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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. 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.

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

    PubMed

    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

  4. 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

  5. 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).

  6. 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.

  7. 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.

  8. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    PubMed Central

    Jenrow, Kenneth A.; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs. PMID:25324981

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. The Effects of Fenugreek on Radiation Induced Toxicity for Human Blood T-Cells in Radiotherapy.

    PubMed

    Tavakoli, Mohamed Bagher; Kiani, Ali; Roayaei, Mahnaz

    2015-01-01

    Many cellular damages either in normal or cancerous tissues are the outcome of molecular events affected by ionizing radiation. T-cells are the most important among immune system agents and are used for biological radiation dose measurement in recommended standard methods. The herbs with immune modulating properties may be useful to reduce the risk of the damages and subsequently the diseases. The T-cells as the most important immune cells being targeted for biological dosimetry of radiation. This study proposes a flowcytometric-method based on fluorescein isothiocyanate- and propidium iodide (PI)-labeled annexin-V to assess apoptosis in blood T-cells after irradiation in both presence and absence of fenugreek extract. T-cells peripheral blood lymphocyte isolated from blood samples of healthy individuals with no irradiated job background. The media of cultured cells was irradiated 1-h after the fenugreek extract was added. The number of apoptotic cells was assessed by annexin-V protocol and multicolor flowcytometry. An obvious variation in apoptotic cells number was observed in presence of fenugreek extract (>80%). The results suggest that fenugreek extract can potentiate the radiation induced apoptosis or radiation toxicity in blood T-cells (P < 0.05). PMID:26284174

  14. 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.

  15. Reporting Late Rectal Toxicity in Prostate Cancer Patients Treated With Curative Radiation Treatment

    SciTech Connect

    Faria, Sergio L. Souhami, Luis; Joshua, Bosede; Vuong, Te; Freeman, Carolyn R.

    2008-11-01

    Purpose: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation. Methods and Materials: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature. Results: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up. Conclusion: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients.

  16. Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer.

    PubMed

    Tomita, Natsuo; Soga, Norihito; Ogura, Yuji; Hayashi, Norio; Shimizu, Hidetoshi; Kubota, Takashi; Ito, Junji; Hirata, Kimiko; Ohshima, Yukihiko; Tachibana, Hiroyuki; Kodaira, Takeshi

    2013-09-01

    The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student's t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student's t-test) was performed. The median follow-up time was 35 months. Late Grade 2-3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose-volume modeling to predict rectal complications after HT.

  17. 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

  18. Thiazolidine prodrugs as protective agents against gamma-radiation-induced toxicity and mutagenesis in V79 cells.

    PubMed

    Wilmore, B H; Cassidy, P B; Warters, R L; Roberts, J C

    2001-08-01

    Representatives of two classes of thiazolidine prodrug forms of the well-known radioprotective agents L-cysteine, cysteamine, and 2-[(aminopropyl)amino]ethanethiol (WR-1065) were synthesized by condensing the parent thiolamine with an appropriate carbonyl donor. Inherent toxicity of the prodrugs was assessed in V79 cells using a clonogenic survival assay. Protection against radiation-induced cell death was measured similarly after exposure to 0--8 Gy gamma ((137)Cs) radiation. Antimutagenic activity was determined at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus. All thiazolidine prodrugs exhibited less toxicity than their parent thiolamines, sometimes dramatically so. Protection against radiation-induced cell death was observed for the 2-alkylthiazolidine, 2(R,S)-D-ribo-(1',2',3',4'-tetrahydroxybutyl)thiazolidine (RibCyst), which produced a protection factor at 8 Gy of 1.8; the cysteine analogue, 2(R,S)-D-ribo-(1',2',3',4'-tetrahydroxybutyl)thiazolidine-4(R)-carboxylic acid (RibCys), was less active. RibCyst also exhibited excellent antimutational activity, rivaling that of WR-1065. The 2-oxothiazolidine analogues showed little activity in either determination under the conditions tested, perhaps due to their enhanced chemical and biochemical stability. PMID:11472218

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Complementary and alternative medicine in reducing radiation-induced skin toxicity.

    PubMed

    Hu, Jennifer J; Cui, Tengjiao; Rodriguez-Gil, Jorge L; Allen, Glenn O; Li, Jie; Takita, Cristiane; Lally, Brian E

    2014-08-01

    Radiation therapy-induced acute and late effects, particularly skin toxicities, have significant impact on cancer patients' quality of life and long-term survival. To date, no effective topical agents have been routinely used in the clinical setting to prevent skin toxicity. Using SKH-hr1 hairless mice, we investigated two complementary and alternative medicine in their effects on inflammation and ionizing radiation (IR)-induced skin toxicity: Calendula officinalis (CO) and Ching Wan Hung (CWH). They were applied immediately following each IR dosing of 10 Gy/day for 4 days. Skin toxicity and inflammatory factors were evaluated at multiple time points up to 15 days post-radiation. Serum interleukin (IL)-1α, monocyte chemotactic protein-1 (MCP1), keratinocyte-derived chemokine (KC), and granulocyte colony-stimulating factor (G-CSF) were significantly induced by radiation. Both CO and CWH significantly inhibited IR-induced MCP1 (p < 0.01), KC (p < 0.05), and G-CSF (p < 0.001). IR-induced erythema and blood vessel dilation were significantly reduced by CWH (p < 0.001) but not by CO at day 10 post-IR. Both agents inhibited IR-induced IL-1α (p < 0.01), MCP1 (p < 0.05), and vascular endothelial growth factor (p < 0.05). There were continuous inhibitory effects of CWH on IR-induced skin toxicities and inflammation. In contrast, CO treatment resulted in skin reactions compared to IR alone. Our results suggest that both CO and CWH reduce IR-induced inflammation and CWH reduced IR-induced erythema. In summary, CWH showed promising effects in reducing IR-related inflammation and skin toxicities, and future proof-of-principal testing in humans will be critical in evaluating its potential application in preventing IR-induced skin toxicities.

  7. 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

  8. 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.

  9. Modeling late rectal toxicities based on a parameterized representation of the 3D dose distribution

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

    Many models exist for predicting toxicities based on dose-volume histograms (DVHs) or dose-surface histograms (DSHs). This approach has several drawbacks as firstly the reduction of the dose distribution to a histogram results in the loss of spatial information and secondly the bins of the histograms are highly correlated with each other. Furthermore, some of the complex nonlinear models proposed in the past lack a direct physical interpretation and the ability to predict probabilities rather than binary outcomes. We propose a parameterized representation of the 3D distribution of the dose to the rectal wall which explicitly includes geometrical information in the form of the eccentricity of the dose distribution as well as its lateral and longitudinal extent. We use a nonlinear kernel-based probabilistic model to predict late rectal toxicity based on the parameterized dose distribution and assessed its predictive power using data from the MRC RT01 trial (ISCTRN 47772397). The endpoints under consideration were rectal bleeding, loose stools, and a global toxicity score. We extract simple rules identifying 3D dose patterns related to a specifically low risk of complication. Normal tissue complication probability (NTCP) models based on parameterized representations of geometrical and volumetric measures resulted in areas under the curve (AUCs) of 0.66, 0.63 and 0.67 for predicting rectal bleeding, loose stools and global toxicity, respectively. In comparison, NTCP models based on standard DVHs performed worse and resulted in AUCs of 0.59 for all three endpoints. In conclusion, we have presented low-dimensional, interpretable and nonlinear NTCP models based on the parameterized representation of the dose to the rectal wall. These models had a higher predictive power than models based on standard DVHs and their low dimensionality allowed for the identification of 3D dose patterns related to a low risk of complication.

  10. 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

  11. 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.

  12. 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.

  13. Estimation of {alpha}/{beta} for Late Rectal Toxicity Based on RTOG 94-06

    SciTech Connect

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

    2011-10-01

    Purpose: To estimate {alpha}/{beta}, the parameter ratio from the linear-quadratic (LQ) model, for Grade {>=}2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06; and to determine whether correcting the rectal dose-volume histogram (DVH) for differences in dose per fraction, based on the LQ model, significantly improves the fit to these data of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model. Methods and Materials: The generalized LKB model was fitted to the Grade {>=}2 late rectal toxicity data in two ways: by using DVHs representing physical dose to rectum, and by using a modified approach in which dose bins in the rectal DVH were corrected for differences in dose per fraction using the LQ model, with {alpha}/{beta} estimated as an additional unknown parameter. The analysis included only patients treated with the same treatment plan throughout radiotherapy, so that the dose per fraction to each voxel of rectum could be determined from the DVH. The likelihood ratio test was used to assess whether the fit of the LQ-corrected model was significantly better than the fit of the LKB model based on physical doses to rectum. Results: The analysis included 509 of the 1,084 patients enrolled on RTOG 94-06. The estimate of {alpha}/{beta} from the LQ-corrected LKB model was 4.8 Gy, with 68% confidence interval 0.6 Gy to 46 Gy. The fit was not significantly different from the fit of the LKB model based on physical dose to rectum (p = 0.236). Conclusions: The estimated fractionation sensitivity for Grade {>=}2 late rectal toxicity is consistent with values of {alpha}/{beta} for rectum found previously in human beings and in rodents. However, the confidence interval is large, and there is no evidence that LQ correction of the rectal DVH significantly changes the fit or predictions of the LKB model for this endpoint.

  14. 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. PMID:24068742

  15. 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).

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Principal Component Analysis-Based Pattern Analysis of Dose-Volume Histograms and Influence on Rectal Toxicity

    SciTech Connect

    Soehn, Matthias Alber, Markus; Yan Di

    2007-09-01

    Purpose: The variability of dose-volume histogram (DVH) shapes in a patient population can be quantified using principal component analysis (PCA). We applied this to rectal DVHs of prostate cancer patients and investigated the correlation of the PCA parameters with late bleeding. Methods and Materials: PCA was applied to the rectal wall DVHs of 262 patients, who had been treated with a four-field box, conformal adaptive radiotherapy technique. The correlated changes in the DVH pattern were revealed as 'eigenmodes,' which were ordered by their importance to represent data set variability. Each DVH is uniquely characterized by its principal components (PCs). The correlation of the first three PCs and chronic rectal bleeding of Grade 2 or greater was investigated with uni- and multivariate logistic regression analyses. Results: Rectal wall DVHs in four-field conformal RT can primarily be represented by the first two or three PCs, which describe {approx}94% or 96% of the DVH shape variability, respectively. The first eigenmode models the total irradiated rectal volume; thus, PC1 correlates to the mean dose. Mode 2 describes the interpatient differences of the relative rectal volume in the two- or four-field overlap region. Mode 3 reveals correlations of volumes with intermediate doses ({approx}40-45 Gy) and volumes with doses >70 Gy; thus, PC3 is associated with the maximal dose. According to univariate logistic regression analysis, only PC2 correlated significantly with toxicity. However, multivariate logistic regression analysis with the first two or three PCs revealed an increased probability of bleeding for DVHs with more than one large PC. Conclusions: PCA can reveal the correlation structure of DVHs for a patient population as imposed by the treatment technique and provide information about its relationship to toxicity. It proves useful for augmenting normal tissue complication probability modeling approaches.

  2. 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.

  3. 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.

  4. 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

  5. Correlation Between Dosimetric Parameters and Late Rectal and Urinary Toxicities in Patients Treated With High-Dose-Rate Brachytherapy Used as Monotherapy for Prostate Cancer

    SciTech Connect

    Konishi, Koji; Yoshioka, Yasuo; Isohashi, Fumiaki; Sumida, Iori; Kawaguchi, Yoshifumi; Kotsuma, Tadayuki; Adachi, Kana; Morimoto, Masahiro; Fukuda, Shoichi; Inoue, Takehiro

    2009-11-15

    Purpose: To evaluate the correlation between dosimetric parameters and late rectal and urinary toxicities in high-dose-rate brachytherapy (HDR-BT) used as monotherapy for prostate cancer. Methods and Materials: The data of 83 patients treated with HDR-BT alone for prostate cancer from 2001 through 2005 at Osaka University Hospital were analyzed. Median follow-up time was 36 months (range, 18-70). The total prescribed dose was 54 Gy in nine fractions over 5 days. Correlation between dosimetric parameters and late toxicities was examined. Results: The means of V30, V40, V50, V60, V70, D1cc, D2cc, D5cc, and D10cc of the rectum were significantly higher in 18 patients who presented with late rectal toxicity (Grades 1-3 rectal bleeding) than in the other 65 patients who did not. A significant difference was observed for D1cc-10cc but not for D5-90. The statistically most significant difference was observed for V40 and D5cc. Late rectal toxicity rate was significantly higher for patients with rectal V40 >= 8 cc than those with the rectal V40 < 8 cc (42% vs. 8%; p < 0.001), as well as for patients with rectal D5cc >= 27 Gy compared with those with rectal D5cc < 27 Gy (50% vs. 11%; p < 0.001). Dosimetric parameters of the urethra of 15 patients with late urinary toxicity were not significantly different from the 68 patients without toxicity. Conclusion: Rectal V40 < 8 cc and D5cc < 27 Gy may be dose-volume constraints in HDR-BT used as monotherapy for prostate cancer.

  6. 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.

  7. 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. PMID:26247629

  8. 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.

  9. 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.

  10. Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

    SciTech Connect

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

    2012-10-01

    Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportion of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.

  11. 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

  12. Modeling of α/β for late rectal toxicity from a randomized phase II study: conventional versus hypofractionated scheme for localized prostate cancer

    PubMed Central

    Marzi, Simona; Saracino, Biancamaria; Petrongari, Maria G; Arcangeli, Stefano; Gomellini, Sara; Arcangeli, Giorgio; Benassi, Marcello; Landoni, Valeria

    2009-01-01

    Background Recently, the use of hypo-fractionated treatment schemes for the prostate cancer has been encouraged due to the fact that α/β ratio for prostate cancer should be low. However a major concern on the use of hypofractionation is the late rectal toxicity, it is important to be able to predict the risk of toxicity for alternative treatment schemes, with the best accuracy. The main purpose of this study is to evaluate the response of rectum wall to changes in fractionation and to quantify the α/β ratio for late rectal toxicity Methods 162 patients with localized prostate cancer, treated with conformal radiotherapy, were enrolled in a phase II randomized trial. The patients were randomly assigned to 80 Gy in 40 fractions over 8 weeks (arm A) or 62 Gy in 20 fractions over 5 weeks (arm B). The median follow-up was 30 months. The late rectal toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale. It was assumed ≥ Grade 2 (G2) toxicity incidence as primary end point. Fit of toxicity incidence by the Lyman-Burman-Kutcher (LKB) model was performed. Results The crude incidence of late rectal toxicity ≥ G2 was 14% and 12% for the standard arm and the hypofractionated arm, respectively. The crude incidence of late rectal toxicity ≥ G2 was 14.0% and 12.3% for the arm A and B, respectively. For the arm A, volumes receiving ≥ 50 Gy (V50) and 70 Gy (V70) were 38.3 ± 7.5% and 23.4 ± 5.5%; for arm B, V38 and V54 were 40.9 ± 6.8% and 24.5 ± 4.4%. An α/β ratio for late rectal toxicity very close to 3 Gy was found. Conclusion The ≥ G2 late toxicities in both arms were comparable, indicating the feasibility of hypofractionated regimes in prostate cancer. An α/β ratio for late rectal toxicity very close to 3 Gy was found. PMID:19689825

  13. 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.

  14. 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.

  15. Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397)

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Sydes, Matthew R.; Dearnaley, David P.; Partridge, Mike

    2009-11-01

    Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dose-surface histogram (DSH) was determined. Correlations between these measures and seven clinically relevant rectal-toxicity endpoints were quantified by maximally selected standardized Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints, the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with the lateral extent of the dose distribution. For loose stools, the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and outcome differed considerably between the different endpoints. Due to these significant correlations, it is desirable to use shape-based tools in order to assess the quality of a dose distribution.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. A Pattern of Early Radiation-Induced Inflammatory Cytokine Expression Is Associated with Lung Toxicity in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Siva, Shankar; MacManus, Michael; Kron, Tomas; Best, Nickala; Smith, Jai; Lobachevsky, Pavel; Ball, David; Martin, Olga

    2014-01-01

    Purpose Lung inflammation leading to pulmonary toxicity after radiotherapy (RT) can occur in patients with non-small cell lung cancer (NSCLC). We investigated the kinetics of RT induced plasma inflammatory cytokines in these patients in order to identify clinical predictors of toxicity. Experimental Design In 12 NSCLC patients, RT to 60 Gy (30 fractions over 6 weeks) was delivered; 6 received concurrent chemoradiation (chemoRT) and 6 received RT alone. Blood samples were taken before therapy, at 1 and 24 hours after delivery of the 1st fraction, 4 weeks into RT, and 12 weeks after completion of treatment, for analysis of a panel of 22 plasma cytokines. The severity of respiratory toxicities were recorded using common terminology criteria for adverse events (CTCAE) v4.0. Results Twelve cytokines were detected in response to RT, of which ten demonstrated significant temporal changes in plasma concentration. For Eotaxin, IL-33, IL-6, MDC, MIP-1α and VEGF, plasma concentrations were dependent upon treatment group (chemoRT vs RT alone, all p-values <0.05), whilst concentrations of MCP-1, IP-10, MCP-3, MIP-1β, TIMP-1 and TNF-α were not. Mean lung radiation dose correlated with a reduction at 1 hour in plasma levels of IP-10 (r2 = 0.858, p<0.01), MCP-1 (r2 = 0.653, p<0.01), MCP-3 (r2 = 0.721, p<0.01), and IL-6 (r2 = 0.531, p = 0.02). Patients who sustained pulmonary toxicity demonstrated significantly different levels of IP-10 and MCP-1 at 1 hour, and Eotaxin, IL-6 and TIMP-1 concentration at 24 hours (all p-values <0.05) when compared to patients without respiratory toxicity. Conclusions Inflammatory cytokines were induced in NSCLC patients during and after RT. Early changes in levels of IP-10, MCP-1, Eotaxin, IL-6 and TIMP-1 were associated with higher grade toxicity. Measurement of cytokine concentrations during RT could help predict lung toxicity and lead to new therapeutic strategies. PMID:25289758

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Morphine Rectal

    MedlinePlus

    Rectal morphine is used to relieve moderate to severe pain. Morphine is in a class of medications called opiate ( ... Rectal morphine comes as a suppository to insert in the rectum. It is usually inserted every 4 hours. Use ...

  9. Patient Specific Characteristics Are an Important Factor That Determines the Risk of Acute Grade ≥ 2 Rectal Toxicity in Patients Treated for Prostate Cancer with IMRT and Daily Image Guidance Based on Implanted Gold Markers

    PubMed Central

    Liu, Xiaonan; Li, Jing; Wu, Teresa; Schild, Steven E; Schild, Michael H; Wong, William; Vora, Sujay; Fatyga, Mirek

    2016-01-01

    Aim To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics. Methods A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models. Results Sixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1–0.16), slope m=0.09 (0.08–0.11), and threshold dose TD50=56.8 (53.7–59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was PSAtox = 5.77 ± 2.27 and it was PSAnotox = 9.5 ± 7.8 for the

  10. 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.

  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. Different rectal toxicity tolerance with and without simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving hypofractionated prostate radiotherapy

    PubMed Central

    2014-01-01

    Purpose To investigate added morbidity associated with the addition of pelvic elective nodal irradiation (ENI) to hypofractionated radiotherapy to the prostate. Methods and materials Two-hundred twelve patients, treated with hypofractionated radiotherapy to the prostate between 2004 and 2011, met the inclusion criteria for the analysis. All patients received 70 Gy to the prostate delivered over 28 fractions and 103 (49%) received ENI consisting of 50.4 Gy to the pelvic lymphatics delivered simultaneously in 1.8 Gy fractions. The mean dose-volume histograms were compared between the two subgroups defined by use of ENI, and various dose-volume parameters were analyzed for effect on late lower gastrointestinal (GI) and genitourinary (GU) toxicity. Results Acute grade 2 lower GI toxicity occurred in 38 (37%) patients receiving ENI versus 19 (17%) in those who did not (p = 0.001). The Kaplan-Meier estimate of grade ≥ 2 lower GI toxicity at 3 years was 15.3% for patients receiving ENI versus 5.3% for those who did not (p = 0.026). Each rectal isodose volume was increased for patients receiving ENI up to 50 Gy (p ≤ 0.021 for each 5 Gy increment). Across all patients, the absolute V70 of the rectum was the only predictor of late GI toxicity. When subgroups, defined by the use of ENI, were analyzed separately, rectal V70 was only predictive of late GI toxicity for patients who received ENI. For patients receiving ENI, V70 > 3 cc was associated with an increased risk of late GI events. Conclusions Elective nodal irradiation increases the rates of acute and late GI toxicity when delivered simultaneously with hypofractioanted prostate radiotherapy. The use of ENI appears to sensitize the rectum to hot spots, therefore we recommend added caution to minimize the volume of rectum receiving 100% of the prescription dose in these patients. PMID:24893842

  13. [{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

  14. 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.

  15. Rectal Disorders

    MedlinePlus

    The rectum is the lower part of your large intestine where your body stores stool. Problems with rectum are common. They include hemorrhoids, abscesses, incontinence and cancer. Many people are embarrassed to talk about rectal ...

  16. Mesalamine Rectal

    MedlinePlus

    Rectal mesalamine is used to treat ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum), proctitis (swelling in the rectum), and ...

  17. 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.

  18. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2016-03-28

    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

  19. Small Bowel Dose Parameters Predicting Grade ≥3 Acute Toxicity in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation: An Independent Validation Study Comparing Peritoneal Space Versus Small Bowel Loop Contouring Techniques

    SciTech Connect

    Banerjee, Robyn; Chakraborty, Santam; Nygren, Ian; Sinha, Richie

    2013-04-01

    Purpose: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. Methods and Materials: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3 small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. Conclusion: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity.

  20. 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.

  1. 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.

  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 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.

  4. 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.

  5. 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

  6. 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.

  7. Radiation-induced leukemias in ankylosing spondylitis

    SciTech Connect

    Toolis, F.; Potter, B.; Allan, N.C.; Langlands, A.O.

    1981-10-01

    Three cases of leukemia occurred in patients with ankylosing spondylitis treated by radiotherapy. In each case, the leukemic process exhibited bizarre features suggesting that radiation is likely to induce atypical forms of leukemia possessing unusual attributes not shared by spontaneously developing leukemia. The likely distinctive aspects of radiation-induced leukemia are discussed.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Radiatively induced quark and lepton mass model

    NASA Astrophysics Data System (ADS)

    Nomura, Takaaki; Okada, Hiroshi

    2016-10-01

    We propose a radiatively induced quark and lepton mass model in the first and second generation with extra U (1) gauge symmetry and vector-like fermions. Then we analyze the allowed regions which simultaneously satisfy the FCNCs for the quark sector, LFVs including μ- e conversion, the quark mass and mixing, and the lepton mass and mixing. Also we estimate the typical value for the (g - 2) μ in our model.

  13. Management of radiation-induced urethral strictures

    PubMed Central

    Hofer, Matthias D.

    2015-01-01

    Radiation as a treatment option for prostate cancer has been chosen by many patients. One of the side effects encountered are radiation-induced urethral strictures which occur in up to 11% of patients. Radiation damage has often left the irradiated field fibrotic and with poor vascularization which make these strictures a challenging entity to treat. The mainstay of urologic management remains an urethroplasty procedure for which several approaches exist with variable optimal indication. Excision and primary anastomoses are ideal for shorter bulbar strictures that comprise the majority of radiation-induced urethral strictures. One advantage of this technique is that it does not require tissue transfers and success rates of 70-95% have consistently been reported. Substitution urethroplasty using remote graft tissue such as buccal mucosa are indicated if the length of the stricture precludes a tension-free primary anastomosis. Despite the challenge of graft survival in radiation-damaged and poorly vascularized recipient tissue, up to 83% of patients have been treated successfully although the numbers described in the literature are small. The most extensive repairs involve the use of tissue flaps, for example gracilis muscle, which may be required if the involved periurethral tissue is unable to provide sufficient vascular support for a post-operative urethral healing process. In summary, radiation-induced urethral strictures are a challenging entity. Most strictures are amenable to excision and primary anastomosis (EPA) with encouraging success rates but substitution urethroplasty may be indicated when extensive repair is needed. PMID:26816812

  14. 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.

  15. 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.

  16. 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.

  17. 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. PMID:23584263

  18. 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.

  19. 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. PMID:27209205

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    PubMed

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

    2016-08-21

    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

  12. 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

  13. 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.

  14. Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.

    PubMed

    Teh, Bin S; Dong, Lei; McGary, John E; Mai, Wei-Yuan; Grant, Walter; Butler, E Brian

    2005-01-01

    The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Loktrade mark bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2x2-cm field size. The dose beyond the

  15. Rectal culture (image)

    MedlinePlus

    A rectal culture test is performed by inserting a cotton swab in the rectum. The swab is rotated gently, and withdrawn. A smear of the swab is placed in culture media to encourage the growth of microorganisms. The ...

  16. Understanding Minor Rectal Bleeding

    MedlinePlus

    ... fever or significant rectal bleeding. Laser or infrared coagulation and sclerotherapy (injection of medicine directly into the ... or if symptoms persist despite rubber band ligation, coagulation or sclerotherapy. What are anal fissures? Tears that ...

  17. 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

  18. 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.

  19. 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.

  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. Theory Of Radiation-Induced Attenuation In Optical Fibers

    NASA Technical Reports Server (NTRS)

    Liu, Tsuen-Hsi; Johnston, Alan R.

    1996-01-01

    Improved theory of radiation-induced attenuation of light in optical fibers accounts for effects of dose rates. Based on kinetic aspects of fundamental physics of color centers induced in optical fibers by radiation. Induced attenuation is proportional to density of color centers, and part of this density decays by thermal-annealing/recombination process after irradiation.

  2. 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.

  3. 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

  4. Cathodoluminescence of radiation-induced zircon

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Y.; Nishido, H.; Kayama, M.; Noumi, Y.

    2013-12-01

    Zircon occurs as a common accessory mineral in igneous, metamorphic and sedimentary rocks, and maintains much information on thermal history, metamorphic process and natural radiation dose accumulated in the mineral. U-Pb zircon dating (e.g., SHRIMP) is an important tool to interpret a history of the minerals at a micrometer-scale, where cathodoluminescence (CL) image has been used for identification of internal zones and domains having different chemical compositions and/or structures with a high spatial resolution. The CL of zircon is derived from various types of emission centers, which are derived from impurities such as rare earth elements (REE) and structural defects. In fact, the CL features of zircon are closely related to metamorphic process and radiation from contained radionuclides as well as geochemical condition of its formation. Most zircon has yellow emission, which seems to be assigned to UO2 centers or radiation-induced defect during metamictization of the lattice by alpha particles from the decay of U and Th. In this study, the radiation effects on zircon CL have been studied for He+ ion-implanted samples annealed at various temperatures to clarify radiation-induced defect centers involved with the yellow CL emission in zircon. Single crystals of zircon from Malawi (MZ), Takidani granodiorite (TZ) and Kurobegawa granite (KZ) were selected for He+ ion implantation experiments. The polished plates of the samples were implanted by He+ ion 4.0 MeV corresponding to energy of alpha particle from 238 U and 232Th. CL spectra in the range from 300 to 800 nm with 1 nm step were measured by a scanning electron microscopy-cathodoluminescence (SEM-CL). CL spectra of untreated and annealed zircon show emission bands at ~370 nm assigned to intrinsic defect centers and at ~480, ~580 and ~760 nm to trivalent Dy impurity centers (Cesbron et al., 1995; Gaft et al, 2005). CL emissions in the yellow-region were observed in untreated zircon. The TZ and KZ indicate

  5. Rectal ulcer: Due to ketoprofen, argon plasma coagulation and prostatic brachytherapy.

    PubMed

    Koessler, Thibaud; Servois, Vincent; Mariani, Pascale; Aubert, Emilie; Cacheux, Wulfran

    2014-12-01

    Prostatic brachytherapy with permanent seed implants is a recent and safe radiation therapy technique associated with radiation-induced digestive disease. Argon plasma coagulation procedure is a validated modality in the management of haemorrhagic radiation proctitis, which is known to occasionally induce chronic rectal ulcers. We report here an original case report of an acute painful rectal ulcer as a consequence of the combination of short-term therapy with non-steroidal anti-inflammatory drugs therapy, prostatic brachytherapy with malposition of seed implants and argon plasma coagulation procedure in a patient with haemorrhagic radiation proctitis. The description of this clinical observation is essential to recommend the discontinuation of non-steroidal anti-inflammatory drugs therapy and the control of the position of seed implants in case of prostatic brachytherapy before argon plasma coagulation for radiation-induced proctitis.

  6. Rectal leiomyosarcoma: a rare and long-term complication of radiation therapy

    PubMed Central

    Futuri, Solaiman; Donohoe, Kelsey; Spaccavento, Colette; Yudelman, Ian

    2014-01-01

    Leiomyosarcoma of the rectum can develop as a late complication in patients with a history of pelvic irradiation. We report the case of a patient who developed rectal leiomyosarcoma 13 years after receiving radiation for treatment of a stage 2 squamous cell cancer of the anus. This was detected on physical examination. Based on a discussion with the patient, we decided to manage conservatively. Overall, leiomyosarcomas constitute 5–12% of radiation-induced sarcomas. Rectal leiomyosarcoma is rare, accounting for 0.1–0.5% of all malignant tumours of the rectum. As radiation therapy plays a major role in the management of anal cancer, it is important that clinicians are aware of the possible development of radiation-induced sarcomas that may occur decades after initial management. PMID:25315801

  7. 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

  8. Rectal Microbicide Development

    PubMed Central

    Dezzutti, Charlene

    2014-01-01

    The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmaco-dynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2–3 years. PMID:23612991

  9. General Information about Rectal Cancer

    MedlinePlus

    ... Research Rectal Cancer Treatment (PDQ®)–Patient Version General Information About Rectal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  10. 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.

  11. Radiation-induced nausea and vomiting

    PubMed Central

    Habibi, Mohsen; Namimoghadam, Amir; Korouni, Roghaye; Fashiri, Paria; Borzoueisileh, Sajad; Elahimanesh, Farideh; Amiri, Fatemeh; Moradi, Ghobad

    2016-01-01

    Abstract Despite the improvements in cancer screening and treatment, it still remains as one of the leading causes of mortality worldwide. Nausea and vomiting as the side effects of different cancer treatment modalities, such as radiotherapy, are multifactorial and could affect the treatment continuation and patient quality of life. Therefore, the aim of this study was to assess the possible linkage between ABO blood groups and radiation-induced nausea and vomiting (RINV), also its incidence and affecting factors. One hundred twenty-eight patients referring to Tohid hospital of Sanandaj, Iran, were selected and the patients and treatment-related factors were determined in a cross-sectional study. Patients’ nausea and vomiting were recorded from the onset of treatment until 1 week after treatment accomplishment. Also, previous possible nausea and vomiting were recorded. The frequencies of nausea and vomiting and their peak time were examined during the treatment period. The association between ABO blood group and the incidence of radiotherapy-induced nausea and vomiting (RINV) were significant and it seems that A blood group patients are the most vulnerable individuals to these symptoms. The association between Rhesus antigen and the time of maximum severity of RINV may indicate that Rhesus antigen affects the time of maximum severity of RINV. The incidence of RINV was not affected by karnofsky performance status, but it was related to the severity of RINV. Furthermore, among the factors affecting the incidence of nausea and vomiting, nausea and vomiting during patient's previous chemotherapy, radiotherapy region, and background gastrointestinal disease were shown to be three important factors. In addition to familiar RINV-affecting factors, ABO blood group may play an important role and these results address the needs for further studies with larger sample size. PMID:27495037

  12. 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.

  13. 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.

  14. Advances in dosimetry and biological predictors of radiation-induced esophagitis

    PubMed Central

    Yu, Yang; Guan, Hui; Dong, Yuanli; Xing, Ligang; Li, Xiaolin

    2016-01-01

    Objective To summarize the research progress about the dosimetry and biological predictors of radiation-induced esophagitis. Methods We performed a systematic literature review addressing radiation esophagitis in the treatment of lung cancer published between January 2009 and May 2015 in the PubMed full-text database index systems. Results Twenty-eight eligible documents were included in the final analysis. Many clinical factors were related to the risk of radiation esophagitis, such as elder patients, concurrent chemoradiotherapy, and the intense radiotherapy regimen (hyperfractionated radiotherapy or stereotactic body radiotherapy). The parameters including Dmax, Dmean, V20, V30, V50, and V55 may be valuable in predicting the occurrence of radiation esophagitis in patients receiving concurrent chemoradiotherapy. Genetic variants in inflammation-related genes are also associated with radiation-induced toxicity. Conclusion Dosimetry and biological factors of radiation-induced esophagitis provide clinical information to decrease its occurrence and grade during radiotherapy. More prospective studies are warranted to confirm their prediction efficacy. PMID:26869804

  15. 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.

