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Sample records for chronic radiation-induced myeloproliferative

  1. Chronic Myeloproliferative Neoplasms Treatment

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  2. Analyses of critical target cell responses during preclinical phases of evolving chronic radiation-induced myeloproliferative disease-exploitation of a unique canine model

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.; Frazier, M.E.

    1988-01-01

    This document briefly summarizes and highlights ongoing studies on the cellular and molecular processes involved in the induction and progression of myeloid leukemia in dogs chronically exposed to low daily doses of wholebody gamma irradiation. Under such conditions, select groups of dogs exhibit extremely high frequencies of myeloproliferative disease (MPD) (i.e., /congruent/50%) of which myeloid leukemia is most prominent. 2 figs.

  3. Treatment Option Overview (Chronic Myeloproliferative Neoplasms)

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  4. Treatment Options for Chronic Myeloproliferative Neoplasms

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  5. General Information about Chronic Myeloproliferative Neoplasms

    Science.gov (United States)

    ... way to treat some chronic myeloproliferative neoplasms. Platelet apheresis Platelet apheresis is a treatment that uses a special machine ... using interferon alfa or pegylated interferon alpha . Platelet apheresis . A clinical trial of a new treatment. Check ...

  6. Philadelphia-negative chronic myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Rosane Isabel Bittencourt

    2012-01-01

    Full Text Available Chronic myeloproliferative diseases without the Philadelphia chromosome marker (Ph-, although first described 60 years ago, only became the subject of interest after the turn of the millennium. In 2001, the World Health Organization (WHO defined the classification of this group of diseases and in 2008 they were renamed myeloproliferative neoplasms based on morphological, cytogenetic and molecular features. In 2005, the identification of a recurrent molecular abnormality characterized by a gain of function with a mutation in the gene encoding Janus kinase 2 (JAK2 paved the way for greater knowledge of the pathophysiology of myeloproliferative neoplasms. The JAK2 mutation is found in 90-98% of polycythemia vera and in about 50% essential thrombocytosis and primary myelofibrosis. In addition to the JAK2 mutation, other mutations involving TET2 (ten-eleven translocation, LNK (a membrane-bound adaptor protein; IDH1/2 (isocitrate dehydrogenase 1/2 enzyme; ASXL1 (additional sex combs-like 1 genes were found in myeloproliferative neoplasms thus showing the importance of identifying molecular genetic alterations to confirm diagnosis, guide treatment and improve our understanding of the biology of these diseases. Currently, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia and mastocytosis are included in this group of myeloproliferative neoplasms, but are considered different situations with individualized diagnostic methods and treatment. This review updates pathogenic aspects, molecular genetic alterations, the fundamental criteria for diagnosis and the best approach for each of these entities.

  7. Anagrelide treatment in 52 patients with chronic myeloproliferative diseases

    DEFF Research Database (Denmark)

    Penninga, E; Jensen, B A; Hansen, P B

    2004-01-01

    In this retrospective multi-centre study, we report our experience with anagrelide in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases. Our study included 52 patients (age 20-78 years). The initial anagrelide dose was, in general, 0.5 mg once daily and mean...

  8. Hematopoietic Growth Factors, Signaling and the Chronic Myeloproliferative Disorders

    OpenAIRE

    Kaushansky, Kenneth

    2006-01-01

    The chronic myeloproliferative diseases (CMDs) are a group of conditions characterized by unregulated blood cell production, that due either to excessive numbers of erythrocytes, leukocytes or platelets, or their defective function cause symptoms and signs of fatigue, headache, ruddy cyanosis, hemorrhage, abdominal distension, and the complications of vascular thrombosis. In the late 19th century Vaquez provided the first description of polycythemia vera (PV) and Hueck defined idiopathic myel...

  9. Pulmonary hypertension in patients with chronic myeloproliferative disorders

    Directory of Open Access Journals (Sweden)

    Yochai Adir

    2015-09-01

    Full Text Available Pulmonary hypertension (PH is a major complication of several haematological disorders. Chronic myeloproliferative diseases (CMPDs associated with pulmonary hypertension have been included in group five of the clinical classification for pulmonary hypertension, corresponding to pulmonary hypertension for which the aetiology is unclear and/or multifactorial. The aim of this review is to discuss the epidemiology, pathogenic mechanism and treatment approaches of the more common forms of pulmonary hypertension in the context of CMPD's: chronic thromboembolic pulmonary hypertension, precapillary pulmonary hypertension and drug-induced PH.

  10. Chronic radiation-induced dermatitis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Spałek M

    2016-12-01

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

  11. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation.

    Science.gov (United States)

    Hermouet, Sylvie; Bigot-Corbel, Edith; Gardie, Betty

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.

  12. Hemopoiesis in Ph-negative chronic myeloproliferative disorders.

    Science.gov (United States)

    Spanoudakis, Emmanouil; Tsatalas, Costas

    2009-05-01

    Chronic myeloproliferative disorders (cMPDs) are clonal hemopoietic malignancies arising at the multipotent stem cell level. These conditions are characterized by increased blood count, marrow hyperplasia and extramedulary hemopoiesis. Vascular events might complicate their course, and transformation to either acute leukemia or myelofibrosis can finally occur. Among cMPDs, Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) belong to the group of Ph-negative cMPDs. Although they share common pathogenetic features, these entities have a quite different prognosis. The common pathogenetic basis of Ph-negative cMPDs was recognized long ago, and it was suggested that a stimulating factor might enhance bone marrow hemopoietic activity. Hemopoietic progenitors from cMPDs show hypersensitivity to low levels of a variety of hemopoietic cytokines. The independency of erythroid precursors from erythropoietin became the first surrogate marker of an abnormal hemopoietic clone. This clone is characterized by increased proliferation and survival, as well as by decreased apoptosis, leading to the accumulation of mature blood cells that additionally show a phenotype of activated cells. Recently four independent groups have described an activating point mutation in the JAK2 kinase as a key pathogenetic event in Ph-negative cMPDs. JAK2 is a tyrosine kinase that acts as a second intracellular messenger for many hemopoietic cytokine receptors. It is now believed that jacking up hemopoiesis can explain many features of myeloproliferation. Interestingly, some features are associated with intracellular levels of mutated JAK2 (the "dosage hypothesis"). The mutation in JAK2 kinase is not an example of a genetic defect leading to a single disease, since it occurs in many other myeloid disorders, and probably represents a secondary hit in a multistep ongogenetic process. Nevertheless, it has changed the way we approach cMPD patients and has clarified many

  13. The mevalonate pathway as a therapeutic target in the Ph-negative chronic myeloproliferative disorders

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Riley, Caroline H

    2007-01-01

    The Ph-negative chronic myeloproliferative disorders (CMPDs) polycythaemia vera, essential thrombocytosis and idiopathic myelofibrosis are acquired stem cell disorders, which pathophysiologically are featured by clonal myeloproliferation and accumulation of myeloid cells, the latter being...... being partly explained by a proteolytic bone marrow mileu owing to excessive release of various proteases with ensuing extracellular matrix degradation and constitutive mobilisation of CD34+ cells into the peripheral blood. Thrombohaemorrhagic complications are major clinical problems contributing...

  14. Increased gene expression of histone deacetylases in patients with Philadelphia-negative chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads

    2012-01-01

    proteins in favor of apoptosis (enhanced apoptosis) and also to inhibit angiogenesis. Recently, enhanced HDAC enzyme activity has been found in CD34+cells from patients with PMF, enzyme activity levels highly exceeding those recorded in other chronic myeloproliferative neoplasms (CMPNs). The raised levels...... identified that the HDAC6 gene is progressively expressed in patients with ET, PV and PMF, reflecting a steady accumulation of abnormally expressed HDAC6 during disease evolution. Our results lend further support to HDACs as important epigenetic targets in the future treatment of patients with CMPNs. Since...

  15. Are chronic myeloproliferative neoplasms associated with age-related macular degeneration?

    DEFF Research Database (Denmark)

    Bak, M.; Sorensen, T. L.; Flachs, E. M.

    2015-01-01

    of the eye have not been thoroughly investigated in these patients. Previously reported studies show signs of systemic inflammation in patients with MPN as well as in patients with Age-Related Macular Degeneration (AMD). Our hypothesis is that the presence of MPN predisposes some individuals to develop AMD...... and this might be explained by the degree of systemic inflammation. Objective. To describe the prevalence of Age-Related Macular Degeneration in patients with Chronic Myeloproliferative cancer at time of diagnosis compared to the general population in Denmark. Materials and Methods. We conducted a retrospective...

  16. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Larsen, Thomas Stauffer; Riley, Caroline Hasselbalch;

    2011-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F...... mutation in the large majority of patients with PV and in half of those with ET and PMF. A number of studies have shown that the "tumor burden" may be monitored at the molecular level in JAK2-positive patients using highly sensitive real-time quantitative PCR. During the last 25 years several studies have...

  17. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Larsen, Thomas Stauffer; Riley, Caroline Hasselbalch;

    2011-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F...... shown that interferon-alpha (IFN-alpha) induces complete haematological remissions in a large proportion of the patients. However, its use in clinical practice has unfortunately been limited due to side effects with high drop-out rates in most studies. Recently, IFN-alpha2 has been shown to induce deep...

  18. Novel Insights into the Biology and Treatment of Chronic Myeloproliferative Neoplasms*

    Science.gov (United States)

    Mughal, Tariq I.; Barbui, Tiziano; Abdel-Wahab, Omar; Kralovics, Robert; Jamieson, Catriona; Kvasnicka, Hans-Michael; Mullaly, Ann; Rampal, Raajit; Mesa, Ruben; Kiladjian, Jean-Jacques; Deininger, Michael; Prchal, Joseph; Hehlmann, Rüdiger; Saglio, Giuseppe; Van Etten, Richard A.

    2016-01-01

    Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoiesis characterized by a high frequency of genetic alterations and include chronic myeloid leukemia (CML) and the BCR-ABL1-negative MPNs. Herein we summarize recent advances and controversies in our understanding of the biology and therapy of these disorders, as discussed at the 8th post-American Society of Hematology CML-MPN workshop. The principal areas addressed include the breakthrough discovery of CALR mutations in patients with JAK2/MPL wild type MPN, candidate therapies based on novel genetic findings in leukemic transformation and new therapeutic targets in MPNs, and an appraisal of bone marrow histopathology in MPNs with a focus on the potential new clinical entity of “ masked ” polycythemia vera. An update on clinical trials of Janus kinase (JAK) inhibitors is presented as well as current understanding regarding the definitions and mechanisms of resistance to JAK inhibitors, and updated information on the safety and efficacy of discontinuation of tyrosine kinase inhibitors in patients with CML. PMID:25330439

  19. Janus kinase 2 mutations in cases with BCR-ABL-negative chronic myeloproliferative disorders from Turkey

    Science.gov (United States)

    Yildiz, Ismail; Yokuş, Osman; Gedik, Habip

    2017-01-01

    Objective: We aimed to investigate the frequency of Janus kinase 2 (JAK2) mutations in cases with chronic myeloproliferative disorders (CMDs), and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. Materials and Methods: Patients, who were diagnosed with BCR-ABL-negative CMDs according to diagnosis criteria of the World Health Organization and followed up at the hematology clinic between 2013 and 2015, were investigated in terms of the frequency of JAK2 mutation in cases with CMDs, and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. Results: In total, 100 patients, who were diagnosed with BCR-ABL-negative CMDs, were evaluated retrospectively. The mean age of the patients with JAK2 positivity was significantly higher compared to patients with negative. JAK2-positivity rates in the age groups were significantly different. Gender, diagnosis, splenomegaly, and leukocytosis were not statistically different for JAK2 positivity between the groups. Conclusion: JAK2 V617F mutation is more commonly seen in older age as a risk for complications related to CDMS. Splenomegaly and leukocytosis are not associated with JAK2 V617F mutation. PMID:28182037

  20. The role of JAK1/2 inhibitors in the treatment of chronic myeloproliferative neoplasms.

    Science.gov (United States)

    Keohane, Clodagh; Mesa, Ruben; Harrison, Claire

    2013-01-01

    In 2005, the description of the JAK2V617F mutation for the first time provided a molecular key to enable more rapid diagnosis and target for novel therapeutics in the myeloproliferative neoplasms. In 2007, the first-in-class agent INC18424, ruxolitinib, JAKafi, or JAKAVI was first tested in patients with intermediate-risk 2 or high-risk myelofibrosis regardless of whether they possessed the JAK2V617F mutation. Patients treated with this agent had major reduction in splenomegaly as well as impressive reduction, and in some cases resolution, of symptoms. This study was followed by the two Controlled Myelofibrosis Study with Oral JAK Inhibitor Therapy (COMFORT) trials (the first-ever phase III trials in myelofibrosis), which confirmed results in these aspects were superior to either placebo or standard care, and updated results show a survival advantage with this therapy. This paper discusses these results and data from other JAK inhibitors while speculating on the future of these therapies. It also reflects on the fact that the true targets and agents' mode of action are uncertain. Unlike targeted therapy for chronic myeloid leukemia (CML), these agents do not deliver molecular remission, and it is not clear whether their predominant benefit is mediated via JAK2, JAK1, or both. Nonetheless, the advent of the JAK inhibitor is a welcome advance and has made a dramatic improvement to the therapeutic landscape of these conditions.

  1. Correlation between leukocytosis and thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms.

    Science.gov (United States)

    Caramazza, Domenica; Caracciolo, Clementina; Barone, Rita; Malato, Alessandra; Saccullo, Giorgia; Cigna, Valeria; Berretta, Salvatore; Schinocca, Luciana; Quintini, Gerlando; Abbadessa, Vincenzo; Di Raimondo, Francesco; Siragusa, Sergio

    2009-10-01

    The evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates. We found that white blood cells (WBC) count above 9.5 x 10(9)/L at diagnosis (baseline analysis) was associated with thrombosis during the follow-up (Hazard Ratio [HR] of 1.8, p 0.03). At the time-dependent analysis, therapy with hydroxyurea (HU), lowering by 35% the baseline WBC level, reduced such strength of association giving a HR of 1.3 (p value non significant). We found a trend between WBC level and thrombosis in untreated low-risk patients (RR of 1.9, 95% CI 0.9 to 3.1); in high-risk patients treated with HU this correlation was clearly lost (RR 1.1, 95% CI 0.2 to 2.7). Finally, we could not identify the presence of JAK2 (V617F) as a risk factor for thrombosis. Properly designed prospective studies should corroborate such results.

  2. Effects of chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes.

    Science.gov (United States)

    Katsube, Takanori; Wang, Bing; Tanaka, Kaoru; Ninomiya, Yasuharu; Varès, Guillaume; Kawagoshi, Taiki; Shiomi, Naoko; Kubota, Yoshihisa; Liu, Qiang; Morita, Akinori; Nakajima, Tetsuo; Nenoi, Mitsuru

    2017-01-01

    Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53(+/-)) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53(+/+)) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53(+/+) C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.

  3. Detection and clinical significance of JAK2 V617F mutation in Chinese and Uyghur patients with chronic myeloproliferative in Xinjiang

    Institute of Scientific and Technical Information of China (English)

    张晓燕

    2013-01-01

    Objective To investigate the frequency of JAK2 V617F gene(hereinafter,the JAK2 gene) mutation in Uyghur patients with chronic myeloproliferative neoplasm(MPN) and its relationship with the clinical characteristics,and further compare differences of mutation rates in

  4. Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

    DEFF Research Database (Denmark)

    Riley, C.H.; Morten Krogh, Jensen; Brimnes, M.K.;

    2011-01-01

    have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4 CD25Foxp3 T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients treated with IFN...

  5. Management of side effects of BCR/ABL-negative chronic myeloproliferative neoplasm therapies. Focus on anagrelide.

    Science.gov (United States)

    Antelo, María Luisa; de Las Heras, Natalia; Gonzalez Porras, Jose Ramón; Kerguelen, Ana; Raya, Jose María

    2015-12-01

    Although hydroxyurea is considered the first-line cytoreductive therapy in high-risk patients with polycythemia vera or essential thrombocythemia, approximately 20-25% of patients develop resistance or intolerance and they need an alternative therapy. Anagrelide is the treatment of choice in patients with essential thrombocythemia intolerant or with resistance to hydroxyurea. Anagrelide is usually well tolerated. Although there is concern about the increased risk of cardiac side effects, in most cases these are mild, and easily manageable. In this paper, the available evidence about the management of patients with myeloproliferative neoplasms, with a special focus on the side effects of drug therapies is reviewed.

  6. The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

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    Boissinot, Marjorie [Translational Neuro-Oncology Group, Leeds Institute of Cancer and Pathology, University of Leeds, Level 5 Wellcome Trust Brenner Building, St James’s Hospital, Leeds LS9 7TF (United Kingdom); Vilaine, Mathias [Institute of Research on Cancer and Aging (IRCAN), CNRS-Inserm-UNS UMR 7284, U 1081, Centre A. Lacassagne, 33 Avenue Valombrose, Nice 06189 (France); Hermouet, Sylvie, E-mail: sylvie.hermouet@univ-nantes.fr [Centre Hospitalier Universitaire (CHU), Place Alexis Ricordeau, Nantes 44093 (France); Inserm UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 8 quai Moncousu, Nantes cedex 44007 (France)

    2014-08-12

    Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs)

  7. Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

    Science.gov (United States)

    Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

    2014-01-01

    Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

  8. Nuclear magnetic resonance investigation of erythrocyte membranes in chronic myeloproliferative disorders.

    Science.gov (United States)

    Morariu, V V; Petrov, L

    1986-07-01

    The temperature dependence of the apparent water diffusional exchange through erythrocyte membranes in cases of policitemia vera, chronic granulocytic leukemia and primary myelofibrosis was measured by using a nuclear magnetic resonance method in the presence of Mn2+. The thermal transition shifted to lower temperatures in all cases, regardless of the stage of the disease, suggesting a structural alteration of the membrane. The shift of transition indirectly suggests a lower penetration of the erythrocytes by Mn2+. The water exchange time at 37 degrees C also increased, mainly in the blast crisis; it seems to have a prognostic value of some clinical interest. No simple correlation of the water exchange and the following clinical investigations was observed: the white count, the percentage of promyelocites and myeloblasts, the sedimentation rate of blood, the osmotic fragility of erythrocytes, the total concentration of proteins, albumin and immunoglobulins, respectively, in plasma.

  9. Treatment Options for Myelodysplastic/Myeloproliferative Neoplasms

    Science.gov (United States)

    ... Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version General Information About Myelodysplastic/ Myeloproliferative ...

  10. Expansion of circulating CD56bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α

    DEFF Research Database (Denmark)

    Riley, Caroline H; Hansen, Morten; Brimnes, Marie K

    2015-01-01

    In recent years, major molecular remissions have been observed in patients with JAK2-positive chronic myeloproliferative neoplasms (MPNs) after therapy with IFN-α. IFN-α is known to have altering effects on immune cells involved in immune surveillance and might consequently enhance anti-tumor imm......In recent years, major molecular remissions have been observed in patients with JAK2-positive chronic myeloproliferative neoplasms (MPNs) after therapy with IFN-α. IFN-α is known to have altering effects on immune cells involved in immune surveillance and might consequently enhance anti......-tumor immune response against the JAK2-mutated clone. The objective of this study was to investigate circulating levels and phenotype of natural killer cells in 29 JAK2-positive MPN patients during IFN-α treatment. Furthermore, functional studies of NK cells upon target-cell recognition and cytokine...... with IFN-α skews the human NK population toward a helper type that may assist in CD8(+) T cell priming in lymphoid tissues at the expense of their immediate cytotoxic functions in peripheral blood and tissues....

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

    Energy Technology Data Exchange (ETDEWEB)

    Foro, Palmira, E-mail: pforo@parcdesalutmar.cat [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Algara, Manuel [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Lozano, Joan [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Rodriguez, Nuria; Sanz, Xavier [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Torres, Erica [Pathology Department, Parc de Salut Mar, Barcelona (Spain); Carles, Joan [Universitat Autonoma de Barcelona, Barcelona (Spain); Department of Oncology, Hospital Vall d' Hebron, Barcelona (Spain); Reig, Anna; Membrive, Ismael [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Quera, Jaume [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Fernandez-Velilla, Enric; Pera, Oscar [Department of Radiation Oncology, Parc de Salut Mar, Barcelona (Spain); Lacruz, Marti [Universitat Pompeu Fabra, Barcelona (Spain); Radiation Protection Department, Parc de Salut Mar, Barcelona (Spain); Bellosillo, Beatriz [Universitat Pompeu Fabra, Barcelona (Spain); Pathology Department, Parc de Salut Mar, Barcelona (Spain)

    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

  12. Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

    Science.gov (United States)

    Portas, M; Mansilla, E; Drago, H; Dubner, D; Radl, A; Coppola, A; Di Giorgio, M

    2016-09-01

    Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy.

  13. Increase in circulating CD4⁺CD25⁺Foxp3⁺ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

    DEFF Research Database (Denmark)

    Riley, Caroline Hasselbalch; Jensen, Morten Krogh; Brimnes, Marie Klinge;

    2011-01-01

    blood have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4(+)CD25(+)Foxp3(+) T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients...

  14. Advances in the biology and therapy of chronic myeloid leukemia (CML): Proceedings from the 6th Post-ASH International CML and Myeloproliferative Neoplasms Workshop

    Science.gov (United States)

    Van Etten, Richard A.; Mauro, Michael; Radich, Jerald P.; Goldman, John M.; Saglio, Giuseppe; Jamieson, Catriona; Soverini, Simona; Gambacorti-Passerini, Carlo; Hehlmann, Rüdiger; Martinelli, Giovanni; Perrotti, Danilo; Scadden, David T.; Skorski, Tomasz; Tefferi, Ayalew; Mughal, Tariq I.

    2012-01-01

    Following the 53rd annual meeting of the American Society of Hematology in San Diego in December 2011, a group of clinical and laboratory investigators convened for the 6th post-ASH International Workshop on chronic myeloid leukemia (CML) and myeloproliferative neoplasms (MPN). The workshop took place on the 13th–14th December at the Estancia, La Jolla, California, USA. This report summarizes the most recent advances in the biology and therapy of CML that were presented at ASH and discussed at the Workshop. Preclinical studies focused on the CML stem cell and its niche, and on early results of deep sequencing of CML genomes. Clinical advances include updates on 2nd and 3rd generation TKIs, molecular monitoring, TKI discontinuation studies, and new therapeutic agents. A report summarizing the pertinent advances in MPN has been published separately. PMID:23121619

  15. Oncogenes in myeloproliferative disorders.

    Science.gov (United States)

    Tefferi, Ayalew; Gilliland, D Gary

    2007-03-01

    Myeloproliferative disorders (MPDs) constitute a group of hematopoietic malignancies that feature enhanced proliferation and survival of one or more myeloid lineage cells. William Dameshek is credited for introducing the term "MPDs" in 1951 when he used it to group chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) under one clinicopathologic category. Since then, other myeloid neoplasms have been added to the MPD member list: chronic neutrophilic (CNL), eosinophilic (CEL) and myelomonocytic (CMML) leukemias; juvenile myelomonocytic leukemia (JMML); hypereosinophilic syndrome (HES); systemic mastocytosis (SM); and others. Collectively, MPDs are stem cell-derived clonal proliferative diseases whose shared and diverse phenotypic characteristics can be attributed to dysregulated signal transduction--a consequence of acquired somatic mutations. The most recognized among the latter is BCR-ABL, the disease-causing mutation in CML. Other mutations of putative pathogenetic relevance in MPDs include: JAK2V617F in PV, ET, and PMF; JAK2 exon 12 mutations in PV; MPLW515L/K in PMF and ET; KITD816V in SM; FIP1L1-PDGFRA in CEL-SM; rearrangements of PDGFRB in CEL-CMML and FGFR1 in stem cell leukemia-lymphoma syndrome; and RAS/PTPN11/NF1 mutations in JMML. This increasing repertoire of mutant molecules has streamlined translational research and molecularly targeted drug development in MPDs.

  16. Leucemia mieloide crônica e outras doenças mieloproliferativas crônicas Chronic myeloid leukemia and other chronic myeloproliferative disorders

    Directory of Open Access Journals (Sweden)

    Vaneuza M. Funke

    2010-05-01

    Full Text Available A leucemia mieloide crônica (LMC é uma doença clonal da medula óssea caracterizada pela presença do cromossomo Philadelphia (Ph, resultante da translocação entre os cromossomos 9 e 22. O gene híbrido assim formado, BCR-ABL codifica proteínas com atividade de tirosinoquinases que regulam o crescimento celular. A partir da década de 80, o transplante alogênico de células-tronco hematopoéticas (TCTH se tornou tratamento de escolha para pacientes com idade menor que 55 anos de idade e doador compatível. Não obstante, a partir do advento dos inibidores de tirosinoquinases, drogas de alta eficácia e baixa toxicidade, houve uma mudança no algoritmo de tratamento da LMC. As indicações do TCTH foram restritas em decorrência da mortalidade relacionada a este procedimento e o mesilato de imatinibe tornou-se o novo tratamento de escolha para esta enfermidade. No Brasil e possivelmente em outros países em desenvolvimento, as condições socioeconômicas fazem com que o TCTH ainda seja considerado como primeira linha de tratamento em algumas situações. O TCTH permanece indicado nas doenças (ou neoplasias mieloproliferativas, como a mielofibrose primária em situações de alto risco e pacientes portadores de policitemia vera ou trombocitose essencial que tenham evoluído para mielofibrose com características de alto risco.Chronic myeloid leukemia (CML is a clonal disease of the bone marrow characterized by the presence of Philadelphia chromosome (Ph which results from translocation between chromosome nine and 22. The hybrid gene, BCR-ABL, encodes proteins with tyrosine kinase activity that regulate cell growth. From the 80´s allogeneic hematopoietic stem cell transplantation (HSCT has become the treatment of choice for patients younger than 55 years of age and donor. However, from the advent of tyrosine kinase inhibitors, drugs of high efficacy and low toxicity, there was a change in the treatment algorithm of CML. The indications of

  17. Protective Effect of Topically Applied Polypeptide from Chlamys farreri Against Ultraviolet Radiation-Induced Chronic Skin Damage in Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    迟明亮; 曹鹏利; 于国英; 朱莉; 王跃军; 王春波

    2003-01-01

    Polypeptide from Chlamys farreri (PCF) , a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed:(1)PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner.(2)PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px.(3)The differences among the PCF groups and UV model group were significant (P<0.05, P<0.01). These results indicated that topical application of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

  18. A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia.

    Science.gov (United States)

    Pratz, Keith W; Rudek, Michelle A; Gojo, Ivana; Litzow, Mark R; McDevitt, Michael A; Ji, Jiuping; Karnitz, Larry M; Herman, James G; Kinders, Robert J; Smith, B Douglas; Gore, Steven D; Carraway, Hetty E; Showel, Margaret M; Gladstone, Douglas E; Levis, Mark J; Tsai, Hua-Ling; Rosner, Gary; Chen, Alice; Kaufmann, Scott H; Karp, Judith E

    2017-02-15

    Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML).Results: A total of 99 patients received veliparib 10-100 mg orally twice daily on days 1-8, 1-14, or 1-21 along with continuous infusion topotecan 1.0-1.2 mg/m(2)/d + carboplatin 120-150 mg/m(2)/d on days 3-7. The MTD was veliparib 80 mg twice daily for up to 21 days with topotecan 1.2 mg/m(2)/d + carboplatin 150 mg/m(2)/d. Mucositis was dose limiting and correlated with high veliparib concentrations. The response rate was 33% overall (33/99: 14 CR, 11 CRi, 8 PR) but was 64% (14/22) for patients with antecedent or associated aggressive MPNs or CMML. Leukemias with baseline DNA repair defects, as evidenced by impaired DNA damage-induced FANCD2 monoubiquitination, had improved survival [HR = 0.56 (95% confidence interval, 0.27-0.92)]. A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX phosphorylation in CD34(+) leukemia cells, with greater phosphorylation in cells from responders.Conclusions: The veliparib/topotecan/carboplatin combination warrants further investigation, particularly in patients with aggressive MPNs, CMML, and MPN- or CMML-related acute leukemias. Clin Cancer Res; 23(4); 899-907. ©2016 AACR.

  19. [Radiation induced tumors].

    Science.gov (United States)

    Gutiérrez Bayard, L; Delgado López, L; Tirado Bejarano, C; Gómez Puerto, A; García Fernández, J L

    1998-04-01

    Radiations at cellular level produce different effects, depending on type of radiation and irradiated tissue. The radiation-induced cancers are associated to non-letals genetics mutations, and to classify like radiation induced tumors is necessary that appear in the treatment volume, a long latency period (years), histolo-different to the primary lesion, enough doses quantitatively and that exists a greater incidence in the irradiated populations. The genetics mutations affect at tumoral suppressors gen(Gen RB I, p53, BRCA I, BRCA 2) and repressors gen (hMSH 2, hMLH I,...), they could be longer and multifocals mutations, and produce lack of cellular control and a greater predisposition to develop tumors and a probable risk of increment of radiosensitivity. We present some of the more representatives studies about radiation-induced tumors.

  20. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  1. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

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

  2. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. Neurological Findings in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Semra Paydas

    2013-04-01

    Full Text Available Myeloproliferative neoplasms (MPN arise from genetic deficiencies at the level of pluripotent stem cells. Each of these neoplasms is a clonal stem cell disorder with specific phenotypic, genetic and clinical properties. Age is one of the most important factors in the development of symptoms and complications associated with MPNs.High white blood cell counts in chronic myelocytic leukemia also known as leukocytosis may lead to central nervous system findings. Tumors developing outside the bone marrow named as extramedullary myeloid tumors (EMMT could be detected at the initial diagnosis or during the prognosis of the disease, which may cause neurological symptoms due to pressure of leukemic cell mass on various tissues along with spinal cord. Central nervous system involvement and thrombocytopenic hemorrhage may lead to diverse neurological symptoms and findings.Transient ischemic attack and thrombotic stroke are the most common symptoms in polycythemia vera. Besides thrombosis and hemorrage, transformation to acute leukemia can cause neurological symptoms and findings. Transient ischemic attack, thrombotic stroke and specifically hemorrage can give rise to neurological symptoms similar to MPN in essential thrombocytosis.Extramedullary hematopoiesis refers to hematopoietic centers arise in organ/tissues other than bone marrow in myelofibrosis. Extramedullar hematopoietic centers may cause intracranial involvement, spinal cord compression, seizures and hydrocephalia. Though rare, extramedullary hematopoiesis can be detected in cranial/spinal meninges, paraspinal tissue and intracerebral regions. Extramedullary hematopoiesis has been reported in peripheral neurons, choroid plexus, pituitary, orbits, orbital and lacrimal fossa and in sphenoidal sinuses. [Cukurova Med J 2013; 38(2.000: 157-169

  4. Radiation-induced intestinal inflammation

    Institute of Scientific and Technical Information of China (English)

    Meritxell Mollà; Julián Panés

    2007-01-01

    Radiation induces an important inflammatory response in the irradiated organs, characterized by leukocyte infiltration and vascular changes that are the main limiting factor in the application of this therapeutic modality for the treatment of cancer. Recently, a considerable investigative effort has been directed at determining the molecular mechanisms by which radiation induces leukocyte recruitment, in order to create strategies to prevent intestinal inflammatory damage. In these review, we consider current available evidence on the factors governing the process of leukocyte recruitment in irradiated organs, mainly derived from experimental studies, with special attention to adhesion molecules, and their value as therapeutic targets.

  5. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  6. Myeloproliferative disease in a cat

    Energy Technology Data Exchange (ETDEWEB)

    Yates, R.W.; Weller, R.E.; Feldman, B.F.

    1984-10-01

    Myeloproliferative disorders, a complex of cytologic abnormalities arising in the bone marrow, are among domestic animals most frequently recognized in cats but are relatively uncommon. A 4-year-old female Siamese, with splenomegaly and weight loss, was listless, anorectic, pale and dehydrated. A hemogram showed severe, macrocytic normochromic anemia, leukocytosis and reticulocytosis, with abnormally high numbers of nucleated RBC and undifferentiated blast cells. Bone marrow smears contained predominantly undifferentiated blast cells, RBC precursors and myeloblasts. The fluorescent antibody test for FeLV was positive. The cat died 66 days later despite a blood transfusion and chemotherapy. Necropsy confirmed a diagnosis of myeloproliferative disease, with hepatic and splenic invasion. 15 references, 5 figures, 1 table.

  7. The Importance of Identification of M-BCRABL Oncogene and JAK2V617F Mutation in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Szántó Annamária

    2014-04-01

    Full Text Available Background: The elucidation of the genetic background of the myeloproliferative neoplasms completely changed the management of these disorders: the presence of the Philadelphia chromosome and/or the BCR-ABL oncogene is pathognomonic for chronic myeloid leukemia and identification of JAK2 gene mutations are useful in polycytemia vera (PV, essential thrombocytemia (ET and myelofibrosis (PMF. The aim of this study was to investigate the role of molecular biology tests in the management of myeloproliferative neoplasms.

  8. Radiation-induced cardiovascular effects

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. Rabbit model of radiation-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Zhen-Zong Du; Hua Ren; Jian-Fei Song; Li-Fei Zhang; Feng Lin; Hai-Yong Wang

    2013-01-01

    Objective:To explore the feasibility of establishing an animal model of chronic radiation-induced lung injury.Methods:Twenty-eightNewZealand white rabbits were randomly divided into3 groups(the right lung irradiation group, the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established by high-does radiotherapy in the irradiation groups, then all rabbits underwentCT and pathological examinations at1,2,4,8,12,16 weeks, respectively after radiation.Results:Within4 weeks of irradiation, some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At8-12 weeks after irradiation,CT scanning showed ground glass samples signs, patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

  11. Calreticulin Mutations in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Noa Lavi

    2014-10-01

    Full Text Available With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph− myeloproliferative neoplasms (MPNs in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET and primary myelofibrosis (PMF. At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations and recurrent 5-bp insertions (type 2 mutations in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review.

  12. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes

    Directory of Open Access Journals (Sweden)

    Sochacki AL

    2016-04-01

    Full Text Available Andrew L Sochacki,1 Melissa A Fischer,1 Michael R Savona1,2 1Department of Internal Medicine, Vanderbilt University Medical Center, 2Vanderbilt-Ingram Cancer Center, Nashville, TN, USA Abstract: The discovery of JAK2V617F a decade ago led to optimism for a rapidly developing treatment revolution in Ph- myeloproliferative neoplasms. Unlike BCR–ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF, post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS/myeloproliferative neoplasm (MPN syndromes. JAK–STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK–STAT, hedgehog, PI3K–Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease. Keywords: MDS/MPN neoplasms, emerging therapy

  13. 3 cases of radiation-induced sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, K.; Fukuma, H.; Beppu, Y.; Hirota, T. (National Cancer Center, Tokyo (Japan). Hospital); Shinohara, N.

