangiectasia) that are prone to rupture. Cancer patients receiving radiotherapy develop similar vascular damage in normal tissues lying in the irradiation field. If located in the mucosa, irradiation-induced telangiectasia can lead to severe bleeding. Therefore, this study was aimed at investigating the role of endoglin in radiation-induced telangiectasia formation. Kidneys of endoglin heterozygous (Eng(+/-)) or wild type mice were irradiated with 16 Gy. Mice were sacrificed after 20 weeks and changes in gene expression and protein levels were analysed. Expression of TGF-beta target genes involved in radiation-induced fibrosis and fibrosis development in the kidney decreased in Eng(+/-) compared to wild type mice. Unexpectedly, Eng(+/-) mice also displayed reduced telangiectasia formation in the irradiated kidney. Endoglin plays an important role in the development of irradiation-induced normal tissue damage. Future studies will show whether interfering with endoglin functions protects tissues from late radiation toxicity.

  9. Ionizing radiation induces senescence and differentiation of human dental pulp stem cells.

    PubMed

    Havelek, R; Soukup, T; Ćmielová, J; Seifrtová, M; Suchánek, J; Vávrová, J; Mokrý, J; Muthná, D; Řezáčová, M

    2013-01-01

    Head and neck cancer is one of the most common cancers in Europe. Many current anti-cancer treatments, including ionizing radiation, induce apoptosis via DNA damage. Unfortunately, such treatments are non-selective to cancer cells and produce similar toxicity in normal cells, including adult stem cells. One of the fundamental properties of an adult stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. However, under certain stimuli, unspecialized adult stem cells can give rise to specialized cells to generate replacements for cells that are lost during one's life or due to injury or disease. Nevertheless, specialization of stem cells must be controlled by specific milieu and also initiated at the proper time, making the entire process beneficial for tissue recovery and maintaining it for a long time. In this paper we assess whether irradiated dental pulp stem cells have maintained open their options to mature into specialized cells, or whether they have lost their unspecialized (immature) state following irradiation. Our findings showed radiation-induced premature differentiation of dental pulp stem cells towards odonto-/osteoblast lineages in vitro. Matrix calcification was visualized from Day 6 or Day 9 following irradiation of cells expressing low or high levels of CD146, respectively.

  10. Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

    SciTech Connect

    Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G.

    2013-08-01

    Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following

  11. Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

    PubMed

    Price, Jeremy G; Stone, Nelson N; Stock, Richard G

    2013-08-01

    To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights

  12. Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children

    PubMed Central

    Sharif, Mohammad Reza; Haji Rezaei, Mostafa; Aalinezhad, Marzieh; Sarami, Golbahareh; Rangraz, Masoud

    2016-01-01

    Background Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti-inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. Objectives This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. Patients and Methods This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. Results The average rectal temperature in the Paracetamol group was 39.6 ± 1.13°C, and 39.82 ± 1.07°C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 ± 0.89°C and 38.95 ± 1.09°C, respectively (P = 0.02). Average temperature changes were 0.65 ± 0.17°C in the Paracetamol group and 1.73 ± 0.69°C in the Diclofenac group (P < 0.001). Conclusions In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories. PMID:26889398

  13. Rectal contrast increases rectal dose during vaginal cuff brachytherapy.

    PubMed

    Sabater, Sebastia; Andres, Ignacio; Jimenez-Jimenez, Esther; Berenguer, Roberto; Sevillano, Marimar; Lopez-Honrubia, Veronica; Rovirosa, Angeles; Sanchez-Prieto, Ricardo; Arenas, Meritxell

    2016-01-01

    To evaluate the impact of rectal dose on rectal contrast use during vaginal cuff brachytherapy (VCB). A retrospective review of gynecology patients who received some brachytherapy fractions with and without rectal contrast was carried out. Rectal contrast was instilled at the clinician's discretion to increase rectal visibility. Thirty-six pairs of CT scans in preparation for brachytherapy were analyzed. Pairs of CTs were segmented and planned using the same parameters. The rectum was always defined from 1 cm above the cylinder tip up to 1.5 cm below the last activated dwell source position. An individual plan was computed at every VCB fraction. A set of values (Dmax, D(0.1cc), D(1cc), and D(2cc)) derived from dose-volume histograms were extracted and compared according to the rectal status. Rectal volume was 26.7% larger in the fractions with rectal contrast. Such an increase in volume represented a significant increase from 7.7% to 10.4% in all parameters analyzed except Dmax dose-volume histogram. Avoiding rectal contrast is a simple way of decreasing the rectal dose parameters of VCB, which would mean a better therapeutic ratio. Results also suggest that action directed at maintaining the rectum empty might have the same effect. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Oligomer formation in the radiation-induced polymerization of styrene

    NASA Astrophysics Data System (ADS)

    Harayma, Hiroshi; Al-Sheikhly, Mohamad; Silverman, Joseph

    2003-12-01

    Analyses of the oligomers formed in radiation-induced polymerization of purified styrene were performed. The principal dimeric products were cis- and trans-diphenyl-cyclobutane with a relatively small amount of 1-phenyltetralin; the trimeric products were the optical isomers of 1-phenyl-4-[1'-phenylethyl-(1')]-tetralin in gamma-ray and 60 MeV proton irradiation. Oligomer formation increased with increasing dose, but more gradually than the linear formation of high polymer with dose. The yield was 0.25-3.1 μmol/J at low doses and decreased to an asymptotic value of 0.15 at higher doses. It appears that oligomers act as chain transfer agents during the polymerization reaction which would account for the observed decrease in molecular weight of the high polymer with increase in dose. Although the thermal and radiation-induced polymerization of styrene have different initiation steps, the oligomers produced by both reactions are similar in composition.

  15. Radiation-induced decomposition of explosives under extreme conditions

    SciTech Connect

    Giefers, Hubertus; Pravica, Michael; Yang, Wenge; Liermann, Peter

    2008-11-03

    We present high-pressure and high temperature studies of the synchrotron radiation-induced decomposition of powder secondary high explosives pentaerythritol tetranitrate (PETN) and 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) using white beam synchrotron radiation at the 16 BM-B and 16 BM-D sectors of the HP-CAT beamline at the Advanced Photon Source. The radiation-induced decomposition rate TATB showed dramatic slowing with pressure up to 26.6 GPa (the highest pressure studied), implying a positive activation volume of the activated complex. The decomposition rate of PETN varied little with pressure up to 15.7 GPa (the highest pressure studied). Diffraction line intensities were measured as a function of time using energy-dispersive methods. By measuring the decomposition rate as a function of pressure and temperature, kinetic and other constants associated with the decomposition reactions were extracted.

  16. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    NASA Astrophysics Data System (ADS)

    Jiang, Erkang; Wu, Lijun

    2009-04-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy α-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose α-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE).

  17. Radioadaptive response for protection against radiation-induced teratogenesis.

    PubMed

    Okazaki, Ryuji; Ootsuyama, Akira; Norimura, Toshiyuki

    2005-03-01

    To clarify the characteristics of the radioadaptive response in mice, we compared the incidence of radiation-induced malformations in ICR mice. Pregnant ICR mice were exposed to a priming dose of 2 cGy (667 muGy/min) on day 9.5 of gestation and to a challenging dose of 2 Gy (1.04 Gy/min) 4 h later and were killed on day 18.5 of gestation. The incidence of malformations and prenatal death and fetal body weights were studied. The incidence of external malformations was significantly lower (by approximately 10%) in the primed (2 cGy + 2 Gy) mice compared to the unprimed (2 Gy alone) mice. However, there were no differences in the incidence of prenatal death or the skeletal malformations or the body weights between primed and unprimed mice. These results suggest that primary conditioning with low doses of radiation suppresses radiation-induced teratogenesis.

  18. Radiation induced viscous flow in amorphous thin films

    NASA Astrophysics Data System (ADS)

    Mayr, S. G.; Ashkenazy, Y.; Averback, R. S.

    2003-03-01

    We investigate surface roughness and stress relaxation in amorphous thin films during ion beam irradiation by a combination of experiments and molecular dynamics simulations. These experiments show, that smoothing occurs by a viscous mechanism. With computer simulations we investigate the model system CuTi, and find that radiation induced viscous flow is independent of the recoil energy between 100 and 15keV, when compared on the basis of defect production. Additionally we can identify a threshold recoil energy for flow of approximately 10eV. We show, that point defects can mediate the flow, by injection of interstitial and vacancy-like defects, which induce the same amount of flow as recoil events. The results are compared with the thermal spike model of radiation induced viscous flow.

  19. Radiation-induced transient darkening of optically transparent polymers

    SciTech Connect

    Downey, S.W.; Builta, L.A.; Carlson, R.L.; Czuchlewski, S.J.; Moir, D.C.

    1986-11-15

    Results are presented for the radiation-induced transient darkening of thin organic polymer films normally used as Cerenkov light emissions sources. The radiation source is a 27-MeV, 10-..mu..C, 200-ns electron beam generated by the PHERMEX accelerator. The typical dose for a single pulse is 5 Mrad. At this dose, the broadband time-resolved percent transmission above 520 nm was measured for four common polymers: polyimide (Kapton-H), polyethylene terephthalate (Mylar), cellulose acetate, and high-density polyethylene. Kapton was found to darken the most and polyethylene darkened the least. The recovery time to normal transmission for Kapton was found to be greater than 10--20 ..mu..s. The radiation-induced attenuation coefficient is shown to depend on electronic band energy separation. The results show that Kapton is not the material of choice for a Cerenkov light source.

  20. Prosthodontic management of radiation induced xerostomic patient using flexible dentures

    PubMed Central

    Murthy, Varsha; V, Yuvraj; Nair, Preeti P; Thomas, Shaji

    2012-01-01

    Xerostomia causes discomfort for complete denture wearers as the tissues become dry and friable due to lack of lubricating properties of saliva. Common problems faced by such patients are glossitis, mucositis, angular chelitis, dysgeusia and difficulty in chewing and swallowing. This case report describes a new method in addressing such issues by using flexible complete denture construction in radiation induced xerostomic patient with minimal tissue damage during and after denture construction procedures. PMID:22605708

  1. Follistatin attenuates radiation-induced fibrosis in a murine model

    PubMed Central

    Forrester, Helen B.; de Kretser, David M.; Leong, Trevor; Hagekyriakou, Jim; Sprung, Carl N.

    2017-01-01

    Purpose Fibrosis can be a disabling, severe side effect of radiotherapy that can occur in patients, and for which there is currently no effective treatment. The activins, proteins which are members of the TGFβ superfamily, have a major role in stimulating the inflammatory response and subsequent fibrosis. Follistatin is an endogenous protein that binds the activins virtually irreversibly and inhibits their actions. These studies test if follistatin can attenuate the fibrotic response using a murine model of radiation-induced fibrosis. Experimental design C57BL/6 mice were subcutaneously injected with follistatin 24 hours prior to irradiation. Mice were irradiated in a 10 x 10 mm square area of the right hind leg with 35 Gy and were given follistatin 24 hours before radiation and three times a week for six months following. Leg extension was measured, and tissue was collected for histological and molecular analysis to evaluate the progression of the radiation-induced fibrosis. Results Leg extension was improved in follistatin treated mice compared to vehicle treated mice at six months after irradiation. Also, epidermal thickness and cell nucleus area of keratinocytes were decreased by the follistatin treatment compared to the cells in irradiated skin of control mice. Finally, the gene expression of transforming growth factor β1 (Tgfb1), and smooth muscle actin (Acta2) were decreased in the irradiated skin and Acta2 and inhibin βA subunit (Inhba) were decreased in the irradiated muscle of the follistatin treated mice. Conclusions Follistatin attenuated the radiation-induced fibrotic response in irradiated mice. These studies provide the data to support further investigation of the use of follistatin to reduce radiation-induced fibrosis in patients undergoing radiotherapy for cancer. PMID:28301516

  2. Follistatin attenuates radiation-induced fibrosis in a murine model.

    PubMed

    Forrester, Helen B; de Kretser, David M; Leong, Trevor; Hagekyriakou, Jim; Sprung, Carl N

    2017-01-01

    Fibrosis can be a disabling, severe side effect of radiotherapy that can occur in patients, and for which there is currently no effective treatment. The activins, proteins which are members of the TGFβ superfamily, have a major role in stimulating the inflammatory response and subsequent fibrosis. Follistatin is an endogenous protein that binds the activins virtually irreversibly and inhibits their actions. These studies test if follistatin can attenuate the fibrotic response using a murine model of radiation-induced fibrosis. C57BL/6 mice were subcutaneously injected with follistatin 24 hours prior to irradiation. Mice were irradiated in a 10 x 10 mm square area of the right hind leg with 35 Gy and were given follistatin 24 hours before radiation and three times a week for six months following. Leg extension was measured, and tissue was collected for histological and molecular analysis to evaluate the progression of the radiation-induced fibrosis. Leg extension was improved in follistatin treated mice compared to vehicle treated mice at six months after irradiation. Also, epidermal thickness and cell nucleus area of keratinocytes were decreased by the follistatin treatment compared to the cells in irradiated skin of control mice. Finally, the gene expression of transforming growth factor β1 (Tgfb1), and smooth muscle actin (Acta2) were decreased in the irradiated skin and Acta2 and inhibin βA subunit (Inhba) were decreased in the irradiated muscle of the follistatin treated mice. Follistatin attenuated the radiation-induced fibrotic response in irradiated mice. These studies provide the data to support further investigation of the use of follistatin to reduce radiation-induced fibrosis in patients undergoing radiotherapy for cancer.

  3. Heavy-ion radiation induced bystander effect in mice

    NASA Astrophysics Data System (ADS)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  4. Torin2 Suppresses Ionizing Radiation-Induced DNA Damage Repair.

    PubMed

    Udayakumar, Durga; Pandita, Raj K; Horikoshi, Nobuo; Liu, Yan; Liu, Qingsong; Wong, Kwok-Kin; Hunt, Clayton R; Gray, Nathanael S; Minna, John D; Pandita, Tej K; Westover, Kenneth D

    2016-05-01

    Several classes of inhibitors of the mammalian target of rapamycin (mTOR) have been developed based on its central role in sensing growth factor and nutrient levels to regulate cellular metabolism. However, its ATP-binding site closely resembles other phosphatidylinositol 3-kinase-related kinase (PIKK) family members, resulting in reactivity with these targets that may also be therapeutically useful. The ATP-competitive mTOR inhibitor, Torin2, shows biochemical activity against the DNA repair-associated proteins ATM, ATR and DNA-PK, which raises the possibility that Torin2 and related compounds might radiosensitize cancerous tumors. In this study Torin2 was also found to enhance ionizing radiation-induced cell killing in conditions where ATM was dispensable, confirming the requirement for multiple PIKK targets. Moreover, Torin2 did not influence the initial appearance of γ-H2AX foci after irradiation but significantly delayed the disappearance of radiation-induced γ-H2AX foci, indicating a DNA repair defect. Torin2 increased the number of radiation-induced S-phase specific chromosome aberrations and reduced the frequency of radiation-induced CtIP and Rad51 foci formation, suggesting that Torin2 works by blocking homologous recombination (HR)-mediated DNA repair resulting in an S-phase specific DNA repair defect. Accordingly, Torin2 reduced HR-mediated repair of I-Sce1-induced DNA damage and contributed to replication fork stalling. We conclude that radiosensitization of tumor cells by Torin2 is associated with disrupting ATR- and ATM-dependent DNA damage responses. Our findings support the concept of developing combination cancer therapies that incorporate ionizing radiation therapy and Torin2 or compounds with similar properties.

  5. Thermodynamic models of radiation-induced processes in solids

    NASA Astrophysics Data System (ADS)

    Yurov, V. M.; Eremin, E. N.; Kasymov, S. S.; Laurinas, V. CH; Chernyavskii, A. V.

    2017-01-01

    A thermodynamic model is proposed to qualitatively describe the radiation-induced processes in solids: temperature dependence of the X-ray radio luminescence output, dependence of these processes on the excitation density, energy accumulating in a solid under exposure to ionizing radiation and its temperature dependence. The proposed model and the formula derived can be used to develop radiation-resistant and radiation-sensitive materials.

  6. Process and Radiation Induced Defects in Electronic Materials and Devices

    NASA Technical Reports Server (NTRS)

    Washington, Kenneth; Fogarty, T. N.

    1997-01-01

    Process and radiation induced defects are characterized by a variety of electrical techniques, including capacitance-voltage measurements and charge pumping. Separation of defect type into stacking faults, displacement damage, oxide traps, interface states, etc. and their related causes are discussed. The defects are then related to effects on device parameters. Silicon MOS technology is emphasized. Several reviews of radiation effects and silicon processing exist.

  7. Dynamics of radiation-induced amorphization in intermetallic compounds

    SciTech Connect

    Lam, N.Q.; Okamoto, P.R. ); Devanathan, R. Northwestern Univ., Evanston, IL . Dept. of Materials Science and Engineering); Meshii, M. . Dept. of Materials Science and Engineering)

    1992-06-01

    Recent progress in molecular-dynamics simulations of radiation-induced crystalline-to-amorphous transition in intermetallic compounds and the relationship between amorphization and melting are discussed. By focusing on the mean-square static displacement, which provides a generic measure of energy stored in the lattice in the forms of chemical and topological disorder, a unified description of solid-state amorphization as a disorder-induced, isothermal melting process can be developed within the framework of a generalized Lindemann criterion.

  8. Process and Radiation Induced Defects in Electronic Materials and Devices

    NASA Technical Reports Server (NTRS)

    Washington, Kenneth; Fogarty, T. N.

    1997-01-01

    Process and radiation induced defects are characterized by a variety of electrical techniques, including capacitance-voltage measurements and charge pumping. Separation of defect type into stacking faults, displacement damage, oxide traps, interface states, etc. and their related causes are discussed. The defects are then related to effects on device parameters. Silicon MOS technology is emphasized. Several reviews of radiation effects and silicon processing exist.

  9. Modeling radiation induced segregation in Iron-Chromium alloys

    SciTech Connect

    Senninger, Oriane; Soisson, Frederic; Martinez Saez, Enrique; Nastar, Maylise; Fu, Chu-Chun; Brechet, Yves

    2015-10-16

    Radiation induced segregation in ferritic Fe-Cr alloys is studied by Atomistic Kinetic Monte Carlo simulations that include di usion of chemical species by vacancy and interstitial migration, recombination, and elimination at sinks. The parameters of the di usion model are tted to DFT calculations. Transport coe cients that control the coupling between di usion of defects and chemical species are measured in dilute and concentrated alloys. Radiation induced segregation near grain boundaries is directly simulated with this model. We nd that the di usion of vacancies toward sinks leads to a Cr depletion. Meanwhile, the di usion of self-interstitials causes an enrichment of Cr in the vicinity of sinks. For concentrations lower than 15%Cr, we predict that sinks will be enriched with Cr for temperatures lower than a threshold. When the temperature is above this threshold value, the sinks will be depleted in Cr. These results are compared to previous experimental studies and models. Cases of radiation induced precipitation and radiation accelerated precipitation are considered.

  10. Modeling radiation induced segregation in Iron-Chromium alloys

    DOE PAGES

    Senninger, Oriane; Soisson, Frederic; Martinez Saez, Enrique; ...

    2015-10-16

    Radiation induced segregation in ferritic Fe-Cr alloys is studied by Atomistic Kinetic Monte Carlo simulations that include di usion of chemical species by vacancy and interstitial migration, recombination, and elimination at sinks. The parameters of the di usion model are tted to DFT calculations. Transport coe cients that control the coupling between di usion of defects and chemical species are measured in dilute and concentrated alloys. Radiation induced segregation near grain boundaries is directly simulated with this model. We nd that the di usion of vacancies toward sinks leads to a Cr depletion. Meanwhile, the di usion of self-interstitials causesmore » an enrichment of Cr in the vicinity of sinks. For concentrations lower than 15%Cr, we predict that sinks will be enriched with Cr for temperatures lower than a threshold. When the temperature is above this threshold value, the sinks will be depleted in Cr. These results are compared to previous experimental studies and models. Cases of radiation induced precipitation and radiation accelerated precipitation are considered.« less

  11. Radiation-induced cataract in astronauts and cosmonauts.

    PubMed

    Rastegar, Noushin; Eckart, Peter; Mertz, Manfred

    2002-07-01

    Opacification of the ocular lens is an important effect of exposure to ionizing radiation. Astronauts and cosmonauts are exposed to relatively high doses of all types of radiation in space, including high-energy particle radiation. A study was initiated to examine the lenses of the eyes of astronauts/cosmonauts to detect signs of radiation-induced cataracts. The aim of this study was to take a first step towards gaining improved, quantitative insight into the risk of radiation-induced cataract associated with long space missions. The lenses of 21 former astronauts and cosmonauts were examined, using an upgraded Topcon SL-45 B Scheimpflug camera system. The degrees of opacification in this group of astronauts and cosmonauts were compared with the measurements in a reference group. This reference group was established by examining a cohort of 395 persons using the same Scheimpflug system. Initial results indicated that opacity values in most of the astronauts and cosmonauts were slightly to strongly increased in regions IV (posterior cortex) and V (posterior capsule), compared with the average opacity values for the respective age-group of the reference cohort. The aim of this study - to conduct first examinations of astronauts' and cosmonauts' ocular lenses with regard to signs of radiation-induced cataract - was successfully achieved in a total of 21 astronauts and cosmonauts using a Scheimpflug camera system. It is planned to examine a larger group of astronauts and cosmonauts in the future.

  12. Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice.

    PubMed

    Lee, Seung Jun; Yi, Chin-ok; Heo, Rok Won; Song, Dae Hyun; Cho, Yu Ji; Jeong, Yi Yeong; Kang, Ki Mun; Roh, Gu Seob; Lee, Jong Deog

    2015-01-01

    Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis.