  16. Treatment of radiation-induced cystitis with hyperbaric oxygen

    SciTech Connect

    Weiss, J.P.; Boland, F.P.; Mori, H.; Gallagher, M.; Brereton, H.; Preate, D.L.; Neville, E.C.

    1985-08-01

    The effects of hyperbaric oxygen on radiation cystitis have been documented in 3 patients with radiation-induced hemorrhagic cystitis refractory to conventional therapy. Cessation of gross hematuria and reversal of cystoscopic bladder changes were seen in response to a series of hyperbaric oxygen treatments of 2 atmosphere absolute pressure for 2 hours. To our knowledge this is the first report of cystoscopically documented healing of radiation-induced bladder injury.

  17. Radiation-induced reactions in polymer films

    NASA Astrophysics Data System (ADS)

    Biscoglio, Michael Benedict

    Since the 1950's, there has been a considerable interest in the effects of ionizing radiation on the physical properties of polymer systems. Radiation induced chemical changes that were found to be helpful in producing specialty polymers, but also potentially harmful by degrading the physical performance of the material. Therefore, solute molecules, which act as excited state quenchers, and free radical scavengers, have been incorporated into the polymers in order to regulate the crosslinking, scission and desaturation reactions. This work is focused on using spectroscopic techniques to characterize the physical properties of polymeric media and the reactions occurring within them following pulsed radiolysis. This is done primarily by using arene doped polymer films which have highly absorbing excited states and radical ions that are easily monitored by transient studies. The probes are used to characterize the polymeric microenvironment, to monitor reaction rates, and to interfere in the radical reactions. Photophysical and photochemical characterization of partially crystalline polyethylene complements data previously obtained by conventional physical techniques for polymer characterization. Probe molecules are excluded from crystalline zones and distributed in a networked structure of amorphous zones. Upon high energy radiolysis, it is found that polyolefin systems efficiently donate all radical ions and excited states to the solute molecules, even when the energy is absorbed within the polymer crystalline zones. Studies of the subsequent reactions of the solute excited states and radical ions reveal information about their long term effectiveness as protectants. It is found that highly excited states formed by the recombination of solute radical ions are energetic enough to cause dissociation of halo-arenes. Also, arenes are found to become attached to the polymer chain through a polymer-aryl radical intermediate. These intermediates have been isolated and

  18. 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

  19. 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

  20. 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

  1. 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

  2. Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome

    PubMed Central

    Haderlein, Marlen

    2016-01-01

    Background. Apoptotic rates in peripheral blood lymphocytes can predict radiation induced normal tissue toxicity. We studied whether apoptosis in lymphocytes has a prognostic value for therapy outcome. Methods. Lymphocytes of 87 rectal cancer patients were ex vivo irradiated with 2 Gy, 8 Gy, or a combination of 2 Gy ionizing radiation and Oxaliplatin. Cells were stained with Annexin V and 7-Aminoactinomycin D and apoptotic and necrotic rates were analyzed by multicolor flow cytometry. Results. After treatment, apoptotic and necrotic rates in CD8+ cells are consistently higher than in CD4+ cells, with lower corresponding necrotic rates. Apoptotic and necrotic rates of CD4+ cells and CD8+ cells correlated well within the 2 Gy, 8 Gy, and 2 Gy and Oxaliplatin arrangements (p ≤ 0.009). High apoptotic CD8+ rates after 2 Gy, 8 Gy, and 2 Gy + Oxaliplatin treatment were prognostically favorable for metastasis-free survival (p = 0.009, p = 0.038, and p = 0.009) and disease-free survival (p = 0.013, p = 0.098, and p = 0.013). Conclusions. Ex vivo CD8+ apoptotic rates are able to predict the patient outcome in regard to metastasis-free or disease-free survival. Patients with higher CD8+ apoptotic rates in the peripheral blood have a more favorable prognosis. In addition to the prediction of late-toxicity by utilization of CD4+ apoptotic rates, the therapy outcome can be predicted by CD8+ apoptotic rates. PMID:27340400

  3. Chemotherapy or radiation-induced oral mucositis.

    PubMed

    Lalla, Rajesh V; Saunders, Deborah P; Peterson, Douglas E

    2014-04-01

    Oral mucositis is a significant toxicity of systemic chemotherapy and of radiation therapy to the head and neck region. The morbidity of oral mucositis can include pain, nutritional compromise, impact on quality of life, alteration in cancer therapy, risk for infection, and economic costs. Management includes general symptomatic support and targeted therapeutic interventions for the prevention or treatment of oral mucositis. Evidence-based clinical practice guidelines are available to guide clinicians in the selection of effective management strategies.

  4. [Laparoscopic rectal resection technique].

    PubMed

    Anthuber, M; Kriening, B; Schrempf, M; Geißler, B; Märkl, B; Rüth, S

    2016-07-01

    The quality of radical oncological operations for patients with rectal cancer determines the rate of local recurrence and long-term survival. Neoadjuvant chemoradiotherapy for locally advanced tumors, a standardized surgical procedure for rectal tumors less than 12 cm from the anus with total mesorectal excision (TME) and preservation of the autonomous nerve system for sexual and bladder function have significantly improved the oncological results and quality of life of patients. The TME procedure for rectal resection has been performed laparoscopically in Germany for almost 20 years; however, no reliable data are available on the frequency of laparoscopic procedures in rectal cancer patients in Germany. The rate of minimally invasive procedures is estimated to be less than 20 %. A prerequisite for using the laparoscopic approach is implicit adherence to the described standards of open surgery. Available data from prospective randomized trials, systematic reviews and meta-analyses indicate that in the early postoperative phase the generally well-known positive effects of the minimally invasive approach to the benefit of patients can be realized without any long-term negative impact on the oncological results; however, the results of many of these studies are difficult to interpret because it could not be confirmed whether the hospitals and surgeons involved had successfully completed the learning curve. In this article we would like to present our technique, which we have developed over the past 17 years in more than 1000 patients. Based on our experiences the laparoscopic approach can be highly recommended as a suitable alternative to the open procedure. PMID:27277556

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

    PubMed

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

    2010-09-01

    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.

  7. Hyperbaric oxygen: Primary treatment of radiation-induced hemorrhagic cystitis

    SciTech Connect

    Weiss, J.P.; Neville, E.C.

    1989-07-01

    Of 8 patients with symptoms of advanced cystitis due to pelvic radiation treated with hyperbaric oxygen 7 are persistently improved during followup. All 6 patients treated for gross hematuria requiring hospitalization have been free of symptoms for an average of 24 months (range 6 to 43 months). One patient treated for stress incontinence currently is dry despite little change in bladder capacity, implying salutary effect from hyperbaric oxygen on the sphincter mechanism. One patient with radiation-induced prostatitis failed to respond. This experience suggests that hyperbaric oxygen should be considered the primary treatment for patients with symptomatic radiation-induced hemorrhagic cystitis.

  8. 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

  9. Rectal bleeding induced by Dipyridamole.

    PubMed

    Bayer, I; Kyzer, S; Creter, D; Lewinski, U H

    1986-02-01

    Nineteen patients treated continuously with Dipyridamole were evaluated for rectal bleeding. Thirteen suffered from overt rectal bleeding and six served as controls. Hemorrhoids were found in all patients. Contact bleeding was found in 16. The bleeding continued despite rubber band ligation, and stopped only on withdrawal of the drug. PMID:3484697

  10. 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.

  11. 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. PMID:9257424

  12. Radiation-induced segregation in alloy X-750

    SciTech Connect

    Kenik, E.A.

    1996-12-31

    Microstructural and microchemical evolution of an Alloy X-750 heat under neutron irradiation was studied in order to understand the origin of irradiation-assisted stress corrosion cracking. Both clustering of point defects and radiation-induced segregation at interfaces were observed. Although no significant changes in the precipitate structure were observed, boundaries exhibited additional depletion of Cr and Fe and enrichment of Ni.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Subcutaneous Administration of Bovine Superoxide Dismutase Protects Lungs from Radiation-Induced Lung Injury

    PubMed Central

    Jackson, Isabel L.; Vujaskovic, Zeljko

    2016-01-01

    Background The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation (RT) exposure mitigates development of pulmonary toxicity in rats. Methods 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+5mg/kg bSOD; and (6) sham RT+15mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 hours postradiation. 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+, 4HNE+ cells), macrophage activation (ED1+), and expression of profibrotic TGF-β in irradiated tissue. Results Radiation led to an increase in all evaluated parameters. Treatment with 15mg/kg bSOD significantly decreased levels of all 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. Conclusions The single application of bSOD (15mg/kg) ameliorates radiation induced lung injury through suppression of ROS/RNS dependent tissue damage. PMID:26110460

  18. 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. PMID:27209188

  19. Rectal cancer: Neoadjuvant chemoradiotherapy.

    PubMed

    Rödel, Claus; Hofheinz, Ralf; Fokas, Emmanouil

    2016-08-01

    The monolithic approach to apply the same schedule of preoperative 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) to all patients with clinically staged TNM stage II/III rectal cancer need to be questioned. Five randomized trials have been completed to determine if the addition of oxaliplatin to preoperative 5-FU/capecitabine-based CRT offers an advantage compared with single-agent CRT. In contrast to the German CAO/ARO/AIO-04 trial, results from the ACCORD 12, STAR-01, PETACC-6 and NSAPB R-04 trials failed to demonstrate a significant improvement of early or late efficacy endpoints with the addition of oxaliplatin. Most of the phase II trials incorporating cetuximab into CRT reported disappointingly low rates of pCR; the combination of CRT with VEGF inhibition showed encouraging pCR rates but at the cost of increased surgical complications. Novel clinical trials currently address (1) the role of induction and consolidation chemotherapy before or after CRT, (2) minimal or omitted surgery following complete response to CRT, or (3) the omission of radiotherapy for selected patients with response to neoadjuvant chemotherapy. The notion of different multimodal treatment concepts according to tumor stage, location, mesorectal fascia margin status, molecular profiles, tumor response, and patients' preferences becomes increasingly popular and will render the multimodal treatment approach of rectal cancer more risk-adapted. PMID:27644910

  20. 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.

  1. 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.

  2. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    PubMed Central

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu; LaRiviere, Patrick J.; Sammani, Saad; Lussier, Yves A.; Dudek, Steven M.; Natarajan, Viswanathan; Weichselbaum, Ralph R.; Garcia, Joe G. N.

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1−/−) or with reduced expression of S1P receptors (S1PR1+/−, S1PR2−/−, and S1PR3−/−) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.—Mathew, B., Jacobson, J. R., Berdyshev, E., Huang, Y., Sun, X., Zhao, Y., Gerhold, L. M., Siegler, J., Evenoski, C., Wang, T., Zhou, T., Zaidi, R., Moreno-Vinasco, L., Bittman, R., Chen, C. T., LaRiviere, P. J., Sammani, S., Lussier, Y. A., Dudek, S. M., Natarajan, V., Weichselbaum, R. R., Garcia, J. G. N. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. PMID:21712494

  3. [Symptoms and treatment of radiation-induced reactions].

    PubMed

    Brzozowska, Anna; Idziak, Magdalena; Burdan, Franciszek; Mazurkiewicz, Maria

    2015-05-01

    Radiotherapy is one of the main methods of cancer treatment alone or in combination with chemotherapy. It is applied in about 60% of oncological patients. However, in spite of its clinical usefulness, radiotherapy is associated with a high risk of radiation-induced side effects, including dermatitis, enteritis, cystitis, pericarditis, pneumonia or depression, sexual function disorders, cardiomiopathy, coronary heart disease, anomalies of heart valves and development of second malignant tumor. The early diagnosis and proper treatment of radiation-induced side effects have a major impact on patients` quality of life and future prognosis. Radiation reactions can be categorized as acute or late, occurring before and after six months after radiotherapy. Among the most common acute reactions there were observed: skin rash, mucositis, nausea, vomiting, fever and radiation pneumonitis. Within reference to the late complications, we distinguish for instance fibrosis of organs, a radiation necrosis of bone, ulcers, fistulas, sexual dysfunction and the development of second malignant carcinomas. PMID:26039025

  4. Using Imaging Methods to Interrogate Radiation-Induced Cell Signaling

    SciTech Connect

    Shankaran, Harish; Weber, Thomas J.; Freiin von Neubeck, Claere H.; Sowa, Marianne B.

    2012-04-01

    There is increasing emphasis on the use of systems biology approaches to define radiation induced responses in cells and tissues. Such approaches frequently rely on global screening using various high throughput 'omics' platforms. Although these methods are ideal for obtaining an unbiased overview of cellular responses, they often cannot reflect the inherent heterogeneity of the system or provide detailed spatial information. Additionally, performing such studies with multiple sampling time points can be prohibitively expensive. Imaging provides a complementary method with high spatial and temporal resolution capable of following the dynamics of signaling processes. In this review, we utilize specific examples to illustrate how imaging approaches have furthered our understanding of radiation induced cellular signaling. Particular emphasis is placed on protein co-localization, and oscillatory and transient signaling dynamics.

  5. Radiation-induced Cochlea hair cell death: mechanisms and protection.

    PubMed

    Tan, Pei-Xin; Du, Sha-Sha; Ren, Chen; Yao, Qi-Wei; Yuan, Ya-Wei

    2013-01-01

    Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini- review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC) , are claimed to be effective at reducing radiation- inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre- examined in order to minimize the damage to cochlea hair cells.

  6. Radiation-induced lung injury: a hypersensitivity pneumonitis

    SciTech Connect

    Gibson, P.G.; Bryant, D.H.; Morgan, G.W.; Yeates, M.; Fernandez, V.; Penny, R.; Breit, S.N.

    1988-08-15

    Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.

  7. Ionizing Radiation Induces HMGB1 Cytoplasmic Translocation and Extracellular Release

    PubMed Central

    Wang, Lili; He, Li; Bao, Guoqiang; He, Xin; Fan, Saijun; Wang, Haichao

    2016-01-01

    Objective A nucleosomal protein, HMGB1, can be secreted by activated immune cells or passively released by dying cells, thereby amplifying rigorous inflammatory responses. In this study we aimed to test the possibility that ionizing radiation similarly induces cytoplasmic HMGB1 translocation and extracellular release. Method Human skin fibroblast (GM0639) and bronchial epithelial (16HBE) cells and animals (rats) were exposed to X-ray radiation, and HMGB1 translocation and release were assessed by immunocytochemistry and immunoassay, respectively. Results At a wide dose range (4.0 – 12.0 Gy), X-ray radiation induced a dramatic cytoplasmic HMGB1 translocation, and triggered a time- and dose-dependent HMGB1 release both in vitro and in vivo. The radiation-mediated HMGB1 release was associated with noticeable chromosomal DNA damage and loss of cell viability. Conclusion radiation induces HMGB1 cytoplasmic translocation and extracellular release through active secretion and passive leakage processes. PMID:27331198

  8. Biological determinants of radiation-induced human breast cancer

    SciTech Connect

    Feig, S.A.

    1980-01-01

    This is the second in a three part series on the hypothetical risk from x-ray mammography. It will review those aspects of breast anatomy, histology, physiology, and pathology which are pertinent to radiation carcinogenesis. Radiation-induced breast cancers are histologically identical to the naturally occurring type in that they arise from the ductal epithelium and consist of a similar proportion of infiltrating and intraductal lesions. Possible explanations for the increased resistance to radiation effect in women over 30 years of age at time of exposure include regression of the glandular target tissue, hormonal changes, and parity. Examples of age-related sensitivity and hormonal dependence in other radiation-induced human and animal tumors will be discussed.

  9. 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.

  10. 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).

  11. Techniques for measuring radiation induced effects of acousto optic devices

    SciTech Connect

    Taylor, E.W.

    1995-08-01

    Innovative measurement techniques for determining radiation induced changes in acousto optic devices are briefly discussed. Measurements of acousto optic operational parameters such as signal transmission efficiency, diffraction efficiency, spatial intensity and bandwidth responses during electron irradiations are described. During exposure to pulsed electrons, only transient perturbations to the acousto optic operational parameters were experienced. Examples of new measurement procedures and typical data resulting from the measurements are presented.

  12. 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.

  13. Repair of radiation induced genetic damage under microgravity.

    PubMed

    Pross, H D; Kost, M; Kiefer, J

    1994-10-01

    The influence of microgravity on the repair of radiation induced genetic damage in a temperature-conditional repair mutant of the yeast Saccharomyces cerevisiae (rad 54-3) was investigated onboard the IML-1 mission (January 22nd-30th 1992, STS-42). Cells were irradiated before the flight, incubated under microgravity at the permissive (22 degrees C) and restrictive (36 degrees C) temperature and afterwards tested for survival. The results suggest that repair may be reduced under microgravity.

  14. Radiation-induced products of peptides and their enzymatic digestibility

    SciTech Connect

    Gajewski, E.

    1983-01-01

    Chemical characterization of radiation-induced products of peptides and proteins is essential for understanding the effect of ionizing radiation on peptides and proteins. Furthermore, peptides containing radiation-altered amino acid residues might not be completely digestible by proteolytic enzymes. In this work, small homopeptides of Ala, Phe and Met were chosen as model peptides. Lysozyme was used to investigate the effect of ionizing radiation on a small protein. All peptides and lysozyme were irradiated in diluted, oxygen free, N/sub 2/O-saturated aqueous solutions, using a /sup 60/Co-..gamma..-source. HPLC, capillary GC and GC-MS were applied to isolate and characterize the radiation-induced products. The enzymatic digestibility of the products was investigated using aminopeptidase M, leucine aminopeptidase, carboxypeptidase A and carboxypeptidase Y. It was found that irradiation of peptides examined in this work leads to racemization and alteration of amino acid residues and crosslinks between the peptide chains. In addition, it was established that exopeptidases act differently on radiation-induced dimers of peptides composed of aliphatic, aromatic and sulfur-containing amino acids.

  15. Molecular targets in radiation-induced blood-brain barrier disruption

    SciTech Connect

    Nordal, Robert A.; Wong, C. Shun . E-mail: shun.wang@sw.ca

    2005-05-01

    Disruption of the blood-brain barrier (BBB) is a key feature of radiation injury to the central nervous system. Studies suggest that endothelial cell apoptosis, gene expression changes, and alteration of the microenvironment are important in initiation and progression of injury. Although substantial effort has been directed at understanding the impact of radiation on endothelial cells and oligodendrocytes, growing evidence suggests that other cell types, including astrocytes, are important in responses that include induced gene expression and microenvironmental changes. Endothelial apoptosis is important in early BBB disruption. Hypoxia and oxidative stress in the later period that precedes tissue damage might lead to astrocytic responses that impact cell survival and cell interactions. Cell death, gene expression changes, and a toxic microenvironment can be viewed as interacting elements in a model of radiation-induced disruption of the BBB. These processes implicate particular genes and proteins as targets in potential strategies for neuroprotection.

  16. 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

  17. 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.

  18. A Genetically Determined Dose-Volume Histogram Predicts for Rectal Bleeding among Patients Treated With Prostate Brachytherapy

    SciTech Connect

    Cesaretti, Jamie A. . E-mail: jamie.cesaretti@msnyuhealth.org; Stock, Richard G.; Atencio, David P.; Peters, Sheila A.; Peters, Christopher A.; Burri, Ryan J.; Stone, Nelson N.; Rosenstein, Barry S.

    2007-08-01

    Purpose: To examine whether possession of genetic alterations in the ATM (ataxia telangiectasia) gene is associated with rectal bleeding in a dose-dependent and volume-dependent manner. Methods and Materials: One hundred eight prostate cancer patients who underwent brachytherapy using either an {sup 125}I implant, a {sup 103}Pd implant, or the combination of external beam radiotherapy with a {sup 103}Pd implant and had a minimum of 1 year follow-up were screened for DNA sequence variations in the 62 coding exons of the ATM gene using denaturing high-performance liquid chromatography. Rectal dose was reported as the volume (in cubic centimeters) of rectum receiving the brachytherapy prescription dose. The two-sided Fisher exact test was used to compare differences in proportions. Results: A significant correlation between the presence of any ATM sequence alteration and Grade 1 to 2 proctitis was obtained when the radiation dose to rectal tissue was quantified. Rectal bleeding occurred in 4 of 13 patients (31%) with a variant versus 1 of 23 (4%) without a genetic alteration for patients who had <0.7 cm{sup 3} of rectal tissue receiving the implant prescription dose (p = 0.05). Of patients in whom 0.7-1.4 cm{sup 3} of the rectum received the implant prescription, 4 of 11 (36%) with an ATM alteration exhibited Grade 1 to 2 proctitis, whereas 1 of 21 (5%) without a variant (p = 0.04) developed this radiation-induced late effect. Conclusions: The possession of genetic variants in the ATM gene is associated with the development of radiation-induced proctitis after prostate cancer radiotherapy for patients who receive the full prescription dose to either a low or a moderate volume of rectal tissue.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Radiation-induced physical changes in UHMWPE implant components.

    PubMed

    Naidu, S H; Bixler, B L; Moulton, M J

    1997-02-01

    Post-irradiation aging of ultra-high molecular weight polyethylene (UHMWPE) is not well understood. Retrieval studies and in vitro aged specimens have shown oxidative changes along with increases in crystallinity. Critical analysis and review of the polymer science and polymer physics literature shows that while oxidation may be important during the first year post-irradiation, subsequent aging occurs because of initial gamma radiation-induced chain scission leading to eventual isothermal crystallization of polymer chains in the amorphous regions of the UHMWPE bulk. Mechanical properties of aged UHMWPE are not as yet clear and, until such data become available, gamma irradiation sterilization must be used with caution.

  8. Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis.

    PubMed

    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

  9. 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.

  10. Radiation-induced segregation in candidate fusion-reactor alloys

    SciTech Connect

    Brimhall, J.L.; Baer, D.R.; Jones, R.H.

    1981-07-01

    The effect of radiation on surface segregation of minor and impurity elements has been studied in four candidate fusion reactor alloys. Radiation induced surface segregation of phosphorus was found in both 316 type stainless steel and in Nimonic PE-16. Segregation and depletion of the other alloying elements in 316 stainless steel agreed with that reported by other investigators. Segregation of nitrogen in ferritic HT-9 was enhanced by radiation but no phosphorus segregation was detected. No significant radiation enhanced or induced segregation was observed in a Ti-6Al-4V alloy. The results indicate that radiaton enhanced grain boundary segregation could contribute to the embrittlement of 316 SS and PE-16.

  11. 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.

  12. 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

  13. 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.

  14. Radiation-induced apoptosis in the eye structures: a review

    NASA Astrophysics Data System (ADS)

    Belkacémi, Yazid; Huchet, Aymeri; Baudouin, Christophe; Lartigau, Éric

    2005-02-01

    Apoptosis plays a crucial role in tissue homeostasis and in the removal of damaged cells from tissues. Both increased and insufficient cell death can lead to human diseases. Apoptotic process is under the control of physiological metabolism as well as a panel of genes. After exposure to radiation, membrane damages induce the membrane pathway signal transduction for cell apoptosis. The importance of the radiation-induced apoptosis in the different ocular tissues and its relationship to the radiation parameters are reviewed in this article. This topic of ocular research has not been addressed in detail in the literature.

  15. Radiation-induced collisional pumping of molecules containing few atoms

    SciTech Connect

    Vasil'ev, G.K.; Chernyshev, Y.A.; Makarov, E.F.; Yakushev, V.G.

    1986-01-01

    The authors analyze the radiation-induced collisional pumping of few-atom molecules by laser emission taking into account both collisional and noncollisional processes of vibrational energy transfer in a molecule. For typical values of the parameters the vibrational energy of the molecules was found to depend on the laser emission intensity; regions of weak absorption, optimum absorption, and saturation appear as the pumping rate rises. Qualitative general conclusions are reached concerning the optimum conditions for the realization, in a medium absorbing laser emission, of either nonequilibrium dissociation or a chemical reaction involving vibrationally excited molecules.

  16. Radiation-induced salivary gland tumors: report of a case.

    PubMed

    Smith, S A

    1976-09-01

    I discuss radiation-induced salivary gland tumors, with special emphasis on those tumors thought to be secondary to childhood head and neck irradiation for benign diseases. I report such a case and review the literature. Statistically, 77.6% of irradiation-induced tumors occur in the parotid gland and 22.4% in the submaxillary and minor salivary glands. A greater proportion of malignant tumors are noted in the submaxillary and minor salivary glands. At present, there is no demonstrable relationship between tumor occurrence and the amount of radiation recieved. Young children are more susceptible to irradiation-induced salivary tumors than older individuals.

  17. Drugs Approved for Colon and Rectal Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Colon and Rectal Cancer This page ... and rectal cancer that are not listed here. Drugs Approved for Colon Cancer Avastin (Bevacizumab) Bevacizumab Camptosar ( ...

  18. 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

  19. 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

  20. 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.

  1. Management of extraperitoneal rectal injuries.

    PubMed

    Bostick, P J; Johnson, D A; Heard, J F; Islas, J T; Sims, E H; Fleming, A W; Sterling-Scott, R P

    1993-06-01

    Twenty-eight consecutive extraperitoneal rectal injuries for a period of 34 months ending in May 1990 were reviewed retrospectively. All injuries were due to penetrating gunshot wounds. The rectal exam was positive in 75% of patients versus 80.8% with proctosigmoidoscopy. All 28 patients had diversion of the fecal stream. Diverting colostomies were performed in 17 patients, Hartmann's colostomies in 7 patients, and proximal loop colostomies in 4 patients. Presacral drainage was used in 25 patients (89.3%). Distal irrigation was performed in 13 patients (46.4%) and primary repair in 9 patients (32.1%). There was one infectious complication (3.6%) and no deaths (0%). Fecal diversion and presacral drainage are the mainstay of therapy for civilian rectal injuries. The importance of distal irrigation of the rectum has not been established. Primary repair of the rectum has no effect on morbidity and mortality.

  2. 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

  3. 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.

  4. 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.

  5. Enhancement of radiation-induced apoptosis by Podophyllum hexandrum.

    PubMed

    Prem Kumar, I; Rana, S V S; Samanta, N; Goel, H C

    2003-09-01

    The aqueous extract of Podophyllum hexandrum (RP-1), which has been recently reported to manifest radioprotective and anti-tumour properties, has been investigated for its mode of action. RP-1, under in-vitro conditions dose-dependently chelated metal ions, inhibited radiation or metal ion-induced hydroxyl radicals and lipid peroxidation and scavenged superoxide anions. Intraperitoneal administration of RP-1 to mice pre-irradiation (10 Gy) induced more DNA fragmentation and lipid peroxidation in thymocytes maximally at 4 and 8 h, respectively, in comparison with RP-1 treatment or irradiation. Flow-cytometric quantification of sub-diploid peak, oligonucleosomal cleavage assay (ladder) and depletion of total thiols also corroborated the ability of RP-1 to enhance radiation-induced apoptosis. RP-1 in presence of 100 microM CuSO(4) induced strand breaks in plasmid DNA and addition of metal chelators (EDTA and deferoxamine) inhibited the strand scission. Treatment with a major constituent of RP-1, podophyllin, did not cause strand breaks, but isolated constituents of RP-1, quercetin or podophyllotoxin, induced strand breaks. Depending on its concentration in the milieu, RP-1 acted as a pro- or antioxidant modifying the radiation-induced apoptosis and therefore could be exploited for cancer management.

  6. 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

    2012-10-01

    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.

  7. Nature of radiation-induced defects in quartz.

    PubMed

    Wang, Bu; Yu, Yingtian; Pignatelli, Isabella; Sant, Gaurav; Bauchy, Mathieu

    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. PMID:26178116

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. UV-radiation-induced degradation of fluorinated polyimide films

    NASA Astrophysics Data System (ADS)

    Chang, Li-Hsin; Saha, Naresh C.

    1994-12-01

    Fully cured fluorinated polyimide (FPI) films with low dielectric constants ( less than or equal to 3.0) have been found to be chemically altered when exposed to UV radiation during a process integration study. This chemical modification is manifested in the loss of film thickness after it is subjected to UV radiation followed by photoresist stripping. The UV-radiation-induced surface modifications of the FPI film have been characterized by X-ray photoelectron spectroscopy (XPS). The XPS data show the presence of C=O and COO(-) sites in the FPI molecule following UV exposure. Under prolonged UV exposure in a stepper, the FPI film acts as a positive working photoresist. However, a 2 kA plasma enhanced chemically vapor-deposited oxide mask and/or a typical 12 kA photoresist mask effectively shields the FPI from UV-radiation-induced degradation. The effects of FPI on UV radiation present during other normal wafer processing steps such as plasma deposition and reactive ion-etching were also studied and found to be negligible.

  15. Radiation induced corrosion of copper for spent nuclear fuel storage

    NASA Astrophysics Data System (ADS)

    Björkbacka, Åsa; Hosseinpour, Saman; Johnson, Magnus; Leygraf, Christofer; Jonsson, Mats

    2013-11-01

    The long term safety of repositories for radioactive waste is one of the main concerns for countries utilizing nuclear power. The integrity of engineered and natural barriers in such repositories must be carefully evaluated in order to minimize the release of radionuclides to the biosphere. One of the most developed concepts of long term storage of spent nuclear fuel is the Swedish KBS-3 method. According to this method, the spent fuel will be sealed inside copper canisters surrounded by bentonite clay and placed 500 m down in stable bedrock. Despite the importance of the process of radiation induced corrosion of copper, relatively few studies have been reported. In this work the effect of the total gamma dose on radiation induced corrosion of copper in anoxic pure water has been studied experimentally. Copper samples submerged in water were exposed to a series of total doses using three different dose rates. Unirradiated samples were used as reference samples throughout. The copper surfaces were examined qualitatively using IRAS and XPS and quantitatively using cathodic reduction. The concentration of copper in solution after irradiation was measured using ICP-AES. The influence of aqueous radiation chemistry on the corrosion process was evaluated based on numerical simulations. The experiments show that the dissolution as well as the oxide layer thickness increase upon radiation. Interestingly, the evaluation using numerical simulations indicates that aqueous radiation chemistry is not the only process driving the corrosion of copper in these systems.

  16. A rare cause of severe rectal bleeding: solitary rectal ulcer syndrome.

    PubMed

    Urganc, Nafiye; Kalyoncu, Derya; Usta, Merve; Eken, Kamile Gulcin

    2014-10-01

    Solitary rectal ulcer syndrome is a rare benign disorder in children which often goes unrecognized or easily misdiagnosed with other common diseases. It usually presents with rectal bleeding, constipation, mucous discharge, prolonged straining, tenesmus, and lower abdominal pain. The rectal bleeding varies from a little fresh blood to severe hemorrhage that requires blood transfusion. We report herein a pediatric case of solitary rectal ulcer syndrome who admitted to pediatric emergency department with severe rectal bleeding for reminding this rare syndrome.

  17. 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

  18. Rectal-wall dose dependence on postplan timing after permanent-seed prostate brachytherapy

    SciTech Connect

    Taussky, Daniel; Yeung, Ivan; Williams, Theresa; Pearson, Shannon; McLean, Michael; Pond, Gregory; Crook, Juanita . E-mail: Juanita.crook@rmp.uhn.on.ca

    2006-06-01

    Purpose: Dose to rectal wall after permanent-seed prostate brachytherapy is dependent on distance between posterior prostatic seeds and anterior rectal wall and is influenced by postimplant periprostatic edema. We analyzed the effect of postplan timing on anterior rectal-wall dose. Methods and Materials: Twenty patients received permanent seed {sup 125}I brachytherapy as monotherapy (145 Gy). Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out by use of preloaded needles. Postimplant dosimetry was calculated by use of magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of rectal wall and as the RV100 in cc. Results: The dose to rectal wall increased progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p < 0.001). Conclusion: Although periprostatic edema cannot be quantified by postimplant imaging, the dose to the anterior rectal wall increases significantly over time as prostatic and periprostatic edema resolve. Critical-organ dose reporting and guidelines for minimizing toxicity must take into account the time of the assessment.