    1982-03-01

    Criteria for the diagnosis of radiation-induced sarcoma have been previously described. All cases must have a history of irradiation and the second neoplasm must have arisen in the area of the radiation field. A latent period of several years must have elapsed after irradiation before clinical evidence of a second malignant neoplasm. Most important thing is that, all suspected cases must have been proved histologically. We have experienced 3 cases of radiation-induced sarcoma, they were 42-years-old man who developed an osteosarcoma of the lumbar spine at the field of postoperative irradiation for seminoma 7 years previously, 69-years-old woman who developed a malignant fibrous histiocytoma of the buttock at the field of radical radiation for uterine carcinoma 7 years previously and 59-years-old woman who developed an extraskeletal osteosarcoma of the abdominal wall at the field of postoperative irradiation for uterine sarcoma 7 years previously. The last case is very rare and only 8 cases of radiation-induced extraskeletal osteosarcoma have been reported. Since there has been a definite trend in the treatment of cancer toward employing radiation for more favorable cases, in addition to technical improvements in the administration of radiotherapy and more modern equipment, survival data may have been altered considerably in many malignant tumors. Accordingly, more radiation-induced tumors may be encountered in the future. The clinical presentation and histopathology of these radiation-induced sarcomas are presented with a review of the literature.

  14. 妊娠合并慢性骨髓增殖性疾病11例临床分析%Clinical analysis of eleven patients with chronic myeloproliferative disorders complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    白月婷; 张超; 王建六; 梁梅英; 张晓红

    2010-01-01

    Objective To investigate the clinical characteristics, the antenatal management, the outcome and prognosis of chronic myeloproliferative disorders (CMPD) complicating pregnancy. Methods Retrospectively analyze the clinical data of eleven patients with CMPD complicating pregnancy hospitalized in Peking University People' s Hospital from 2000 to 2009, including five patients with essential thrombocythemia, one with primary myelofibrosis and five with chronic myeloid leukemia. Results (1)Five pregnancies had periodic antenatal care and laboratory monitorings like full blood count. Reasonable anti-coagulation therapy was given to prevent the complications. One patient with PMF diagnosed before conception had her first pregnancy ended with mild pre-eclampsia and intrauterine death at the gestational age of 32 weeks. During the first trimester of her second pregnancy two years later, the test for anti-β2 glycoprotein antibody was positive. She received low-dose aspirin and low-molecular-weight heparin as anticoagulants. An uneventful course was obtained and she delivered a healthy term infant. (2) Five pregnancies had occasional antenatal examination, including two patients with ET and three patients with CML One patient with ET developed severe pre-eclampsia at the gestational age of 25 weeks. Umbilical artery Doppler showed reversed end-diastolic velocity. The management with anti-convulsants, antihypertensives and anti-coagulants showed no effect. An emergency cesarean section had to be performed because of the aggressive hypertension and placental abruption, with still birth as a result. Two pregnancies never had an antenatal care. Both of them were admitted on labor and the diagnoses of CML were made. (3)Four pregnancies developed oligohydramnios and three developed preelampsia(two severe pre-eclampsia and one mild pre-eclampsia). There was no other hemorrhage and thrombosis event. (4) Eight pregnancies reached full-term with four cesarean sections and four vaginal

  15. Myeloproliferative neoplasms in five multiple sclerosis patients

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis

    2013-01-01

    The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007-2012. We describe the patients' history and treatment...

  16. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    Michael eRobbins

    2012-07-01

    Full Text Available 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

  17. Safety and efficacy of combination therapy of interferon-alpha2 + JAK1-2 Inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the danish combi-trial-an open label, single arm, non-randomized multicenter phase II study

    DEFF Research Database (Denmark)

    Mikkelsen, S. U.; Kjaer, L.; Skov, V.

    2015-01-01

    Background: The Philadelphia-negative, chronic myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) (PMF). Chronic inflammation and a deregulated immune system are considered important for clonal evolution and disease....... Hct control without phlebotomy was achieved by week 4 in 78 % of pts (7 of 9), who at baseline had an elevated hct. Only 3 pts required a total of 3 phlebotomies after initiation of CT. In Figure 1 median hct levels at 0, 1, 3, 6 months are shown. Overall, complete response (CR) was achieved as best......) or major response (n=2) was achieved in 4 pts (57.1%) by week 2 or 1 month, and NR in 3 pts (42.8%). Among PPV-MF pts, 2 pts (66.7%) achieved CR and 1 patient (33,3%) PR by week 2. Furthermore, JAK2V617F% declined significantly as depicted in Figure 2 (JAK2V617F% over time for each patient) and 3 (median...

  18. Predictive Factors of Radiation-Induced Lung Toxicity in Lung Cancer Patients: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Maher Soliman

    2016-07-01

    Full Text Available Background: Radiation-induced lung toxicity is an important dose-limiting toxicity in lung cancer radiotherapy, for which there are no generally accepted predictive factors. This study seeks to identify risk factors associated with the development of severe radiation-induced lung toxicity using clinical and dosimetric parameters. Methods: We reviewed the medical records of 54 patients with histologically proven stage III non-small cell lung cancer treated with three dimensional-conformal radiotherapy at Alexandria Main University Hospital between January 2008 and December 2011. The original treatment plans for those patients were restored and imported to a treatment planning system. Lung dose–volume histograms and various dosimetric parameters were calculated. Univariate and multivariate logistic regression analyses were performed. Results: The following grades of radiation-induced lung toxicity were observed in patients - grade 0: 17 (31.5%, grade 1: 5 (9.3%, grade 2: 13 (24.1%, grade 3: 15 (27.8%, and grade 5: 4 (7.4%. A total of 19 (35.2% patients developed grade ≥3 and were considered to have an event. Univariate analysis showed that age, presence of chronic obstructive pulmonary disease and location of the primary tumor had significant associations with severe radiation-induced lung toxicity. Other dosimetric variables such as tumor side, histology, forced expiratory volume in 1 s, smoking, and gender showed no significant correlations with severe radiation-induced lung toxicity. Multivariate analysis showed that the presence of chronic obstructive pulmonary disease (P=0.001 and location of the primary tumor (P=0.010 were the only predictive factors for severe radiation-induced lung toxicity. Conclusion: This study demonstrates that patients with chronic obstructive pulmonary disease and lower lung lobe tumors have a high risk of severe radiationinduced lung toxicity when treated with combined chemoradiotherapy. These easily obtained

  19. Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2016-05-19

    Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Polycythemia Vera; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  20. Acquired uniparental disomy in myeloproliferative neoplasms.

    Science.gov (United States)

    Score, Joannah; Cross, Nicholas C P

    2012-10-01

    The finding of somatically acquired uniparental disomy, where both copies of a chromosome pair or parts of chromosomes have originated from one parent, has led to the discovery of several novel mutated genes in myeloproliferative neoplasms and related disorders. This article examines how the development of single nucleotide polymorphism array technology has facilitated the identification of regions of acquired uniparental disomy and has led to a much greater understanding of the molecular pathology of these heterogeneous diseases.

  1. Myeloproliferative neoplasms: A decade of discoveries and treatment advances.

    Science.gov (United States)

    Tefferi, Ayalew

    2016-01-01

    Myeloproliferative neoplasms (MPN) are clonal stem cell diseases, first conceptualized in 1951 by William Dameshek, and historically included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In 1960, Nowell and Hungerford discovered an invariable association between the Philadelphia chromosome (subsequently shown to harbor the causal BCR-ABL1 mutation) and CML; accordingly, the term MPN is primarily reserved for PV, ET, and PMF, although it includes other related clinicopathologic entities, according to the World Health Organization (WHO) classification system. In 2005, William Vainchenker and others described a Janus kinase 2 mutation (JAK2V617F) in MPN and this was followed by a series of additional descriptions of mutations that directly or indirectly activate JAK-STAT: JAK2 exon 12, myeloproliferative leukemia virus oncogene (MPL) and calreticulin (CALR) mutations. The discovery of these, mostly mutually exclusive, "driver" mutations has contributed to revisions of the WHO diagnostic criteria and risk stratification in MPN. Mutations other than JAK2, CALR and MPL have also been described in MPN and shown to provide additional prognostic information. From the standpoint of treatment, over the last 50 years, Louis Wasserman from the Unites States and Tiziano Barbui from Italy had skillfully organized and led a number of important clinical trials, whose results form the basis for current treatment strategies in MPN. More recently, allogeneic stem cell transplant, as a potentially curative treatment modality, and JAK inhibitors, as palliative drugs, have been added to the overall therapeutic armamentarium in myelofibrosis. In the current review, I will summarize the important advances made in the last 10 years regarding the science and practice of MPN.

  2. Radiation induced fracture of the scapula

    Energy Technology Data Exchange (ETDEWEB)

    Riggs, J.H. III; Schultz, G.D.; Hanes, S.A. (Los Angeles College of Chiropractic, Whittier, CA (USA))

    1990-10-01

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

  3. Radiatively induced quark and lepton mass model

    Science.gov (United States)

    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.

  4. Study of chemical and radiation induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Radiation induced glioblastoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Naoki; Kayama, Takamasa; Sakurada, Kaori; Saino, Makoto; Kuroki, Akira [Yamagata Univ. (Japan). School of Medicine

    2000-05-01

    We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. A autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and secondary glioblastoma. (author)

  6. Radiation-Induced Heart Disease: Pathologic Abnormalities and Putative Mechanisms

    Directory of Open Access Journals (Sweden)

    Neil K Taunk

    2015-02-01

    Full Text Available Breast cancer is a common diagnosis in women. Breast radiation has become a critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation induced heart disease (RIHD comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation.

  7. Probabilistic methodology for estimating radiation-induced cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2

    NARCIS (Netherlands)

    Nangalia, J.; Massie, C.E.; Baxter, E.J.; Nice, F.L.; Gundem, G.; Wedge, D.C.; Avezov, E.; Li, J.; Kollmann, K.; Kent, D.G.; Aziz, A.; Godfrey, A.L.; Hinton, J.; Martincorena, I.; Loo, P. Van; Jones, A.V.; Guglielmelli, P.; Tarpey, P.; Harding, H.P.; Fitzpatrick, J.D.; Goudie, C.T.; Ortmann, C.A.; Loughran, S.J.; Raine, K.; Jones, D.R.; Butler, A.P.; Teague, J.W.; O'Meara, S.; McLaren, S.; Bianchi, M.; Silber, Y.; Dimitropoulou, D.; Bloxham, D.; Mudie, L.; Maddison, M.; Robinson, B.; Keohane, C.; Maclean, C.; Hill, K.; Orchard, K.; Tauro, S.; Du, M.Q.; Greaves, M.; Bowen, D.; Huntly, B.J.; Harrison, C.N.; Cross, N.C.; Ron, D.; Vannucchi, A.M.; Papaemmanuil, E.; Campbell, P.J.; Green, A.R.

    2013-01-01

    BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing

  9. Effects of the PI-3K/AKT signal transduction pathway on the chronic myeloproliferative diseases with JAK2 gene mutation%CMPN基因突变及其机制与生物学意义的探讨

    Institute of Scientific and Technical Information of China (English)

    牛志云; 郭晓玲; 张敬宇; 杨琳; 罗建民

    2013-01-01

    目的:分析JAK2基因突变阳性的慢性骨髓增殖性疾病(myeloproliferative neoplaspsms,CMPN)患者多种细胞因子受体和关键蛋白的表达变化,探讨其可能的发病机制.方法:采用Taqman-MGB探针联合RT-PCR法从50例CMPN患者中筛选出JAK2V617F突变阳性患者,计算突变率,并对突变结果进行测序分析.实时荧光定量PCR检测真性红细胞增多症(polycythernia vera,V)患者、原发性血小板增多症(essential thrombocytosisET)患者和原发性骨髓纤维化(idiopathic myelofibrosis,MF)患者骨髓中G-CSFR、EPOR和TPOR mRNA的表达,蛋白质印迹法检测PV患者、ET患者和IMF患者骨髓中PI-3K、P-AKT和AKT总蛋白的表达.结果:PV、ET和IMF患者的突变率分别为75.0%(15/20)、46.7%(7/15)和26.7%(4/15).与健康志愿者相比,PV、ET和IMF患者骨髓中G-CSFR mRNA相对表达水平分别增加了263.16%、276.32%和247.37%,EPOR mRNA表达量分别增加了213.95%、220.93%和218.61%,TPOR mRNA表达量分别增加了172.55%、176.47%和182.35%.PI-3K蛋白表达水平分别增加了115.79%、92.11%和100.00%,P-AKT蛋白表达水平分别增加了226.09%、243.48%和200.00%,差异均有统计学意义,P<0.05;总AKT蛋白水平各组之间比较差异无统计学意义,P>0.05.结论:JAK2V617F点突变存在于大多数CMPN中,此突变可能通过介导EPOR、TPOR和G-CSFR在内的多种细胞因子的信号转导,激活PI-3K/AKT信号转导通路,进而促进细胞增殖,抑制细胞凋亡参与CMPD的发病机制.%OBJECTIVE:To investigate the pathogenesis of myeloproliferative neoplaspsms(CMPN) with JAK2 gene mutation.METHODS:The patients of CMPN with JAK2/V617F gene mutation were selected by Taqman-MGB and RT-PCR,and the mutation rates were calculated.The JAK2/V617F gene mutation was detected by Sequence analysis software.The expression levels of G-CSFR,EPOR and TPOR-mRNA were measured by real-time fluorescent relative-quantification reverse

  10. Radiation induces acute alterations in neuronal function.

    Directory of Open Access Journals (Sweden)

    Peter H Wu

    Full Text Available Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(ARs. These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

  11. Radiation induced erosion of autoelectron emitter surface

    CERN Document Server

    Mazilova, T I; Ksenofontov, V A

    2001-01-01

    The peculiarities of erosion of the needle-shaped autoemitter surface under the effect of the helium ions bombardment are studied. The analysis of the radiation-induced formation of the surface atomic roughness testifies to the nondynamic character of shifting the surface atoms by the ions energies below the threshold of the Frenkel stable pairs formation and cathode sputtering. The quasistatic mechanism of the surface erosion due to the atoms shift into the low-coordination positions by releasing the energy of the helium internodal atoms formation is discussed

  12. Radiation-induced intracranial malignant fibrous histiocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Vitale, J.C.; Slavin, R.E.; McQueen, J.D.

    1976-06-01

    An autopsy case of radiation-induced intracranial malignant fibrous histiocytoma (fibroxanthosarcoma) is reported. The tumor developed in the region of the sella turcica 11 years after high dose radiotherapy of a chromophobe adenoma of the pituitary. The tumor had infiltrated the base of the brain as well as the base of the skull. Metastases were not found. The tumor was composed of an admixture of bizarre fibroblasts, histiocytes and giant cells, xanthoma cells and siderophages, with a storiform fibrous stroma. This appears to be the first documented instance of a malignant fibrous histiocytoma occurring intracranially after local x irradiation.

  13. Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia

    Directory of Open Access Journals (Sweden)

    M B Agarwal

    2015-01-01

    Full Text Available According to the 2008 revision of the World Health Organization (WHO classification of myeloid malignancies, philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs include clonal, hematologic disorders such as polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Recent years have witnessed major advances in the understanding of the molecular pathophysiology of these rare subgroups of chronic, myeloproliferative disorders. Identification of somatic mutations in genes associated with pathogenesis and evolution of these myeloproliferative conditions (Janus Kinase 2; myeloproliferative leukemia virus gene; calreticulin led to substantial changes in the international guidelines for diagnosis and treatment of Ph-negative MPN during the last few years. The MPN-Working Group (MPN-WG, a panel of hematologists with expertise in MPN diagnosis and treatment from various parts of India, examined applicability of this latest clinical and scientific evidence in the context of hematology practice in India.This manuscript summarizes the consensus recommendations formulated by the MPN-WG that can be followed as a guideline for management of patients with Ph-negative MPN in the context of clinical practice in India.

  14. Future therapies for the myeloproliferative neoplasms.

    Science.gov (United States)

    Scherber, Robyn; Mesa, Ruben A

    2011-03-01

    Ever since their description as "myeloproliferative syndromes" by William Dameshek in 1951, the myeloproliferative neoplasms (MPNs) have been managed by the selective use of rather mundane, nonspecific therapies that rely on either antiplatelet effects or myelosuppression. The year 2005 ushered in a new era of drug development and discovery for the MPNs after the description of the JAK2 V617F mutation and the role this constitutively active tyrosine kinase has in MPN pathogenesis. Subsequently, multiple pharmacologic agents have begun (or are about to begin) testing for the inhibition of JAK2 in an attempt to improve the treatment of MPNs. Both primary myelofibrosis and myelofibrosis following essential thrombocythemia or polycythemia vera have been the targets of the most extensive testing of these agents to date. Responses to these oral JAK2 inhibitors have been primarily intended to reduce splenomegaly and meaningfully improve symptoms; effects on the JAK2 V617F allele burden or marrow histology are limited. Toxicities have ranged from myelosuppression to significant diarrhea. Additional agents with other mechanisms of action are also targeting JAK2, including histone deacetylase inhibitors and mTOR inhibitors. The results of preliminary trials of JAK2 inhibitors in polycythemia vera and essential thrombocythemia have been mixed but are premature. Many questions remain as to the optimal JAK2 inhibitory strategy and the full extent of the benefit of single-agent JAK2 inhibition.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    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.

  16. Triptolide Mitigates Radiation-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    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

  17. Radiation-induced esophagitis in lung cancer

    Directory of Open Access Journals (Sweden)

    Baker S

    2016-10-01

    Full Text Available Sarah Baker, Alysa Fairchild Department of Radiation Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada Abstract: Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed. Keywords: non–small cell lung cancer, acute, late, toxicity, stricture

  18. Radiation-Induced Esophagitis Exacerbated by Everolimus

    Directory of Open Access Journals (Sweden)

    Yuji Miura

    2013-06-01

    Full Text Available Background: Everolimus, a potent mammalian target of rapamycin (mTOR inhibitor, has shown anticancer activity against various types of cancer, including renal cell carcinoma (RCC; however, little information is available on the efficacy and safety of the combination of everolimus and radiotherapy. We report a case of radiation-induced esophagitis that might have been exacerbated by the sequential administration of everolimus. Case Presentation: A 63-year-old Japanese man with RCC complained of back pain, and magnetic resonance imaging revealed vertebral metastases. He received radiotherapy (30 Gy/10 fractions to the T6-10 vertebrae. Everolimus was administered immediately after the completion of radiotherapy. One week later, he complained of dysphagia, nausea and vomiting. An endoscopic examination of the esophagus showed erosive esophagitis in the middle to lower portions of his thoracic esophagus, corresponding to the irradiation field. Conclusion: Clinicians should be aware that everolimus might lead to the unexpected exacerbation of radiation toxicities.

  19. Radiation-induced valvular heart disease.

    Science.gov (United States)

    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.

  20. Hemorrhagic and thrombotic complications in patients with myeloproliferative diseases

    Directory of Open Access Journals (Sweden)

    Carla Valladares Vignal

    Full Text Available OBJECTIVE: To correlate the incidence of hemorrhage and thrombosis to bleeding time (BT and platelet aggregation in 27 consecutive patients with myeloproliferative diseases (MPD. DESIGN: Retrospective study. SETTING: Public tertiary referral center. PATIENTS: Eighteen patients with chronic myelogenous leukemia (CML, 5 with polycytemia vera (PV, 2 with essential thrombocytemia (ET and 2 with idiopathic myelofibrosis (MF. Duke's BT and epinephrine-induced platelet aggregation were performed on the patients and on 10 healthy individuals. RESULTS: Eleven patients presented symptoms (41 %: 9 with hemorrhage (33% and 5 with thrombosis (19%.There were less symptomatic patients in the CML group (28% than in the other MPD (67%, without statistical significance (Fisher, p=0.06. Duke's BT was longer in symptomatic patients (Mann-Whitney, p<0.05. Platelet aggregation was abnormal in 7 patients (26% and 71% of them were symptomatic (Fisher, p = 0.07. CONCLUSIONS: The high incidence of bleeding and thrombosis in patients with MPD was related to prolonged BT, but not to platelet aggregation abnormalities.

  1. Pathological consequences of chronic low daily dose gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Miller, A.C.; Ramakrishnan, N. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States); Fritz, T.E.

    2000-07-01

    The quantitative relationships between the chronic radiation exposure parameters of dose-rate and total dose in relation to associated health risks was examined in dogs. At a dose-rate of 75, 128, and 263 mGy/d the incidence of acute lymphohematopoietic suppression (aplastic anemia) and associated septic complications was 73%, 87%, and 100%, respectively, and it increased in dose-dependent manner. By contrast, at dose-rates below 75 mGy/d, late cancers contributed significantly to the death of relatively long-lived animals, whose mean survival time was 1800 days. Myeloproliferative disease (MPD), mainly myeloid leukemia, was the dominant pathology seen at the higher daily dose-rates (18.8-75 mGy/d). When daily exposure was carried out continuously, the incidence of MPD was quite high. It should be noted that the induction radiation-induced MPD in this study was highly significant, because spontaneous MPD is exceedingly rare in the dog. However, when the daily dose-rate was reduced further or exposure was discontinued, the incidence of MPD declined significantly. At these lower dose-rates, solid tumors contributed heavily to the life-shortening effects of chronic irradiation. The induction and progression of these survival-compromising, late forms of pathology appeared to be driven by the degree of hematopoietic suppression that occurred early during the exposure phase, and in turn by the capacity of hematopoietic system to repair itself, recover, and to accommodate under chronic radiation stress. (K.H.)

  2. Myelodysplastic and myeloproliferative disorders of childhood

    DEFF Research Database (Denmark)

    Hasle, Henrik

    2016-01-01

    Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each...... with refractory anemia with excess blasts are candidates for HSCT; children age 12 years or older have a higher risk of treatment-related death, and the conditioning regimens should be adjusted accordingly. Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL...... with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure...

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

    Science.gov (United States)

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

    2017-03-28

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

  4. Molecular biology of Philadelphia-negative myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Paulo Vidal Campregher

    2012-01-01

    Full Text Available Myeloproliferative neoplasms are clonal diseases of hematopoietic stem cells characterized by myeloid hyperplasia and increased risk of developing acute myeloid leukemia. Myeloproliferative neoplasms are caused, as any other malignancy, by genetic defects that culminate in the neoplastic phenotype. In the past six years, since the identification of JAK2V617F, we have experienced a substantial increase in our knowledge about the genetic mechanisms involved in the genesis of myeloproliferative neoplasms. Mutations described in several genes have revealed a considerable degree of molecular homogeneity between different subtypes of myeloproliferative neoplasms. At the same time, the molecular differences between each subtype have become clearer. While mutations in several genes, such as JAK2, myeloproliferative leukemia (MPL and LNK have been validated in functional assays or animal models as causative mutations, the roles of other recurring mutations in the development of disease, such as TET2 and ASXL1 remain to be elucidated. In this review we will examine the most prevalent recurring gene mutations found in myeloproliferative neoplasms and their molecular consequences.

  5. Radiation-induced cancer in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Shoji; Sekizuka, Eiichi [National Saitama Hospital, Wako (Japan); Yamashita, Hisao [Keio Cancer Center, Tokyo (Japan); Takami, Akira [Yamawaki Coll., Tokyo (Japan); Kubo, Atsushi [Keio Univ., Tokyo (Japan). School of Medicine

    2001-12-01

    Results of two questionnaire surveys on radiation-induced malignant tumors conducted in 1977 and 1984 in Japan are briefly summarized. A total of 234 universities and general hospitals (139 in 1977, and 95 in 1984) responded and provided data from 1945 to 1977 and from 1978 to 1984. The number of patients with benign disease who developed secondary malignant tumors following radiation therapy was 150 in the first survey (1977) and 86 in the second survey (1984). The underlying benign diseases of these patients included tuberculous lymphadenitis, skin disease, hemangioma, and thyroid disease, and the most frequent radiation-induced malignant tumors in these patients were malignant tumors of the pharynx (80), cancer of the larynx (26), malignant tumors of the thyroid gland (22), cancer of the esophagus (219), and skin cancer (21). In patients with head and neck diseases the highest correlation between underlying benign disease and radiation-induced malignant tumors was between cervical tuberculous lymphadenitis and tumors of the pharynx (67 patients), followed by cancer of the larynx (19), and malignant tumors of the thyroid gland (11). There were also correlations between thyroid disease and malignant tumors of the thyroid gland (8 patients), hemangioma and skin cancer (7), and skin disease and skin cancer (8). The ratio of the observed values to predicted values (O/E ratio) in these patients was highest for cancer of the pharynxy (118), followed by cancer of the parotid gland (42), skin cancer (31), cancer of the esophagus (22), malignant tumors of the thyroid gland (21), and cancer of the larynx (16). The number of patients with malignant tumors who developed secondary malignant tumors following radiation therapy was 140 in 1977 and 108 in 1984, and the underlying malignant tumors in these patients included tumors of the uterus (106), breast (32), and head and neck (80). The most frequent secondary malignant tumors were soft tissue tumors, followed by leukemia

  6. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  7. Operative treatment of radiation-induced fistulae

    Energy Technology Data Exchange (ETDEWEB)

    Balslev, I.; Harling, H.

    1987-01-01

    Out of 136 patients with radiation-induced intestinal complications, 45 had fistulae. Twenty-eight patients had rectovaginal fistulae while the remainder had a total of 13 different types of fistulae. Thirty-seven patients were treated operatively and eight were treated conservatively. Thirty-three patients were submitted to operation for rectal fistulae. Of these, 28 were treated by defunctioning colostomy, three were treated by Hartmann's method and resection and primary anastomosis was carried out in two patients. In the course of the period of observation, 35% of the patients developed new radiation damage. The frequency in the basic material without fistulae was 21% (0.05

  8. Novel concepts in radiation-induced cardiovascular disease.

    Science.gov (United States)

    Cuomo, Jason R; Sharma, Gyanendra K; Conger, Preston D; Weintraub, Neal L

    2016-09-26

    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.

  9. Radiation-Induced Alopecia after Endovascular Embolization under Fluoroscopy

    Directory of Open Access Journals (Sweden)

    Vipawee Ounsakul

    2016-01-01

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

  10. A case of radiation induced cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ozawa, Kazuyoshi; Tsuchikawa, Kohzo; Sato, Akira; Kato, Joji (Nippon Dental Univ., Niigata (Japan). School of Dentistry at Niigata)

    1994-06-01

    A case of carcinoma on the right buccal mucosa is presented. The case was suspected to have been induced by irradiation therapy for a carcinoma on the left buccal mucosa. An external radiotherapy, 6-MeV Linac, had been done for the carcinoma on the left buccal mucosa in a 55-year-old female, with single lateral direction from the left to the right in 1977. In 1985, a papillary lesion on the right buccal mucosa was detected, and histological examination revealed a papilloma without atypism. In 1991, as an ulcer on the right upper buccal fold as well as three papillary lesions in the central portion of the right buccal mucosa were found, the patient was referred to our clinic. Microscopical findings were consistent with the early invasive carcinomas. A surgical excision of these whole lesions and skin graft were completed. The criteria of this case for the suspicion of radiation-induced carcinoma were as follows. There was a long latent period of 14 years. The previous dose of irradiation, 60 Gy, was sufficient. The right buccal mucosa was involved in the radiation field. A severe scar on the left cheek resulted from the previous irradiation. Anatomically, there is no evidence of the secondary carcinoma on the right buccal mucosa with the primary carcinoma on the left buccal mucosa. No evidence for recurrence of the tumors on both sides of buccal mucosa has been detected so far. Further observations will be necessary to detect other tumors in the irradiated field later on. (author).

  11. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Rauch, Philipp J. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Faculty of Medicine, University of Heidelberg, Heidelberg (Germany); Park, Henry S. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Knisely, Jonathan P.S. [Department of Radiation Medicine, North Shore University Hospital, Manhasset, New York (United States); Chiang, Veronica L. [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States); Vortmeyer, Alexander O., E-mail: alexander.vortmeyer@yale.edu [Departments of Pathology and Neurosurgery, Yale University School of Medicine, New Haven, Connecticut (United States)

    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.

  12. The genetic basis of myeloproliferative disorders.

    Science.gov (United States)

    Skoda, Radek

    2007-01-01

    For many decades, myeloproliferative disorders (MPD) were largely neglected orphan diseases. The conceptual work of William Dameshek in 1951 provided the basis for understanding MPD as a continuum of related syndromes, possibly with a common pathogenetic cause. Recognition of the clonal origin of peripheral blood cells in MPD in 1976 and the ability to grow erythroid colonies in vitro in the absence of added growth factors in 1974 initiated the search for genetic alterations that might be responsible for myeloproliferation. Mutations in the genes for the erythropoietin receptor, thrombopoietin and the von Hippel-Lindau protein were found to cause familial syndromes resembling MPD, but despite their phenotypic similarities, none of these mutations were later found in patients with the sporadic form of MPD. The discovery of activating mutations in the Janus kinase 2 (JAK2) in most patients with MPD has fully transformed and energized the MPD field. Sensitive assays for detecting the JAK2-V617F mutation have become an essential part of the diagnostic work-up, and JAK2 now constitutes a prime target for developing specific inhibitors for the treatment of patients with MPD. Despite this progress, many questions remain unsolved, including how a single JAK2 mutation causes three different MPD phenotypes, what other genes might be involved in the pathogenesis, and what are the factors determining the progression to acute leukemia.

  13. Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis.

    Science.gov (United States)

    Borab, Zachary; Mirmanesh, Michael D; Gantz, Madeleine; Cusano, Alessandro; Pu, Lee L Q

    2017-04-01

    Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

    2014-09-15

    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.

  15. Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2

    Science.gov (United States)

    Baxter, E.J.; Nice, F.L.; Gundem, G.; Wedge, D.C.; Avezov, E.; Li, J.; Kollmann, K.; Kent, D.G.; Aziz, A.; Godfrey, A.L.; Hinton, J.; Martincorena, I.; Van Loo, P.; Jones, A.V.; Guglielmelli, P.; Tarpey, P.; Harding, H.P.; Fitzpatrick, J.D.; Goudie, C.T.; Ortmann, C.A.; Loughran, S.J.; Raine, K.; Jones, D.R.; Butler, A.P.; Teague, J.W.; O’Meara, S.; McLaren, S.; Bianchi, M.; Silber, Y.; Dimitropoulou, D.; Bloxham, D.; Mudie, L.; Maddison, M.; Robinson, B.; Keohane, C.; Maclean, C.; Hill, K.; Orchard, K.; Tauro, S.; Du, M.-Q.; Greaves, M.; Bowen, D.; Huntly, B.J.P.; Harrison, C.N.; Cross, N.C.P.; Ron, D.; Vannucchi, A.M.; Papaemmanuil, E.; Campbell, P.J.; Green, A.R.

    2014-01-01

    BACKGROUND Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with

  16. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  17. Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan;

    2008-01-01

    BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... with variable risk of RIF (grouped into five classes from low to high risk) were irradiated with two different schemes: 1x3.5Gy with RNA isolated 2 and 24h after irradiation, and a fractionated scheme with 3x3.5Gy in intervals of 24h with RNA isolated 2h after the last dose. RNA was also isolated from non...... risk from low risk-patients after the fractionated scheme. CONCLUSIONS: The classifier of 18 genes may provide basis for a predictive assay for normal tissue reactions after radiotherapy, and provide new insight into the molecular mechanisms of RIF....

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

    AIM: To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during threedimensional conformal radiotherapy (3D-CRT). METHODS: We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria.RESULTS: Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, nograde 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P= 0.0001<0.01).CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

  19. Ionizing radiation induced cataract; Katarakt-Induktion durch ionisierende Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, W.U. [Universitaetsklinikum Essen (Germany). Inst. fuer Medizinische Strahlenbiologie

    2013-07-01

    Until recently it was believed that the cataract (opacity of the eye lens) is a deterministic effect with a dose threshold of several Gray in dependence on the exposure conditions. Studies in Hiroshima and Nagasaki, in the vicinity of Chernobyl, of American radiologic technologists, astronauts, and patients after having received several computer tomographies of the head region, however, have shown that this assumption is not correct. It had been overlooked in the past that with decreasing dose the latency period is increasing. Therefore, the originally available studies were terminated too early. The more recent studies show that, in the case of a threshold existing at all, it is definitely below 0.8 Gy independently of an acute or a chronic exposure. All studies, however, include 0 Gy in the confidence interval, so that the absence of a dose threshold cannot be excluded. The German Commission on Radiological Protection (Strahlenschutzkommission, SSK) suggested therefore among others: targeted recording of the lens dose during activities which are known to be associated with possible significant lens exposure, examination of the lens should be included as appropriate in the medical monitoring of people occupationally exposed to radiation, if there is potentially high lens exposure, adoption of research strategies to develop a basic understanding of the mechanisms underlying radiation induced cataracts. The International Commission on Radiological Protection (ICRP) actually assumes a threshold dose of 0.5 Gy and, based on this assumption, has recommended in 2011 to reduce the dose limit for the eye lens from 150 mSv in a year to 20 mSv in a year for people occupationally exposed to ionising radiation. (orig.)

  20. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Joseph Tripodi

    2010-09-01

    Full Text Available Joseph Tripodi1, Ronald Hoffman1, Vesna Najfeld2, Rona Weinberg31The Myeloproliferative Disorders Program, Tisch Cancer Institute, Department of Medicine and 2Department of Medicine and Pathology, Mount Sinai School of Medicine, 3The Myeloproliferative Disorders Program, Cellular Therapy Laboratory, The New York Blood Center, New York, NY, USAAbstract: The Philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2 on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4% who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%.Keywords: TET2, myeloproliferative neoplasms, fluorescence in situ hybridization, cytogenetics

  1. Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

    Science.gov (United States)

    Schnegg, Caroline Isabel

    As a result of improvements in cancer therapy and health care, the population of long-term cancer survivors is growing. For these approximately 12 million long-term cancer survivors, brain metastases are a significant risk. Fractionated partial or whole-brain irradiation (fWBI) is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year. Recent reports indicate that radiation-induced brain injury is associated with chronic inflammatory and oxidative stress responses, as well as increased microglial activation in the brain. Anti-inflammatory drugs may, therefore, be a beneficial therapy to mitigate radiation-induced brain injury. We hypothesized that activation of peroxisomal proliferator activated receptor delta (PPARō) would prevent or ameliorate radiation-induced brain injury, including cognitive impairment, in part, by alleviating inflammatory responses in microglia. For our in vitro studies, we hypothesized that PPARō activation would prevent the radiation-induced inflammatory response in microglia following irradiation. Incubating BV-2 murine microglial cells with the (PPAR)ō agonist, L-165041, prevented the radiation-induced increase in: i) intracellular ROS generation, ii) Cox-2 and MCP-1 expression, and iii) IL-1β and TNF-α message levels. This occured, in part, through PPARō-mediated modulation of stress activated kinases and proinflammatory transcription factors. PPARō inhibited NF-κB via transrepression by physically interacting with the p65 subunit, and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular ROS generation. These data support the hypothesis that PPARō activation can modulate the radiation-induced oxidative stress and inflammatory responses in

  2. Prophylactic role of melatonin against radiation induced damage in mouse cerebellum with special reference to Purkinje cells

    Energy Technology Data Exchange (ETDEWEB)

    Sisodia, Rashmi; Kumari, Seema; Verma, Rajesh Kumar; Bhatia, A L [Neurobiology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004 (India)

    2006-06-15

    Melatonin, a hormone with a proven antioxidative efficacy, crosses all morphophysiological barriers, including the blood-brain barrier, and distributes throughout the cell. The present study is an attempt to investigate the prophylactic influence of a chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss albino mice, with special reference to Purkinje cells. After 15 days of treatment the mice were sacrificed at various intervals from 1 to 30 days. Biochemical parameters included lipid peroxidation (LPO) and glutathione (GSH) levels as the endpoints. The quantitative study included alterations in number and volume of Purkinje cells. Swiss albino mice were orally administered a very low dose of melatonin (0.25 mg/mouse/day) for 15 consecutive days before single exposure to 4 Gy gamma radiation. Melatonin checked the augmented levels of LPO, by approximately 55%, by day 30 day post-exposure. Radiation induced depleted levels of GSH could be raised by 68.9% by day 30 post-exposure. Radiation exposure resulted in a reduction of the volume of Purkinje cells and their total number. The administration of melatonin significantly protected against the radiation induced decreases in Purkinje cell volume and number. Results indicate the antioxidative properties of melatonin resulting in its prophylactic property against radiation induced biochemical and cellular alterations in the cerebellum. The findings support the idea that melatonin may be used as an anti-irradiation drug due to its potent free radical scavenging and antioxidative efficacy.