  13. Clarithromycin Attenuates Radiation-Induced Lung Injury in Mice

    PubMed Central

    Lee, Seung Jun; Yi, Chin-ok; Heo, Rok Won; Song, Dae Hyun; Cho, Yu Ji; Jeong, Yi Yeong; Kang, Ki Mun; Roh, Gu Seob; Lee, Jong Deog

    2015-01-01

    Radiation-induced lung injury (RILI) is a common and unavoidable complication of thoracic radiotherapy. The current study was conducted to evaluate the ability of clarithromycin (CLA) to prevent radiation-induced pneumonitis, oxidative stress, and lung fibrosis in an animal model. C57BL/6J mice were assigned to control, irradiation only, irradiation plus CLA, and CLA only groups. Test mice received single thoracic exposures to radiation and/or oral CLA (100 mg/kg/day). Histopathologic findings and markers of inflammation, fibrosis, and oxidative stress were compared by group. On a microscopic level, CLA inhibited macrophage influx, alveolar fibrosis, parenchymal collapse, consolidation, and epithelial cell changes. The concentration of collagen in lung tissue was lower in irradiation plus CLA mice. Radiation-induced expression of tumor necrosis factor (TNF)-α, TNF receptor 1, acetylated nuclear factor kappa B, cyclooxygenase 2, vascular cell adhesion molecule 1, and matrix metallopeptidase 9 were also attenuated by CLA. Expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, transforming growth factor-β1, connective tissue growth factor, and type I collagen in radiation-treated lungs were also attenuated by CLA. These findings indicate that CLA ameliorates the deleterious effects of thoracic irradiation in mice by reducing pulmonary inflammation, oxidative damage, and fibrosis. PMID:26114656

  14. Radiation-induced grain boundary segregation in austenitic stainless steels

    SciTech Connect

    Bruemmer, S.M.; Charlot, L.A.; Vetrano, J.S.; Simonen, E.P.

    1994-11-01

    Radiation-induced segregation (RIS) to grain boundaries in Fe-Ni-Cr-Si stainless alloys has been measured as a function of irradiation temperature and dose. Heavy-ion irradiation was used to produce damage levels from 1 to 20 displacements per atom (dpa) at temperatures from 175 to 550{degrees}C. Measured Fe, Ni, and Cr segregation increased sharply with irradiation dose (from G to 5 dpa) and temperature (from 175 to about 350{degrees}C). However, grain boundary concentrations did not change significantly as dose or temperatures were further increased. Although interfacial compositions were similar, the width of radiation-induced enrichment or depletion profiles increased consistently with increasing dose or temperature. Impurity segregation (Si and P) was also measured, but only Si enrichment appeared to be radiation-induced. Grain boundary Si peaked at levels approaching 10 at% after irradiation doses to 10 dpa at an intermediate temperature of 325{degrees}C. No evidence of grain boundary silicide precipitation was detected after irradiation at any temperature. Equilibrium segregation of P was measured in the high-P alloys, but interfacial concentration did not increase with irradiation exposure. Comparisons to reported RIS in neutron-irradiated stainless steels revealed similar grain boundary compositional changes for both major alloying and impurity elements.

  15. Bioinformatics Methods for Learning Radiation-Induced Lung Inflammation from Heterogeneous Retrospective and Prospective Data

    PubMed Central

    Spencer, Sarah J.; Almiron Bonnin, Damian; Deasy, Joseph O.; Bradley, Jeffrey D.; El Naqa, Issam

    2009-01-01

    Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospective analysis of treatment planning archives. In addition, biomarkers for this model are extracted from a prospective clinical trial that collects blood serum samples at multiple time points. We utilize a 3-way proteomics methodology to screen for differentially expressed proteins that are related to RP. Our preliminary results demonstrate that kernel methods can capture nonlinear dose-volume interactions, but fail to address missing biological factors. Our proteomics strategy yielded promising protein candidates, but their role in RP as well as their interactions with dose-volume metrics remain to be determined. PMID:19704920

  16. Bioinformatics methods for learning radiation-induced lung inflammation from heterogeneous retrospective and prospective data.

    PubMed

    Spencer, Sarah J; Bonnin, Damian Almiron; Deasy, Joseph O; Bradley, Jeffrey D; El Naqa, Issam

    2009-01-01

    Radiotherapy outcomes are determined by complex interactions between physical and biological factors, reflecting both treatment conditions and underlying genetics. Recent advances in radiotherapy and biotechnology provide new opportunities and challenges for predicting radiation-induced toxicities, particularly radiation pneumonitis (RP), in lung cancer patients. In this work, we utilize datamining methods based on machine learning to build a predictive model of lung injury by retrospective analysis of treatment planning archives. In addition, biomarkers for this model are extracted from a prospective clinical trial that collects blood serum samples at multiple time points. We utilize a 3-way proteomics methodology to screen for differentially expressed proteins that are related to RP. Our preliminary results demonstrate that kernel methods can capture nonlinear dose-volume interactions, but fail to address missing biological factors. Our proteomics strategy yielded promising protein candidates, but their role in RP as well as their interactions with dose-volume metrics remain to be determined.

  17. Treatment of radiation-induced cystitis and vulvodynia via a ganglion impar block using a lateral approach under computed tomography guidance: a case report

    PubMed Central

    Lee, Jeong-Eun; Kwak, Kyung-Hwa; Hong, Seong Wook; Jung, Hoon; Chung, Seung-Yeon

    2017-01-01

    Adjuvant radiation therapy (RT) after colorectal cancer surgery can prevent local recurrence, but has several side effects. Precise injection of drugs into the affected areas is complicated by radiation-induced fibrosis of soft or connective tissue. A 48-year-old woman experienced severe intractable perineal pain, dysuria, urinary urgency, and frequent urination after rectal cancer surgery and adjuvant RT, and was diagnosed with radiation-induced cystitis and vulvodynia. Her symptoms persisted despite two fluoroscopy-guided ganglion impar blocks. Fluoroscopy revealed atypical needle tip positioning and radiolucent dye distribution, presumably due to radiation-induced fibrosis in the target region. We performed two computed tomography (CT)-guided ganglion impar blocks by using a lateral approach, which allowed more accurate po-sitioning of the needle tip. Her pain visual analog score decreased from 9 to 3, and she recently resumed sexual intimacy. CT guidance is a viable alternative to fluoroscopy guidance when performing ganglion impar blocks in fibrotic areas. PMID:28184272

  18. Successful treatment of radiation-induced proctitis pain by blockade of the ganglion impar in an elderly patient with prostate cancer: a case report.

    PubMed

    Khosla, Ankur; Adeyefa, Oludayo; Nasir, Syed

    2013-05-01

    Chronic rectal pain secondary to radiation-induced proctitis is fast-becoming a leading cause of chronic pain, especially for prostate cancer survivors. Currently, many elderly patients resort to increased opioid intake to alleviate the pain. However, this increase in opioid consumption often leads to constipation and further aggravates the anorectal pain, thus leading to a perpetual, vicious cycle. We reasoned that blocking the ganglion impar could attenuate this sympathetically maintained pain, which would lead to a reduction in the consumption of opioids, lessen constipation, and lead to an improvement in the patient's quality of life. Case report. An academic tertiary pain management clinic. The authors report the case of a 73-year-old African American man with a history of prostate cancer who presented to the pain management clinic for evaluation and treatment of his chronic anorectal pain secondary to radiation-induced proctitis. The patient underwent a ganglion impar block, using the transcoccygeal technique, and consequently reported excellent pain relief with little or no use for opioid pain medications at a 2-month follow-up. Ultimately, this approach led to improved mobility and an increase in the patient's quality of life. Based on this case's success, a prospective study or randomized control trial evaluating the efficacy of the ganglion impar block as a treatment option for chronic anorectal pain secondary to radiation-induced proctitis appears warranted. Wiley Periodicals, Inc.

  19. Mitigation and Treatment of Radiation-Induced Thoracic Injury With a Cyclooxygenase-2 Inhibitor, Celecoxib

    SciTech Connect

    Hunter, Nancy R.; Valdecanas, David; Liao Zhongxing; Milas, Luka; Thames, Howard D.; Mason, Kathy A.

    2013-02-01

    Purpose: To test whether a cyclooxygenase-2 inhibitor (celecoxib) could reduce mortality resulting from radiation-induced pneumonitis. Methods and Materials: Celecoxib was given to mice twice daily for 40 consecutive days starting on the day of local thoracic irradiation (LTI) or 40 or 80 days later. C3Hf/KamLaw mice were observed for morbidity, and time to death was determined. Results were analyzed using the Cox proportional hazards model. Results: Timing of celecoxib relative to LTI determined efficacy. A significant reduction in time to death was achieved only when celecoxib was started 80 days after LTI, corresponding to the time when pneumonitis is expressed. For these mice the reduction in mortality was quantified as a hazard ratio for mortality of treated vs untreated of 0.36 (95% confidence interval [CI] 0.24-0.53), thus significantly less than 1.0. Correspondingly, the median lethal dose for treated mice (12.9 Gy; 95% CI 12.55-13.25 Gy) was significantly (P=.026) higher than for untreated mice (12.4 Gy; 95% CI 12.2-12.65 Gy). Conclusions: Celecoxib significantly reduced lung toxicity when administered months after LTI when the deleterious effects of radiation were expressed. The schedule-dependent reduction in fatal pneumonitis suggests that celecoxib could be clinically useful by reintroduction of treatment months after completion of radiation therapy. These findings may be important for designing clinical trials using cyclooxygenase-2 inhibitors to treat radiation-induced lung toxicity as a complement to concurrent radiation therapy of lung cancers.

  20. Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer

    ClinicalTrials.gov

    2017-09-14

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  1. Favorable Outcomes of Pediatric Patients Treated With Radiotherapy to the Central Nervous System Who Develop Radiation-Induced Meningiomas

    SciTech Connect

    Galloway, Thomas J.; Indelicato, Daniel J.; Amdur, Robert J.; Swanson, Erika L.; Morris, Christopher G.; Marcus, Robert B.

    2011-01-01

    Purpose: To report the outcome of patients treated at the University of Florida who developed meningiomas after radiation to the central nervous system (CNS) for childhood cancer. Methods and Materials: We retrospectively identified 10 patients aged {<=}19 years who received radiotherapy to sites in the craniospinal axis and subsequently developed a meningioma. We report the histology of the radiation-induced meningioma, treatment received, and ultimate outcome among this cohort of patients. Results: Meningioma was diagnosed at a median of 23.5 years after completion of the primary radiation. Fifty percent of second meningiomas were World Health Organization Grade 2 (atypical) or higher. All cases were managed with a single modality: resection alone (n = 7), fractionated radiotherapy (n = 2), and stereotactic radiosurgery (n = 1). The actuarial event-free survival and overall survival rate at 5 years after treatment for a radiation-induced meningioma was 89%. Three patients who underwent resection for retreatment experienced a Grade 3 toxicity. Conclusions: Radiation-induced meningiomas after treatment of pediatric CNS tumors are effectively managed with single-modality therapy. Such late-effect data inform the overall therapeutic ratio and support the continued role of selective irradiation in managing pediatric CNS malignancies.

  2. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  3. Evaluation of potent phytomedicine for treatment of psoriasis using UV radiation induced psoriasis in rats.

    PubMed

    Nagar, Hemant K; Srivastava, Amit K; Srivastava, Rajnish; Ranawat, Mahendra S

    2016-12-01

    The aim of present study was to determine the effect of newly formulated gels and suspensions of extractive Phytoconstituents of Woodfordia fructicosa flowers and Gardenia gummifera leaves by using UV Radiation induced psoriasis in rats. Both plants are traditionally claimed to be useful in treatment of number of skin diseases. However, there are no established scientific reports for their potential in psoriasis. Formulated Gels and Suspensions of ethanolic extract of both plants were tested for acute dermal and oral toxicity study respectively. The results of acute dermal toxicity at concentration 1% w/w and oral toxicity at dose 1000mg/kg showed that the gels and suspensions were safe. Psoriasis was induced in Wistar rats by espousing 10% area of total body by UV radiations. Anti-psoriatic activity was performed by applying 0.1% gel and orally at a dose 100mg/kg body weight in rats. Severity Index, histological study and biochemical estimation were analyzed. The results of our studies showed that the test formulations (Gels and Suspensions) of both plant extracts exhibited potential effect in anti-psoriatic activity.

  4. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma

    PubMed Central

    Lee, Chang-Lung; Castle, Katherine D.; Moding, Everett J.; Blum, Jordan M.; Williams, Nerissa; Luo, Lixia; Ma, Yan; Borst, Luke B.; Kim, Yongbaek; Kirsch, David G.

    2015-01-01

    Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using KrasLA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic KrasG12D. However, blocking p53 during TBI significantly suppresses the expansion of KrasG12D-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma. PMID:26399548

  5. Measurements of prompt radiation induced conductivity of Kapton.

    SciTech Connect

    Preston, Eric F.; Zarick, Thomas Andrew; Sheridan, Timothy J.; Hartman, E. Frederick; Stringer, Thomas Arthur

    2010-10-01

    We performed measurements of the prompt radiation induced conductivity in thin samples of Kapton (polyimide) at the Little Mountain Medusa LINAC facility in Ogden, UT. Three mil samples were irradiated with a 0.5 {mu}s pulse of 20 MeV electrons, yielding dose rates of 1E9 to 1E10 rad/s. We applied variable potentials up to 2 kV across the samples and measured the prompt conduction current. Analysis rendered prompt conductivity coefficients between 6E-17 and 2E-16 mhos/m per rad/s, depending on the dose rate and the pulse width.

  6. Radiation-Induced Premelting of Ice at Silica Interfaces

    SciTech Connect

    Schoeder, S.; Reichert, H.; Schroeder, H.; Mezger, M.; Okasinski, J. S.; Dosch, H.; Honkimaeki, V.; Bilgram, J.

    2009-08-28

    The existence of surface and interfacial melting of ice below 0 deg. C has been confirmed by many different experimental techniques. Here we present a high-energy x-ray reflectivity study of the interfacial melting of ice as a function of both temperature and x-ray irradiation dose. We found a clear increase of the thickness of the quasiliquid layer with the irradiation dose. By a systematic x-ray study, we have been able to unambiguously disentangle thermal and radiation-induced premelting phenomena. We also confirm the previously announced very high water density (1.25 g/cm{sup 3}) within the emerging quasiliquid layer.

  7. A model of radiatively induced quark and lepton mass model

    NASA Astrophysics Data System (ADS)

    Nomura, Takaaki

    2017-07-01

    We discuss a radiatively induced quark and lepton mass model in the rst and second generation introducing extra U(1) gauge symmetry, discrete Z 2 symmetry, vector-like fermions and exotic scalar elds. Then we analyze the allowed parameter regions which simultaneously satisfy the constraints of FCNCs for the quark sector and of LFVs including μ - e conversion, observed quark mass and mixing, and the lepton mass and mixing. In addition, the typical value for the (g - 2) μ in our model is presented. We also show extension of the model in which Majorana type neutrino masses are generated at the two loop level.

  8. Mechanisms of Radiation Induced Effects in Carbon Nanotubes

    DTIC Science & Technology

    2016-10-01

    kilogram ( C kg –1 ) rad [absorbed dose] 1 × 10 –2 joule per kilogram (J kg –1 ) [gray (Gy)] rem [equivalent and effective dose] 1 × 10–2 joule per...8725 John J. Kingman Road, MS 6201 Fort Belvoir, VA 22060-6201 T E C H N IC A L R E P O R T DTRA-TR-17-5 Mechanisms of Radiation-Induced...CLASSIFICATION OF: a. REPORT b. ABSTRACT c . THIS PAGE 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 00-10-2016 Final Oct 5, 2010 - Dec 31, 2015 Mechanisms of

  9. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  10. Measurements of prompt radiation induced conductivity in Teflon (PTFE).

    SciTech Connect

    Hartman, E. Frederick; Zarick, Thomas Andrew; Sheridan, Timothy J.; Preston, E.

    2013-05-01

    We performed measurements of the prompt radiation induced conductivity (RIC) in thin samples of Teflon (PTFE) at the Little Mountain Medusa LINAC facility in Ogden, UT. Three mil (76.2 microns) samples were irradiated with a 0.5 %CE%BCs pulse of 20 MeV electrons, yielding dose rates of 1E9 to 1E11 rad/s. We applied variable potentials up to 2 kV across the samples and measured the prompt conduction current. Details of the experimental apparatus and analysis are reported in this report on prompt RIC in Teflon.

  11. Skeletal Scintigraphy in Radiation-Induced Fibrosis With Lymphedema.

    PubMed

    Wang, Jieqi; Iranmanesh, Arya M; Oates, M Elizabeth

    2017-03-01

    Despite increasing reliance on CT, MRI, and FDG PET/CT for oncological imaging, whole-body skeletal scintigraphy remains a frontline modality for staging and surveillance of osseous metastatic disease. We present a 54-year-old woman with metastatic breast cancer who received palliative external-beam radiation to the left ilium. Serial follow-up Tc-MDP bone scans demonstrated progressive soft-tissue uptake in her left lower extremity, extending from thigh to leg, with associated enlargement and skin thickening, consistent with lymphedema related to radiation-induced fibrosis. Correlative abdominopelvic CT scans confirmed fibrotic changes in the left thigh.

  12. Exaggerated radiation-induced fibrosis in patients with systemic sclerosis

    SciTech Connect

    Varga, J.; Haustein, U.F.; Creech, R.H.; Dwyer, J.P.; Jimenez, S.A. )

    1991-06-26

    Four patients with stable systemic sclerosis and limited skin involvement received radiation for the treatment of solid malignant neoplasms. Following localized irradiation, each patient developed an exaggerated cutaneous and internal fibrotic reaction in the irradiated areas. The surface area of fibrosis extended beyond the radiation portals employed, and the fibrotic process was poorly responsive to antifibrotic therapy. Three of the patients died of complications caused by fibrous encasement of internal organs. The extent and severity of postradiation fibrosis in these patients was distinctly unusual. These observations suggest that patients with systemic sclerosis are particularly susceptible to developing excessive radiation-induced fibrosis.

  13. Atorvastatin Ameliorates Radiation-Induced Cardiac Fibrosis in Rats.

    PubMed

    Zhang, KunYi; He, XuYu; Zhou, Yingling; Gao, Lijuan; Qi, Zhengyu; Chen, Jiyan; Gao, Xiuren

    2015-12-01

    Radiation-induced heart injury is one of the major side effects of radiotherapy for thoracic malignancies. Previous studies have shown that radiotherapy induced myocardial fibrosis and intensified myocardial remodeling. In this study, we investigated whether atorvastatin could inhibit radiation-induced heart fibrosis in Sprague-Dawley rats, which were randomly divided into six groups: control; radiation only; and four treatment groups receiving atorvastatin plus radiation (E1, E2, E3 and E4). All rats, except the control group, received local heart irradiation in 7 daily fractions of 3 Gy for a total of 21 Gy. Rats in groups E1 (10 mg/kg/day) and E2 (20 mg/kg/day) received atorvastatin and radiation treatment until week 12 after exposure. Rats in groups E3 (10 mg/kg/day) and E4 (20 mg/kg/day) received atorvastatin treatment from 3 months before irradiation to week 12 after irradiation. The expressions of TGF-β1, Smad2, Smad3, fibronectin, ROCK I and p-Akt in heart tissues were evaluated using real-time PCR or Western blot analyses. Atorvastatin significantly reduced the expression of TGF-β1, Smad3/P-Smad3, ROCK I and p-Akt in rats of the E1-E4 groups and in a dose-dependent manner. Fibronectin exhibited a similar pattern of expression changes. In addition, echocardiography showed that atorvastatin treatment can inhibit the increase of left ventricular end-diastolic dimension, left ventricular end-systolic diameter and left ventricular posterior wall thickness, and prevent the decrease of ejection fraction and fraction shortening in E1-E4 groups compared with the radiation only group. This study demonstrated that radiation exposure increased the expression of fibronectin in cardiac fibroblasts and induced cardiac fibrosis through activation of the TGF-β1/Smad3, RhoA/ROCK, and PI3K/AKT signaling pathways. Statins ameliorated radiation-induced cardiac fibrosis in Sprague-Dawley rats. Our results suggest that atorvastatin is effective for the treatment of radiation-induced

  14. Radiation-Induced Premelting of Ice at Silica Interfaces

    NASA Astrophysics Data System (ADS)

    Schöder, S.; Reichert, H.; Schröder, H.; Mezger, M.; Okasinski, J. S.; Honkimäki, V.; Bilgram, J.; Dosch, H.

    2009-08-01

    The existence of surface and interfacial melting of ice below 0°C has been confirmed by many different experimental techniques. Here we present a high-energy x-ray reflectivity study of the interfacial melting of ice as a function of both temperature and x-ray irradiation dose. We found a clear increase of the thickness of the quasiliquid layer with the irradiation dose. By a systematic x-ray study, we have been able to unambiguously disentangle thermal and radiation-induced premelting phenomena. We also confirm the previously announced very high water density (1.25g/cm3) within the emerging quasiliquid layer.

  15. Facial reconstruction for radiation-induced skin cancer

    SciTech Connect

    Panje, W.R.; Dobleman, T.J. )

    1990-04-01

    Radiation-induced skin cancers can be difficult to diagnose and treat. Typically, a patient who has received orthovoltage radiotherapy for disorders such as acne, eczema, tinea capitis, skin tuberculosis, and skin cancer can expect that aggressive skin cancers and chronic radiodermatitis may develop subsequently. Cryptic facial cancers can lead to metastases and death. Prophylactic widefield excision of previously irradiated facial skin that has been subject to multiple recurrent skin cancers is suggested as a method of deterring future cutaneous malignancy and metastases. The use of tissue expanders and full-thickness skin grafts offers an expedient and successful method of subsequent reconstruction.

  16. Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis

    PubMed Central

    Zwaans, Bernadette M.M.; Nicolai, Heinz G.; Chancellor, Michael B.; Lamb, Laura E.