  19. 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

  20. Sleeping position and rectal temperature.

    PubMed

    Petersen, S A; Anderson, E S; Lodemore, M; Rawson, D; Wailoo, M P

    1991-08-01

    The effects of sleeping position upon body temperature were assessed by continuous monitoring of rectal temperature in 137 babies sleeping at home under conditions chosen by their parents. There were three groups of subjects: (1) normal babies aged 12-22 weeks whose temperature rhythms were developed, (2) normal babies aged 6-12 weeks who were developing their night time temperature rhythms, and (3) babies the night after diphtheria, pertussis, and tetanus immunisation, whose temperature rhythms were disturbed. Sleeping in the prone position was not associated with higher rectal temperatures at any time of night in young babies, nor did it exaggerate the disturbance of rectal temperature rhythm after immunisation. In older normal babies the prone position did not disturb rectal temperature in the first part of the night, though prone sleepers warmed a little faster prior to walking, especially in warm conditions. Prone sleepers were, however, born earlier in gestation and tended to be of lower birth weight. Normal babies can therefore thermoregulate effectively whatever their sleeping posture, even in warm conditions, though the prone position may make it slightly more difficult to lose heat. It is difficult to see how the prone position, even interacting with warm conditions, could induce lethal hyperthermia in otherwise normal babies. Perhaps the prone position is associated with other risk factors for sudden infant death syndrome.

  1. 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.

  2. Solar radiation induced rotational bursting of interplanetary particles

    NASA Technical Reports Server (NTRS)

    Sparrow, J. G.

    1975-01-01

    It is suggested that the magnitudes of the two radiation-induced rotational bursting mechanisms (Radzieskii effect and windmill effect) have been overestimated and that they do not work significantly faster than the Poynting-Robertson effect in removing interplanetary particles. These two mechanisms are described, and serious doubts are raised regarding the derivation of their radiation pressure-torque proportionality constants, which are required for calculating their magnitudes. It is shown that both mechanisms will cause the alignment of elongated particles and, consequently, the polarization of zodiacal light. Since no positive polarization has been measured at the antisolar point, it is concluded that the magnitudes of the rotational bursting mechanisms are smaller than that of the Poynting-Robertson effect.

  3. Imaging for assessment of radiation-induced normal tissue effects

    PubMed Central

    Jeraj, Robert; Cao, Yue; Ten Haken, Randall K.; Hahn, Carol; Marks, Lawrence

    2010-01-01

    Imaging can provide quantitative assessment of radiation-induced normal tissue effects. Identifying an early sign of normal tissue damage with imaging would have the potential to predict organ dysfunction, thereby allowing re-optimization of treatment strategies based upon individual patients’ risks and benefits. Early detection with non-invasive imaging may enable interventions to mitigate therapy-associated injury prior to its clinical manifestation. Further, successive imaging may provide an objective assessment of the impact of such mitigation therapies. However, many problems make application of imaging to normal tissue assessment challenging, and further work is required to establish imaging biomarkers as surrogate endpoints of clinical outcome. The performance of clinical trials where normal tissue injury is a clearly defined endpoint would greatly aid in realization of these goals. PMID:20171509

  4. 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.

  5. Radiation induced crystallinity damage in poly( L-lactic acid)

    NASA Astrophysics Data System (ADS)

    Kantoǧlu, Ömer; Güven, Olgun

    2002-12-01

    The radiation-induced crystallinity damage in poly( L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature ( Tg) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units ( G(- u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  6. A model of radiation-induced myelopoiesis in space.

    PubMed

    Esposito, R D; Durante, M; Gialanella, G; Grossi, G; Pugliese, M; Scampoli, P; Jones, T D

    2001-01-01

    Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space. PMID:11771552

  7. 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.

  8. 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.

  9. 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).

  10. 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.

  11. [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. PMID:19860183

  12. 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.

  13. UVA and UVB radiation-induced oxidation products of quercetin.

    PubMed

    Fahlman, Brian M; Krol, Ed S

    2009-12-01

    The flavonol quercetin is believed to provide protection against ultraviolet (UV) radiation-induced damage in plants. As part of our investigations into the potential for quercetin to protect skin against UV radiation-induced damage we have investigated the products of quercetin exposed to UV radiation in vitro. UVA (740 microW cm(-2) at 365 nm) or UVB (1300 microW cm(-2) at 310 nm) irradiation of quercetin in methanol results in a small conversion (less than 20%) to C-ring breakdown products over 11 h. When the triplet sensitizer benzophenone is added, greater than 90% conversion by UVA or UVB occurs within 1h. The major photoproducts from either UVA or UVB radiation are 2,4,6-trihydroxybenzaldehyde (1), 2-(3',4'-dihydroxybenzoyloxy)-4,6-dihydroxybenzoic acid (2) and 3,4-dihydroxyphenylethanol (3). Product 2 has previously been observed as a product of oxidative metabolism of quercetin, however products 1 and 3 appear to be the result of a unique UV-dependent pathway. In conclusion we have determined that quercetin undergoes slow decomposition to a mixture of C-ring-opened products, two of which to our knowledge have not been previously observed for quercetin decomposition, and that the presence of a triplet sensitizer greatly increases UV radiation-mediated quercetin decomposition. The presence of endogenous photosensitizers in the skin could potentially affect the UV stability of quercetin, suggesting that further study of quercetin for both its photoprotective properties and photostabilty in skin are warranted.

  14. Radiation-induced meningioma: a distinct molecular genetic pattern?

    PubMed

    Shoshan, Y; Chernova, O; Juen, S S; Somerville, R P; Israel, Z; Barnett, G H; Cowell, J K

    2000-07-01

    Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors. PMID:10901233

  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 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

  17. 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.

  18. 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.

  19. Characterization of a Novel Radiation-Induced Sarcoma Cell Line

    PubMed Central

    Lang, J.E.; Zhu, W.; Nokes, B.T.; Sheth, G.R.; Novak, P.; Fuchs, L.; Watts, G.S.; Futscher, B.W.; Mineyev, N.; Ring, A.; LeBeau, L.; Nagle, R.; Cranmer, L.D.

    2014-01-01

    Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS. Synopsis We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a radiation-induced sarcoma (RIS). Our novel RIS cell line constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. PMID:25644184

  20. [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.

  1. Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

    PubMed

    Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

    2015-12-01

    Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities. PMID:27512575

  2. 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.

  3. 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

  4. Correlation between tumor regression grade and rectal volume in neoadjuvant concurrent chemoradiotherapy for rectal cancer

    PubMed Central

    Lee, Hong Seok; Choi, Doo Ho; Park, Hee Chul; Park, Won; Yu, Jeong Il; Chung, Kwangzoo

    2016-01-01

    Purpose To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results Average rectal volume and ARA were 11.3 mL and 2.9 cm². After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary. PMID:27592514

  5. Silencing Egr1 Attenuates Radiation-induced Apoptosis in Normal Tissues while Killing Cancer Cells and Delaying Tumor Growth

    PubMed Central

    Zhao, Diana Yi; Jacobs, Keith M; Hallahan, Dennis E; Thotala, Dinesh

    2015-01-01

    Normal tissue toxicity reduces the therapeutic index of radiotherapy and decreases the quality of life for cancer survivors. Apoptosis is a key element of the radiation response in normal tissues like the hippocampus and small intestine, resulting in neurocognitive disorders and intestinal malabsorption. The Early Growth Response 1 (Egr1) transcription factor mediates radiation-induced apoptosis by activating the transcription of pro-apoptosis genes in response to ionizing radiation (IR). Therefore, we hypothesized that the genetic abrogation of Egr1 and the pharmacological inhibition of its transcriptional activity could attenuate radiation-induced apoptosis in normal tissues. We demonstrated that Egr1 null mice had less apoptosis in the hippocampus and intestine following irradiation as compared to their wild-type littermates. A similar result was achieved using Mithramycin A (MMA) to prevent binding of Egr1 to target promoters in the mouse intestine. Egr1 expression using shRNA dampened apoptosis and enhanced the clonogenic survival of irradiated HT22 hippocampal neuronal cells and IEC6 intestinal epithelial cells. Mechanistically, these events involved an abrogation of p53 induction by IR and an increase in the ratio of Bcl-2/Bax expression. In contrast, targeted silencing of Egr1 in two cancer cell lines (GL261 glioma cells, HCT116 colorectal cancer cells) was not radioprotective, since it reduced their growth while also sensitizing them to radiation-induced death. Further, Egr1 depletion delayed the growth of heterotopically implanted GL261 and HCT116 tumors. These results support the potential of silencing Egr1 in order to minimize the normal tissue complications associated with radiotherapy while enhancing tumor control. PMID:26206332

  6. 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

  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. 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.

  9. [The acute bleeding rectal ulcer].

    PubMed

    Hansen, H

    1985-06-14

    An acute bleeding rectal ulcer was the solitary condition in four patients. The cause of such an ulcer, which always results in heavy arterial bleeding, remains unknown. The source of bleeding is demonstrated by rectoscopy which may at times be difficult because of the large amount of blood in the rectum and the hidden position of the small ulcer. Sclerosing or circumferential suturing of the ulcer provides immediate cessation of bleeding and cure.

  10. Effects of Prostate-Rectum Separation on Rectal Dose From External Beam Radiotherapy

    SciTech Connect

    Susil, Robert C.; McNutt, Todd R.; DeWeese, Theodore L.; Song, Danny

    2010-03-15

    Purpose: In radiotherapy for prostate cancer, the rectum is the major dose-limiting structure. Physically separating the rectum from the prostate (e.g., by injecting a spacer) can reduce the rectal radiation dose. Despite pilot clinical studies, no careful analysis has been done of the risks, benefits, and dosimetric effects of this practice. Methods and Materials: Using cadaveric specimens, 20 mL of a hydrogel was injected between the prostate and rectum using a transperineal approach. Imaging was performed before and after spacer placement, and the cadavers were subsequently dissected. Ten intensity-modulated radiotherapy plans were generated (five before and five after separation), allowing for characterization of the rectal dose reduction. To quantify the amount of prostate-rectum separation needed for effective rectal dose reduction, simulations were performed using nine clinically generated intensity-modulated radiotherapy plans. Results: In the cadaveric studies, an average of 12.5 mm of prostate-rectum separation was generated with the 20-mL hydrogel injections (the seminal vesicles were also separated from the rectum). The average rectal volume receiving 70 Gy decreased from 19.9% to 4.5% (p < .05). In the simulation studies, a prostate-rectum separation of 10 mm was sufficient to reduce the mean rectal volume receiving 70 Gy by 83.1% (p <.05). No additional reduction in the average rectal volume receiving 70 Gy was noted after 15 mm of separation. In addition, spacer placement allowed for increased planning target volume margins without exceeding the rectal dose tolerance. Conclusion: Prostate-rectum spacers can allow for reduced rectal toxicity rates, treatment intensification, and/or reduced dependence on complex planning and treatment delivery techniques.

  11. The outcomes of therapeutic decision in lower 3rd rectal cancer patients.

    PubMed

    Chen, Chien-Hsin; Wei, Po-Li; Hsieh, Mao-Chih; Lin, En-Kwang; Chiou, Jeng-Fong; Lu, Yen-Jung; Wu, Szu-Yuan

    2016-09-01

    To investigate the outcomes of the selective neoadjuvant concurrent chemoradiotherapy (CCRT) in lower 3rd rectal cancer patients in different groups (with or without neoadjuvant CCRT), especially in survival rate, local recurrence rate, and sphincter preservation rate.From January 1999 to December 2012, 69 consecutive patients who had histologically proven adenocarcinoma of lower 3rd rectum, defined preoperatively as lower tumor margin within 7 cm from the anal verge as measured by rigid sigmoidoscopy, received total mesorectum excision (TME). Our inclusion criteria of neoadjuvant CCRT are lower 3rd rectal cancer, stage II/III, and large (diameter >5 cm or >1/2 of circumference). Neoadjuvant concurrent CCRT had begun to apply lower 3rd rectal cancer patients or not. The radiation techniques of neoadjuvant CCRT for lower 3rd rectal cancer patients were all conventional fraction intensity modulated radiotherapy (IMRT) and concurrent fluoropyrimidine chemotherapy.Five-year overall survival rate, disease-free survival rate, and local recurrence rate for lower 3rd rectal cancer patients in group I were 51%, 45%, and 25%, respectively. On the contrary, 5-year overall survival rate, disease-free survival rate, and local recurrence rate for lower rectal cancer patients in group II were 70%, 70%, and 3%, respectively. The 5-year sphincter sparing rate was increased from 38.2% to 100% after the beginning of neoadjuvant CCRT. Analyzing local recurrence, overall survival rate, disease-specific survival rate, and sphincter sparing rate in group II were statistically significant superior to group I.Five-year overall survival rate, disease-free survival rate, and sphincter sparing rate for lower 3rd rectal cancer patients were improved after the addition of neoadjuvant CCRT. No unacceptable toxicity was noted after conventional fraction IMRT and concurrent fluoropyrimidine chemotherapy. Our study showed neoadjuvant CCRT could be valuable for lower 3rd rectal cancer patients

  12. 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

  13. Rectal Ischemia Mimicked Tumor Mass

    PubMed Central

    Zikos, Nicolaos; Aggeli, Panagiota; Louka, Evangelia; Pappas-Gogos, George

    2013-01-01

    Ischemic proctitis is a rare disease which is usually encountered in elderly with comorbidities. We present a case of an 80-year old man with severe coronary disease who presented with severe hematochezia and hypotension. Endoscopy revealed a rectal mass 3-4 cm above the dental line and rectosigmoid mucosal inflammation compatible with ischemic colitis. The rectal insult was so intense that it resembled a neoplasmatic lesion. We discuss the causes, the prognostic factors, and the clinical and therapeutic challenges of this rare, albeit life-threatening entity, and we review the relative literature. A percentage of 10%–20% of patients with ischemic colitis usually have a distal potentially obstructing lesion or disorder such as cancer, diverticulitis or fecal impaction. Ischemic colitis, when mucosal and submucosal edema is severe and hemorrhagic nodules are large enough, can mimic a neoplasmatic lesion. The best treatment approach is a conservative management initially with a close clinical followup and after stabilization a repetition of rectal endoscopy with new biopsies. Early recognition of this clinical entity is of paramount importance to implement appropriate therapy (conservative or surgical) and avoid potentially fatal treatment of presumed inflammatory or infectious bowel diseases. PMID:24109523

  14. Optimizing Treatment for Rectal Prolapse.

    PubMed

    Hrabe, Jennifer; Gurland, Brooke

    2016-09-01

    Rectal prolapse is associated with debilitating symptoms and leads to both functional impairment and anatomic distortion. Symptoms include rectal bulge, mucous drainage, bleeding, incontinence, constipation, tenesmus, as well as discomfort, pressure, and pain. The only cure is surgical. The optimal surgical repair is not yet defined though laparoscopic rectopexy with mesh is emerging as a more durable approach. The chosen approach should be individually tailored, taking into account factors such as presence of pelvic floor defects and coexistence of vaginal prolapse, severe constipation, surgical fitness, and whether the patient has had a previous prolapse procedure. Consideration of a multidisciplinary approach is critical in patients with concomitant vaginal prolapse. Surgeons must weigh their familiarity with each approach and should have in their armamentarium both perineal and abdominal approaches. Previous barriers to abdominal procedures, such as age and comorbidities, are waning as minimally invasive approaches have gained acceptance. Laparoscopic ventral rectopexy is one such approach offering relatively low morbidity, low recurrence rates, and good functional improvement. However, proficiency with this procedure may require advanced training. Robotic rectopexy is another burgeoning approach which facilitates suturing in the pelvis. Successful rectal prolapse surgeries improve function and have low recurrence rates, though it is important to note that correcting the prolapse does not assure functional improvement. PMID:27582654

  15. Strategies for managing radiation-induced mucositis in head and neck cancer.

    PubMed

    Rosenthal, David I; Trotti, Andrea

    2009-01-01

    Radiation-induced mucositis (RIM) is a common toxicity for head and neck cancer (HNC) patients. The frequency has increased because of the use of more intensive altered radiation fractionation and concurrent chemotherapy regimens. The extent of the injury is directly related to the mucosal volume irradiated, anatomic subsite exposed, treatment intensity, and individual patient predisposition. The consequences of mucositis include pain, dysphagia including feeding tube dependency, dehydration, micronutrient deficiencies, weight loss, and potentially life-threatening aspiration. Currently, there is no Food and Drug Administration-approved cytoprotective agent that reliably prevents RIM for HNC, but several are under investigation. Strategies to limit the extent of mucositis and to manage its symptoms include basic oral care and supportive medications. Limiting the use of aggressive treatments to truly high-risk cancers and special attention to radiation therapy planning techniques can also help restrict the scope of the problem. This review focuses on mucositis recognition, patient treatment selection, and RIM symptom-management strategies. PMID:19028343

  16. An Unusual Cause of Rectal Stenosis

    PubMed Central

    Gruber, Maja; Füglistaler, Ida; Zettel, Andreas; Fox, Mark; Manz, Michael

    2016-01-01

    Solitary rectal ulcer syndrome (SRUS) is a benign disease that is often misdiagnosed. It is characterized by a combination of symptoms, endoscopic findings and histology. Patients present with constipation, rectal bleeding, mucous discharge, pain and a sensation of incomplete defecation. There are many different manifestations of this disease, with or without rectal prolapse. We report an unusual presentation of SRUS as a circular stenosis in a middle-aged male.

  17. Chemoradiotherapy response in recurrent rectal cancer

    PubMed Central

    Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

    2014-01-01

    The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan–Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P < 0.01). There was no difference in OS for either primary or recurrent rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified. PMID:24403010

  18. 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.

  19. 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.

  20. 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.

  1. 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

    2016-01-01

    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

  2. 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.

  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. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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. PMID:8862451

  11. 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.

  12. 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.

  13. 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.

  14. Simvastatin attenuates radiation-induced salivary gland dysfunction in mice

    PubMed Central

    Xu, Liping; Yang, Xi; Chen, Jiayan; Ge, Xiaolin; Qin, Qin; Zhu, Hongcheng; Zhang, Chi; Sun, Xinchen

    2016-01-01

    Objective Statins are widely used lipid-lowering drugs, which have pleiotropic effects, such as anti-inflammation, and vascular protection. In our study, we investigated the radioprotective potential of simvastatin (SIM) in a murine model of radiation-induced salivary gland dysfunction. Design Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent + sham irradiation (IR) (Group I), SIM + sham IR (Group II), IR + solvent (Group III), and IR + SIM (Group IV). SIM (10 mg/kg body weight, three times per week) was administered intraperitoneally 1 week prior to IR through to the end of the experiment. Saliva and submandibular gland tissues were obtained for biochemical, morphological (hematoxylin and eosin staining and Masson’s trichrome), and Western blot analysis at 8 hours, 24 hours, and 4 weeks after head and neck IR. Results IR caused a significant reduction of salivary secretion and amylase activity but elevation of malondialdehyde. SIM remitted the reduction of saliva secretion and restored salivary amylase activity. The protective benefits of SIM may be attributed to scavenging malondialdehyde, remitting collagen deposition, and reducing and delaying the elevation of transforming growth factor β1 expression induced by radiation. Conclusion SIM may be clinically useful to alleviate side effects of radiotherapy on salivary gland. PMID:27471375

  15. 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.

  16. Radiation induced oxidative damage modification by cholesterol in liposomal membrane

    NASA Astrophysics Data System (ADS)

    Pandey, B. N.; Mishra, K. P.

    1999-05-01

    Ionizing radiation induced structural and chemical alterations in egg lecithin liposomal membrane have been studied by measurements of lipid peroxides, conjugated diene and fluorescence polarization. Predominantly unilamellar phospholipid vesicles prepared by sonication procedure were subjected to radiation doses of γ-rays from Co-60 in aerated, buffered aqueous suspensions. The oxidative damage in irradiated lipid molecules of liposomes has been determined spectrophotometrically by diene conjugate formation and thiobarbituric acid reactive (TBAR) method as a function of radiation dose. A correlation was found between the radiation dose applied (0.1-1 kGy) and the consequent lipid oxidation. The damage produced in irradiated liposomal membrane was measured by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence decay and polarization. The observed decrease in DPH fluorescence and increase in polarization was found dependent on the radiation dose suggesting alterations in rigidity or organizational order in phospholipid bilayer after irradiation. Furthermore, irradiated liposome vesicles composed of cholesterol showed marked reduction in observed radiation mediated peroxide formation and significantly affected the DPH fluorescence parameters. The magnitude of these modifying effects were found dependent on the mole fraction of cholesterol. It is concluded that modulation of structural order in unilamellar vesicle membrane by variations in basic molecular components controlled the magnitude of lipid peroxidation and diene conjugate formation. These observations contribute to our understanding of mechanism of radical reaction mediated damage caused by ionizing radiation in phospholipid membrane.

  17. 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.

  18. 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.

  19. Processability improvement of polyolefins through radiation-induced branching

    NASA Astrophysics Data System (ADS)

    Cheng, Song; Phillips, Ed; Parks, Lewis

    2010-03-01

    Radiation-induced long-chain branching for the purpose of improving melt strength and hence the processability of polypropylene (PP) and polyethylene (PE) is reviewed. Long-chain branching without significant gel content can be created by low dose irradiation of PP or PE under different atmospheres, with or without multifunctional branching promoters. The creation of long-chain branching generally leads to improvement of melt strength, which in turn may be translated into processability improvement for specific applications in which melt strength plays an important role. In this paper, the changes of the melt flow rate and the melt strength of the irradiated polymer and the relationship between long-chain branching and melt strength are reviewed. The effects of the atmosphere and the branching promoter on long-chain branching vs. degradation are discussed. The benefits of improved melt strength on the processability, e.g., sag resistance and strain hardening, are illustrated. The implications on practical polymer processing applications such as foams and films are also discussed.

  20. 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.

  1. 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.

  2. 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.

  3. Spectroscopic characterization of radiation-induced defects in gallium nitride

    NASA Astrophysics Data System (ADS)

    Yang, Qing

    Radiation damage studies of GaN provide insights into the fundamental properties of the material as well as the basic knowledge needed to predict degradation of GaN-based devices in space-based applications or other radiation environments. The main interests are in investigating the properties of radiation-induced defects at the microscopic level and providing data to evaluate the radiation hardness of the material. Selective damage of the N-sublattice is achieved with 0.42 MeV electron irradiation. Two new luminescence lines at 3.4732 eV and 3.4545 eV are detected by time-resolved photoluminescence after irradiation. The two lines are associated with the ground state bound exciton of a new donor B1 and its two-electron transition. The donor binding energy of B1 is determined as 24.9 +/- 0.4 meV, shallower than the impurity donors ON and Si Ga. Among the possible defects, the nitrogen vacancy (VN) is the best candidate for the new donor B1. In addition, a change under focused 267 nm laser beam is observed at cryogenic temperatures in the excitonic luminescence of the irradiated sample. The donor bound exciton intensity of ON and SiGa, the total band edge luminescence intensity, and the luminescence decay lifetime of free and bound excitons all increase with laser exposure time. In contrast, the relative intensity of the B 1 bound exciton emission decreases. The change is not observed with below bandgap illumination. We propose that the light-induced change reflects the illumination-assisted dissociation of non-radiative defect complexes O N-Ni and SiGa-Ni, and subsequently the migration of Ni and at least partial annihilation of N i at VN. The new donor B1 bound exciton emission and the light-induced change starts to disappear at annealing temperature around 300°C, indicating the annihilation of the irradiation-induced vacancy and interstitial defects. An activation energy of 1.5 eV is obtained, which is proposed to be the sum of the dissociation energy of the ON

  4. 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.

  5. 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.

  6. Role of PECAM-1 in radiation-induced liver inflammation.

    PubMed

    Malik, Ihtzaz Ahmed; Stange, Ina; Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens Friedrich; Ellenrieder, Volker; Wolff, Hendrik Andreas

    2015-10-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation. Immunohistologically, an increased number of neutrophil granulocytes (NG) (but not of mononuclear phagocytes) was observed in the liver of WT and PECAM-1-KO mice at 6 hrs after irradiation. The number of recruited NG was higher and prolonged until 24 hrs in KO compared to WT-mice. Correspondingly, a significant induction of hepatic tumour necrosis factor (TNF)-α and CXC-chemokines (KC/CXCL1 interleukin-8/CXCL8) was detected together with an elevation of serum liver transaminases (6-24 hrs) in WT and KO-mice. Likewise, phosphorylation of signal transducer and activator of transcription-3 (STAT-3) was observed in both animal groups after irradiation. The level of all investigated proteins as well as of the liver transaminases was significantly higher in KO than WT-mice. In the cell-line U937, irradiation led to a reduction in PECAM-1 in parallel to an increased ICAM-1 expression. TNF-α-blockage by anti-TNF-α prevented this change in both proteins in cell culture. Radiation-induced stress conditions induce a transient accumulation of granulocytes within the liver by down-regulation/absence of PECAM-1. It suggests that reduction/lack in PECAM-1 may lead to greater and prolonged inflammation which can be prevented by anti-TNFα. PMID:26177067

  7. 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

  8. 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.

  9. 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

  10. Rectal mucocoele following subtotal colectomy for colitis.

    PubMed

    Appleton, N; Day, N; Walsh, C

    2014-09-01

    We present a unique case of a rectal mucocoele affecting a patient several years after his subtotal colectomy for ulcerative colitis. This was secondary to both a benign anorectal stenosis and a benign mucus secreting rectal adenoma. This case highlights the importance of surveillance in such patients.

  11. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  12. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

  13. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

  14. 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...

  15. Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

    ClinicalTrials.gov

    2015-10-24

    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

  16. Dose-Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

    SciTech Connect

    Gulliford, Sarah L.; Foo, Kerwyn; Morgan, Rachel C.; Aird, Edwin G.; Bidmead, A. Margaret; Critchley, Helen; Evans, Philip M. D.Phil.; Gianolini, Stefano; Mayles, W. Philip; Moore, A. Rollo; Sanchez-Nieto, Beatriz; Partridge, Mike; Sydes, Matthew R. C.Stat; Webb, Steve; Dearnaley, David P.

    2010-03-01

    Purpose: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>=50 Gy). Evidence is emerging that lower doses could also be important. Methods and Materials: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. Results: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<=80%, V40<=65%, V50<=55%, V60<=40%, V65<=30%, V70<=15%, and V75<=3%. Conclusion: Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

  17. Nonoperative management of rectal cancer.

    PubMed

    Torok, Jordan A; Palta, Manisha; Willett, Christopher G; Czito, Brian G

    2016-01-01

    Surgery has long been the primary curative modality for localized rectal cancer. Neoadjuvant chemoradiation has significantly improved local control rates and, in a significant minority, eradicated all disease. Patients who achieve a pathologic complete response to neoadjuvant therapy have an excellent prognosis, although the combination treatment is associated with long-term morbidity. Because of this, a nonoperative management (NOM) strategy has been pursued to preserve sphincter function in select patients. Clinical and radiographic findings are used to identify patients achieving a clinical complete response to chemoradiation, and they are then followed with intensive surveillance. Incomplete, nonresponding and those demonstrating local progression are referred for salvage with standard surgery. Habr-Gama and colleagues have published extensively on this treatment strategy and have laid the groundwork for this approach. This watch-and-wait strategy has evolved over time, and several groups have now reported their results, including recent prospective experiences. Although initial results appear promising, several significant challenges remain for NOM of rectal cancer. Further study is warranted before routine implementation in the clinic.

  18. Targets for, and consequences of, radiation-induced chromosomal instability

    NASA Astrophysics Data System (ADS)

    Kaplan, Mark Isaac

    Chromosomal instability has been demonstrated in a human- hamster hybrid cell line, GM10115, after exposure to x- rays. Chromosomal instability in these cells is characterized by the appearance of novel chromosomal rearrangements multiple generations after exposure to ionizing radiation. To identify the cellular target(s) for radiation-induced chromosomal instability, cells were treated with 125I-labeled compounds. Labeling cells with 125I-iododeoxyuridine, which caused radiation damage to the DNA and associated nuclear structures, did induce chromosomal instability. While cell killing and first-division chromosomal rearrangements increased with increasing numbers of 125I decays, the frequency of chromosomal instability was independent of dose. Incorporation of an 125I-labeled protein, 125I-succinyl- concanavalin A, into either the plasma membrane or the cytoplasm, failed to elicit chromosomal instability. These results show that radiation damage to the nucleus, and not to extranuclear regions, contributes to the induction of chromosomal instability. To determine the role of DNA strand breaks as a molecular lesion responsible for initiating chromosomal instability, cells were treated with a variety of DNA strand breaking agents. Agents capable of producing complex DNA double strand breaks, including X-rays, Neocarzinostatin and bleomycin, were able to induce chromosomal instability. In contrast, double strand breaks produced by restriction endonucleases as well as DNA strand breaks produced by hydrogen peroxide failed to induce chromosomal instability. This demonstrates that the type of DNA breakage is important in the eventual manifestation of chromosomal instability. In order to understand the relationship between chromosomal instability and other end points of genomic instability, chromosomally stable and unstable clones were analyzed for sister chromatid exchange, delayed reproductive cell death, delayed mutation, mismatch repair and delayed gene amplification

  19. Radiation induced chemical activity at iron and copper oxide surfaces

    NASA Astrophysics Data System (ADS)

    Reiff, Sarah C.

    The radiolysis of three iron oxides, two copper oxides, and aluminum oxide with varying amounts of water were performed using gamma-rays and 5 MeV 4He ions. The adsorbed water on the surfaces was characterized using temperature programmed desorption and diffuse reflectance infrared spectroscopy, which indicated that all of the oxides had chemisorbed water on the surface. Physisorbed water was observed on the Fe2O 3 and Al2O3 surfaces as well. Molecular hydrogen was produced from adsorbed water only on Fe2O3 and Al 2O3, while the other compounds did not show any hydrogen production due to the low amounts of water on the surfaces. Slurries of varying amounts of water were also examined for hydrogen production, and they showed yields that were greater than the yield for bulk water. However, the yields of hydrogen from the copper compounds were much lower than those of the iron suggesting that the copper oxides are relatively inert to radiation induced damage to nearby water. X-ray diffraction measurements did not show any indication of changes to the bulk crystal structure due to radiolysis for any of the oxides. The surfaces of the oxides were analyzed using Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). For the iron samples, FeO and Fe3O4, Raman spectroscopy revealed areas of Fe2O3 had formed following irradiation with He ions. XPS indicated the formation of a new oxygen species on the iron oxide surfaces. Raman spectroscopy of the copper oxides did not reveal any changes in the surface composition, however, XPS measurements showed a decrease in the amount of OH groups on the surface of Cu2O, while for the CuO samples the amount of OH groups were found to increase following radiolysis. Pristine Al2O3 showed the presence of a surface oxyhydroxide layer which was observed to decrease following radiolysis, consistent with the formation of molecular hydrogen.

  20. Radiation-induced osteosarcomas in the pediatric population

    SciTech Connect

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

    2005-11-15

    Purpose: Radiation-induced osteosarcomas (R-OS) have historically been high-grade, locally invasive tumors with a poor prognosis. The purpose of this study was to perform a comprehensive literature review and analysis of reported cases dealing with R-OS in the pediatric population to identify the characteristics, prognostic factors, optimal treatment modalities, and overall survival of these patients. Methods and Materials: A MEDLINE/PubMed search of articles written in the English language dealing with OSs occurring after radiotherapy (RT) in the pediatric population yielded 30 studies from 1981 to 2004. Eligibility criteria included patients <21 years of age at the diagnosis of the primary cancer, cases satisfying the modified Cahan criteria, and information on treatment outcome. Factors analyzed included the type of primary cancer treated with RT, the radiation dose and beam energy, the latency period between RT and the development of R-OS, and the treatment, follow-up, and final outcome of R-OS. Results: The series included 109 patients with a median age at the diagnosis of primary cancer of 6 years (range, 0.08-21 years). The most common tumors treated with RT were Ewing's sarcoma (23.9%), rhabdomyosarcoma (17.4%), retinoblastoma (12.8%), Hodgkin's disease (9.2%), brain tumor (8.3%), and Wilms' tumor (6.4%). The median radiation dose was 47 Gy (range, 15-145 Gy). The median latency period from RT to the development of R-OS was 100 months (range, 36-636 months). The median follow-up after diagnosis of R-OS was 18 months (1-172 months). The 3- and 5-year cause-specific survival rate was 43.6% and 42.2%, respectively, and the 3- and 5-year overall survival rate was 41.7% and 40.2%, respectively. Variables, including age at RT, primary site, type of tumor treated with RT, total radiation dose, and latency period did not have a significant effect on survival. The 5-year cause-specific and overall survival rate for patients who received treatment for R-OS involving

  1. Radiation-Induced Topological Disorder in Irradiated Network Structures

    SciTech Connect

    Hobbs, Linn W.