  3. Radiation-induced osteosarcoma of the calvaria; Case report

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Yasuo; Shigemori, Minoru; Miyagi, Jun; Ochiai, Satoshi; Lee, Souichi; Watanabe, Toshinori; Abe, Hitoshi; Morimatsu, Minoru (Kurume Univ., Fukuoka (Japan). School of Medicine)

    1992-01-01

    The authors report a case of radiation-induced calvarial osteosarcoma. A 58-year-old female received subtotal removal of the pituitary adenoma and 5000 rads postoperative irradiation. Seven years later, an osteoblastic osteosarcoma occurred in the frontotemporal region. She received total tumor removal and chemotherapy. However, computed tomography subsequently revealed multiple small lesions at the margin of the bone flap. A chest x-ray film demonstrated lung metastasis. Local recurrence and lung metastasis require careful attention in radiation-induced osteosarcoma patients. (author).

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

    NARCIS (Netherlands)

    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    White, D.P. [Oak Ridge National Lab., TN (United States)

    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.

  8. The modulation of radiation-induced cell death by genistein in K562 cells:Activation of thymidine kinase 1

    Institute of Scientific and Technical Information of China (English)

    Min Ho JEONG; Young Hee JIN; Eun Young KANG; Wol Soon JO; Hwan Tae PARK; Jae Dong LEE; Yeo Jin YOO; Soo Jin JEONG

    2004-01-01

    Ionizing radiation is one of the most effective tools in cancer therapy. In a previous study, we reported that protein tyrosine kinase (PTK) inhibitors modulate the radiation responses in the human chronic myelogenous leukemia (CML)cell line K562. The receptor tyrosine kinase inhibitor, genistein, delayed radiation-induced cell death, while non-recepter tyrosine kinase inhibitor, herbimycin A (HMA) enhances radiation-induced apoptosis. In this study, we focused on the modulation of radiation-induced cell death by genistein and performed PCR-select suppression subtractive hybridization(SSH) to understand its molecular mechanism. We identified human thymidine kinase 1 (TK1), which is cell cycle regulatory gene and confirmed expression of TK1 mRNA by Northern blot analysis. Expression of TK1 mRNA and TK 1enzymatic activity were parallel in their increase and decrease. TK1 is involved in G1-S phase transition of cell cycle progression. In cell cycle analysis, we showed that radiation induced G2 arrest in K562 cells but it was not able to sustain. However, the addition of genistein to irradiated cells sustained a prolonged G2 arrest up to 120 h. In addition,the expression of cell cycle-related proteins, cyclin A and cyclin B 1, provided the evidences of G1/S progression and G2-arrest, and their relationship with TK1 in cells treated with radiation and genistein. These results suggest that the activation of TK1 may be critical to modulate the radiation-induced cell death and cell cycle progression in irradiated K562 cells.

  9. Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin [Leipzig University, Department of Radiotherapy and Radiation Oncology, Leipzig (Germany)

    2015-10-15

    In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [German] In den letzten Jahren haben Bewegungsstoerungen von Wirbelsaeule und paraspinaler Muskulatur in

  10. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

    Directory of Open Access Journals (Sweden)

    Jianhong Ye

    Full Text Available PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs, internal carotid arteries (ICAs and basal artery (BA were estimated through Transcranial Color Doppler (TCD. The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05. IMT had positive correlation with post radiation interval (p = 0.049. Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001. Plaques were more common in patients with TLN than patients without TLN (p = 0.038. In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001. Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001. CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

  11. Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms

    Science.gov (United States)

    Bhagwat, Neha; Koppikar, Priya; Keller, Matthew; Marubayashi, Sachie; Shank, Kaitlyn; Rampal, Raajit; Qi, Jun; Kleppe, Maria; Patel, Hardik J.; Shah, Smit K.; Taldone, Tony; Bradner, James E.; Chiosis, Gabriela

    2014-01-01

    The discovery of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to clinical development of Janus kinase (JAK) inhibitors for treatment of MPN. These inhibitors improve constitutional symptoms and splenomegaly but do not significantly reduce mutant allele burden in patients. We recently showed that chronic exposure to JAK inhibitors results in inhibitor persistence via JAK2 transactivation and persistent JAK–signal transducer and activator of transcription signaling. We performed genetic and pharmacologic studies to determine whether improved JAK2 inhibition would show increased efficacy in MPN models and primary samples. Jak2 deletion in vivo led to profound reduction in disease burden not seen with JAK inhibitors, and deletion of Jak2 following chronic ruxolitinib therapy markedly reduced mutant allele burden. This demonstrates that JAK2 remains an essential target in MPN cells that survive in the setting of chronic JAK inhibition. Combination therapy with the heat shock protein 90 (HSP90) inhibitor PU-H71 and ruxolitinib reduced total and phospho-JAK2 and achieved more potent inhibition of downstream signaling than ruxolitinib monotherapy. Combination treatment improved blood counts, spleen weights, and reduced bone marrow fibrosis compared with ruxolitinib alone. These data suggest alternate approaches that increase JAK2 targeting, including combination JAK/HSP90 inhibitor therapy, are warranted in the clinical setting. PMID:24470592

  12. Overexpression of matrix metalloproteinase-12 (MMP-12) correlates with radiation-induced lung fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Gu; Jeong, Ye Ji; Lee, Haejune [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Sujae [Hanyang Univ., Seoul (Korea, Republic of)

    2014-05-15

    MMPs are classified into five subgroups: collagenases (MMP-1, MMP-8, MMP-13), gelatinases (MMP-2, MMP-9), stromelysins (MMP-3, MMP-10, MMP-11), as well as metalloelastase (MMP-12), the membrane-type MMPs (MMP14, MMP15), and other MMPS (e. g., MMP-19, and MMP20). MMP-12 (matrix metalloproteinase12), also known as macrophage metalloelastase, was first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages 30 years ago. MMP-12 degrades extracellular matrix (ECM) components to facilitate tissue remodeling. It can degrade elastin and other substrates, such as type IV collagen, fibronectin, laminin, gelatin, vitronectin, entactin, heparin, and chondroitin sulfates. In the lung, MMP-12 is identified in alveolar macrophages of cigarette smokers as an elastolytic MMP. Inactivation of the MMP-12 gene in knockout mice demonstrates a critical role of MMP-12 in smoking-induced chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the effects of MMP-12 by radiation in lung, so we evaluate that MMP-12 expression pattern in normal lung tissue and cancer cell following radiation. Radiation induced lung injury most commonly occurs as a result of radiation therapy administered to treat cancer. The present study demonstrates that MMP-12 was highly increased in the lung damaged by radiation Thus, MMP-12 might be of potential relevance as a clinically diagnostic tool and sensitive biomarker for radiation induced lung injury and fibrosis.

  13. Lack of p53 function promotes radiation-induced mitotic catastrophe in mouse embryonic fibroblast cells

    Directory of Open Access Journals (Sweden)

    Phillips Stacia L

    2006-04-01

    Full Text Available Abstract Background We have demonstrated that in some human cancer cells both chronic mild heat and ionizing radiation exposures induce a transient block in S and G2 phases of the cell cycle. During this delay, cyclin B1 protein accumulates to supranormal levels, cyclin B1-dependent kinase is activated, and abrogation of the G2/M checkpoint control occurs resulting in mitotic catastrophe (MC. Results Using syngenic mouse embryonic fibroblasts (MEF with wild-type or mutant p53, we now show that, while both cell lines exhibit delays in S/G2 phase post-irradiation, the mutant p53 cells show elevated levels of cyclin B1 followed by MC, while the wild-type p53 cells present both a lower accumulation of cyclin B1 and a lower frequency of MC. Conclusion These results are in line with studies reporting the role of p53 as a post-transcriptional regulator of cyclin B1 protein and confirm that dysregulation of cyclin B1 promote radiation-induced MC. These findings might be exploited to design strategies to augment the yield of MC in tumor cells that are resistant to radiation-induced apoptosis.

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

    Science.gov (United States)

    Okazaki, Ryuji; Ootsuyama, Akira; Norimura, Toshiyuki

    2005-03-01

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

  15. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Institute of Scientific and Technical Information of China (English)

    JIANG Erkang; WU Lijun

    2009-01-01

    A bstract In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy a-particle irradiated and non-irradiated by- stander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensi- tive 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 a-particle radiation-induced damage in ir- radiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE).

  16. A case of radiation-induced cancer of the hypopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Kouji; Shimizu, Yukio; Yura, Jirou; Itoh, Yasufumi; Ikeda, Tsuneko [Matsunami General Hospital, Kasamatsu, Gifu (Japan); Outsubo, Toshio; Saitou, Hitoshi

    2001-06-01

    We report a case of radiation-induced cancer of the hypopharynx in a 65-year-old woman. The patient had received radiation treatment for Basedow's disease for several years starting at the age of 10 years. On June 26, 1993, she was examined at our hospital because of hoarseness and dysphagia. On July 22, right lobectomy was performed for suspected thyroid cancer. During this operation, endoscopy revealed hypopharyngeal cancer. Twenty-two days after surgery, total pharyngolaryngectomy and total esophagectomy were performed and a pharyngogastrostomy and a permanent tracheostomy were created. Histologic examination revealed moderately differentiated squamous cell cancer. This case was diagnosed as radiation-induced caner according to the diagnostic criteria of Sakai. (author)

  17. Radiation-induced defect formation in chalcogenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O.I.; Filipecki, J. [Physics Institute of Pedagogical University of Czestochowa, Al. Armii Krajowej 13/15, Czestochowa 42201 (Poland); Kozdras, A. [Physics Laboratory of Opole Technical University, 75 ul. Ozimska, Opole, PL-45370 (Poland); Kavetskyy, T.S. [Lviv Scientific Research Institute of Materials of Scientific Research Company ' Carat' , Stryjska Str. 202, Lviv, UA-79031 (Ukraine)

    2003-10-01

    The modified model of native and radiation-induced microvoid-type positron traps in vitreous chalcogenide semiconductors is developed to explain compositional features of positron annihilation lifetime measurements in stoichiometric As{sub 2}S{sub 3}-GeS{sub 2} and non-stoichiometric As{sub 2}S{sub 3}-Ge{sub 2}S{sub 3} chalcogenide glasses before and after {gamma}-irradiation.

  18. Radiation-induced morphea of the breast: a case report

    Directory of Open Access Journals (Sweden)

    Cheah Nellie LC

    2008-04-01

    Full Text Available Abstract Radiation-induced morphea (RIM of the breast is a rare complication of radiotherapy. It is disfiguring, painful and defeats the purpose of achieving a good cosmesis in breast-conservation surgery. This report describes a severe case of RIM in a breast cancer patient together with photographic illustrations of the serial changes over time and histopathology slides. A review of the literature is provided.

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

    Science.gov (United States)

    Washington, Kenneth; Fogarty, T. N.

    1997-01-01

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

  20. Radiation-induced edge effects in deep submicron CMOS transistors

    CERN Document Server

    Faccio, F

    2005-01-01

    The study of the TID response of transistors and isolation test structures in a 130 nm commercial CMOS technology has demonstrated its increased radiation tolerance with respect to older technology nodes. While the thin gate oxide of the transistors is extremely tolerant to dose, charge trapping at the edge of the transistor still leads to leakage currents and, for the narrow channel transistors, to significant threshold voltage shift-an effect that we call Radiation Induced Narrow Channel Effect (RINCE).

  1. Radiation-Induced Differentiation in Human Lung Fibroblast

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-10-15

    One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of {alpha}-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-{beta}), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-{beta} with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-{beta} but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90.

  2. Radiation Induces Cathepsin S through ROS-IFN-{gamma} Pathways: Involvement of Cellular Radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Haeng Ran; Lee, Yun-Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Joon [Korea University, Seoul (Korea, Republic of)

    2008-05-15

    Ionizing radiation can elicit an activated phenotype that promotes rapid and persistent remodeling of the extracellular matrix (ECM) through the induction of proteases and growth factors, as well as in response to chronic production of reactive oxygen species (ROS). In addition, the results of previously conducted cDNA microarrays and real-time RT-PCR analysis (unpublished) suggest that radiation-induced mammary tumors were specifically induced by cathepsin S (CTSS), but that dimethylbenz(a)anthracene (DMBA)-induced mammary tumors were not. CTSS is a lysosomal cystein protease that is synthesized as an inactive precursor (36kDa) and activated in the acidic environment of lysosomes by proteolytic cleavage of its propeptide. In this study, we further investigate the mechanism by which CTSS is induced by radiation as well as its function.

  3. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Vijayalakshmi; Tripathi, Preeti [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Sharma, Sunil [Department of Radiation Oncology, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Moros, Eduardo G. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Zheng, Junying [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hauer-Jensen, Martin [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas (United States); Boerma, Marjan, E-mail: mboerma@uams.edu [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States)

    2014-01-01

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

  4. Correlation between JAK2 allele burden and pulmonary arterial hypertension and hematological parameters in Philadelphia negative JAK2 positive myeloproliferative neoplasms. An Egyptian experience.

    Science.gov (United States)

    Mattar, Mervat M; Morad, Mohammed Abdel Kader; El Husseiny, Noha M; Ali, Noha H; El Demerdash, Doaa M

    2016-10-01

    Myeloproliferative neoplasms are characterized by a common stem cell-derived clonal proliferation, but are phenotypically diverse. JAK2 is mutated (V617F) in more than 90 % of patients with polycythemia vera (PV) and approximately 60 % of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Pulmonary arterial hypertension (PAH) is a major complication of several hematological disorders. Chronic myeloproliferative disorders associated with PAH have been included in group five for which the etiology is unclear and/or multifactorial. The aim of this study is to screen Egyptian Philadelphia negative JAK2 positive myeloproliferative neoplasm patients for the presence of PAH and its correlation with JAK2 allele burden. We also made a review for correlation of JAK2 allele with hematological parameters comparing our results to others. We enrolled 60 patients with Philadelphia negative myeloproliferative neoplasms. All patients enrolled in the study were subjected to laboratory and imaging workup in the form of CBC, liver, kidney profile, bone marrow examination, abdominal ultrasonography, and transthoracic echocardiography. Our results revealed that 7 patients out of 60 (11.67 %) had pulmonary arterial hypertension, 3 patients with PMF, 2 patients with PRV, and 2 patients with ET, and its correlation with JAK2 allele burden was not statistically significant. Correlation analysis between JAK2 V617F allele burden and other parameters revealed: statistical significant correlation with age, HB, HCT, PLT, UA, LDH, and splenic diameter but insignificant correlation with WBCs and PAH. Pulmonary arterial hypertension prevalence in our study was 11.67 % and no significant correlation with JAK 2 allele burden. Our study is the largest one up to our knowledge that studies the association between its prevalence and JAK2 burden.

  5. p53-dependent apoptosis suppresses radiation-induced teratogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan). School of Medicine

    1999-06-01

    About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions. Experimental studies with mice have established that irradiation during the preimplantation period of the embryo induces a high incidence of prenatal deaths but virtually no malformations. This suggests that some mechanism is screening out the damaged fetuses. In order to elucidate the mechanisms of tissue repair of radiation-induced teratogenic injury, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53{sup -/-}) and wild-type (p53{sup +/+}) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53{sup -/-} mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53{sup +/+} mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that the p53 gene protects embryos and fetuses against the teratogenic effects of radiation by eliminating cells that have been badly damaged. In fact, after X-irradiation, the frequency of dying cells by apoptosis was greatly increased in tissues of the p53{sup +/+} fetuses but not at all in those of the p53{sup -/-} fetuses. Mammals are protected from radiation-induced injury by two mechanisms, p53-dependent apoptotic tissue repair in addition to well known DNA repair. Therefore, there are threshold doses below which there is no induction of teratogenic and carcinogenic effects after exposure to low-level radiation. (author)

  6. Construction of radiation - induced metastasis model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Kim, Jae Sung; Hwang, Sang Gu; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    In treatment of cancer, distant metastases are important limiting factor because an estimated 50% of all cancer patients will develop metastases, and the metastases are major causing of cancer treatment failure. Recently a few reports indicated {gamma}-radiation induced an increase of invasiveness of several cancer cells. In this study, we had tried to show the possibility that radiation could also induce metastasis in vivo system. To prove our hypothesis, we constructed primary tumor by using C6-TL transfectant cell line expressing HSV1-tk and firefly luciferase (fLuc), and then {gamma}-radiation was treated to xenografts locally. Treatment of {gamma}-radiation to primary C6-TL xenografts of mice reduced size of xenografts and elongated survival of mice than those of mock control mice. But we also show that {gamma}-radiation treatment was followed by the growth of dormant metastases in various organs including lung and intestine after 2-4 weeks of {gamma}-radiation treatment. When bioluminescence imaging indicated growth of tumor in organs in mice, we sacrificed the mice and repeat acquired bioluminescence imaging after repeatedly. These images presented tumor growth locations exactly in organs. Because metastatic tumor candidates have morphology of foci, biopsies were performed for histological analysis or PCR analysis to confirm metastases. In most foci, histological analysis indicated several features of typical cancer tissue and PCR analysis showed present of fLuc gene in metastases. Detection of fLuc gene in metastases indicated these foci were originated from primary C6-TL xenografts, and the results suggest that {gamma}-radiation could promote metastasis in vivo as well as in vitro system. Although we need to understand changes of intracellular signaling or physiological phenomena of the radiation-induced metastasis yet, these results also imply that {gamma}-radiation treatment only to cancer patients need to pay attention carefully, and development of new

  7. Radiation-induced erectile dysfunction: Recent advances and future directions

    Directory of Open Access Journals (Sweden)

    Javed Mahmood, PhD

    2016-07-01

    Full Text Available Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to

  8. Sensitization of radiation-induced cell death by genistein

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Rim; Kim, In Gyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2010-03-15

    A number of epidemiological studies as well as biological experiments, showed that genistein, one of the isoflavone, prevents prostate cancer occurrence. In this study, we showed that genistein inhibited the cell proliferation of human promyeoltic leukemia HL-60 cells and induced G2/M phase arrest. In addition, combination of genistein treatment and {gamma}-irradiation displayed synergistic effect in apoptotic cell death of HL-60 cells. This means that the repair of genistein-induced DNA damage was hindered by {gamma}-irradiation and thus cell death was increased. In conclusion, genistein is one of the important chemicals that sensitize radiation-induced cell death.

  9. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Lee, Su-Jae; Bae, Sang-Woo; Lee, Yun-Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung-Ho [Chonnam National University, Gwangju (Korea, Republic of)

    2006-07-01

    Irradiation (IR) delivered to the head and neck is a common treatment for malignancies. Salivary glands in the irradiation field are severely damaged, and consequently this resulted in marked salivary hypofunction. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that inducible heat shock protein 70 (HSP70i) induced radioresistance in vitro. Moreover, HSP70i localized to salivary glands by gene transfer has great potential for the treatment of salivary gland. Herein, we investigated whether HSP70 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, E. Frederick; Zarick, Thomas Andrew; Sheridan, Timothy J.; Preston, E. [ITT Exelis Mission Systems, Colorado Springs, CO

    2013-05-01

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

  11. Measurements of prompt radiation induced conductivity of Kapton.

    Energy Technology Data Exchange (ETDEWEB)

    Preston, Eric F. (ITT Corporation, Colorado Springs, CO); Zarick, Thomas Andrew; Sheridan, Timothy J.; Hartman, E. Frederick; Stringer, Thomas Arthur (ITT Corporation, Colorado Springs, CO)

    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.

  12. Sensitivity to Radiation-Induced Cancer in Hemochromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Bull. Richard J.; Anderson, Larry E.

    2000-06-01

    The objectives of this pilot project using HFE-knockout homozygotes and heterozygotes are to (1) determine whether the knock-out mice have greater sensitivity to radiation-induced cancer of the colon, liver and breast, (2) establish the dependence of this sensitivity on the accumulation of iron, (3) determine the extent to which cell replication and apoptosis occur in these target tissues with varying iron load, and (4) correlate the increases in sensitivity with changes in insulin-related signaling in tumors and normal tissue from each target organ. Three experimental designs will be used in the pilot project. The sequence of experiments is designed to first explore the influence of iron load on the response and demonstrate that HFE knockout mice are more sensitive than the wild type to radiation-induced cancer in one or more of three target tissues (liver, colon and breast). The dose response relationships with a broader set of radiation doses will be explored in the second experiment. The final experiment is designed to explore the extent to which heterozygotes display the increased susceptibility to cancer induction and to independently assess the importance of iron load to the initiation versus promotion of tumors.

  13. Ionizing Radiation Induces HMGB1 Cytoplasmic Translocation and Extracellular Release

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    Objective A nucleosomal protein,HMGBI,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 radiation similarly induces cytoplasmic HMGB1 translocation and release.Methods Human skin fibroblast (GM0639) and bronchial epithelial (16HBE) cells and rats were exposed to X-ray radiation,and HMGB1 translocation and release were then 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 also associated with noticeable chromosomal DNA damage and loss of cell viability.Conclusions Radiation induces HMGB1 cytoplasmic translocation and extracellular release through active secretion and passive leakage processes.

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

    Science.gov (United States)

    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 genomic instability in Caenorhabditis elegans.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. Therapy and prophylaxis of acute and late radiation-induced sequelae of the esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, F.B.; Geinitz, H.; Feldmann, H.J. [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Muenchen (Germany)

    1998-11-01

    Background: Radiation-induced esophagitis is a frequent acute side effect in curative and palliative radiotherapy of thoracal and cervical tumors. Late reactions are rare but might be severe. Methods: A resarch for reports on prophylactic and supportive therapies of radiation-induced esophagitis was performed (Medline, Cancerlit, and others). Results: Nutrition must be ensured and symptomatic relief of sequelae is important, especially in the case of dysphagia. The latter can be improved by topic or systemic analgetics. If esophageal spasm occurs, calcium antagonists might help. In case of gastro-esophageal reflux proton pump inhibitors should be used. There is no effective prophylactic measure for radiation esophagitis. Late side effects with clinical relevance are rare in conventional radiotherapy. Chronic ulcera, fistula or stenosis may develop. Before any treatment, a tumor infiltration of the esophagus should be excluded by biopsy. This can lead more often to late complications than radiation therapy itself. Nutrition should be ensured by endoscopic dilation, stent-implantation, or endoscopic percutaneous gastrostomy. Local injection of steroids might be used to avoid an early restenosis. Conclusions: An intensive symptomatic therapy of acute esophagitis is reasonable. Effective prophylaxis do not exist. Late radiation induced sequelae is rare. Therefore, a tumor recurrenc e should be excluded in cases of dysphagia. Securing nutrition by PEG, stent, or port is well in the fore. (orig.) [Deutsch] Hintergrund: Die radiogene Oesophagitis ist eine haeufige akute Nebenwirkung bei kurativen wie palliativen Bestrahlungen thorakaler und zervikaler Tumoren. Spaete Gewebereaktionen sind selten, koennen aber schwerwiegend sein. Methode: Es wurde eine Literaturrecherche nach prophylaktischen und supportiven Therapien der radiogen verursachten Oesophagitis durchgefuehrt (Medline, Cancerlit und andere). Ergebnisse: Therapeutisch stehen die Sicherung der Ernaehrung und die

  18. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    Science.gov (United States)

    2016-10-07

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  19. Radiation induced genome instability: multiscale modelling and data analysis

    Science.gov (United States)

    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. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    Science.gov (United States)

    2017-03-21

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  1. JAK2 GGCC haplotype in MPL mutated myeloproliferative neoplasms.

    Science.gov (United States)

    Pietra, Daniela; Casetti, Ilaria; Da Vià, Matteo C; Elena, Chiara; Milanesi, Chiara; Rumi, Elisa

    2012-07-01

    JAK2 (V617F) is associated with a genetic predisposition to its acquisition,as it is preferentially found in subjects with a common constitutional JAK2 haplotype known as 46/1 or GGCC. A recent study suggests that a genetic predisposition to acquisition of MPL mutation may exist in sporadic patients, since an association was found with the JAK2 46/1 haplotype. We genotyped 509 patients with myeloproliferative neoplasms (MPN), 7% of which carrying a somatic mutation of MPL Exon 10. We found that the JAK2 GGCC haplotype was closely associated with JAK2 (V617F) (OR 1.84, P < 0.001) but not with MPL mutations (OR 0.98), suggesting a different genetic background for these molecular lesions.

  2. Mouse models of myeloproliferative neoplasms: JAK of all grades

    Directory of Open Access Journals (Sweden)

    Juan Li

    2011-05-01

    Full Text Available In 2005, several groups identified a single gain-of-function point mutation in the JAK2 kinase that was present in the majority of patients with myeloproliferative neoplasms (MPNs. Since this discovery, much effort has been dedicated to understanding the molecular consequences of the JAK2V617F mutation in the haematopoietic system. Three waves of mouse models have been produced recently (bone marrow transplantation, transgenic and targeted knock-in, which have facilitated the understanding of the molecular pathogenesis of JAK2V617F-positive MPNs, providing potential platforms for designing and validating novel therapies in humans. This Commentary briefly summarises the first two types of mouse models and then focuses on the more recently generated knock-in models.

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

    CERN Document Server

    Kantoglu, O

    2002-01-01

    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 (T sub g) 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.

  4. Invertase immobilization onto radiation-induced graft copolymerized polyethylene pellets

    Science.gov (United States)

    de Queiroz, Alvaro Antonio Alencar; Vitolo, Michele; de Oliveira, Rômulo Cesar; Higa, Olga Zazuco

    1996-06-01

    The graft copolymer poly(ethylene-g-acrylic acid) (LDPE-g-AA) was prepared by radiation-induced graft copolymerization of acrylic acid onto low density polyethylene (LDPE) pellets, and characterized by infrared photoacoustic spectroscopy and scanning electron microscopy (SEM). The presence of the grafted poly(acrylic acid) (PAA) was established. Invertase was immobilized onto the graft polymer and the thermodynamic parameters of the soluble and immobilized enzyme were determined. The Michaelis constant, Km, and the maximum reaction velocity, Vmax, were determined for the free and the immobilized invertase. The Michaelis constant, Km was larger for the immobilized invertase than for the free enzyme, whereas Vmax was smaller for the immobilized invertase. The thermal stability of the immobilized invertase was higher than that of the free enzyme.

  5. Radiation induced defects and thermoluminescence mechanism in aluminum oxide

    Energy Technology Data Exchange (ETDEWEB)

    Atobe, K.; Kobayashi, T.; Awata, T. [Naruto Univ. of Education, Tokushima (Japan); Okada, M. [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst; Nakagawa, M. [Kagawa Univ., Faculty of Education, Takamatsu, Kagawa (Japan)

    2001-01-01

    The thermoluminescence of the irradiated aluminum oxides were measured to study the radiation induced defects and their behaviors. Neutron and {gamma}-ray irradiation were performed for a shingle crystal of the high purity aluminum oxide. The thermoluminescence glow curve and its activation energy were measured. The spectroscopy measurement on the thermoluminescence and the absorption are also carried out. The observed 430 and 340 nm peaks are discussed relating to the F{sup +} and F centers, respectively. Activation state of the F center transits to 3P state through 1P state by emitting phonons. Trapped electron on 3P state emits phonon of 2.9 eV (430 nm) during transition to the ground state. The above reaction can be written by the equation. F{sup +} + e {yields} (F){sup *} {yields} F + h{nu}(2.9 eV, 470 nm). (Katsuta, H.)

  6. HSP25 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June; Lee, Yoon Jin; Kwon, Hee Choong; Lee, Su Jae; Bae, Sang Woo; Lee, Yun Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung Ho [Chonnam National Univ., Gwangju (Korea, Republic of)

    2005-07-01

    Irradiation (IR) is a central treatment modality administered for head and neck malignancies. A significant consequence of this IR treatment is irreversible damage to salivary gland in the IR field. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that heat shock protein 25 (HSP25) induced radioresistance in vitro. HSP25 interferes negatively with apoptosis through several pathways which involve its direct interaction with cytochrome c, protein kinase c delta or Akt. And localized gene transfer to salivary glands has great potential for the treatment of salivary gland. Herein, we investigated whether HSP25 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  7. Radiation-induced spindle cell sarcoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Khan Mubeen

    2009-01-01

    Full Text Available Ionizing radiation has been known to induce malignant transformation in human beings. Radiation-induced sarcomas are a late sequel of radiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gray (Gy and above, with a dose ranging from 16 to 112 Gys. Spindle cell sarcomas, arising after radiotherapy given to treat the carcinoma of head and neck region is a very uncommon sequel. This is a rare case report of spindle cell sarcoma of left maxilla, in a 24-year-old male, occurring as a late complication of radiotherapy with Cobalt-60 given for the treatment of retinoblastoma of the left eye 21 years back.

  8. Temperature dependence of radiation-induced attenuation of optical fibers

    Institute of Scientific and Technical Information of China (English)

    Jingming Song; Jianhua Guo; Xueqin Wang; Jing Jin

    2012-01-01

    We investigate the temperature dependence of radiation-induced attenuation (RIA) at 1 310 nm for a Ge/P co-doped fiber after a steady-state γ-ray irradiation.A γ irradiation facility 60Co source is used to irradiate the fiber at a dose rate of 0.5 Gy/min,satisfying a total dose of 100 Gy.The test temperature ranges from-40 to 60 ℃ by 20 ℃,and the RIA of the fiber is obtained using a power measuring device.The experimental result demonstrates that RIA exhibits a steady,monotonic,and remarkable temperature dependence after approximately 48 h of accelerated annealing at 70 ℃.The optical fiber irradiated with a high dose and annealed sufficiently can be used as a temperature sensor.

  9. Radiatively induced breaking of conformal symmetry in a superpotential

    Science.gov (United States)

    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.

  10. Radiatively Induced Breaking of Conformal Symmetry in a Superpotential

    CERN Document Server

    Arbuzov, A B

    2015-01-01

    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.

  11. Radiatively induced breaking of conformal symmetry in a superpotential

    Energy Technology Data Exchange (ETDEWEB)

    Arbuzov, A.B. [Bogoliubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Department of Higher Mathematics, Dubna State University, 141982 Dubna (Russian Federation); Cirilo-Lombardo, D.J., E-mail: diego777jcl@gmail.com [Bogoliubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); National Institute of Plasma Physics (INFIP-CONICET), Department of Physics, FCEyN, Universidad de Buenos Aires, Buenos Aires 1428 (Argentina)

    2016-07-10

    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.

  12. Acupuncture treatment of patients with radiation-induced xerostomia

    Energy Technology Data Exchange (ETDEWEB)

    Blom, M.; Dawidson, I.; Johnson, G.; Angmar-Maansson, B. [Karolinska Inst., Huddinge (Sweden). Dept. of Cardiology; Fernberg, J.-O. [Karolinska Hospital, Stockholm (Sweden). Dept. of General Oncology

    1996-05-01

    Xerostomia is a common and usually irreversible side effect in patients receiving radiation therapy (>50 Gy) for head and neck cancer. Of 38 patients with radiation-induced xerostomia, 20 in the experimental group were treated with classical acupuncture and 18 patients in the control group received superficial acupuncture as placebo. Within both groups the patients showed significantly increased salivary flow rates after the acupuncture treatment. In the experimental group 68% and in the control group 50% of the patients had increased salivary flow rates at the end of the observation period. Among those patients who had had all their salivary glands irradiated, 50% in both groups showed increased salivary flow rates (>20%) by the end of the observation period of 1 year. The study indicates that among the patients who had increased salivary flow rates already after the first 12 acupuncture sessions, the majority had high probability of continual improvement after the completion of acupuncture treatment. (Author).

  13. Radiation-induced cisplatin resistance in two human cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Eichholtz-Wirth, H.; Stotzer, O. [GSF-Institute of Radiobiology and Cytometry, Neuherberg (Germany); Marx, K. [Medical Clin. III, University, Munich (Germany)

    1997-03-01

    Cisplatin resistance has been induced in human HT-29 and HeLa cells after low-dose fractionated {gamma}-irradiation. The drug resistance is modest and does not confer cross-resistance to irradiation. Alterations that were recently shown to correlate with radiation-induced cisplatin resistance in murine cells are not involved in the resistant HeLa-C3 cells. Scavengers, such as GSH or metallothioneins are unchanged and there is no alteration of the cGMP transduction pathway. Preliminary results in HeLa-C3 cells indicate that resistance is associated with differences of the apoptotic pathway, with enhancement of the p53 suppressor protein after cisplatin treatment but unchanged bcl-2 protein expression. (authors)

  14. Measurements of prompt radiation induced conductivity of alumina and sapphire

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, E. Frederick [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Zarick, Thomas Andrew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sheridan, Timothy J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Preston, Eric F. [ITT Coporation, Colorado Springs, CO (United States)

    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.

  15. Factors that modify risks of radiation-induced cancer

    Energy Technology Data Exchange (ETDEWEB)

    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).

  16. Defense mechanisms against radiation induced teratogenic damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, (Japan)

    2002-07-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair.

  17. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    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.