    2016-01-01

    As diagnosis and treatment of cancer is improving, medical and social issues related to cancer survivorship are becoming more prevalent. Hemorrhagic cystitis (HC), a rare but serious disease that may affect patients after pelvic radiation or systemic chemotherapy, has significant unmet medical needs. Although no definitive treatment is currently available, various interventions are employed for HC. Effects of nonsurgical treatments for HC are of modest success and studies aiming to control radiation-induced bladder symptoms are lacking. In this review, we present current and advanced therapeutic strategies for HC to help cancer survivors deal with long-term urologic health issues. PMID:27601964

  17. Radiation-Induced Intraspinal Chondrosarcoma: A Case Report

    PubMed Central

    Obid, Peter; Vierbuchen, Mathias; Wolf, Eduard; Reichl, Michael; Niemeyer, Thomas; Übeyli, Hüseyin; Richter, Alexander

    2015-01-01

    Study Design Case report and review of the literature. Objective To report a unique case of an intraspinal chondrosarcoma that was diagnosed 18 years after radiotherapy for a cervical carcinoma and its remarkably unusual clinical presentation. Methods A retrospective case description of an intraspinal mass lesion that occurred 6 weeks after previous spinal surgery. Results Within ∼9 weeks, the tumor had infiltrated the peritoneal cavity and reached the lumbar subcutaneous tissue. Conclusion Radiation-induced sarcomas are rare, are highly aggressive, and may be difficult to diagnose. Furthermore, the only means of achieving long-term survival is through early and extensive surgery. PMID:26430606

  18. Pathology and biology of radiation-induced cardiac disease

    PubMed Central

    Tapio, Soile

    2016-01-01

    Heart disease is the leading global cause of death. The risk for this disease is significantly increased in populations exposed to ionizing radiation, but the mechanisms are not fully elucidated yet. This review aims to gather and discuss the latest data about pathological and biological consequences in the radiation-exposed heart in a comprehensive manner. A better understanding of the molecular and cellular mechanisms underlying radiation-induced damage in heart tissue and cardiac vasculature will provide novel targets for therapeutic interventions. These may be valuable for individuals clinically or occupationally exposed to varying doses of ionizing radiation. PMID:27422929

  19. Radiation-induced breast angiosarcoma: a case report

    PubMed Central

    Tato-Varela, Sara; Albalat-Fernández, Rosa; Pabón-Fernández, Sara; Núñez-García, Diego; Calle-Marcos, Manolo La

    2016-01-01

    Radiation-induced breast angiosarcoma is a severe but rare late complication in the breast-preserving management of breast cancer through surgery and radiotherapy [1]. Often the initial diagnosis of this entity is complex given its relatively anodyne nature and usually being present in the form of typically multifocal reddish-purple papular skin lesions [2]. Because of the low incidence of this tumour, there is a limited number of studies regarding its optimal therapeutic management [3]. The preferred treatment is aggressive surgical removal and the prognosis is poor with an overall survival rate of 12–20% at five years [4]. PMID:28101140

  20. Development of a Standardized Method for Contouring the Lumbosacral Plexus: A Preliminary Dosimetric Analysis of this Organ at Risk Among 15 Patients Treated With Intensity-Modulated Radiotherapy for Lower Gastrointestinal Cancers and the Incidence of Radiation-Induced Lumbosacral Plexopathy

    SciTech Connect

    Yi, Sun K.; Mak, Walter; Yang, Claus C.; Liu Tianxiao; Cui Jing; Chen, Allen M.; Purdy, James A.; Monjazeb, Arta M.; Do, Ly

    2012-10-01

    Purpose: To generate a reproducible step-wise guideline for the delineation of the lumbosacral plexus (LSP) on axial computed tomography (CT) planning images and to provide a preliminary dosimetric analysis on 15 representative patients with rectal or anal cancers treated with an intensity-modulated radiotherapy (IMRT) technique. Methods and Materials: A standardized method for contouring the LSP on axial CT images was devised. The LSP was referenced to identifiable anatomic structures from the L4-5 interspace to the level of the sciatic nerve. It was then contoured retrospectively on 15 patients treated with IMRT for rectal or anal cancer. No dose limitations were placed on this organ at risk during initial treatment planning. Dosimetric parameters were evaluated. The incidence of radiation-induced lumbosacral plexopathy (RILSP) was calculated. Results: Total prescribed dose to 95% of the planned target volume ranged from 50.4 to 59.4 Gy (median 54 Gy). The mean ({+-}standard deviation [SD]) LSP volume for the 15 patients was 100 {+-} 22 cm{sup 3} (range, 71-138 cm{sup 3}). The mean maximal dose to the LSP was 52.6 {+-} 3.9 Gy (range, 44.5-58.6 Gy). The mean irradiated volumes of the LSP were V40Gy = 58% {+-} 19%, V50Gy = 22% {+-} 23%, and V55Gy = 0.5% {+-} 0.9%. One patient (7%) was found to have developed RILSP at 13 months after treatment. Conclusions: The true incidence of RILSP in the literature is likely underreported and is not a toxicity commonly assessed by radiation oncologists. In our analysis the LSP commonly received doses approaching the prescribed target dose, and 1 patient developed RILSP. Identification of the LSP during IMRT planning may reduce RILSP. We have provided a reproducible method for delineation of the LSP on CT images and a preliminary dosimetric analysis for potential future dose constraints.

  1. Radiation-induced transmissable chromosomal instability in haemopoietic stem cells

    NASA Astrophysics Data System (ADS)

    Kadhim, M. A.; Wright, E. G.

    Heritable radiation-induced genetic alterations have long been assumed to be ``fixed'' within the first cell division. However, there is a growing body of evidence that a considerable fraction of cells surviving radiation exposure appear normal, but a variety of mutational changes arise in their progeny due to a transmissible genomic instability. In our investigations of G-banded metaphases, non-clonal cytogenetic aberrations, predominantly chromatid-type aberrations, have been observed in the clonal descendants of murine and human haemopoietic stem cells surviving low doses (~1 track per cell) of alpha-particle irradiations. The data are consistent with a transmissible genetic instability induced in a stem cell resulting in a diversity of chromosomal aberrations in its clonal progeny many cell divisions later. Recent studies have demonstrated that the instability phenotype persists in vivo and that the expression of chromosomal instability has a strong dependence on the genetic characteristics of the irradiated cell. At the time when cytogenetic aberrations are detected, an increased incidence of hprt mutations and apoptotic cells have been observed in the clonal descendants of alpha-irradiated murine haemopoietic stem cells. Thus, delayed chromosomal abnormalities, delayed cell death by apoptosis and late-arising specific gene mutations may reflect diverse consequences of radiation-induced genomic instability. The relationship, if any, between these effects is not established. Current studies suggest that expression of these delayed heritable effects is determined by the type of radiation exposure, type of cell and a variety of genetic factors.

  2. Radiation-induced dural fibrosarcoma with unusually short latent period

    SciTech Connect

    Ghatak, N.R.; Aydin, F.; Leshner, R.T. Tulane Univ., New Orleans, LA )

    1993-05-01

    Although rare, the occurrence of radiation-induced intracranial neoplasms of various types is well known. Among these tumors, fibrosarcomas, especially in the region of seila turcica, seem to be the most common type. These tumors characteristically occur after a long latent period, usually several years, following radiation therapy. The authors now report a case of apparently radiation-induced fibrosarcoma with some unusual features in a 10-year-old boy who was treated with radiation for medulloblastoma. He received a total dose of 53.2 Gy radiation delivered at 1.8 per fraction with 6 MV acceleration using the standard craniospinal technique. An MRI at 15 months after the completion of radiotherapy showed a mass over the cerebral convexity, which increased two-fold in size within a period of 4 months. A well circumscribed tumor was removed from the fronto-parietal convexity. The tumor measured 5x4.5x1.5 cm and was attached to the dura with invasion of the overlying bone. Histologically, it displayed the characteristic features of a low-grade fibrosarcoma. The patient remains free of tumor 18 months after the surgery. This case emphasizes the potential risk for the development of a second neoplasm following therapeutic radiation and also documents, to the authors' knowledge, the shortest latent period reported so far between administration of radiotherapy and development of an intracranial tumor.

  3. Novel Radiomitigator for Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

    2016-01-01

    Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

  4. Sestrin2 protects the myocardium against radiation-induced damage.

    PubMed

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Zeng, Jing; Gao, Song; Chen, Jia-Jia; Wang, Hong-Mei; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong

    2016-05-01

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.

  5. Radiation-induced recurrent intestinal pseudo-obstruction

    SciTech Connect

    Conklin, J.L.; Anuras, S.

    1981-06-01

    The syndrome of intestinal pseudo-obstruction is a complex of signs and symptoms of intestinal obstruction without evidence of mechanical obstruction of the intestinal lumen. A patient with radiation-induced intestinal pseudoobstruction is described. The patient is a 74-year old woman with a history of chronic diarrhea, recurrent episodes of crampy abdominal pain, nausea and vomiting since receiving a 13,000 rad radiation dose to the pelvis in 1954. She has been hospitalized on many occasions for symptoms and signs of bowel obstruction. Upper gastrointestinal contrast roentgenograms with small bowel follow-through done during these episodes revealed multiple dilated loops of small bowel with no obstructing lesion. Barium enemas revealed no obstructing lesion. Each episode resolved with conservative therapy. Other secondary causes for intestinal pseudo-obstruction were ruled out in our patient. She gave no history of familial gastrointestinal disorders. Although postirradiation motility abnormalities have been demonstrated experimentally this is the first report of radiation induced intestinal pseudo-obstruction.

  6. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    SciTech Connect

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-03-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor.

  7. DNA damage in cells exhibiting radiation-induced genomic instability

    SciTech Connect

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.

  8. Genetic variation in radiation-induced cell death.

    PubMed

    Smirnov, Denis A; Brady, Lauren; Halasa, Krzysztof; Morley, Michael; Solomon, Sonia; Cheung, Vivian G

    2012-02-01

    Radiation exposure through environmental, medical, and occupational settings is increasingly common. While radiation has harmful effects, it has utility in many applications such as radiotherapy for cancer. To increase the efficacy of radiation treatment and minimize its risks, a better understanding of the individual differences in radiosensitivity and the molecular basis of radiation response is needed. Here, we integrated human genetic and functional genomic approaches to study the response of human cells to radiation. We measured radiation-induced changes in gene expression and cell death in B cells from normal individuals. We found extensive individual variation in gene expression and cellular responses. To understand the genetic basis of this variation, we mapped the DNA sequence variants that influence expression response to radiation. We also identified radiation-responsive genes that regulate cell death; silencing of these genes by small interfering RNA led to an increase in radiation-induced cell death in human B cells, colorectal and prostate cancer cells. Together these results uncovered DNA variants that contribute to radiosensitivity and identified genes that can be targeted to increase the sensitivity of tumors to radiation.

  9. Sensitivity to Radiation-Induced Cancer in Hemochromatosis

    SciTech Connect

    Bull. Richard J.; Anderson, Larry E.

    2000-06-01

    The objectives of this pilot project using HFE-knockout homozygotes and heterozygotes are to (1) determine whether the knock-out mice have greater sensitivity to radiation-induced cancer of the colon, liver and breast, (2) establish the dependence of this sensitivity on the accumulation of iron, (3) determine the extent to which cell replication and apoptosis occur in these target tissues with varying iron load, and (4) correlate the increases in sensitivity with changes in insulin-related signaling in tumors and normal tissue from each target organ. Three experimental designs will be used in the pilot project. The sequence of experiments is designed to first explore the influence of iron load on the response and demonstrate that HFE knockout mice are more sensitive than the wild type to radiation-induced cancer in one or more of three target tissues (liver, colon and breast). The dose response relationships with a broader set of radiation doses will be explored in the second experiment. The final experiment is designed to explore the extent to which heterozygotes display the increased susceptibility to cancer induction and to independently assess the importance of iron load to the initiation versus promotion of tumors.

  10. Radiation-induced genomic instability in Caenorhabditis elegans.

    PubMed

    Huumonen, Katriina; Immonen, Hanna-Kaisa; Baverstock, Keith; Hiltunen, Mikko; Korkalainen, Merja; Lahtinen, Tapani; Parviainen, Juha; Viluksela, Matti; Wong, Garry; Naarala, Jonne; Juutilainen, Jukka

    2012-10-09

    Radiation-induced genomic instability has been well documented, particularly in vitro. However, the understanding of its mechanisms and their consequences in vivo is still limited. In this study, Caenorhabditis elegans (C. elegans; strain CB665) nematodes were exposed to X-rays at doses of 0.1, 1, 3 or 10Gy. The endpoints were measured several generations after exposure and included mutations in the movement-related gene unc-58, alterations in gene expression analysed with oligoarrays containing the entire C. elegans genome, and micro-satellite mutations measured by capillary electrophoresis. The progeny of the irradiated nematodes showed an increased mutation frequency in the unc-58 gene, with a maximum response observed at 1Gy. Significant differences were also found in gene expression between the irradiated (1Gy) and non-irradiated nematode lines. Differences in gene expression did not show clear clustering into certain gene categories, suggesting that the instability might be a chaotic process rather than a result of changes in the function of few specific genes such as, e.g., those responsible for DNA repair. Increased heterogeneity in gene expression, which has previously been described in irradiated cultured human lymphocytes, was also observed in the present study in C. elegans, the coefficient of variation of gene expression being higher in the progeny of irradiated nematodes than in control nematodes. To the best of our knowledge, this is the first publication reporting radiation-induced genomic instability in C. elegans.

  11. Nature of radiation-induced defects in quartz

    SciTech Connect

    Wang, Bu; Yu, Yingtian; Bauchy, Mathieu; Pignatelli, Isabella; Sant, Gaurav

    2015-07-14

    Although quartz (α-form) is a mineral used in numerous applications wherein radiation exposure is an issue, the nature of the atomistic defects formed during radiation-induced damage has not been fully clarified. Especially, the extent of oxygen vacancy formation is still debated, which is an issue of primary importance as optical techniques based on charged oxygen vacancies have been utilized to assess the level of radiation damage in quartz. In this paper, molecular dynamics simulations are applied to study the effects of ballistic impacts on the atomic network of quartz. We show that the defects that are formed mainly consist of over-coordinated Si and O, as well as Si–O connectivity defects, e.g., small Si–O rings and edge-sharing Si tetrahedra. Oxygen vacancies, on the contrary, are found in relatively low abundance, suggesting that characterizations based on E′ centers do not adequately capture radiation-induced structural damage in quartz. Finally, we evaluate the dependence on the incident energy, of the amount of each type of the point defects formed, and quantify unambiguously the threshold displacement energies for both O and Si atoms. These results provide a comprehensive basis to assess the nature and extent of radiation damage in quartz.

  12. DNA damage in cells exhibiting radiation-induced genomic instability

    DOE PAGES

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

  13. Radiation-induced skin carcinomas of the head and neck

    SciTech Connect

    Ron, E.; Modan, B.; Preston, D.; Alfandary, E.; Stovall, M.; Boice, J.D. Jr. )

    1991-03-01

    Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City. This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy.

  14. The thermal stability of radiation-induced defects in illite

    NASA Astrophysics Data System (ADS)

    Riegler, T.; Allard, T.; Beaufort, D.; Cantin, J.-L.; von Bardeleben, H. J.

    2016-01-01

    High-purity illite specimens from the Mesoproterozoic unconformity-related uranium deposits of Kiggavik, Thelon basin, Nunavut (Canada), and Shea Creek (Athabasca basin, Saskatchewan, Canada) have been studied using electron paramagnetic resonance spectroscopy to determine the thermal stability of the main radiation-induced defects and question the potential of using illite as a natural dosimeter. The observed spectra are complex as they can show in the same region several contributions: (1) an unstable native defect, (2) the main stable defect named Ai by reference to a previous study (Morichon et al. in Phys Chem Minerals 35:339-346, 2008), (3) a signal at g = 2.063 assigned to a new defect, not yet fully characterized, named Ai2 center and (4) impurities such as vanadyl complex or divalent manganese. Isochronal heating shows that the new signal corresponds to a stable species. Isothermal heating experiments at 400 and 450 °C provide values of half-life extrapolated at room temperature and activation energy of 1.9-29,109 years and 1.3-1.4 eV, respectively, corresponding to the Ai center. These parameters allow the use of stable radiation-induced defects as a record of radioactivity down to the Paleoproterozoic period.

  15. Characterization of radiation-induced emesis in the ferret

    SciTech Connect

    King, G.L.

    1988-01-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral cobalt 60 gamma radiation at 100 cGy min at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED 50 was calculated as 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously or subcutaneously with 30 to 300 micrograms /kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n=4) or 401 (n=4) cGy radiation and their emetic responses were compared with NaCi-injected-irradiated controls (n=8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.

  16. Characterization of radiation-induced emesis in the ferret

    SciTech Connect

    King, G.L.

    1988-06-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral /sup 60/Co gamma radiation at 100 cGy min-1 at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED50 was calculated at 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously or subcutaneously with 30 to 300 micrograms/kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n = 4) or 401 (n = 4) cGy radiation and their emetic responses were compared with NaCl-injected-irradiated controls (n = 8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.

  17. [Radiation-induced genomic instability: phenomenon, molecular mechanisms, pathogenetic significance].

    PubMed

    Mazurik, V K; Mikhaĭlov, V F

    2001-01-01

    The recent data on the radiation-induced genome instability as a special state of progeny of cells irradiated in vitro as well as after a whole body exposure to ionizing radiation, that make these cells considerably different from normal, unirradiated cells, were considered. This state presents a number of cytogenetical, molecular-biological, cytological and biochemical manifestations untypical for normal cells. The state is controlled by the mechanisms of regulation of checkpoints of cell cycle, and apoptosis, that is under gene p53 control. The proof has been found that this state transfers from irradiated maternal cells to their surviving progeny by the epigenetical mechanisms and would exist until the cells restore the original state of response on the DNA damage. From the point of view of the genome instability conception, that considers the chromatine rearrangement as the adaptive-evolution mechanism of adaptation of the species to changeable environmental conditions, the radiation-induced genome instability may be considered as transition of irradiated progeny to the state of read these to adaptation changes with two alternative pathways. The first leads to adaptation to enviromental conditions and restoring of normal cell functions. The second presents the cell transition into the transformed state with remain genome instability and with increase of tumour growth probability.

  18. Radiation Induced DNA Double-Strand Breaks in Radiology.

    PubMed

    Kuefner, M A; Brand, M; Engert, C; Schwab, S A; Uder, M

    2015-10-01

    Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on physical measurements or mathematical algorithms with standardized dose simulations. γ-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the prinicple of the γ-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations. Radiologic examinations including CT and angiography induce DNA double-strand breaks. Even after mammography a slight but significant increase is detectable in peripheral blood lymphocytes. The number of radiation induced double-strand breaks correlates well with the radiation dose. Individual factors including radiation sensitivity, DNA repair capacity and the application of iodinated contrast media has an influence on the DNA damage level. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats

    PubMed Central

    Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

    2013-01-01

    Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-α levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. PMID:22915786

  20. Exposure to Heavy Ion Radiation Induces Persistent Oxidative Stress in Mouse Intestine

    PubMed Central

    Datta, Kamal; Suman, Shubhankar; Kallakury, Bhaskar V. S.; Fornace, Albert J.

    2012-01-01

    Ionizing radiation-induced oxidative stress is attributed to generation of reactive oxygen species (ROS) due to radiolysis of water molecules and is short lived. Persistent oxidative stress has also been observed after radiation exposure and is implicated in the late effects of radiation. The goal of this study was to determine if long-term oxidative stress in freshly isolated mouse intestinal epithelial cells (IEC) is dependent on radiation quality at a dose relevant to fractionated radiotherapy. Mice (C57BL/6J; 6 to 8 weeks; female) were irradiated with 2 Gy of γ-rays, a low-linear energy transfer (LET) radiation, and intestinal tissues and IEC were collected 1 year after radiation exposure. Intracellular ROS, mitochondrial function, and antioxidant activity in IEC were studied by flow cytometry and biochemical assays. Oxidative DNA damage, cell death, and mitogenic activity in IEC were assessed by immunohistochemistry. Effects of γ radiation were compared to 56Fe radiation (iso-toxic dose: 1.6 Gy; energy: 1000 MeV/nucleon; LET: 148 keV/µm), we used as representative of high-LET radiation, since it's one of the important sources of high Z and high energy (HZE) radiation in cosmic rays. Radiation quality affected the level of persistent oxidative stress with higher elevation of intracellular ROS and mitochondrial superoxide in high-LET 56Fe radiation compared to unirradiated controls and γ radiation. NADPH oxidase activity, mitochondrial membrane damage, and loss of mitochondrial membrane potential were greater in 56Fe-irradiated mice. Compared to γ radiation oxidative DNA damage was higher, cell death ratio was unchanged, and mitotic activity was increased after 56Fe radiation. Taken together our results indicate that long-term functional dysregulation of mitochondria and increased NADPH oxidase activity are major contributing factors towards heavy ion radiation-induced persistent oxidative stress in IEC with potential for neoplastic transformation. PMID

  1. Modulation of ionizing radiation induced oxidative imbalance by semi-fractionated extract of Piper betle

    PubMed Central

    Verma, Savita; Dutta, Ajaswrata; Sankhwar, Sanghmitra; Shukla, Sandeep Kumar

    2010-01-01

    The study was planned to evaluate modulatory effect of aqueous extract of Piper betle leaf (PBL) on ionizing radiation mediated oxidative stress leading to normal tissues damage during radiotherapy and other radiation exposures. The total polyphenols and flavonoids known as free radical scavenger (chelators) were measured in the extract. To ascertain antioxidant potential of PBL extract, we studied free radical scavenging, metal chelation, reducing power, lipid peroxidation inhibition and ferric reducing antioxidant properties (FRAP ) using in vitro assays. Mice were exposed to varied radiation doses administered with the same extract prior to irradiation to confirm its oxidative stress minimizing efficacy by evaluating ferric reducing ability of plasma, reduced glutathione, lipid peroxidation and micro-nuclei frequency. PBL extract was effective in scavenging DPPH (up to 92% at 100 µg/ml) and superoxide radicals (up to 95% at 80 µg/ml), chelated metal ions (up to 83% at 50 µg/ml) and inhibited lipid peroxidation (up to 45.65% at 500 µg/ml) in a dose dependant manner using in vitro model. Oral administration of PBL extract (225 mg/kg body weight) 1 hr before irradiation in mice significantly enhanced (p < 0.01) radiation abated antioxidant potential of plasma and GSH level in all the observed organs. The treatment with extract effectively lowered the radiation induced lipid peroxidation at 24 hrs in all the selected organs with maximum inhibition in thymus (p < 0.01). After 48 hrs, lipid peroxidation was maximally inhibited in the group treated with the extract. Frequency of radiation induced micronucleated cells declined significantly (34.78%, p < 0.01) at 24 hrs post-irradiation interval by PBL extract administration. The results suggest that PBL extract has high antioxidant potential and relatively non-toxic and thus could be assertively used to mitigate radiotherapy inflicted normal tissues damage and also injuries caused by moderate doses of radiation

  2. Acute Radiation-Induced Nocturia in Prostate Cancer Patients Is Associated With Pretreatment Symptoms, Radical Prostatectomy, and Genetic Markers in the TGF{beta}1 Gene

    SciTech Connect

    De Langhe, Sofie; De Ruyck, Kim; Ost, Piet; Fonteyne, Valerie; Werbrouck, Joke; De Meerleer, Gert; De Neve, Wilfried; Thierens, Hubert

    2013-02-01

    Purpose: After radiation therapy for prostate cancer, approximately 50% of the patients experience acute genitourinary symptoms, mostly nocturia. This may be highly bothersome with a major impact on the patient's quality of life. In the past, nocturia is seldom reported as a single, physiologically distinct endpoint, and little is known about its etiology. It is assumed that in addition to dose-volume parameters and patient- and therapy-related factors, a genetic component contributes to the development of radiation-induced damage. In this study, we investigated the association among dosimetric, clinical, and TGF{beta}1 polymorphisms and the development of acute radiation-induced nocturia in prostate cancer patients. Methods and Materials: Data were available for 322 prostate cancer patients treated with primary or postoperative intensity modulated radiation therapy (IMRT). Five genetic markers in the TGF{beta}1 gene (-800 G>A, -509 C>T, codon 10 T>C, codon 25 G>C, g.10780 T>G), and a high number of clinical and dosimetric parameters were considered. Toxicity was scored using an symptom scale developed in-house. Results: Radical prostatectomy (P<.001) and the presence of pretreatment nocturia (P<.001) are significantly associated with the occurrence of radiation-induced acute toxicity. The -509 CT/TT (P=.010) and codon 10 TC/CC (P=.005) genotypes are significantly associated with an increased risk for radiation-induced acute nocturia. Conclusions: Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGF{beta}1 -509 C>T and codon 10 T>C are identified as factors involved in the development of acute radiation-induced nocturia. These findings may contribute to the research on prediction of late nocturia after IMRT for prostate cancer.