    2002-12-21

    This report summarizes results of a research program investigating the fundamental principles underlying the phenomenon of topological disordering in a radiation environment. This phenomenon is known popularly as amorphization, but is more formally described as a process of radiation-induced structural arrangement that leads in crystals to loss of long-range translational and orientational correlations and in glasses to analogous alteration of connectivity topologies. The program focus has been on a set compound ceramic solids with directed bonding exhibiting structures that can be described as networks. Such solids include SiO2, Si3N4, SiC, which are of interest to applications in fusion energy production, nuclear waste storage, and device manufacture involving ion implantation or use in radiation fields. The principal investigative tools comprise a combination of experimental diffraction-based techniques, topological modeling, and molecular-dynamics simulations that have proven a rich source of information in the preceding support period. The results from the present support period fall into three task areas. The first comprises enumeration of the rigidity constraints applying to (1) more complex ceramic structures (such as rutile, corundum, spinel and olivine structures) that exhibit multiply polytopic coordination units or multiple modes of connecting such units, (2) elemental solids (such as graphite, silicon and diamond) for which a correct choice of polytope is necessary to achieve correct representation of the constraints, and (3) compounds (such as spinel and silicon carbide) that exhibit chemical disorder on one or several sublattices. With correct identification of the topological constraints, a unique correlation is shown to exist between constraint and amorphizability which demonstrates that amorphization occurs at a critical constraint loss. The second task involves the application of molecular dynamics (MD) methods to topologically-generated models

  2. Single-Dose Radiation-Induced Oral Mucositis Mouse Model

    PubMed Central

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

    2016-01-01

    The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23 g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25 Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10 μm, respectively, compared to 200 μm in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25 Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25 Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1 mL of 0.9% saline/6 h for 24 h yielded a 100% survival only with 18 Gy self-resolved RIOM, which had 5.6 ± 0.3 days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival. PMID:27446800

  3. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

    SciTech Connect

    Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won; Oh, Sang Ho; Lee, Yun-Sil; Lee, Eun-Jung; Cho, Jaeho

    2015-05-08

    Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.

  4. Carbon and iron ion radiation-induced cytotoxicity and transformation in vitro

    PubMed Central

    Zhou, Zhaozong; Ware, Jeffrey H.; Kennedy, Ann R.

    2011-01-01

    The present study was undertaken to characterize carbon and iron ion radiation-induced adverse biological effects in terms of toxicity and transformation in vitro. HTori-3 human thyroid epithelial cells were irradiated with 0.3-GeV/n (13.6 KeV/µm) carbon ions and 1-GeV/n (150 KeV/µm) iron ions, both of which represent high-mass, high atomic number (Z) and high-energy particles known as HZE particles, as well as γ-rays. The survival of the irradiated cells was determined by a clonogenic survival assay. The yield of colonies growing in soft agar was used as a surrogate endpoint biomarker for transformation in vitro. The results showed that HZE particles and γ-ray radiations are effective in increasing the yield of anchorage-independent colonies. Based on the relative biological effectiveness (RBE) values in the clonogenic survival assays, 0.3-GeV/n carbon ions and 1-GeV/n iron ions were 2.9 and 2.4 times, respectively, as effective as γ-rays at killing the irradiated HTori-3 cells. At a dose of 200 cGy, 0.3-GeV/n carbon ions and 1-GeV/n iron ions were found to be 3.5 and 7.3 times, respectively, as effective as γ-rays at inducing anchorage-independent growth. These results suggest that the carcinogenic potential of 0.3-GeV/n carbon ions, as represented by the ability to induce anchorage-independent growth, may be lower than that of 1-GeV/n iron ions. PMID:22866150

  5. Pharmacologic approaches to protection against radiation-induced lethality and other damage.

    PubMed Central

    Weiss, J F

    1997-01-01

    other cytokines. Their potential usefulness against radiation-induced mutagenesis of pre- and postexposure administration of phosphorothioates and other classes of protectors should be corroborated in humans. PMID:9467066

  6. Genetic Mutations in Blood and Tissue Samples in Predicting Response to Treatment in Patients With Locally Advanced Rectal Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2015-09-03

    Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; 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. Radiation induced degradation of ketoprofen in dilute aqueous solution

    NASA Astrophysics Data System (ADS)

    Illés, Erzsébet; Takács, Erzsébet; Dombi, András; Gajda-Schrantz, Krisztina; Gonter, Katalin; Wojnárovits, László

    2012-09-01

    The intermediates and final products of ketoprofen degradation were investigated in 0.4 mmol dm-3 solution by pulse radiolysis and gamma radiolysis. For observation of final products UV-vis spectrophotometry and HPLC separation with diode array detection were used, and for identification MS was used. The reactions of •OH lead to hydroxycyclohexadienyl type radical intermediates, in their further reactions hydroxylated derivatives of ketoprofen form as final products. The hydrated electron is scavenged by the carbonyl oxygen and the electron adduct protonates to ketyl radical •OH is more effective in decomposing ketoprofen than hydrated electron. Chemical oxygen demand and total organic carbon content measurements on irradiated aerated solutions showed that using irradiation technology ketoprofen can be mineralised. The initial toxicity of the solution monitored by the Daphnia magna test steadily decreases with irradiation. Using 5 kGy dose no toxicity of the solution was detected with this test.

  8. Rectal Duplication Cyst: A Rare Cause of Rectal Prolapse in a Toddler.

    PubMed

    Khushbakht, Samreen; ul Haq, Anwar

    2015-12-01

    Rectal duplication cysts are rare congenital anomalies. They constitute only 4% of the total gastrointestinal anomalies. They usually present in childhood. The common presenting symptoms are mass or pressure effects like constipation, tenesmus, urinary retention, local infection or bleeding due to presence of ectopic gastric mucosa. We are reporting a rare presenting symptom of rectal duplication cyst in a 4-year-old boy/toddler who presented with rectal prolapse. He also had bleeding per rectum. Rectal examination revealed a soft mass palpable in the posterior rectal wall. CT scan showed a cystic mass in the posterior wall of the rectum. It was excised trans-anally and the postoperative recovery was uneventful. Biopsy report showed rectal duplication cyst. PMID:26691370

  9. PET-MRI in Diagnosing Patients With Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-11-25

    Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  10. [Ultrasonographic study of rectal carcinoid tumors].

    PubMed

    Nomura, M; Fujita, N; Matsunaga, A; Ando, M; Tominaga, G; Noda, Y; Kobayashi, G; Kimura, K; Yuki, T; Ishida, K; Yago, A; Mochizuki, F; Chonan, A

    1996-11-01

    To compare intraluminal ultrasonographic (ILUS) findings with histological findings of rectal carcinoid tumors, 35 patients with rectal carcinoid tumors were reviewed. The results were as follows: 1) The rectal wall was visualized as a seven- or nine-layer structure by means of ILUS in 81% of the patients. 2) The possibility that the thin hyperechoic third layer above the tumor on ILUS corresponds to the muscularis mucosae and fibrointerstitium above the tumor histologically. 3) In cases with relatively high internal echoes, the amount of fibrointerstitium exceeded that of tumor cells histologically. 4) In cases with nonuniform internal echo patterns, tumor cells were separated by thick fibrointerstitium forming nodular nests.

  11. MRI staging of low rectal cancer.

    PubMed

    Shihab, Oliver C; Moran, Brendan J; Heald, Richard J; Quirke, Philip; Brown, Gina

    2009-03-01

    Low rectal tumours, especially those treated by abdominoperineal excision (APE), have a high rate of margin involvement when compared with tumours elsewhere in the rectum. Correct surgical management to minimise this rate of margin involvement is reliant on highly accurate imaging, which can be used to plan the planes of excision. In this article we describe the techniques for accurate magnetic resonance imaging (MRI) assessment and a novel staging system for low rectal tumours. Using this staging system it is possible for the radiologist to demonstrate accurately tumour-free planes for surgical excision of low rectal tumours. PMID:18810451

  12. SU-E-J-93: Parametrisation of Dose to the Mucosa of the Anterior Rectal Wall in Transrectal Ultrasound Guided High-Dose-Rate Brachytherapy of the Prostate

    SciTech Connect

    Aitkenhead, A; Hamlett, L; Wood, D; Choudhury, A

    2014-06-01

    Purpose: In high-dose-rate (HDR) brachytherapy of the prostate, radiation is delivered from a number of radioactive sources which are inserted via catheter into the target volume. The rectal mucosa also receives dose during the treatment, which may lead to late toxicity effects. To allow possible links between rectal dose and toxicity to be investigated, suitable methods of parametrising the rectal dose are needed. Methods: During treatment of a series of 95 patients, anatomy and catheter locations were monitored by transrectal ultrasound, and target volume positions were contoured on the ultrasound scan by the therapist. The anterior rectal mucosal wall was identified by contouring the transrectal ultrasound balloon within the ultrasound scan. Source positions and dwell times, along with the dose delivered to the patient were computed using the Oncentra Prostate treatment planning system (TPS). Data for the series of patients were exported from the TPS in Dicom format, and a series of parametrisation methods were developed in a Matlab environment to assess the rectal dose. Results: Contours of the anterior rectal mucosa were voxelised within Matlab to allow the dose to the rectal mucosa to be analysed directly from the 3D dose grid. Dose parametrisations based on dose-surface (DSH) and dose-line (DLH) histograms were obtained. Both lateral and longitudinal extents of the mucosal dose were parametrised using dose-line histograms in the relevant directions. Conclusion: We have developed a series of dose parametrisations for quantifying the dose to the rectal mucosa during HDR prostate brachytherapy which are suitable for future studies investigating potential associations between mucosal dose and late toxicity effects. The geometry of the transrectal probe standardises the rectal anatomy, making this treatment technique particularly suited to studies of this nature.

  13. Synchrotron-Radiation Induced X-Ray Emission (SRIXE)

    SciTech Connect

    Jones, Keith W.

    1999-09-01

    and increase in scientific use can be maintained for the synchrotron x-ray source. A short summary of the present state of the synchrotron radiation-induced x-ray emission (SRIXE) method is presented here. Basically, SRIXE experiments can include any that depend on the detection. of characteristic x-rays produced by the incident x-ray beam born the synchrotron source as they interact with a sample. Thus, experiments done to measure elemental composition, chemical state, crystal, structure, and other sample parameters can be considered in a discussion of SRIXE. It is also clear that the experimentalist may well wish to use a variety of complementary techniques for study of a given sample. For this reason, discussion of computed microtomography (CMT) and x-ray diffraction is included here. It is hoped that this present discussion will serve as a succinct introduction to the basic ideas of SRIXE for those not working in the field and possibly help to stimulate new types of work by those starting in the field as well as by experienced practitioners of the art. The topics covered include short descriptions of (1) the properties of synchrotron radiation, (2) a description of facilities used for its production, (3) collimated microprobe, (4) focused microprobes, (5) continuum and monoenergetic excitation, (6) detection limits, (7) quantitation, (8) applications of SRIXE, (9) computed microtomography (CMT), and (10)chemical speciation using x-ray absorption near-edge structure (XANES) and extended x-ray absorption fine structure (EXAFS). An effort has been made to cite a wide variety of work from different laboratories to show the vital nature of the field.

  14. Image-based modeling of radiation-induced foci

    NASA Astrophysics Data System (ADS)

    Costes, Sylvain; Cucinotta, Francis A.; Ponomarev, Artem; Barcellos-Hoff, Mary Helen; Chen, James; Chou, William; Gascard, Philippe

    Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage occurs. To test this assumption, we used Monte Carlo simulations to predict the spatial distribution of DSB in human nuclei exposed to high or low-LET radiation. We then compared these predictions to the distribution patterns of three DNA damage sensing proteins, i.e. 53BP1, phosphorylated ATM and γH2AX in human mammary epithelial. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We first used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. Simulations showed a very good agreement for high-LET, predicting 0.7 foci/µm along the path of a 1 GeV/amu Fe particle against measurement of 0.69 to 0.82 foci/µm for various RIF 5 min following exposure (LET 150 keV/µm). On the other hand, discrepancies were shown in foci frequency for low-LET, with measurements 20One drawback using a theoretical model for the nucleus is that it assumes a simplistic and static pattern for DNA densities. However DNA damage pattern is highly correlated to DNA density pattern (i.e. the more DNA, the more likely to have a break). Therefore, we generalized our Monte Carlo approach to real microscope images, assuming pixel intensity of DAPI in the nucleus was directly proportional to the amount of DNA in that pixel. With such approach we could predict DNA damage pattern in real images on a per nucleus basis. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. As expected, simulations produced DNA-weighted random (Poisson) distributions. In

  15. [Perianal and rectal impalement injuries].

    PubMed

    Joos, A K; Herold, A; Palma, P; Post, S

    2006-09-01

    Perianal impalement injuries with or without involvement of the anorectum are rare. Apart from a high variety of injury patterns, there is a multiplicity of diagnostic and therapeutic options. Causes of perianal impalement injury are gunshot, accidents, and medical treatment. The diagnostic work-up includes digital rectal examination followed by rectoscopy and flexible endoscopy under anaesthesia. We propose a new classification for primary extraperitoneal perianal impalement injuries in four stages in which the extension of sphincter and/or rectum injury is of crucial importance. Therapeutic aspects such as wound treatment, enterostomy, drains, and antibiotic treatment are discussed. The proposed classification encompasses recommendations for stage-adapted management and prognosis of these rare injuries. PMID:16896899

  16. Rectal temperature after marathon running.

    PubMed Central

    Maughan, R J; Leiper, J B; Thompson, J

    1985-01-01

    Rectal temperature was measured in 62 male runners who competed in the 1983 Dundee marathon race: all measurements were made immediately after the race. Competitors' times were noted at 5, 10, 15 and 20 miles (8.0, 16.1, 24.1, 32.2 km) and at the finish (26.2 miles, 42.2 km). Mean finishing time of the group was 3 hr 33 min +/- 48 min (mean +/- S.D.; range = 2 hr 17 min-5 hr 11 min). Mean running speed of the group decreased progressively as the distance covered increased. Mean post-race rectal temperature was 38.7 +/- 0.9 degrees C (range 35.6-40.3 degrees C). The post-race temperature was correlated (p less than 0.01) with the time taken to cover the last 6.2 miles (10 km) of the race, but not with the overall finishing time (p greater than 0.05). Only the fastest runners were able to maintain an approximately constant pace throughout the race, whereas the slower runners slowed down progressively. The runners with the highest post-race temperature, although not necessarily the fastest runners, also tended to maintain a steady pace throughout. The runners with the lowest post-race temperature slowed down markedly only over the last 6.2 mile section of the race. The results clearly indicate that runners forced by fatigue or injury to slow down in the latter stages of races held at low ambient temperatures may already be hypothermic or at serious risk of hypothermia. Images p192-a p192-b p192-c PMID:4092138

  17. Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

    SciTech Connect

    Seidensticker, Max; Burak, Miroslaw; Kalinski, Thomas; Garlipp, Benjamin; Koelble, Konrad; Wust, Peter; Antweiler, Kai; Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Ricke, Jens

    2015-02-15

    PurposeRadiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).MethodsPatients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.ResultsFourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.ConclusionsAbsence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.

  18. Protective effect of an antithyroid compound against γ-radiation-induced damage in human colon cancer cells.

    PubMed

    Perona, Marina; Dagrosa, Maria A; Pagotto, Romina; Casal, Mariana; Pignataro, Omar; Pisarev, Mario A; Juvenal, Guillermo J

    2014-08-01

    We have previously reported the radioprotective effect of propylthiouracil (PTU) on thyroid cells. The aim of the present study was to analyze whether tumor cells and normal cells demonstrate the same response to PTU. Human colon carcinoma cells were irradiated with γ-irradiation with or without PTU. We evaluated the clonogenic survival, intracellular reactive oxygen species levels, catalase, superoxide dismutase and glutathione peroxidase activities, and apoptosis by nuclear cell morphology and caspase-3 activity assays. Cyclic AMP (cAMP) levels were measured by radioimmunoassay. PTU treatment increased surviving cell fraction at 2 Gy (SF2) from 56.9 ± 3.6 in controls to 75.0 ± 3.5 (p < 0.05) and diminished radiation-induced apoptosis. In addition, we observed that the level of antioxidant enzymes' activity was increased in cells treated with PTU. Moreover, pretreatment with PTU increased intracellular levels of cAMP. Forskolin (p < 0.01) and dibutyryl cAMP (p < 0.05) mimicked the effect of PTU on SF2. Co-treatment with H89, an inhibitor of protein kinase A, abolished the radioprotective effect of PTU. PTU reduces the toxicity of ionizing radiation by increasing cAMP levels and also possibly through a reduction in apoptosis levels and in radiation-induced oxidative stress damage. We therefore conclude that PTU protects both normal and cancer cells during exposure to radiation in conditions mimicking the radiotherapy.

  19. Drugs Approved for Colon and Rectal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  20. Low Rectal Cancer Study (MERCURY II)

    ClinicalTrials.gov

    2016-03-11

    Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

  1. Scrotal cooling increases rectal temperature in man.

    PubMed

    Vash, Peter D; Engels, Thomas M; Kandeel, Fouad R; Greenway, Frank

    2002-02-01

    The aim of this study was to evaluate the effect of scrotal cooling on rectal temperature in man. Pilot studies suggested that immersing the scrotum in a 30 degrees C water bath increased rectal temperature, but immersing the scrotum in a 0 degree C water bath did not. Six healthy young men immersed their scrotums in a 35 degrees C water bath for 11 min followed by 21 min at 30 degrees C. Rectal temperature rose by 0.38 +/- 0.04 degrees C (P < 0.01) in response to the 30 degrees C water bath. Repetition of the study by immersing the hands instead of the scrotum in the water bath had no effect on rectal temperature. The scrotum appears to play a role in human temperature regulation.

  2. Radiation-Induced Breast Cancer Incidence and Mortality from Digital Mammography Screening: A Modeling Study

    PubMed Central

    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.

    2016-01-01

    Background Estimates of radiation-induced breast cancer risk from mammography screening have not previously considered dose exposure variation or diagnostic work-up after abnormal screening. Objective To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening, considering exposure from screening and diagnostic mammography and dose variation across women. Design Two simulation-modeling approaches using common data on screening mammography from the Breast Cancer Surveillance Consortium and radiation dose from mammography from the Digital Mammographic Imaging Screening Trial. Setting U.S. population. Patients Women aged 40–74 years. Interventions Annual or biennial digital mammography screening from age 40, 45, or 50 until 74. Measurements Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality per 100,000 women screened (harms). Results On average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers (95% confidence interval [CI]=88–178) leading to 16 deaths (95% CI=11–23) relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 radiation-induced breast cancers leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete breast examination (8% of population) were projected to have higher radiation-induced breast cancer incidence and mortality (266 cancers, 35 deaths per 100,000 women), compared to women with small or average breasts (113 cancers, 15 deaths per 100,000 women). Biennial screening starting at age 50 reduced risk of radiation-induced cancers 5-fold. Limitations We were unable to estimate years of life lost from radiation-induced breast cancer. Conclusions Radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by dose

  3. Problems in family practice. Rectal bleeding.

    PubMed

    Graham, J

    1978-07-01

    The diagnosis and management of rectal bleeding problems varies with the urgency of the situation, the age of the patient, and the applicability of available diagnostic methods. Every instance of rectal bleeding is a problem that demands investigation by endoscopic, radiographic, and laboratory means. A physician can be misled by the patient's understatement or underobservance of bleeding. A good history obtained as quickly as possible in urgent circumstances and in great detail under more relaxed circumstances is of immeasurable diagnostic value.

  4. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    SciTech Connect

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  5. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway.

    PubMed

    Liu, Yunen; Tan, Dehong; Tong, Changci; Zhang, Yubiao; Xu, Ying; Liu, Xinwei; Gao, Yan; Hou, Mingxiao

    2015-12-01

    The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague-Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 μg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation-induced lung injury, likely through the PKR signaling pathway. PMID:26551926

  6. Blueberry anthocyanins ameliorate radiation-induced lung injury through the protein kinase RNA-activated pathway.

    PubMed

    Liu, Yunen; Tan, Dehong; Tong, Changci; Zhang, Yubiao; Xu, Ying; Liu, Xinwei; Gao, Yan; Hou, Mingxiao

    2015-12-01

    The purpose of this study was to explore the effect of blueberry anthocyanins (BA) on radiation-induced lung injury and investigate the mechanism of action. Seven days after BA(20 and 80 mg/kg/d)administration, 6 weeks old male Sprague-Dawley rats rats were irradiated by LEKTA precise linear accelerator at a single dose of 20 Gy only once. and the rats were continuously treated with BA for 4 weeks. Moreover, human pulmonary alveolar epithelial cells (HPAEpiC) were transfected with either control-siRNA or siRNA targeting protein kinase R (PKR). Cells were then irradiated and treated with 75 μg/mL BA for 72 h. The results showed that BA significantly ameliorated radiation-induced lung inflammation, lung collagen deposition, apoptosis and PKR expression and activation. In vitro, BA significantly protected cells from radiation-induced cell death through modulating expression of Bcl-2, Bax and Caspase-3. Suppression of PKR by siRNA resulted in ablation of BA protection on radiation-induced cell death and modulation of anti-apoptotic and pro-apoptotic proteins, as well as Caspase-3 expression. These findings suggest that BA is effective in ameliorating radiation-induced lung injury, likely through the PKR signaling pathway.

  7. Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury.

    PubMed

    Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won; Oh, Sang Ho; Lee, Yun-Sil; Lee, Eun-Jung; Cho, Jaeho

    2015-05-01

    Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. PMID:25797627

  8. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  9. Management of rectal varices in portal hypertension

    PubMed Central

    Al Khalloufi, Kawtar; Laiyemo, Adeyinka O

    2015-01-01

    Rectal varices are portosystemic collaterals that form as a complication of portal hypertension, their prevalence has been reported as high as 94% in patients with extrahepatic portal vein obstruction. The diagnosis is typically based on lower endoscopy (colonoscopy or sigmoidoscopy). However, endoscopic ultrasonography has been shown to be superior to endoscopy in diagnosing rectal varices. Color Doppler ultrasonography is a better method because it allows the calculation of the velocity of blood flow in the varices and can be used to predict the bleeding risk in the varices. Although rare, bleeding from rectal varices can be life threatening. The management of patients with rectal variceal bleeding is not well established. It is important to ensure hemodynamic stability with blood transfusion and to correct any coagulopathy prior to treating the bleeding varices. Endoscopic injection sclerotherapy has been reported to be more effective in the management of active bleeding from rectal varices with less rebleeding rate as compared to endoscopic band ligation. Transjugular intrahepatic portsystemic shunt alone or in combination with embolization is another method used successfully in control of bleeding. Balloon-occluded retrograde transvenous obliteration is an emerging procedure for management of gastric varices that has also been successfully used to treat bleeding rectal varices. Surgical procedures including suture ligation and porto-caval shunts are considered when other methods have failed. PMID:26730278

  10. Radiation-induced undifferentiated pleomorphic sarcoma after radiation therapy for a desmoid tumour.

    PubMed

    Di Marco, J; Kaci, R; Orcel, P; Nizard, R; Laredo, J-D

    2016-02-01

    Radiation-induced sarcoma is a long-term complication of radiation therapy. The most common secondary neoplasia is the undifferentiated pleomorphic sarcoma, which is usually described in the deep soft tissue of the trunk or extremities. Radiation-induced sarcomas have a poor prognosis. An early diagnosis and management are needed to improve the survival rate of such patients. We presently report a case of a radiation-induced undifferentiated pleomorphic sarcoma of the left gluteus maximus muscle, which developed 25 years after an initial diagnosis of aggressive fibromatosis and 21 years after a tumour recurrence. This case study illustrates the risk of developing a sarcoma in a radiation field and the need for long-term follow-up after radiation therapy. Unnecessary radiation therapy, in particular in the case of benign conditions in young patients, should be avoided.

  11. Radiation-induced genomic instability and its implications for radiation carcinogenesis

    NASA Technical Reports Server (NTRS)

    Huang, Lei; Snyder, Andrew R.; Morgan, William F.

    2003-01-01

    Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.

  12. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract.

    PubMed

    Sinha, Mahuya; Das, Dipesh Kr; Datta, Sanjukta; Ghosh, Santinath; Dey, Sanjit

    2012-03-01

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. PMID:22439436

  13. Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance

    SciTech Connect

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

    1988-01-01

    An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself.

  14. Genetic background influences loss of heterozygosity patterns in radiation-induced mouse thymic lymphoma

    PubMed Central

    Hang, Michael; Huang, Yurong; Snijders, Antoine M.; Mao, Jian-Hua

    2015-01-01

    Previous studies have revealed that p53 heterozygous (p53+/−) mice are extremely susceptible to radiation-induced tumorigenesis. To investigate whether genetic background influences radiation induced tumor susceptibility, we crossed p53+/− 129/Sv mice with genetically diverse strains to generate p53+/− F1 hybrids. The results showed that genetic background had a profound impact on tumor latency after exposure to gamma radiation, while the tumor spectrum did not change. We further characterized the thymic lymphomas that arose in the p53+/− mice by genome-wide loss of heterozygosity (LOH) analyses and found that genetic background strongly influenced the frequency of LOH and the loss of which parental allele on different chromosomes. Further research is needed to identify which genetic variations control the LOH patterns in radiation-induced thymic lymphomas and to evaluate its relevance to human cancers. PMID:25932465

  15. CDDO-Me protects against space radiation-induced transformation of human colon epithelial cells.

    PubMed

    Eskiocak, Ugur; Kim, Sang Bum; Roig, Andres I; Kitten, Erin; Batten, Kimberly; Cornelius, Crystal; Zou, Ying S; Wright, Woodring E; Shay, Jerry W

    2010-07-01

    Radiation-induced carcinogenesis is a major concern both for astronauts on long-term space missions and for cancer patients being treated with therapeutic radiation. Exposure to radiation induces oxidative stress and chronic inflammation, which are critical initiators and promoters of carcinogenesis. Many studies have demonstrated that non-steroidal anti-inflammatory drugs and antioxidants can reduce the risk of radiation-induced cancer. In this study, we found that a synthetic triterpenoid, CDDO-Me (bardoxolone methyl), was able to protect human colon epithelial cells (HCECs) against radiation-induced transformation. HCECs that were immortalized by ectopic expression of hTERT and cdk4 and exhibit trisomy for chromosome 7 (a non-random chromosome change that occurs in 37% of premalignant colon adenomas) can be transformed experimentally with one combined exposure to 2 Gy of protons at 1 GeV/nucleon followed 24 h later by 50 cGy of (56)Fe ions at 1 GeV/nucleon. Transformed cells showed an increase in proliferation rate and in both anchorage-dependent and independent colony formation ability. A spectrum of chromosome aberrations was observed in transformed cells, with 40% showing loss of 17p (e.g. loss of one copy of p53). Pretreatment of cells with pharmacological doses of CDDO-Me, which has been shown to induce antioxidative as well as anti-inflammatory responses, prevented the heavy-ion-induced increase in proliferation rate and anchorage-dependent and independent colony formation efficiencies. Taken together, these results demonstrate that experimentally immortalized human colon epithelial cells with a non-random chromosome 7 trisomy are valuable premalignant cellular reagents that can be used to study radiation-induced colorectal carcinogenesis. The utility of premalignant HCECs to test novel compounds such as CDDO-Me that can be used to protect against radiation-induced neoplastic transformation is also demonstrated. PMID:20681796

  16. Identification of capsaicin-sensitive rectal mechanoreceptors activated by rectal distension in mice.

    PubMed

    Spencer, N J; Kerrin, A; Singer, C A; Hennig, G W; Gerthoffer, W T; McDonnell, O

    2008-05-01

    Rodents detect visceral pain in response to noxious levels of rectal distension. However, the mechanoreceptors that innervate the rectum and respond to noxious levels of rectal distension have not been identified. Here, we have identified the mechanoreceptors of capsaicin-sensitive rectal afferents and characterized their properties in response to circumferential stretch of the rectal wall. We have also used the lethal spotted (ls/ls) mouse to determine whether rectal mechanoreceptors that respond to capsaicin and stretch may also develop in an aganglionic rectum that is congenitally devoid of enteric ganglia. In wild type (C57BL/6) mice, graded increases in circumferential stretch applied to isolated rectal segments activated a graded increase in firing of slowly-adapting rectal mechanoreceptors. Identical stimuli applied to the aganglionic rectum of ls/ls mice also activated similar graded increases in firing of stretch-sensitive rectal afferents. In both wild type and aganglionic rectal preparations, focal compression of the serosal surface using von Frey hairs identified mechanosensitive "hot spots," that were associated with brief bursts of action potentials. Spritzing capsaicin (10 microM) selectively onto each identified mechanosensitive hot spot activated an all or none discharge of action potentials in 32 of 56 identified hot spots in wild type mice and 24 of 62 mechanosensitive hot spots in the aganglionic rectum of ls/ls mice. Each single unit activated by both capsaicin and circumferential stretch responded to low mechanical thresholds (1-2 g stretch). No high threshold rectal afferents were ever recorded in response to circumferential stretch. Anterograde labeling from recorded rectal afferents revealed two populations of capsaicin-sensitive mechanoreceptor that responded to stretch: one population terminated within myenteric ganglia, the other within the circular and longitudinal smooth muscle layers. In the aganglionic rectum of ls/ls mice, only the

  17. Antimicrobial fabric adsorbed iodine produced by radiation-induced graft polymerization

    NASA Astrophysics Data System (ADS)

    Aoki, Shoji; Fujiwara, Kunio; Sugo, Takanobu; Suzuki, Koichi

    2013-03-01

    Antimicrobial fabric was synthesized by radiation-induced graft polymerization of N-vinyl pyrrolidone onto polyolefine nonwoven fabric and subsequent adsorption of iodine. In response of the huge request for the antimicrobial material applied to face masks for swine flu in 2009, operation procedure of continuous radiation-induced graft polymerization apparatus was improved. The improved grafting production per week increased 3.8 times compared to the production by former operation procedure. Shipped antimicrobial fabric had reached 130,000 m2 from June until December, 2009.

  18. Gamma radiation-induced blue shift of resonance peaks of Bragg gratings in pure silica fibres

    NASA Astrophysics Data System (ADS)

    Faustov, A. V.; Gusarov, A. I.; Mégret, P.; Wuilpart, M.; Kinet, D.; Zhukov, A. V.; Novikov, S. G.; Svetukhin, V. V.; Fotiadi, A. A.

    2016-02-01

    We report the first observation of a significant gamma radiation-induced blue shift of the reflection/transmission peak of fibre Bragg gratings inscribed into pure-silica core fibres via multiphoton absorption of femtosecond pulses. At a total dose of ~100 kGy, the shift is ~20 pm. The observed effect is attributable to the ionising radiation-induced decrease in the density of the silica glass when the rate of colour centre formation is slow. We present results of experimental measurements that provide the key parameters of the dynamics of the gratings for remote dosimetry and temperature sensing.

  19. [A case of prednisolone therapy for radiation-induced hemorrhagic cystitis].

    PubMed

    Yanagi, Masato; Nishimura, Taiji; Kurita, Susumu; Lee, Chorsu; Kondo, Yukihiro; Yamazaki, Keiichi

    2011-05-01

    Hemorrhagic cystitis resulting from radiation to pelvic visceral malignant lesions often might be incurable and there have been no established definitive treatment. We experienced a case with severe radiation-induced hemorrhagic cystitis refractory to conventional therapy. The treatment with oral administration of prednisolone was performed and obtained a successful result. Gross hematuria disappeared in 2 weeks in this case. This experience suggested that oral administration of prednisolone could be considered the treatment for patients with radiation-induced hemorrhagic cystitis when usual treatments including transurethral electro-coagulation are unsuccessful. PMID:21846069

  20. [A case of prednisolone therapy for radiation-induced hemorrhagic cystitis].

    PubMed

    Yanagi, Masato; Nishimura, Taiji; Kurita, Susumu; Lee, Chorsu; Kondo, Yukihiro; Yamazaki, Keiichi

    2011-05-01

    Hemorrhagic cystitis resulting from radiation to pelvic visceral malignant lesions often might be incurable and there have been no established definitive treatment. We experienced a case with severe radiation-induced hemorrhagic cystitis refractory to conventional therapy. The treatment with oral administration of prednisolone was performed and obtained a successful result. Gross hematuria disappeared in 2 weeks in this case. This experience suggested that oral administration of prednisolone could be considered the treatment for patients with radiation-induced hemorrhagic cystitis when usual treatments including transurethral electro-coagulation are unsuccessful.