  18. Radiation-induced thyroid cancer after radiotherapy for childhood cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiravova, M. [Department of Nuclear Medicine and Endocrinology, Faculty Hospital Motol, Uk, Prague (Czech Republic)

    2012-07-01

    Full text of the publication follows: The thyroid gland in children is among the most sensitive organs to the carcinogenic effects of ionizing radiation, and very young children are at especially high risk. Due to extreme sensitivity of the thyroid gland in children, there is a risk of radiation - induced thyroid cancer even when the thyroid gland is outside the irradiated field. Increased incidence of thyroid cancer has been noted following radiotherapy not only for childhood Hodgkin disease (majority of observed patients), but also for non-Hodgkin lymphoma, neuroblastoma, Wilms tumor, acute lymphocytic leukemia and tumors of the central nervous system also. Radiation-induced tumors begin to appear 5-10 years after irradiation and excess risk persists for decades, perhaps for the remainder of life. The incidence of thyroid cancer is two- to threefold higher among females than males. Most of the thyroid cancers that occur in association with irradiation are of the papillary type, for which the cure rate is high if tumors are detected early. Our Department in co-operation with Department of Children Hematology and Oncology Charles University Second Faculty of Medicine and Faculty Hospital Motol monitors patients after therapy for cancer in childhood for the long term period. The monitoring is focused on detection of thyroid disorders that occur as last consequences of oncology therapy, especially early detection of nodular changes in thyroid gland and thyroid carcinogenesis. The survey presents two patients observed in our department that were diagnosed with the papillary thyroid carcinoma which occurred 15 and more years after radiotherapy for childhood cancer. After total thyroidectomy they underwent therapy with radioiodine. After radiotherapy it is necessary to pursue a long-term following and assure interdisciplinary co-operation which enables early detection of last consequences of radiotherapy, especially the most serious ones as secondary carcinogenesis

  19. Radiation-induced brachial plexus neuropathy in breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, N.K.; Pfeiffer, P.; Mondrup, K.; Rose, C. (Odense Univ. Hospital (Denmark). Dept. of Neurology Odense Univ. Hospital (Denmark). Dept. of Clinical Neurophysiology Odense Univ. Hospital (Denmark). Dept. of Oncology R)

    1990-01-01

    The incidence and latency period of radiation-induced brachial plexopathy (RBP) were assessed in 79 breast cancer patients by a neurological follow-up examination at least 60 months (range 67-130 months) after the primary treatment. All patients were treated primarily with simple mastectomy, axillary nodal sampling and radiotherapy (RT). Postoperatively, pre- and postmenopausal patients were randomly allocated chemotherapy for antiestrogen treatment. All patients were recurrence-free at time of examination. Clinically, 35% (25-47%) of the patients had RBP; 19% (11-29%) had definite RBP, i.e. were physically disabled, and 16% (9-26%) had probable RBP. Fifty percent (31-69%) had affection of the entire plexus, 18% (7-35%) of the upper trunk only, and 4% (1-18%) of the lower trunk. In 28% (14-48%) of cases assessment of a definite level was not possible. RBP was more common after radiotherapy and chemotherapy (42%) than after radiotherapy alone (26%) but the difference was not statistically significant (p = 0.10). The incidence of definite RBP was significantly higher in the younger age group (p = 0.02). This could be due to more extensive axillary surgery but also to the fact that chemotherapy was given to most premenopausal patients. In most patients with RBP the symptoms began during or immediately after radiotherapy, and were thus without significant latency. Chemotherapy might enhance the radiation-induced effect on nerve tissue, thus diminishing the latency period. Lymphedema was present in 22% (14-32%), especially in the older patients, and not associated with the development of RBP. In conclusion, the damaging effect of RT on peripheral nerve tissue was documented. Since no successful treatment is available, restricted use of RT to the brachial plexus is warranted, especially when administered concomitantly with cytotoxic therapy. (orig.).

  20. A mutação JAK2 V617F e as síndromes mieloproliferativas JAK2 V617F mutation and the myeloproliferative disorders

    Directory of Open Access Journals (Sweden)

    Bárbara C. R. Monte-Mór

    2008-01-01

    Full Text Available Síndromes mieloproliferativas (SMPs são doenças hematopoéticas de origem clonal que apresentam amplificação de uma ou mais linhagens mielóides. Policitemia vera (PV, trombocitemia essencial (TE, mielofibrose idiopática (MF e leucemia mielóide crônica (LMC são consideradas SMPs clássicas e apresentam características clínicas e biológicas comuns. Ao contrário de LMC, cuja etiologia está relacionada à proteína constitutivamente ativa Bcr-Abl, o mecanismo molecular de PV, TE e MF permaneceu por muito tempo desconhecido. Esta revisão se foca na recente descoberta da mutação JAK2 V617F em pacientes com PV, TE e MF, sua relação com o fenótipo mieloproliferativo e implicações na abordagem clínica de pacientes.Myeloproliferative disorders are clonal hematopoietic diseases that are characterized by the amplification of one or more myeloid lineages. Polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis and chronic myeloid leukemia are considered classic myeloproliferative disorders and share common clinical and biological features. While the genetic basis of chronic myeloid leukemia is shown to be the constitutive active protein BCR-ABL, the main molecular lesions in polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis remain unknown. This review focuses on the recent discovery of the JAK2 V617F mutation, its relationship to the myeloproliferative phenotype and implications in the clinical approach of patients.

  1. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    Energy Technology Data Exchange (ETDEWEB)

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R., E-mail: akennedy@mail.med.upenn.edu

    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.

  2. Increased risk of lymphoid neoplasms in patients with Philadelphia chromosome-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Vannucchi, Alessandro M; Masala, Giovanna; Antonioli, Elisabetta; Chiara Susini, Maria; Guglielmelli, Paola; Pieri, Lisa; Maggi, Laura; Caini, Saverio; Palli, Domenico; Bogani, Costanza; Ponziani, Vanessa; Pancrazzi, Alessandro; Annunziato, Francesco; Bosi, Alberto

    2009-07-01

    Association of myeloproliferative neoplasm (MPN) with lymphoproliferative neoplasm (LPN) has been occasionally reported. The aim of this study, which included 353 patients with polycythemia vera and 467 with essential thrombocythemia, was to assess whether the risk of developing LPN is increased in MPN patients. Expected numbers of LPN incident cases were calculated based on 5-year age group, gender, and calendar time-specific cancer incidence rates in the general population of the same area. Standardized incidence ratios were computed to estimate the relative risk of developing LPN. Analyses were carried out for the whole series and then separately for essential thrombocythemia and polycythemia vera, gender, and JAK2V617F genotype. With 4,421 person-years, we found 11 patients developing LPN, including four chronic lymphocytic leukemias, five non-Hodgkin's lymphomas, and two plasma cell disorders, after a median interval time of 68 months from MPN diagnosis. Cumulative risk to develop LPN at 5 and 10 years was 0.93% (95% confidence interval, 0.39-2.22) and 2.96% (95% confidence interval, 1.52-5.72), respectively. There was a 3.44-fold increased risk of LPN compared with the general population, ranging from 2.86 for plasma cell disorder to 12.42 for chronic lymphocytic leukemia; the risk was significantly increased in JAK2V617F mutated patients (5.46-fold) and in males (4.52-fold). The JAK2V617F mutation was found in lymphoid tumor cells in two of three cases evaluated, indicating that, in some patients, LPN originated in a JAK2V617F mutated common lymphoid-myeloid hematopoietic progenitor cell. We conclude that the risk of developing LPN is significantly increased in MPN patients compared with the general population.

  3. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    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.

  4. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    Science.gov (United States)

    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

  5. Influence of radiation induced defect clusters on silicon particle detectors

    Energy Technology Data Exchange (ETDEWEB)

    Junkes, Alexandra

    2011-10-15

    The Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) addresses some of today's most fundamental questions of particle physics, like the existence of the Higgs boson and supersymmetry. Two large general-purpose experiments (ATLAS, CMS) are installed to detect the products of high energy protonproton and nucleon-nucleon collisions. Silicon detectors are largely employed in the innermost region, the tracking area of the experiments. The proven technology and large scale availability make them the favorite choice. Within the framework of the LHC upgrade to the high-luminosity LHC, the luminosity will be increased to L=10{sup 35} cm{sup -2}s{sup -1}. In particular the pixel sensors in the innermost layers of the silicon trackers will be exposed to an extremely intense radiation field of mainly hadronic particles with fluences of up to {phi}{sub eq}=10{sup 16} cm{sup -2}. The radiation induced bulk damage in silicon sensors will lead to a severe degradation of the performance during their operational time. This work focusses on the improvement of the radiation tolerance of silicon materials (Float Zone, Magnetic Czochralski, epitaxial silicon) based on the evaluation of radiation induced defects in the silicon lattice using the Deep Level Transient Spectroscopy and the Thermally Stimulated Current methods. It reveals the outstanding role of extended defects (clusters) on the degradation of sensor properties after hadron irradiation in contrast to previous works that treated effects as caused by point defects. It has been found that two cluster related defects are responsible for the main generation of leakage current, the E5 defects with a level in the band gap at E{sub C}-0.460 eV and E205a at E{sub C}-0.395 eV where E{sub C} is the energy of the edge of the conduction band. The E5 defect can be assigned to the tri-vacancy (V{sub 3}) defect. Furthermore, isochronal annealing experiments have shown that the V{sub 3} defect

  6. Ion beam induced luminescence: Relevance to radiation induced bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, S.B., E-mail: ahmad.rabilal@gmail.com [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); McNeill, F.E., E-mail: fmcneill@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Byun, S.H., E-mail: soohyun@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Prestwich, W.V., E-mail: prestwic@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Seymour, C., E-mail: seymouc@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada); Mothersill, C.E., E-mail: mothers@mcmaster.ca [Medical Physics and Applied Radiation Sciences, University of McMaster, Hamilton, Ontario (Canada)

    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 Multiplication-Sign 10{sup 13} H{sup +}/cm{sup 2} s. The average saturation value for the photon output was found to be 40 Multiplication-Sign 10{sup 6} 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 Multiplication-Sign 10{sup 3}, 10 Multiplication-Sign 10{sup 6}, and 35 Multiplication-Sign 10{sup 6} 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{sup -14} cm{sup 2}. 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.

  7. Radiation-induced defects in clay minerals: A review

    Energy Technology Data Exchange (ETDEWEB)

    Allard, Th., E-mail: thierry.allard@impmc.upmc.fr [IMPMC, UMR CNRS 7590, Universite Pierre et Marie Curie, Universite Denis Diderot, IRD, IPGP, Case 115, 4 Place Jussieu, 75005 Paris (France); Balan, E.; Calas, G.; Fourdrin, C.; Morichon, E.; Sorieul, S. [IMPMC, UMR CNRS 7590, Universite Pierre et Marie Curie, Universite Denis Diderot, IRD, IPGP, Case 115, 4 Place Jussieu, 75005 Paris (France)

    2012-04-15

    Extensive information has been collected on radiation effects on clay minerals over the last 35 years, providing a wealth of information on environmental and geological processes. The fields of applications include the reconstruction of past radioelement migrations, the dating of clay minerals or the evolution of the physico-chemical properties under irradiation. The investigation of several clay minerals, namely kaolinite, dickite, montmorillonite, illite and sudoite, by Electron Paramagnetic Resonance Spectroscopy has shown the presence of defects produced by natural or artificial radiations. These defects consist mostly of electron holes located on oxygen atoms of the structure. The various radiation-induced defects are differentiated through their nature and their thermal stability. Most of them are associated with a {pi} orbital on a Si-O bond. The most abundant defect in clay minerals is oriented perpendicular to the silicate layer. Thermal annealing indicates this defect in kaolinite (A-center) to be stable over geological periods at ambient temperature. Besides, electron or heavy ion irradiation easily leads to an amorphization in smectites, depending on the type of interlayer cation. The amorphization dose exhibits a bell-shaped variation as a function of temperature, with a decreasing part that indicates the influence of thermal dehydroxylation. Two main applications of the knowledge of radiation-induced defects in clay minerals are derived: (i) The use of defects as tracers of past radioactivity. In geological systems where the age of the clay can be constrained, ancient migrations of radioelements can be reconstructed in natural analogues of high level nuclear waste repositories. When the dose rate may be assumed constant over time, the paleodose is used to date clay populations, an approach applied to fault gouges or laterites of the Amazon basin. (ii) The influence of irradiation over physico-chemical properties of clay minerals. An environmental

  8. Hyperbaric Oxygen Therapy for Radiation-Induced Cystitis and Proctitis

    Energy Technology Data Exchange (ETDEWEB)

    Oliai, Caspian; Fisher, Brandon; Jani, Ashish; Wong, Michael; Poli, Jaganmohan; Brady, Luther W. [Department of Radiation Oncology, Drexel University College of Medicine, Philadelphia, Pennsylvania (United States); Komarnicky, Lydia T., E-mail: lydia.komarnicky-kocher@drexelmed.edu [Department of Radiation Oncology, Drexel University College of Medicine, Philadelphia, Pennsylvania (United States)

    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. Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.

    Science.gov (United States)

    Rumi, Elisa; Harutyunyan, Ashot; Elena, Chiara; Pietra, Daniela; Klampfl, Thorsten; Bagienski, Klaudia; Berg, Tiina; Casetti, Ilaria; Pascutto, Cristiana; Passamonti, Francesco; Kralovics, Robert; Cazzola, Mario

    2011-12-01

    Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders may undergo phenotypic shifts, and may specifically evolve into secondary myelofibrosis (MF) or acute myeloid leukemia (AML). We studied genomic changes associated with these transformations in 29 patients who had serial samples collected in different phases of disease. Genomic DNA from granulocytes, i.e., the myeloproliferative genome, was processed and hybridized to genome-wide human SNP 6.0 arrays. Most patients in chronic phase had chromosomal regions with uniparental disomy (UPD) and/or copy number changes. Disease progression to secondary MF or AML was associated with the acquisition of additional chromosomal aberrations in granulocytes (P = 0.002). A close relationship was observed between aberrations of chromosome 9p (UPD and/or gain) and progression from PV to post-PV MF (P = 0.002). The acquisition of one or more aberrations involving chromosome 5, 7, or 17p was specifically associated with progression to AML (OR 5.9, 95% CI 1.2-27.7, P = 0.006), and significantly affected overall survival (HR 18, 95% CI 1.9-164, P = 0.01). These observations indicate that disease progression from chronic-phase MPN to secondary MF or AML is associated with specific chromosomal aberrations that can be detected by means of high-resolution SNP array analysis of granulocyte DNA.

  10. Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.

    Science.gov (United States)

    Malli, Theodora; Buxhofer-Ausch, Veronika; Rammer, Melanie; Erdel, Martin; Kranewitter, Wolfgang; Rumpold, Holger; Marschon, Renate; Deutschbauer, Sabine; Simonitsch-Klupp, Ingrid; Valent, Peter; Muellner-Ammer, Kirsten; Sebesta, Christian; Birkner, Thomas; Webersinke, Gerald

    2016-01-01

    Myeloid and lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) abnormalities, also known as 8p11 myeloproliferative syndrome (EMS), represent rare and aggressive disorders, associated with chromosomal aberrations that lead to the fusion of FGFR1 to different partner genes. We report on a third patient with a fusion of the translocated promoter region (TPR) gene, a component of the nuclear pore complex, to FGFR1 due to a novel ins(1;8)(q25;p11p23). The fact that this fusion is a rare but recurrent event in EMS prompted us to examine the localization and transforming potential of the chimeric protein. TPR-FGFR1 localizes in the cytoplasm, although the nuclear pore localization signal of TPR is retained in the fusion protein. Furthermore, TPR-FGFR1 enables cytokine-independent survival, proliferation, and granulocytic differentiation of the interleukin-3 dependent myeloid progenitor cell line 32Dcl3, reflecting the chronic phase of EMS characterized by myeloid hyperplasia. 32Dcl3 cells transformed with the TPR-FGFR1 fusion and treated with increasing concentrations of the tyrosine kinase inhibitors ponatinib (AP24534) and infigratinib (NVP-BGJ398) displayed reduced survival and proliferation with IC50 values of 49.8 and 7.7 nM, respectively. Ponatinib, a multitargeted tyrosine kinase inhibitor, is already shown to be effective against several FGFR1-fusion kinases. Infigratinib, tested only against FGFR1OP2-FGFR1 to date, is also efficient against TPR-FGFR1. Taking its high specificity for FGFRs into account, infigratinib could be beneficial for EMS patients and should be further investigated for the treatment of myeloproliferative neoplasms with FGFR1 abnormalities.

  11. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  12. Radiation induced destruction of thebaine, papaverine and noscapine in methanol

    Science.gov (United States)

    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.

  13. Radiation-Induced Notch Signaling in Breast Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lagadec, Chann [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Vlashi, Erina [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California (United States); Alhiyari, Yazeed; Phillips, Tiffany M.; Bochkur Dratver, Milana [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Pajonk, Frank, E-mail: fpajonk@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California (United States); Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California (United States)

    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.

  14. Processability improvement of polyolefins through radiation-induced branching

    Science.gov (United States)

    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.

  15. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Gamma radiation induces hydrogen absorption by copper in water

    Science.gov (United States)

    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.

  17. Gamma radiation induced changes in nuclear waste glass containing Eu

    Science.gov (United States)

    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.

  18. Radiation-induced optic neuropathy: A magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Guy, J.; Mancuso, A.; Beck, R.; Moster, M.L.; Sedwick, L.A.; Quisling, R.G.; Rhoton, A.L. Jr.; Protzko, E.E.; Schiffman, J. (Univ. of Florida, Gainesville (USA))

    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.

  19. Radiation-induced hypopituitarism is dose-dependent

    Energy Technology Data Exchange (ETDEWEB)

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Robinson, E.L.; Sutton, M.L. (Christie Hospital and Holt Radium Inst., Manchester (UK) Withington Hospital, Manchester (UK))

    1989-09-01

    Radiation-induced hypopituitarism has been studies prospectively for up to 12 years in 251 adult patients treated for pituitary disease with external radiotherapy, ranging in dose from 20 Gy in eight fractions over 11 days to 45 Gy in 15 fractions over 21 days. Ten further patients were studied 2-4 years after whole-body irradiation for haematological malignancies using 12 Gy in six fractions over 3 days and seven patients were studied 3-11 years after whole-brain radiotherapy for a primary brain tumour (30 Gy, eight fractions, 11 days). Five years after treatment, patients who received 20 Gy had an incidence of TSH deficiency of 9% and in patients treated with 35-37 Gy, 40 Gy and 42-45 Gy, the incidence of TSH deficiency increased significantly with increasing dose. A similar relationship was observed for both ACTH and gonadotrophin deficiencies when the 20 Gy group was compared to patients treated with 35-45 Gy. Growth hormone deficiency was universal by 5 years over the dose range 35-45 Gy. In seven patients who were treated with 30 Gy in eight fractions over 11 days, deficiencies were observed at a similar frequency to the 40 Gy group (15 fractions, 21 days). No evidence of pituitary dysfunction was detected in the ten patients who received 12 Gy (six fractions, 3 days). (author).

  20. Radiation-induced tumours of the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Laan, B.F.A.M. van der; Baris, G.; Gregor, R.T.; Hilgers, F.J.M.; Balm, A.J.M. [Nederlands Kanker Inst. `Antoni van Leeuwenhoekhuis`, Amsterdam (Netherlands)

    1995-04-01

    In order to study the induction of malignancy in normal tissues due to ionizing radiation, we reviewed the files of 2500 patients with a tumour of the head and neck treated at the Netherlands Cancer Institute (Antoni van Leeuwenhoek Ziekenhuis), Amsterdam, from 1977 to 1993. We then checked whether or not these patients had been previously irradiated. Patients with a thyroid carcinoma or skin cancer were excluded from the study, since it is generally known that previous irradiation is a risk factor in these tumours. Eighteen patients were found to have a malignancy within a previous irradiated area (0.70 per cent). The mean interval between radiation and diagnosis of the head and neck tumour was 36.5 years. There were five soft tissue sarcomas, nine squamous cell carcinomas and four salivary gland tumours. Fourteen patients were operated upon whereas four received palliative treatment only. The median survival of the total group was 3.5 years. Particularly in young patients, because of the better cancer therapy and prolonged survival, one must be aware of the increased risk of radiation-induced tumours. (author).

  1. Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development.

    Science.gov (United States)

    Geyer, Holly L; Dueck, Amylou C; Scherber, Robyn M; Mesa, Ruben A

    2015-01-01

    Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF) are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO) tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms) and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development.

  2. Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development

    Directory of Open Access Journals (Sweden)

    Holly L. Geyer

    2015-01-01

    Full Text Available Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development.

  3. Defining the Thrombotic Risk in Patients with Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Fabrizio Vianello

    2011-01-01

    Full Text Available Polycythemia vera (PV and essential thrombocythemia (ET are two Philadelphia-negative myeloproliferative neoplasms (MPN associated with an acquired mutation in the JAK2 tyrosine kinase gene. There is a rare incidence of progression to myelofibrosis and myeloid metaplasia in both disorders, which may or may not precede transformation to acute myeloid leukemia, but thrombosis is the main cause of morbidity and mortality. The pathophysiology of thrombosis in patients with MPN is complex. Traditionally, abnormalities of platelet number and function have been claimed as the main players, but increased dynamic interactions between platelets, leukocytes, and the endothelium do probably represent a fundamental interplay in generating a thrombophilic state. In addition, endothelial dysfunction, a well-known risk factor for vascular disease, may play a role in the thrombotic risk of patients with PV and ET. The identification of plasma markers translating the hemostatic imbalance in patients with PV and ET would be extremely helpful in order to define the subgroup of patients with a significant clinical risk of thrombosis.

  4. The spectrum of JAK2-positive myeloproliferative neoplasms.

    Science.gov (United States)

    Kiladjian, Jean-Jacques

    2012-01-01

    The discovery of the JAK2V617F mutation triggered an unexpected flowering of basic and clinical studies in the field of myeloproliferative neoplasms (MPNs), resulting after just a few years in an exceptional amount of new information. One important consequence of those new findings was the modification of the World Health Organization classification and diagnostic algorithms for these diseases, which is still based on the original concept developed by William Dameshek in 1951 and keeps distinct entities under the umbrella of classical Philadelphia-negative MPNs. These MPNs are essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Could a new molecular classification be a better tool to manage MPN patients? Several studies have shown that essential thrombocythemia and primary myelofibrosis can be divided into distinct subtypes based on the presence of the JAK2V617F mutation. Can we now define JAK2-positive diseases to depict a distinct entity from JAK2-negative MPNs? This chapter reviews the significance of JAK2 mutation positivity in the diagnosis, prognosis, and therapy of MPNs.

  5. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells.

    Science.gov (United States)

    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.

  6. Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Yoo Seob Shin

    Full Text Available PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC, a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP, reactive oxygen species (ROS generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. RESULTS: EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.

  7. Increased incidence of another cancer in myeloproliferative neoplasms patients at the time of diagnosis.

    Science.gov (United States)

    Pettersson, Helna; Knutsen, Håvar; Holmberg, Erik; Andréasson, Björn

    2015-02-01

    Several studies have reported an increased incidence of coexistent cancer in patients with myeloproliferative neoplasms (MPN), and myelosuppressive treatment has been speculated to be one of the causes. In this study, we have concentrated on malignancies diagnosed before the MPN diagnosis to eliminate the possible influence of MPN treatment. The patients were recruited from the Swedish and Norwegian cancer registries. One thousand seven hundred and 45 patients from the Swedish MPN Quality Registry and 468 patients from the Norwegian National Cancer Registry were included in this study covering a 3-yr period. The results show that primary concurrent cancer is higher among patients with MPN compared to the general population. When pooled together, the Swedish and the Norwegian cohort showed increased prevalence of all types of cancer in general compared with the general population, standard prevalence ratio (SPR) of 1.20 (95% CI 1.07-1.34). Significantly high SPRs were reached for skin malignant melanoma [1.89 (95% CI 1.33-2.62)], prostate cancer [1.39 (95% CI 1.11-1.71)], and hematologic cancer [1.49 (95% CI 1.00-2.12)]. In the polycythemia vera group, the risk of having prior malignant melanoma of the skin was significant, with an SPR of 2.20 (95% CI 1.17-3.77). For patients with essential thrombocythemia and primary myelofibrosis, no significant risks were found. Coexisting cancers have a high impact on the treatment strategies of MPN, as it narrows down the treatment options. Chronic inflammation, as a common denominator of MPN with other cancers, can catalyze each other's existence and progression.

  8. Treatment of gastric varices with partial splenic embolization in a patient with portal vein thrombosis and a myeloproliferative disorder.

    Science.gov (United States)

    Gianotti, Robert; Charles, Hearns; Hymes, Kenneth; Chandarana, Hersh; Sigal, Samuel

    2014-10-21

    Therapeutic options for gastric variceal bleeding in the presence of extensive portal vein thrombosis associated with a myeloproliferative disorder are limited. We report a case of a young woman who presented with gastric variceal bleeding secondary to extensive splanchnic venous thrombosis due to a Janus kinase 2 mutation associated myeloproliferative disorder that was managed effectively with partial splenic embolization.

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

    Science.gov (United States)

    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

  10. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  11. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Pan, Charlie C. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Amarnath, Sudha [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Ensminger, William D. [Department of Internal Medicine, Division of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Lawrence, Theodore S.; Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

    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.

  12. Role of tyrosine-kinase inhibitors in myeloproliferative neoplasms: comparative lessons learned

    Directory of Open Access Journals (Sweden)

    Pinilla-Ibarz J

    2016-08-01

    Full Text Available Javier Pinilla-Ibarz, Kendra L Sweet, Gabriela M Corrales-Yepez, Rami S Komrokji Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: An important pathogenetic distinction in the classification of myeloproliferative neoplasms (MPNs is the presence or absence of the BCR–ABL fusion gene, which encodes a unique oncogenic tyrosine kinase. The BCR–ABL fusion, caused by the formation of the Philadelphia chromosome (Ph through translocation, constitutes the disease-initiating event in chronic myeloid leukemia. The development of successive BCR–ABL-targeted tyrosine-kinase inhibitors has led to greatly improved outcomes in patients with chronic myeloid leukemia, including high rates of complete hematologic, cytogenetic, and molecular responses. Such levels of treatment success have long been elusive for patients with Ph-negative MPNs, because of the difficulties in identifying specific driver proteins suitable as drug targets. However, in recent years an improved understanding of the complex pathobiology of classic Ph-negative MPNs, characterized by variable, overlapping multimutation profiles, has prompted the development of better and more broadly targeted (to pathway rather than protein treatment options, particularly JAK inhibitors. In classic Ph-negative MPNs, overactivation of JAK-dependent signaling pathways is a central pathogenic mechanism, and mutually exclusive mutations in JAK2, MPL, and CALR linked to aberrant JAK activation are now recognized as key drivers of disease progression in myelofibrosis (MF. In clinical trials, the JAK1/JAK2 inhibitor ruxolitinib – the first therapy approved for MF worldwide – improved disease-related splenomegaly and symptoms independent of JAK2V617F mutational status, and prolonged survival compared with placebo or standard therapy in patients with advanced MF. In separate trials, ruxolitinib also provided comprehensive hematologic control in

  13. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    Science.gov (United States)

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  14. Design Methodologies and to Combat Radiation Induced Corruption in FPGAs and SoCs Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Traditional radiation hardened by process (RHBP) and radiation hardened by design (RHBD) techniques have seen success in mitigating the effects of radiation induced...

  15. Radiation-Induced Topological Disorder in Irradiated Network Structures

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun; Kang, Jeong Wook [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Dong Won [Department of Plastic Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Oh, Sang Ho [Department of Dermatology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Yun-Sil [College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewah Womans University, Seoul 120-750 (Korea, Republic of); Lee, Eun-Jung [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    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.

  17. Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease

    Directory of Open Access Journals (Sweden)

    Marine M. Tanashyan

    2016-09-01

    Full Text Available Background: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph myeloproliferative disorders (MPD including essential thrombocythemia (ET, polycythemia vera (PV, and primary myelofibrosis (PM. Materials and Methods: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years, those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years. Results: In 79% (n = 81 of cases in the study group (with Ph-MPD, patients had chronic CVD, with the most frequently identified symptoms being asthenia (92% and headache (72%. Headache in Ph-MPD patients was more frequently (86% associated with PM, while in patients with PV and ET it was equally distributed (70%. Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21% patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery was severely impaired in all study groups (median 5% with normal cut-off at 10%, the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011. Conclusion: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jingbo [Department of Radiation Oncology, University of Michigan/Ann Arbor Veterans Health System, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Cancer Hospital, Chinese Academic Medical Sciences and Peking Union Medical College, Beijing (China); Cao, Jianzhong [Department of Radiation Oncology, Cancer Hospital, Chinese Academic Medical Sciences and Peking Union Medical College, Beijing (China); Yuan, Shuanghu [Department of Radiation Oncology, University of Michigan/Ann Arbor Veterans Health System, Ann Arbor, Michigan (United States); Ji, Wei [Department of Radiation Oncology, Cancer Hospital, Chinese Academic Medical Sciences and Peking Union Medical College, Beijing (China); Arenberg, Douglas [Department of Internal Medicine, University of Michigan/Ann Arbor Veterans Health System, Ann Arbor, Michigan (United States); Dai, Jianrong [Department of Radiation Oncology, Cancer Hospital, Chinese Academic Medical Sciences and Peking Union Medical College, Beijing (China); Stanton, Paul; Tatro, Daniel; Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan/Ann Arbor Veterans Health System, Ann Arbor, Michigan (United States); Wang, Luhua, E-mail: wlhwq@yahoo.com [Department of Radiation Oncology, Cancer Hospital, Chinese Academic Medical Sciences and Peking Union Medical College, Beijing (China); Kong, Feng-Ming, E-mail: fengkong@med.umich.edu [Department of Radiation Oncology, University of Michigan/Ann Arbor Veterans Health System, Ann Arbor, Michigan (United States)

    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.

  19. Prevention of radiation-induced salivary gland dysfunction utilizing a CDK inhibitor in a mouse model.

    Directory of Open Access Journals (Sweden)

    Katie L Martin

    Full Text Available BACKGROUND: Treatment of head and neck cancer with radiation often results in damage to surrounding normal tissues such as salivary glands. Permanent loss of function in the salivary glands often leads patients to discontinue treatment due to incapacitating side effects. It has previously been shown that IGF-1 suppresses radiation-induced apoptosis and enhances G2/M arrest leading to preservation of salivary gland function. In an effort to recapitulate the effects of IGF-1, as well as increase the likelihood of translating these findings to the clinic, the small molecule therapeutic Roscovitine, is being tested. Roscovitine is a cyclin-dependent kinase inhibitor that acts to transiently inhibit cell cycle progression and allow for DNA repair in damaged tissues. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with Roscovitine prior to irradiation induced a significant increase in the percentage of cells in the G(2/M phase, as demonstrated by flow cytometry. In contrast, mice treated with radiation exhibit no differences in the percentage of cells in G(2/M when compared to unirradiated controls. Similar to previous studies utilizing IGF-1, pretreatment with Roscovitine leads to a significant up-regulation of p21 expression and a significant decrease in the number of PCNA positive cells. Radiation treatment leads to a significant increase in activated caspase-3 positive salivary acinar cells, which is suppressed by pretreatment with Roscovitine. Administration of Roscovitine prior to targeted head and neck irradiation preserves normal tissue function in mouse parotid salivary glands, both acutely and chronically, as measured by salivary output. CONCLUSIONS/SIGNIFICANCE: These studies suggest that induction of transient G(2/M cell cycle arrest by Roscovitine allows for suppression of apoptosis, thus preserving normal salivary function following targeted head and neck irradiation. This could have an important clinical impact by preventing the negative side

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. JAK2 exon 12 mutations in patients with Philadelphia(Ph) chromosome-negative myeloproliferative neoplasms

    Institute of Scientific and Technical Information of China (English)

    王婕妤

    2012-01-01

    Objective To investigate JAK2 exon 12 mutations in patients with Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPN) and the clinical characteristics of patients with JAK2 exon 12 mutants. Methods Allele-specific PCR(AS-PCR) was applied to identify JAK2 V617F mutation.

  2. 2012478 Biological characteristics of bone marrow mesenchymal stem cells and JAK2 mutation in myeloproliferative neoplasms

    Institute of Scientific and Technical Information of China (English)

    田竑

    2012-01-01

    Objective To study the biological characteristics of bone marrow mesenchymal stem cells(BMSCs) and detect JAK2 mutation in BMSCs from myeloproliferative neoplasms(MPN) patients. Methods JAK2 V617F mutation and exon 12 mutation in 70 MPN patients’ blood or bone marrow samples were detected.

  3. Renal thrombotic microangiopathy and FIP1L1/PDGFRα-associated myeloproliferative variant of hypereosinophilic syndrome.

    Science.gov (United States)

    Langlois, Anne Lyse; Shehwaro, Nathalie; Rondet, Claire; Benbrik, Youssef; Maloum, Karim; Gueutin, Victor; Rouvier, Philippe; Izzedine, Hassane

    2013-08-01

    We report a case of renal thrombotic microangiopathy (TMA) in a myeloproliferative variant of hypereosinophilic syndrome (HES) in a 24-year-old man which resolved with imatinib therapy. This is one of a few cases in the literature to date describing TMA in HES, suggesting that the pathogenesis of thrombosis is at least in part related to damage from activated eosinophils.

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

    Energy Technology Data Exchange (ETDEWEB)

    Seidensticker, Max, E-mail: max.seidensticker@med.ovgu.de [Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin (Germany); Burak, Miroslaw [Pomeranian Medical University, Department of Diagnostic Imaging and Interventional Radiology (Poland); Kalinski, Thomas [Universitätsklinik Magdeburg, Institut für Pathologie (Germany); Garlipp, Benjamin [Universitätsklinik Magdeburg, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie (Germany); Koelble, Konrad [Philipps Universität Marburg, Fachbereich Medizin der, Abteilung für Neuropathologie (Germany); Wust, Peter [Charité Universitätsmedizin Berlin, Klinik für Radioonkologie und Strahlentherapie (Germany); Antweiler, Kai [Universitätsklinik Magdeburg, Institut für Biometrie und Medizinische Informatik (Germany); Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Ricke, Jens [Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin (Germany)

    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.

  5. Functional magnetic resonance imaging for evaluation of radiation-induced renal damage; Funktionelle MRT der Niere zur Erfassung strahleninduzierter Nierenschaedigungen

    Energy Technology Data Exchange (ETDEWEB)

    Haneder, S.; Schoenberg, S.O.; Michaely, H.J. [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim der Universitaet Heidelberg, Institut fuer Klinische Radiologie und Nuklearmedizin, Mannheim (Germany); Boda-Heggemann, J. [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim der Universitaet Heidelberg, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany)

    2012-03-15

    The diagnosis of radiation-induced (especially chronic) renal alterations/damage is difficult and currently relies primarily on clinical evaluation. The importance of renal diagnostic evaluation will increase continuously due to the increasing number of long-term survivors after radiotherapy. This article evaluates the potentia diagnostic contribution of magnetic resonance (MR) imaging with a focus on functional MRI. The following functional MRI approaches are briefly presented and evaluated: blood oxygenation level-dependent imaging (BOLD), diffusion-weighted imaging (DWI) or diffusion tensor imaging (DTI), MR perfusion measurements and {sup 23}Na imaging. In summary, only DWI and contrast-enhanced MR perfusion currently seem to be suitable approaches for a broader, clinical implementation. However, up to now valid data from larger patient studies are lacking for both techniques in regard to radiation-induced renal alterations. The BOLD and {sup 23}Na imaging procedures have a huge potential but are currently neither sufficiently evaluated with regard to radiation-induced renal alterations nor technically simple and reliable for implementation into the clinical routine. (orig.) [German] Die Diagnostik strahleninduzierter, insbesondere chronischer Schaedigungen der Niere ist nach wie vor schwierig und beruht primaer auf der klinischen Beurteilung. Durch die zunehmende Anzahl von Langzeitueberlebenden nach einer Strahlentherapie wird die Bedeutung dieser Diagnostik jedoch weiter zunehmen. In diesem Beitrag wird der Frage nachgegangen, in wieweit hierzu die MRT-Bildgebung und hier besonders die funktionellen Bildgebungsmodalitaeten ihren Beitrag leisten koennen. Die folgenden Verfahren werden kurz vorgestellt und bewertet: die Blood-oxygenation-level-dependent-Bildgebung (BOLD), die diffusionsgewichtete Bildgebung (''diffusion-weighted imaging'', DWI) bzw. das ''diffusion tensor imaging'' (DTI), die MR-Perfusionsmessungen, und

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

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    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.