  3. Human Collagen Injections to Reduce Rectal Dose During Radiotherapy

    SciTech Connect

    Noyes, William R.; Hosford, Charles C.; Schultz, Steven E.

    2012-04-01

    Objectives: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. Methods: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectal space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. Results: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. Conclusions: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.

  4. Human collagen injections to reduce rectal dose during radiotherapy.

    PubMed

    Noyes, William R; Hosford, Charles C; Schultz, Steven E

    2012-04-01

    The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectal space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    NASA Astrophysics Data System (ADS)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  6. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    DTIC Science & Technology

    2005-07-01

    repair of radiation-induced damage. Furthermore, cells possessing a mutated copy of this gene are more radiosensitive than cells from individuals with...AD Award Number: DAMD17-02-1-0503 TITLE: ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast...2005 Annual 1 Jul 2004 - 30 Jun 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER ATM Mutations and the Development of Severe Radiation-Induced Morbidity

  7. Hydrogen Protects Mice from Radiation Induced Thymic Lymphoma in BALB/c Mice

    PubMed Central

    Zhao, Luqian; Zhou, Chuanfeng; Zhang, Jian; Gao, Fu; Li, Bailong; Chuai, Yunhai; Liu, Cong; Cai, Jianming

    2011-01-01

    Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Moreover, an easy and effective method to protect mice from radiation induced thymic lymphoma is still unknown. Hydrogen, or H2, is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H2 protects mice from radiation induced thymic lymphoma in BALB/c mice. PMID:21448340

  8. Effects of N-acetylcysteine amide (NACA), a thiol antioxidant on radiation-induced cytotoxicity in Chinese hamster ovary cells.

    PubMed

    Wu, Wei; Abraham, Linu; Ogony, Joshua; Matthews, Richard; Goldstein, Glenn; Ercal, Nuran

    2008-05-23

    Ionizing radiation is known to cause tissue damage in biological systems, mainly due to its ability to produce reactive oxygen species (ROS) in cells. Many thiol antioxidants have been used previously as radioprotectors, but their application has been limited by their toxicity. In this investigation, we have explored the possible radioprotective effects of a newly synthesized thiol antioxidant, N-acetylcysteine amide (NACA), in comparison with N-acetylcysteine (NAC), a commonly used antioxidant. Protective effects of NACA and NAC were assessed using Chinese hamster ovary (CHO) cells, irradiated with 6 gray (Gy) radiation. Oxidative stress parameters, including levels of reduced glutathione (GSH), cysteine, malondialdehyde (MDA), and activities of antioxidant enzymes like glutathione peroxidase, glutathione reductase, and catalase, were measured. Results indicate that NACA was capable of restoring GSH levels in irradiated cells in a dose dependent manner. In addition, NACA prevented radiation-induced loss in cell viability. NACA further restored levels of malondialdehyde, caspase-3 activity, and antioxidant enzyme activities to control levels. Although NAC affected cells in a similar manner to NACA, its effects were not as significant. Further, NAC was also found to be cytotoxic to cells at higher concentrations, whereas NACA was non-toxic at similar concentrations. These results suggest that NACA may be able to attenuate radiation-induced cytotoxicity, possibly by its ability to provide thiols to cells.

  9. Radiation induced genome instability: multiscale modelling and data analysis

    NASA Astrophysics Data System (ADS)

    Andreev, Sergey; Eidelman, Yuri

    2012-07-01

    Genome instability (GI) is thought to be an important step in cancer induction and progression. Radiation induced GI is usually defined as genome alterations in the progeny of irradiated cells. The aim of this report is to demonstrate an opportunity for integrative analysis of radiation induced GI on the basis of multiscale modelling. Integrative, systems level modelling is necessary to assess different pathways resulting in GI in which a variety of genetic and epigenetic processes are involved. The multilevel modelling includes the Monte Carlo based simulation of several key processes involved in GI: DNA double strand breaks (DSBs) generation in cells initially irradiated as well as in descendants of irradiated cells, damage transmission through mitosis. Taking the cell-cycle-dependent generation of DNA/chromosome breakage into account ensures an advantage in estimating the contribution of different DNA damage response pathways to GI, as to nonhomologous vs homologous recombination repair mechanisms, the role of DSBs at telomeres or interstitial chromosomal sites, etc. The preliminary estimates show that both telomeric and non-telomeric DSB interactions are involved in delayed effects of radiation although differentially for different cell types. The computational experiments provide the data on the wide spectrum of GI endpoints (dicentrics, micronuclei, nonclonal translocations, chromatid exchanges, chromosome fragments) similar to those obtained experimentally for various cell lines under various experimental conditions. The modelling based analysis of experimental data demonstrates that radiation induced GI may be viewed as processes of delayed DSB induction/interaction/transmission being a key for quantification of GI. On the other hand, this conclusion is not sufficient to understand GI as a whole because factors of DNA non-damaging origin can also induce GI. Additionally, new data on induced pluripotent stem cells reveal that GI is acquired in normal mature

  10. Radiation-induced lichen sclerosus of the vulva : First report in the medical literature.

    PubMed

    Edwards, Lisa R; Privette, Emily D; Patterson, James W; Tchernev, Georgi; Chokoeva, Anastasiya Atanasova; Wollina, Uwe; Lotti, Torello; Wilson, Barbara B

    2017-03-01

    A 67-year-old woman presented with a firm plaque in the perineal region, 16 months after diagnosis of a high-grade basaloid squamous cell carcinoma of the vagina and treatment by external beam radiation therapy and vaginal cuff brachytherapy. The differential diagnosis included radiation-induced morphea, radiation dermatitis, or, possibly, radiation-induced lichen sclerosus. Biopsy findings, including special staining, confirmed the diagnosis of radiation-induced lichen sclerosus. To our knowledge, this is the first report of radiation-induced lichen sclerosus of the vulvar region.

  11. Calculation of radiation-induced creep and stress relaxation

    NASA Astrophysics Data System (ADS)

    Nagakawa, Johsei

    1995-08-01

    Numerical calculation based on a computer simulation of point defect kinetics under stress was performed to predict radiation-induced deformation in an Inconel X-750 bolt in a LWR core and for a 316 stainless steel blanket in experimental fusion reactors with the water-coolant scenario. Although the displacement rate is rather low, modest irradiation creep with nearly linear stress dependence was predicted below 200 MPa at 300°C in the LWR core. This low stress dependence causes significant stress relaxation, which coincides with the experimental data to 2 dpa. An almost equal amount of enhanced irradiation creep strain was predicted at 60°C in both solution annealed and cold worker 316 stainless steel in the water-cooled blanket. The stress relaxation is practically not expected without irradiation in both the cases, but the calculation predicts that it is definitely expected under irradiation.

  12. Factors that modify risks of radiation-induced cancer

    SciTech Connect

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors).

  13. Measurements of prompt radiation induced conductivity of alumina and sapphire

    SciTech Connect

    Hartman, E. Frederick; Zarick, Thomas Andrew; Sheridan, Timothy J.; Preston, Eric F.

    2011-04-01

    We performed measurements of the prompt radiation induced conductivity in thin samples of Alumina and Sapphire at the Little Mountain Medusa LINAC facility in Ogden, UT. Five mil thick samples were irradiated with pulses of 20 MeV electrons, yielding dose rates of 1E7 to 1E9 rad/s. We applied variable potentials up to 1 kV across the samples and measured the prompt conduction current. Analysis rendered prompt conductivity coefficients between 1E10 and 1E9 mho/m/(rad/s), depending on the dose rate and the pulse width for Alumina and 1E7 to 6E7 mho/m/(rad/s) for Sapphire.

  14. Radiation Induced Cystitis and Proctitis - Prediction, Assessment and Management.

    PubMed

    Mallick, Supriya; Madan, Renu; Julka, Pramod K; Rath, Goura K

    2015-01-01

    Cystitis and proctitis are defined as inflammation of bladder and rectum respectively. Haemorrhagic cystitis is the most severe clinical manifestation of radiation and chemical cystitis. Radiation proctitis and cystitis are major complications following radiotherapy. Prevention of radiation-induced haemorrhagic cystitis has been investigated using various oral agents with minimal benefit. Bladder irrigation remains the most frequently adopted modality followed by intra-vesical instillation of alum or formalin. In intractable cases, surgical intervention is required in the form of diversion ureterostomy or cystectomy. Proctitis is more common in even low dose ranges but is self-limiting and improves on treatment interruption. However, treatment of radiation proctitis is broadly non-invasive or invasive. Non-invasive treatment consists of non-steroid anti-inflammatory drugs (NSAIDs), anti-oxidants, sucralfate, short chain fatty acids and hyperbaric oxygen. Invasive treatment consists of ablative procedures like formalin application, endoscopic YAG laser coagulation or argon plasma coagulation and surgery as a last resort.

  15. Radiatively induced breaking of conformal symmetry in a superpotential

    NASA Astrophysics Data System (ADS)

    Arbuzov, A. B.; Cirilo-Lombardo, D. J.

    2016-07-01

    Radiatively induced symmetry breaking is considered for a toy model with one scalar and one fermion field unified in a superfield. It is shown that the classical quartic self-interaction of the superfield possesses a quantum infrared singularity. Application of the Coleman-Weinberg mechanism for effective potential leads to the appearance of condensates and masses for both scalar and fermion components. That induces a spontaneous breaking of the initial classical symmetries: the supersymmetry and the conformal one. The energy scales for the scalar and fermion condensates appear to be of the same order, while the renormalization scale is many orders of magnitude higher. A possibility to relate the considered toy model to conformal symmetry breaking in the Standard Model is discussed.

  16. Dose-dependent radiation-induced hypotension in the canine

    SciTech Connect

    Cockerham, L.G.; Hampton, J.D.; Doyle, T.F.

    1986-01-01

    Radiation-induced early transient incapacitation (ETI) is often accompanied by severe systemic hypotension. However, postradiation hypotension does not occur with equal frequency in all species and is not reported with consistency in the canine. In an attempt to clarify the differences in reported canine post-radiation blood pressures, canine systemic blood pressures were determined both before and after exposure to gamma radiation of either 80 or 100 Gy. Data obtained from six sham-radiated beagles and 12 radiated beagles indicated that 100-Gy, whole-body, gamma radiation produced a decrease in systemic mean blood pressure while 80-Gy, whole-body, gamma radiation did not. Analysis of this data could be consistent with a quantal response to a gamma radiation dose between 80 Gy and 100 Gy.

  17. Radiation-induced cerebral meningioma: a recognizable entity.

    PubMed

    Rubinstein, A B; Shalit, M N; Cohen, M L; Zandbank, U; Reichenthal, E

    1984-11-01

    The authors retrospectively analyzed the clinical and histopathological findings in 201 patients with intracranial meningiomas operated on in the period 1978 to 1982. Forty-three of the patients (21.4%) had at some previous time received radiation treatment to their scalp, the majority for tinea capitis. The findings in these 43 irradiated patients were compared with those in the 158 non-irradiated patients. Several distinctive clinical and histological features were identified in the irradiated group, which suggest that radiation-induced meningiomas can be defined as a separate nosological subgroup. The use of irradiation in large numbers of children with tinea capitis in the era prior to the availability of griseofulvin may be responsible for a significantly increased incidence of intracranial meningiomas.

  18. The Dose Window for Radiation-Induced Protective Adaptive Responses

    PubMed Central

    Mitchel, Ronald E. J.

    2009-01-01

    Adaptive responses to low doses of low LET radiation occur in all organisms thus far examined, from single cell lower eukaryotes to mammals. These responses reduce the deleterious consequences of DNA damaging events, including radiation-induced or spontaneous cancer and non-cancer diseases in mice. The adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGy for a single low dose rate exposure. However, these thresholds for protection are not a fixed function of total dose, but also vary with dose rate, additional radiation or non-radiation stressors, tissue type and p53 functional status. Exposures above the upper threshold are generally detrimental, while exposures below the lower threshold may or may not increase either cancer or non-cancer disease risk. PMID:20585438

  19. Study of radiation induced cancers in a breast screening programme.

    PubMed

    León, A; Verdú, G; Cuevas, M D; Salas, M D; Villaescusa, J I; Bueno, F

    2001-01-01

    It is demonstrated that screening mammography programmes reduce breast cancer mortality considerably. Nevertheless, radiology techniques have an intrinsic risk, the most important being the late somatic effect of the induction of cancer. This study was carried out in order to evaluate the risk to the population produced by the Comunidad Valenciana Breast Screening Programme. All the calculations are carried out for two risk models, UNSCEAR 94 and NRPB 93. On the one hand, screening series detriments are investigated as a function of doses delivered and other parameters related to population structure and X ray equipment. On the other hand the radiation induced cancer probability for a woman who starts at 45 years and remains in the programme until 65 years old is calculated as a function of mammography units' doses and average compression breast thickness. Finally, risk comparison between a screening programme starting at 45 years old and another one starting at 50 years old is made.

  20. [Radiation-induced and therapy-related AML/MDS].

    PubMed

    Inaba, Toshiya

    2009-10-01

    Radiation induced acute myeloid leukemia (AML) was recognized a century ago, soon after mankind found radiation. Atomic bomb survivors developed de novo AML with relatively short latency with very high frequency. By contrast, excess occurrence of myelodysplastic syndrome (MDS) as well as solid tumors was found decades late. This difference may be due to etiology that many de novo AML patients harbor chimeric leukemogenic genes caused by chromosomal translocations, while MDS patients rarely carry chimeras. In addition, epigenetic change would play important roles. Therapy related leukemia is mainly caused by topoisomerase II inhibitors that cause de novo AML with an 11q23 translocation or by alkyrating agents that induce MDS/AML with an AML1 point mutation and monosomy 7.

  1. Modification of microcrystalline cellulose by gamma radiation-induced grafting

    NASA Astrophysics Data System (ADS)

    Madrid, Jordan F.; Abad, Lucille V.

    2015-10-01

    Modified microcrystalline cellulose (MCC) was prepared through gamma radiation-induced graft polymerization of glycidyl methacrylate (GMA). Simultaneous grafting was employed wherein MCC with GMA in methanol was irradiated with gamma radiation in nitrogen atmosphere. The effects of different experimental factors such as monomer concentration, type of solvent and absorbed dose on the degree of grafting, Dg, were studied. The amount of grafted GMA, expressed as Dg, was determined gravimetrically. Information from grafted samples subjected to Fourier transformed infrared spectroscopy (FTIR) in attenuated total reflectance (ATR) mode showed peaks corresponding to GMA which indicates successful grafting. The X-ray diffraction (XRD) analysis revealed that the crystalline region of MCC was not adversely affected after grafting with GMA. The thermogravimetric analysis (TGA) data showed that the decomposition of grafted MCC occurred at higher temperature compared to the base MCC polymer.

  2. Radiation-induced polymerization for the immobilization of penicillin acylase

    SciTech Connect

    Boccu, E.; Carenza, M.; Lora, S.; Palma, G.; Veronese, F.M.

    1987-06-01

    The immobilization of Escherichia coli penicillin acylase was investigated by radiation-induced polymerization of 2-hydroxyethyl methacrylate at low temperature. A leak-proof composite that does not swell in water was obtained by adding the cross-linking agent trimethylolpropane trimethacrylate to the monomer-aqueous enzyme mixture. Penicillin acylase, which was immobilized with greater than 70% yield, possessed a higher Km value toward the substrate 6-nitro-3-phenylacetamidobenzoic acid than the free enzyme form (Km = 1.7 X 10(-5) and 1 X 10(-5) M, respectively). The structural stability of immobilized penicillin acylase, as assessed by heat, guanidinium chloride, and pH denaturation profiles, was very similar to that of the free-enzyme form, thus suggesting that penicillin acylase was entrapped in its native state into aqueous free spaces of the polymer matrix.

  3. Invertase immobilization onto radiation-induced graft copolymerized polyethylene pellets

    NASA Astrophysics Data System (ADS)

    de Queiroz, Alvaro Antonio Alencar; Vitolo, Michele; de Oliveira, Rômulo Cesar; Higa, Olga Zazuco

    1996-06-01

    The graft copolymer poly(ethylene-g-acrylic acid) (LDPE-g-AA) was prepared by radiation-induced graft copolymerization of acrylic acid onto low density polyethylene (LDPE) pellets, and characterized by infrared photoacoustic spectroscopy and scanning electron microscopy (SEM). The presence of the grafted poly(acrylic acid) (PAA) was established. Invertase was immobilized onto the graft polymer and the thermodynamic parameters of the soluble and immobilized enzyme were determined. The Michaelis constant, Km, and the maximum reaction velocity, Vmax, were determined for the free and the immobilized invertase. The Michaelis constant, Km was larger for the immobilized invertase than for the free enzyme, whereas Vmax was smaller for the immobilized invertase. The thermal stability of the immobilized invertase was higher than that of the free enzyme.

  4. Pulsed radiation-induced attenuation in certain optical fibers

    SciTech Connect

    Weiss, J.D. )

    1992-05-01

    Using the X-ray pulse from the HERMES II simulation machine at Sandia National Laboratories, the pulsed radiation-induced attenuation was measured in two optical fibers considered to be 'nonrad-hard': the 50-micron-core, graded-index fiber from Corning and the plastic (PMMA) fiber from the Mitsubishi Rayon Company. These fibers were exposed to radiation up to doses of 19.5 and 28 krad(Si), respectively. In addition, fits of their post-radiation recovery were made to the geminate recombination model, from which the recombination-rate and generation constants, characteristic of this theory, were determined. These parameters should be useful in determining the response of the fibers to radiation conditions other than those encountered here. 18 refs.

  5. Potential targets for intervention in radiation-induced heart disease.

    PubMed

    Boerma, M; Hauer-Jensen, M

    2010-11-01

    Radiotherapy of thoracic and chest wall tumors, if all or part of the heart was included in the radiation field, can lead to radiation-induced heart disease (RIHD), a late and potentially severe side effect. RIHD presents clinically several years after irradiation and manifestations include accelerated atherosclerosis, pericardial and myocardial fibrosis, conduction abnormalities, and injury to cardiac valves. The pathogenesis of RIHD is largely unknown, and a treatment is not available. Hence, ongoing pre-clinical studies aim to elucidate molecular and cellular mechanisms of RIHD. Here, an overview of recent pre-clinical studies is given, and based on the results of these studies, potential targets for intervention in RIHD are discussed.

  6. Radiation-induced degradation of 4-chloroaniline in aqueous solution

    NASA Astrophysics Data System (ADS)

    Sánchez, M.; Wolfger, H.; Getoff, N.

    2002-12-01

    The radiation-induced decomposition of 4-chloroaniline (4-ClA) was studied under steady-state conditions using aqueous solutions saturated with air, pure oxygen, N 2O, argon and argon in the presence of t-Butanol. Using HPLC-method, the initial G-values of the substrate degradation as well as of a number of radiolytic products were determined. The formation of aminophenols, chlorophenols, aniline and phenol in addition to chloride, ammonia, formaldehyde and mixture of aldehydes as well as carboxylic acids was studied as a function of absorbed dose. Based on the experimental data, probable reaction mechanisms for the degradation of 4-ClA by γ-rays and the formation of the identified products are presented.

  7. Modulation of radiation-induced hemopoietic suppression by acute thrombocytopenia

    SciTech Connect

    Ebbe, S.; Phalen, E.; Threatte, G.; Londe, H.