  1. Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

    PubMed

    King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

    2016-06-01

    Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration. PMID:27098922

  2. Radiation-induced tumor neoantigens: imaging and therapeutic implications

    PubMed Central

    Corso, Christopher D; Ali, Arif N; Diaz, Roberto

    2011-01-01

    Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular changes. One way that IR can affect tumor cells is through the development of neoantigens which are new molecules that tumor cells express at the cell membrane following some insult or change to the cell. There have been numerous reports in the literature of changes in both tumor and tumor vasculature cell surface molecule expression following treatment with IR. The usefulness of neoantigens for imaging and therapeutic applications lies in the fact that they are differentially expressed on the surface of irradiated tumor cells to a greater extent than on normal tissues. This differential expression provides a mechanism by which tumor cells can be “marked” by radiation for further targeting. Drug delivery vehicles or imaging agents conjugated to ligands that recognize and interact with the neoantigens can help to improve tumor-specific targeting and reduce systemic toxicity with cancer drugs. This article provides a review of the molecules that have been reported to be expressed on the surface of tumor cells in response to IR either in vivo or in vitro. Additionally, we provide a discussion of some of the methods used in the identification of these antigens and applications for their use in drug delivery and imaging. PMID:21969260

  3. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    SciTech Connect

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed; Safran, Howard

    2012-01-01

    Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

  4. Radiation-induced dementia in patients cured of brain metastases

    SciTech Connect

    DeAngelis, L.M.; Delattre, J.Y.; Posner, J.B.

    1989-06-01

    When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review.

  5. Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients With Prior Pelvic Irradiation

    SciTech Connect

    Das, Prajnan; Delclos, Marc E.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Feig, Barry W.; Chang, George J.; Eng, Cathy; Bedi, Manpreet; Krishnan, Sunil; Crane, Christopher H.

    2010-05-01

    Purpose: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. Methods and Materials: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. Results: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of <=2 years (p = 0.001). Conclusions: Hyperfractionated, accelerated reirradiation was well tolerated, with low rates of acute toxicity and moderate rates of late toxicity. Reirradiation may help improve pelvic control in rectal cancer patients with a history of pelvic radiotherapy.

  6. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    PubMed Central

    2013-01-01

    Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273. PMID:23336502

  7. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies

    PubMed Central

    Fleenor, Courtney J.; Higa, Kelly; Weil, Michael M.; DeGregori, James

    2015-01-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  8. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  9. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    EPA Science Inventory

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  10. A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

    SciTech Connect

    Boomsma, Marjolein J.; Bijl, Hendrik P.; Christianen, Miranda E.M.C.; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J.H.M.; Laan, Bernard F.A.M. van der; Oosting, Sjoukje F.; Schilstra, Cornelis; Langendijk, Johannes A.

    2012-11-01

    Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm{sup 3}). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.

  11. Deep Friction Massage in Treatment of Radiation-induced Fibrosis: Rehabilitative Care for Breast Cancer Survivors.

    PubMed

    Warpenburg, Mary J

    2014-10-01

    Treatment for invasive breast cancer usually involves some combination of surgery, radiation therapy, chemotherapy, hormone therapy, and/or targeted therapy. For approximately 50% of patients, radiation therapy is a component of the therapies used. As a result, radiation-induced fibrosis is becoming a common and crippling side effect, leading to muscle imbalance with a lessened range of motion as well as pain and dysfunction of the vascular and lymphatic systems. No good estimates are available for how many patients experience complications from radiation. Radiation-induced fibrosis can affect the underlying fascia, muscles, organs, and bones within the primary target field and the larger secondary field that is caused by the scatter effect of radioactive elements. For breast cancer patients, the total radiation field may include the neck, shoulder, axillary, and thoracic muscles and the ribs for both the ipsilateral (cancer-affected) and contralateral sides. This case study indicates that therapy using deep friction massage can affect radiation-induced fibrosis beneficially, particularly in the thoracic muscles and the intercostals (ie, the muscles between the ribs). When delivered in intensive sessions using deep friction techniques, massage has the potential to break down fibrotic tissues, releasing the inflammation and free radicals that are caused by radiation therapy. In the course of the massage, painful and debilitating spasms resulting from fibrosis can be relieved and the progressive nature of the radiation-induced fibrosis interrupted. PMID:26770116

  12. Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice

    PubMed Central

    Li, Ming; Du, Aonan; Xu, Jing; Ma, Yanchao; Cao, Han; Yang, Chao; Yang, Xiao-Dong; Xing, Chun-Gen; Chen, Ming; Zhu, Wei; Zhang, Shuyu; Cao, Jianping

    2016-01-01

    The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure. PMID:27436572

  13. Use of iron colloid-enhanced MRI for study of acute radiation-induced hepatic injury

    SciTech Connect

    Suto, Yuji; Ametani, Masaki; Kato, Takashi; Hashimoto, Masayuki; Kamba, Masayuki; Sugihara, Syuji; Ohta, Yoshio

    1996-03-01

    We present a case with acute radiation-induced hepatic injury using chondroitin sulfate iron colloid (CSIC)-enhanced MRI. Uptake of CSIC was decreased in the irradiated portion of the liver. CSIC-enhanced MRI is useful for obtaining information on the function of the reticuloendothelial system and demarcates between irradiated and nonirradiated zones. 18 refs., 3 figs

  14. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    SciTech Connect

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  15. Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

    PubMed Central

    Balentova, Sona; Adamkov, Marian

    2015-01-01

    Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

  16. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies.

    PubMed

    Fleenor, Courtney J; Higa, Kelly; Weil, Michael M; DeGregori, James

    2015-10-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  17. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization.

    PubMed

    Meng, Zhen; Gan, Ye-Hua

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation.

  18. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats.

    PubMed

    Bakkal, B H; Gultekin, F A; Guven, B; Turkcu, U O; Bektas, S; Can, M

    2013-09-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  19. Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

    NASA Technical Reports Server (NTRS)

    Weil, M. M.; Kittrell, F. S.; Yu, Y.; McCarthy, M.; Zabriskie, R. C.; Ullrich, R. L.

    2001-01-01

    Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

  20. Californium-252 brachytherapy for anal and ano-rectal carcinoma

    SciTech Connect

    Cross, B.; Maruyama, Y.; Proudfoot, W.; Malcolm, A.

    1986-01-01

    Surgery has historically been the standard treatment for anal, ano-rectal and rectal carcinoma but is prone to local or regional failure. Over the past 15 years there has been increasing interest in and success with radiation therapy and combined chemoradiotherapy for treatment of anal and ano-rectal cancers. Cf-252 brachytherapy combined with external beam teletherapy has been investigated for anal and ano-rectal lesions at the Univ. of Kentucky with encouraging results.

  1. Stapled transanal rectal mucosectomy ten years after.

    PubMed

    Pescatori, M; Aigner, F

    2007-03-01

    Stapled mucosectomy (SM) was first proposed for the management of patients with rectal internal mucosal prolapse and obstructed defecation, but gained popularity worldwide for the treatment of hemorrhoids. The present review highlights the advantages and disadvantages of the operation. SM tends to decrease postoperative pain and shortens convalescence after hemorrhoid surgery, but may be followed by severe complications, e.g. rectal obliteration and pelvic sepsis requiring a diverting stoma, more frequently than after standard hemorrhoidectomy. Moreover it carries a higher recurrence rate in the treatment of fourth-degree piles. A recent Cochrane metaanalysis demonstrated that SM is less effective than standard hemorrhoidectomy since it carries a higher recurrence rate (OR=3.6) and reintervention rate (OR=2.3). When used for rectal mucosal prolapse and obstructed defecation, SM is reported to have variable results. A better outcome is likely to be achieved in patients without anismus and psychoneurosis operated on by specialists trained with this technique.

  2. Management and imaging of low rectal carcinoma.

    PubMed

    Salerno, Gisella; Daniels, Ian; Heald, R J; Brown, Gina; Moran, B J

    2004-01-01

    Large variations in recurrence rates have been reported with the best results following total mesorectal excision (TME) surgery for low and middle rectal cancers. However, the low rectal cancers still have higher rates of local recurrence (up to 30%) whether operated by low anterior resection or abdominoperineal excision (APE) due to high rates of circumferential margin involvement. The treatment of choice for low rectal cancers that encroach upon the potential circumferential resection margin is surgery combined with preoperative neoadjuvant treatment. Preoperative chemotherapy combined with long-term radiotherapy reduces recurrence rates and preoperative loco-regional staging can help to select the patients more likely to benefit from neo-adjuvant therapy. Surface coil MRI is the most promising modality for patient selection, which can provide good views of the circumferential resection margin especially the presence or absence of tumour encroaching the intersphincteric plane. PMID:15572087

  3. Rectal mucosa in cows' milk allergy.

    PubMed Central

    Iyngkaran, N; Yadav, M; Boey, C G

    1989-01-01

    Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants. PMID:2817945

  4. Detecting Radiation-Induced Injury Using Rapid 3D Variogram Analysis of CT Images of Rat Lungs

    SciTech Connect

    Jacob, Rick E.; Murphy, Mark K.; Creim, Jeffrey A.; Carson, James P.

    2013-10-01

    A new heterogeneity analysis approach to discern radiation-induced lung damage was tested on CT images of irradiated rats. The method, combining octree decomposition with variogram analysis, demonstrated a significant correlation with radiation exposure levels, whereas conventional measurements and pulmonary function tests did not. The results suggest the new approach may be highly sensitive for assessing even subtle radiation-induced changes

  5. Silicone elastomer sling for rectal prolapse in cats

    PubMed Central

    Corgozinho, Katia Barão; Belchior, Cristiane; de Souza, Heloisa Justen Moreira; Ferreira, Ana Maria; Resende, Carolina; Damico, Brandão; Cunha, Simone

    2010-01-01

    This study reports 2 cases of recurrent rectal prolapse secondary to anal abnormality in cats. In both cases the anus was wide, leading to a rectal mucosal prolapse during defecation. A silicone elastomer sling was introduced around the anus, and the rectal prolapse was definitively resolved. PMID:20676293

  6. Primary Transanal Management of Rectal Atresia in a Neonate.

    PubMed

    M, Braiek; A, Ksia; I, Krichen; S, Belhassen; K, Maazoun; S, Ben Youssef; N, Kechiche; M, Mekki; A, Nouri

    2016-01-01

    Rectal atresia (RA) with a normal anus is a rare anomaly. We describe a case of rectal atresia in a newborn male presenting with an abdominal distension and failure of passing meconium. The rectal atresia was primarily operated by transanal route.

  7. Primary Transanal Management of Rectal Atresia in a Neonate

    PubMed Central

    M, Braiek; A, Ksia; I, Krichen; S, Belhassen; K, Maazoun; S, Ben youssef; N, Kechiche; M, Mekki; A, Nouri

    2016-01-01

    Rectal atresia (RA) with a normal anus is a rare anomaly. We describe a case of rectal atresia in a newborn male presenting with an abdominal distension and failure of passing meconium. The rectal atresia was primarily operated by transanal route. PMID:27123404

  8. Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

    PubMed Central

    Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett. D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

    2016-01-01

    Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered

  9. On the mechanism of radiation-induced emesis: The role of serotonin

    SciTech Connect

    Scarantino, C.W.; Ornitz, R.D.; Hoffman, L.G.

    1994-11-15

    The aim of this study was to determine the mechanism of action of radiation-induced emesis by determining the incidence of radiation-induced emesis following hemibody irradiation; the effects of specific antiemetics especially ondansetron, a 5-hydroxytryptamine receptor antagonist, and to determine the relationship between radiation-induced emesis and serotonin (5-hydroxytryptamine) through its active metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Forty-one patients received 53 hemibody treatments of 5-8 Gy following intravenous hydration. The patients were divided into three groups according to prehemibody irradiation treatment: Group A: no pretreatment antiemetics, 30 patients; Group B: nonondansetron antiemetics (metoclopramide, dexamethasone, prochlorperazine), ten patients; and Group C: ondansetron, 13 patient. The incidence of radiation-induced emesis was determined prehemibody irradiation or baseline and at 1 h posthemibody irradiation in 38 patients and the results expressed as the percent change in 5-HIAA (ng/ug creatinine). The incidence of radiation-induced emesis was 82% (14/17) following upper/mid hemibody irradiation and 15% (2/11) following lower hemibody irradiation in Group A; 50% (3/6) and 25% (1/4) following upper/mid and lower hemibody irradiation respectively, in Group B/; and 0% (p/13) after upper/mid hemibody irradiation in Group C. The incidence of emesis was significantly different (p<0.001) between the patients of Group A and C who received upper/mid hemibody irradiation. The percent change in 5-HIAA excretion following upper/mid hemibody irradiation were greatest in Group A and smallest in Group C (p<0.002). The degree of change following lower hemibody irradiation (15% incidence of emesis) in Group A was lower than upper/mid hemibody irradiation of the same group. 17 refs., 3 figs., 2 tabs.

  10. Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jelvehgaran, Pouya; Alderliesten, Tanja; Salguero, Javier; Borst, Gerben; Song, Ji-Ying; van Leeuwen, Ton G.; de Boer, Johannes F.; de Bruin, Daniel M.; van Herk, Marcel B.

    2016-03-01

    Lung cancer survival is poor and radiotherapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to reduced food intake or even fistula formation. Only few direct techniques exist to measure radiation-induced esophageal damage, for which knowledge is needed to improve the balance between risk of tumor recurrence and complications. Optical coherence tomography (OCT) is a minimally-invasive imaging technique that obtains cross-sectional, high-resolution (1-10µm) images and is capable of scanning the esophageal wall up to 2-3mm depth. In this study we investigated the feasibility of OCT to detect esophageal radiation damage in mice. In total 30 mice were included in 4 study groups (1 main and 3 control groups). Mice underwent cone-beam CT imaging for initial setup assessment and dose planning followed by single-fraction dose delivery of 4, 10, 16, and 20Gy on 5mm spots, spaced 10mm apart. Mice were repeatedly imaged using OCT: pre-irradiation and up to 3 months post-irradiation. The control groups received either OCT only, irradiation only, or were sham-operated. We used histopathology as gold standard for radiation-induced damage diagnosis. The study showed edema in both the main and OCT-only groups. Furthermore, radiation-induced damage was primarily found in the highest dose region (distal esophagus). Based on the histopathology reports we were able to identify the radiation-induced damage in the OCT images as a change in tissue scattering related to the type of induced damage. This finding indicates the feasibility and thereby the potentially promising role of OCT in radiation-induced esophageal damage assessment.

  11. Principal component analysis for the comparison of metabolic profiles from human rectal cancer biopsies and colorectal xenografts using high-resolution magic angle spinning 1H magnetic resonance spectroscopy

    PubMed Central

    Seierstad, Therese; Røe, Kathrine; Sitter, Beathe; Halgunset, Jostein; Flatmark, Kjersti; Ree, Anne H; Olsen, Dag Rune; Gribbestad, Ingrid S; Bathen, Tone F

    2008-01-01

    Background This study was conducted in order to elucidate metabolic differences between human rectal cancer biopsies and colorectal HT29, HCT116 and SW620 xenografts by using high-resolution magnetic angle spinning (MAS) magnetic resonance spectroscopy (MRS) and for determination of the most appropriate human rectal xenograft model for preclinical MR spectroscopy studies. A further aim was to investigate metabolic changes following irradiation of HT29 xenografts. Methods HR MAS MRS of tissue samples from xenografts and rectal biopsies were obtained with a Bruker Avance DRX600 spectrometer and analyzed using principal component analysis (PCA) and partial least square (PLS) regression analysis. Results and conclusion HR MAS MRS enabled assignment of 27 metabolites. Score plots from PCA of spin-echo and single-pulse spectra revealed separate clusters of the different xenografts and rectal biopsies, reflecting underlying differences in metabolite composition. The loading profile indicated that clustering was mainly based on differences in relative amounts of lipids, lactate and choline-containing compounds, with HT29 exhibiting the metabolic profile most similar to human rectal cancers tissue. Due to high necrotic fractions in the HT29 xenografts, radiation-induced changes were not detected when comparing spectra from untreated and irradiated HT29 xenografts. However, PLS calibration relating spectral data to the necrotic fraction revealed a significant correlation, indicating that necrotic fraction can be assessed from the MR spectra. PMID:18439252

  12. Effects of Probiotic Lactobacillus Casei DN-114 001 in Prevention of Radiation-Induced Diarrhea: Results From Multicenter, Randomized, Placebo-Controlled Nutritional Trial

    SciTech Connect

    Giralt, Jordi Regadera, Jose Perez; Verges, Ramona; Romero, Jesus; Fuente, Isabel de la; Biete, Albert; Villoria, Jesus; Cobo, Jose Maria; Guarner, Francisco

    2008-07-15

    Purpose: To determine whether a probiotic drink containing Lactobacillus casei DN-114 001 reduces the incidence of radiation-induced diarrhea in patients with gynecologic cancer. Methods and Materials: Patients who were undergoing pelvic radiotherapy (45-50 Gy, conventional fractionation) for either cervical carcinoma (radiotherapy and weekly cisplatin) or endometrial adenocarcinoma (postoperative radiotherapy) were randomly assigned to a probiotic drink or placebo, in a double-blind fashion. The probiotic drink consisted of liquid yogurt containing L. casei DN-114 001 at 10{sup 8} CFU/g. The patients recorded the daily the number of bowel movements and scored the stool consistency using the Bristol scale. Diarrhea was graded weekly according the Common Toxicity Criteria system. The primary endpoint was to reduce the incidence of diarrhea, defined by a Common Toxicity Criteria Grade of 2 or greater or the need for loperamide. Results: A total of 85 patients were enrolled. Grade 2 or greater diarrhea and/or the use of loperamide was observed in 24 of 41 patients in the placebo group and 30 of 44 in the probiotic group (p = 0.568). No differences were found in the median time to the presentation of the primary endpoint. Probiotic intervention had a significant effect on stool consistency (p = 0.04). The median time for patients to present with Bristol scale stools of Type 6 or greater was 14 days for patients receiving the probiotic drink vs. 10 days for those receiving placebo. Conclusion: Nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhea as defined by a Common Toxicity Criteria Grade 2 or greater. However, it had a significant effect on stool consistency as measured by the Bristol scale.

  13. Effect of Tinospora cordifolia on the reduction of ultraviolet radiation-induced cytotoxicity and DNA damage in PC12 cells.

    PubMed

    Masuma, Runa; Okuno, Tsutomu; Kabir Choudhuri, Mohammad Shahabuddin; Saito, Takeshi; Kurasaki, Masaaki

    2014-01-01

    The safety of Tinospora cordifolia and its potential to protect against ultraviolet radiation-induced cytotoxicity and DNA damage in PC12 cells were investigated. To evaluate the safety of T. cordifolia, cell viability and agarose gel electrophoresis were carried out using PC12 cells treated with 0 to 100 μg mL(-1) of methanol extract of T. cordifolia. T. cordifolia extracts did not show cytotoxicity ranging 0 to 100 μg mL(-1). In addition, T. cordifolia extracts significantly increased cell viability at 1 ng, 10 ng and 1 μg mL(-1) concentrations in serum-deprived medium compared to control. To confirm the protective role against UV-induced damage, PC12 cells alone or in the presence of 10 ng, 100 ng, or 1 μg mL(-1) of T. cordifolia extract were exposed to 250, 270 and 290 nm of UV radiation, which corresponded to doses of 120, 150 and 300 mJ cm(-2), respectively. Treatment with T. cordifolia extracts significantly increased the cell survival rate irradiated at 290 nm. In addition, T. cordifolia extracts significantly reduced cyclobutane pyrimidine dimer formation induced by UV irradiation at all wavelengths. In conclusion, T. cordifolia is not toxic and safe for cells. Our findings can support its application as phototherapy in the medical sector. PMID:24762179

  14. The inhibition of radiation-induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065

    SciTech Connect

    Diamond, A.M.; Murray, J.L.; Dale, P. |

    1997-08-01

    In order to evaluate the anti-mutagenic effects of the potential chemoprotective compounds selenium and S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-1065), CHO AA8 cells were exposed to both compounds either individually or in combination prior to irradiation. Mutation frequency following exposure to 8 Gy was evaluated by quantitation of the mutations detected at the hprt locus of these cells. Protection against radiation-induced mutation was observed for both 30 nM sodium selenite or 4 mM WR-1065. In addition, the protection against mutation induction provided by the combination of these agents appeared additive. In contrast, sodium selenite did not provide protection against radiation toxicity when provided either alone or in conjunction with WR-1065. In order to evaluate the possible mechanisms of the anti-mutagenic effects observed in these cells, glutathione peroxidase (GPx) activity was evaluated following exposure to the chemopreventative compounds. The addition of sodium selenite to the culture media resulted in a 5-fold increase in GPX activity, which was unaltered by the presence of the WR-1065. Northern analysis of RNA derived from these cells indicated that selenium supplementation resulted in a marginal increase in the mRNA for the cytosolic GPx (GSHPx-1) which was insufficient to account for the stimulation of GPx activity observed in cellular extracts. These results suggest that selenium and WR-1065 offer protection via independent mechanisms and that GPX stimulation remains a possible mechanism of the anti-mutagenic effect of selenium.

  15. The polyhydroxylated fullerene derivative C{sub 60}(OH){sub 24} protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

    SciTech Connect

    Cai Xiaoqing; Hao Jiejie; Zhang Xiaoyong; Yu Bozhang; Ren Jinming; Luo Cheng; Li Qingnuan; Huang Qing; Shi Xianglin; Li Wenxin; Liu Jiankang

    2010-02-15

    Although the protective effect of the polyhydroxylated fullerene derivative C{sub 60}(OH){sub n} against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C{sub 60} and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C{sub 60}(OH){sub 24} for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body gamma-irradiation (from a {sup 60}Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C{sub 60}(OH){sub 24} pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C{sub 60}(OH){sub 24} pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C{sub 60}(OH){sub 24} pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C{sub 60}(OH){sub 24} protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

  16. Molecular Genetic Changes Associated With Colorectal Carcinogenesis Are Not Prognostic for Tumor Regression Following Preoperative Chemoradiation of Rectal Carcinoma

    SciTech Connect

    Zauber, N. Peter Marotta, Steven P.; Berman, Errol; Grann, Alison; Rao, Maithili; Komati, Naga; Ribiero, Kezia; Bishop, D. Timothy

    2009-06-01

    Purpose: Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis. Methods and Materials: Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen. Results: Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression. Conclusions: Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.

  17. 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... dilator is a device designed to dilate the anal sphincter and canal when the size of the anal opening...

  18. A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments.

    PubMed

    Kennedy, Ann R; Maity, Amit; Sanzari, Jenine K

    2016-08-01

    Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation. To determine whether irradiated humans have RIC biomarkers, blood samples were obtained from radiotherapy patients who received treatment for different types of malignancies. Blood samples from allogeneic hematopoietic cell transplantation (allo-HCT) patients obtained before, during and after irradiation indicated that exposure led to prolonged clot formation times, increased levels of thrombin-antithrombin III (TAT) complex and increased circulating nucleosome/histone (cNH) levels, which suggest potential coagulopathies in the allo-HCT patients. Since these allo-HCT patients received chemotherapy prior to radiotherapy, it is possible that the chemical agents could have influenced the observed results. Frozen plasma samples from radiotherapy patients with prostate, lung and breast cancer were also obtained for analyses of cNH levels. The results indicated that some of these patients had very high cNH blood levels. Analysis of cNH levels in plasma samples from irradiated ferrets also indicated increased cNH levels compared to preirradiation baseline levels. The results from irradiated animals and some radiotherapy patients suggest the possibility that anti-histone antibodies, which block the toxic effects of elevated cNH levels in the blood, might be useful as therapeutic agents for adverse biological radiation-induced effects. The detection of increased levels of cNH in some radiotherapy patient blood samples demonstrates its potential as a biomarker for

  19. A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments

    PubMed Central

    Kennedy, Ann R.; Maity, Amit; Sanzari, Jenine K.

    2016-01-01

    Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation. To determine whether irradiated humans have RIC biomarkers, blood samples were obtained from radiotherapy patients who received treatment for different types of malignancies. Blood samples from allogeneic hematopoietic cell transplantation (allo-HCT) patients obtained before, during and after irradiation indicated that exposure led to prolonged clot formation times, increased levels of thrombin-antithrombin III (TAT) complex and increased circulating nucleosome/ histone (cNH) levels, which suggest potential coagulopathies in the allo-HCT patients. Since these allo-HCT patients received chemotherapy prior to radiotherapy, it is possible that the chemical agents could have influenced the observed results. Frozen plasma samples from radiotherapy patients with prostate, lung and breast cancer were also obtained for analyses of cNH levels. The results indicated that some of these patients had very high cNH blood levels. Analysis of cNH levels in plasma samples from irradiated ferrets also indicated increased cNH levels compared to preirradiation baseline levels. The results from irradiated animals and some radiotherapy patients suggest the possibility that anti-histone antibodies, which block the toxic effects of elevated cNH levels in the blood, might be useful as therapeutic agents for adverse biological radiation-induced effects. The detection of increased levels of cNH in some radiotherapy patient blood samples demonstrates its potential as a biomarker for

  20. Modulation of radiation-induced apoptosis and G{sub 2}/M block in murine T-lymphoma cells

    SciTech Connect

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N.

    1995-03-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to {sup 137}Cs {gamma} irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of {gamma} radiation. We studied the effect of several pharmacological agents on the radiation-induced G{sub 2}/M block and DNA fragmentation. The agents which reduced the radiation-induced G{sub 2}/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G{sub 2}/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G{sub 2}/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G{sub 2}/M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs.

  1. Podophyllum hexandrum prevents radiation-induced neuronal damage in postnatal rats exposed in utero.

    PubMed

    Sajikumar, S; Goel, H C

    2003-08-01

    Podophyllum hexandrum has been shown to mitigate radiation injuries and especially the haemopoietic syndrome in adult mice. To monitor the radiation-induced changes in the nervous system, the neurons of postnatal young mice and their modification by P. hexandrum, were studied histologically for differences in the apical and basal dendritic branching and intersections in the CA1 neurons of the hippocampal region of rats which were delivered a 2 Gy gamma dose while in utero (day 17 of gestation). Irradiation significantly reduced the dendritic branching and intersections but pre-irradiation administration of the extract of P. hexandrum (i.p. 200 mg/kg/b.w., 2 h) reduced the damage in postnatal young mice. These studies indicate that P. hexandrum provides protection to neurons against radiation-induced damage and the mechanism of neuronal damage and its repair need to be investigated further.

  2. Protective effect of α-lipoic acid against radiation-induced fibrosis in mice

    PubMed Central

    Ryu, Seung-Hee; Park, Eun-Young; Kwak, Sungmin; Heo, Seung-Ho; Ryu, Je-Won; Park, Jin-hong

    2016-01-01

    Radiation-induced fibrosis (RIF) is one of the most common late complications of radiation therapy. We found that α-lipoic acid (α-LA) effectively prevents RIF. In RIF a mouse model, leg contracture assay was used to test the in vivo efficacy of α-LA. α-LA suppressed the expression of pro-fibrotic genes after irradiation, both in vivo and in vitro, and inhibited the up-regulation of TGF-β1-mediated p300/CBP activity. Thus, α-LA prevents radiation-induced fibrosis (RIF) by inhibiting the transcriptional activity of NF-κB through inhibition of histone acetyltransferase activity. α-LA is a new therapeutic methods that can be used in the prevention-treatment of RIF. PMID:26799284

  3. Gamma radiation induced effects in floppy and rigid Ge-containing chalcogenide thin films

    SciTech Connect

    Ailavajhala, Mahesh S.; Mitkova, Maria; Gonzalez-Velo, Yago; Barnaby, Hugh; Kozicki, Michael N.; Holbert, Keith; Poweleit, Christian; Butt, Darryl P.

    2014-01-28

    We explore the radiation induced effects in thin films from the Ge-Se to Ge-Te systems accompanied with silver radiation induced diffusion within these films, emphasizing two distinctive compositional representatives from both systems containing a high concentration of chalcogen or high concentration of Ge. The studies are conducted on blanket chalcogenide films or on device structures containing also a silver source. Data about the electrical conductivity as a function of the radiation dose were collected and discussed based on material characterization analysis. Raman Spectroscopy, X-ray Diffraction Spectroscopy, and Energy Dispersive X-ray Spectroscopy provided us with data about the structure, structural changes occurring as a result of radiation, molecular formations after Ag diffusion into the chalcogenide films, Ag lateral diffusion as a function of radiation and the level of oxidation of the studied films. Analysis of the electrical testing suggests application possibilities of the studied devices for radiation sensing for various conditions.

  4. Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome

    SciTech Connect

    Weiss, K.S.; Zidar, B.L.; Wang, S.; Magovern, G.J. Sr.; Raju, R.N.; Lupetin, A.R.; Shackney, S.E.; Simon, S.R.; Singh, M.; Pugh, R.P.

    1987-09-15

    A patient with a pleomorphic intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presented clinically with a superior vena cava syndrome. A latent period of 29 years elapsed between receiving orthovoltage radiation to the neck and right side of chest to treat recurrent ganglioneuroblastoma, and the appearance of a leiomyosarcoma and subsequent recurrences. The patient underwent partial resection of the tumor, received adjunct chemotherapy, and was shown to be free of disease by clinical tests and by magnetic resonance imaging (MRI) 17 months after completion of chemotherapy. The criteria for the diagnosis of radiation-induced sarcomas are reviewed in relation to the present case. The critical role of magnetic resonance imaging in both the diagnosis and continued follow-up of the patient is described. This would appear to be the first reported case of radiation-induced intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presenting as a superior vena cava syndrome.

  5. The effect of temperature on radiation-induced radicals in irradiated chicken drumstick bones

    NASA Astrophysics Data System (ADS)

    Polat, M.; Korkmaz, M.; Korkmaz, Ö.

    1997-04-01

    The effect of temperature on the ESR spectra of well characterized unirradiated and irradiated samples of chicken drumstick bones under standardized experimental conditions has been investigated in detail over the temperature range 100-150 K. No significant changes in the linewidth and g factor of the endogenous signal were observed, but the signal intensity was found to decrease markedly in an irreversible way when the temperature was increased. The radiation-induced signal turned out to be the sum of a narrow and a broad line which were assigned to an inorganic and an organic radical, respectively. The thermal stability of the radiation-induced inorganic radical used in poultry irradiation dose determination and in dating was found to be much better than that of organic and endogenous radicals. The results of the present work highlight the need to define properly calibration factors which can be used in conjunction with pre- or post-irradiation thermal treatment of chicken drumstick bones.

  6. A case of radiation-induced mucosal melanoma in an immunohistochemically S-100-negative patient.

    PubMed

    Rodriguez, Michael; Patil, Yash; Gupta, Arun

    2016-08-01

    We report a case of radiation-induced mucosal melanoma in a 41-year-old woman with a history of childhood rhabdomyosarcoma of the nasal cavity that had been treated with radiotherapy. During the workup for the melanoma, the patient was found to be negative for S-100 protein on immunostaining. While many melanotic markers for the histologic confirmation of melanoma exist, they can be negative in some cases, such as ours. To the best of our knowledge, only 1 case of radiation-induced melanoma has been previously reported in the English-language literature, and in that case the patient was S-100-positive. Although our case is rare, it suggests another possible long-term adverse effect of radiotherapy. We also describe the morphologies and histology associated with diagnosing melanoma in an S-100-negative patient. PMID:27551844

  7. Anti-apoptotic peptides protect against radiation-induced cell death

    SciTech Connect

    McConnell, Kevin W.; Muenzer, Jared T.; Chang, Kathy C.; Davis, Chris G.; McDunn, Jonathan E.; Coopersmith, Craig M.; Hilliard, Carolyn A.; Hotchkiss, Richard S.; Grigsby, Perry W.; Hunt, Clayton R. . E-mail: chunt@radonc.wustl.edu

    2007-04-06

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues.

  8. Protective effect of α-lipoic acid against radiation-induced fibrosis in mice.

    PubMed

    Ryu, Seung-Hee; Park, Eun-Young; Kwak, Sungmin; Heo, Seung-Ho; Ryu, Je-Won; Park, Jin-Hong; Choi, Kyung-Chul; Lee, Sang-Wook

    2016-03-29

    Radiation-induced fibrosis (RIF) is one of the most common late complications of radiation therapy. We found that α-lipoic acid (α-LA) effectively prevents RIF. In RIF a mouse model, leg contracture assay was used to test the in vivo efficacy of α-LA. α-LA suppressed the expression of pro-fibrotic genes after irradiation, both in vivo and in vitro, and inhibited the up-regulation of TGF-β1-mediated p300/CBP activity. Thus, α-LA prevents radiation-induced fibrosis (RIF) by inhibiting the transcriptional activity of NF-κB through inhibition of histone acetyltransferase activity. α-LA is a new therapeutic methods that can be used in the prevention-treatment of RIF.