  7. Establishment of an animal model for radiation-induced vomiting in rats using pica

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Kouichi; Yamatodani, Atsushi [Osaka Univ., Suita (Japan). Medical School; Takeda, Noriaki [Tokushima Univ. (Japan). School of Medicine

    2002-06-01

    We investigated whether radiation-induced pica, a behavior characterized by the eating of a non-food substance, such as kaolin, can be used as an index of radiation-induced vomiting in rats. Since there was an individual difference in the susceptibility to pica, we selected rats that actually ate kaolin following X-ray irradiation, and used them for the experiment. The total-body irradiation (TBI) increased kaolin consumption in a dose-dependent manner (sham, 0.05{+-}0.03 (SEM) g; 2 Gy, 0.38{+-}0.11 g; 4 Gy, 1.54{+-}0.28 g; 8 Gy, 3.55{+-}0.67 g), and the increased kaolin consumption after 4 Gy of TBI was inhibited by a pretreatment with the serotonin 5-HT{sub 3} receptor antagonist ondansetron (2 mg/kg, i.p.) (saline, 1.49{+-}0.33 g; ondansetron, 0.75{+-}0.11 g). Furthermore, 4 Gy of abdominal irradiation was more effective to induce pica than that of head irradiation (abdomen: 0.37{+-}0.05 g, head: 0.06{+-}0.01 g). These findings suggested that peripheral serotonergic pathway is predominantly involved in the development of radiation-induced pica in rats and that the radiation-induced pica could be useful as a behavioral index for the severity of radiation-induced vomiting in rats. (author)

  8. Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

    Science.gov (United States)

    Appelmann, Iris; Kreher, Stephan; Parmentier, Stefani; Wolf, Hans-Heinrich; Bisping, Guido; Kirschner, Martin; Bergmann, Frauke; Schilling, Kristina; Brümmendorf, Tim H; Petrides, Petro E; Tiede, Andreas; Matzdorff, Axel; Griesshammer, Martin; Riess, Hanno; Koschmieder, Steffen

    2016-04-01

    Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.

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

    Science.gov (United States)

    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.

  10. Prevention of γ-radiation induced cellular genotoxicity by tempol: protection of hematopoietic system.

    Science.gov (United States)

    Ramachandran, Lakshmy; Nair, Cherupally Krishnan Krishnan

    2012-09-01

    Tempol (TPL) under in vitro conditions reduced the extent of gamma radiation induced membrane lipid peroxidation and disappearance of covalently closed circular form of plasmid pBR322. TPL protected cellular DNA from radiation-induced damage in various tissues under ex vivo and in vivo conditions as evidenced by comet assay. TPL also prevented radiation induced micronuclei formation (in peripheral blood leucocytes) and chromosomal aberrations (in bone marrow cells) in whole body irradiated mice. TPL enhanced the rate of repair of cellular DNA (blood leucocytes and bone marrow cells) damage when administered immediately after radiation exposure as revealed from the increased Cellular DNA Repair Index (CRI). The studies thus provided compelling evidence to reveal the effectiveness of TPL to protect hematopoietic system from radiation injury.

  11. [Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?].

    Science.gov (United States)

    Piskunov, A K; Nikitin, K V; Potapov, A A

    2015-01-01

    Investigation of the mechanisms of radiation-induced brain injury is a relevant fundamental objective of radiobiology and neuroradiology. Damage to the healthy brain tissue is the key factor limiting the application of radiation therapy in patients with nervous systems neoplasms. Furthermore, postradiation brain injury can be clinically indiscernible from continued tumor growth and requires differential diagnosis. Thus, there exists high demand for biomarkers of radiation effects on the brain in neurosurgery and radiobiology. These markers could be used for better understanding and quantifying the effects of ionizing radiation on brain tissues, as well as for elaborating personalized therapy. Despite the high demand, biomarkers of radiation-induced brain injury have not been identified thus far. The cellular and molecular mechanisms of the effect of ionizing radiation on the brain were analyzed in this review in order to identify potential biomarkers of radiation-induced injury to nervous tissue.

  12. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O, E-mail: shpotyuk@novas.lviv.ua

    2010-11-15

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As{sub x}Se{sub 100-x} (10 {<=} x {<=} 42) and As{sub x}S{sub 100-x} (30 {<=} x {<=} 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As{sub x}S{sub 100-x} within 30 {<=} x < 40 range, while As{sub x}Se{sub 100-x} glasses from the same compositional interval do not show any measurable changes in DSC curves after {gamma}-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of {gamma}-induced excitations within sulfur-based network in comparison with selenium-based one.

  13. Low dose ionizing radiation induced acoustic neuroma: A putative link?

    Directory of Open Access Journals (Sweden)

    Sachin A Borkar

    2012-01-01

    Full Text Available Although exposure to high dose ionizing radiation (following therapeutic radiotherapy has been incriminated in the pathogenesis of many brain tumors, exposure to chronic low dose ionizing radiation has not yet been shown to be associated with tumorigenesis. The authors report a case of a 50-year-old atomic reactor scientist who received a cumulative dose of 78.9 mSv over a 10-year period and was detected to have an acoustic neuroma another 15 years later. Although there is no proof that exposure to ionizing radiation was the cause for the development of the acoustic neuroma, this case highlights the need for extended follow-up periods following exposure to low dose ionizing radiation.

  14. Evaluation of the Photoprotective Effect of Dongchongxiacao (Paecilomyces japonica) Extract against Ultraviolet Radiation-induced Skin Wrinkling and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Moon, Chang Jong; Kim, Jong Choon; Kim Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of); Jang, Jong Sik [Department of Animal Science, Kyungpook National University, Daegu (Korea, Republic of)

    2012-03-15

    To evaluate the ability of Dongchongxiacao (Paecilomyces japonica ) extract (PJE) to protect the skin from photo damage, the gross and microscopic changes in the skin of hairless mice and PJE-treated mice exposed chronically to ultraviolet (UV) were examined. The skin of the UV-irradiated mice showed characteristic signs of photo aging, such as deep wrinkles across the back. PJE-treated mice showed a significantly decreased wrinkling score. By the 22nd week, 88.9% (i.p. with saline) or 44.4% (topical administration with cream base) of the UV-irradiated mice developed at least one tumor. PJE delayed tumor onset significantly. PJE (i.p.) was also effective in reducing the occurrence of UV radiation-induced skin tumors and reduced the number of tumors per mouse. After 22 weeks of treatment, 80.0% (i.p.) and 75.0% (topical) of the mice treated with PJE were tumor-free. Tumor multiplicity was reduced by 96.2% (i.p.) in the PJE treated groups. It is noted that skin that is chronically exposed to UV is subject to photo aging and photo carcinogenesis and regular use of PJE would prevent these photo damaging effects of UV.

  15. Consistency in Perturbative Calculations and Radiatively Induced Lorentz and CPT Violations

    CERN Document Server

    Battistel, O A

    2002-01-01

    The origin of the radiatively induced Lorentz and CPT violations, in perturbative evaluations, of an extended version of QED, is investigated. Using a very general calculational method, concerning the manipulations and calculations involving divergent amplitudes, we clearly identify the possible sources of contributions for the violating terms. We show that consistency in the perturbative calculations, in a broader sense, leaves no room for the existence of radiatively induced contributions which is in accordance with what was previously conjectured and recently advocated by some authors supported on general arguments.

  16. Macro-Bending Influence on Radiation Induced Attenuation Measurement in Optical Fibres

    CERN Document Server

    Guillermain, E; Ricci, D; Weinand, U

    2014-01-01

    Influence of the bending radius on the measurement of radiation induced attenuation in glass optical fibres is discussed in this paper. Radiation induced attenuation measured in two single-mode fibre types shows discrepancies when coiled around a low bending radius spool: the observed attenuation is lower than expected. A series of dedicated tests reveals that this invalid measurement is related to the displacement of the mode field towards the cladding when the fibre is bent with a low radius, and to the different radiation resistances of the core and cladding glasses. For irradiation tests of optical fibres, the spool radius should therefore be carefully chosen.

  17. A Rare Case of Radiation-Induced Osteosarcoma of the Ethmoid Sinus

    Directory of Open Access Journals (Sweden)

    Musaed Alzahrani

    2011-01-01

    Full Text Available Radiation therapy has been recognized as a useful modality of treatment in head and neck malignant tumors. However, radiation over 10 Gy may predispose to secondary tumors. Radiation-induced osteosarcoma of the ethmoid sinus is unusual. These tumors may present long after radiation with epistaxis. Computed tomography, magnetic resonance imaging, and biopsy are the modalities of diagnosis. We report a case of radiation-induced osteosarcoma of the ethmoid sinus 9 years after initial exposure. We describe the clinical presentation, the radiological findings, and the management.

  18. Detection of radiation-induced hydrocarbons in baked sponged cake prepared with irradiated liquid egg

    Science.gov (United States)

    Schulzki, G.; Spiegelberg, A.; Bögl, K. W.; Schreiber, G. A.

    1995-02-01

    For identification of irradiated food, radiation-induced volatile hydrocarbons (HC) are determined by gas chromatography in the non-polar fraction of fat. However, in complex food matrices the detection is often disturbed by fat-associated compounds. On-line coupling of high performance liquid chromatography (LC) and gas chromatography (GC) is very efficient to remove such compounds from the HC fraction. The high sensitivity of this fast and efficient technique is demonstrated by the example of detection of radiation-induced HC in fat isolated from baked sponge cake which had been prepared with irradiated liquid egg.

  19. Detection of radiation-induced hydrocarbons in baked sponge cake prepared with irradiated liquid egg

    Energy Technology Data Exchange (ETDEWEB)

    Schulzki, G.; Spiegelberg, A.; Boegl, K.W.; Schreiber, G.A. [Federal Institute for Health Protection of Consumers and Veterinary Medicine, Berlin (Germany)

    1995-10-01

    For identification of irradiated food, radiation-induced volatile hydrocarbons (HC) are determined by gas chromatography in the non-polar fraction of fat. However, in complex food matrices the detection is often disturbed by fat-associated compounds. On-line coupling of high performance liquid chromatography (LC) and gas chromatography (GC) is very efficient to remove such compounds from the HC fraction. The high sensitivity of this fast and efficient technique is demonstrated by the example of detection of radiation-induced HC in fat isolated from baked sponge cake which had been prepared with irradiated liquid egg. (Author).

  20. Growth hormone used to control intractable bleeding caused by radiation-induced gastritis.

    Science.gov (United States)

    Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

    2015-08-21

    Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis.

  1. Redox Chemistry in Radiation Induced Dissolution of Spent Nuclear Fuel : from Elementary Reactions to Predictive Modeling

    OpenAIRE

    Roth, Olivia

    2008-01-01

    The focus of this doctoral thesis is the redox chemistry involved in radiation induced oxidative dissolution of spent nuclear fuel and UO2 (as a model substance for spent nuclear fuel). It is shown that two electron oxidants are more efficient than one electron oxidants in oxidative dissolution of UO2 at low oxidant concentrations. Furthermore, it is shown that H2O2 is the only oxidant that has to be taken into account in radiation induced dissolution of UO2 under deep repository conditions (...

  2. Consistency in perturbative calculations and radiatively induced Lorentz and CPT violations

    Energy Technology Data Exchange (ETDEWEB)

    Battistel, O.A. [Department of Physics-CCNE, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)]. E-mail: orimar@ccne.ufsm.br; Dallabona, G. [Department of Physics-ICEx, Universidade Federal de Minas Gerais, Belo Horizonte (Brazil)]. E-mail: dalla@fisica.ufmg.br

    2002-08-01

    The origin of the radiatively induced Lorentz and CPT violations, in perturbative evaluations, of an extended version of QED, is investigated. Using a very general calculational method, concerning the manipulations and calculations involving divergent amplitudes, we clearly identify the possible sources of contributions for the violating terms. We show that consistency in the perturbative calculations, in a broader sense, leaves no room for the existence of radiatively induced contributions, which is in accordance with what was previously conjectured and recently advocated by some authors supported on general arguments. (author). Letter-to-the-editor.

  3. Validation and the first results of clinical use of an EORTC QLQ PRT-23 module to assess quality of life in patients with radiation-induced rectitis

    Directory of Open Access Journals (Sweden)

    O. E. Lutsevich

    2015-01-01

    yielded significantly different results between the patients without chronic radiation-induced rectitis (Stage 0 and those with the endoscopic manifestations of Stages III and IV radiation-induced rectitis (p0–III < 0.0006; p0–IV < 0.0004. The values of the EORTC QLQ С-30 and QLQ PRT-23 questionnaires were statistically significantly different in the patients with endoscopically verified radiation-induced rectitis and in those without this condition (p0–I < 0.03; p0–II < 0.02; p0–III < 0.0016; p0–IV < 0.00009. Conclusion. The EORTC QLQ С-30 and QLQ PRT-23 questionnaires may be used in the patients with chronic radiation-induced rectitis for assessment of the quality-of-life index, for determination of the integral values over time (before, during, and after treatment, for informed involvement of a patient during treatment, for estimation of patient satisfaction with the therapy performed. The EORTC QLQ С-30 questionnaire supplemented by the QLQ PRT-23 module is a subjective method. Our study provided support for the fact that the QLQ С-30 and QLQ PRT-23 questionnaires for staging chronic radiation-induced rectitis must be used in combination with any third questionnaire. 

  4. Radiation-induced proctitis cystica profunda in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Geisinger, K.R.; Scobey, M.W.; Northway, M.G.; Cassidy, K.T.; Castell, D.O. (Wake Forest Univ., Winston-Salem, NC (USA))

    1990-07-01

    Therapeutic pelvic irradiation is notorious for the production of clinically significant sequela after a long latency. One of the rarest of these complications is proctitis cystica profunda (PCP). To study the histologic changes of chronic radiation proctitis, we evaluated 35 female Wistar rats that had received a single exposure of 22.5 Gy of radiation to the rectum and were then followed for one year. We identified PCP and its precursor lesions in 18 rats. The fully developed lesion consisted of a focal expansion of the submucosa by dilated cystic spaces lined by a single layer of benign epithelial cells. Usually, PCP evolved as glands herniated between small defects in the muscularis mucosae. Mitotic figures were not recognized in the cells lining the herniating glands. In two rats, the radiation had apparently caused large ulcers, which had subsequently reepithelialized, resulting in prominent submucosal glandular tissue. Although the number of goblet cells in the displaced epithelium was reduced, the cells had rather mature appearances ultrastructurally. Glands displaced into the submucosa were encased by an intact basal lamina but lacked in muscularis.

  5. Molecular monitoring of 8p11 myeloproliferative syndrome in an infant.

    Science.gov (United States)

    Zhang, Wenyong W; Habeebu, Sultan; Sheehan, Andrea M; Naeem, Rizwan; Hernandez, Vivian S; Dreyer, Zoann E; López-Terrada, Dolores

    2009-11-01

    The 8p11 myeloproliferative syndrome is a rare hematologic malignancy derived from a pluripotent hematopoietic stem cell associated with rearrangements involving the fibroblast growth factor receptor 1 (FGFR1) gene located on chromosome 8p11. The most common translocation, t(8;13) (p11;q13), results in a ZNF198-FGFR1 fusion gene and constitutively active FGFR1 tyrosine kinase activity. Typical pathologic findings include myeloid hyperplasia, lymphadenopathy, precursor T-lymphoblastic lymphoma, and eosinophilia. The disease is usually associated with an aggressive course and progression to acute myeloid leukemia is frequent. We report here the first case of 8p11 myeloproliferative syndrome in an infant and demonstrate the value of molecular testing in the diagnosis and minimal disease monitoring of this rare disease.

  6. Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

    Directory of Open Access Journals (Sweden)

    Matthew D Fountain

    2016-11-01

    Full Text Available Introduction: Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. Methods: C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by H&E, Masson’s Trichrome and Ki-67 staining at 1, 4, 10, 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45 respectively. Results: Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as one week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.Conclusions: Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.

  7. TGF-beta, radiation-induced pulmonary Injury and lung cancer

    NARCIS (Netherlands)

    Vujaskovic, Z; Groen, HJM

    2000-01-01

    Purpose: To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients. Materials and methods: Plasma TGF-beta was investigated in 27 patients with stag

  8. CLONING AND EXPRESSION OF A GENE MEDIATINGγ-RADIATION-INDUCED APOPTOSIS IN HL-60 CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To identify the member of the caspase family proteases involved in γ-radiation-induced apoptosis in HL-60 cells and to study the expression of the caspase gene in normal, apoptotic cells and in immortal tu mor cells. Methods By using degenerate oligonucleotide primers encoding the highly conserved peptides that were pre sent in all known caspases, we performed RT-PCR on poly(A)RNA from γ-radiation-induced apoptotic HL-60 cells. Caspase-3 mRNA in apoptotic HL-60 cells and in human tumor cell lines was analyzed by Northern blot. Results The amplified DNA fragment was identified with caspase-3 cDNA by cloning and sequencing. The Northern blot analysis of caspase-3 mRNA of different human tumor cell lines showed that the caspase-3 gene transcript was more highly ex pressed in leukemia cell lines and the SH-SY5Y cell line than in HeLa and MCF-7 cells. It was more highly expressed in the radiation-induced apoptotic HL-60 cells than in control HL-60 cells. Conclusion These results indicated that caspase-3 was involved in γ-radiation-induced apoptosis in HL-60 cells. The high level of expression of caspase-3 may aid efforts to understand the insensitivity of some tumor cells to radiation, their inherent ability to survive, and apop tosis.

  9. THE ROLE OF SECRETORY GRANULES IN RADIATION-INDUCED DYSFUNCTION OF RAT SALIVARY-GLANDS

    NARCIS (Netherlands)

    PETER, B; VANWAARDE, MAWH; VISSINK, A; SGRAVENMADE, EJ; KONINGS, AWT

    1995-01-01

    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 o

  10. The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore.

    Science.gov (United States)

    Jacobs, G P; Samuni, A; Czapski, G

    1985-06-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.

  11. Contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P. (Hebrew Univ., Jerusalem (Israel). School of Pharmacy); Samuni, A. (Hebrew Univ., Jerusalem (Israel). School of Medicine); Czapski, G. (Hebrew Univ., Jerusalem (Israel). Dept. of Physical Chemistry)

    1985-06-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.

  12. Radiation induced renal arterial stenosis detected by color duplex ultrasonography: case report

    Institute of Scientific and Technical Information of China (English)

    Jing Gao; Byong K Park; Arnold Alday

    2005-01-01

    Renal artery stenosis as a complication from radiation therapy is not common, but it is life threatening and needs to be corrected urgently in order to prevent renal failure even losing kidney. The diagnostic criteria of renal artery stenosis in the adults by color duplex ultrasonography have been established, which may play an important role in screening radiation induced renal artery stenosis.

  13. Mechanism of radiation-induced diacylglycerol production in primary cultured rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Tetsuo; Yukawa, Osami [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    Protein kinase C (PKC) is known to be a key enzyme in radiation-induced signal transduction pathways. We have previously demonstrated that {gamma}-irradiation induces PKC activation and translocation from cytosol to membranes as a consequence of membrane lipid peroxidation in cultured rat hepatocytes (Int. J. Radiat. Biol. 70, 473-480, 1996). The present study was undertaken to investigate production of diacylglycerol, an endogenous activator of PKC, following {gamma}-irradiation of hepatocytes. Diacylglycerol content increased 3 min after irradiation, then decreased at 15 min and increased again at 30 min, indicating a biphasic pattern. This result implies participation of diacylglycerol in the radiation-induced activation of PKC in hepatocytes. In order to clarify the mechanism of the initial process of radiation-induced diacylglycerol production, the effects of reactive oxygens were investigated. Treatment of cells with hydroxyl radical, a major oxygen radical produced by radiation, induced diacylglycerol production without any change in the content of phosphatidylcholine, showing a peak at 1 min after treatment. No change in the diacylglycerol content was observed at that time by hydrogen peroxide treatment. Furthermore, the diacylglycerol production by hydroxyl radical was inhibited by pretreatment with neomycin sulfate, a phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor. These results suggest that radiation exerts PI-PLC activation through hydroxyl radical generation, followed by diacylglycerol production and PKC activation. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

    2013-09-27

    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.

  15. Radiation-induced apoptosis in relation to acute impairment of rat salivary gland function

    NARCIS (Netherlands)

    Paardekooper, GMRM; Cammelli, S; Zeilstra, LJW; Coppes, RP; Konings, AWT

    1998-01-01

    Purpose: To find an answer to the question: Are the acute radiation effects on salivary gland function, as seen in earlier studies, causally related to radiation-induced apoptosis? Materials and methods: Rat parotid and submandibular glands were X-irradiated with doses up to 25 Gy and morphological

  16. Radiation induced cell loss in rat submandibular gland and its relation to gland function

    NARCIS (Netherlands)

    Zeilstra, LJW; Vissink, A; Konings, AWT; Coppes, RP

    2000-01-01

    Purpose: To understand early and late radiation-induced loss of function of the submandibular gland, changes in cell number were documented and correlated with data on gland function. Modulation of the radiation effect by sialogogues was used to investigate possible mechanisms of action. Materials a

  17. RADIATION-INDUCED CELL-PROLIFERATION IN THE PAROTID AND SUBMANDIBULAR GLANDS OF THE RAT

    NARCIS (Netherlands)

    PETER, B; VANWAARDE, MAWH; VISSINK, A; SGRAVENMADE, EJ; KONINGS, AWT

    1994-01-01

    Repopulation of tissues with cells at damaged sites is an important feature in the recovery of radiation-induced tissue injury. To obtain insight into the regenerative process in salivary gland tissue, proliferative activity was measured as a function of time in the different epithelial cell compart

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

    Directory of Open Access Journals (Sweden)

    B.H. Bakkal

    2013-09-01

    Full Text Available 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. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    2009-01-01

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their poten

  20. Stem cells and the repair of radiation-induced salivary gland damage

    NARCIS (Netherlands)

    Coppes, R. P.; Stokman, M. A.

    2011-01-01

    Hyposalivation underlying xerostomia after radiotherapy is still a major problem in the treatment of head and neck cancer. Stem cell therapy may provide a means to reduce radiation-induced hyposalivation and improve the quality of life of patients. This review discusses the current status in salivar

  1. Radiation-induced hypothyroidism in head and neck cancer patients : A systematic review

    NARCIS (Netherlands)

    Boomsma, Marjolein J.; Bijl, Hendrik P.; Langendijk, Johannes A.

    2011-01-01

    Purpose: To review literature on the relationship between the dose distribution in the thyroid gland and the incidence of radiation-induced hypothyroidism in adults. Material and Methods: Articles were identified through a search in MEDLINE, EMBASE and the Cochrane Library. Approximately 2449 articl

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

    NARCIS (Netherlands)

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

    2012-01-01

    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 measure

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

    Energy Technology Data Exchange (ETDEWEB)

    Boomsma, Marjolein J.; Bijl, Hendrik P.; Christianen, Miranda E.M.C.; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J.H.M. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Laan, Bernard F.A.M. van der [Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Oosting, Sjoukje F. [Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A., E-mail: j.a.langendijk@umcg.nl [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); 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.

  5. Radiation-induced medulloblastoma in an adult: A functional imaging study

    Directory of Open Access Journals (Sweden)

    Padma M

    2004-01-01

    Full Text Available We describe functional imaging findings using MRI, 1H-Magnetic resonance spectroscopy and positron emission tomography in a case of radiation-induced medulloblastoma following radiotherapy for pineal gland tumor. MRS showed a prominent choline peak; FDG, 11C-Met and 11C-Choline PET showed a minimal glucose, increased methionine and choline uptake.

  6. High-LET radiation-induce malignant and benign tumors in rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Burns, F.J. [Institute of Environmental Medicine, New York University Medical Center, New York, NY (United States); Zhao, P.; Hiz, Z.; Chen, S.; Roy, N.

    1999-03-01

    In the multistage theory of carcinogenesis, cells progress to cancer through a series of mutations in cancer-relevant genes, and sometimes the intermediate stages become benign neoplastic lesions. Although cancer induction by low LET radiation is subject to repair or recovery in the sense that multiple exposures produce fewer cancers than the same single dose, this recovery is not seen following exposure to high LET radiation. Data are presented on squamous and basal cell carcinoma and fibroma induction in rat skin exposed to: 1. an electron beam (LET=0.34 kV/{mu}), 2. a neon ion beam (LET=30 kV/{mu} ) and 3. an argon ion beam (LET=125 kV/{mu}). Cancer yields were fitted by a LET-dependent quadratic equation, and equation parameters were estimated by regression analysis for each type of radiation. The results are consistent with the interpretation that carcinoma induction can be explained by a pathway involving 2 radiation-induced events, 1 radiation-induced mutation and 1 spontaneous mutation, while benign fibromas can be explained by a pathway involving 1 radiation-induced event and 1 radiation-induced mutation. (author)

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

    Science.gov (United States)

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

    2015-10-01

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

  8. 3D ultrasound Nakagami imaging for radiation-induced vaginal fibrosis

    Science.gov (United States)

    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. Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP

    Energy Technology Data Exchange (ETDEWEB)

    Kimler, B.F.; Leeper, D.B.; Snyder, M.H.; Rowley, R.; Schneiderman, M.H. (Thomas Jefferson Univ., Philadelphia, PA (USA). Hospital)

    1982-01-01

    The mitotic selection procedure for cell cycle analysis was utilized to investigate the concentration-dependent modification of x-radiation-induced division delay in Chinese hamster ovary (CHO) cells by methyl xanthines (caffeine, theophylline, and theobromine) and by dibutyryl cyclic AMP. The methyl xanthines (concentrations from 0.5 to 1000 ..mu..g/ml) all reduced radiation-induced division delay with the effect being linear between approximately 100 and 1000 ..mu..g/ml. After doses of 100-300 rad, delay was reduced by 75, 94 or 83 per cent at 1000 ..mu..g/ml for each drug, respectively. However, the addition of dibutyryl cyclic AMP had an opposite effect: radiation-induced delay was increased by the concentration range of 0.3 to 300 ..mu..g/ml. These results indicate that in mammalian cells the control of cell cycle progression and the modification of radiation-induced division delay are not simply related to intracellular levels of cyclic AMP. Rather, there appear to be at least two competing mechanisms which are differentially affected by caffeine analogues or by direct addition of dibutyryl cyclic AMP. The direct effect of caffeine and the methyl xanthines on membrane calcium permeability is considered.

  10. Radiological and functional assessment of radiation-induced lung injury in the rat

    NARCIS (Netherlands)

    Vujaskovic, Z; Down, JD; van t'Veld, AA; Mooyaart, EL; Meertens, H; Piers, DA; Szabo, BG; Konings, AWT

    1998-01-01

    The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anaesthetized and the right lung irradiated wi

  11. Review of current classification, molecular alterations, and tyrosine kinase inhibitor therapies in myeloproliferative disorders with hypereosinophilia

    Directory of Open Access Journals (Sweden)

    Havelange V

    2013-08-01

    Full Text Available Violaine Havelange,1,2 Jean-Baptiste Demoulin1 1de Duve Institute, Université catholique de Louvain, Brussels, Belgium; 2Department of Hematology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium Abstract: Recent advances in our understanding of the molecular mechanisms underlying hypereosinophilia have led to the development of a 'molecular' classification of myeloproliferative disorders with eosinophilia. The revised 2008 World Health Organization classification of myeloid neoplasms included a new category called “myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1.” Despite the molecular heterogeneity of PDGFR (platelet-derived growth factor receptor rearrangements, tyrosine kinase inhibitors at low dose induce rapid and complete hematological remission in the majority of these patients. Other kinase inhibitors are promising. Further discoveries of new molecular alterations will direct the development of new specific inhibitors. In this review, an update of the classifications of myeloproliferative disorders associated with hypereosinophilia is discussed together with open and controversial questions. Molecular mechanisms and promising results of tyrosine kinase inhibitor treatments are reviewed. Keywords: hypereosinophilia, classification, myeloproliferative disorders, molecular alterations, tyrosine kinase inhibitor

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. Effect of radiation-induced emission of Schottky defects on the formation of colloids in alkali halides

    NARCIS (Netherlands)

    Dubinko, [No Value; Vainshtein, DI; Den Hartog, HW

    2003-01-01

    Formation of vacancy clusters in irradiated crystals is considered taking into account radiation-induced Schottky defect emission (RSDE) from extended defects. RSDE acts in the opposite direction compared with Frenkel pair production, and it results in the radiation-induced recovery processes. In th

  14. Adenosine kinase inhibition protects against cranial radiation-induced cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Munjal M Acharya

    2016-06-01

    Full Text Available 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, and contextual fear conditioning 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 fear conditioning 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 also against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS

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

    Science.gov (United States)

    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.

  16. Applications of Natural Radiation-Induced Paramagnetic Defects in Quartz to Exploration in Sedimentary Basins

    Institute of Scientific and Technical Information of China (English)

    Pan Y M; Botis S; Nokhrin S

    2006-01-01

    Quartz grains in contact with uranium-bearing minerals or fluids are characterized by natural radiation-induced paramagnetic defects (e. G. , oxygen vacancy centers, silicon vacancy centers, and peroxy radicals), which are amenable to study by electron paramagnetic resonance (EPR) spectroscopy.These natural radiation-induced paramagnetic defects, except for the oxygen vacancy centers, in quartz are concentrated in narrow bands penetrated by α particles: (1) in halos around U- and Th-bearing mineral inclusions and (2) in outer rims or along fractures. The second type of occurrence provides information about uranium mineralization or remobilization (I. E. , sources of uranium, timing of mineralization or remobilization, pathways of uranium-bearing fluids). It can also be used to evaluate sedimentary basins for potential of uranium mineralization. In particular, the peroxy radicals are stable up to 800℃and, therefore, are useful for evaluating metasedimentary rocks (e. G. , Paleoproterozoic metasedimentary sequences in the central zone of the North China craton). EPR study of the Changcheng Series can focus on quartz from the sediment-basement unconformity and faults to determine the presence and types of natural radiation-induced paramagnetic defects, with which to identify and prioritize uranium anomalies. Other potential applications of natural radiation-induced paramagnetic defects in quartz include uranium-bearing hydrocarbon deposits in sedimentary basins. For example, the Junggar, Ordos, and Tarim basins in northwestern China all contain important oil and natural gas fields and are well known for elevated uranium concentrations, including economic sandstone-hosted uranium deposits. Therefore,systematic studies on the distribution of natural radiation-induced paramagnetic defects in quartz from host sedimentary sequences are expected to provide information about the migration of oil and natural gas in those basins.

  17. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, H.C.; Larsen, T.S.; Riley, C.H.

    2011-01-01

    mutation in the large majority of patients with PV and in half of those with ET and PMF. A number of studies have shown that the "tumor burden" may be monitored at the molecular level in JAK2-positive patients using highly sensitive real-time quantitative PCR. During the last 25 years several studies have...

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

    Energy Technology Data Exchange (ETDEWEB)

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N. [Harvard Medical School, Boston, MA (United States)

    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.

  19. Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Varshney, R.; Kale, R.K. (Jawaharlal Nehru Univ., New Delhi (India). School of Life Sciences)

    1990-11-01

    Rat liver microsomes were irradiated with {gamma}-rays at a dose of 1.31 Gy s{sup -1}. The extent of lipid peroxidation, measured in terms of malondialdehyde (MDA) formed, increased with radiation dose. The presence of calmodulin antagonists during irradiation decreased lipid peroxidation. The order of their protective efficiency was: chlorpromazine (CPZ)>promethazine (PMZ)>trimeprazine (TMZ). Their protective effect was diminished in the presence of ferrous (Fe{sup 2+}) ions and was restored on addition of EDTA. However, calmodulin antagonists considerably inhibited radiation-induced lipid peroxidation in the presence of ferric (Fe{sup 3+}) ions. Calmodulin antagonists also decreased the cytochrome P-450 content of microsomes. These results are discussed with respect to their applicability to radiotherapy. A possible mechanism for the inhibition of radiation-induced lipid peroxidation is suggested. (author).

  20. Reconstitution studies on the involvement of radiation-induced lipid peroxidation in damage to membrane enzymes.

    Science.gov (United States)

    Yukawa, O; Nagatsuka, S; Nakazawa, T

    1983-04-01

    The effect of radiation on the drug-metabolizing enzyme system of microsomes, reconstituted with liposomes of microsomal phospholipids, NADPH-cytochrome P-450 reductase and cytochrome P-450, was examined to elucidate the role of lipid peroxidation of membranes in radiation-induced damage to membrane-bound enzymes. The reconstituted system of non-irradiated enzymes with irradiated liposomes showed a low activity of hexobarbital hydroxylation, whereas irradiated enzymes combined with non-irradiated liposomes exhibited an activity equal to that of unirradiated controls. Irradiation of liposomes caused a decrease in cytochrome P-450 content by destruction of the haem of cytochrome P-450 and also inhibited the binding capacity of cytochrome P-450 for hexobarbital. The relationship between radiation-induced lipid peroxidation and membrane-bound enzymes is discussed.

  1. Reconstitution studies on the involvement of radiation-induced lipid peroxidation in damage to membrane enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, O.; Nagatsuka, S.; Nakazawa, T. (National Inst. of Radiological Sciences, Chiba (Japan))

    1983-04-01

    The effect of ..gamma..-radiation on the drug-metabolizing enzyme system of microsomes, reconstituted with liposomes of microsomal phospholipids, NADPH-cytochrome P-450 reductase and cytochrome P-450, was examined to elucidate the role of lipid peroxidation of membranes in radiation-induced damage to membrane-bound enzymes. The reconstituted system of non-irradiated enzymes with irradiated liposomes showed a low activity of hexobarbital hydroxylation, whereas irradiated enzymes combined with non-irradiated liposomes exhibited an activity equal to that of unirradiated controls. Irradiation of liposomes caused a decrease in cytochrome P-450 content by destruction of the haem of cytochrome P-450 and also inhibited the binding capacity of cytochrome P-450 for hexobarbital. The relationship between radiation-induced lipid peroxidation and membrane-bound enzymes is discussed.

  2. Treatment of radiation-induced hemorrhagic gastritis with prednisolone: A case report

    Institute of Scientific and Technical Information of China (English)

    Lan Zhang; Xiao-Ying Xie; Yan Wang; Yan-Hong Wang; Yi Chen; Zheng-Gang Ren

    2012-01-01

    Radiation-induced gastritis is an infrequent cause of gastrointestinal bleeding.It is a serious complication arising from radiation therapy,and the standard treatment method has not been established.The initial injury is characteristically acute inflammation of gastric mucosa.We presented a 46-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for metastatic retroperitoneal lymph node of hepatocellular carcinoma.The endoscopic examination showed diffuse edematous hyperemicmucosa with telangiectasias in the whole muscosa of the stomach and duodenal bulb.Mlultiple hemorrhagic patches with active oozing were found over the antrum.Anti-secretary therapy was initiated for hemostasis,but melena still occurred off and on.Finally,he was successfully treated by prednisolone therapy.We therefore strongly argue in favor of perdnisolone therapy to effectively treat patients with radiation-induced hemorrhagic gastritis.

  3. A case of radiation-induced osteosarcoma treated effectively by boron neutron capture therapy.

    Science.gov (United States)

    Futamura, Gen; Kawabata, Shinji; Siba, Hiroyuki; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji; Sakurai, Yoshinori; Tanaka, Minoru; Todo, Tomoki; Miyatake, Shin-Ichi

    2014-11-04

    We treated a 54-year-old Japanese female with a recurrent radiation-induced osteosarcoma arising from left occipital skull, by reactor-based boron neutron capture therapy (BNCT). Her tumor grew rapidly with subcutaneous and epidural extension. She eventually could not walk because of cerebellar ataxia. The tumor was inoperable and radioresistant. BNCT showed a marked initial therapeutic effect: the subcutaneous/epidural tumor reduced without radiation damage of the scalp except hair loss and the patient could walk again only 3 weeks after BNCT. BNCT seems to be a safe and very effective modality in the management of radiation-induced osteosarcomas that are not eligible for operation and other treatment modalities.