    1985-01-01

    Modifications of radiation-induced hemopoietic suppression by acute thrombocytopenia were evaluated. Immediately before or after exposure to sublethal irradiation, mice were given a single injection of anti-mouse platelet serum (APS), normal heterologous serum, neuraminidase (N'ase), or saline, or no further treatment was provided. Hemopoiesis was evaluated by blood cell counts, hematocrits, and incorporation of (75Se)selenomethionine into platelets. APS and N'ase induced an acute thrombocytopenia from which there was partial recovery before the platelet count started to fall from the radiation. During the second post-treatment week, both thrombocytopoiesis and erythropoiesis were greater in mice that received APS or N'ase in addition to radiation than in control irradiated mice. Differences in leukopoiesis were not apparent. Therefore, both thrombocytopoiesis and erythropoiesis appeared to be responsive to a stimulus generated by acute thrombocytopenia in sublethally irradiated mice.

  8. Probabilistic methodology for estimating radiation-induced cancer risk

    SciTech Connect

    Dunning, D.E. Jr.; Leggett, R.W.; Williams, L.R.

    1981-01-01

    The RICRAC computer code was developed at Oak Ridge National Laboratory to provide a versatile and convenient methodology for radiation risk assessment. The code allows as input essentially any dose pattern commonly encountered in risk assessments for either acute or chronic exposures, and it includes consideration of the age structure of the exposed population. Results produced by the analysis include the probability of one or more radiation-induced cancer deaths in a specified population, expected numbers of deaths, and expected years of life lost as a result of premature fatalities. These calculatons include consideration of competing risks of death from all other causes. The program also generates a probability frequency distribution of the expected number of cancers in any specified cohort resulting from a given radiation dose. The methods may be applied to any specified population and dose scenario.

  9. [Nonsurgical treatment of chronic radiation-induced hemorrhagic proctitis].

    PubMed

    de Parades, Vincent; Bauer, Pierre; Marteau, Philippe; Chauveinc, Laurent; Bouillet, Thierry; Atienza, Patrick

    2008-01-01

    The incidence of radiation-induced chronic hemorrhagic proctitis is less than 10 to 20%. The onset of this proctitis is delayed relative to the radiation therapy and generally develops from 6 to 24 months later. There are numerous predisposing factors, the most important of which is the radiation therapy dose: risk increases exponentially above 40-45 Gy. Its pathophysiology involves progressive obliterating endarteritis and transmural interstitial fibrosis, which induce chronic ischemia that is irreversible and progressive during the years after radiation therapy. Its diagnosis depends most often on the combination of clinical history and typical endoscopic appearance (congestive mucosa and/or telangiectases). Topical administrative of sucralfate or corticosteroids as well as argon plasma coagulation, with formalin treatment if necessary, provides relief for most patients.

  10. Radiation-induced cationic polymerization of. beta. -pinene

    SciTech Connect

    Adur, A.M.; Williams, F.

    1981-03-01

    The radiation-induced polymerization of ..beta..-pinene carried out in bulk at ca.25/sup 0/ has been studied for different methods of monomer drying. It has been confirmed that the polymerization is sensitive to adventitious moisture and that substantial polymer yields (ca. 10% conversion per Mrad) can only be obtained under extremely dry conditions. Complete inhibition of the reaction by added tripropylamine corroborates the view that the polymerization is cationic. About half of the polymer formed is insoluble in the monomer. The number-average molecular weights for the soluble poly(..beta..-pinene) fraction have been measured by vapor pressure osmometry and are in the narrow range from 1700 to 2400 with little or no dependence on the degree of monomer conversion to polymer, at least up to 80%. The results are compared with literature reports on the polymerization of ..beta..-pinene by catalytic initiators.

  11. Bystander effects in radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Morgan, William F.; Hartmann, Andreas; Limoli, Charles L.; Nagar, Shruti; Ponnaiya, Brian

    2002-01-01

    Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

  12. Intercellular Adhesion Molecule 1 Knockout Abrogates Radiation Induced Pulmonary Inflammation

    NASA Astrophysics Data System (ADS)

    Hallahan, Dennis E.; Virudachalam, Subbulakshmi

    1997-06-01

    Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration

  13. Radiation-induced leukemia: Comparative studies in mouse and man

    SciTech Connect

    Haas, M.

    1991-01-01

    We now have a clear understanding of the mechanism by which radiation-induced (T-cell) leukemia occurs. In irradiated mice (radiation-induced thymic leukemia) and in man (acute lymphoblastic T-cell leukemia, T-ALL) the mechanism of leukemogenesis is surprisingly similar. Expressed in the most elementary terms, T-cell leukemia occurs when T-cell differentiation is inhibited by a mutation, and pre-T cells attempt but fail to differentiate in the thymus. Instead of leaving the thymus for the periphery as functional T-cells they continue to proliferate in the thymus. The proliferating pre- (pro-) T-cells constitute the (early) acute T-cell leukemia (A-TCL). This model for the mechanism of T-cell leukemogenesis accounts for all the properties of both murine and human A-TCL. Important support for the model has recently come from work by Ilan Kirsch and others, who have shown that mutations/deletions in the genes SCL (TAL), SIL, and LCK constitute primary events in the development of T-ALL, by inhibiting differentiation of thymic pre- (pro-) T-cells. This mechanism of T-cell leukemogenesis brings several specific questions into focus: How do early A-TCL cells progress to become potently tumorigenic and poorly treatable Is it feasible to genetically suppress early and/or progressed A-TCL cells What is the mechanism by which the differentiation-inhibited (leukemic) pre-T cells proliferate During the first grant year we have worked on aspects of all three questions.

  14. Radiation-induced fibrosis: mechanisms and implications for therapy

    PubMed Central

    Straub, Jeffrey M.; New, Jacob; Hamilton, Chase D.; Lominska, Chris; Shnayder, Yelizaveta

    2015-01-01

    Purpose Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition. Methods A literature review of publications describing mechanisms or treatments of RIF was performed. Specific databases utilized included PubMed and clinicaltrials.gov, using keywords “Radiation-Induced Fibrosis,” “Radiotherapy Complications,” “Fibrosis Therapy,” and other closely related terms. Results RIF is the result of a misguided wound healing response. In addition to causing direct DNA damage, ionizing radiation generates reactive oxygen and nitrogen species that lead to localized inflammation. This inflammatory process ultimately evolves into a fibrotic one characterized by increased collagen deposition, poor vascularity, and scarring. Tumor growth factor beta serves as the primary mediator in this response along with a host of other cytokines and growth factors. Current therapies have largely been directed toward these molecular targets and their associated signaling pathways. Conclusion Although RIF is widely prevalent among patients undergoing radiation therapy and significantly impacts quality of life, there is still much to learn about its pathogenesis and mechanisms. Current treatments have stemmed from this understanding, and it is anticipated that further elucidation will be essential for the development of more effective therapies. PMID:25910988

  15. Bystander effects in radiation-induced genomic instability

    NASA Technical Reports Server (NTRS)

    Morgan, William F.; Hartmann, Andreas; Limoli, Charles L.; Nagar, Shruti; Ponnaiya, Brian

    2002-01-01

    Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

  16. Radiation-induced fibrosis: mechanisms and implications for therapy.

    PubMed

    Straub, Jeffrey M; New, Jacob; Hamilton, Chase D; Lominska, Chris; Shnayder, Yelizaveta; Thomas, Sufi M

    2015-11-01

    Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition. A literature review of publications describing mechanisms or treatments of RIF was performed. Specific databases utilized included PubMed and clinicaltrials.gov, using keywords "Radiation-Induced Fibrosis," "Radiotherapy Complications," "Fibrosis Therapy," and other closely related terms. RIF is the result of a misguided wound healing response. In addition to causing direct DNA damage, ionizing radiation generates reactive oxygen and nitrogen species that lead to localized inflammation. This inflammatory process ultimately evolves into a fibrotic one characterized by increased collagen deposition, poor vascularity, and scarring. Tumor growth factor beta serves as the primary mediator in this response along with a host of other cytokines and growth factors. Current therapies have largely been directed toward these molecular targets and their associated signaling pathways. Although RIF is widely prevalent among patients undergoing radiation therapy and significantly impacts quality of life, there is still much to learn about its pathogenesis and mechanisms. Current treatments have stemmed from this understanding, and it is anticipated that further elucidation will be essential for the development of more effective therapies.

  17. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    NASA Astrophysics Data System (ADS)

    Ahmad, S. B.; McNeill, F. E.; Byun, S. H.; Prestwich, W. V.; Seymour, C.; Mothersill, C. E.

    2012-10-01

    The aim of this work is quantify the light emitted as a result of charged particle interaction in materials which may be of relevance to radiation induced "bystander effects" studies. We have developed a system which employs single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. The system uses a fast photomultiplier tube with a peak cathode response at 420 nm. It has been tested in a proof-of-principle experiment using polystyrene targets. Light output, as a result of irradiation, was measured. The luminescence yield appears to have a non-linear behavior with the incident ion fluence: it rises exponentially to an asymptotic value. The target was irradiated with beam energies varying from 1 to 2 MeV and showed saturation at or before an incident fluence rate of 3 × 1013 H+/cm2 s. The average saturation value for the photon output was found to be 40 × 106 cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28 × 103, 10 × 106, and 35 × 106 cps for wavelengths of 280 ± 5 nm, 320 ± 5 nm and 340 ± 5 nm respectively. The light output reaches a maximum value because of damage induced in the polymer. Our measurements indicate a "damage cross section" of the order of 10-14 cm2. The average radiant intensity was found to increase at wavelengths of 280 and 320 nm when the proton energy was increased. This was not found to occur at 340 nm. In conclusion, the light emission at specific wavelengths was found to depend upon the incident proton fluence and the proton energy. The wavelengths of the emitted light measured in this study have significance for the understanding of radiation induced bystander effects.

  18. Barriers to Radiation-Induced In Situ Tumor Vaccination

    PubMed Central

    Wennerberg, Erik; Lhuillier, Claire; Vanpouille-Box, Claire; Pilones, Karsten A.; García-Martínez, Elena; Rudqvist, Nils-Petter; Formenti, Silvia C.; Demaria, Sandra

    2017-01-01

    The immunostimulatory properties of radiation therapy (RT) have recently generated widespread interest due to preclinical and clinical evidence that tumor-localized RT can sometimes induce antitumor immune responses mediating regression of non-irradiated metastases (abscopal effect). The ability of RT to activate antitumor T cells explains the synergy of RT with immune checkpoint inhibitors, which has been well documented in mouse tumor models and is supported by observations of more frequent abscopal responses in patients refractory to immunotherapy who receive RT during immunotherapy. However, abscopal responses following RT remain relatively rare in the clinic, and antitumor immune responses are not effectively induced by RT against poorly immunogenic mouse tumors. This suggests that in order to improve the pro-immunogenic effects of RT, it is necessary to identify and overcome the barriers that pre-exist and/or are induced by RT in the tumor microenvironment. On the one hand, RT induces an immunogenic death of cancer cells associated with release of powerful danger signals that are essential to recruit and activate dendritic cells (DCs) and initiate antitumor immune responses. On the other hand, RT can promote the generation of immunosuppressive mediators that hinder DCs activation and impair the function of effector T cells. In this review, we discuss current evidence that several inhibitory pathways are induced and modulated in irradiated tumors. In particular, we will focus on factors that regulate and limit radiation-induced immunogenicity and emphasize current research on actionable targets that could increase the effectiveness of radiation-induced in situ tumor vaccination. PMID:28348554

  19. Role of Oxidative Damage in Radiation-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  20. [Radiation-induced cancers: state of the art in 1997].

    PubMed

    Cosset, J M

    1997-01-01

    Scientists now have available a large amount of data dealing with radiation-induced neoplasms. These data went back to anecdotal observations which were made in the very first years of utilization of X-rays and radioactive elements. In fact, it is essentially the strict follow-up of the Japanese populations irradiated by the Hiroshima and Nagasaki bombing which allowed a more precise evaluation of the carcinogenicity of ionizing radiations. Further refinements came from therapeutical irradiations: it is now possible to study large cohorts of patients given well-known doses in well-defined volumes and followed for more than 20 years. Last but not least, a significant increase in the incidence and mortality of thyroid cancer has been detected in children contaminated by iodine radioisotopes after the Tchernobyl accident. Recently, some data suggested the emergence of "clusters" of leukemias close to some nuclear facilities, but this question remains highly polemical, both in France and in the UK. Other questions are still waiting for a precise answer; of course, the extrapolation of our available data to very low doses delivered at very low dose rates, but also the carcinogenic risk at high doses. For these "high" doses (about 30 to 70 Gy), a competition between mutagenesis and cell killing was expected, so that these dose levels were expected to be less carcinogenic than lower (a few sieverts) doses. Actually, recent data suggest that the carcinogenic risk goes on increasing up to relatively important doses. In addition, carcinogenic factors, such as tabacco, anticancer chemotherapy and individual susceptibility, are found more and more to be closely intricated with ionizing radiation in the genesis of a given cancer. Even if a number of questions are still pending, the already available data allow specialists, both in medicine and radioprotection, to edict strict rules which can be reasonably expected to have significantly reduced the risk of radiation-induced

  1. Simulating Space Radiation-Induced Breast Tumor Incidence Using Automata.

    PubMed

    Heuskin, A C; Osseiran, A I; Tang, J; Costes, S V

    2016-07-01

    Estimating cancer risk from space radiation has been an ongoing challenge for decades primarily because most of the reported epidemiological data on radiation-induced risks are derived from studies of atomic bomb survivors who were exposed to an acute dose of gamma rays instead of chronic high-LET cosmic radiation. In this study, we introduce a formalism using cellular automata to model the long-term effects of ionizing radiation in human breast for different radiation qualities. We first validated and tuned parameters for an automata-based two-stage clonal expansion model simulating the age dependence of spontaneous breast cancer incidence in an unexposed U.S. We then tested the impact of radiation perturbation in the model by modifying parameters to reflect both targeted and nontargeted radiation effects. Targeted effects (TE) reflect the immediate impact of radiation on a cell's DNA with classic end points being gene mutations and cell death. They are well known and are directly derived from experimental data. In contrast, nontargeted effects (NTE) are persistent and affect both damaged and undamaged cells, are nonlinear with dose and are not well characterized in the literature. In this study, we introduced TE in our model and compared predictions against epidemiologic data of the atomic bomb survivor cohort. TE alone are not sufficient for inducing enough cancer. NTE independent of dose and lasting ∼100 days postirradiation need to be added to accurately predict dose dependence of breast cancer induced by gamma rays. Finally, by integrating experimental relative biological effectiveness (RBE) for TE and keeping NTE (i.e., radiation-induced genomic instability) constant with dose and LET, the model predicts that RBE for breast cancer induced by cosmic radiation would be maximum at 220 keV/μm. This approach lays the groundwork for further investigation into the impact of chronic low-dose exposure, inter-individual variation and more complex space radiation

  2. Radiation-induced sarcomas of bone: factors that affect outcome.

    PubMed

    Kalra, S; Grimer, R J; Spooner, D; Carter, S R; Tillman, R M; Abudu, A

    2007-06-01

    We identified 42 patients who presented to our unit over a 27-year period with a secondary radiation-induced sarcoma of bone. We reviewed patient, tumour and treatment factors to identify those that affected outcome. The mean age of the patients at presentation was 45.6 years (10 to 84) and the mean latent interval between radiotherapy and diagnosis of the sarcoma was 17 years (4 to 50). The median dose of radiotherapy given was estimated at 50 Gy (mean 49; 20 to 66). There was no correlation between radiation dose and the time to development of a sarcoma. The pelvis was the most commonly affected site (14 patients (33%)). Breast cancer was the most common primary tumour (eight patients; 19%). Metastases were present at diagnosis of the sarcoma in nine patients (21.4%). Osteosarcoma was the most common diagnosis and occurred in 30 cases (71.4%). Treatment was by surgery and chemotherapy when indicated: 30 patients (71.4%) were treated with the intention to cure. The survival rate was 41% at five years for those treated with the intention to cure but in those treated palliatively the mean survival was only 8.8 months (2 to 22), and all had died by two years. The only factor found to be significant for survival was the ability to completely resect the tumour. Limb sarcomas had a better prognosis (66% survival at five years) than central ones (12% survival at five years) (p = 0.009). Radiation-induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by the treatment received previously by the patient.

  3. Sci—Thur AM: YIS - 02: Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    SciTech Connect

    Coates, J; Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; El Naqa, I

    2014-08-15

    Inter-patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation-induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 and 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross-validation. Binary variables were evaluated using Chi-squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ{sup 2}=14.6, p<0.001 and ED: χ{sup 2}=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ{sup 2}=0.278, p=0.599 and ED: χ{sup 2}=0.112, p=0.732). Radiogenomic modeling yielded significant, cross-validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

  4. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    PubMed Central

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

    2014-01-01

    Purpose/Objectives(s) The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events (SPEs), as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials Ferrets were exposed to 0 – 2 Gray (Gy) of whole body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results The lethal dose of radiation to 50% of the population, known as the LD50, of ferrets was established at ~ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 post-irradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early times post-irradiation when coagulopathies were present and progressively becoming more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions The data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is solely due to the cell killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation induced death at relatively low doses in large mammals. PMID:24495588

  5. Evidence for radiation-induced disseminated intravascular coagulation as a major cause of radiation-induced death in ferrets.

    PubMed

    Krigsfeld, Gabriel S; Savage, Alexandria R; Billings, Paul C; Lin, Liyong; Kennedy, Ann R

    2014-03-15

    The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    SciTech Connect

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  7. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A. )

    1990-01-01

    Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine.

  8. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

  9. Common European Mitochondrial Haplogroups in the Risk for Radiation-induced Subcutaneous Fibrosis in Breast Cancer Patients.

    PubMed

    Terrazzino, S; Deantonio, L; Cargnin, S; Donis, L; Pisani, C; Masini, L; Gambaro, G; Canonico, P L; Genazzani, A A; Krengli, M

    2016-06-01

    The contribution of mitochondrial DNA (mtDNA) variations to clinical radiosensitivity is largely unknown. In the present study, we evaluated the association between mtDNA haplogroups and the risk of radiation-induced subcutaneous fibrosis after postoperative radiotherapy in breast cancer patients. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale in 286 Italian breast cancer patients who received radiotherapy after breast-conserving surgery. Eight mtDNA single nucleotide polymorphisms that define the nine major haplogroups in the European population were determined by polymerase chain reaction restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood. In a Kaplan-Meier analysis evaluated by the Log-rank test, carriers of haplogroup H were found to be at lower risk of grade ≥2 subcutaneous fibrosis (P = 0.018) compared with all other haplotypes combined. In the multivariate Cox regression analysis adjusted for clinical factors (body mass index, breast diameter, adjuvant treatment, dose per fraction, radiation type and acute skin toxicity), haplogroup H emerged as a protective factor for moderate to severe radiation-induced fibrosis at a nominal significance level (hazard ratio: 0.50, 95% confidence interval 0.27-0.92, P = 0.027), which did not survive correction for multiple testing. Our results suggest a protective effect of the mitochondrial haplogroup H in the development of radiation-induced fibrosis in breast cancer patients. However, the loss of statistical significance after correction for multiple comparisons and the lack of an independent validation cohort make our findings preliminary, requiring further confirmation in large-scale prospective studies. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  10. [Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome].

    PubMed

    Yoshimura, Junichi; Natsumeda, Manabu; Nishihira, Yasushi; Nishiyama, Kenichi; Saito, Akihiko; Okamoto, Kouichirou; Takahashi, Hitoshi; Fujii, Yukihiko

    2013-06-01

    A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome.

  11. Hyperbaric Oxygen Therapy for Radiation-Induced Cystitis and Proctitis

    SciTech Connect

    Oliai, Caspian; Fisher, Brandon; Jani, Ashish; Wong, Michael; Poli, Jaganmohan; Brady, Luther W.; Komarnicky, Lydia T.

    2012-11-01

    Purpose: To provide a retrospective analysis of the efficacy of hyperbaric oxygen therapy (HBOT) for treating hemorrhagic cystitis (HC) and proctitis secondary to pelvic- and prostate-only radiotherapy. Methods and Materials: Nineteen patients were treated with HBOT for radiation-induced HC and proctitis. The median age at treatment was 66 years (range, 15-84 years). The range of external-beam radiation delivered was 50.0-75.6 Gy. Bleeding must have been refractory to other therapies. Patients received 100% oxygen at 2.0 atmospheres absolute pressure for 90-120 min per treatment in a monoplace chamber. Symptoms were retrospectively scored according to the Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) scale to evaluate short-term efficacy. Recurrence of hematuria/hematochezia was used to assess long-term efficacy. Results: Four of the 19 patients were lost to follow-up. Fifteen patients were evaluated and received a mean of 29.8 dives: 11 developed HC and 4 proctitis. All patients experienced a reduction in their LENT-SOMA score. After completion of HBOT, the mean LENT-SOMA score was reduced from 0.78 to 0.20 in patients with HC and from 0.66 to 0.26 in patients with proctitis. Median follow-up was 39 months (range, 7-70 months). No cases of hematuria were refractory to HBOT. Complete resolution of hematuria was seen in 81% (n = 9) and partial response in 18% (n = 2). Recurrence of hematuria occurred in 36% (n = 4) after a median of 10 months. Complete resolution of hematochezia was seen in 50% (n = 2), partial response in 25% (n = 1), and refractory bleeding in 25% (n = 1). Conclusions: Hyperbaric oxygen therapy is appropriate for radiation-induced HC once less time-consuming therapies have failed to resolve the bleeding. In these conditions, HBOT is efficacious in the short and long term, with minimal side effects.

  12. Radiation-Induced Bystander Effects in Cultured Human Stem Cells

    PubMed Central

    Sokolov, Mykyta V.; Neumann, Ronald D.