  9. Radiation-induced glioblastoma multiforme in a remitted acute lymphocytic leukemia patient.

    PubMed

    Joh, Daewon; Park, Bong Jin; Lim, Young Jin

    2011-09-01

    Radiation therapy has been widely applied for cancer treatment. Childhood acute lymphocytic leukemia (ALL), characterized by frequent central nervous system involvement, is a well documented disease for the effect of prophylactic cranio-spinal irradiation. Irradiation, however, acts as an oncogenic factor as a delayed effect and it is rare that glioblastoma multiforme develops during the remission period of ALL. We experienced a pediatric radiation-induced GBM patient which developed during the remission period of ALL, who were primarily treated with chemotherapeutic agents and brain radiation therapy for the prevention of central nervous system (CNS) relapse. Additionally, we reviewed the related literature regarding on the effects of brain irradiation in childhood and on the prognosis of radiation induced GBM.

  10. [Radiation-Induced Radiculopathy with Paresis of the Neck and Autochthonous Back Muscles with Additional Myopathy].

    PubMed

    Ellrichmann, G; Lukas, C; Adamietz, I A; Grunwald, C; Schneider-Gold, C; Gold, R

    2016-06-01

    Radiation-induced tissue damage is caused by ionizing radiation mainly affecting the skin, vascular, neuronal or muscle tissue. Early damages occur within weeks and months while late damages may occur months or even decades after radiation.Radiation-induced paresis of the spine or the trunk muscles with camptocormia or dropped-head syndrome are rare but have already been described as long-term sequelae after treatment of Hodgkin's lymphoma. The differential diagnosis includes limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy (FSHD) or lysosomal storage diseases (e. g. Acid Maltase Deficiency). We present the case of a patient with long lasting diagnostics over many months due to different inconclusive results. PMID:27391986

  11. Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis

    PubMed Central

    Weigel, Christoph; Veldwijk, Marlon R.; Oakes, Christopher C.; Seibold, Petra; Slynko, Alla; Liesenfeld, David B.; Rabionet, Mariona; Hanke, Sabrina A.; Wenz, Frederik; Sperk, Elena; Benner, Axel; Rösli, Christoph; Sandhoff, Roger; Assenov, Yassen; Plass, Christoph; Herskind, Carsten; Chang-Claude, Jenny; Schmezer, Peter; Popanda, Odilia

    2016-01-01

    Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy. PMID:26964756

  12. Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis.

    PubMed

    Weigel, Christoph; Veldwijk, Marlon R; Oakes, Christopher C; Seibold, Petra; Slynko, Alla; Liesenfeld, David B; Rabionet, Mariona; Hanke, Sabrina A; Wenz, Frederik; Sperk, Elena; Benner, Axel; Rösli, Christoph; Sandhoff, Roger; Assenov, Yassen; Plass, Christoph; Herskind, Carsten; Chang-Claude, Jenny; Schmezer, Peter; Popanda, Odilia

    2016-03-11

    Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse if epigenetic regulation might explain inter-individual differences in fibrosis risk. DNA methylation profiling of dermal fibroblasts obtained from breast cancer patients prior to irradiation identifies differences associated with fibrosis. One region is characterized as a differentially methylated enhancer of diacylglycerol kinase alpha (DGKA). Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. Conversely, inhibition of DGKA has pronounced effects on diacylglycerol-mediated lipid homeostasis and reduces profibrotic fibroblast activation. Collectively, DGKA is an epigenetically deregulated kinase involved in radiation response and may serve as a marker and therapeutic target for personalized radiotherapy.

  13. Radiation-induced segregation and precipitation behaviours around cascade clusters under electron irradiation.

    PubMed

    Sueishi, Yuichiro; Sakaguchi, Norihito; Shibayama, Tamaki; Kinoshita, Hiroshi; Takahashi, Heishichiro

    2003-01-01

    We have investigated the formation of cascade clusters and structural changes in them by means of electron irradiation following ion irradiation in an austenitic stainless steel. Almost all of the cascade clusters, which were introduced by the ion irradiation, grew to form interstitial-type dislocation loops or vacancy-type stacking fault tetrahedra after electron irradiation at 623 K, whereas a few of the dot-type clusters remained in the matrix. It was possible to recognize the concentration of Ni and Si by radiation-induced segregation around the dot-type clusters. After electron irradiation at 773 K, we found that some cascade clusters became precipitates (delta-Ni2Si) due to radiation-induced precipitation. This suggests that the cascade clusters could directly become precipitation sites during irradiation.

  14. Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy

    SciTech Connect

    Guy, J.; Schatz, N.J.

    1986-08-01

    Four patients with radiation-induced optic neuropathies were treated with hyperbaric oxygen. They had received radiation therapy for treatment of pituitary tumors, reticulum cell sarcoma, and meningioma. Two presented with amaurosis fugax before the onset of unilateral visual loss and began hyperbaria within 72 hours after development of unilateral optic neuropathy. Both had return of visual function to baseline levels. The others initiated treatment two to six weeks after visual loss occurred in the second eye and had no significant improvement of vision. Treatment consisted of daily administration of 100% oxygen under 2.8 atmospheres of pressure for 14-28 days. There were no medical complications of hyperbaria. While hyperbaric oxygen is effective in the treatment of radiation-induced optic neuropathy, it must be instituted within several days of deterioration in vision for restoration of baseline function.

  15. The potential influence of radiation-induced microenvironments in neoplastic progression

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

  16. Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

    2000-01-01

    Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

  17. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    SciTech Connect

    Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali; Hemati, Simin

    2015-07-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

  18. Radiation-induced intermediates in irradiated glassy ionic liquids at low temperature

    NASA Astrophysics Data System (ADS)

    Saenko, Elizaveta V.; Lukianova, Mariia A.; Shiryaeva, Ekaterina S.; Takahashi, Kenji; Feldman, Vladimir I.

    2016-07-01

    The primary radiation-induced processes in irradiated low-temperature pyrrolidinium- and piperidinium-type ionic liquids were investigated by EPR and optical absorption spectroscopy. A narrow singlet signal in the EPR spectra of irradiated ionic liquids was attributed to the physically stabilized electron. Broad absorption band in visible region was ascribed to "hole" species. Aromatic scavengers react with "hole" species in glassy irradiated ionic liquids at 77 K.

  19. Energy Distribution of Electrons in Radiation Induced-Helium Plasmas. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Lo, R. H.

    1972-01-01

    Energy distribution of high energy electrons as they slow down and thermalize in a gaseous medium is studied. The energy distribution in the entire energy range from source energies down is studied analytically. A helium medium in which primary electrons are created by the passage of heavy-charged particles from nuclear reactions is emphasized. A radiation-induced plasma is of interest in a variety of applications, such as radiation pumped lasers and gaseous core nuclear reactors.

  20. Argon plasma coagulation therapy for a hemorrhagic radiation-induced gastritis in patient with pancreatic cancer.

    PubMed

    Shukuwa, Kazutaka; Kume, Keiichiro; Yamasaki, Masahiro; Yoshikawa, Ichiro; Otsuki, Makoto

    2007-01-01

    Radiation-induced gastritis is a serious complication of radiation therapy for pancreatic cancer which is difficult to manage. A 79-year-old man had been diagnosed as having inoperable pancreatic cancer (stage IVa). We encountered this patient with hemorrhagic gastritis induced by external radiotherapy for pancreatic cancer that was well-treated using argon plasma coagulation (APC). After endoscopic treatment using APC, anemia associated with hemorrhagic radiation gastritis improved and required no further blood transfusion. PMID:17603236

  1. Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy

    NASA Astrophysics Data System (ADS)

    Murray, Louise J.; Thompson, Christopher M.; Lilley, John; Cosgrove, Vivian; Franks, Kevin; Sebag-Montefiore, David; Henry, Ann M.

    2015-02-01

    Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute

  2. Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy.

    PubMed

    Murray, Louise J; Thompson, Christopher M; Lilley, John; Cosgrove, Vivian; Franks, Kevin; Sebag-Montefiore, David; Henry, Ann M

    2015-02-01

    Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute

  3. Loss of Matrix Metalloproteinase-13 Attenuates Murine Radiation-Induced Pulmonary Fibrosis

    SciTech Connect

    Flechsig, Paul; Hartenstein, Bettina; Teurich, Sybille; Dadrich, Monika; Hauser, Kai; Abdollahi, Amir; Groene, Hermann-Josef; Angel, Peter; Huber, Peter E.

    2010-06-01

    Purpose: Pulmonary fibrosis is a disorder of the lungs with limited treatment options. Matrix metalloproteinases (MMPs) constitute a family of proteases that degrade extracellular matrix with roles in fibrosis. Here we studied the role of MMP13 in a radiation-induced lung fibrosis model using a MMP13 knockout mouse. Methods and Materials: We investigated the role of MMP13 in lung fibrosis by investigating the effects of MMP13 deficiency in C57Bl/6 mice after 20-Gy thoracic irradiation (6-MV Linac). The morphologic results in histology were correlated with qualitative and quantitative results of volume computed tomography (VCT), magnetic resonance imaging (MRI), and clinical outcome. Results: We found that MMP13 deficient mice developed less pulmonary fibrosis than their wildtype counterparts, showed attenuated acute pulmonary inflammation (days after irradiation), and a reduction of inflammation during the later fibrogenic phase (5-6 months after irradiation). The reduced fibrosis in MMP13 deficient mice was evident in histology with reduced thickening of alveolar septi and reduced remodeling of the lung architecture in good correlation with reduced features of lung fibrosis in qualitative and quantitative VCT and MRI studies. The partial resistance of MMP13-deficient mice to fibrosis was associated with a tendency towards a prolonged mouse survival. Conclusions: Our data indicate that MMP13 has a role in the development of radiation-induced pulmonary fibrosis. Further, our findings suggest that MMP13 constitutes a potential drug target to attenuate radiation-induced lung fibrosis.

  4. Effect of top electrode material on radiation-induced degradation of ferroelectric thin film structures

    NASA Astrophysics Data System (ADS)

    Brewer, Steven J.; Deng, Carmen Z.; Callaway, Connor P.; Paul, McKinley K.; Fisher, Kenzie J.; Guerrier, Jonathon E.; Rudy, Ryan Q.; Polcawich, Ronald G.; Jones, Jacob L.; Glaser, Evan R.; Cress, Cory D.; Bassiri-Gharb, Nazanin

    2016-07-01

    The effects of gamma irradiation on the dielectric and piezoelectric responses of Pb[Zr0.52Ti0.48]O3 (PZT) thin film stacks were investigated for structures with conductive oxide (IrO2) and metallic (Pt) top electrodes. The samples showed, generally, degradation of various key dielectric, ferroelectric, and electromechanical responses when exposed to 2.5 Mrad (Si) 60Co gamma radiation. However, the low-field, relative dielectric permittivity, ɛr, remained largely unaffected by irradiation in samples with both types of electrodes. Samples with Pt top electrodes showed substantial degradation of the remanent polarization and overall piezoelectric response, as well as pinching of the polarization hysteresis curves and creation of multiple peaks in the permittivity-electric field curves post irradiation. The samples with oxide electrodes, however, were largely impervious to the same radiation dose, with less than 5% change in any of the functional characteristics. The results suggest a radiation-induced change in the defect population or defect energy in PZT with metallic top electrodes, which substantially affects motion of internal interfaces such as domain walls. Additionally, the differences observed for stacks with different electrode materials implicate the ferroelectric-electrode interface as either the predominant source of radiation-induced effects (Pt electrodes) or the site of healing for radiation-induced defects (IrO2 electrodes).

  5. Leaf extract of Moringa oleifera prevents ionizing radiation-induced oxidative stress in mice.

    PubMed

    Sinha, Mahuya; Das, Dipesh K; Bhattacharjee, Surajit; Majumdar, Subrata; Dey, Sanjit

    2011-10-01

    The present study evaluated the hepatoprotective effect of aqueous ethanolic Moringa oleifera leaf extract (MoLE) against radiation-induced oxidative stress, which is assessed in terms of inflammation and lipid peroxidation. Swiss albino mice were administered MoLE (300 mg/kg of body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of ⁶⁰Co γ-irradiation. Mice were sacrificed at 4 hours after irradiation. Liver was collected for immunoblotting and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were augmented, whereas the superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and ferric reducing antioxidant power (FRAP) values were decreased by radiation exposure. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited, whereas increases in SOD, CAT, GSH, and FRAP were observed in the mice treated with MoLE prior to irradiation. Therefore pretreatment with MoLE protected against γ-radiation-induced liver damage. The protection may be attributed to the free radical scavenging activity of MoLE, through which it can ameliorate radiation-induced oxidative stress. PMID:21861723

  6. Altered gastric emptying and prevention of radiation-induced vomiting in dogs. [Cobalt 60 irradiation

    SciTech Connect

    Dubois, A.; Jacobus, J.P.; Grissom, M.P.; Eng, R.R.; Conklin, J.J.

    1984-03-01

    The relation between radiation-induced vomiting and gastric emptying is unclear and the treatment of this condition is not established. We explored, therefore, (a) the effect of cobalt 60 irradiation on gastric emptying of solids and liquids and (b) the possibility of preventing radiation-induced vomiting with the dopamine antagonist, domperidone. Twenty dogs were studied on two separate days, blindly and in random order, after i.v. injection of either a placebo or 0.06 mg/kg domperidone. On a third day, they received 8 Gy (800 rads) whole body irradiation with cobalt 60 gamma-rays after either placebo (n . 10) or domperidone (n . 10). Before each study, each dog was fed chicken liver tagged in vivo with 99mTc-sulfur colloid (solid marker), and water containing 111In-diethylenetriamine pentaacetic acid (liquid marker). Dogs were placed in a Pavlov stand for the subsequent 3 h and radionuclide imaging was performed at 10-min intervals. Irradiation produced vomiting in 9 of 10 dogs given placebo but only in 1 of 10 dogs pretreated with domperidone (p less than 0.01). Gastric emptying of liquids and solids was significantly suppressed by irradiation (p less than 0.01) after both placebo and domperidone. These results demonstrate that radiation-induced vomiting is accompanied by suppression of gastric emptying. Furthermore, domperidone prevents vomiting produced by ionizing radiation but does not alter the accompanying delay of gastric emptying.

  7. Radiation induced oral mucositis: a review of current literature on prevention and management.

    PubMed

    Mallick, Supriya; Benson, Rony; Rath, G K

    2016-09-01

    Oral mucositis (OM) is a major limiting acute side effect of radiotherapy for head and neck cancer. The spectrum of problems associated with mucositis includes oral pain, odynophagia, reduced oral intake, and secondary infections. Incidence of mucositis is increased with addition of concurrent chemotherapy as well as altered fractionation schedules. This leads to treatment interruption and suboptimal disease control. Hence, prevention as well as timely management of OM is necessary for optimum tumor control. We reviewed the English literature with key words "Radiation induced mucositis, Mucositis, Oral Mucositis" to find relevant articles describing incidence, pathophysiology, prophylaxis, and treatment of oral mucositis. Prevention and treatment of OM is an active area of research. Maintenance of oral hygiene is an important part in prevention of OM. A battery of agents including normal saline and alkali (soda bicarbonate) mouth washes, low level laser therapy, and benzydamine (non-steroidal analgesic and anti-inflammatory) have effectiveness in the prevention and treatment of radiation induced oral mucositis. Chlorhexidine mouth gargles are recommended for prevention of chemotherapy induced oral mucositis but is not recommended for radiotherapy associated mucositis. Treatment of co-existing infection is also important and both topical (povidone iodine) and systemic anti fungals should be used judiciously. Radiation induced oral mucositis is a common problem limiting the efficacy of radiation by increasing treatment breaks. Adequate prophylaxis and treatment may limit the severity of radiation mucositis and improve compliance to radiation which may translate in better disease control and survival. PMID:26116012

  8. Role of the area postrema in radiation-induced taste aversion learning and emesis in cats

    SciTech Connect

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

    1986-01-01

    The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.

  9. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

  10. Leaf extract of Moringa oleifera prevents ionizing radiation-induced oxidative stress in mice.

    PubMed

    Sinha, Mahuya; Das, Dipesh K; Bhattacharjee, Surajit; Majumdar, Subrata; Dey, Sanjit

    2011-10-01

    The present study evaluated the hepatoprotective effect of aqueous ethanolic Moringa oleifera leaf extract (MoLE) against radiation-induced oxidative stress, which is assessed in terms of inflammation and lipid peroxidation. Swiss albino mice were administered MoLE (300 mg/kg of body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of ⁶⁰Co γ-irradiation. Mice were sacrificed at 4 hours after irradiation. Liver was collected for immunoblotting and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were augmented, whereas the superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and ferric reducing antioxidant power (FRAP) values were decreased by radiation exposure. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited, whereas increases in SOD, CAT, GSH, and FRAP were observed in the mice treated with MoLE prior to irradiation. Therefore pretreatment with MoLE protected against γ-radiation-induced liver damage. The protection may be attributed to the free radical scavenging activity of MoLE, through which it can ameliorate radiation-induced oxidative stress.

  11. Dynamics of wound healing signaling as a potential therapeutic target for radiation-induced tissue damage.

    PubMed

    Chung, Yih-Lin; Pui, Newman N M

    2015-01-01

    We hypothesized the histone deacetylase inhibitor phenylbutyrate (PB) has beneficial effects on radiation-induced injury by modulating the expression of DNA repair and wound healing genes. Hamsters received a radiosurgical dose of radiation (40 Gy) to the cheek and were treated with varying PB dosing regimens. Gross alteration of the irradiated cheeks, eating function, histological changes, and gene expression during the course of wound healing were compared between treatment groups. Pathological analysis showed decreased radiation-induced mucositis, facilitated epithelial cell growth, and preventing ulcerative wound formation, after short-term PB treatment, but not after vehicle or sustained PB. The radiation-induced wound healing gene expression profile exhibited a sequential transition from the inflammatory and DNA repair phases to the tissue remodeling phase in the vehicle group. Sustained PB treatment resulted in a prolonged wound healing gene expression profile and delayed the wound healing process. Short-term PB shortened the duration of inflammatory cytokine expression, triggered repeated pulsed expression of cell cycle and DNA repair-regulating genes, and promoted earlier oscillatory expression of tissue remodeling genes. Distinct gene expression patterns between sustained and short-term treatment suggest dynamic profiling of wound healing gene expression can be an important part of a biological therapeutic strategy to mitigate radiation-related tissue injury.

  12. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

    PubMed

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk. PMID:27345200

  13. The effect of probiotics for preventing radiation-induced morphological changes in intestinal mucosa of rats.

    PubMed

    Ki, Yongkan; Kim, Wontaek; Cho, Heunglae; Ahn, Kijung; Choi, Youngmin; Kim, Dongwon

    2014-10-01

    Radiation therapy is an important treatment modality for abdominal or pelvic cancer, but there is a common and serious complication such as radiation-induced enteritis. Probiotics is reported to have positive effects against radiation-induced enteropathy. In this study, morphological changes of bowel mucosa were analyzed in rats to presume the effect of probiotics on radiation-induced enteritis and its correlation with radiation dose. A total of 48 adult male Sprague-Dawley rats were randomly assigned to two groups and received a solution containing 1.0×10(8) colony-forming units of Lactiobacillus acidophilus or water once daily for 10 days. Each of two groups was divided into three subgroups and abdomino-pelvic area of each subgroup was irradiated with 10, 15, and 20 Gy, respectively on the seventh day of feeding the solutions. All rats were sacrificed 3 days after irradiation and the mucosal thickness and villus height of jejunum, ileum and colon were measured. The morphological parameters of the small intestine represented significant differences between two solution groups irradiated 10 or 15 Gy, except for villus height of jejunum in 15 Gy-subgroup (P=0.065). There was no significant morphometric difference between two groups irradiated with 20 Gy of radiation. Probiotics appear to be effective for the morphological shortening of small intestinal mucosa damaged by radiation less than or equal to 15 Gy. PMID:25368490

  14. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

    PubMed

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

  15. The Efficacy of Nardostachys Jatamansi Against The Radiation Induced Haematological Damage In Rats

    PubMed Central

    Gowda, Damodara K M; Shetty, Lathika; A P, Krishna; Kumari, Suchetha N; Sanjeev, Ganesh; P, Naveen

    2013-01-01

    Introduction: Radiation is increasingly being used for medical purposes and it is an established weapon in the diagnosis and the therapy of cancer. An exposure to 1-2 Gys causes the NVD (Nausea, vomiting, diarrhoea) syndrome, whereas an exposure to 2-6 Gys causes the haematopoietic syndrome. The aim of the present study was to investigate the protective effect of the Nardostachys jatamansi root extract (NJE) on the radiation induced haematological damage in rats. Materials and Methods: EBR was performed at the Microtron Centre, Mangalore University, India. Rats were treated with NJE once daily for 15 days before and after the irradiation. After the irradiation, blood was collected for determining the peripheral blood counts (RBC and WBC), haemoglobin, the platelet count and the packed cell volume (PCV) at 6 hours, 12 hours, 24 hours, 48 hours and 5, 10 and 15 days post irradiation. The data was analyzed by one way ANOVA, followed by the Tukey’s test for multiple comparisons. Result: NJE provided protection against the radiation induced haematological disorders. The rats treated with NJE exhibited a time dependent significant elevation in all the haematological parameters which were studied and its modulation upto the near normal level was recorded. Conclusion: From this study, we concluded that, NJE provides protection by modulating the radiation induced damage on the haematopoietic system. PMID:23905085

  16. Effects of NOX1 on fibroblastic changes of endothelial cells in radiation-induced pulmonary fibrosis

    PubMed Central

    CHOI, SEO-HYUN; KIM, MISEON; LEE, HAE-JUNE; KIM, EUN-HO; KIM, CHUN-HO; LEE, YOON-JIN

    2016-01-01

    Lung fibrosis is a major complication in radiation-induced lung damage following thoracic radiotherapy, while the underlying mechanism has remained to be elucidated. The present study performed immunofluorescence and immunoblot assays on irradiated human pulmonary artery endothelial cells (HPAECs) with or without pre-treatment with VAS2870, a novel NADPH oxidase (NOX) inhibitor, or small hairpin (sh)RNA against NOX1, -2 or -4. VAS2870 reduced the cellular reactive oxygen species content induced by 5 Gy radiation in HPAECs and inhibited phenotypic changes in fibrotic cells, including increased alpha smooth muscle actin and vimentin, and decreased CD31 and vascular endothelial cadherin expression. These fibrotic changes were significantly inhibited by treatment with NOX1 shRNA, but not by NOX2 or NOX4 shRNA. Next, the role of NOX1 in pulmonary fibrosis development was assessed in the lung tissues of C57BL/6J mice following thoracic irradiation using trichrome staining. Administration of an NOX1-specific inhibitor suppressed radiation-induced collagen deposition and fibroblastic changes in the endothelial cells (ECs) of these mice. The results suggested that radiation-induced pulmonary fibrosis may be efficiently reduced by specific inhibition of NOX1, an effect mediated by reduction of fibrotic changes of ECs. PMID:27053172

  17. The role of secretory granules in radiation-induced dysfunction of rat salivary glands

    SciTech Connect

    Peter, B.; Van Waarde, M.A.W.H.; Konings, A.W.T.; Vissink, A. |; `s-Gravenmade, E.J.

    1995-02-01

    To investigate the possible role of secretory granules in radiation-induced salivary gland dysfunction, rats were pretreated with isoproterenol (5 mg/kg intraperitoneally) to degranulate salivary gland acini. At maximal depletion, salivary glands were locally irradiated with a single dose of 15 Gy of X rays. Parotid and submandibular/sublingual saliva samples were collected before and 1-10 days after irradiation. The lag phase, flow rate, concentrations of potassium and sodium, and amylase secretion were determined. Sham-treated, isoproterenol-treated and irradiated animals provided reference data. In the parotid gland, but not in the submandibular gland, protection against radiation-induced changes in flow rate and composition of saliva occurred after pretreatment with isoproterenol. Combining morphological data from a previous study with data from the current study, it is suggested that improvement of parotid gland function is attributed predominantly to a proliferative stimulus on acinar cells by isoproterenol and not to its degranulation effect. After pretreatment with isoproterenol, an earlier expression of radiation-induced acinar cell damage leading to death was observed, followed by a faster tissue recovery. Thus the proliferative stimulus on acinar cells may accelerate the unmasking of latent lethal damage, resulting in the earlier replacement of dead cells by new, functionally intact cells. 33 refs., 2 figs.

  18. Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

    Abstract: Radiation-induced bystander effect was 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 and proteomics plays 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 Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

  19. Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

    PubMed Central

    Shim, Grace; Ricoul, Michelle; Hempel, William M.; Azzam, Edouard I.; Sabatier, Laure

    2014-01-01

    It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. PMID:24486376

  20. Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

    SciTech Connect

    Wan, X. Steven; Ware, Jeffrey H.; Zhou, Zhaozong; Donahue, Jeremiah J.; Guan, Jun; Kennedy, Ann R. . E-mail: akennedy@mail.med.upenn.edu

    2006-04-01

    Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, {alpha}-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, {gamma}-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects.

  1. Transanal Evisceration Caused by Rectal Laceration

    PubMed Central

    Torres Sánchez, María Teresa; Richart Aznar, Jose Manuel; Martí Martínez, Eva María; Martínez-Abad, Manuel

    2014-01-01

    Transrectal evisceration caused by colorectal injury is an unusual entity. This pathology is more frequent in elderly patients and it is usually produced spontaneously. Rectal prolapse is the principal predisposing factor. An 81-year-old woman was taken to the hospital presenting exit of intestinal loops through the anus. After first reanimation measures, an urgent surgery was indicated. We observed the absence of almost every small intestine loop in the abdominal cavity; these had been moved to the pelvis. After doing the reduction, a 3 to 4 cm linear craniocaudal perforation in upper rectum was objectified, and Hartmann's procedure was performed. We investigated and knew that she frequently manipulate herself to extract her faeces. The fast preoperative management avoided a fatal conclusion or an extensive intestinal resection. Reasons that make us consider rectal self-injury as the etiologic factor are explained. PMID:24639971

  2. High-frequency detection of the formation and stabilization of a radiation-induced defect cluster in semiconductor structures

    SciTech Connect

    Puzanov, A. S.; Obolenskiy, S. V. Kozlov, V. A.; Volkova, E. V.; Paveliev, D. G.

    2015-12-15

    The processes of the formation and stabilization of a radiation-induced defect cluster upon the arrival of a fast neutron to the space-charge region of a semiconductor diode are analyzed. The current pulse formed by secondary electrons is calculated and the spectrum of the signal generated by the diode (detector) under the action of an instantaneous neutron flux of the fission spectrum is determined. The possibility of experimental detection of the picosecond radiation-induced transition processes is discussed.

  3. The Evaluation of Rectal Bleeding in Adults

    PubMed Central

    Allen, Elizabeth; Nicolaidis, Christina; Helfand, Mark

    2005-01-01

    BACKGROUND Though primary care patients commonly present with rectal bleeding, the optimal evaluation strategy remains unknown. OBJECTIVE To compare the cost-effectiveness of four diagnostic strategies in the evaluation of rectal bleeding. DESIGN Cost-effectiveness analysis using a Markov decision model. DATA SOURCES Systematic review of the literature, Medicare reimbursement data, Surveillance, Epidemiology, and End Results (SEER) Cancer Registry. TARGET POPULATION Patients over age 40 with otherwise asymptomatic rectal bleeding. TIME HORIZON The patient's lifetime. PERSPECTIVE Modified societal perspective. INTERVENTIONS Watchful waiting, flexible sigmoidoscopy, flexible sigmoidoscopy followed by air contrast barium enema (FS+ACBE), and colonoscopy. OUTCOME MEASURES Incremental cost-effectiveness ratio. RESULTS OF BASE-CASE ANALYSIS The incremental cost-effectiveness ratio for colonoscopy compared with flexible sigmoidoscopy was $5,480 per quality-adjusted year of life saved (QALY). Watchful waiting and FS+ACBE were more expensive and less effective than colonoscopy. RESULTS OF SENSITIVITY ANALYSES The cost of colonoscopy was reduced to $1,686 per QALY when age at entry was changed to 45. Watchful waiting became the least expensive strategy when community procedure charges replaced Medicare costs, when age at entry was maximized to 80, or when the prevalence of polyps was lowered to 7%, but the remaining strategies provided greater life expectancy at relatively low cost. The strategy of FS+ACBE remained more expensive and less effective in all analyses. In the remaining sensitivity analyses, the incremental cost-effectiveness of colonoscopy compared with flexible sigmoidoscopy never rose above $34,000. CONCLUSIONS Colonoscopy is a cost-effective method to evaluate otherwise asymptomatic rectal bleeding, with a low cost per QALY compared to other strategies. PMID:15693933

  4. MicroRNA in rectal cancer

    PubMed Central

    Azizian, Azadeh; Gruber, Jens; Ghadimi, B Michael; Gaedcke, Jochen

    2016-01-01

    In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters. PMID:27190581

  5. [Multidisciplinary treatment of locally advanced rectal cancer].

    PubMed

    Faes, Seraina; Gié, Olivier; Demartines, Nicolas; Hahnloser, Dieter

    2016-06-15

    Treatment of patients with locally advanced rectal cancer remains challenging. Preoperative imaging with pelvic MRI allows to identify patients for multimodal treatment including induction chemothe- rapy or neoadjuvant radio-chemotherapy and an extended surgical resection. With multidisciplinary approach and an experienced team, excellent oncologic results may be achieved, as well as a good function and quality of life, even with preservation of the anus in the majority of patients. PMID:27487624

  6. Importance of surgical margins in rectal cancer.

    PubMed

    Mukkai Krishnamurty, Devi; Wise, Paul E

    2016-03-01

    Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter-saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs. PMID:27094456

  7. Acute rectal obstruction after PPH stapled haemorrhoidectomy.

    PubMed

    Cipriani, S.; Pescatori, M.

    2002-09-01

    An unusual case of acute intestinal obstruction following a PPH stapled haemorrhoidectomy is reported: the complication was due to an almost complete interruption of the rectal lumen tightened by a purse-string suture anchored by staples. The stricture was dilated and the suture released thus restoring intestinal continuity. Surgeons should be aware that such troublesome complication may occur and can be treated successfully by a transanal approach.

  8. Spiral rectal valves: Anatomy, eponyms, and clinical significance.

    PubMed

    Ikard, Robert W

    2015-05-01

    Rectal wall valves are obscure anatomic parts that rarely are considered in current medical practice. Yet from the seminal analysis of them in the early nineteenth century by the Irish anatomist and surgeon, John Houston, their structure, purpose, and clinical significance were topics of surprising disagreement. Were they true structures? What function might they have? Did disease originate in rectal valves? Were special operations required for any such diseases? Because Houston's anatomic analyses of rectal valves were substantiated, they came to be known in the English literature as the Spiral Rectal Valves of Houston. In the mid-nineteenth century, a single mid-rectal valve was described by the Hanoverian, Otto Kohlrausch., creating confusion with the established eponym "Houston's Valves." Many hypotheses about rectal valves have been discredited; and their physiologic functions are still unknown.

  9. Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

    SciTech Connect

    Chapet, Olivier; Udrescu, Corina; Tanguy, Ronan; Ruffion, Alain; Fenoglietto, Pascal; Sotton, Marie-Pierre; Devonec, Marian; Colombel, Marc; Jalade, Patrice; Azria, David

    2014-02-01

    Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs according to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.