  4. Radiation-induced color centers in La-doped PbWO sub 4 crystals

    CERN Document Server

    Deng, Q; Zhu, R Y

    1999-01-01

    This report presents the result of a study on radiation-induced color center densities in La-doped lead tungstate (PbWO sub 4) crystals. The creation and annihilation constants of radiation-induced color centers were determined by using transmittance data measured for a PbWO sub 4 sample before and during sup 6 sup 0 Co gamma-ray irradiation at a dose rate of 15 rad/h. Following a model of color center kinetics, these constants were used to calculate color center densities under irradiations at 100 rad/h. The result was found to be in good agreement with experimental data, indicating that the behaviour of PbWO sub 4 crystals under irradiation can be predicted according to this model.

  5. The effects of herbs on the radiation-induced apoptosis in intestinal crypt cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; An, Mi Ra; Nah, Seung Yeol; Lee, Jong Hwan; Kim, Jae Ha; Shin, Dong Ho [Chonnam National Univ., Gwangju (Korea, Republic of); Jo, Sung Kee [KAERI, Daejeon (Korea, Republic of); Jang, Jong Sik [Sangju National Univ., Sangju (Korea, Republic of)

    2001-03-15

    This study was performed to determine the effect of several herbs on radiation-induced apoptosis in jejunal crypt cells. Longyanrou(Euphoris logana), Suanzaoren(Zizyphus vulgaris), Yuanzhi(Polygala tenuifolia), Rensan(Panax ginseng), Fuling(Poria cocos), Muxiang(Saussurea lappa), Chuanxiong(Cnidium offcinale), Baishaoyao(Paeonia lactifolia), Shengma(Cimicifuga heracleifolia), Chaihu(Bupleurum falcatum) and Dongchongxiacao(Paecilomyces japonica) reduced the frequency of radiation-induced apoptosis(p<0.05). Although the mechanisms of this effect remain to be elucidated, these results indicated that Longyanrou, Suanzaoren, Yuanzhi, Rensan, Fuling, Muxiang, Chuanxiong, Baishaoyao, Shengma, Chaihu and Dongchongxiacao might be useful inhibitors of apoptosis, especially since these are relative nontoxic natural products.

  6. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1989-08-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

  7. Recombination of charge carriers on radiation-induced defects in silicon doped by transition metals impurities

    CERN Document Server

    Kazakevich, L A

    2003-01-01

    It has been studied the peculiarities of recombination of nonequilibrium charge carriers on radiation-induced defects in received according to Czochralski method p-silicon (p approx 3 - 20 Ohm centre dot cm), doped by one of the impurities of transition metals of the IV-th group of periodic table (titanium, zirconium, hafnium). Experimental results are obtained out of the analysis of temperature and injection dependence of the life time of charge carriers. The results are explained taking into consideration the influences of elastic stress fields created by the aggregates of transition metals atoms on space distribution over the crystal of oxygen and carbon background impurities as well as on the migration of movable radiation-induced defects during irradiation. (authors).

  8. Modulation of radiation-induced biochemical changes in cerebrum of Swiss albino mice by Grewia Asiatica.

    Science.gov (United States)

    Sisodia, Rashmi; Ahaskar, Muktika; Sharma, K V; Singh, Smita

    2008-01-01

    The present study evaluates the possible radioprotective effect of Grewia asiatica fruit (rich in anthocyanin, carotenes, vitamin C, etc.) pulp extract (GAE) on cerebrum of Swiss albino mice exposed to 5 Gy gamma radiation. For this, healthy mice from an inbred colony were divided into four groups: (1) Control (vehicle treated) (2) GAE treated - mice in this group were orally supplemented with GAE (700 m/kg. b.w./day) once daily for fifteen consecutive days, (3) Vehicle treated irradiated mice, and (4) GAE + Irradiated - Mice in this group received distilled water orally equivalent to GAE (700 m/kg. b.w/day) for fifteen days consecutively. Mice were sacrificed at various intervals viz. 1-30 days. Radiation-induced augmentation in the levels of lipid peroxidation of mice cerebrum was significantly ameliorated by GAE pretreatment. Radiation-induced depletion in the level of glutathione and protein was prevented significantly by GAE administration.

  9. Effect of radiation induced deep level traps on Si detector performance

    CERN Document Server

    Eremin, V; Li, Z

    2002-01-01

    The main factor, which leads to semiconductor detector degradation in high-energy physics experiments, is the introduction of lattice defects in the detector material produced by radiation. Based on the spectrum of radiation induced defects in the silicon bulk, the overview of effects and mechanisms responsible for the changes in the main detector parameters such as effective concentration of the space charge in the depleted region, space charge sign inversion, charge collection efficiency, and detector breakdown voltage are considered. Special attention is paid to the electric field distortion related with high concentration of radiation induced deep traps, which is the key question for the design of detectors operating at cryogenic temperature. In particular, the charge collection recovery at low temperature, often refereed as the Lazarus effect, and the limitation for the detection rate related to the polarization effect are considered.

  10. Modification of polyethylene by radiation-induced graft polymerization of acrylic acid

    Science.gov (United States)

    Sidorova, L. P.; Aliev, A. D.; Zlobin, V. B.; Aliev, R. E.; Chalykh, A. E.; Kabanov, V. Ya.

    The kinetics investigation of the radiation-induced graft polymerization of acrylic acid onto low density polyethylene by direct method in aqueous solution in the presence of Mohr's salt, was performed. The technique of the contrasting of polyacrylic acid (PAA) graft layer was worked out by Ag +-ions. The structural and morphological peculiarities of grafted copolymers of PE with PAA were determined by the method of electron probe, and X-ray microanalysis by means of the electron microscopy.

  11. Radiation-induced solid state polymerization of N-substituted acrylamides and methacrylamides at reduced temperature

    Energy Technology Data Exchange (ETDEWEB)

    Zurakowska-Orszagh, J.; Gumulka, A.; Bartnik, J. (Warsaw Univ. (Poland). Dept. of Chemistry)

    1984-01-01

    Radiation-induced solid state in-source polymerization and post-polymerization at reduced temperature of a series of N-tert-alkylacrylamides and pairs of monomers of the acrylamide and methacrylamide series with identical aliphatic aromatic and alicyclic substituents has been studied. The effect of the changes in the structure of particular monomers on their reactivity at reduced temperature as compared with their reactivity at room temperature has been considered.

  12. Dynamics of radiation-induced charging and discharging of foil electrets

    Science.gov (United States)

    Fallone, B. G.; Podgorsak, E. B.

    1983-04-01

    The time dependence of the polarization and depolarization current densities, the effective electric field in the electret chamber, and the electret surface charge densities are presented for the radiation-induced foil electret. With the use of the hyperbolic dependence of the ionization-chamber current density on the effective electric field, one obtains excellent agreement between calculated and measured electret polarization and depolarization current densities.

  13. Radiation-induced effects in chalcogenide glasses: Topological mechanisms and application

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O.I. E-mail: karat@ipm.lviv.ua

    2000-05-02

    Structural transformations in vitreous As{sub 2}S{sub 3}-based chalcogenide semiconducting glasses induced by {gamma}-irradiation have been considered on the basis of IR Fourier spectroscopy results as destruction-polymerization changes of the covalent chemical bonds, associated with specific coordination defects formation. The whole variety of these processes has been taken into account in order to construct the physically real variants of the radiation-induced structural changes.

  14. Photon Radiation Induced by Multiple Parton Rescattering in Deeply Inelastic Scattering

    Institute of Scientific and Technical Information of China (English)

    张本威; 王恩科

    2003-01-01

    Photon radiation induced by multiple parton rescattering and corresponding parton energy loss in eA deeply inelastic scattering are investigated by using the generalized factorization of higher twist parton distributions beyond the helicity amplitude approximation. It turns out that the behaviour of the nuclear size dependence of the parton energy loss is different in the photon and gluon radiation cases. The parton energy loss due to photon radiation depends linearly, instead of quadratically, on nuclear size due to gluon radiation.

  15. Radiation Induced Crosslinking of Polyethylene in the Presence of Bifunctional Vinyl Monomers

    DEFF Research Database (Denmark)

    Joshi, M. S.; Singer, Klaus Albert Julius; Silverman, J.

    1977-01-01

    Several reports have been published showing that the radiation induced grafting of bifunctional vinyl monomers to low density polyethylene results in a product with an unusually high density of crosslinks. The same grafting reactions are shown to reduce the incipient gel dose by more than a factor...... of fifty. This paper is concerned with the apparent crosslinking produced by the radiation grafting of two monomers to polyethylene: acrylic acid and acrylonitrile....

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

    Directory of Open Access Journals (Sweden)

    Dipankar Ray

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. THE EFFECT OF POLAR ADDITIVES ON THE γ RADIATION INDUCED POLYMERIZATION OF STYRENE

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xujia; HA Hongfei; WU Jilan; WEI Genshuan

    1994-01-01

    The γ induced polymerization of styrene in the presence of polar additives such as tributyl phosphate, triethyl amine and ethanol was studied at dose rate of 5.0 × 1017 eV/ml. min. The result shows that radiation induced polymerization of styrene was sensitized by the three kinds of additives at the approximate same rate and the experimental results were in agreement with the theoretical calculation of WAS equation. The cause of sensitization is due to the proton transfer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ghorbanzadeh-Moghaddam, Amir [Medical Student' s Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Gholamrezaei, Ali, E-mail: Gholamrezaei@med.mui.ac.ir [Medical Student' s Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Poursina Hakim Research Institution, Isfahan (Iran, Islamic Republic of); Hemati, Simin [Department of Radiotherapy Oncology, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of)

    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.

  1. C-V and DLTS studies of radiation induced Si-SiO2 interface defects

    Science.gov (United States)

    Capan, I.; Janicki, V.; Jacimovic, R.; Pivac, B.

    2012-07-01

    Interface traps at the Si-SiO2 interface have been and will be an important performance limit in many (future) semiconductor devices. In this paper, we present a study of fast neutron radiation induced changes in the density of Si-SiO2 interface-related defects. Interface related defects (Pb centers) are detected before and upon the irradiation. The density of interface-related defects is increasing with the fast neutron fluence.

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

    Energy Technology Data Exchange (ETDEWEB)

    Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C., E-mail: prabhat-goswami@uiowa.edu

    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.

  3. Isolation of dual-tropic murine leukemia virus from radiation-induced thymoma in RF mouse

    Energy Technology Data Exchange (ETDEWEB)

    Okumoto, M.; Nishikawa, R.; Takamori, Y.; Iwai, Y.; Iwai, M. (Radiation Center of Osaka Prefecture, Sakai (Japan))

    1981-03-01

    Two different murine leukemia viruses (MuLV) were isolated from radiation-induced thymoma in RF mouse by co-cultivation method with mink lung cells. One is ecotropic MuLV, which replicates efficiently in NIH Swiss mouse embryo (NIH ME) and SC-1 cells and was able to form XC plaques. The other was dualtropic MuLV, which replicates in both mink lung cells and NIH ME cells but was unable to form XC plaques.

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

    OpenAIRE

    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 retrospectiv...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

    Science.gov (United States)

    Chu, JianJun; Zhang, Xiaojun; Jin, Liugen; Chen, Junliang; Du, Bin; Pang, Qingfeng

    2015-03-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of β-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

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

    Energy Technology Data Exchange (ETDEWEB)

    Peter, B.; Van Waarde, M.A.W.H.; Konings, A.W.T. [Univ. of Groningen (Netherlands); Vissink, A. [Univ. of Groningen (Netherlands)]|[Univ. Hospital, Groningen (Netherlands); `s-Gravenmade, E.J. [Univ. Hospital, Groningen (Netherlands)

    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.

  10. Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Menz, R.; Andres, R.; Larsson, B.; Ozsahin, M.; Crompton, N.E.A. [Department of Life Sciences, Paul Scherrer Institute, CH-5232 Villigen-PSI (Switzerland); Trott, K. [St. Bartholemew`s and the Royal London School of Medicine and Dentistry, University of London (United Kingdom)

    1997-09-01

    An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is described. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunofluorescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a characteristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis increased for up to 5 days after irradiation. Optimal dose discrimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% {+-} 0.5% per 0.1 Gy. In controlled, dose-response experiments the lowest dose level at which the radiation-induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incubation, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the potential of this assay as a biological dosimeter. (orig.) With 5 figs., 2 tabs., 19 refs.

  11. Antioxidant activity of capsaicin on radiation-induced oxidation of murine hepatic mitochondrial membrane preparation

    Directory of Open Access Journals (Sweden)

    Gangabhagirathi R

    2015-06-01

    Full Text Available Ramachandran Gangabhagirathi,1 Ravi Joshi,2 1Bioorganic Division, 2Radiation and Photochemistry Division, Bhabha Atomic Research Center, Trombay, Mumbai, India Abstract: Capsaicin is the major capsaicinoid in chili peppers and is widely used as a spice. It is also used for topical applications in cases of peripheral neuropathy. The present study deals with its role in modulation of gamma radiation-induced damages of the biochemical constituents of rat liver mitochondrial membrane (RLM preparation. The extent of lipid hydroperoxide formation, depletion in protein thiols, and formation of protein carbonyls have been biochemically assessed in the presence of varying concentrations of capsaicin in RLM. Decrease in the activities of the important antioxidant enzyme superoxide dismutase, which is involved in the scavenging of free radicals, and the mitochondrial marker enzyme succinate dehydrogenase have been also looked into. Capsaicin has been found to efficiently inhibit radiation-induced biochemical alterations, namely lipid peroxidation and protein oxidation. It also significantly prevented radiation-induced loss in the activity of antioxidant enzyme and the important endogenous antioxidant glutathione. The study suggests that capsaicin can act as an antioxidant and radioprotector in physiological systems. Keywords: capsaicin, gamma radiation, radioprotection, lipid peroxidation, protein oxidation, enzyme activity

  12. Identification of differentially expressed radiation-induced genes in cervix carcinoma cells using suppression subtractive hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Sang; Lee, Young Sook; Lee, Jeung Hoon; Lee, Woong Hee; Seo, Eun Young; Cho, Moon June [Chungnam National University, Daejeon (Korea, Republic of)

    2005-03-15

    A number of genes and their products are induced early or late following exposure of cells to ionizing radiation. These radiation-induced genes have various effects of irradiated cells and tissues. Suppression subtractive hybridization (SSH) based on PCR was used to identify the differentially expressed genes by radiation in cervix carcinoma cells. Total RNA and poly (A){sup +} mRNA were isolated from irradiated and non-irradiated HeLa cells. Forward-and reverse-subtracted cDNA libraries were constructed using SSH. Eighty-eight clones of each were used to randomly select differentially expressed genes using reverse Northern blotting (dot blot analysis). Northern blotting was used to verify the screened genes. Of the 176 clones, 10 genes in the forward-subtracted library and 9 genes in the reverse-subtracted library were identified as differentially expressed radiation-induced genes by PCR-select differential screening. Three clones from the forward-subtracted library were confirmed by Northern blotting, and showed increased expression in a dose-dependent manner, including a telomerase catalytic subunit and sodium channel-like protein gene, and an ESTs (expressed sequence tags) gene. We identified differentially expressed radiation-induced genes with low-abundance genes with SSH, but further characterization of theses genes are necessary to clarify the biological functions of them.

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

    Science.gov (United States)

    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.

  14. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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).

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Yu Y

    2016-01-01

    Full Text Available Yang Yu,1 Hui Guan,1 Yuanli Dong,1 Ligang Xing,2 Xiaolin Li2 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan, 2Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong Province, People’s Republic of China 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. Keywords: lung cancer, esophagitis, radiation injuries, predictors

  19. Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis

    Directory of Open Access Journals (Sweden)

    Murray Lynne A

    2010-07-01

    Full Text Available Abstract Purpose To evaluate the effect of the anti-fibrotic protein serum amyloid P (SAP on radiation-induced oral mucositis (OM and fibrosis in a hamster cheek-pouch model. Experimental Design Hamsters received a single dose of radiation (40 Gy to the left everted cheek pouch to induce significant OM. The protective therapeutic potential of SAP was evaluated using varying dosing regimens. The extent of OM was measured using a validated six-point scoring scheme ranging from 0 (normal tissue, no mucositis to 5 (complete ulceration. Fibrotic remodeling was also visualized histologically and quantified at later time points using collagen gene expression. Results SAP treatment attenuated the profile of radiation-induced oral mucositis by delaying the time of onset, reducing the peak value, and enhancing the resolution of injury. The peak mucositis score was reduced by approximately 0.5 grade in SAP-treated animals. The number of animal days with a score of ≥ 3 was reduced by 48% in the SAP-treated group, compared with the saline control group (P Conclusions SAP treatment significantly attenuated radiation-induced injury. In particular, SAP attenuated the severity of OM and inhibited pathogenic remodeling. This suggests that SAP may be a useful therapy for the palliation of side effects observed during treatment for head and neck cancer.

  20. Karyotypic findings in chronic myeloid leukemia cases undergoing treatment

    OpenAIRE

    Anupam Kaur; Simran Preet Kaur; Amarjit Singh; Jai Rup Singh

    2012-01-01

    Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative expansion of primitive hematopoietic progenitor cells. Materials and Methods: In the present study, CML samples were collected from various hospitals in Amritsar, Jalandhar and Ludhiana. Results: Chromosomal alterations seen in peripheral blood lymphocytes of these treated and untreated cases of CML were satellite associations, double minutes, random loss, gain of C group chromosomes and presence of marker chr...

  1. Coverage and accuracy of myeloproliferative and myelodysplastic neoplasms in the Finnish Cancer Registry.

    Science.gov (United States)

    Leinonen, Maarit K; Rantanen, Matti; Pitkäniemi, Janne; Malila, Nea

    2016-06-01

    Background Registration of haematological malignancies presents specific challenges, and a wide range of data is required to ensure case ascertainment and proper classification of these diseases. We studied the data quality of myeloproliferative and myelodysplastic neoplasms in the Finnish Cancer Registry (FCR), comparing information with hospital discharges. Material and methods Hospital discharges (HILMO) in 2007-2013 including diagnostic codes of myeloproliferative and myelodysplastic neoplasms were extracted. Patients were individually linked to the FCR database for all haematological malignancies registered in 1953-2013. Coverage and accuracy of the FCR and agreement between registers was estimated. Results In total 5289 individuals were retrieved from two registers. Of these, 1406 were common, 1080 only found in the FCR and 2803 only in the HILMO. Coverage of myeloproliferative and myelodysplastic neoplasms in the FCR was 47.0% (95% CI 45.7-48.4%). Almost one quarter of the registrations in the FCR was based on a death certificate only. The accuracy of diagnosis was 51.4% (95% CI 49.4-53.3%), but it varied substantially by disease category. Kappa statistic for agreement between registers was excellent (0.83, 95% CI 0.80-0.85) for common cases. 7.6% of cases in the HILMO was registered as leukaemias in the FCR. Conclusions More than half of the patients found in the HILMO were entirely missing from the FCR. However, some of the diagnoses in HILMO may be preliminary and this represents the maximal number of missing cases. Cancer registers benefit from supplementary data sources, such as hospital discharges, to increase coverage and accuracy of register data on haematological malignancies.

  2. What is the Incidence of Kidney Stones after Chemotherapy in Patients with Lymphoproliferative or Myeloproliferative Disorders?

    Directory of Open Access Journals (Sweden)

    Hossein S. Mirheydar

    2014-12-01

    Full Text Available Introduction This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. Materials and Methods From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. Results A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316. Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013, calcium (p<0.001, and potassium (p=0.039 levels were higher in stone formers. Diabetes mellitus (p<0.001, hypertension (p=0.003, and hyperlipidemia (p<0.001 were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. Conclusions We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy.

  3. 20 alpha-hydroxysteroid dehydrogenase expression in a murine virus-induced myeloproliferative syndrome.

    Science.gov (United States)

    Marcovistz, R; Le Bousse-Kerdiles, M C; Maillere, B; Smadja-Joffe, F; Poirrier, V; Jasmin, C

    1991-11-01

    The myeloproliferative sarcoma virus (MPSV) infection in DBA/2 mice leads to important quantitative and qualitative changes in their hemopoiesis. These findings suggest a disturbance in the production and action of a certain hemopoietic factor similar to IL3. Here, we show that the level of the 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) expression, which can be induced by IL3, is dramatically increased in spleen and thymus of MPSV-infected mice. Our results suggest that quantification of 20 alpha-SDH activity can be used to indicate abnormal production of a growth factor similar to IL3 in hemopoietic system diseases.

  4. Forward current enhanced elimination of the radiation induced boron-oxygen complex in silicon n+-p diodes

    CERN Document Server

    Makarenko, L F; Yakushevich, H S; Moll, M; Pintilie, I

    2014-01-01

    Using forward current injection with densities in the range 15-30A/cm(2) we can effectively eliminate the radiation-induced boron-oxygen complex, which is the main compensating center in irradiated Si solar cells. It was found that for a given forward current density the elimination rate is decreasing with increasing irradiation dose. Additionally, some evidences have been obtained on the negative-U properties of the radiation-induced boron-oxygen complex.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 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.

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

    Science.gov (United States)

    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.

  8. Radiation-induced graft polymerization of acrylamide and acrylic acid onto polyethylene

    Science.gov (United States)

    Grushevskaya, L. N.; Aliev, R. E.; Kabanov, V. Ya.

    The radiation-induced grafting of acrylamide onto low-density polyethylene by the different methods and under different conditions was investigated: by the direct liquid phase method from this monomer solution in water (in neutral and acid media) and acetone, and by the pre-irradiation method from aqueous solutions as well as from its sublimated vapour. The molecular masses of polyacrylamide homopolymers were determined. The discussion and comparison of different methods of acrylamide grafting are performed. The relationship between rates of graft polymerization onto polyethylene and homopolymerization of acrylic acid in the presence of metal ions is considered.

  9. Suppression of radiation-induced point defects by rhenium and osmium interstitials in tungsten

    Science.gov (United States)

    Suzudo, Tomoaki; Hasegawa, Akira

    2016-11-01

    Modeling the evolution of radiation-induced defects is important for finding radiation-resistant materials, which would be greatly appreciated in nuclear applications. We apply the density functional theory combined with comprehensive analyses of massive experimental database to indicate a mechanism to mitigate the effect of radiation on W crystals by adding particular solute elements that change the migration property of interstitials. The resultant mechanism is applicable to any body-centered-cubic (BCC) metals whose self-interstitial atoms become a stable crowdion and is expected to provide a general guideline for computational design of radiation-resistant alloys in the field of nuclear applications.

  10. Suppression of radiation-induced point defects by rhenium and osmium interstitials in tungsten

    Science.gov (United States)

    Suzudo, Tomoaki; Hasegawa, Akira

    2016-01-01

    Modeling the evolution of radiation-induced defects is important for finding radiation-resistant materials, which would be greatly appreciated in nuclear applications. We apply the density functional theory combined with comprehensive analyses of massive experimental database to indicate a mechanism to mitigate the effect of radiation on W crystals by adding particular solute elements that change the migration property of interstitials. The resultant mechanism is applicable to any body-centered-cubic (BCC) metals whose self-interstitial atoms become a stable crowdion and is expected to provide a general guideline for computational design of radiation-resistant alloys in the field of nuclear applications. PMID:27824134

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

    Science.gov (United States)

    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.

  12. Radiation-induced cholecystitis after hepatic radioembolization: do we need to take precautionary measures?

    Science.gov (United States)

    Prince, Jip F; van den Hoven, Andor F; van den Bosch, Maurice A A J; Elschot, Mattijs; de Jong, Hugo W A M; Lam, Marnix G E H

    2014-11-01

    Controversy exists over the need to take precautionary measures during hepatic radioembolization to minimize the risk of radiation-induced cholecystitis. Strategies for a variety of clinical scenarios are discussed on the basis of a literature review. Precautionary measures are unnecessary in the majority of patients and should be taken only when single photon-emission computed tomography (CT; SPECT)/CT shows a significant concentration of technetium-99m macroaggregated albumin in the gallbladder wall. In this case report with quantitative SPECT analysis, it is illustrated how an adjustment of the catheter position can effectively reduce the absorbed dose of radiation delivered to the gallbladder wall by more than 90%.

  13. Chemical modification of radiation-induced changes in erythroid cells of mouse bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Bhagat, R.M.; Kumar, A. (Himachal Pradesh Univ., Simla (India). Dept. of Bio-sciences)

    1983-01-01

    Adult male Swiss albino mice were given 20 mg/kg body weight of MGP (2-mercaptopropionylglycine) intraperitoneally 15-30 minutes before /sup 45/Ca injection at dose 37 kBq/g body weight. MPG was also administered at various repeated doses. Radioprotective effects of MPG were studied on total erythroid cells (pronormoblasts and normoblasts) at various autopsy intervals (1, 3, 7, 14 and 28 days) posttreatment. It has been observed that MPG in repeated doses is effective in reducing the radiation-induced changes in the erythroid cells of bone marrow in Swiss albino mice following /sup 45/Ca internal irradiation.

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

    Science.gov (United States)

    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

  15. Effect of G/M ratio on the radiation-induced degradation of sodium alginate

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Murat, E-mail: msen@hacettepe.edu.t [Hacettepe University, Department of Chemistry, Beytepe 06800, Ankara (Turkey); Rendevski, Stojan [Institute of Physics, Faculty of Natural Sciences and Mathematics, University ' Ss. Cyril and Methodius' , Gazi Baba, bb., Skopje (Macedonia, The Former Yugoslav Republic of); Kavakli, Pinar Akkas; Sepehrianazar, Amir [Hacettepe University, Department of Chemistry, Beytepe 06800, Ankara (Turkey)

    2010-03-15

    Radiation-induced degradation of sodium alginate (NaAlg) having different G/M ratios was investigated. NaAlg samples were irradiated with gamma rays in air at ambient temperature in the solid state at low dose rate. Change in their molecular weights was followed by size exclusion chromatography (SEC). Changes in their rheological properties and viscosity values as a function of temperature, shear rate and irradiation dose were also determined. Chain scission yields, G(S), and degradation rates were calculated. It was observed that G/M ratio was an important factor controlling the G(S) and degradation rate of sodium alginate.

  16. Effect of G/M ratio on the radiation-induced degradation of sodium alginate

    Science.gov (United States)

    Şen, Murat; Rendevski, Stojan; Kavaklı, Pınar Akkaş; Sepehrianazar, Amir

    2010-03-01

    Radiation-induced degradation of sodium alginate (NaAlg) having different G/M ratios was investigated. NaAlg samples were irradiated with gamma rays in air at ambient temperature in the solid state at low dose rate. Change in their molecular weights was followed by size exclusion chromatography (SEC). Changes in their rheological properties and viscosity values as a function of temperature, shear rate and irradiation dose were also determined. Chain scission yields, G( S), and degradation rates were calculated. It was observed that G/M ratio was an important factor controlling the G( S) and degradation rate of sodium alginate.

  17. Delayed radiation-induced necrosis of the brain stem; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi (National Kure Hospital, Hiroshima (Japan)); Uozumi, Toru

    1993-03-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author).

  18. Acute limb ischemia secondary to radiation-induced arteritis: case report

    Directory of Open Access Journals (Sweden)

    Jose Emerson dos Santos Souza

    2013-09-01

    Full Text Available Radiation-induced arteritis is a rare but well-known complication of radiotherapy. This report describes the case of a 34-year-old woman with uterine cervical cancer who was diagnosed with left iliofemoral deep vein thrombosis (DVT 2 years after radiotherapy, and 2 months later, during the treatment of DVT with effective anticoagulation, developed an episode of acute arterial ischemia of the left lower limb secondary to a long subocclusive lesion of the external iliac artery. The patient was treated with angioplasty and stenting of the lesion and recovered uneventfully after the endovascular procedure.

  19. Radiation-induced defects in chalcogenide glasses characterized by combined optical spectroscopy, XPS and PALS methods

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O. [Institute of Physics of Jan Dlugosz University, 13/15 al. Armii Krajowej, Czestochowa 42201 (Poland); Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States); Lviv Institute of Materials of SRC ' ' Carat' ' , 202, Stryjska str., 79031 Lviv (Ukraine); Kovalskiy, A.; Jain, H. [Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States); Golovchak, R. [Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States); Lviv Institute of Materials of SRC ' ' Carat' ' , 202, Stryjska str., 79031 Lviv (Ukraine); Zurawska, A. [Opole University of Technology, 75, Ozimska str., Opole 45370 (Poland)

    2007-03-15

    Temperature-dependent optical absorption spectroscopy, high-resolution X-ray photoelectron spectroscopy and positron annihilation lifetimes spectroscopy are utilized to understand radiation-induced changes in Ge-Sb-S chalcogenide glasses. Theoretically predicted topological scheme of {gamma}-induced coordination defect formation in stoichiometric Ge{sub 23.5}Sb{sub 11.8}S{sub 64.7} glass composition is supported by these measurements. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  20. Radiation-induced defects formation in Bi-containing vitreous chalcogenides

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O.; Vakiv, M.; Balitska, V.; Kovalskiy, A. [Institute of Materials, Lvov (Ukraine)

    1997-12-01

    Processes of formation and annihilation of coordination defects in As{sub 2}Se{sub 3}Bi{sub y} and (As{sub 2}Se{sub 3})(Bi{sub 2}Se{sub 3}){sub y} amorphous chalcogenide semiconductors induced by influence of Co{sup 60} gamma-irradiation are investigated by photoelectric spectroscopy method. It is obtained that radiation-induced changes of photoelectrical properties on bioconcentration of As{sub 2}Se{sub 3}Bi{sub y} glasses are characterized by anomalous concentration dependence. The nature of this effect is associated with diamagnetic coordination defects formation. (author). 19 refs, 3 figs.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Quenching the radiation induced luminescence in quartz fibers under light monitoring

    CERN Document Server

    Demenkov, P V; Stepanov, V A; Stepanov, P A

    2002-01-01

    Measurements of the luminescence intensity in the optical fiber with the quartz glass core by the reactor pulsed irradiation in the visible range are carried out. Decrease in the intensity of the radiation-induced luminescence with growth of the sounding light intensity is determined by sounding the light guide by the laser radiation (the wave length of 532 and 632 nm). The decrease in the luminescence intensity takes place by the wave lengths greater, smaller or equal to the sounding light wave length

  3. Characterization of radiation induced defects in EUROFER 97 after neutron irradiation

    Science.gov (United States)

    Klimenkov, M.; Materna-Morris, E.; Möslang, A.

    2011-10-01

    Specimens of EUROFER 97 prepared for impact tests have been irradiated to an average dose of 16.3 dpa at irradiation temperatures of 250-450 °C. TEM investigations have been performed to study radiation induced changes in the microstructure. The characterization and statistical analysis show the temperature dependant formation of small dislocation loops and He bubbles. The Burgers vector of dislocation loops was ½. A novel feature is that within statistical uncertainty the maximum in the dislocation density observed around 300 °C decreased with decreasing irradiation temperature down to 250 °C. The TEM data are correlated with tensile and instrumented Charpy test results.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States)

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Victor H.F., E-mail: vhflee@hku.hk [Department of Clinical Oncology, University of Hong Kong, Queen Mary Hospital (Hong Kong); Ng, Sherry C.Y.; Leung, T.W.; Au, Gordon K.H.; Kwong, Dora L.W. [Department of Clinical Oncology, University of Hong Kong, Queen Mary Hospital (Hong Kong)

    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

  6. Radiation-Induced Cataractogenesis: A Critical Literature Review for the Interventional Radiologist

    Energy Technology Data Exchange (ETDEWEB)

    Seals, Kevin F., E-mail: KSeals@mednet.ucla.edu; Lee, Edward W., E-mail: EdwardLee@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Division of Interventional Radiology, Department of Radiology, UCLA Medical Center (United States); Cagnon, Christopher H., E-mail: CCagnon@mednet.ucla.edu [University of California at Los Angeles, Department of Radiology (United States); Al-Hakim, Ramsey A., E-mail: RAlhakim@mednet.ucla.edu; Kee, Stephen T., E-mail: SKee@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Division of Interventional Radiology, Department of Radiology, UCLA Medical Center (United States)

    2016-02-15

    Extensive research supports an association between radiation exposure and cataractogenesis. New data suggests that radiation-induced cataracts may form stochastically, without a threshold and at low radiation doses. We first review data linking cataractogenesis with interventional work. We then analyze the lens dose typical of various procedures, factors modulating dose, and predicted annual dosages. We conclude by critically evaluating the literature describing techniques for lens protection, finding that leaded eyeglasses may offer inadequate protection and exploring the available data on alternative strategies for cataract prevention.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lathika, K.M. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mishra, K.P. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: kpm@magnum.barc.ernet.in

    2006-03-15

    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 {gamma}-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.

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

    Science.gov (United States)

    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.

  9. Effect of acoustic, deformation on radiation-induced luminescence of pyrolytic boron nitride

    CERN Document Server

    Kardashev, B K; Plaksin, O A; Stepanov, V A; Stepanov, P A; Chernov, V M

    2001-01-01

    The effect of the ultrasound oscillations with the frequency of approximately 100 kHz on the radiation-induced luminescence on the pyrolytic boron nitride, originating by the protons irradiation (the energy of 8 MeV, the flux of 1.6 x 10 sup 1 sup 2 p/cm s), is studied. The impact of the ultrasound oscillations manifests itself by high deformation amplitudes (approximately 10 sup - sup 4), when the nonlinear, amplitude-dependent ultrasound absorption is observed. The obtained data are explained by the change in the kinetics of recrystallization, induced by irradiation, whereby the disappearance (radiation annealing) of the small angle boundaries occurs

  10. Experimental study on the inhibitory effect of MSCs on radiation-induced thymoma in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-Long Zhang

    2016-01-01

    Objective:To study the inhibitory effect of MSCs on radiation-induced thymoma in mice. Methods:C57BL/6 mice were selected as the research objects, model group and MSCs group induced thymoma by radiation, and MSCs group received intravenous injection of mesenchymal stem cell for therapy. Six months after treatment, macroscopic morphology of thymus tissue, contents of T lymphocyte subsets as well as expression of tumor suppressor gene PTEN and proliferation marker molecule Ki-67 were detected.Results:(1) macroscopic morphology: thymus tissue weight of model group was significantly greater than that of control group and thymus tissue weight of MSCs group was lower than that of control group; (2) cells and molecules: compared with control group, contents of CD4-CD8-, CD4+CD8- and CD4-CD8+ T cells as well as expression of PTEN in thymus tissue of model group significantly decreased, and CD4+CD8+ T cell content as well as Ki-67 expression significantly increased; compared with model group, contents of CD4-CD8-, CD4+CD8- and CD4-CD8+ T cells as well as expression of PTEN in thymus tissue of MSCs group significantly increased, and CD4+CD8+ T cell content as well as Ki-67 expression significantly decreased.Conclusions:MSCs have inhibitory effect on radiation-induced thymoma in mice, manifested as promoting CD4+CD8- and CD4-CD8+ T cell maturation as well as inhibiting cell proliferation.

  11. The role of alveolar epithelium in radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Celine Almeida

    Full Text Available 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.

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

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    Mikio Shimada

    Full Text Available 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.