    2010-01-01

    Background The radiation-induced “bystander effect” (RIBE) was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR). RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC) are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed. Methodology/Principal Findings Human bone-marrow mesenchymal stem cells (hMSC) and embryonic stem cells (hESC) were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05). A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05). Conclusions/Significance These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative

  13. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    PubMed Central

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  14. Protective effect of an aminothiazole compound against γ-radiation induced oxidative damage.

    PubMed

    De, Strayo; Devasagayam, Thomas P A

    2011-11-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. During radiotherapy of cancer, one of the undesirable side-effects is toxicity to normal cells. Compounds with antioxidant activities are being tried as 'prophylactic radioprotectants' to overcome this problem. We evaluated the protective effect of an aminothiazole compound, in the form of dendrodoine analogue (DA) originally derived from a marine tunicate, against γ-radiation-induced damage to lipid, protein, and DNA besides its cytotoxicity. Oxidative damage was examined by different biochemcial assays. Our studies reveal that DA gave significant protection, in fairly low concentrations, against damage induced by γ-radiation to rat liver mitochondria, plasmid pBR322 DNA, and mouse splenic lymphocytes in vitro. It also protected against oxidative damage in whole-body irradiated mice exposed to therapeutic dose of radiation (2 Gy) in vivo. Spleen, a major target organ for radiation damage, of the irradiated mice showed significant protection when treated with DA, as examined by histopathology. In conclusion, due to the possible protective effects against normal cells/tissues both in vitro and in vivo, DA shows potential to be a radioprotector for possible use during radiotherapy.

  15. Radiation-induced blood-brain barrier changes: pathophysiological mechanisms and clinical implications.

    PubMed

    d'Avella, D; Cicciarello, R; Angileri, F F; Lucerna, S; La Torre, D; Tomasello, F

    1998-01-01

    The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely understood. The possibility of a primary change in blood-brain barrier (BBB) associated with microvascular damage was investigated. Rats were exposed to conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid (AIB) technique coupled with standard electron microscopy (EM) and morphometric techniques as well as studies of the transcapillary passage of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB increased significantly in cerebral cortex. EM disclosed vesicular transport of HRP across the intact endothelium without opening of the tight junctions. Ninety days after WBR, well-defined alterations of the microvasculature were observed. The main feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Data suggest a possible association between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain cerebral dysfunction. We hypothesize the following sequence of pathophysiological events: WBR causes an early increase in BBB permeability, which produces perivascular edema and microvascular collapse. The interference with microcirculation affects blood flow and energy supply to the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

  16. Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis.

    PubMed

    Mavragani, Ifigeneia V; Nikitaki, Zacharenia; Souli, Maria P; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy; Georgakilas, Alexandros G

    2017-07-18

    Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15-20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent "danger" signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

  17. Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

    PubMed Central

    Mavragani, Ifigeneia V.; Nikitaki, Zacharenia; Souli, Maria P.; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy

    2017-01-01

    Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair. PMID:28718816

  18. Novel Regenerative Peptide TP508 Mitigates Radiation-Induced Gastrointestinal Damage By Activating Stem Cells and Preserving Crypt Integrity

    PubMed Central

    Kantara, Carla; Moya, Stephanie M.; Houchen, Courtney W.; Umar, Shahid; Ullrich, Robert L.; Singh, Pomila; Carney, Darrell H.

    2015-01-01

    In recent years, increasing threats of radiation exposure and nuclear disasters have become a significant concern for the United States and countries worldwide. Exposure to high doses of radiation triggers a number of potentially lethal effects. Among the most severe is the gastrointestinal (GI) toxicity syndrome caused by the destruction of the intestinal barrier, resulting in bacterial translocation, systemic bacteremia, sepsis and death. The lack of effective radioprotective agents capable of mitigating radiation-induced damage has prompted a search for novel countermeasures that can mitigate the effects of radiation post-exposure, accelerate tissue repair in radiation-exposed individuals, and prevent mortality. We report that a single injection of regenerative peptide TP508 (rusalatide acetate, Chrysalin®) 24h after lethal radiation exposure (9Gy, LD100/15) appears to significantly increase survival and delay mortality by mitigating radiation-induced intestinal and colonic toxicity. TP508 treatment post-exposure prevents the disintegration of gastrointestinal crypts, stimulates the expression of adherens junction protein E-cadherin, activates crypt cell proliferation, and decreases apoptosis. TP508 post-exposure treatment also up-regulates the expression of DCLK1 and LGR5 markers of stem cells that have been shown to be responsible for maintaining and regenerating intestinal crypts. Thus, TP508 appears to mitigate the effects of GI toxicity by activating radioresistant stem cells and increasing the stemness potential of crypts to maintain and restore intestinal integrity. These results suggest that TP508 may be an effective emergency nuclear countermeasure that could be delivered within 24h post-exposure to increase survival and delay mortality, giving victims time to reach clinical sites for advanced medical treatment. PMID:26280221

  19. Novel regenerative peptide TP508 mitigates radiation-induced gastrointestinal damage by activating stem cells and preserving crypt integrity.

    PubMed

    Kantara, Carla; Moya, Stephanie M; Houchen, Courtney W; Umar, Shahid; Ullrich, Robert L; Singh, Pomila; Carney, Darrell H

    2015-11-01

    In recent years, increasing threats of radiation exposure and nuclear disasters have become a significant concern for the United States and countries worldwide. Exposure to high doses of radiation triggers a number of potentially lethal effects. Among the most severe is the gastrointestinal (GI) toxicity syndrome caused by the destruction of the intestinal barrier, resulting in bacterial translocation, systemic bacteremia, sepsis, and death. The lack of effective radioprotective agents capable of mitigating radiation-induced damage has prompted a search for novel countermeasures that can mitigate the effects of radiation post exposure, accelerate tissue repair in radiation-exposed individuals, and prevent mortality. We report that a single injection of regenerative peptide TP508 (rusalatide acetate, Chrysalin) 24 h after lethal radiation exposure (9 Gy, LD100/15) appears to significantly increase survival and delay mortality by mitigating radiation-induced intestinal and colonic toxicity. TP508 treatment post exposure prevents the disintegration of GI crypts, stimulates the expression of adherens junction protein E-cadherin, activates crypt cell proliferation, and decreases apoptosis. TP508 post-exposure treatment also upregulates the expression of DCLK1 and LGR5 markers of stem cells that have been shown to be responsible for maintaining and regenerating intestinal crypts. Thus, TP508 appears to mitigate the effects of GI toxicity by activating radioresistant stem cells and increasing the stemness potential of crypts to maintain and restore intestinal integrity. These results suggest that TP508 may be an effective emergency nuclear countermeasure that could be delivered within 24 h post exposure to increase survival and delay mortality, giving victims time to reach clinical sites for advanced medical treatment.

  20. Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

    SciTech Connect

    Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher; Christie, Alana; Lotan, Yair; Pistenmaa, David; Kavanagh, Brian D.; Nanda, Akash; Kueplian, Patrick; Brindle, Jeffrey; Cooley, Susan; Perkins, Alida; Raben, David; Xie, Xian-Jin; Timmerman, Robert D.

    2014-07-01

    Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.

  1. Clinical effect of multileaf collimator width on the incidence of late rectal bleeding after high-dose intensity-modulated radiotherapy for localized prostate carcinoma.

    PubMed

    Inokuchi, Haruo; Mizowaki, Takashi; Norihisa, Yoshiki; Takayama, Kenji; Ikeda, Itaru; Nakamura, Kiyonao; Nakamura, Mitsuhiro; Hiraoka, Masahiro

    2016-02-01

    Several studies have confirmed a dosimetric advantage associated with use of a smaller leaf in intensity-modulated radiation therapy (IMRT). However, no studies have identified any clinical benefits. We investigated the effect of a smaller multileaf collimator (MLC) width on the onset of late rectal bleeding after high-dose prostate IMRT. Two hundred and five prostate cancer patients were treated with a total dose of 78 Gy in 39 fractions by use of a dynamic MLC technique; however, two different MLC were used: a 10-mm-wide device and a 5-mm-wide device. Gastrointestinal toxicity and several clinical factors were assessed. The 5-year actuarial risk of grade 2 or higher rectal bleeding was 6.9 % for the 10-mm-wide group (n = 132) and 1.8 % for the 5-mm-wide group (n = 73) (p = 0.04). The median estimated rectal doses for the two groups were 55.1 and 50.6 Gy (p < 0.001), respectively. Univariate analysis showed that acute toxicity, rectal V30-60, median rectal dose, normal tissue complication probability (NTCP), and MLC type were significant predictive factors for late rectal toxicity. In multivariate analysis, acute toxicity and NTCP remained significant. In our planning approach for prostate IMRT, a decrease in MLC width from 10 to 5 mm contributed to further rectal dose reduction, which was the most important predictor of late rectal toxicity.

  2. Investigations of radiation-induced and carrier-enhanced conductivity

    NASA Astrophysics Data System (ADS)

    Meulenberg, A., Jr.; Parker, L. W.; Yadlowski, E. J.; Hazelton, R. C.

    1985-03-01

    A steady-state carrier computer code, PECK (Parker Enhanced Carrier Kinetics), that predicts the radiation-induced conductivity (RIC) produced in a dielectric by an electron beam was developed. The model, which assumes instantly-trapped holes, was then applied to experimental measurements on thin Kapton samples penetrated by an electron beam. Measurements at high bias were matched in the model by an appropriate choice for the trap-modulated electron mobility. A fractional split between front and rear currents measured at zone bias is explained on the basis of beam-scattering. The effects of carrier-enhanced conductivity (CEC) on data obtained for thick, free-surface Kapton samples is described by using an analytical model that incorporates field injection of carriers from the RIC region. The computer code, LWPCHARGE, modified for carrier transport, is also used to predict partial penetration effects associated with CEC in the unirradiated region. Experimental currents and surface voltages, when incorporated in the appropriate models, provide a value for the trap modulated mobility that is in essential agreement with the RIC results.

  3. Investigations of radiation-induced and carrier-enhanced conductivity

    NASA Technical Reports Server (NTRS)

    Meulenberg, A., Jr.; Parker, L. W.; Yadlowski, E. J.; Hazelton, R. C.

    1985-01-01

    A steady-state carrier computer code, PECK (Parker Enhanced Carrier Kinetics), that predicts the radiation-induced conductivity (RIC) produced in a dielectric by an electron beam was developed. The model, which assumes instantly-trapped holes, was then applied to experimental measurements on thin Kapton samples penetrated by an electron beam. Measurements at high bias were matched in the model by an appropriate choice for the trap-modulated electron mobility. A fractional split between front and rear currents measured at zone bias is explained on the basis of beam-scattering. The effects of carrier-enhanced conductivity (CEC) on data obtained for thick, free-surface Kapton samples is described by using an analytical model that incorporates field injection of carriers from the RIC region. The computer code, LWPCHARGE, modified for carrier transport, is also used to predict partial penetration effects associated with CEC in the unirradiated region. Experimental currents and surface voltages, when incorporated in the appropriate models, provide a value for the trap modulated mobility that is in essential agreement with the RIC results.

  4. Space-radiation-induced Photon Luminescence of the Moon

    NASA Technical Reports Server (NTRS)

    Wilson, Thomas; Lee, Kerry

    2008-01-01

    We report on the results of a study of the photon luminescence of the Moon induced by Galactic Cosmic Rays (GCRs) and space radiation from the Sun, using the Monte Carlo program FLUKA. The model of the lunar surface is taken to be the chemical composition of soils found at various landing sites during the Apollo and Luna programs, averaged over all such sites to define a generic regolith for the present analysis. This then becomes the target that is bombarded by Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) above 1 keV in FLUKA to determine the photon fluence albedo produced by the Moon's surface when there is no sunlight and Earthshine. This is to be distinguished from the gamma-ray spectrum produced by the radioactive decay of radiogenic constituents lying in the surface and interior of the Moon. From the photon fluence we derive the spectrum which can be utilized to examine existing lunar spectral data and to design orbiting instrumentation for measuring various components of the space-radiation-induced photon luminescence present on the Moon.

  5. Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

    PubMed Central

    Chen, Jinmei; Zhang, Weijian; Zhang, Lurong; Zhang, Jiemin; Chen, Xiuying; Yang, Meichun; Chen, Ting; Hong, Jinsheng

    2017-01-01

    Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway. PMID:27672101

  6. Radiation-induced conductivity control in polyaniline blends/composites

    NASA Astrophysics Data System (ADS)

    Güven, Olgun

    2007-08-01

    Polyaniline (PANI) blends with chlorine-containing polymers and copolymers and composites with HCl-releasing compounds were prepared to investigate their radiation response in terms of induced conductivities. Blends of non-conductive PANI with poly(vinyl chloride) (PVC), poly(vinylidene chloride- co-vinyl acetate), [P(VDC- co-VAc)], poly(vinylidene chloride- co-vinyl chloride), [P(VDC- co-VC)] were prepared in the form of as-cast films. A number of blends which are different in composition were exposed to gamma radiation and accelerated electrons to various doses, and the effects of irradiation type and composition of polymers on the conductivity of films were investigated by using conductivity measurements and UV-vis and FT-IR spectroscopy. The results clearly showed that ionizing radiation is an effective tool to induce and control conductivity in the blends of PANI-base with chlorine-carrying polymers as well as its composites prepared from HCl-releasing compounds such as chloral hydrate. The main mechanism behind this radiation-induced conductivity is in situ doping of PANI-base with HCl released from partner polymers and low molecular weight compounds by the effect of radiation.

  7. Gamma radiation induced changes in nuclear waste glass containing Eu

    NASA Astrophysics Data System (ADS)

    Mohapatra, M.; Kadam, R. M.; Mishra, R. K.; Kaushik, C. P.; Tomar, B. S.; Godbole, S. V.

    2011-10-01

    Gamma radiation induced changes were investigated in sodium-barium borosilicate glasses containing Eu. The glass composition was similar to that of nuclear waste glasses used for vitrifying Trombay research reactor nuclear waste at Bhabha Atomic Research Centre, India. Photoluminescence (PL) and electron paramagnetic resonance (EPR) techniques were used to study the speciation of the rare earth (RE) ion in the matrix before and after gamma irradiation. Judd-Ofelt ( J- O) analyses of the emission spectra were done before and after irradiation. The spin counting technique was employed to quantify the number of defect centres formed in the glass at the highest gamma dose studied. PL data suggested the stabilisation of the trivalent RE ion in the borosilicate glass matrix both before and after irradiation. It was also observed that, the RE ion distributes itself in two different environments in the irradiated glass. From the EPR data it was observed that, boron oxygen hole centre based radicals are the predominant defect centres produced in the glass after irradiation along with small amount of E’ centres. From the spin counting studies the concentration of defect centres in the glass was calculated to be 350 ppm at 900 kGy. This indicated the fact that bulk of the glass remained unaffected after gamma irradiation up to 900 kGy.

  8. Space-radiation-induced Photon Luminescence of the Moon

    NASA Technical Reports Server (NTRS)

    Wilson, Thomas; Lee, Kerry

    2008-01-01

    We report on the results of a study of the photon luminescence of the Moon induced by Galactic Cosmic Rays (GCRs) and space radiation from the Sun, using the Monte Carlo program FLUKA. The model of the lunar surface is taken to be the chemical composition of soils found at various landing sites during the Apollo and Luna programs, averaged over all such sites to define a generic regolith for the present analysis. This then becomes the target that is bombarded by Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) above 1 keV in FLUKA to determine the photon fluence albedo produced by the Moon's surface when there is no sunlight and Earthshine. This is to be distinguished from the gamma-ray spectrum produced by the radioactive decay of radiogenic constituents lying in the surface and interior of the Moon. From the photon fluence we derive the spectrum which can be utilized to examine existing lunar spectral data and to design orbiting instrumentation for measuring various components of the space-radiation-induced photon luminescence present on the Moon.

  9. Gamma radiation induces hydrogen absorption by copper in water

    NASA Astrophysics Data System (ADS)

    Lousada, Cláudio M.; Soroka, Inna L.; Yagodzinskyy, Yuriy; Tarakina, Nadezda V.; Todoshchenko, Olga; Hänninen, Hannu; Korzhavyi, Pavel A.; Jonsson, Mats

    2016-04-01

    One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H2(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories.

  10. Molecular Mechanisms and Treatment of Radiation-Induced Lung Fibrosis

    PubMed Central

    Ding, Nian-Hua; Li, Jian Jian; Sun, Lun-Quan

    2014-01-01

    Radiation-induced lung fibrosis (RILF) is a severe side effect of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury combined with chronic inflammation and exaggerated organ repair. RILF is a major barrier to improving the cure rate and well-being of lung cancer patients because it limits the radiation dose that is required to effectively kill tumor cells and diminishes normal lung function. Although the exact mechanism is unclear, accumulating evidence suggests that various cells, cytokines and regulatory molecules are involved in the tissue reorganization and immune response modulation that occur in RILF. In this review, we will summarize the general symptoms, diagnostics, and current understanding of the cells and molecular factors that are linked to the signaling networks implicated in RILF. Potential approaches for the treatment of RILF will also be discussed. Elucidating the key molecular mediators that initiate and control the extent of RILF in response to therapeutic radiation may reveal additional targets for RILF treatment to significantly improve the efficacy of radiotherapy for lung cancer patients. PMID:23909719

  11. Radiation-induced chromosomal instability in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  12. Radiation-Induced Notch Signaling in Breast Cancer Stem Cells

    SciTech Connect

    Lagadec, Chann; Vlashi, Erina; Alhiyari, Yazeed; Phillips, Tiffany M.; Bochkur Dratver, Milana; Pajonk, Frank

    2013-11-01

    Purpose: To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation. Methods and Materials: Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription–polymerase chain reaction to study the Notch pathway in response to radiation. Results: We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose–dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells. Additionally, radiation activated the Notch pathway. Treatment with a γ-secretase inhibitor prevented radiation-induced Notch family gene expression and led to a significant reduction in the size of the breast cancer stem cell pool. Conclusions: Our results indicate that, if combined with radiation, γ-secretase inhibitors may prevent up-regulation of Notch receptor and ligand family members and thus reduce the number of surviving breast cancer stem cells.

  13. Radiation-induced optic neuropathy: A magnetic resonance imaging study

    SciTech Connect

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J. )

    1991-03-01

    Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.

  14. Perinatal radiation-induced renal damage in the beagle

    SciTech Connect

    Jaenke, R.S.; Angleton, G.M. )

    1990-04-01

    The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated.

  15. Effects of contrast medium on radiation-induced chromosome aberrations

    SciTech Connect

    Matsubara, S.; Suzuki, S.; Suzuki, H.; Kuwabara, Y.; Okano, T.

    1982-07-01

    The effects of contrast material (meglumine iothalamate) on radiation-induced chromosome aberrations were investigated in studies on the lymphocytes of patients who had undergone diagnostic radiography and in in vitro experiments with diagnostic x rays and /sup 60/Co gamma rays. Chromosome and chromatid aberrations were found to increase significantly with increasing concentrations of contrast material that were added at irradiation. However, the aberrations were not associated with elevation of the ratio of dicentric and ring chromosomes to the number of cells with unstable chromosome aberrations at the first mitosis. Lymphocytes irradiated in the absence of contrast material did not show an increase in chromosome-type aberrations when the agent was given in increasing concentrations during subsequent incubation, but there were greater numbers of chromatid gaps and breaks. When lymphocytes were exposed to 400 R (103.2 mC/kg) of /sup 60/Co gamma rays, the presence of contrast agent did not increase the yield of dicentric and ring chromosomes, but induced a marked delay in cell proliferation, especially in lymphocytes with more heavily damaged chromosomes. In additional examination, the contrast agent itself induced sister chromatid exchanges in lymphocytes.

  16. Radiation-induced removal of sulphadiazine antibiotics from wastewater.

    PubMed

    Liu, Yuankun; Hu, Jun; Wang, Jianlong

    2014-08-01

    The radiation-induced removal of sulphadiazine (SD) belonging to the heterocyclic sulphonamides pharmaceuticals was investigated by gamma irradiation at different conditions in laboratory scale. The influence of initial SD concentrations, pH values, 02 and N2 on SD degradation was determined. The experimental results showed that gamma-ray irradiation was efficient for removing SD from wastewater. SD could be completely removed at an absorbed dose of 10 kGy. The degradation kinetics of SD conformed to the first-order kinetic equation. When SD concentration was in the range of 10-30 mg/L, the dose constant (d) decreased with an increasing initial SD concentration. The mineralization of SD, in terms of total organic carbon removal, was not obvious at a low absorbed dose, but it increased to more than 75% at 100 kGy. The biodegradability of SD was improved after irradiation, suggesting that irradiation could be used as a pretreatment technology for treating SD-containing wastewater. The possible degradation pathway of SD was tentatively proposed based on the analysis of intermediate products during gamma irradiation.

  17. Gamma radiation induces hydrogen absorption by copper in water

    PubMed Central

    Lousada, Cláudio M.; Soroka, Inna L.; Yagodzinskyy, Yuriy; Tarakina, Nadezda V.; Todoshchenko, Olga; Hänninen, Hannu; Korzhavyi, Pavel A.; Jonsson, Mats

    2016-01-01

    One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H2(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories. PMID:27086752

  18. Early corticosteroid administration in experimental radiation-induced heart disease

    SciTech Connect

    Reeves, W.C.; Stryker, J.A.; Abt, A.A.; Chung, C.K.; Whitesell, L.; Zelis, R.

    1980-02-01

    The ability of dexamethasone (DEX) to reduce the severity of the late stage of radiation-induced heart disease (RIHD) was assessed in 25 New Zealand white rabbits. Ten rabbits served as unirradiated controls (CONT). In Group A, seven rabbits received intravenous DEX prior to irradiation and every 24 hours for three consecutive days. DEX was not administered to the eight rabbits in Group B. At 100 days postirradiation, the severity of the late state was determined by microscopic examination (MICRO) for myocardial fibrosis and determination of myocardial hydroxyproline content (MHP). Myocardial fibrosis was evident in groups A (40%) and B (80%) while none was present in CONT by MICRO. One rabbit in Group B with no fibrosis by MICRO had abnormally increased MHP. MHP was significantly increased in Groups A and B, as compared to CONT (p < 0.01). In addition to less fibrosis by MICRO, Group A demonstrated a significant reduction of MHP when compared to Group B (p < 0.05). Determination of MHP may be superior to MICRO in the detection of the late stage of RIHD. Also, early DEX administration appears to reduce myocardial collagen content (fibrosis) in this experimental model.