  10. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  11. Hyperbaric Oxygen Treatment in Radiation-Induced Cystitis and Proctitis: A Prospective Cohort Study on Patient-Perceived Quality of Recovery

    SciTech Connect

    Oscarsson, Nicklas; Arnell, Per; Lodding, Pär; Ricksten, Sven-Erik; Seeman-Lodding, Heléne

    2013-11-15

    Purpose: In this prospective cohort study, the effects of hyperbaric oxygen treatment (HBOT) were evaluated concerning patient-perceived symptoms of late radiation-induced cystitis and proctitis secondary to radiation therapy for pelvic cancer. Methods and Materials: Thirty-nine patients, 35 men and 4 women with a mean age of 71 (range, 35-84) years were included after informed consent and institutional ethics approval. They had all been treated with radiation therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood transfusion were excluded. The HBOT was delivered with 100% oxygen for 90 minutes at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40). Symptoms were prospectively assessed using the Expanded Prostate Index Composite score before, during, and 6 to 12 months after HBOT. Results: The HBOT was successfully conducted, and symptoms were alleviated in 76% for patients with radiation cystitis, 89% for patients with radiation proctitis, and 88% of patients with combined cystitis and proctitis. Symptom reduction was demonstrated by an increased Expanded Prostate Index Composite score in the urinary domain from 50 ± 16 to 66 ± 20 after treatment (P<.001) and in the bowel domain from 48 ± 18 to 68 ± 18 after treatment (P<.001). For 31% of the patients with cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The improvement was sustained at follow-up in both domains 6 to 12 months after HBOT. No severe side effects were observed related to HBOT, and treatment compliance was high. Conclusions: HBOT can be an effective and safe treatment modality for late radiation therapy-induced soft tissue injuries in the pelvic region.

  12. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-06-10

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  13. [Rectal cancer in a pregnant woman, a case report].

    PubMed

    Højgaard, Helle Manfeld; Rahr, Hans

    2012-06-25

    A case of disseminated rectal cancer in a 32-year-old pregnant woman is described. Pain was her main complaint, but this had been ascribed to haemorrhoids and treated with topical agents. She was diagnosed with rectal cancer late in the third trimester when her midwife referred her for surgical assessment. Following caesarian section, diagnostic workup showed multiple liver metastases. Rectal cancer in pregnancy is rare, while haemorrhoids are common. We recommend keeping the differential diagnoses in mind and performing a digital rectal examination if pregnant women have anal symptoms.

  14. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin.

    PubMed

    Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2013-05-01

    Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.

  15. Case report: Sigmoid strangulation from evisceration through a perforated rectal prolapse ulcer – An unusual complication of rectal prolapse

    PubMed Central

    Li, Jennifer Z.; Kittmer, Tiffaney; Forbes, Shawn; Ruo, Leyo

    2015-01-01

    Introduction Rectal prolapse occurs particularly in elder females and presentation can sometimes lead to complications such as strangulation and evisceration of other organs through the necrotic mucosa. Presentation of case This is a case of a 61 year-old female with rectal prolapse complicated by rectal perforation through which a segment of sigmoid colon eviscerated and became strangulated. This patient initially presented with sepsis requiring ICU admission, but fully recovered following a Hartmann’s procedure with a sacral rectopexy. Discussion Complications of rectal prolapse include incarceration, strangulation, and rarely, perforation with evisceration of other viscera requiring urgent operation. This report provides a brief overview of complications associated with rectal prolapse, reviews similar cases of transrectal evisceration, and discusses the management of chronic rectal prolapse. Conclusion Prompt surgical consult is warranted if any signs or symptoms suggestive of complications from prolapse are present. PMID:25680532

  16. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    PubMed Central

    Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

    2014-01-01

    Background Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III “pain ladder” drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient’s refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures), and to evaluate the effect of the mode of administration (intrathecal versus rectal) on the bupivacaine plasma concentration. Cases We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours). The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 mL every 4.5–11 hours). Methods Total bupivacaine plasma concentrations were determined using the high-performance liquid chromatography-ultraviolet method. Results Effective pain control was achieved with intrathecal bupivacaine (0.077–0.154 mg·kg−1) and bupivacaine in enema (1.820 mg·kg−1). Intrathecal bupivacaine (0.5%, 2 mL) caused a drop in blood pressure; other side effects were absent in both cases. Total plasma bupivacaine concentrations following intrathecal and rectal bupivacaine application did not exceed 317.2 ng·mL−1 and 235.7 ng·mL−1, respectively. Bupivacaine elimination was

  17. Radiation-induced brain injury: low-hanging fruit for neuroregeneration.

    PubMed

    Burns, Terry C; Awad, Ahmed J; Li, Matthew D; Grant, Gerald A

    2016-05-01

    Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system. PMID:27132524

  18. Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells.

    PubMed

    Perona, Marina; Dagrosa, María A; Pagotto, Romina; Casal, Mariana; Pignataro, Omar P; Pisarev, Mario A; Juvenal, Guillermo J

    2013-03-01

    Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of γ irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 2',7'-dichlorofluorescein-diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P < 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and time-dependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme's activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage.

  19. Regulation of ionizing radiation-induced apoptosis by a manganese porphyrin complex

    SciTech Connect

    Lee, Jin Hyup; Lee, You Mie; Park, Jeen-Woo . E-mail: parkjw@knu.ac.kr

    2005-08-26

    Ionizing radiation induces the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on apoptosis. Superoxide dismutase (SOD) mimetics have been shown to be protective against cell injury caused by reactive oxygen species. We investigated the effects of the manganese (III) tetrakis(N-methyl-2-pyridyl)porphyrin (MnTMPyP), a cell-permeable SOD mimetic, on ionizing radiation-induced apoptosis. Upon exposure to 2 Gy of {gamma}-irradiation, there was a distinct difference between the control cells and the cells pre-treated with 5 {mu}M MnTMPyP for 2 h with regard to apoptotic parameters, cellular redox status, mitochondria function, and oxidative damage to cells. MnTMPyP effectively suppressed morphological evidence of apoptosis and DNA fragmentation in U937 cells exposed to ionizing radiation. The [GSSG]/[GSH + GSSG] ratio and the generation of intracellular reactive oxygen species were higher and the [NADPH]/[NADP{sup +} + NADPH] ratio was lower in control cells compared to MnTMPyP-treated cells. The ionizing radiation-induced mitochondrial damage reflected by the altered mitochondrial permeability transition, the increase in the accumulation of reactive oxygen species, and the reduction of ATP production were significantly higher in control cells compared to MnTMPyP-treated cells. MnTMPyP pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax and p53, and down-regulation of Bcl-2 compared to control cells upon exposure to ionizing radiation. This study indicates that MnTMPyP may play an important role in regulating the apoptosis induced by ionizing radiation presumably through scavenging of reactive oxygen species.

  20. Protection of DNA From Ionizing Radiation-Induced Lesions by Asiaticoside.

    PubMed

    Joy, Jisha; Alarifi, Saud; Alsuhaibani, Entissar; Nair, Cherupally K Krishnan

    2015-01-01

    This study aims to investigate whether asiaticoside, a triterpene glycoside, can afford protection to DNA from alterations induced by gamma radiation under in vitro, ex vivo, and in vivo conditions. In vitro studies were done on plasmid pBR322 DNA, ex vivo studies were done on cellular DNA of human peripheral blood leukocytes, and in vivo investigations were conducted on cellular DNA of spleen and bone marrow cells of mice exposed to whole-body gamma radiation. The supercoiled form of the plasmid pBR322 DNA upon exposure to the radiation was converted into relaxed open circular form due to induction of strand breaks. Presence of asiaticoside along with the DNA during irradiation prevented the relaxation of the supercoiled form to the open circular form. When human peripheral blood leukocytes were exposed to gamma radiation, the cellular DNA suffered strand breaks as evidenced by the increased comet parameters in an alkaline comet assay. Asiaticoside, when present along with blood during irradiation ex vivo, prevented the strand breaks and the comet parameters were closer to that of the controls. Whole-body exposure of mice to gamma radiation resulted in a significant increase in comet parameters of DNA of bone marrow and spleen cells of mice as a result of radiation-induced strand breaks in DNA. Administration of asiaticoside prior to whole-body radiation exposure of the mice prevented this increase in radiation-induced increase in comet parameters, which could be the result of protection to DNA under in vivo conditions of radiation exposure. Thus, it can be concluded from the results that asiaticoside can offer protection to DNA from radiation-induced alterations under in vitro, ex vivo, and in vivo conditions.

  1. Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides.

    PubMed

    Shukla, Sandeep Kumar; Chaudhary, Pankaj; Kumar, Indracanti Prem; Samanta, Namita; Afrin, Farhat; Gupta, Manju Lata; Sharma, Upendra Kumar; Sinha, Arun Kumar; Sharma, Yogendra Kumar; Sharma, Rakesh Kumar

    2006-12-01

    Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan traditional medicine for the treatment of circulatory disorders, ischemic heart disease, hepatic injury, and neoplasia. In the present study, we have evaluated the radioprotective potential of REC-1001, a fraction isolated from the berries of H. rhamnoides. Chemical analysis of the extract indicated that REC-1001 was approximately 68% by weight polyphenols, and contained kaempferol, isorhamnetin, and quercetin. The effect of REC-1001 on modulating radiation-induced DNA damage was determined in murine thymocytes by measuring nonspecific nuclear DNA damage at the whole genome level using the alkaline halo assay and by measuring sequence/gene-specific DNA damage both in nuclear DNA (beta-globin gene) and in mitochondrial DNA using a quantitative polymerase chain reaction. Treatment with 10 Gy resulted in a significant amount of DNA damage in the halo assay and reductions in the amplification of both the beta-globin gene and mitochondrial DNA. REC-1001 dose-dependently reduced the amount of damage detected in each assay, with the maximum protective effects observed at the highest REC-1001 dose evaluated (250 micro g/ml). Studies measuring the nicking of naked plasmid DNA further established the radioprotective effect of REC-1001. To elucidate possible mechanisms of action, the antioxidant properties and the free-radical scavenging activities of REC-1001 were evaluated. REC-1001 dose-dependently scavenged radiation-induced hydroxyl radicals, chemically-generated superoxide anions, stabilized DPPH radicals, and reduced Fe(3+) to Fe(2+). The results of the study indicate that the REC-1001 extract of H. rhamnoides protects mitochondrial and genomic DNA from radiation-induced damage. The polyphenols/flavonoids present in the extract might be responsible for the free radical scavenging and DNA protection afforded by REC-1001. PMID:16948057

  2. Role of Ferulic Acid in the Amelioration of Ionizing Radiation Induced Inflammation: A Murine Model

    PubMed Central

    Das, Ujjal; Manna, Krishnendu; Sinha, Mahuya; Datta, Sanjukta; Das, Dipesh Kr; Chakraborty, Anindita; Ghosh, Mahua; Saha, Krishna Das; Dey, Sanjit

    2014-01-01

    Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy 60Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/β and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation. PMID:24854039

  3. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression

    SciTech Connect

    Patchen, M.L.; MacVittie, T.J.; Williams, J.L.; Schwartz, G.N.; Souza, L.M. )

    1991-02-01

    Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.

  4. Radiation induced bystander effect by GAP junction channels in human fibroblast cell

    NASA Astrophysics Data System (ADS)

    Furusawa, Y.; Shao, C.; Aoki, M.; Kobayashi, Y.; Funayama, T.; Ando, K.

    The chemical factor involved in bystander effect and its transfer pathway were investigated in a confluent human fibroblast cell (AG1522) population. Micronuclei (MN) and G1-phase arrest were detected in cells irradiated by carbon (~100 keV/μm) ions at HIMAC. A very low dose irradiation showed a high effectiveness in producing MN, suggesting a bystander effect. This effectiveness was enhanced by 8-Br-cAMP treatment that increases gap junctional intercellular communication (GJIC). On the other hand, the effect was reduced by 5% DMSO treatment, which reduce the reactive oxygen species (ROS), and suppressed by 100 μM lindane treatment, an inhibitor of GJIC. In addition, the radiation-induced G1-phase arrest was also enhanced by cAMP, and reduced or suppressed by DMSO or lindane. A microbeam device (JAERI) was also used for these studies. It was found that exposing one single cell in a confluent cell population to exactly one argon (~1260 keV/μm) or neon (~430 keV/ μm) ion, additional MN could be detected in many other unirradiated cells. The yield of MN increased with the number of irradiated cells. However, there was no significant difference in the MN induction when the cells were irradiated by increasing number of particles. MN induction by bystander effect was partly reduced by DMSO, and effectively suppressed by lindane. Our results obtained from both random irradiation and precise numbered irradiation indicate that both GJIC and ROS contributed to the radiation-induced bystander effect, but the cell gap junction channels likely play an essential role in the release and transfer of radiation-induced chemical factors.

  5. Radiation-Induced Autophagy Contributes to Cell Death and Induces Apoptosis Partly in Malignant Glioma Cells

    PubMed Central

    Jo, Guk Heui; Bögler, Oliver; Chwae, Yong-Joon; Yoo, Heon; Lee, Seung Hoon; Park, Jong Bae; Kim, Youn-Jae; Kim, Jong Heon; Gwak, Ho-Shin

    2015-01-01

    Purpose Radiation-induced autophagy has been shown to play two different roles, in malignant glioma (MG) cells, cytocidal or cytoprotective. However, neither the role of radiation-induced autophagy for cell death nor the existence of autophagy-induced apoptosis, a well-known cell-death pathway after irradiation, has been verified yet. Materials and Methods We observed both temporal and dose-dependent response patterns of autophagy and apoptosis to radiation in MG cell lines. Additionally, we investigated the role of autophagy in apoptosis through knockdown of autophagy-related proteins. Results Autophagic activity measured by staining of acidic vesicle organelles and Western blotting of LC-3 protein increased in proportion to radiation dose from day 1 to 5 after irradiation. Apoptosis measured by annexin-V staining and Western blotting of cleaved poly(ADP-ribose) polymerase demonstrated relatively late appearance 3 days after irradiation that increased for up to 7 days. Blocking of pan-caspase (Z-VAD-FMK) did not affect apoptosis after irradiation, but silencing of Atg5 effectively reduced radiation-induced autophagy, which decreased apoptosis significantly. Inhibition of autophagy in Atg5 knockdown cells was shown to be beneficial for cell survival. Stable transfection of GFP-LC3 cells was observed after irradiation. Annexin-V was localized in cells bearing GFP-LC3 punctuated spots, indicating autophagy in immunofluorescence. Some of these punctuated GFP-LC3 bearing cells formed conglomerated spots and died in final phase. Conclusion These findings suggest that autophagy appears earlier than apoptosis after irradiation and that a portion of the apoptotic population that appears later is autophagy-dependent. Thus, autophagy is a pathway to cell death after irradiation of MG cells. PMID:25410762

  6. Targeted Overexpression of Mitochondrial Catalase Prevents Radiation-Induced Cognitive Dysfunction

    PubMed Central

    Parihar, Vipan K.; Allen, Barrett D.; Tran, Katherine K.; Chmielewski, Nicole N.; Craver, Brianna M.; Martirosian, Vahan; Morganti, Josh M.; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M.; Nelson, Gregory A.; Allen, Antiño R.

    2015-01-01

    Abstract Aims: Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Results: Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2. Innovation: Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology. Conclusion: Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain. Antioxid. Redox Signal. 22, 78–91. PMID:24949841

  7. Smad, but not MAPK, pathway mediates the expression of type I collagen in radiation induced fibrosis

    SciTech Connect

    Yano, Hiroyuki; Hamanaka, Ryoji; Nakamura, Miki; Sumiyoshi, Hideaki; Matsuo, Noritaka; Yoshioka, Hidekatsu

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer We examine how radiation affects the expression level and signal pathway of collagen. Black-Right-Pointing-Pointer TGF-{beta}1 mRNA is elevated earlier than those of collagen genes after irradiation. Black-Right-Pointing-Pointer Smad pathway mediates the expression of collagen in radiation induced fibrosis. Black-Right-Pointing-Pointer MAPK pathways are not affected in the expression of collagen after irradiation. -- Abstract: Radiation induced fibrosis occurs following a therapeutic or accidental radiation exposure in normal tissues. Tissue fibrosis is the excessive accumulation of collagen and other extracellular matrix components. This study investigated how ionizing radiation affects the expression level and signal pathway of type I collagen. Real time RT-RCR showed that both {alpha}1and {alpha}2 chain of type I collagen mRNA were elevated from 48 h after irradiation with 10 Gy in NIH3T3 cells. The relative luciferase activities of both genes and type I collagen marker were elevated at 72 h. TGF-{beta}1 mRNA was elevated earlier than those of type I collagen genes. A Western blot analysis showed the elevation of Smad phosphorylation at 72 h. Conversely, treatment with TGF-{beta} receptor inhibitor inhibited the mRNA and relative luciferase activity of type I collagen. The phosphorylation of Smad was repressed with the inhibitor, and the luciferase activity was cancelled using a mutant construct of Smad binding site of {alpha}2(I) collagen gene. However, the MAPK pathways, p38, ERK1/2 and JNK, were not affected with specific inhibitors or siRNA. The data showed that the Smad pathway mediated the expression of type I collagen in radiation induced fibrosis.

  8. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    SciTech Connect

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-08-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-{alpha}, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-{alpha}, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

  9. Radiation-induced formation, annealing and ordering of voids in crystals: Theory and experiment

    NASA Astrophysics Data System (ADS)

    Dubinko, V. I.; Guglya, A. G.; Donnelly, S. E.

    2011-07-01

    Void ordering has been observed in very different radiation environments ranging from metals to ionic crystals bombarded with energetic particles. The void ordering is often accompanied by a saturation of the void swelling with increasing irradiation dose, which makes an understanding of the underlying mechanisms to be both of scientific significance and of practical importance for nuclear engineering. We show that both phenomena can be explained by the original mechanism based on the anisotropic energy transfer provided by self-focusing discrete breathers or quodons (energetic, mobile, highly localized lattice solitons that propagate great distances along close-packed crystal directions). The interaction of quodons with voids can result in radiation-induced “annealing” of selected voids, which results in the void ordering under special irradiation conditions. We observe experimentally radiation-induced void annealing by lowering the irradiation temperature of nickel and copper samples pre-irradiated to produce voids or gas bubbles. The bulk recombination of Frenkel pairs increases with decreasing temperature resulting in suppression of the production of freely migrating vacancies (the driving force of the void growth). On the other hand, the rate of radiation-induced vacancy emission from voids due to the void interaction with quodons remains essentially unchanged, which results in void dissolution. The experimental data on the void shrinkage and void lattice formation obtained for different metals and irradiating particles are explained by the present model assuming the quodon propagation length to be in the micron range, which is consistent with independent data on the irradiation-induced diffusion of interstitial ions in austenitic stainless steel.

  10. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    PubMed Central

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Luijk, Peter Van

    2014-01-01

    Abstract Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for restoring functionality to the irradiated tissue bed. Recent Advances: Preclinical studies presented in this review provide encouraging proof of concept regarding the therapeutic potential of stem cells for treating the adverse side effects associated with radiotherapy in different organs. Early-stage clinical data for radiation-induced lung, bone, and skin complications are promising and highlight the importance of selecting the appropriate stem cell type to stimulate tissue regeneration. Critical Issues: While therapeutic efficacy has been demonstrated in a variety of animal models and human trials, a range of additional concerns regarding stem cell transplantation for ameliorating radiation-induced normal tissue sequelae remain. Safety issues regarding teratoma formation, disease progression, and genomic stability along with technical issues impacting disease targeting, immunorejection, and clinical scale-up are factors bearing on the eventual translation of stem cell therapies into routine clinical practice. Future Directions: Follow-up studies will need to identify the best possible stem cell types for the treatment of early and late radiation-induced normal tissue injury. Additional work should seek to optimize cellular dosing regimes, identify the best routes of administration, elucidate optimal transplantation windows for introducing cells into more receptive host tissues, and improve immune tolerance for longer-term engrafted cell survival into the irradiated microenvironment. Antioxid. Redox Signal. 21: 338–355. PMID:24147585

  11. Protection of DNA From Ionizing Radiation-Induced Lesions by Asiaticoside.

    PubMed

    Joy, Jisha; Alarifi, Saud; Alsuhaibani, Entissar; Nair, Cherupally K Krishnan

    2015-01-01

    This study aims to investigate whether asiaticoside, a triterpene glycoside, can afford protection to DNA from alterations induced by gamma radiation under in vitro, ex vivo, and in vivo conditions. In vitro studies were done on plasmid pBR322 DNA, ex vivo studies were done on cellular DNA of human peripheral blood leukocytes, and in vivo investigations were conducted on cellular DNA of spleen and bone marrow cells of mice exposed to whole-body gamma radiation. The supercoiled form of the plasmid pBR322 DNA upon exposure to the radiation was converted into relaxed open circular form due to induction of strand breaks. Presence of asiaticoside along with the DNA during irradiation prevented the relaxation of the supercoiled form to the open circular form. When human peripheral blood leukocytes were exposed to gamma radiation, the cellular DNA suffered strand breaks as evidenced by the increased comet parameters in an alkaline comet assay. Asiaticoside, when present along with blood during irradiation ex vivo, prevented the strand breaks and the comet parameters were closer to that of the controls. Whole-body exposure of mice to gamma radiation resulted in a significant increase in comet parameters of DNA of bone marrow and spleen cells of mice as a result of radiation-induced strand breaks in DNA. Administration of asiaticoside prior to whole-body radiation exposure of the mice prevented this increase in radiation-induced increase in comet parameters, which could be the result of protection to DNA under in vivo conditions of radiation exposure. Thus, it can be concluded from the results that asiaticoside can offer protection to DNA from radiation-induced alterations under in vitro, ex vivo, and in vivo conditions. PMID:26756427

  12. Radiation-Induced Reduction of Ceria in Single and Polycrystalline Thin Films

    SciTech Connect

    Kumar, Amit; Devanathan, Ramaswami; Shutthanandan, V.; Kuchibhatla, Satyanarayana V N T; Karakoti, Ajay S.; Yang, Yong; Thevuthasan, Suntharampillai; Seal, Sudipta

    2012-01-12

    Ceria (CeO{sub 2}) is a technologically important ceramic material with a wide range of neoteric applications in catalysis, solid oxide fuel cells, oxygen gas sensors, hydrogen production, and ultraviolet shielding. Recent research has revealed promising biomedical applications of ceria. Nanoparticles of ceria have been shown to protect healthy cells from radiation-induced cellular damage. The mechanisms governing the radioprotection characteristics of ceria nanoparticles are not well understood and it has been hypothesized that reversible switching between Ce{sup 4+} and Ce{sup 3+} states may enable ceria nanoparticles to mop up free radicals.

  13. Protective effects of L-selenomethionine on space radiation induced changes in gene expression.

    PubMed

    Stewart, J; Ko, Y-H; Kennedy, A R

    2007-06-01

    Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of L-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 microM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have

  14. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury

    PubMed Central

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-01-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5+ (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5+ cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in abdominally

  15. Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in IMRT for Nasopharyngeal Cancer

    SciTech Connect

    Lee, Victor H.F.; Ng, Sherry C.Y.; Leung, T.W.; Au, Gordon K.H.; Kwong, Dora L.W.

    2012-09-01

    Purpose: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC). Methods and Materials: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression. Results: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis. Conclusions: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs, and

  16. Immobilization of yeast cells on hydrogel carriers obtained by radiation-induced polymerization

    NASA Astrophysics Data System (ADS)

    Xin, Lu Zhao; Carenza, Mario; Kaetsu, Isao; Kumakura, Minoru; Yoshida, Masaru; Fujimura, Takashi

    Polymer hydrogels were obtained by radiation-induced copolymerization at -78°C of aqueous solutions of acrylic and methacrylic esters. The matrices were characterized by equilibrium water content measurements, by optical microscopy observations and by scanning electron microscopy analysis. Yeast cells were immobilized on these hydrogels and the ethanol productivity by batch fermentation was determined. Matrix hydrophilicity and porosity were found to deeply influence the adhesion of yeast cells and, hence, the ethanol productivity. The latter as well as other physico-chemical properties were also affected by the presence of a crosslinking agent added in small amounts to the polymerizing mixture.

  17. Radiation-induced meningiomas after BNCT in patients with malignant glioma.

    PubMed

    Kageji, T; Sogabe, S; Mizobichi, Y; Nakajima, K; Shinji, N; Nakagawa, Y

    2015-12-01

    Of the 180 patients with malignant brain tumors whom we treated with boron neutron capture therapy (BNCT) since 1968, only one (0.56%) developed multiple radiation-induced meningiomas. The parasagittal meningioma that had received 42 Gy (w) for BNCT showed more rapid growth on Gd-enhanced MRI scans and more atypical features on histopathologic studies than the temporal convexity tumor that had received 20 Gy (w). Long-term follow up MRI studies are necessary in long-survivors of malignant brain tumors treated by BNCT. PMID:26122975

  18. Observation of linear-polarization-sensitivity in the microwave-radiation-induced magnetoresistance oscillations

    SciTech Connect

    Mani, R. G.; Ramanayaka, A. N.; Wegscheider, W.

    2013-12-04

    We examine the linear polarization sensitivity of the radiation- induced magneto-resistance oscillations by investigating the effect of rotating in-situ the electric field of linearly polarized microwaves relative to the current, in the GaAs/AlGaAs system. We find that the frequency and the phase of the photo-excited magneto-resistance oscillations are insensitive to the polarization. On the other hand, the amplitude of the resistance oscillations are strongly sensitive to the relative orientation between the microwave antenna and the current-axis in the specimen.

  19. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    NASA Astrophysics Data System (ADS)

    Pandey, B. N.; Lathika, K. M.; Mishra, K. P.

    2006-03-01

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after γ-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  20. Radiation induced failures of complementary metal oxide semiconductor containing pacemakers: a potentially lethal complication

    SciTech Connect

    Lewin, A.A.; Serago, C.F.; Schwade, J.G.; Abitbol, A.A.; Margolis, S.C.

    1984-10-01

    New multi-programmable pacemakers frequently employ complementary metal oxide semiconductors (CMOS). This circuitry appears more sensitive to the effects of ionizing radiation when compared to the semiconductor circuits used in older pacemakers. A case of radiation induced runaway pacemaker in a CMOS device is described. Because of this and other recent reports of radiation therapy-induced CMOS type pacemaker failure, these pacemakers should not be irradiated. If necessary, the pacemaker can be shielded or moved to a site which can be shielded before institution of radiation therapy. This is done to prevent damage to the CMOS circuit and the life threatening arrythmias which may result from such damage.

  1. Protective effects of L-selenomethionine on space radiation induced changes in gene expression.

    PubMed

    Stewart, J; Ko, Y-H; Kennedy, A R

    2007-06-01

    Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of L-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 microM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have

  2. Radiation-induced electrical breakdown of helium in fusion reactor superconducting magnet systems

    SciTech Connect

    Perkins, L.J.

    1983-12-02

    A comprehensive theoretical study has been performed on the reduction of the electrical breakdown potential of liquid and gaseous helium under neutron and gamma radiation. Extension of the conventional Townsend breakdown theory indicates that radiation fields at the superconducting magnets of a typical fusion reactor are potentially capable of significantly reducing currently established (i.e., unirradiated) helium breakdown voltages. Emphasis is given to the implications of these results including future deployment choices of magnet cryogenic methods (e.g., pool-boiling versus forced-flow), the possible impact on magnet shielding requirements and the analogous situation for radiation-induced electrical breakdown in fusion RF transmission systems.

  3. Rubber products prepared from silica modified by radiation-induced admicellar polymerization

    NASA Astrophysics Data System (ADS)

    Pongprayoon, Thirawudh; Yooprasert, Narissara; Suwanmala, Phiriyatorn; Hemvichian, Kasinee

    2012-05-01

    Unmodified silica, silica modified with Si69, silica modified by thermal admicellar polymerization and silica modified by radiation-induced admicellar polymerization were applied as rubber reinforcement. Mechanical properties of these different rubber formulae were subsequently tested. The results revealed that the mechanical properties of rubber reinforced with silica modified by admicellar polymerization were superior to those reinforced with unmodified silica or silica modified with Si69. As for the silica modified by admicellar polymerization, cetyltrimethyl ammonium bromide (CTAB) proved to be the most effective surfactant, compared to dodecyltrimethyl ammonium bromide (DTAB) and tetradecyltrimethyl ammonium bromide (TTAB).

  4. Summary of round robin measurements of radiation induced conductivity in Wesgo AL995 alumina

    SciTech Connect

    Zinkle, S.J.

    1996-10-01

    This existing data on radiation induced conductivity (RIC) measurements performed on the same heat of the IEA reference ceramic insulator are summarized. Six different sets of RIC measurements have been performed on Wesgo AL995 at dose rates between 10 Gy/s and 1 MGy/s. In general, good agreement was obtained between the different groups of researchers. The data indicate that the RIC at a test temperature of 400-500{degrees}C is approximately linear with ionizing dose rate up to {approximately}1000 Gy/s, and exhibits an approximately square root dependence on dose rate between 1 kGy/s and 1 MGy/s.

  5. [Radiation-induced changes in structural state of membranes of human blood cells].

    PubMed

    Burlakova, E B; Atkarskaia, M V; Fatkullina, L D; Andreev, S G

    2014-01-01

    To evaluate radiation-induced changes in the structural state of the membranes, blood samples of healthy donors were subjected to gamma radiation in the range of small (1-10 cGy) and medium doses (50 cGy-2 Gy). After irradiation, the microviscosity of lipid membranes of red and white blood cells was measured by ESR spin probe method. At doses exceeding 1 cGy, statistically significant changes of the degree of spontaneous erythrocyte hemolysis and of the lymphocyte plasma membrane microviscosity were observed. Under identical irradiation conditions, the stability of lymphocyte membranes was less as compared to erythrocyte membranes.

  6. Reversal of gamma-radiation-induced leukemogenesis in mice by immunomodulation with thiabendazole and dinitrofluorobenzene

    SciTech Connect

    Elgebaly, S.A.; Barton, R.; Forouhar, F.

    1985-04-01

    The effect of thiabendazole (TBZ) and dinitrofluorobenzene (DNFB) on radiation-induced leukemogenesis was investigated in the C57BL/6 mouse model. Administration of TBZ-DNFB during, post, or during and post irradiation successfully blocked leukemogenesis, as indicated by the absence of leukemia blast cells in thymus and peripheral blood, as well as prevented thymic lymphoma. TBZ-DNFB treatment prevented the development of leukemia when studies were terminated both after 7 months of last irradiation (disease fully developed) and after 5 months of last irradiation (disease in the process of development). This TBZ-DNFB treatment also resulted in a significant increase in survival.

  7. Radiation induced dechlorination of some chlorinated hydrocarbons in aqueous suspensions of various solid particles

    NASA Astrophysics Data System (ADS)

    Múčka, V.; Buňata, M.; Čuba, V.; Silber, R.; Juha, L.

    2015-07-01

    Radiation induced dechlorination of trichloroethylene (TCE) and tetrachloroethylene (PCE) in aqueous solutions containing the active carbon (AC) or cupric oxide (CuO) as the modifiers was studied. The obtained results were compared to the previously studied dechlorination of polychlorinated biphenyls (PCBs). Both modifiers were found to decrease the efficiency of dechlorination. The AC modifier acts mainly via adsorption of the aliphatic (unlike the aromatic) hydrocarbons and the CuO oxide mainly inhibits the mineralization of the perchloroethylene. The results presented in this paper will be also helpful for the studies of the impact of chlorinated hydrocarbons on the membrane permeability of living cells.

  8. Bias control of long term radiation-induced transients in GaAs MESFETs

    NASA Astrophysics Data System (ADS)

    Casey, R. H.; Herman, W. N.; Lacombe, D. J.; Ragonese, L. J.; Immorlica, A.

    1988-12-01

    The effect of guard-ring bias and self-bias on radiation-induced long-term transients in GaAs D-MESFETs was measured for dose rates up to 1 Trad(GaAs)/sec. Results are presented for both ohmic and Schottky guard rings, with the substrate-bottom grounded as well as separately biased. Significant reduction in recovery times and transient amplitudes suggests that these are viable radiation-hardening techniques, allowing less dependence on the device fabrication process.

  9. The influence of infrared radiation on short-term ultraviolet-radiation-induced injuries

    SciTech Connect

    Kaidbey, K.H.; Witkowski, T.A.; Kligman, A.M.

    1982-05-01

    Because heat has been reported to influence adversely short- and long-term ultraviolet (UV)-radiation-induced skin damage in animals, we investigated the short-term effects of infrared radiation on sunburn and on phototoxic reactions to topical methoxsalen and anthracene in human volunteers. Prior heating of the skin caused suppression of the phototoxic response to methoxsalen as evidenced by an increase in the threshold erythema dose. Heat administered either before or after exposure to UV radiation had no detectable influence on sunburn erythema or on phototoxic reactions provoked by anthracene.

  10. β-Arrestin-2 modulates radiation-induced intestinal crypt progenitor/stem cell injury.