  13. Research work of radiation induced graft polymerization for synthesis and modification of polymer materials in CRICI

    Energy Technology Data Exchange (ETDEWEB)

    Hu Fumin; Ma Xueming [Chenguan Research Institute of Chemical Industry, Chengdu (China)

    2000-03-01

    The direct and post radiation induced graft polymerization had been studied in CRICI (Chenguan Research Institute of Chemical Industry). The method consists of irradiation of various polymer substrates in the presence (or absence) of monomers in a liquid, saturated vapour or gaseous and non-saturated vapour. 1. Grafting of functional monomers. --- It is possible to divide the grafting into two main approaches for synthesis of functional polymer materials. The first is grafting of monomers attached required functional group such as unsaturated carboxylic acid (acrylic and methacrylic acid), unsaturated nitrogen containing (alkali) base (vinylpyridine), monomers with hydrophilic unionized and polar groups (acrylamide, N-vinylpyrrolidone glycidylmethacrylate) and so on. The second is grafting of monomers capable of continuing chemical modification after graft polymerization. This approach essentially expands synthetic possibility of RGP for preparing functional polymers. 2. The effect of some salts on aqueous solution graft polymerization. The grafting of AA or AAm onto PE by direct or post radiation method in the presence of Mohr's salt or cupric nitrate was studied in detail. 3. Radiation induced graft polymerization by gaseous phase of monomers. This method consists of irradiation or preirradiation of various polymer substrates in the presence (or absence for preirradiation) of monomer in a gaseous of nonsaturated vapour state. (J.P.N.)

  14. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.

  15. Sorafenib Enhances Radiation-Induced Apoptosis in Hepatocellular Carcinoma by Inhibiting STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chao-Yuan [Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Radiological Technology, Yuanpei University, Hsinchu, Taiwan (China); Lin, Chen-Si [School of Veterinary Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Tai, Wei-Tien; Hsieh, Chi-Ying [Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan (China); Shiau, Chung-Wai [Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan (China); Cheng, Ann-Lii [Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Kuen-Feng, E-mail: kfchen1970@ntu.edu.tw [Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-07-01

    Purpose: Hepatocellular carcinoma (HCC) is one of the most common and lethal human malignancies. Lack of efficient therapy for advanced HCC is a pressing problem worldwide. This study aimed to determine the efficacy and mechanism of combined sorafenib and radiation therapy treatment for HCC. Methods and Materials: HCC cell lines (PLC5, Huh-7, Sk-Hep1, and Hep3B) were treated with sorafenib, radiation, or both, and apoptosis and signal transduction were analyzed. Results: All 4 HCC cell lines showed resistance to radiation-induced apoptosis; however, this resistance could be reversed in the presence of sorafenib. Inhibition of phospho-STAT3 was found in cells treated with sorafenib or sorafenib plus radiation and subsequently reduced the expression levels of STAT3-related proteins, Mcl-1, cyclin D1, and survivin. Silencing STAT3 by RNA interference overcame apoptotic resistance to radiation in HCC cells, and the ectopic expression of STAT3 in HCC cells abolished the radiosensitizing effect of sorafenib. Moreover, sorafenib plus radiation significantly suppressed PLC5 xenograft tumor growth. Conclusions: These results indicate that sorafenib sensitizes resistant HCC cells to radiation-induced apoptosis via downregulating phosphorylation of STAT3 in vitro and in vivo.

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

    Science.gov (United States)

    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. Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats

    Science.gov (United States)

    Kim, Jin Hyun; Kim, Kyung Mi; Jung, Myeong Hee; Jung, Jung Hwa; Kang, Ki Mun; Jeong, Bae Kwon; Kim, Jin Pyeong; Park, Jung Je; Woo, Seung Hoon

    2016-01-01

    Purpose Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. Results ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-β1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. Materials and Methods Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. Conclusions Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer. PMID:27072584

  18. The role of sucralfate oral suspension in prevention of radiation induced mucositis

    Directory of Open Access Journals (Sweden)

    Hamid Emami

    2008-12-01

    Full Text Available

    • BACKGROUND: Mucositis is one of the most common complications of radiotherapy in head and neck cancers. The aim of this study was to evaluate sucralfate mouthwash in prevention of radiation induced mucositis.
    • METHODS: A clinical randomized trial performed on 52 patients with head and neck cancers in Sayyed-Al-Shohada Hospital of Isfahan University of Medical Sciences. These patients randomly assigned in 2 groups of 26 patients. Placebo and sucralfate was used for control and experimental patients respectiv ly, from the beginning of radiotherapy. Patients were visited weekly until the end of treatment. Grade of the mucositis was evaluated according to WHO grading scale.
    • RESULTS: Sucralfate significantly reduced the mean grade of mucositis in weeks one to four (with P-values of 0.02, 0.02, 0.001 and 0.004, respectively. Development of grade3 mucositis was also lower in sucralfate group (P-value = 0.0001. But, time interval between radiotherapy and appearance of mucositis was not statistically different in the two groups (P-value = 0.9
    • CONCLUSIONS: This study indicated that using oral suspension of sucralfate reduced the grade of radiation-induced mucositis, but did not prevent or delay it.
    • KEYWORDS: Mucositis, radiotherapy, sucralfate, head and neck cancers.

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

    Directory of Open Access Journals (Sweden)

    Bernardino Clavo

    2015-01-01

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

  20. Radiation-induced effects in polarization-maintaining optical fibers for interferometric gyroscope

    Institute of Scientific and Technical Information of China (English)

    Xueqin Wang; Chunxi Zhang; Jing Jin; Ningfang Song

    2011-01-01

    @@ Radiation-induced attenuation (RIA) in four types of polarization-maintaining optical fibers for interferometric fiberoptic gyroscope (IFOG) at 1310 nm is measured.The measurements are conducted during and after steady-state γ-ray irradiation using a 60Co source in order to observe significantly different RIA behavior and recovery kinetics.Mechanisms involving dopants and manufacturing process are introduced to analyze the RIA discrepancy as well as to guide the choice and hardening of optical fibers during the design of IFOG.Medium-accuracy IFOG using Ge-F-codoped fiber and pure silica core fiber can survive in the space radiation environment.%Radiation-induced attenuation (RIA) in four types of polarization-maintaining optical fibers for interferometric fiberoptic gyroscope (IFOG) at 1310 nm is measured. The measurements are conducted during and after steady-state γ-ray irradiation using a 60Co source in order to observe significantly different RIA behavior and recovery kinetics. Mechanisms involving dopants and manufacturing process are introduced to analyze the RIA discrepancy as well as to guide the choice and hardening of optical fibers during the design of IFOG. Medium-accuracy IFOG using Ge-F-codoped fiber and pure silica core fiber can survive in the space radiation environment.

  1. Evening Primrose Oil Attenuates Certain Radiation Induced Functional and structural Disorders in Female Rats

    Directory of Open Access Journals (Sweden)

    Fatma, L.R. and Rezk R. G

    2004-09-01

    Full Text Available The aim of the present study was to evaluate the modulator role of evening primrose oil (EPO on the radiation induced changes in certain biochemical and histological abnormalities. Female rats were exposed to 5 Gy whole body -irradiation delivered as single dose. EPO was orally administrated to rats (9 ml/100g b.wt 7 days before irradiation exposure. Animals were sacrificed 1 day (oestrus stage, 6 days (one estrus cycle and 12 days (two estrus cycle after irradiation. The results obtained revealed that treatment with EPO diminished the increase in total cholesterol, urea and creatinine levels in plasma in comparison with the levels recorded in the plasma of irradiated rats. Significant amelioration of the radiation induced changes in RBC,s WBC,s count and the haemoglobin concentration, calcium level, FSH and LH hormones were also recorded in the plasma of EPO treated and irradiated rats. Histological observations of photomicrograph of kidney and ovary sections showed that irsaoiaun resulted in irradiation induced ruptured, dilated, haemorrhage glomerulei dissolution of the majority of primary follicles, and atrophy in ovary size. All these changes were obviously improved in animals supplied with EPO. It could be concluded that EPO could be useful adjunct for maintaining the integrity of biochemical functions and restoring the original histological architecture of kidney and ovary after irradiation.

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

    Science.gov (United States)

    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.

  3. Effects of gargle with Inchin-gorei-san for radiation-induced stomatitis

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, Tetsuo; Kato, Takao; Kaneko, Takahiro [Saitama Medical School, Kawagoe (Japan). Saitama Medical Center] (and others)

    1999-11-01

    One of the adverse effects of radiotherapy for oral cancer is radiation-induced stomatitis. To relieve this severe mucosal condition, we tried the use of gargling with Inchin-gorei-san solution. Eleven patients (gargle group) gargled daily with Inchin-gorei-san in combination with steroid ointment application. The Inchin-gorei-san solution was used at 7.5 g/l in distilled water. Seven patients (control group) received application of steroid ointment without using the gargle. The period until the appearance of pain ranged from 0 to 25 days (median, 12.9 days) in the gargle group and 5 to 17 days (median, 8.9 days) in the control group. The duration of pain in the gargle and control groups was 0 to 46 days and 10 to 43 days, respectively. The period until the appearance of stomatitis was 3 to 20 days (median, 11.6 days) in the gargle group and 3 to 17 days (median, 7.7 days) in the control group. The duration of stomatitis in the gargle and control groups was 5 to 17 days and 10 to 54 days, respectively. These findings suggest that gargling with Inchin-gorei-san is a useful treatment for radiation-induced oral stomatitis. (author)

  4. Efficacy and safety of polaprezinc as a preventive drug for radiation-induced stomatitis

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Masayuki; Kamikonya, Norihiko; Tsuboi, Keita; Nakao, Norio [Hyogo Coll. of Medicine, Nishinomiya (Japan); Irie, Miwa [Takarazuka Municipal Hospital, Hyogo (Japan); Izumi, Masayuki [Minamiosaka Total Health Care Center, Osaka (Japan); Irie, Toshihiko; Fujisawa, Hiromi; Muro, Chikaaki [Hyogo Coll. of Medicine, Nishinomiya (Japan). Hospital

    2002-03-01

    Radiation-induced stomatitis is one of the adverse effects of total body irradiation (TBI). We examined the usefulness of oral polaprezinc as a preventive drug for stomatitis. The present study was conducted with 19 patients who were diagnosed with hematologic malignancy and who underwent TBI as pretreatment for bone marrow transplantation, peripheral blood stem transplantation, or cord blood stem cell transplantation. Eleven patients ingested the suspension of polaprezinc and 2% carmellose sodium (carboxymethylcellulose sodium: CMC) beginning the day before TBI (P-CMC group), while the other eight patients did not ingest P-CMC (control group). The severity of stomatitis was assessed in each group during a four-weeks period. Stomatitis (Grade:{>=}3) developed in one of 11 patients in the polaprezinc group and in 4 of 8 patients in the control group (P=0.046). The times at which stomatitis development ranged between weeks 1 and 2 after the onset of TBI in the two groups. No adverse reaction owing to the ingestion of P-CMC was observed. These results suggested the efficacy and safety of polaprezinc as a preventive drug for radiation-induced stomatitis. (author)

  5. The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats

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    Fatma Nesrin Turan

    2012-12-01

    Full Text Available Objective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO, Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px, and the malondialdehyde (MDA were measured.Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin.Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.

  6. Acupuncture for the prevention of radiation-induced xerostomia in patients with head and neck cancer

    Directory of Open Access Journals (Sweden)

    Fabio do Prado Florence Braga

    2011-04-01

    Full Text Available The aim of this study was to evaluate the effectiveness of acupuncture in minimizing the severity of radiation-induced xerostomia in patients with head and neck cancer. A total of 24 consecutive patients receiving > 5000 cGy radiotherapy (RT involving the major salivary glands bilaterally were assigned to either the preventive acupuncture group (PA, n = 12, treated with acupuncture before and during RT, or the control group (CT, n = 12, treated with RT and not receiving acupuncture. After RT completion, clinical response was assessed in all patients by syalometry, measuring the resting (RSFR and stimulated (SSFR salivary flow rates, and by the visual analogue scale (VAS regarding dry mouth-related symptoms. Statistical analyses were performed with repeated-measures using a mixed-effect modeling procedure and analysis of variance. An alpha level of 0.05 was accepted for statistical significance. Although all patients exhibited some degree of impairment in salivary gland functioning after RT, significant differences were found between the groups. Patients in the PA group showed improved salivary flow rates (RSFR, SSFR; p < 0.001 and decreased xerostomia-related symptoms (VAS, p < 0.05 compared with patients in the CT group. Although PA treatment did not prevent the oral sequelae of RT completely, it significantly minimized the severity of radiation-induced xerostomia. The results suggest that acupuncture focused in a preventive approach can be a useful therapy in the management of patients with head and neck cancer undergoing RT.

  7. Hepatocyte growth factor gene therapy prevents radiation-induced liver damage

    Institute of Scientific and Technical Information of China (English)

    Chau-Hua Chi; I-Li Liu; Wei-Yu Lo; Bor-Song Liaw; Yu-Shan Wang; Kwan-Hwa Chi

    2005-01-01

    AIM: To transfer human HGF gene into the liver of rats by direct electroporation as a means to prevent radiationinduced liver damage.METHODS: Rat whole liver irradiation model was accomplished by intra-operative approach. HGF plasmid was injected into liver and transferred by electroporation using a pulse generator. Control rats (n = 8) received electrogene therapy (EGT) vehicle plasmid and another 8rats received HGF-EGT 100 μg 48 h before WLIR.Expression of HGF in liver was examined by RT-PCR and ELISA methods. Apoptosis was determined by TUNEL assay. Histopathology was evaluated 10 wk after whole liver irradiation.RESULTS: Marked decrease of apoptotic cells and downregulation of transforming growth factor-beta 1 (TGF-β1)mRNA were observed in the HGF-EGT group 2 d after liver irradiation compared to control animals. Less evidence of radiation-induced liver damage was observed morphologically in liver specimen 10 wk after liver irradiation and longer median survival time was observed from HGF-EGT group (14 wk) compared to control rats (5 wk). (P = 0.031).CONCLUSION: For the first time it has been demonstrated that HGF-EGT would prevent liver from radiation-induced liver damage by preventing apoptosis and down-regulation of TGF-β1.

  8. H 2O 2 and radiation induced dissolution of UO 2 and SIMFUEL pellets

    Science.gov (United States)

    Nilsson, Sara; Jonsson, Mats

    2011-03-01

    Dissolution of the UO 2 matrix is of major importance in the safety assessment of a future deep repository for spent nuclear fuel. The aim of this work is to elucidate if the observed differences in dissolution rates between SIMFUEL and UO 2 can be attributed to differences in oxidant reactivity towards these two materials. To elucidate this, the oxidative dissolution of U(VI) and consumption of H 2O 2 have been studied for UO 2 and SIMFUEL pellets under N 2 and H 2 atmosphere. The H 2O 2 and U(VI) concentrations have been measured as a function of reaction time. In addition, γ-radiation induced dissolution UO 2 and SIMFUEL pellets have been studied. The experiments show that while the reactivity of the two types of pellets towards H 2O 2 is almost identical and in good agreement with the previously determined rate constant for the reaction, the dissolution rates differ considerably. The significantly lower rate of dissolution of the SIMFUEL pellet is attributed to an increased fraction of catalytic decomposition of H 2O 2. The radiation chemical experiments reveal a similar but less pronounced difference between the two types of pellets. This implies that the relative impact of the radiolytic oxidants in radiation induced UO 2 dissolution differs between a pure UO 2 pellet and SIMFUEL.

  9. H 2 inhibition of radiation induced dissolution of spent nuclear fuel

    Science.gov (United States)

    Trummer, Martin; Roth, Olivia; Jonsson, Mats

    2009-01-01

    In order to elucidate the effect of noble metal clusters in spent nuclear fuel on the kinetics of radiation induced spent fuel dissolution we have used Pd particle doped UO 2 pellets. The catalytic effect of Pd particles on the kinetics of radiation induced dissolution of UO 2 during γ-irradiation in HCO3- containing solutions purged with N 2 and H 2 was studied in this work. Four pellets with Pd concentrations of 0%, 0.1%, 1% and 3% were produced to mimic spent nuclear fuel. The pellets were placed in 10 mM HCO3- aqueous solutions and γ-irradiated, and the dissolution of UO22+ was measured spectrophotometrically as a function of time. Under N 2 atmosphere, 3% Pd prevent the dissolution of uranium by reduction with the radiolytically produced H 2, while the other pellets show a rate of dissolution of around 1.6 × 10 -9 mol m -2 s -1. Under H 2 atmosphere already 0.1% Pd effectively prevents the dissolution of uranium, while the rate of dissolution for the pellet without Pd is 1.4 × 10 -9 mol m -2 s -1. It is also shown in experiments without radiation in aqueous solutions containing H 2O 2 and O 2 that ɛ-particles catalyze the oxidation of the UO 2 matrix by these molecular oxidants, and that the kinetics of the catalyzed reactions is close to diffusion controlled.

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

    Science.gov (United States)

    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

    2016-03-31

    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.

  11. The role of alveolar epithelium in radiation-induced lung injury.

    Science.gov (United States)

    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 (137)Cs 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.

  12. Considerations for comparing radiation-induced chromosome aberration data with predictions from biophysical models

    Science.gov (United States)

    Wu, H.; Furusawa, Y.; George, K.; Kawata, T.; Cucinotta, F.

    Biophysical models addressing the formation of radiation-induced chromosome aberrations are usually based on the assumption that chromosome aberrations are formed by DNA double strand break (DSB) misrejoining, via either the homologous or the non-homologous repair pathway. However, comparing chromosome aberration data with model predictions is not always straightforward. In this paper we discuss some of the aspects that must be considered to make these comparisons meaningful. Firstly, biophysical models are usually applied to DSB rejoining and misrejoining in the G0/G1 phase of the cell cycle, while most chromosome aberration data reported in the literature are analyzed in metaphase. Since cells must progress through the cell cycle check points in order to reach mitosis, model predictions that differ from the metaphase chromosome analysis may actually agree with the aberration data in chromosomes collected in interphase. Secondly, high- LET radiation generally produces more complex aberrations involving exchanges between three or more DSB. While some models have successfully provided quantitative predictions of high-LET radiation induced complex aberrations in human lymphocytes, applying such models to other cell types requires special considerations due to the lack of geometric symmetry of the nucleus. Chromosome aberration data for non-spherical human fibroblast cells bombarded from various directions by high-LET charged particles will be presented, and their implication on physical modeling will be discussed.

  13. Paradoxical relationship between Mn superoxide dismutase deficiency and radiation-induced cognitive defects.

    Directory of Open Access Journals (Sweden)

    Rikki Corniola

    Full Text Available Radiation therapy of the CNS, even at low doses, can lead to deficits in neurocognitive functions. Reduction in hippocampal neurogenesis is usually, but not always, associated with cognitive deficits resulting from radiation therapy. Generation of reactive oxygen species is considered the main cause of radiation-induced tissue injuries, and elevated levels of oxidative stress persist long after the initial cranial irradiation. Consequently, mutant mice with reduced levels of the mitochondrial antioxidant enzyme, Mn superoxide dismutase (MnSOD or Sod2, are expected to be more sensitive to radiation-induced changes in hippocampal neurogenesis and the related functions. In this study, we showed that MnSOD deficiency led to reduced generation of immature neurons in Sod2-/+ mice even though progenitor cell proliferation was not affected. Compared to irradiated Sod2+/+ mice, which showed cognitive defects and reduced differentiation of newborn cells towards the neuronal lineage, irradiated Sod2-/+ mice showed normal hippocampal-dependent cognitive functions and normal differentiation pattern for newborn neurons and astroglia. However, we also observed a disproportional decrease in newborn neurons in irradiated Sod2-/+ following behavioral studies, suggesting that MnSOD deficiency may render newborn neurons more sensitive to stress from behavioral trainings following cranial irradiation. A positive correlation between normal cognitive functions and normal dendritic spine densities in dentate granule cells was observed. The data suggest that maintenance of synaptic connections, via maintenance of dendritic spines, may be important for normal cognitive functions following cranial irradiation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Azuddin, A. Yusof [School of Applied Physics, Faculty of Sciences and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia and Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 53000 Kuala Lumpur (Malaysia); Rahman, I. Abdul; Mohamed, F. [School of Applied Physics, Faculty of Sciences and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor (Malaysia); Siah, N. J. [Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 53000 Kuala Lumpur (Malaysia); Saadc, M. [Department of Oncology, University Malaya Medical Center, 50603 Kuala Lumpur (Malaysia); Ismail, F. [Department of Oncology and Radiotherapy, Universiti Kebangsaan Malaysia Medical Centre, 56000 Cheras, Kuala Lumpur (Malaysia)

    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.

  15. Evaluation of the efficacy of zoledronic acid and amifostine on radiation induced bone loss in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Wook; Lee, Sueum; Kang, Sohi; Moon, Cahng Jong; Kim, Jong Choon; Kim, Sung Ho [College of Veterinary Medicine, Chonnam National University, Gwangju (Korea, Republic of); Jung, Uhee; Jo, Sung Kee [Advanced Radiation Technology Institute, Jeungeup (Korea, Republic of); Jang, Jong Sik [College of Ecology and Environmental Science, Kyungpook National University, Sangju (Korea, Republic of)

    2016-09-15

    This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Treatment of ZA (100 μg·kg{sup -1}·week{sup -1}) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. The results indicate that ZA can prevent radiation-induced bone loss in mice.

  16. Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant Extract

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    2011-01-01

    Full Text Available The primary objective of this investigation is to determine the deleterious effects of sub lethal gamma radiation on testes and their possible inhibition by Tinospora cordifolia extract (TCE. For this purpose, one group of male Swiss albino mice was exposed to 7.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day orally for 5 consecutive days half an hr before irradiation to serve as experimental. Exposure of animals to 7.5 Gy gamma radiation resulted into significant decrease in body weight, tissue weight, testes- body weight ratio and tubular diameter up to 15 days of irradiation. Cent percent mortality was recorded by day 17th in irradiated control, whereas all animals survived in experimental group. TCE pretreatment rendered significant increase in body weight, tissue weight, testes- body weight ratio and tubular diameter at various intervals as compared to irradiated group. Radiation induced histological lesions in testicular architecture were observed more severe in irradiated control then the experimental. TCE administration before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radio- protective potential of Tinospora cordifolia root extract in testicular constituents against gamma irradiation in mice.

  17. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    Science.gov (United States)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  18. Gamma radiation induced micronuclei and erythrocyte cellular abnormalities in the fish Catla catla

    Energy Technology Data Exchange (ETDEWEB)

    Anbumani, S. [Biodosimetry Laboratory, Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, Tamilnadu 603102 (India); Mohankumar, Mary N., E-mail: marynmk@rediffmail.com [Biodosimetry Laboratory, Radiological Safety Division, Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam, Tamilnadu 603102 (India)

    2012-10-15

    Ionizing radiation induced DNA damage in fishes is a scarcely studied topic and very few studies are available in fishes exposed to ionizing radiation using the erythrocyte micronucleus assay under laboratory conditions. Since radionuclides released accidentally or during a nuclear disaster can contaminate inland water bodies, biomonitoring methods are required for assessing the impacts of high and low levels of radiation that may ultimately result in ionizing radiation exposure to both humans and non-human biota. Fresh water fish, Catla catla were subjected to protracted (0.002 Gy/min) and acute (3.2 Gy/min) gamma radiation to a total dose of 5 Gy. Peripheral blood samples were collected at different intervals (days 3, 6, 12, 18, 30, 45, 90, 135, 202) and analyzed by the erythrocyte micronucleus assay. Nuclear anomalies observed were micronuclei (MN), deformed nuclei (DN), nuclear bud (NBu), nuclear bridge (NBr), vacuolated nucleus (VN), binucleated cell (BNC), apoptotic cells (AC) while cytoplasmic abnormalities detected were vacuolated cytoplasm (VC), anisochromasia (AN), echinocytes (EC) and enucleus (EN). Both exposures caused a statistically significant increase in nuclear and cytoplasmic abnormalities that correlated with micronucleus and other nuclear anomalies. However, the extent of damage is higher after an acute exposure lasting for a longer period leading to apoptosis. Nuclear and cytoplasmic abnormalities are the resultants of gamma radiation induced genotoxicity and cytotoxicity.

  19. Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11)

    Science.gov (United States)

    Chamseddine, A. N.; Etancelin, P.; Penther, D.; Parmentier, F.; Kuadjovi, C.; Camus, V.; Contentin, N.; Lenain, P.; Bastard, C.; Tilly, H.; Jardin, F.

    2015-01-01

    BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT). To the best of our knowledge, this is the thirteenth case reported worldwide to describe a BCR-JAK2 fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. Regarding BCR-ABL1  negative MPN patients this case report provides strong support for a role of JAK2 activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated. PMID:25789185

  20. Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22(p24;q11

    Directory of Open Access Journals (Sweden)

    A. N. Chamseddine

    2015-01-01

    Full Text Available BCR-ABL1 negative myeloproliferative neoplasms (MPNs are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24 that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U showing a t(9;22(p24;q11, which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most reported JAK2 fusions cases reveal an aggressive clinical course and long-term remissions have only been achieved after allogeneic stem cell transplantation (ASCT. To the best of our knowledge, this is the thirteenth case reported worldwide to describe a BCR-JAK2 fusion transcript in MPN-U. The present report revealed a sustained complete clinical, hematologic, and cytogenetic remission 35 months after diagnosis and ~24 months after ASCT. Regarding BCR-ABL1  negative MPN patients this case report provides strong support for a role of JAK2 activation in the oncogenesis and suggests a possible diagnostic and therapeutic target that should be investigated.

  1. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

    Science.gov (United States)

    Brissot, Eolia; Cahu, Xavier; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Peterlin, Pierre; Le Bourgeois, Amandine; Harousseau, Jean-Luc; Milpied, Noel; Bene, Marie-Christine; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

    2015-04-01

    In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.

  2. Radiation induced changes in electrical conductivity of chemical vapor deposited silicon carbides under fast neutron and gamma-ray irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchiya, Bun, E-mail: btsuchiya@meijo-u.ac.jp [Department of General Education, Faculty of Science and Technology, Meijo University, 1-501, Shiogamaguchi, Tempaku-ku, Nagoya 468-8502 (Japan); Shikama, Tatsuo; Nagata, Shinji; Saito, Kesami [Institute for Materials Research, Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai 980-8577 (Japan); Yamamoto, Syunya [Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233, Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Ohnishi, Seiki [Tokai Research and Development Center, Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); Nozawa, Takashi [Aomori Research and Development Center, Japan Atomic Energy Agency, 2-166, Omotedate, Obuchi, Rokkasho, Aomori 039-3212 (Japan)

    2011-10-15

    The radiation-induced changes in the volume electrical conductivities of chemical vapor deposited silicon carbides (CVD-SiCs) were in-site investigated by performing irradiation using 1.17 and 1.33-MeV gamma-ray and 14-MeV fast neutron beams in air and vacuum. Under gamma-ray irradiation at ionization dose rates of 3.6 and 5.9 Gy/s and irradiation temperature of approximately 300 K, the initial rapid increase in electrical conductivity; this is indicative of radiation-induced conductivity (RIC), occurred due to electronic excitation, and a more gradual increase followed up to a dose of approximately 10-50 kGy corresponding to the results in base conductivity without radiation; this is indicative of radiation-induced electrical degradation (RIED). However, the radiation-induced phenomena were not observed at irradiation temperatures above 373 K. Under neutron irradiation at a further low dose rate below approximately 2.1 Gy/s, a fast neutron flux of 9.2 x 10{sup 14} n/m{sup 2} s, and 300 K, the RIED-like behavior according to radiation-induced modification of the electrical property occurred with essentially no displacement damage, but ionizing effects (radiolysis).

  3. Gender and Vascular Complications in the JAK2 V617F-Positive Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Brady L. Stein

    2011-01-01

    Full Text Available We previously found that gender influenced the JAK2 V617F allele burden, but it is unknown whether this gender difference in molecular epidemiology influences complications in the myeloproliferative neoplasms (MPNs. Historically, vascular complications represented the most common cause of mortality in polycythemia vera and essential thrombocytosis and contributed to morbidity in primary myelofibrosis. To determine the influence of gender on vascular complications, we retrospectively analyzed associations between gender and vascular complications. Despite their younger age, less prevalent dyslipidemia or smoking history, lower white blood counts, and lower JAK2 V617F allele burden, women had higher rates of abdominal venous thrombosis and comparable rates of all vascular complications. Vascular risk is currently not easily stratified by MPN-disease burden or traditional risk factors. Our analysis contributes to growing literature emphasizing gender differences in the MPN and further supports the important impact of individual and host variation on MPN clinical manifestations, and especially vascular risk.

  4. Myeloproliferative Disease: An Unusual Cause of Raynaud's Phenomenon and Digital Ischaemia.

    Science.gov (United States)

    Beynon, Celia; Huws, Gwenan; Lawson, Tom

    2016-01-01

    We describe a 59-year-old female who presented with ischaemic digits, preceded by a 6-month history of Raynaud's phenomenon affecting her fingers and toes. There were no clinical or laboratory features of primary vasculitis or connective tissue disease, Doppler imaging was normal, and bloods were unremarkable aside from a platelet count of 786 × 109/L (150-400) and white cells of 16 × 109/L (4-11). In view of the thrombocytosis a JAK2 mutation assay was requested which confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET) as the cause. She received treatment with hydroxycarbamide which normalised her platelet count and led to a complete resolution of her Raynaud's symptoms. Raynaud's phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET should be considered in the differential diagnosis of Raynaud's phenomenon and vasculitis.

  5. Mesenteric venous thrombosis secondary to an unsuspected JAK2 V617F-positive myeloproliferative disorder.

    LENUS (Irish Health Repository)

    2012-01-31

    BACKGROUND: Mesenteric venous thrombosis (MVT) is a rare but potentially fatal cause of mesenteric ischaemia. It presents insidiously and often diagnosis is made at emergency surgery. In half of the cases MVT develops without a causative factor, while in cases in which a pro-thrombotic state is found to exist MVT may be the first clinically detected consequence of that state. The myeloproliferative disorders (MPD) are known to contribute to the development of pro-thrombotic states. Recently, the JAK2 V617F mutation has been associated with the MPDs. CONCLUSION: We describe a case of MVT occurring secondary to an unsuspected MPD, in which the patient was subsequently found to carry this mutation. We highlight the necessity to screen for this mutation in cases of intra-abdominal thromboses so that appropriate systemic anticoagulation may be instituted, and the patient may be followed so as to detect the development of an overt MPD.

  6. Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

    Science.gov (United States)

    Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

    2015-05-25

    The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy.

  7. Effectiveness of triclosan in the management of radiation-induced oral mucositis: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Satheeshkumar P

    2010-01-01

    Full Text Available Introduction: Oral care in cancer patients is an important aspect in the quality of life of patients undergoing cancer therpay. Mucositis, trismus, salivary gland dysfunction are the main complications of the cancer therapy, which lead to long-term comlications such as radiation caries, poor oral hygiene and osteoradionecrosis. A timely oral evaluation and intervention in these patients can reduce the severity of the potential complications. Triclosan is an antibacterial agent widely used in periodontal therapy, the effectiveness of triclosan in the management of radiation induced oral mucositis is evaluated here. Aims: 1 To determine the effectiveness of triclosan in the management of radiation-induced oral mucositis. 2 To compare the effectiveness of triclosan mouth rinse with conventional sodium bicarbonate mouth rinse. Materials and Methods: Twenty-four patients who underwent radiation therapy for oral cancer and subsequently developed oral mucositis were included in the study. They were randomly allocated into two groups on noticing grade I mucositis (erythema. The study group was advised to use triclosan mouthwash containing triclosan 0.03% W/V and sodium bicarbonate 2 mg mouth wash for the control group. A weekly follow-up evaluation of body weight, food intake, pain and grading of mucositis were made during the radiation treatment period and post radiation treatment period. Results: Both the groups were statistically identical. All the 24 patients in both the groups passed through grade 3 mucositis on the last day of radiotherapy. However, 10 patients in the control group and only one patient in the study group entered to grade 4 mucositis. A definite change was noticed in the severity of the mucositis, food intake and weight loss. The control group took more than 45 days to resolve while the study group took only less than 28 days. Discussion: The results of the study were evaluated and tried to formulate a hypothesis so as to explain

  8. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the 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 radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  9. Resolving the H 2 effect on radiation induced dissolution of UO 2-based spent nuclear fuel

    Science.gov (United States)

    Trummer, Martin; Jonsson, Mats

    2010-01-01

    In recent years, the impact of H2 on α-radiation induced dissolution of UO2-based spent nuclear fuel has been studied and debated extensively. Experimental results on the effect of H2 on the concentration of H2O2 during α-radiolysis have been shown to disagree with numerical simulations. For this reason, the reaction scheme used in simulations of aqueous radiation chemistry has sometimes been questioned. In this work, we have studied the impact of H2 on the H2O2 concentration in α-irradiated aqueous solution using numerical simulations. The effects of H2 pressure, α-dose rate and HCO3- concentration were investigated by performing systematic variations in these parameters. The simulations show that the discrepancy between the previously published experimental result and numerical simulations is due to the use of a homogeneous dose rate (the energy is assumed to be equally distributed in the whole volume). Taking the actual dose rate of the α-irradiated volume into account, the simulation is in perfect agreement with the experimental results. This shows that the H2 effect is strongly α-dose rate dependent, and proves the reliability of the reaction scheme used in the simulations. The simulations also show that H2 influences the H2O2 concentration under α-radiolysis. The magnitude of the effect depends on the dose rate and the H2 pressure as well as on the concentration of HCO 3-. The impact of the radiolytic H2 effect on the rate of α-radiation induced dissolution of spent nuclear fuel is discussed along with other (α- and γ-) radiation induced processes capable of reducing the concentration of uranium in solution. The radiolytic H2 effect is quantitatively compared to the previously presented noble metal catalyzed H2 effect. This comparison shows that the noble metal catalyzed H2 effect is far more efficient than the radiolytic H2 effect. Reduction of U(VI) in solution due to low dose rate γ-radiolysis in the presence of H2 is proposed to be the cause of

  10. [Differential diagnosis of chronic myeloic leucemia in infancy (author's transl)].

    Science.gov (United States)

    Binder, C; Pichler, E; Radaskiewicz, T; Scheibenreiter, S

    1976-01-01

    A 3 months old girl presented with significant enlargement of liver, spleen and lymphnodes, with moderate anemia, thrombopenia and leucocytosis. In the differential count there was a shift to the left and an increase of monocyte-like cells (35%). Differential diagnosis included leucemoid reaction, infectious mononucleosis, myelo-proliferative disorder with a missing C chromosome and chronic myeloid leucemia. Clinical symptoms, cytochemistry and caryotype of bone marrow cells suggested infantile chronic myeloic leucemia and normal ALP index and possibly normal HbF. Treatment with 6-mercaptopurine was followed by partial remission. The therapeutic consequences of exact differential diagnosis are discussed.

  11. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  12. Post-irradiation dietary vitamin E does not affect the development of radiation-induced lung damage in rats.

    Science.gov (United States)

    Wiegman, Erwin M; van Gameren, Mieke M; Kampinga, Harm H; Szabó, Ben G; Coppes, Rob P

    2004-07-01

    The purpose of this study was to investigate whether application of post-irradiation vitamin E, an anti-oxidant, could prevent the development of radiation induced lung damage. Wistar rats were given vitamin E enriched or vitamin E deprived food starting from 4 weeks after 18Gy single dose irradiation of the right thorax. Neither breathing frequencies nor CT density measurements revealed differences between the groups. It is concluded that post-irradiation vitamin E does not influence radiation-induced fibrosis to the lung.