  19. Radiation-induced sarcomas of the chest wall

    SciTech Connect

    Souba, W.W.; McKenna, R.J. Jr.; Meis, J.; Benjamin, R.; Raymond, A.K.; Mountain, C.F.

    1986-02-01

    Sixteen patients are presented who had sarcomas of the chest wall at a site where a prior malignancy had been irradiated. The first malignancies included breast cancer (ten cases), Hodgkin's disease (four cases), and others (two cases). Radiation doses varied from 4200 to 5500 R (mean, 4900 R). The latency period ranged from 5 to 28 years (mean, 13 years). The histologic types of the radiation-induced sarcomas were as follows: malignant fibrous histiocytoma, nine cases; osteosarcoma, six cases; and malignant mesenchymoma, one case. The only long-term survivor is alive and well 12 years after resection of a clavicular chondroblastic osteosarcoma. Three cases were recently diagnosed. Despite aggressive multimodality treatment, the remaining 13 patients have all died from their sarcomas (mean survival, 13.5 months). All patients have apparently been cured of their first malignancies. Chemotherapy was ineffective. No treatment, including forequarter amputation, appeared to palliate the patients with supraclavicular soft tissue sarcomas. Major chest wall resection offered good palliation for seven of eight patients with sarcomas arising in the sternum or lateral chest wall. Close follow-up is needed to detect signs of these sarcomas in the ever-increasing number of patients receiving therapeutic irradiation.

  20. Radiation-Induced Sarcoma of the Breast: A Systematic Review

    PubMed Central

    Sheth, Grishma R.; Cranmer, Lee D.; Smith, Benjamin D.; Grasso-LeBeau, Lauren

    2012-01-01

    Introduction. Radiation-induced sarcoma (RIS) is a rare, aggressive malignancy. Breast cancer survivors treated with radiotherapy constitute a large fraction of RIS patients. To evaluate evidenced-based practices for RIS treatment, we performed a systematic review of the published English-language literature. Methods. We performed a systematic keyword search of PubMed for original research articles pertaining to RIS of the breast. We classified and evaluated the articles based on hierarchal levels of scientific evidence. Results. We identified 124 original articles available for analysis, which included 1,831 patients. No randomized controlled trials involving RIS patients were found. We present the best available evidence for the etiology, comparative biology to primary sarcoma, prognostic factors, and treatment options for RIS of the breast. Conclusion. Although the evidence to guide clinical practice is limited to single institutional cohort studies, registry studies, case–control studies, and case reports, we applied the available evidence to address clinically relevant questions related to best practice in patient management. Surgery with widely negative margins remains the primary treatment of RIS. Unfortunately, the role of adjuvant and neoadjuvant chemotherapy remains uncertain. This systematic review highlights the need for additional well-designed studies to inform the management of RIS. PMID:22334455

  1. Radiation induced destruction of thebaine, papaverine and noscapine in methanol

    NASA Astrophysics Data System (ADS)

    Kantoğlu, Ömer; Ergun, Ece

    2016-07-01

    The presence of methanol decreases the efficiency of radiation-induced decomposition of alkaloids in wastewater. Intermediate products were observed before the complete degradation of irradiated alkaloids. In order to identify the structure of the by-products and the formation pathway, thebaine, papaverine and noscapine solutions were prepared in pure methanol and irradiated using a 60Co gamma cell at absorbed doses of 0, 1, 3, 5, 7, 10, 30, 50 and 80 kGy. The dose-dependent alkaloid degradation and by-product formation were monitored by ESI mass spectrometer. Molecular structures of the by-products and reaction pathways were proposed. Oxygenated and methoxy group containing organic compounds was observed in the mass spectra of irradiated alkaloids. At initial dose values oxygenated by-products were formed due to the presence of dissolved oxygen in solutions. After the consumption of dissolved oxygen with radicals, the main mechanism was addition of solvent radicals to alkaloid structure. However, it was determined that alkaloids and by-products were completely degraded at doses higher than 50 kGy. The G-value and degradation efficiency of alkaloids were also evaluated.

  2. Mechanisms of radiation-induced neoplastic cell transformation

    SciTech Connect

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  3. [Radiation-induced bronchiolitis obliterans with organizing pneumonia].

    PubMed

    Ducray, J; Vignot, S; Lacout, A; Pougnet, I; Marcy, P-Y; Chapellier, C; Foray, N; Creisson, A; Thariat, J

    2017-04-01

    Bronchiolitis obliterans with organizing pneumonia is an inflammatory reaction that can occur as a consequence of various pulmonary affections. Radiotherapy is not the sole and systematic cause of bronchiolitis obliterans with organizing pneumonia. Radiation-induced should not be confused with post-radiation, dose-dependent, inflammatory pulmonary fibrosis, which is non-immunological and located within the irradiation field. The role of immunity, local inflammation and individual radiosensitivity in bronchiolitis obliterans with organizing pneumonia is not well defined. Bronchiolitis obliterans with organizing pneumonia represents 1% of irradiated patients with breast cancer. It results in fever (flu-like symptoms), a rather dry cough and dyspnea. In the post-radiation context, bronchiolitis obliterans with organizing pneumonia may be diagnosed several months and up to a year after breast irradiation. The treatment consists of prolonged steroids or immunosuppressants, which do not prevent chronicity in 15% of patients and death in up to 5% of cases, the remaining 80% of patients healing without sequelae. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  4. Ionizing Radiation-Induced Cataract in Interventional Cardiology Staff

    PubMed Central

    Bitarafan Rajabi, Ahmad; Noohi, Feridoun; Hashemi, Hassan; Haghjoo, Majid; Miraftab, Mohammad; Yaghoobi, Nahid; Rastgou, Fereydon; Malek, Hadi; Faghihi, Hoshang; Firouzabadi, Hassan; Asgari, Soheila; Rezvan, Farhad; Khosravi, Hamidreza; Soroush, Sara; Khabazkhoob, Mehdi

    2015-01-01

    Background: The use of ionizing radiation has led to advances in medical diagnosis and treatment. Objectives: The purpose of this study was to determine the risk of radiation cataractogenesis in the interventionists and staff performing various procedures in different interventional laboratories. Patients and Methods: This cohort study included 81 interventional cardiology staff. According to the working site, they were classified into 5 groups. The control group comprised 14 professional nurses who did not work in the interventional sites. Participants were assigned for lens assessment by two independent trained ophthalmologists blinded to the study. Results: The electrophysiology laboratory staff received higher doses of ionizing radiation (17.2 ± 11.9 mSv; P < 0.001). There was a significant positive correlation between the years of working experience and effective dose in the lens (P < 0.001). In general, our findings showed that the incidence of lens opacity was 79% (95% CI, 69.9-88.1) in participants with exposure (the case group) and our findings showed that the incidence of lenses opacity was 7.1% (95% CI:2.3-22.6) with the relative risk (RR) of 11.06 (P < 0.001). Conclusions: We believe that the risk of radiation-induced cataract in cardiology interventionists and staff depends on their work site. As the radiation dose increases, the prevalence of posterior eye changes increases. PMID:25789258

  5. Radiation-induced thymine base damage in replicating chromatin

    SciTech Connect

    Warters, R.L.; Childers, T.J.

    1982-06-01

    The efficiency of radiation-induced production of 5',6'-dihydroxydihydrothymine (t/sup ..gamma../)-type damage was determined in nascent and mature chromatin DNA for the dose range of 50 to 150 krad. These large doses affected neither the total fraction of nuclear DNA in chromatin subunits nor the nucleosome subunit repeat length. The DNA in nascent chromatin, however, was found to be 3.3 times more sensitive than mature chromatin DNA to ..gamma..-ray (/sup 137/Cs)-induced t/sup ..gamma../-type damage, while thymine damage of this type was uniformly distributed in the nucleosomal DNA of mature chromatin (i.e., in the nucleosome core and spacer DNA). The half-time for the transition of nascent DNA sensitivity to mature chromatin DNA sensitivity levels was the same as the half-time at 37/sup 0/C for the maturation of nascent into mature chromatin structure. The rate at which nascent chromatin matured was unaffected by radiation doses as large as 150 krad. The most logical explanation for the greater sensitivity of nascent DNA to radiation is the decreased concentration of histone chromosomal proteins in nascent chromatin.

  6. Chromatin Structure and Radiation-Induced Intrachromosome Exchange

    NASA Technical Reports Server (NTRS)

    Mangala; Zhang, Ye; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    We have recently investigated the location of breaks involved in intrachromosomal type exchange events, using the multicolor banding in situ hybridization (mBAND) technique for human chromosome 3. In human epithelial cells exposed to both low- and high-LET radiations in vitro, intrachromosome exchanges were found to occur preferentially between a break in the 3p21 and one in the 3q11. Exchanges were also observed between a break in 3p21 and one in 3q26, but few exchanges were observed between breaks in 3q11 and 3q26, even though the two regions were on the same arm of the chromosome. To explore the relationships between intrachromosome exchanges and chromatin structure, we used probes that hybridize the three regions of 3p21, 3q11 and 3q26, and measured the distance between two of the three regions in interphase cells. We further analyzed fragile sites on the chromosome that have been identified in various types of cancers. Our results demonstrated that the distribution of breaks involved in radiation-induced intrachromosome aberrations depends upon both the location of fragile sites and the folding of chromatins

  7. Epigenetic determinants of space radiation-induced cognitive dysfunction

    PubMed Central

    Acharya, Munjal M.; Baddour, Al Anoud D.; Kawashita, Takumi; Allen, Barrett D.; Syage, Amber R.; Nguyen, Thuan H.; Yoon, Nicole; Giedzinski, Erich; Yu, Liping; Parihar, Vipan K.; Baulch, Janet E.

    2017-01-01

    Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition. PMID:28220892

  8. Radiation induced degradation of dyes--an overview.

    PubMed

    Rauf, M A; Ashraf, S Salman

    2009-07-15

    Synthetic dyes are a major part of our life. Products ranging from clothes to leather accessories to furniture all depend on extensive use of organic dyes. An unfortunate side effect of extensive use of these chemicals is that huge amounts of these potentially carcinogenic compounds enter our water supplies. Various advanced oxidation processes (AOPs) including the use of high-energy radiation have been developed to degrade these compounds. In this review, dye decoloration and degradation as a result of its exposure to high energy radiation such as gamma radiation and pulsed electron beam are discussed in detail. The role of various transient species such as H, OH and e(aq)(-) are taken into account as reported by various researchers. Literature citations in this area show that e(aq)(-) is very effective in decolorization but is less active in the further degradation of the products formed. The degradation of the dyes is initiated exclusively by OH attack on electron-rich sites of the dye molecules. Additionally, various parameters that affect the efficiency of radiation induced degradation of dyes, such as effect of radiation dose, oxygen, pH, hydrogen peroxide, added ions and dye classes are also reviewed and summarized. Lastly, pilot plant application of radiation for wastewater treatment is briefly discussed.

  9. Low dose radiation-induced endothelial cell retraction.

    PubMed

    Kantak, S S; Diglio, C A; Onoda, J M

    1993-09-01

    We characterized in vitro the effects of gamma-radiation (12.5-100 cGy) on pulmonary microvascular endothelial cell (PMEC) morphology and F-actin organization. Cellular retraction was documented by phase-contrast microscopy and the organization of actin microfilaments was determined by immunofluorescence. Characterization included radiation dose effects, their temporal duration and reversibility of the effects. A dose-dependent relationship between the level of exposure (12.5-100 cGy) and the rate and extent of endothelial retraction was observed. Moreover, analysis of radiation-induced depolymerization of F-actin microfilament stress fibres correlated positively with the changes in PMEC morphology. The depolymerization of the stress fibre bundles was dependent on radiation dose and time. Cells recovered from exposure to reform contact inhibited monolayers > or = 24 h post-irradiation. Concomitantly, the depolymerized microfilaments reorganized to their preirradiated state as microfilament stress fibres arrayed parallel to the boundaries of adjacent contact-inhibited cells. The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Our data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema.

  10. Outcome of Carotid Artery Stenting for Radiation-Induced Stenosis

    SciTech Connect

    Dorresteijn, Lucille; Vogels, Oscar; Leeuw, Frank-Erik de; Vos, Jan-Albert; Christiaans, Marleen H.; Ackerstaff, Rob; Kappelle, Arnoud C.

    2010-08-01

    Purpose: Patients who have been irradiated at the neck have an increased risk of symptomatic stenosis of the carotid artery during follow-up. Carotid angioplasty and stenting (CAS) can be a preferable alternative treatment to carotid endarterectomy, which is associated with increased operative risks in these patients. Methods and Materials: We performed a prospective cohort study of 24 previously irradiated patients who underwent CAS for symptomatic carotid stenosis. We assessed periprocedural and nonprocedural events including transient ischemic attack (TIA), nondisabling stroke, disabling stoke, and death. Patency rates were evaluated on duplex ultrasound scans. Restenosis was defined as a stenosis of >50% at the stent location. Results: Periprocedural TIA rate was 8%, and periprocedural stroke (nondisabling) occurred in 4% of patients. After a mean follow-up of 3.3 years (range, 0.3-11.0 years), only one ipsilateral incident event (TIA) had occurred (4%). In 12% of patients, a contralateral incident event was present: one TIA (4%) and two strokes (12%, two disabling strokes). Restenosis was apparent in 17%, 33%, and 42% at 3, 12, and 24 months, respectively, although none of the patients with restenosed vessels became symptomatic. The length of the irradiation to CAS interval proved the only significant risk factor for restenosis. Conclusions: The results of CAS for radiation-induced carotid stenosis are favorable in terms of recurrence of cerebrovascular events at the CAS site.

  11. Radiation-induced chromosomal instability in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Yang, T. C.

    1996-01-01

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  12. Radiation induced oxidation of liquid alkanes as a polymer model

    NASA Astrophysics Data System (ADS)

    Soebianto, Yanti S.; Katsumura, Yosuke; Ishigure, Kenkichi; Kubo, Junichi; Hamakawa, Satoshi; Kudoh, Hisaaki; Seguchi, Tadao

    1996-10-01

    Radiation induced oxidation of liquid n-hexadecane ( n-C 16H 34) and squalene (C 30H 62) as a polymer model has been investigated by the measurements of the gas evolution and O 2 uptake, and analyses of the oxidation products. Low O 2 uptake [G(-O 2 ≈ 6.0] in liquid alkanes, indicates in solid oxidation reaction does not exhibit chain kinetics, which is a big contrast to the process observed in solid, G(-O 2) ≫ 10. H 2 is the main gas product. More than 90% of the consumed O 2 are converted into the oxidation products in liquid phase, mainly carboxylic acids, which is also a big contrast to the results of the radiolysis of liquid cyclohexane in the presence of O 2 and thermal oxidation of hexadecene at elevated temperatures, where ketones and alcohols are major products at the initial stage. In the presence of aromatic additives, energy and charge transfer to the additives taking place despite the presence of O 2 reduce the H 2 evolution and the acid formation in parallel. Although hydroaromatic compounds act as an energy and charge scavenger, the are selectively oxidized through the donation of hydrogen in cyclic alkyl part attached to the phenyl ring, leading to large O 2 uptake and corresponding ketone formation. From the comparison of the G-values of the O 2 uptake, it was found that the oxidation reactions of liquid alkanes reflect well the oxidation of amorphous part in polymers.

  13. A new view of radiation-induced cancer.

    PubMed

    Shuryak, I; Sachs, R K; Brenner, D J

    2011-02-01

    Biologically motivated mathematical models are important for understanding the mechanisms of radiation-induced carcinogenesis. Existing models fall into two categories: (1) short-term formalisms, which focus on the processes taking place during and shortly after irradiation (effects of dose, radiation quality, dose rate and fractionation), and (2) long-term formalisms, which track background cancer risks throughout the entire lifetime (effects of age at exposure and time since exposure) but make relatively simplistic assumptions about radiation effects. Grafting long-term mechanisms on to short-term models is badly needed for modelling radiogenic cancer. A combined formalism was developed and applied to cancer risk data in atomic bomb survivors and radiotherapy patients and to background cancer incidence. The data for nine cancer types were described adequately with a set of biologically meaningful parameters for each cancer. These results suggest that the combined short-long-term approach is a potentially promising method for predicting radiogenic cancer risks and interpreting the underlying biological mechanisms.

  14. Interleukin-32 Positively Regulates Radiation-Induced Vascular Inflammation

    SciTech Connect

    Kobayashi, Hanako; Yazlovitskaya, Eugenia M.; Lin, P. Charles

    2009-08-01

    Purpose: To study the role of interleukin-32 (IL-32), a novel protein only detected in human tissues, in ionizing radiation (IR)-induced vascular inflammation. Methods and Materials: Irradiated (0-6 Gy) human umbilical vein endothelial cells treated with or without various agents-a cytosolic phospholipase A2 (cPLA2) inhibitor, a cyclooxygenase-2 (Cox-2) inhibitor, or lysophosphatidylcholines (LPCs)-were used to assess IL-32 expression by Northern blot analysis and quantitative reverse transcriptase-polymerase chain reaction. Expression of cell adhesion molecules and leukocyte adhesion to endothelial cells using human acute monocytic leukemia cell line (THP-1) cells was also analyzed. Results: Ionizing radiation dramatically increased IL-32 expression in vascular endothelial cells through multiple pathways. Ionizing radiation induced IL-32 expression through nuclear factor {kappa}B activation, through induction of cPLA2 and LPC, as well as induction of Cox-2 and subsequent conversion of arachidonic acid to prostacyclin. Conversely, blocking nuclear factor {kappa}B, cPLA2, and Cox-2 activity impaired IR-induced IL-32 expression. Importantly, IL-32 significantly enhanced IR-induced expression of vascular cell adhesion molecules and leukocyte adhesion on endothelial cells. Conclusion: This study identifies IL-32 as a positive regulator in IR-induced vascular inflammation, and neutralization of IL-32 may be beneficial in protecting from IR-induced inflammation.

  15. Gamma radiation induces hydrogen absorption by copper in water.

    PubMed

    Lousada, Cláudio M; Soroka, Inna L; Yagodzinskyy, Yuriy; Tarakina, Nadezda V; Todoshchenko, Olga; Hänninen, Hannu; Korzhavyi, Pavel A; Jonsson, Mats

    2016-04-18

    One of the most intricate issues of nuclear power is the long-term safety of repositories for radioactive waste. These repositories can have an impact on future generations for a period of time orders of magnitude longer than any known civilization. Several countries have considered copper as an outer corrosion barrier for canisters containing spent nuclear fuel. Among the many processes that must be considered in the safety assessments, radiation induced processes constitute a key-component. Here we show that copper metal immersed in water uptakes considerable amounts of hydrogen when exposed to γ-radiation. Additionally we show that the amount of hydrogen absorbed by copper depends on the total dose of radiation. At a dose of 69 kGy the uptake of hydrogen by metallic copper is 7 orders of magnitude higher than when the absorption is driven by H2(g) at a pressure of 1 atm in a non-irradiated dry system. Moreover, irradiation of copper in water causes corrosion of the metal and the formation of a variety of surface cavities, nanoparticle deposits, and islands of needle-shaped crystals. Hence, radiation enhanced uptake of hydrogen by spent nuclear fuel encapsulating materials should be taken into account in the safety assessments of nuclear waste repositories.

  16. Radiation-induced sarcomas of the head and neck

    PubMed Central

    Thiagarajan, Anuradha; Iyer, N Gopalakrishna

    2014-01-01

    With improved outcomes associated with radiotherapy, radiation-induced sarcomas (RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stage-matched sarcomas that arise independent of irradiation and surgical resection with clear margins seems to offer the best chance for cure. PMID:25493233

  17. Radiation-Induced Bystander Response: Mechanism and Clinical Implications

    PubMed Central

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  18. Radiation-induced chromosome damage in astronauts' lymphocytes.

    PubMed

    Testard, I; Ricoul, M; Hoffschir, F; Flury-Herard, A; Dutrillaux, B; Fedorenko, B; Gerasimenko, V; Sabatier, L

    1996-10-01

    The increased number of manned space missions has made it important to estimate the biological risks encountered by astronauts. As they are exposed to cosmic rays, especially ions with high linear energy transfer (LET), it is necessary to estimate the doses they receive. The most sensitive biological dosimetry used is based on the quantification of radiation-induced chromosome damage to human lymphocytes. After the space missions ANTARES (1992) and ALTAIR (1993), we performed cytogenetic analysis of blood samples from seven astronauts who had spent from 2 weeks to 6 months in space. After 2 or 3 weeks, the X-ray equivalent dose was found to be below the cytogenetic detection level of 20 mGy. After 6 months, the biological dose greatly varied among the astronauts, from 95 to 455 mGy equivalent dose. These doses are in the same range as those estimated by physical dosimetry (90 mGy absorbed dose and 180 mSv equivalent dose). Some blood cells exhibited the same cytogenetic pattern as the 'rogue cells' occasionally observed in controls, but with a higher frequency. We suggest that rogue cells might result from irradiation with high-LET particles of cosmic origin. However, the responsibility of such cells for the long-term effects of cosmic irradiation remains unknown and must be investigated.