    PubMed

    Liu, Z; Tian, H; Jiang, J; Yang, Y; Tan, S; Lin, X; Liu, H; Wu, B

    2016-09-01

    Intestinal crypt progenitor/stem (ICPS) cell apoptosis and vascular endothelial cell apoptosis are responsible for the initiation and development of ionizing radiation (IR)-evoked gastrointestinal syndrome. The signaling mechanisms underlying IR-induced ICPS cell apoptosis remain largely unclear. Our findings provide evidence that β-arrestin-2 (βarr2)-mediated ICPS cell apoptosis is crucial for IR-stimulated intestinal injury. βArr2-deficient mice exhibited decreased ICPS cell and intestinal Lgr5(+) (leucine-rich repeat-containing G-protein-coupled receptor 5-positive) stem cell apoptosis, promoted crypt proliferation and reproduction, and protracted survival following lethal doses of radiation. Radioprotection in the ICPS cells isolated from βarr2-deficient mice depended on prolonged nuclear factor-κB (NF-κB) activation via direct interaction of βarr2 with IκBα and subsequent inhibition of p53-upregulated modulator of apoptosis (PUMA)-mediated mitochondrial dysfunction. Unexpectedly, βarr2 deficiency had little effect on IR-induced intestinal vascular endothelial cell apoptosis in mice. Consistently, βarr2 knockdown also provided significant radioresistance by manipulating NF-κB/PUMA signaling in Lgr5(+) cells in vitro. Collectively, these observations show that targeting the βarr2/NF-κB/PUMA novel pathway is a potential radiomitigator for limiting the damaging effect of radiotherapy on the gastrointestinal system. Significance statement: acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiotherapy. The issue of whether the critical factor for the initiation of radiation-induced intestinal injury is intestinal stem cell apoptosis or endothelial cell apoptosis remains unresolved. βArrs have recently been found to be multifunctional adaptor of apoptosis. Here, we found that β-arrestin-2 (βarr2) deficiency was associated with decreased radiation-induced ICPS cell apoptosis, which prolonged survival in

  11. A review on radiation-induced nucleation and growth of colloidal metallic nanoparticles.

    PubMed

    Abedini, Alam; Daud, Abdul Razak; Abdul Hamid, Muhammad Azmi; Kamil Othman, Norinsan; Saion, Elias

    2013-01-01

    This review presents an introduction to the synthesis of metallic nanoparticles by radiation-induced method, especially gamma irradiation. This method offers some benefits over the conventional methods because it provides fully reduced and highly pure nanoparticles free from by-products or chemical reducing agents, and is capable of controlling the particle size and structure. The nucleation and growth mechanism of metallic nanoparticles are also discussed. The competition between nucleation and growth process in the formation of nanoparticles can determine the size of nanoparticles which is influenced by certain parameters such as the choice of solvents and stabilizer, the precursor to stabilizer ratio, pH during synthesis, and absorbed dose.

  12. Remote sensor response study in the regime of the microwave radiation-induced magnetoresistance oscillations

    SciTech Connect

    Ye, Tianyu; Mani, R. G.; Wegscheider, W.

    2013-11-04

    A concurrent remote sensing and magneto-transport study of the microwave excited two dimensional electron system (2DES) at liquid helium temperatures has been carried out using a carbon detector to remotely sense the microwave activity of the 2D electron system in the GaAs/AlGaAs heterostructure during conventional magneto-transport measurements. Various correlations are observed and reported between the oscillatory magnetotransport and the remotely sensed reflection. In addition, the oscillatory remotely sensed signal is shown to exhibit a power law type variation in its amplitude, similar to the radiation-induced magnetoresistance oscillations.

  13. The effects of hyper velocity impact phenomena on radiation induced defects

    NASA Astrophysics Data System (ADS)

    Yamanaka, C.; Ikeya, M.

    1994-06-01

    Effects of high speed impacts on radiation-induced defects were investigated with a plasma rail-gun. Vitreous quartz targets irradiated by γ-ray were shocked with polycarbonate projectiles at a speed of 7 km/s, then the remaining destroyed pieces were examined by ESR spectroscopy to investigate the degree of "impact-annealing". The white substance from the impact point showed a trace of melting and no ESR signal, while the rest of the scattered pieces showed a decrease of E' center density to 50 ± 10% of the initial density. The defect production efficiency for the impacted silica was almost two-third of the original material.

  14. Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study

    SciTech Connect

    Wong, Raimond K.W.; Deshmukh, Snehal; Wyatt, Gwen; Sagar, Stephen; Singh, Anurag K.; Sultanem, Khalil; Nguyen-Tân, Phuc F.; Yom, Sue S.; Cardinale, Joseph; Yao, Min; Hodson, Ian; Matthiesen, Chance L.; Suh, John; Thakrar, Harish; Pugh, Stephanie L.; Berk, Lawrence

    2015-06-01

    Purpose and Objectives: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Methods and Materials: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. Results: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were −0.53 and −0.27 (P=.45) and −0.6 and −0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. Conclusions: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint—the change in radiation-induced xerostomia symptom burden at 9 MFR—was not significantly different between the ALTENS and PC groups. There was significantly less

  15. Protective Role of Rheum Tanguticum Polysaccharide 1 in Radiation- induced Intestinal Mucosal Injury

    PubMed Central

    Liu, Lin-Na; Shi, Lei; Li, Shi-Cao; Zhang, Wen-Juan; Zhang, Yan; Zhang, Zhi-Pei

    2015-01-01

    The protective effects of Rheum tanguticum polysaccharide 1 (RTP1), which is extracted from the Chinese traditional medicine Rheum tanguticum, on radiation-induced intestinal mucosal injury was investigated. Rat intestinal crypt epithelial cells (IEC-6 cells) and Sprague-Dawley rats were each divided into control, irradiated and RTP1-pretreated irradiated groups. After irradiation, cell survival was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide). assay, and the intracellular reactive oxygen species (ROS) was detected by fluorescent probe method. Apoptosis was observed by acridine orange staining, and cell cycle was analysed by flow cytometry. Histological analysis of the rat intestinal mucosa was conducted by haematoxylin and eosin staining. Irradiation at 8 Gy(Gray) decreased cell survival rate to only 54%, significantly increased intracellular ROS levels and induced apoptosis. RTP1 pretreatment significantly inhibited cell death, reduced the formation of intracellular ROS and partially inhibited apoptosis. Irradiation markedly reduced the height and quantity of rat intestinal villi, but it could be antagonised by RTP1 pretreatment. RTP1 can promote the recovery of intestinal mucosa damage, possibly by inhibiting radiation-induced intestinal epithelial apoptosis and intracellular ROS production. PMID:26330871

  16. Prevention effects of Schisandra polysaccharide on radiation-induced immune system dysfunction.

    PubMed

    Zhao, Lian-Mei; Jia, Yun-Long; Ma, Ming; Duan, Yu-Qing; Liu, Li-Hua

    2015-05-01

    In this study, we investigate the efficacy of SP (Schisandra polysaccharide) in prevention of radiation-induced immune dysfunction and discussed the underlying mechanisms with a Bal/bc mouse model. The data demonstrated that SP could reverse the decreases in the number of white blood cells and lymphocytes in peripheral blood. In addition, the immunoglobulin G (IgG) and complement C3 in blood serum were all decreased after radiation and SP could restore this radiation disorder. Furthermore, SP could reverse the deregulation of CD3(+)CD4(+) and CD3(+)CD8(+) T cell subsets in peripheral blood and thymus of mice after radiotherapy. We also performed terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and Immunohistochemistry (IHC) to investigate the apoptosis and underlying mechanisms of SP in thymus. Data showed that radiation-induced apoptosis of thymocytes could be reversed by SP through inducing upregulation of Bcl-2 expression and downregulation of Fas and Bax levels. Furthermore, SP has no any side-effects on immunity of normal mice. In conclusion, our results indicated that SP could effectively prevent immune injury during radiotherapy by protecting the immune system. This valuable information should be of assistance in choosing a rational design for therapeutic interventions of prevention immune system damage in the radiation treatment.

  17. Proximity within interphase chromosome contributes to the breakpoint distribution in radiation-induced intrachromosomal exchanges

    NASA Astrophysics Data System (ADS)

    Zhang, Ye; Uhlemeyer, Jimmy; Hada, Megumi; Asaithamby, A.; Chen, David J.; Wu, Honglu

    2014-07-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome 3 in human mammary epithelial cells after exposures to either low- or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome 3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations.

  18. Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome

    PubMed Central

    Takemura, Naoki; Kawasaki, Takumi; Kunisawa, Jun; Sato, Shintaro; Lamichhane, Aayam; Kobiyama, Kouji; Aoshi, Taiki; Ito, Junichi; Mizuguchi, Kenji; Karuppuchamy, Thangaraj; Matsunaga, Kouta; Miyatake, Shoichiro; Mori, Nobuko; Tsujimura, Tohru; Satoh, Takashi; Kumagai, Yutaro; Kawai, Taro; Standley, Daron M.; Ishii, Ken J.; Kiyono, Hiroshi; Akira, Shizuo; Uematsu, Satoshi

    2014-01-01

    High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. Tlr3−/− mice show substantial resistance to GIS owing to significantly reduced radiation-induced crypt cell death. Despite showing reduced crypt cell death, p53-dependent crypt cell death is not impaired in Tlr3−/− mice. p53-dependent crypt cell death causes leakage of cellular RNA, which induces extensive cell death via TLR3. An inhibitor of TLR3–RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS. PMID:24637670

  19. Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis

    PubMed Central

    Yang, Yanyong; Li, Bailong; Liu, Cong; Chuai, Yunhai; Lei, Jixiao; Gao, Fu; Cui, Jianguo; Sun, Ding; Cheng, Ying; Zhou, Chuanfeng; Cai, Jianming

    2012-01-01

    Summary Background Radiation often causes depletion of immunocytes in tissues and blood, which results in immunosuppression. Molecular hydrogen (H2) has been shown in recent studies to have potential as a safe and effective radioprotective agent through scavenging free radicals. This study was designed to test the hypothesis that H2 could protect immunocytes from ionizing radiation (IR). Material/Methods H2 was dissolved in physiological saline or medium using an apparatus produced by our department. A 2-[6-(4′-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe was used to detect intracellular hydroxyl radicals (•OH). Cell apoptosis was evaluated by annexin V-FITC and Propidium iodide (PI) staining as well as the caspase 3 activity. Finally, we examined the hematological changes using an automatic Sysmex XE 2100 hematology analyzer. Results We demonstrated H2-rich medium pretreatment reduced •OH level in AHH-1 cells. We also showed H2 reduced radiation-induced apoptosis in thymocytes and splenocytes in living mice. Radiation-induced caspase 3 activation was also attenuated by H2 treatment. Finally, we found that H2 rescued the radiation-caused depletion of white blood cells (WBC) and platelets (PLT). Conclusions This study suggests that H2 protected the immune system and alleviated the hematological injury induced by IR. PMID:22460088

  20. A biological approach to the interspecies prediction of radiation-induced mortality risk

    SciTech Connect

    Carnes, B.A.; Grahn, D.; Olshansky, S.J.

    1997-08-01

    Evolutionary explanations for why sexually reproducing organisms grow old suggest that the forces of natural selection affect the ages when diseases occur that are subject to a genetic influence (referred to here as intrinsic diseases). When extended to the population level for a species, this logic leads to the general prediction that age-specific death rates from intrinsic causes should begin to rise as the force of selection wanes once the characteristic age of sexual maturity is attained. Results consistent with these predictions have been found for laboratory mice, beagles, and humans where, after adjusting for differences in life span, it was demonstrated that these species share a common age pattern of mortality for intrinsic causes of death. In quantitative models used to predict radiation-induced mortality, risks are often expressed as multiples of those observed in a control population. A control population, however, is an aging population. As such, mortality risks related to exposure must be interpreted relative to the age-specific risk of death associated with aging. Given the previous success in making interspecies predictions of age-related mortality, the purpose of this study was to determine whether radiation-induced mortality observed in one species could also be predicted quantitatively from a model used to describe the mortality consequences of exposure to radiation in a different species. Mortality data for B6CF{sub 1} mice and beagles exposed to {sup 60}Co {gamma}-rays for the duration of life were used for analysis.

  1. Astragalus polysaccharide ameliorates ionizing radiation-induced oxidative stress in mice.

    PubMed

    Liu, Yao; Liu, Fang; Yang, Ya; Li, Di; Lv, Jun; Ou, Yangjin; Sun, Fengjun; Chen, Jianhong; Shi, Ying; Xia, Peiyuan

    2014-07-01

    Radioprotective compounds from plant resources may represent safe and cost-effective prophylactic and therapeutic agents. This study was designed to investigate the protective effect of polysaccharide derived from the dried roots of the Astragalus spp. (APS) against ionizing radiation (IR) injury in liver and to explore its role in radiation-induced oxidative stress using a mouse model. Prior to (60)Co γ-irradiation (5Gy, single dose), mice received 7 days of APS at low, mid and high doses (50, 100 or 200mg/kg/day, respectively; n=6 each group), vehicle alone (5mL normal saline orally/daily; n=6). A non-irradiated control group (n=6) received the 7-day distilled water regimen only. At 24h post-irradiation, the APS pre-treated mice showed significantly decreased alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase levels, and NF-κB expression. All APS-treated mice also showed attenuation of the IR-induced increase in thiobarbituric acid reactive substance and resolution of the IR-induced decreases in superoxide dismutase, catalase and glutathione activities (all p<0.05). High dose APS pre-treatment led to remarkably less morphologic features of IR-induced hepatic and pulmonary injury. Thus, APS exerts protective effects against IR-induced injury in liver in mice, and the related molecular mechanism may involve suppressing the radiation-induced oxidative stress reaction. PMID:24820157

  2. Investigation of radiation-induced free radicals and luminescence properties in fresh pomegranate fruits.

    PubMed

    Shahbaz, Hafiz M; Akram, Kashif; Ahn, Jae-Jun; Kwon, Joong-Ho

    2013-05-01

    Radiation-induced free radicals and luminescence properties were investigated in γ-irradiated (0-3 kGy) pomegranate ( Punica granatum L.) fruits. Photostimulated luminescence (PSL) analysis showed limited applicability, and only 3 kGy-irradiated pomegranates showed positive PSL values (>5000 PCs). Thermoluminescence (TL) glow curve features, such as intensity and the presence of maximum glow peak in radiation-specific temperature range (150-250 °C), provided definite proof of irradiation, and the TL ratios (TL1/TL2) also confirmed the reliability of TL results. Scanning electron microscopy energy dispersive X-ray (SEM-EDX) analysis of the separated minerals showed that feldspar and quartz minerals were responsible for the luminescence properties. Radiation-induced cellulose radicals were detected in the seeds and rinds by ESR analysis. The ESR results were better in freeze-dried samples than in alcohol-extracted ones. A positive correlation was found between the ESR and TL signal intensities and irradiation doses; however, the most promising detection of the irradiation status was possible through TL analysis.

  3. Radiofrequency radiation-induced calcium ion efflux enhancement from human and other neuroblastoma cells in culture.

    PubMed

    Dutta, S K; Ghosh, B; Blackman, C F

    1989-01-01

    To test the generality of radiofrequency radiation-induced changes in 45Ca2+ efflux from avian and feline brain tissues, human neuroblastoma cells were exposed to electromagnetic radiation at 147 MHz, amplitude-modulated (AM) at 16 Hz, at specific absorption rates (SAR) of 0.1, 0.05, 0.01, 0.005, 0.001, and 0.0005 W/kg. Significant 45Ca2+ efflux was obtained at SAR values of 0.05 and 0.005 W/kg. Enhanced efflux at 0.05 W/kg peaked at the 13-16 Hz and at the 57.5-60 Hz modulation ranges. A Chinese hamster-mouse hybrid neuroblastoma was also shown to exhibit enhanced radiation-induced 45Ca2+ efflux at an SAR of 0.05 W/kg, using 147 MHz, AM at 16 Hz. These results confirm that amplitude-modulated radiofrequency radiation can induce responses in cells of nervous tissue origin from widely different animal species, including humans. The results are also consistent with the reports of similar findings in avian and feline brain tissues and indicate the general nature of the phenomenon. PMID:2540756

  4. Investigation of radiation-induced free radicals and luminescence properties in fresh pomegranate fruits.

    PubMed

    Shahbaz, Hafiz M; Akram, Kashif; Ahn, Jae-Jun; Kwon, Joong-Ho

    2013-05-01

    Radiation-induced free radicals and luminescence properties were investigated in γ-irradiated (0-3 kGy) pomegranate ( Punica granatum L.) fruits. Photostimulated luminescence (PSL) analysis showed limited applicability, and only 3 kGy-irradiated pomegranates showed positive PSL values (>5000 PCs). Thermoluminescence (TL) glow curve features, such as intensity and the presence of maximum glow peak in radiation-specific temperature range (150-250 °C), provided definite proof of irradiation, and the TL ratios (TL1/TL2) also confirmed the reliability of TL results. Scanning electron microscopy energy dispersive X-ray (SEM-EDX) analysis of the separated minerals showed that feldspar and quartz minerals were responsible for the luminescence properties. Radiation-induced cellulose radicals were detected in the seeds and rinds by ESR analysis. The ESR results were better in freeze-dried samples than in alcohol-extracted ones. A positive correlation was found between the ESR and TL signal intensities and irradiation doses; however, the most promising detection of the irradiation status was possible through TL analysis. PMID:23565691

  5. Geraniin down regulates gamma radiation-induced apoptosis by suppressing DNA damage.

    PubMed

    Bing, So Jin; Ha, Danbee; Kim, Min Ju; Park, Eunjin; Ahn, Ginnae; Kim, Dae Seung; Ko, Ryeo Kyeong; Park, Jae Woo; Lee, Nam Ho; Jee, Youngheun

    2013-07-01

    Gamma ray irradiation triggers DNA damage and apoptosis of proliferating stem cells and peripheral immune cells, resulting in the destruction of intestinal crypts and lymphoid system. Geraniin is a natural compound extracts from an aquatic plant Nymphaea tetragona and possesses good antioxidant property. In this study, we demonstrate that geraniin rescues radiosensitive splenocytes and jejunal crypt cells from radiation-induced DNA damage and apoptosis. Isolated splenocytes from C57BL/6 mice treated with geraniin were protected against radiation injury of 2 Gy irradiation through the enhancement of the proliferation and attenuation of DNA damage. Also, geraniin inhibited apoptosis in radiosensitive splenocytes by reducing the expression level and immunoreactivity of proapoptotic p53 and Bax and increasing those of anti-apoptotic Bcl-2. In mice exposed to radiation, geraniin treatment protected splenocytes and intestinal crypt cells from radiation-induced cell death. Our results suggest that geraniin presents radioprotective effects by regulating DNA damage on splenocytes, exerting immunostimulatory capacities and inhibiting apoptosis of radiosensitive immune cells and jejunal crypt cells. Therefore, geraniin can be a radioprotective agent against γ-irradiation exposure.

  6. Radiation-induced electrical degradation experiments in the Japan materials testing reactor

    NASA Astrophysics Data System (ADS)

    Farnum, Eugene H.; Shikama, Tatsuo; Narui, Minoru; Sagawa, Tsutomu; Scarborough, Kent

    1996-02-01

    An experiment to measure radiation-induced electrical degradation (RIED) in a sapphire sample and in three MgO-insulated cables was conducted at the JMTR light water reactor. The materials were irradiated at about 260°C to a fluence of 3 × 1024 n/m 2 ( E > 1 MeV) with an applied DC electric field between 100 kV/m and 500 kV/m. Even though the results for the sapphire sample are somewhat ambiguous because of an unexplained offset current of about 0.6 μA substantial degradation was not observed in the sapphire: instead, radiation-induced conductivity (RIC) seemed to decrease slightly during the experiment. Substantial increase in leakage current, that increased with applied electric field, occurred in the MgO-insulated cables. This increased conductivity disappeared when the reactor was shut down and sample temperature returned to ambient. However, the physical degradation apparently remained in the material while the reactor was off because restarting the irradiation brought the conductivity back to its previous, degraded, reactor-on value. This effect is different from the RIED effect reported by Hodgson but is similar to previous results reported by Shikama et al. Considerable data were taken to determine the sample temperature and leakage currents during the irradiation.

  7. Radiation-induced loss of unsaturation in 1,2-polybutadiene

    NASA Technical Reports Server (NTRS)

    Golub, M. A.; Cormia, R. D.

    1982-01-01

    The radiation induced loss of unsaturation and methyl production in 1,2-polybutadiene (VB) was studied using IR spectroscopy. It was found that G(-1,2), which depends on the initial vinyl content, decreased from approximately 550 for VB with 98.5% 1,2 initially, to approximately 270 for VB with 85% 1,2 initially. G(-trans-1,4) ranged from approximately 21 for VB with 14% trans-1,4 to nearly zero for VB with less than 1% trans-1,4 initially. Methyl production was found to equal one methyl group formed for every 4-5 vinyl units consumed in the radiation-cyclized VB, in contrast to one methyl formed for every two vinyls reacted during cationic cyclization to give monocyclic structures. The IR spectra of gamma-irradiated VB were very similar to the spectra of UV-irradiated or thermally-treated VB at the same residual vinyl contents. It is suggested that the radiation-induced cyclization of VB occurs by a nonionic, nonradical 'energy chain' mechanism, which apparently holds for the cyclization of VB, whether induced by gamma-rays, UV radiation, or heat.

  8. The Role of Alveolar Epithelium in Radiation-Induced Lung Injury

    PubMed Central

    Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

    2013-01-01

    Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11–13 Gy) and fractionated doses (24–36 Gy) of 137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis. PMID:23326473

  9. Ultraviolet radiation-induced apoptosis in keratinocytes: on the role of cytosolic factors.

    PubMed

    Assefa, Zerihun; Van Laethem, An; Garmyn, Marjan; Agostinis, Patrizia

    2005-07-25

    Epidemiological and experimental evidences have established solar ultraviolet (UV) radiation as the leading cause of skin cancers. Specifically, the frequency of non-melanoma skin cancer, one of the malignancies with the most rapidly increasing incidence, is directly related to the total exposure to solar UV light. As part of a general effort to elucidate the components of cellular signal transduction pathways, the mechanisms of cellular responses to UV radiation have received considerable attention over the last few years. These efforts were driven mainly by the conviction that understanding how normal cells respond to extracellular stimuli such as exposure to UV radiation will undoubtedly help in deciphering what goes wrong in a variety of clinical disorders including skin cancers and will assist in the development of novel therapeutic strategies. Studies over the last decade have established that UV radiation induces a bewildering array of signal transduction pathways, some of which could lead to apoptotic cell death. UV-induced cell death by apoptosis is considered to be a natural protective mechanism that removes damaged keratinocytes and circumvents the risk of malignant transformation. In this review, we summarize some of the most important findings regarding the response and role of mitogen-activated protein kinases in UVA and UVB radiation-induced signaling to apoptosis in keratinocytes. We will also briefly discuss what is known about the role of the BCL-2 family of proteins, the emerging role of lysosomal proteases and other important cytosolic signaling proteins in UV-induced apoptosis.

  10. A non-human primate model of radiation-induced cachexia

    PubMed Central

    Cui, Wanchang; Bennett, Alexander W.; Zhang, Pei; Barrow, Kory R.; Kearney, Sean R.; Hankey, Kim G.; Taylor-Howell, Cheryl; Gibbs, Allison M.; Smith, Cassandra P.; MacVittie, Thomas J.

    2016-01-01

    Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease. PMID:27029502

  11. Geraniin down regulates gamma radiation-induced apoptosis by suppressing DNA damage.

    PubMed

    Bing, So Jin; Ha, Danbee; Kim, Min Ju; Park, Eunjin; Ahn, Ginnae; Kim, Dae Seung; Ko, Ryeo Kyeong; Park, Jae Woo; Lee, Nam Ho; Jee, Youngheun

    2013-07-01

    Gamma ray irradiation triggers DNA damage and apoptosis of proliferating stem cells and peripheral immune cells, resulting in the destruction of intestinal crypts and lymphoid system. Geraniin is a natural compound extracts from an aquatic plant Nymphaea tetragona and possesses good antioxidant property. In this study, we demonstrate that geraniin rescues radiosensitive splenocytes and jejunal crypt cells from radiation-induced DNA damage and apoptosis. Isolated splenocytes from C57BL/6 mice treated with geraniin were protected against radiation injury of 2 Gy irradiation through the enhancement of the proliferation and attenuation of DNA damage. Also, geraniin inhibited apoptosis in radiosensitive splenocytes by reducing the expression level and immunoreactivity of proapoptotic p53 and Bax and increasing those of anti-apoptotic Bcl-2. In mice exposed to radiation, geraniin treatment protected splenocytes and intestinal crypt cells from radiation-induced cell death. Our results suggest that geraniin presents radioprotective effects by regulating DNA damage on splenocytes, exerting immunostimulatory capacities and inhibiting apoptosis of radiosensitive immune cells and jejunal crypt cells. Therefore, geraniin can be a radioprotective agent against γ-irradiation exposure. PMID:23541438

  12. Gene expression and hormone autonomy in radiation-induced tumors of Arabidopsis thaliana

    SciTech Connect

    Persinger, S.M.; Town, C.D. )

    1989-04-01

    In order to study the molecular genetics of factor controlling plant cell growth, we have isolated a group of radiation-induced tumors from Arabidopsis thaliana. Tumors appeared on plants derived from {sup 60}Co gamma-irradiated seed or seedlings, and are capable of hormone-autonomous growth in culture. We have used vertebrate oncogene probes to explore the hypothesis that the tumors arose by the radiation-induced activation of growth-regulating plant oncogenes. One probe, int-2, was used to isolate cDNA clones representing an mRNA differentially expressed between tumors and hormone-dependent callus tissue. The genomic organization and function of this and other differentially expressed Arabidopsis sequences are being further characterized. A second area of study concerns the hormonal status of individual tumors. Tumor tissue varies in color, texture, and degree of differentiation: while some tumors appear undifferentiated, one consistently produces roots, and others occasionally develop shoots or leaflets. The tumors have characteristic growth rates on hormone-free medium, and growth in response to exogenous hormones differs among the tumors themselves and from wild-type. Characterization of the relationships between hormonal status, morphogenesis, and gene expression should yield valuable insights into the mechanisms regulating plant growth and development.

  13. The nucleus is the target for radiation-induced chromosomal instability

    NASA Technical Reports Server (NTRS)

    Kaplan, M. I.; Morgan, W. F.

    1998-01-01

    We have previously described chromosomal instability in cells of a human-hamster hybrid cell line after exposure to X rays. Chromosomal instability in these cells is characterized by the appearance of novel chromosomal rearrangements multiple generations after exposure to ionizing radiation. To identify the cellular target(s) for radiation-induced chromosomal instability, cells were treated with 125I-labeled compounds and frozen. Radioactive decays from 125I cause damage to the cell primarily at the site of their decay, and freezing the cells allows damage to accumulate in the absence of other cellular processes. We found that the decay of 125I-iododeoxyuridine, which is incorporated into the DNA, caused chromosomal instability. While cell killing and first-division chromosomal rearrangements increased with increasing numbers of 125I decays, the frequency of chromosomal instability was independent of dose. Chromosomal instability could also be induced from incorporation of 125I-iododeoxyuridine without freezing the cells for accumulation of decays. This indicates that DNA double-strand breaks in frozen cells resulting from 125I decays failed to lead to instability. Incorporation of an 125I-labeled protein (125I-succinyl-concanavalin A), which was internalized into the cell and/or bound to the plasma membrane, neither caused chromosomal instability nor potentiated chromosomal instability induced by 125I-iododeoxyuridine. These results show that the target for radiation-induced chromosomal instability in these cells is the nucleus.

  14. Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly

    PubMed Central

    Shimada, Mikio; Matsuzaki, Fumio; Kato, Akihiro; Kobayashi, Junya; Matsumoto, Tomohiro; Komatsu, Kenshi

    2016-01-01

    The embryonic brain is one of the tissues most vulnerable to ionizing radiation. In this study, we showed that ionizing radiation induces apoptosis in the neural progenitors of the mouse cerebral cortex, and that the surviving progenitor cells subsequently develop a considerable amount of supernumerary centrosomes. When mouse embryos at Day 13.5 were exposed to γ-rays, brains sizes were reduced markedly in a dose-dependent manner, and these size reductions persisted until birth. Immunostaining with caspase-3 antibodies showed that apoptosis occurred in 35% and 40% of neural progenitor cells at 4 h after exposure to 1 and 2 Gy, respectively, and this was accompanied by a disruption of the apical layer in which mitotic spindles were positioned in unirradiated mice. At 24 h after 1 Gy irradiation, the apoptotic cells were completely eliminated and proliferation was restored to a level similar to that of unirradiated cells, but numerous spindles were localized outside the apical layer. Similarly, abnormal cytokinesis, which included multipolar division and centrosome clustering, was observed in 19% and 24% of the surviving neural progenitor cells at 48 h after irradiation with 1 and 2 Gy, respectively. Because these cytokinesis aberrations derived from excess centrosomes result in growth delay and mitotic catastrophe-mediated cell elimination, our findings suggest that, in addition to apoptosis at an early stage of radiation exposure, radiation-induced centrosome overduplication could contribute to the depletion of neural progenitors and thereby lead to microcephaly. PMID:27367050

  15. Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data?

    SciTech Connect

    Schultz-Hector, Susanne . E-mail: susanne.schultz-hector@helmholtz.de; Trott, Klaus-Ruediger Prof.

    2007-01-01

    The Life Span Study of Japanese atomic bomb survivors demonstrates that radiation exposure significantly increased the risk of developing ischemic heart disease, in particular myocardial infarction. Similarly, epidemiologic investigations in very large populations of patients who had received postoperative radiotherapy for breast cancer or for peptic ulcer demonstrate that radiation exposure of the heart with an average equivalent single dose of approximately 2 Gy significantly increased the risk of developing ischemic heart disease more than 10 years after irradiation. These epidemiologic findings are compatible with radiobiologic data on the pathogenesis of radiation-induced heart disease in experimental animals. The critical target structure appears to be the endothelial lining of blood vessels, in particular arteries, leading to early functional alterations such as pro-inflammatory responses and other changes, which are slowly progressive. Research should concentrate on the interaction of these radiation-induced endothelial changes with the early stages of age-related atherosclerosis to develop criteria for optimizing treatment plans in radiotherapy and also potential interventional strategies.

  16. Ionizing radiation induces immediate protein acetylation changes in human cardiac microvascular endothelial cells

    PubMed Central

    Barjaktarovic, Zarko; Kempf, Stefan J.; Sriharshan, Arundhathi; Merl-Pham, Juliane; Atkinson, Michael J.; Tapio, Soile

    2015-01-01

    Reversible lysine acetylation is a highly regulated post-translational protein modification that is known to regulate several signaling pathways. However, little is known about the radiation-induced changes in the acetylome. In this study, we analyzed the acute post-translational acetylation changes in primary human cardiac microvascular endothelial cells 4 h after a gamma radiation dose of 2 Gy. The acetylated peptides were enriched using anti-acetyl conjugated agarose beads. A total of 54 proteins were found to be altered in their acetylation status, 23 of which were deacetylated and 31 acetylated. Pathway analyses showed three protein categories particularly affected by radiation-induced changes in the acetylation status: the proteins involved in the translation process, the proteins of stress response, and mitochondrial proteins. The activation of the canonical and non-canonical Wnt signaling pathways affecting actin cytoskeleton signaling and cell cycle progression was predicted. The protein expression levels of two nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 1 and sirtuin 3, were significantly but transiently upregulated 4 but not 24 h after irradiation. The status of the p53 protein, a target of sirtuin 1, was found to be rapidly stabilized by acetylation after radiation exposure. These findings indicate that post-translational modification of proteins by acetylation and deacetylation is essentially affecting the radiation response of the endothelium. PMID:25840449

  17. Punica granatum peel extract protects against ionizing radiation-induced enteritis and leukocyte apoptosis in rats.

    PubMed

    Toklu, Hale Z; Sehirli, Ozer; Ozyurt, Hazan; Mayadağli, A Alpaslan; Ekşioğlu-Demiralp, Emel; Cetinel, Sule; Sahin, Hülya; Yeğen, Berrak C; Ulusoylu Dumlu, Melek; Gökmen, Vural; Sener, Göksel

    2009-07-01

    Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a potential to support a successful radiotherapy by protecting against radiation-induced enteritis. PMID:19478462

  18. Harnessing a radiation inducible promoter of Deinococcus radiodurans for enhanced precipitation of uranium.

    PubMed

    Misra, Chitra Seetharam; Mukhopadhyaya, Rita; Apte, Shree Kumar