  19. Mechanism of Hydrophilicity by Radiation-Induced Surface Activation

    NASA Astrophysics Data System (ADS)

    Honjo, Yoshio; Furuya, Masahiro; Takamasa, Tomoji; Okamoto, Koji

    When a metal oxide is irradiated by gamma rays, the irradiated surface becomes hydrophilic. This surface phenomenon is called as radiation-induced surface activation (RISA) hydrophilicity. In order to investigate gamma ray-induced and photoinduced hydrophilicity, the contact angles of water droplets on a titanium dioxide surface were measured in terms of irradiation intensity and time for gamma rays of cobalt-60 and for ultraviolet rays. Reciprocals of the contact angles increased in proportion to the irradiation time before the contact angles reached its super-hydrophilic state. The irradiation time dependency is equal to each other qualitatively. In addition, an effect of ambient gas was investigated. In pure argon gas, the contact angle remains the same against the irradiation time. This clearly indicates that certain humidity is required in ambient gas to take place of RISA hydrophilicity. A single crystal titanium dioxide (100) surface was analyzed by X-ray photoelectron spectrometry (XPS). After irradiation with gamma rays, a peak was found in the O1s spectrum, which indicates the adsorption of dissociative water to a surface 5-fold coordinate titanium site, and the formation of a surface hydroxyl group. We conclude that the RISA hydrophilicity is caused by chemisorption of the hydroxyl group on the surface.

  20. Radiation induced thyroid neoplasms 1920 to 1987: A vanishing problem

    SciTech Connect

    Mehta, M.P.; Goetowski, P.G.; Kinsella, T.J.

    1989-06-01

    Radiation for benign diseases has been implicated as an etiologic factor in thyroid cancer. From 1930-60, over 2 million children may have been exposed to therapeutic radiation and it is estimated that up to 7% may develop thyroid cancer after a 5-40 year latency. Thyroid stimulating hormone, secondary to radioinduced hypothyroidism, has been implicated as causative in animals. Such data has led to expensive screening programs in high risk patients. Because of a decline in irradiation for benign diseases in children over the last 2 decades, we questioned whether the incidence of radiation induced thyroid neoplasms (RITN) was also decreasing. Twenty-six of 227 patients (11%) with thyroid malignancies seen at our institution from 1974-87 had a history of previous head and neck irradiation. These included 13 papillary, 3 follicular, and 7 mixed carcinomas as well as 2 lymphomas and 1 synovial cell sarcoma. None of these 26 patients had abnormal thyroid function tests at presentation. Mean latency from irradiation to the diagnosis of thyroid cancer was 25.4 years (6-55 year range). Compared to the reported increasing incidence of RITN from 1940-70, there appears to be a significant decrease since 1970. Based on our analysis, the use of expensive screening programs in high risk populations may no longer be warranted. Additionally, the routine use of thyroid replacement in previously irradiated chemically hypothyroid patients is not recommended.30 references.

  1. Radiation-induced bystander effect: early process and rapid assessment.

    PubMed

    Wang, Hongzhi; Yu, K N; Hou, Jue; Liu, Qian; Han, Wei

    2015-01-01

    Radiation-induced bystander effect (RIBE) is a biological process that has received attention over the past two decades. RIBE refers to a plethora of biological effects in non-irradiated cells, including induction of genetic damages, gene expression, cell transformation, proliferation and cell death, which are initiated by receiving bystander signals released from irradiated cells. RIBE brings potential hazards to normal tissues in radiotherapy, and imparts a higher risk from low-dose radiation than we previously thought. Detection with proteins related to DNA damage and repair, cell cycle control, proliferation, etc. have enabled rapid assessment of RIBE in a number of research systems such as cultured cells, three-dimensional tissue models and animal models. Accumulated experimental data have suggested that RIBE may be initiated rapidly within a time frame as short as several minutes after radiation. These have led to the requirement of techniques capable of rapidly assessing RIBE itself as well as assessing the early processes involved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Radiation-induced chromosomal instability in human mammary epithelial cells

    NASA Astrophysics Data System (ADS)

    Durante, M.; Grossi, G. F.; Yang, T. C.

    Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.

  3. Temporal distributions of risk for radiation-induced cancers.

    PubMed

    Land, C E

    1987-01-01

    Observations of cancer risk in irradiated human populations over time after exposure suggest that there are at least two, and perhaps more, very different patterns of temporal distribution of risk for radiation-induced cancer. The first, exemplified by bone sarcoma following therapeutic injection of 224Ra and chronic granulocytic leukemia in Japanese A-bomb survivors, is an early, wave-like pulse consisting of an increase in risk followed by a gradual decline back to baseline levels. The second, exemplified by breast cancer following a brief exposure to external gamma ray or X ray, and by lung cancer and stomach cancer in A-bomb survivors, is an increase in relative risk over about 10 years to a value which appears to remain constant over time thereafter. The first pattern suggests that tumor growth kinetics may play a central role in the temporal distribution of risk following exposure, while the second seems more consistent with multi-event models for carcinogenesis, in which radiation or some other cause of early events must be followed by one or more later events whose frequencies depend mainly on attained age. There are, however, other data that appear to conform to neither of the two models just mentioned. Influences of other cancer causes, like tobacco smoking, are potentially serious confounding factors in studies of induction period.

  4. Effect of curcumin analog on gamma-radiation-induced cellular changes in primary culture of isolated rat hepatocytes in vitro.

    PubMed

    Srinivasan, M; Sudheer, A Ram; Rajasekaran, K N; Menon, Venugopal P

    2008-10-22

    The present study was aimed to evaluate the radioprotective effect of curcumin analog, on gamma-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The DNA damage was analysed by single cell gel electrophoresis (comet assay). An increase in the severity of DNA damage was observed with the increase in gamma-radiation dose at 1-4 Gy in cultured rat hepatocytes. The levels of lipid peroxidative indices like thiobarbituric acid reactive substances (TBARSs) were increased significantly, whereas the levels of reduced glutathione (GSH) and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4Gy gamma-irradiation. Pretreatment with different concentrations of curcumin analog (1.38, 6.91 and 13.82 microM) shows a significant decrease in the levels of TBARS and DNA damage. Pretreatment with curcumin analog prevents the loss of enzymic and non-enzymic antioxidants like GSH upon gamma-irradiation. The maximum protection of hepatocytes was observed at 6.91 microM of curcumin analog pretreatment. Thus, our result shows that pretreatment with curcumin analog protects the hepatocytes against gamma-radiation-induced cellular damage.

  5. Normal tissue complication probability modeling of radiation-induced sensorineural hearing loss after head-and-neck radiation therapy.

    PubMed

    Cheraghi, Susan; Nikoofar, Alireza; Bakhshandeh, Mohsen; Khoei, Samideh; Farahani, Saeid; Abdollahi, Hamid; Mahdavi, Seied Rabi

    2017-10-02

    The aim of this study was to generate the dose-response curves by six normal tissue complication probability (NTCP) models and ranking the models for prediction of radiation induced sensorineural hearing loss (SNHL) caused by head and neck radiation therapy (RT). Pure tone audiometry (PTA) was performed on 70 ears of patients for 12 months after the completion of radiation therapy. The SNHL was defined as a threshold shift ≤15 dB at 2 contiguous frequencies according to the common toxicity criteria for adverse events scoring system. The models evaluated were: Lyman and Logit; Mean Dose; Relative Seriality; Individual Critical Volume; and Population Critical Volume models. Maximum likelihood analysis was used to fit the models to experimental data. The appropriateness of the fit was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. The dose of 50% complication rate (D50) was 51-60 Gy. Three of the examined models fitted well with clinical data in a 95% confidence interval. The relative seriality model was ranked as the best model of prediction for radiation induced SNHL. Cochlea shows a different behaviour against different NTCP models; it's may be due to its small size.

  6. Multidisciplinary management of resectable rectal cancer. New developments and controversies.

    PubMed

    Minsky, Bruce D; Guillem, Jose G

    2008-11-15

    Until 2004, initial surgery and, in cases of pT3 and/or node-positive disease, postoperative chemoradiotherapy (radiation plus concurrent chemotherapy) was the conventional approach for patients with clinical T3 and/or node-positive rectal cancer. The German CAO/ARO/AIO 94 trial confirmed that, compared with preoperative chemoradiotherapy, postoperative chemoradiotherapy is associated with significantly higher local failure and toxicity rates as well as a decrease in the incidence of sphincter preservation. These data resulted in a change from postoperative to preoperative chemoradiotherapy. This shift to preoperative therapy has prompted a series of new questions regarding the multidisciplinary management of rectal cancer, including: What is the ideal neoadjuvant approach (short-course vs. combined-modality therapy)? Is postoperative adjuvant chemotherapy necessary for all patients following preoperative chemoradiotherapy? Do patients with node-negative rectal cancer require pelvic radiation? What is the ideal combined-modality regimen? Does an increase in response rate translate into improved local control and survival? And lastly, what is the benefit of novel radiation sensitization and delivery techniques? This review will address these and other questions surrounding the multidisciplinary management of rectal cancer.

  7. American Society of Colon and Rectal Surgeons

    MedlinePlus

    ... Educational Resources ASCRS Textbook, 3rd Edition CARSEP® CREST® Case Study Listserv International Colon and Rectal Societies and Organizations ... Board of Colon and Rectal Surgery CARSEP® Members Case Study Listserv CREST® Young Surgeons Listserv Quality Assessment and ...

  8. ACR Appropriateness Criteria on Resectable Rectal Cancer

    SciTech Connect

    Suh, W. Warren; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-04-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007.

  9. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells.

    PubMed

    Huang, Yao-Huei; Yang, Pei-Ming; Chuah, Qiu-Yu; Lee, Yi-Jang; Hsieh, Yi-Fen; Peng, Chih-Wen; Chiu, Shu-Jun

    2014-07-01

    Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects.

  10. Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

    PubMed

    Miglioretti, Diana L; Lange, Jane; van den Broek, Jeroen J; Lee, Christoph I; van Ravesteyn, Nicolien T; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J; Melnikow, Joy; de Koning, Harry J; Hubbard, Rebecca A

    2016-02-16

    Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. 2 simulation-modeling approaches. U.S. population. Women aged 40 to 74 years. Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Life-years lost from radiation-induced breast cancer could not be estimated. Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

  11. Immunohistochemical analysis of radiation-induced non-healing dermal wounds of the head and neck.

    PubMed

    Riedel, Frank; Philipp, Katrin; Sadick, Haneen; Goessler, Ullrich; Hörmann, Karl; Verse, Thomas

    2005-01-01

    Persistent, poorly healing wounds are a significant clinical problem in patients who have had previous irradiation. The pathology of chronic dermal ulcers is characterised by excessive proteolytic activity which degrades the extracellular matrix (required for cell migration) and growth factors and their receptors. Interestingly, the molecular basis of radiation-induced dermal wounds is poorly understood. The aim of this study was to investigate, by immunohistochemistry, the expression of the endothelial marker vWF, of angiogenic bFGF, VEGF and IL-8, of collagenases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2, in tissue samples from radiation-induced chronic dermal wounds and healthy control skin. Performing immunohistochemical detection of microvessels, an equivalent density of microvessels was observed within tissue samples from normal healthy skin and from radiation-induced non-healing cutaneous wounds. Investigation of angiogenic bFGF and VEGF demonstrated a decreased expression of both factors in the radiation-induced dermal wounds. The expression of angiogenic IL-8 was weak in both the healthy skin samples and the radiation-induced wounds. In addition, an increased expression of collagenases MMP-2 and MMP-9 protein within the radiation-induced wounds was demonstrated. While the expression of TIMP-1 showed no difference of expression between normal control skin and tissue samples from radiation-induced wounds, TIMP-2 expression was slightly increased compared to healthy controls. Our data suggest that radiation-induced dermal injuries often fail to heal because of decreased angiogenesis and persistently high concentrations of MMPs with an imbalance of their tissue inhibitors. The basic mechanisms of wound healing in radiation-induced dermal wounds at the molecular level need to be understood further for the development of innovative treatment strategies.

  12. Rectal cancer: An evidence-based update for primary care providers

    PubMed Central

    Gaertner, Wolfgang B; Kwaan, Mary R; Madoff, Robert D; Melton, Genevieve B

    2015-01-01

    Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers. PMID:26167068

  13. The curative management of synchronous rectal and prostate cancer

    PubMed Central

    Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

    2016-01-01

    Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity

  14. SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

    SciTech Connect

    Park, J; Park, H; Lee, J; Kang, S; Lee, M; Suh, T; Lee, B

    2014-06-01

    Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from the whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea

  15. Local management of rectal neoplasia.

    PubMed

    Touzios, John; Ludwig, Kirk A

    2008-11-01

    The treatment of rectal neoplasia, whether benign or malignant, challenges the surgeon. The challenge in treating rectal cancer is selecting the proper approach for the appropriate patient. In a small number of rectal cancer patients local excision may be the best approach. In an attempt to achieve two goals-cure of disease with a low rate of local failure and maintenance of function and quality of life-multiple approaches can be utilized. The key to obtaining a good outcome for any one patient is balancing the competing factors that impact on these goals. Any effective treatment aimed at controlling rectal cancer in the pelvis must take into account the disease in the bowel wall itself and the disease, or potential disease, in the mesorectum. The major downside of local excision techniques is the potential of leaving untreated disease in the mesorectum. Local management techniques avoid the potential morbidity, mortality, and functional consequences of a major abdominal radical resection and are thus quite effective in achieving the maintenance of function and quality of life goal. The issue for the transanal techniques is how they fare in achieving the first goal-cure of the cancer while keeping local recurrence rates to an absolute minimum. Without removing both the rectum and the mesorectum there is no completely accurate way to determine whether a rectal cancer has moved outside the bowel wall, so any decision on local management of a rectal neoplasm is a calculated risk. For benign neoplasia, the challenge is removing the lesion without having to resort to a major abdominal procedure.

  16. Use of pentoxifylline and tocopherol in radiation-induced fibrosis and fibroatrophy.

    PubMed

    Patel, V; McGurk, M

    2017-04-01

    Radiation-induced fibrosis in the head and neck is a well-established pathophysiological process after radiotherapy. Recently pentoxifylline and tocopherol have been proposed as treatments to combat the late complications of radiation-induced fibrosis and a way of dealing with osteoradionecrosis. They both have a long history in the management of radiation-induced fibrosis at other anatomical sites. In this paper we review their use in sites other than the head and neck to illustrate the potential benefit that they offer to our patients. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Effects of helium and hydrogen on radiation-induced microstructural changes in austenitic stainless steel

    NASA Astrophysics Data System (ADS)

    Jin, Hyung-Ha; Ko, Eunsol; Lim, Sangyeop; Kwon, Junhyun

    2015-09-01

    Microstructural changes in austenitic stainless steel by helium, hydrogen, and iron ion irradiation were investigated with transmission electron microscopy. Typical radiation-induced changes, such as the formation of Frank loops in the matrix and radiation-induced segregation (RIS) or depletion at grain boundaries, were observed after ion irradiation. The helium ion irradiation led to the formation of cavities both at grain boundaries and in the matrix, as well as the development of smaller Frank loops. The hydrogen ion irradiation generated stronger RIS behavior at the grain boundaries compared to irradiation with helium and iron ions. The effects of helium and hydrogen on radiation-induced microstructural changes were discussed.

  18. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A rectal...

  19. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A rectal...

  20. Novel concepts in radiation-induced cardiovascular disease

    PubMed Central

    Cuomo, Jason R; Sharma, Gyanendra K; Conger, Preston D; Weintraub, Neal L

    2016-01-01

    Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future. Thus, there is a pressing need for enhanced understanding of the disease mechanisms, and improved detection methods and treatment strategies. Newly characterized mechanisms responsible for the establishment of chronic fibrosis, such as oxidative stress, inflammation and epigenetic modifications, are discussed and linked to potential treatments currently under study. Novel imaging modalities may serve as powerful screening tools in RICVD, and recent research and expert opinion advocating their use is introduced. Data arguing for the aggressive use of percutaneous interventions, such as transcutaneous valve replacement and drug-eluting stents, are examined and considered in the context of prior therapeutic approaches. RICVD and its treatment options are the subject of a rich and dynamic body of research, and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardio-oncology. PMID:27721934

  1. [Radiation-induced tumors of the nervous system in man].

    PubMed

    Hubert, D; Bertin, M

    1993-11-01

    The risk of developing a tumor of the nervous system in humans is analysed in several studies of populations, exposed to ionising radiation for medical reasons, or exposed to military or occupational radiation. The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia). The type of radiation-induced tumors is variable, but meningioma is more frequent after low doses and glioma and sarcoma after higher doses used in the treatment of neoplastic diseases. A dose-effect relationship appeared between the risk of tumor of the nervous system and the radiation dose. The risk was higher when radiation was delivered at a younger age. Much less data are available after radiotherapy in the adulthood, but an increased risk of cerebral tumor appears in the series of ankylosing spondylitis patients. As for the exposures to radiodiagnosis exams, the main problem is the risk of cerebral tumor in children whose mother has undergone abdominal or pelvic X-rays during pregnancy. No risk of neurologic tumor was found in the A-bomb survivors irradiated at Hiroshima and Nagasaki. Occupational exposure to ionising radiation has been incriminated in the first radiologists exposed to high doses. In nuclear industry workers, the results of epidemiological studies are contradictory and at the present time it is not possible to link their radiologic exposure with a risk of tumor of the nervous system. In populations living near nuclear plants, mortality due to tumors of the nervous system was not increased.

  2. Radiation-Induced Phase Transformations in Ilmenite-Group Minerals

    SciTech Connect

    Mitchell, J. N.

    1997-12-31

    Transmission electron microscopy (TEM) is a powerful tool for characterizing and understanding radiation-induced structural changes in materials. We have irradiated single crystals of ilmenite (FeTiO{sub 3}) and geikielite (MgTiO{sub 3}) using ions and electrons to better understand the response of complex oxides to radiation. Ion irradiation experiments of bulk single crystals at 100 K show that ilmenite amorphized at doses of less than 1x10(exp15) Ar(2+)/sq cm and at a damage level in the peak damage region of 1 displacement per atom (dpa). Transmission electron microscopy and electron diffraction of a cross-sectioned portion of this crystal confirmed the formation of a 150 am thick amorphous layer. Geikielite proved to be more radiation resistant, requiring a flux of 2x10(exp 15) Xe(2+)/sq cm to induce amorphization at 100 K. This material did not amorphize at 470 K, despite a dose of 2.5 x10(exp 16) Xe(2+)/sq cm and a damage level as high as 25 dpa. Low temperature irradiations of electron- transparent crystals with 1 MeV Kr(+) also show that ilmenite amorphized after a damage level of 2.25 dpa at 175 K.Similar experiments on geikielite show that the microstructure is partially amorphous and partially crystalline after 10 dpa at 150 K. Concurrent ion and electron irradiation of both materials with 1 MeV Kr(+) and 0.9 MeV electrons produced dislocation loops in both materials, but no amorphous regions were formed. Differences in the radiation response of these isostructural oxides suggests that in systems with Mg-Fe solid solution, the Mg-rich compositions may be more resistant to structural changes.

  3. Dosimetric Analysis of Radiation-Induced Gastric Bleeding

    PubMed Central

    Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

    2012-01-01

    Purpose Radiation-induced gastric bleeding has been poorly understood. In this study, we describe dosimetric predictors for gastric bleeding after fractionated radiotherapy and compare several predictive models. Materials & Methods The records of 139 sequential patients treated with 3-dimensional conformal radiotherapy (3D-CRT) for intrahepatic malignancies between January 1999 and April 2002 were reviewed. Median follow-up was 7.4 months. Logistic regression and Lyman normal tissue complication probability (NTCP) models for the occurrence of ≥ grade 3 gastric bleed were fit to the data. The principle of maximum likelihood was used to estimate parameters for all models. Results Sixteen of 116 evaluable patients (14%) developed gastric bleeds, at a median time of 4.0 months (mean 6.5 months, range 2.1–28.3 months) following completion of RT. The median and mean of the maximum doses to the stomach were 61 and 63 Gy (range 46 Gy–86 Gy), respectively, after bio-correction to equivalent 2 Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis was most predictive of gastric bleed (AUROC=0.92). Best fit Lyman NTCP model parameters were n =0.10, and m =0.21, with TD50(normal) =56 Gy and TD50(cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD50 value for the cirrhosis patients points out their greater sensitivity. Conclusion This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding, and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation. PMID:22541965

  4. Radiation-induced grafting of acrylic acid onto polyethylene filaments

    NASA Astrophysics Data System (ADS)

    Kaji, K.; Okada, T.; Sakurada, I.

    Radiation-induced grafting of acrylic acid onto high density polyethylene (PE) filaments was carried out in order to raise softening temperature and impart flame retardance and hydrophilic properties. Mutual γ-irradiation method was employed for the grafting in a mixture of acrylic acid (AA), ethylene dichloride and water containing a small amount of ferrous ammonium sulfate. The rate of grafting was very low at room temperature. On the other hand, large percent grafts were obtained when the grafting was performed at an elevated temperature. Activation energy for the initial rate of grafting was found to be 17 {kcal}/{mol} between 20 and 60°C and 10 {kcal}/{mol} between 60 and 80°C. Original PE filament begins to shrink at 70°C, show maximum shrinkage of 50% at 130°C and then breaks off at 136°C. When a 34% AA graft is converted to metallic salt such as sodium and calcium, the graft filament retains its filament form even above 300°C and gives maximum shrinkage of 15%. Burning tests by a wire-netting basket method indicate that graft filaments and its metallic salts do not form melting drops upon burning and are self-extinguishing. Original PE filament shows no moisture absorption, however, that of AA-grafted PE increases with increasing graft percent. The sodium salt of 15% graft shows the same level of moisture regain as cotton. The AA-grafted PE filament and its metallic salts can be dyed with cationic dyes even at 1% graft. Tensile properties of PE filament is impaired neither by grafting nor by conversion to metallic salts.

  5. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    SciTech Connect

    Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

    2012-09-01

    Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of {>=}grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD{sub 50} (normal) = 56 Gy and TD{sub 50} (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD{sub 50} value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

  6. Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Rectal Cancer

    ClinicalTrials.gov

    2013-01-09

    Adenocarcinoma of the Rectum; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Rectum; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

  7. Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

    PubMed Central

    2013-01-01

    Background The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. Methods A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Results At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). Conclusions We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1

  8. Bladder filling variation during conformal radiotherapy for rectal cancer

    NASA Astrophysics Data System (ADS)

    Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

    2017-05-01

    Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between chang