  13. Chondrosarcoma arising within a radiation-induced osteochondroma several years following childhood total body irradiation: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Shuji [Kurume University Hospital, Department of Radiology, Fukuoka (Japan); Shen, Robert K. [Mayo Clinic, Department of Surgery, Rochester, MN (United States); Laack, Nadia N. [Mayo Clinic, Department of Radiation Oncology, Rochester, MN (United States); Inwards, Carrie Y. [Mayo Clinic, Department of Pathology, Rochester, MN (United States); Wenger, Doris E.; Amrami, Kimberly K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2013-08-15

    Malignant degeneration arising in radiation-induced osteochondromas is extremely rare. We report a case of a 34-year-old man with a chondrosarcoma arising from an osteochondroma of the left posterior eighth rib that developed following total body irradiation received as part of the conditioning regimen prior to bone marrow transplantation at age 8. To our knowledge, this is only the fourth reported case of a chondrosarcoma arising within a radiation-induced osteochondroma and the first case occurring following childhood total body irradiation. (orig.)

  14. Measurement of 60CO gamma radiation induced attenuation in multimode step-index POF at 530 nm

    Directory of Open Access Journals (Sweden)

    Kovačević Milan S.

    2013-01-01

    Full Text Available As optical fibres are used ever more extensively in space applications, nuclear industry, medicine and high-energy physics experiments, it has become essential to investigate the influence of ionizing radiation on their characteristics. In this work, the radiation-induced attenuation at 530 nm is investigated experimentally in step-index multimode polymethyl-methacrylate plastic optical fibres exposed to low dose-rate gamma radiation. Cumulative doses ranged from 50 Gy to 500 Gy. The radiation induced attenuation has been empirically found to obey the power law RIA= aDb, where D is the total radiation dose and a and b are the constants determined by fitting.

  15. Chinese Medicine Angelica Sinensis Suppresses Radiation-induced TNF-αand TGF-β_1 Expression in Mice

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionLung is a major organ targeted by radiation in radiotherapy of the thoracic tumors and often suffers from radiation-induced injury such as pneumonitis and excessive fibrosis. Now, the pathogenesis of radiation-induced lung injury is found mainly due to the release of cytokines which can activate many signal transduction pathways~([1]). Among these cytokines, TNF-α and TGF-β_1 are regarded as the key factors responsible for tissue damage. Angelica Sinensis, a Chinese medicine, is currently in u...

  16. Radiation-Induced Centers in Lead Silicate Glasses Irradiated by Stationary and Pulsed Electron Beams

    Science.gov (United States)

    Zhidkov, I. S.; Zatsepin, A. F.; Konev, S. F.; Cholakh, S. O.

    2015-08-01

    Radiation-induced centers formed in heavy flint glasses irradiated by electron beams are investigated by the methods of optical and EPR spectroscopy. It is revealed that stable and short-living optical absorption centers of close natures are formed under irradiation by fast electrons. A correlation is established between the stable optical absorption bands and the EPR signals interpreted as signals of the (Pb2+)/h+ hole centers. The shortliving color centers are formed due to short-term distortion of the O-Pb bonds, and the stable centers are formed due to the spatial separation, thermalization, and subsequent stabilization of excited electrons and holes in tails of the localized states. Irradiation by electron beams leads to a change in the spectral characteristics of the fundamental absorption edge and, in particular, of the Urbach energy that determines the degree of structural disorder.

  17. Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects

    Science.gov (United States)

    Ohshima, Yasuhiro; Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi

    2017-01-01

    Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to a variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced responses that serve to mitigate or repair the injurious effects of γ radiation on the body. Indeed, low doses of radiation may have a net beneficial effect by activating a variety of protective mechanisms, including antitumor immune responses. On the other hand, ATP signaling may be involved in the radiation resistance of cancer cells. Here, focusing on our previous work, we review the evidence that low-dose γ irradiation (0.25-0.5 Gy) induces release of extracellular ATP, and that the released ATP mediates multiple radiation-induced responses, including increased intracellular antioxidant synthesis, cell-mediated immune responses, induction of DNA damage repair systems, and differentiation of regulatory T cells.

  18. Radiation-induced inactivation of enzymes - Molecular mechanism based on inactivation of dehydrogenases

    Science.gov (United States)

    Rodacka, Aleksandra; Gerszon, Joanna; Puchala, Mieczyslaw; Bartosz, Grzegorz

    2016-11-01

    Proteins, which have enzymatic activities play a fundamental role in the cell due to participation in most of biological processes. Oxidative-induced damage of enzymes often have marked effects on cellular processes, which in consequence determine cell functioning and survival. In this review, we focused on the radiation-induced inactivation of enzymes with particular emphasis on the inactivation of dehydrogenases. For a better understanding of this issue, the efficiency of products of water radiolysis (•OH, O2•- and H2O2) in enzyme inactivation has been analysed. Reactions of reactive oxygen species (ROS) with amino acids present in the active site of enzymes appear to have the greatest impact on enzyme inactivation.

  19. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Georgescu, Walter; Tang, Jonathan; Costes, Sylvain V.

    2013-09-03

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  20. Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects.

    Science.gov (United States)

    Kojima, Shuji; Ohshima, Yasuhiro; Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi

    2017-01-01

    Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to a variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced responses that serve to mitigate or repair the injurious effects of γ radiation on the body. Indeed, low doses of radiation may have a net beneficial effect by activating a variety of protective mechanisms, including antitumor immune responses. On the other hand, ATP signaling may be involved in the radiation resistance of cancer cells. Here, focusing on our previous work, we review the evidence that low-dose γ irradiation (0.25-0.5 Gy) induces release of extracellular ATP, and that the released ATP mediates multiple radiation-induced responses, including increased intracellular antioxidant synthesis, cell-mediated immune responses, induction of DNA damage repair systems, and differentiation of regulatory T cells.

  1. Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin

    Energy Technology Data Exchange (ETDEWEB)

    Chiolo, Irene; Tang, Jonathan; Georgescu, Walter; Costes, Sylvain V.

    2013-10-01

    Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.

  2. Radiation-Induced Organizing Pneumonia: A Characteristic Disease that Requires Symptom-Oriented Management

    Science.gov (United States)

    Otani, Keisuke; Seo, Yuji; Ogawa, Kazuhiko

    2017-01-01

    Radiation-induced organizing pneumonia (RIOP) is an inflammatory lung disease that is occasionally observed after irradiation to the breast. It is a type of secondary organizing pneumonia that is characterized by infiltrates outside the irradiated volume that are sometimes migratory. Corticosteroids work acutely, but relapse of pneumonia is often experienced. Management of RIOP should simply be symptom-oriented, and the use of corticosteroids should be limited to severe symptoms from the perspective not only of cost-effectiveness but also of cancer treatment. Once steroid therapy is started, it takes a long time to stop it due to frequent relapses. We review RIOP from the perspective of its diagnosis, epidemiology, molecular pathogenesis, and patient management. PMID:28134830

  3. Functional properties of nisin-carbohydrate conjugates formed by radiation induced Maillard reaction

    Science.gov (United States)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-12-01

    Nisin-carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin-carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin-dextran conjugates possessed better antioxidant potential than nisin-glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry.

  4. Radiation-induced grafting of dimethylaminoethylmethacrylate onto PE/PP nonwoven fabric

    Energy Technology Data Exchange (ETDEWEB)

    Kavakli, Pinar Akkas [Hacettepe University, Department of Chemistry, Beytepe, 06532 Ankara (Turkey)], E-mail: pinar@hacettepe.edu.tr; Kavakli, Cengiz [General Directorate of Ankara Customs and Customs Enforcement, Ankara Central Laboratory, Ankara (Turkey); Seko, Noriaki; Tamada, Masao [Japan Atomic Energy Agency, Quantum Beam Science Directorate, 1233 Watanuki, Takasaki, Gunma (Japan); Gueven, Olgun [Hacettepe University, Department of Chemistry, Beytepe, 06532 Ankara (Turkey)

    2007-12-15

    A new adsorbent was prepared by radiation-induced graft polymerization of dimethylaminoethylmethacrylate (DMAEMA) onto polyethylene/polypropylene (PE/PP) nonwoven fabric. The trunk polymer was irradiated by electron beam at a voltage of 2 MeV and a current of 3 mA in nitrogen atmosphere at dry-ice temperature to different doses. The degree of grafting was determined as a function of irradiation dose, monomer concentration, temperature and reaction time. Grafting conditions were optimized and about 150% grafted samples were used for further experiments. DMAEMA grafted polymer was later protonated in acid solution to prepare specialty adsorbent for the removal of phosphate. Adsorption experiments were performed in column mode for removal of phosphate. It was shown that 2000 bed volumes of phosphate-free water can be produced from 100 ppb phosphate (as P) solution at high space velocity.

  5. Endogenous retrovirus and radiation-induced leukemia in the RMF mouse

    Energy Technology Data Exchange (ETDEWEB)

    Tennant, R.W.; Boone, L.R.; Lalley, P.; Yang, W.K.

    1982-01-01

    The induction of myeloid leukemia in irradiated RFM/Un mice has been associated with retrovirus infection. However, two characteristics of this strain complicate efforts to define the role of the virus. This strain possesses only one inducible host range class of endogenous virus and a unique gene, in addition to the Fv-1/sup n/ locus, which specifically restricts exogenous infection by endogenous viruses. These characteristics possibly account for absence of recombinant viruses in this strain, even though virus is amply expressed during most of the animal's life span. We have examined further the distribution of retrovirus sequences and the chromosomal locus of the inducible virus in this strain. This report describes evidence for additional viral sequences in cells of a radiation-induced myeloid leukemia line and discusses the possible origin of these added copies.

  6. Intestinal Radiation-Induced Stricture Favours Small Bowel Obstruction by Phytobezoar: Report of a Case

    Directory of Open Access Journals (Sweden)

    Alessandra Quercioli

    2009-01-01

    Full Text Available Bezoars represent the fifth most frequent cause of acute small bowel obstruction. Phytobezoar is the most common type of bezoar. It is a concretion of undigestible fibers derived from ingested vegetables and fruits. We report a case of a woman with a 1-year history of recurrent epigastric and periumbilical abdominal pain with intermittent vomiting caused by phytobezoar of the terminal ileum. After careful investigation of the case and review of literature, we identified the factor involved in bezoar formation as radiation-induced ileal stenosis due to previous treatment for a pelvic tumour. This report provides evidence to consider phytobezoar as a possible cause of small bowel obstruction in patients previously treated with abdominal radiotherapy.

  7. Three Cases of Radiation-Induced Hepatitis B Virus Reactivation after Hepatic Tomotherapy: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Moon Kyoo; Hong, Seong Eon; Kim, Byung Ho; Choi, Jin Hyun [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

    2011-03-15

    Radiation-induced liver disease (RILD) has been characterized as a veno-occlusive disease with anicteric elevation of alkaline phosphatase (ALP). However, some RILD patients present with elevated transaminase levels rather than with anicteric elevation of ALP, and these findings are common in the Asia-Pacific region where hepatitis B virus (HBV) infection is associated with 70-90% of hepatocelluar carcinoma (HCC) cases. In addition, the development of RILD is more common in patients with hepatitis B virus-related HCC. These findings indicate that susceptibility to RILD might be different in HBV carriers and non-carriers, and moreover, RILD in patients with HBV-related HCC might be associated with another unique pathogenesis such as HBV reactivation. However, HBV reactivation after hepatic irradiation has been reported in only a few studies. This study reports three cases of HBV reactivation after hepatic tomotherapy for management of HCC.

  8. Investigation on the radiation induced conductivity of space-applied polyimide under cyclic electron irradiation

    Science.gov (United States)

    Yue, Long; Wu, Yiyong; Sun, Chengyue; Xiao, Jingdong; Shi, Yaping; Ma, Guoliang; He, Shiyu

    2012-11-01

    Radiation induced conductivity (RIC) is an important property of dielectric materials to evaluate the charge/discharge effect in orbit-service spacecraft. RIC of space-applied polyimide film was in situ measured and studied under continuous and cyclic electron irradiation in this paper. The results indicate that, for cyclic electron irradiation, there is a similar increasing-mode of RIC to those for continuous irradiation with the electron irradiation time. However, under the cyclic electron irradiation, the RIC of polyimide shows an obvious irradiation-history characteristic, namely preliminary irradiation dose effect (PIDE). In this case, the steady RIC value presents an "overshoot" behavior in the first few irradiation cycles and then decrease to a stable one as that under continuous irradiation. Prolonging the initial irradiation duration may avoid occurrence of overshoot phenomenon. The behaviors of irradiation-induced free radicals in polyimide could be applied to explain the RIC evolution processes.

  9. Radiation induced crosslinking effect on semi - interpenetrating polymer networks of poly(vinyl alcohol

    Directory of Open Access Journals (Sweden)

    2007-07-01

    Full Text Available Semi-IPNs with varying contents of poly(vinyl alcohol (PVA, poly acrylamide (PAM and crosslinker N,N’-methylene bis acrylamide (MBA were prepared by redox polymerization method. The structural and morphological properties were studied by Fourier transform infrared (FTIR spectroscopy, environmental scanning electron microscopy (ESEM and X-ray diffraction (XRD methods, respectively. It was found that the surface of the hydrogel is heterogeneous with separated domains. XRD result shows the semi-crystalline nature of the semi-IPNs. The prepared semi-IPNs of different compositions were subjected to gamma irradiation (2 to 250 kGy and the radiation induced effects on their strength of the semi-IPNs were studied by measuring the surface microhardness using a Vickers microhardness tester. Significant changes were observed in the Vickers microhardness, which were correlated with molecular architecture of the prepared semi-IPNs.

  10. ESR study on radiation-induced radicals in carboxymethyl cellulose aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Seiichi, E-mail: saiki.seiichi@jaea.go.j [Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Nagasawa, Naotsugu; Hiroki, Akihiro; Morishita, Norio; Tamada, Masao [Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Kudo, Hisaaki [Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656 (Japan); Katsumura, Yosuke [Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656 (Japan); Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai, Naka, Ibaraki 319-1195 (Japan)

    2011-02-15

    Carboxymethyl cellulose (CMC) at highly concentrated aqueous solution undergoes radiation crosslinking reaction by ionizing irradiation. It is assumed that this radiation-induced reaction takes place by the indirect effect of water radiolysis, especially through the OH radical. However, the reaction mechanism is not well known. In this topic, ESR spectra of CMC radicals formed by reaction with OH radicals were measured directly in aqueous solution to identify the initially formed radical site. The ESR spectra were observed successfully and were interpreted as the overlapping of two spectra; a TripletxDoublet spectrum and a Doublet spectrum. Each spectrum was assigned to radicals located on carboxymethyl groups linked to C6 and C2/C3.

  11. ESR study on radiation-induced radicals in carboxymethyl cellulose aqueous solution

    Science.gov (United States)

    Saiki, Seiichi; Nagasawa, Naotsugu; Hiroki, Akihiro; Morishita, Norio; Tamada, Masao; Kudo, Hisaaki; Katsumura, Yosuke

    2011-02-01

    Carboxymethyl cellulose (CMC) at highly concentrated aqueous solution undergoes radiation crosslinking reaction by ionizing irradiation. It is assumed that this radiation-induced reaction takes place by the indirect effect of water radiolysis, especially through the OH radical. However, the reaction mechanism is not well known. In this topic, ESR spectra of CMC radicals formed by reaction with OH radicals were measured directly in aqueous solution to identify the initially formed radical site. The ESR spectra were observed successfully and were interpreted as the overlapping of two spectra; a Triplet×Doublet spectrum and a Doublet spectrum. Each spectrum was assigned to radicals located on carboxymethyl groups linked to C6 and C2/C3.

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

    Energy Technology Data Exchange (ETDEWEB)

    Farnum, E.; Scharborough, K. [Los Alamos National Lab., NM (United States); Shikama, Tatsuo [and others

    1995-04-01

    The objective of this experiment is to determine the extent of degradation during neutron irradiation of electrical and optical properties of candidate dielectric materials. The goals are to identify promising dielectrics for ITER and other fusion machines for diagnostic applications and establish the basis for optimization of candidate materials. An experiment to measure radiation-induced electrical degradation (REID) in sapphire and MgO-insulated cables was conducted at the JMTR light water reactor. The materials were irradiated at about 260 {degree}C to a fluence of 3{times}10{sup 24} n/m{sup 2} (E>1 MeV) with an applied DC electric field between 100 kV/m and 500 kV/m.

  13. Measurements of the Radiation Induced Conductivity of Insulating Polymeric Materials for the James Webb Space Telescope

    Science.gov (United States)

    Corbridge, J.; Dennison, J. R.; Hodges, J.; Hoffmann, R. C.; Abbott, J.; Hunt, A.; Spaulding, R.

    2006-10-01

    We report on initial measurements of Radiation Induced Conductivity (RIC) for twelve thin film polymer materials that are used in the cabling of the James Webb Space Telescope. Results will be used to model possible detrimental arching due to space craft charging effects. RIC occurs when incident ionizing radiation deposits energy in a material and excites electrons into the conduction band of insulators. RIC is determined using a constant voltage test method as the difference in the equilibrium sample conductivity under no incident radiation and sample conductivity under an incident flux. An accelerator beam at the Idaho Accelerator Center provides the 2-5 MeV incident flux over a range of 10^2 to 10^+1 rad/sec. Measurements are made for a range of applied voltages and radiation dose rates.

  14. Experimental study of radiation induced electromotive force effects on mineral insulated cables

    Science.gov (United States)

    Van Nieuwenhove, R.; Vermeeren, L.

    2003-11-01

    Measurements of radiation induced electromotive force (RIEMF) effects on mineral insulated cables in a pure gamma field and in a combined neutron and gamma field are presented and compared to model calculations. The effect of materials in the immediate surroundings of the cable, as predicted by the model calculations, is clearly demonstrated. In a fission reactor environment, delayed current contributions due to the neutron activation and subsequent beta emission in base materials as well as in impurities such as Mn are clearly observed and are well reproduced by model calculations. The prediction of the gamma induced current component was severely complicated by its strong sensitivity to the detailed geometry and the spectrum and the directivity of the gamma field. Although the RIEMF effect on MI cables can therefore in general not be completely eliminated, some guidelines are provided to minimize them.

  15. Radiation induced DNA double-strand breaks in radiology; Strahleninduzierte DNA-Doppelstrangbrueche in der Radiologie

    Energy Technology Data Exchange (ETDEWEB)

    Kuefner, M.A. [Dornbirn Hospital (Austria). Dept. of Radiology; Brand, M.; Engert, C.; Uder, M. [Erlangen University Hospital (Germany). Dept. of Radiology; Schwab, S.A. [Radiologis, Oberasbach (Germany)

    2015-10-15

    Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on physical measurements or mathematical algorithms with standardized dose simulations. γ-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the principle of the γ-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations.

  16. Sigmoid exclusion: a new technique in the management of radiation-induced fistula.

    Science.gov (United States)

    Aitken, R J; Elliot, M S

    1985-09-01

    Colovesical and colovaginal fistulas following irradiation for pelvic malignancy represent a formidable surgical problem. Although complex surgical procedures to close the fistulas and restore continence have been described, often a defunctioning colostomy with an associated urinary conduit is the only feasible option. Three patients who have successfully undergone an original procedure (sigmoid exclusion) are presented. Sigmoid exclusion restores continence but avoids a permanent stoma. The involved sigmoid colon was isolated on its mesentery ensuring that the area incorporating the fistulas was not disrupted. The ends of the isolated sigmoid colon were closed and bowel continuity then restored by a colorectal or colo-anal anastomosis. Following closure of a temporary colostomy the patients were continent with no ill effects or sepsis from the excluded colon. This procedure has the dual advantage of restoring continence yet avoiding both an urinary conduit and a permanent colostomy, and represents a useful advance in the surgical management of radiation induced colonic fistulas.

  17. Excision repair of UV radiation-induced DNA damage in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.S.; Hevelone, J.; Dwarakanath, V.; Mitchell, D.L. (Texas Christian Univ., Fort Worth (USA))

    1989-06-01

    Radioimmunoassays were used to monitor the removal of antibody-binding sites associated with the two major UV radiation-induced DNA photoproducts (cyclobutane dimers and (6-4) photoproducts). Unlike with cultured human cells, where (6-4) photoproducts are removed more rapidly than cyclobutane dimers, the kinetics of repair were similar for both lesions. Repair capacity in wild type diminished throughout development. The radioimmunoassays were also employed to confirm the absence of photoreactivation in C. elegans. In addition, three radiation-sensitive mutants (rad-1, rad-2, rad-7) displayed normal repair capacities. An excision defect was much more pronounced in larvae than embryos in the fourth mutant tested (rad-3). This correlates with the hypersensitivity pattern of this mutant and suggests that DNA repair may be developmentally regulated in C. elegans. The mechanism of DNA repair in C. elegans as well as the relationship between the repair of specific photoproducts and UV radiation sensitivity during development are discussed.

  18. Effect of radiation-induced substrate defects on microstrip gas chamber gain behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Pallares, A.; Brom, J.M.; Bergdolt, A.M.; Coffin, J.; Eberle, H.; Sigward, M.H. [Institute de Recherches Subatomiques, 67 - Strasbourg (France); Fontaine, J.C. [Universite de Haute Alsace, GRPHE, 61 rue Albert Camus, 68093 Mulhouse Cedex (France); Barthe, S.; Schunck, J.P. [Laboratoire PHASE (UPR 292 du CNRS), 23 rue du Loess, BP 28, 67037 Strasbourg Cedex 2 (France)

    1998-08-01

    The aim of this work was to quantify the influence of radiation-induced substrate defects on microstrip gas chamber (MSGC) gain behaviour. The first part of this paper focuses on radiation effects on a typical MSGC substrate: Desag D263 glass. Defect generation was studied for Desag D263 with pure silica (Suprasil 1) as a reference. We studied the evolution of defect concentration with respect to accumulated doses up to 480 kGy. Annealing studies of defects in Desag D263 were also performed. In the second part, the radiation sensitivity of Desag D263 glass has been linked to the behaviour of the detector under irradiation. Comparative gain measurements were taken before and after substrate irradiation at 10 and 80 kGy the minimal dose received during LHC operation and the dose for which defect density is maximum (respectively). (orig.) 26 refs.

  19. Modeling of radiation-induced sink evolution in 6061 aluminum alloy in nuclear reactors

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sang Il; Kim, Ji Hyun [Department of Nuclear Science and Engineering, School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan (Korea, Republic of); Lee, Gyeong-Geun; Kwon, Junhyun [Division of Nuclear Materials Research, Korea Atomic Energy Research Institute (KAERI), Daejeon (Korea, Republic of)

    2016-11-15

    The objective of this study is a detailed analysis of the radiation effects on sink generation and growth in order to understand the phenomenon of irradiation hardening of 6061 aluminum alloy in research reactor conditions. In order to have a fundamental understanding, various sink behavior characteristics such as size and number density of dislocation loop, void, and precipitation were calculated and examined. Thereafter, theoretical assessment of various sink effects on irradiation hardening was conducted based on the mean field rate theory (MFRT). Dislocation loop, void, and precipitation were examined by defect flux. For the quantitative analysis of radiation-induced degradation, change in sink size was calculated using number density. 6061 Alloy showed great dependence on precipitation generation and growth. However, dislocation loop and void did not have any significant effect on irradiation hardening. Finally, the behavior of sinks was compared with the experimental results for validation. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Prompt radiation-induced conductivity in polyurethane foam and glass microballoons

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

    We performed measurements and analyses of the prompt radiation-induced conductivity (RIC) in thin samples of polyurethane foam and glass microballoon foam at the Little Mountain Medusa LINAC facility in Ogden, UT. The RIC coefficient was non-linear with dose rate for polyurethane foam; however, typical values at 1E11 rad(si)/s dose rate was measured as 0.8E-11 mho/m/rad/s for 5 lb./cu ft. foam and 0.3E-11 mho/m/rad/s for 10 lb./cu ft. density polyurethane foam. For encapsulated glass microballoons (GMB) the RIC coefficient was approximately 1E-15 mho/m/rad/s and was not a strong function of dose rate.

  1. Graft polymerization using radiation-induced peroxides and application to textile dyeing

    Energy Technology Data Exchange (ETDEWEB)

    Enomoto, Ichiro, E-mail: enomoto.ichiro@iri-tokyo.j [Tokyo Metropolitan Industrial Technology Research Institute, KFC Bldg., 12F, 1-6-1, Yokoami, Sumida-ku, Tokyo 130-0015 (Japan); School of Engineering, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Katsumura, Yosuke [School of Engineering, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata Shirane, Tokai-mura, Ibaraki 319-1195 (Japan); Kudo, Hisaaki [School of Engineering, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Soeda, Shin [Tokyo Metropolitan Industrial Technology Research Institute, KFC Bldg., 12F, 1-6-1, Yokoami, Sumida-ku, Tokyo 130-0015 (Japan)

    2011-02-15

    To improve the dyeing affinity of ultra high molecular weight polyethylene (UHMWPE) fiber, surface treatment by radiation-induced graft polymerization was performed. Methyl methacrylate (MMA), acrylic acid (AA) and styrene (St) were used as the monomers. The grafting yields as a function of storage time after irradiation were examined. Although the grafting yield of St after the sulfonation processing was quite low compared with those of MMA and AA, it was successfully dyed to a dark color with a cationic dye. Some acid dyes can dye the grafted fiber with AA. The acid dye is distributed to the amorphous domains of the AA grafted fiber. The dyeing concentration depended on the grafting yield, and the higher the grafting yield the darker the dye color.

  2. Pilot study of ice-ball cryotherapy for radiation-induced oral mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Ohyama, Waichiro; Ebihara, Satoshi [National Cancer Center Hospital, Tokyo (Japan)

    1996-02-01

    Oral mucositis caused by radiotherapy is intractable and may worsen the patient`s nutritional condition and interrupt treatment. To reduce the incidence and severity of oral mucositis induced by cancer therapy and promote early improvement of its symptoms, we devised cryotherapy by ice balls using Elase (fibrinolysin and deoxyribonuclease, combined). The therapeutic effect of ice-ball cryotherapy was evaluated in 10 patients with carcinoma of the oral cavity and pharynx who were undergoing radiotherapy. Cryotherapy was continued from the development of oral mucositis until its disappearance. The severity of various symptoms of mucositis were reduced by cryotherapy. Healing required 3 to 16 days (median, 7 days) after the end of radiotherapy. Radiotherapy was not interrupted in any cases. This preliminary report suggests that ice-ball cryotherapy is an effective treatment for radiation-induced oral mucositis. (author).

  3. Maintenance of radiation-induced intestinal fibrosis: Cellular and molecular features

    Institute of Scientific and Technical Information of China (English)

    Valérie Haydont; Marie-Catherine Vozenin-Brotons

    2007-01-01

    Recent advances in cell and molecular radiobiology clearly showed that tissue response to radiation injury cannot be restricted to a simple cell-killing process, but depends upon continuous and integrated pathogenic processes, involving cell differentiation and crosstalk between the various cellular components of the tissue within the extracellular matrix. Thus, the prior concept of primary cell target in which a single-cell type (whatever it's epithelial or endothelial cells) dictates the whole tissue response to radiation injury has to be replaced by the occurrence of coordinated multicellular response that may either lead to tissue recovery or to sequel development. In this context, the present review will focus on the maintenance of the radiation-induced wound healing and fibrogenic signals triggered by and through the microenvironment toward the mesencnymal cell compartment, and will highlight how sequential and sustained modifications in cell phenotypes will in cascade modify cell-to-cell interactions and tissue composition.

  4. Radiation-induced vasculopathy implicated by depressed blood flow and metabolism in a pineal glioma

    Energy Technology Data Exchange (ETDEWEB)

    Mineura, K.; Sasajima, T.; Kowada, M. (Akita University Hospital (Japan). Neurosurgical Service); Saitoh, H. (Oodate Municipal Hospital (Japan). Dept. of Neurosurgery); Shishido, F. (Research Inst. of Brain and Blood Vessels, Akita (Japan))

    1993-08-01

    A case of radiation-induced vasculopathy of a pineal glioma was presented with haemodynamic and metabolic changes before and after radiotherapy. After radiation of 60 Gy with conventional fractionation (1.8-2.0 Gy daily, 5 days per week), regional blood flow, oxygen extraction fraction, metabolic rate of oxygen, kinetic metabolic rate of glucose and the rate constants (K2, K3) were markedly depressed (20% or greater) compared with the pre-irradiated study. 7 months after radiotherapy, the patient developed transient episodes of both right and left upper limb convulsion, terminating in generalized convulsion. When she developed status epilepticus, computed tomography showed extensive low density areas in the territory supplied by the right middle cerebral and the right posterior cerebral arteries. (author).

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

    Science.gov (United States)

    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

  6. HGF Gene Modification in Mesenchymal Stem Cells Reduces Radiation-Induced Intestinal Injury by Modulating Immunity.

    Directory of Open Access Journals (Sweden)

    Hua Wang

    Full Text Available Effective therapeutic strategies to address intestinal complications after radiation exposure are currently lacking. Mesenchymal stem cells (MSCs, which display the ability to repair the injured intestine, have been considered as delivery vehicles for repair genes. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF-gene-modified MSCs on radiation-induced intestinal injury (RIII.Female 6- to 8-week-old mice were radiated locally at the abdomen with a single 13-Gy dose of radiation and then treated with saline control, Ad-HGF or Ad-Null-modified MSCs therapy. The transient engraftment of human MSCs was detected via real-time PCR and immunostaining. The therapeutic effects of non- and HGF-modified MSCs were evaluated via FACS to determine the lymphocyte immunophenotypes; via ELISA to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis.The histopathological recovery of the radiation-injured intestine was significantly enhanced following non- or HGF-modified MSCs treatment. Importantly, the radiation-induced immunophenotypic disorders of the mesenteric lymph nodes and Peyer's patches were attenuated in both MSCs-treated groups. Treatment with HGF-modified MSCs reduced the expression and secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α and interferon-gamma (IFN-γ, increased the expression of the anti-inflammatory cytokine IL-10 and the tight junction protein ZO-1, and promoted the proliferation and reduced the apoptosis of intestinal epithelial cells.Treatment of RIII with HGF-gene-modified MSCs reduces local inflammation and promotes the recovery of small intestinal histopathology in a mouse model. These findings might provide an effective therapeutic strategy for RIII.

  7. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.

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    Subhrajit Saha

    Full Text Available BACKGROUND: Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS, resulting from direct cytocidal effects on intestinal stem cells (ISC and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome. METHODOLOGY/PRINCIPAL FINDINGS: Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy or abdominal irradiation (16-20 Gy in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated. CONCLUSION/SIGNIFICANCE: Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of

  8. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  9. The role of niobium carbide in radiation induced segregation behaviour of type 347 austenitic stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Ahmedabadi, Parag, E-mail: adit@barc.gov.in [Materials Science Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Kain, Vivekanand [Materials Science Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Gupta, Manu [PEC University of Technology, Chandigarh (India); Samajdar, I. [Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai 400 076 (India); Sharma, S.C.; Bhagwat, P.; Chowdhury, R. [Nuclear Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2011-08-01

    Highlights: > Characterization of radiation-induced segregation done by EPR and AFM examination. > Variation of DL-EPR values with depth showed trend similar to that of variation of dpa with depth, calculated by SRIM. > Niobium carbides had reduced defect flux toward grain boundaries leading to reduced chromium depletion levels. > Adsorption of point defects at carbide-matrix interface leading to chromium depletion at large carbide clusters. - Abstract: The effect of niobium carbide precipitates on radiation induced segregation (RIS) behaviour in type 347 stainless steel was investigated. The material in the as-received condition was irradiated using double-loop 4.8 MeV protons at 300 deg. C for 0.43 dpa (displacement per atom). The RIS in the proton irradiated specimen was characterized using double-loop electrochemical potentiokinetic reactivation (DL-EPR) test followed by atomic force microscopic examination. The nature of variation of DL-EPR values with the depth matched with the variation of the calculated irradiation damage (dpa) with the depth. The attack on grain boundaries during EPR tests was negligible indicating absence of chromium depletion zones. The interface between niobium carbide and the matrix acts as a sink for point defects generated during irradiation and this had reduced point defect flux toward grain boundaries. The attack was noticed at a few large cluster of niobium carbide after the DL-EPR test at the depth of maximum attack for the irradiated specimen. Pit-like features were not observed within the matrix indicating the absence of chromium depletion regions within the matrix.

  10. Proximity Within Interphase Chromosome Contributes to the Breakpoint Distribution in Radiation-Induced Intrachromosomal Exchanges

    Science.gov (United States)

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

    2015-01-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome3 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 chromosome3. 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. Further investigations suggest that the 3D chromosome folding is cell type and culture condition dependent.

  11. Late infusion of cloned marrow fibroblasts stimulates endogenous recovery from radiation-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Mineo Iwata

    Full Text Available In the current study, we used a canine model of radiation-induced lung injury to test the effect of a single i.v. infusion of 10×10(6/kg of marrow fibroblasts on the progression of damage following 15 Gy exposure to the right lung. The fibroblasts, designated DS1 cells, are a cloned population of immortalized cells isolated from a primary culture of marrow stromal cells. DS1 cells were infused at week 5 post-irradiation when lung damage was evident by imaging with high-resolution computed tomography (CT. At 13 weeks post-irradiation we found that 4 out of 5 dogs receiving DS1 cells had significantly improved pulmonary function compared to 0 out of 5 control dogs (p = 0.047, Fisher's Exact. Pulmonary function was measured as the single breath diffusion capacity-hematocrit (DLCO-Hct, the total inspiratory capacity (IC, and the total lung capacity (TLC, which differed significantly between control and DS1-treated dogs; p = 0.002, p = 0.005, and p = 0.004, respectively. The DS1-treated dogs also had less pneumonitis detected by CT imaging and an increased number of TTF-1 (thyroid transcription factor 1, NKX2-1 positive cells in the bronchioli and alveoli compared to control dogs. Endothelial-like progenitor cells (ELC of host origin, detected by colony assays, were found in peripheral blood after DS1 cell infusion. ELC numbers peaked one day after infusion, and were not detectable by 7 days. These data suggest that infusion of marrow fibroblasts stimulates mobilization of ELC, which is associated with a reduction in otherwise progressive radiation-induced lung injury. We hypothesize that these two observations are related, specifically that circulating ELC contribute to increased angiogenesis, which facilitates endogenous lung repair.

  12. Modulation of modeled microgravity on radiation-induced bystander effects in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China); Sun, Qiao [Space Molecular Biological Lab, China Academy of Space Technology, Beijing 100086 (China); Xu, Wei; Li, Fanghua [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China); Li, Huasheng; Lu, Jinying [Space Molecular Biological Lab, China Academy of Space Technology, Beijing 100086 (China); Wu, Lijun; Wu, Yuejin [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China); Liu, Min [Space Molecular Biological Lab, China Academy of Space Technology, Beijing 100086 (China); Bian, Po [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China)

    2015-03-15

    Highlights: • The effects of microgravity on the radiation-induced bystander effects (RIBE) were definitely demonstrated. • The effects of microgravity on RIBE might be divergent for different biological events. • The microgravity mainly modified the generation or transport of bystander signals at early stage. - Abstract: Both space radiation and microgravity have been demonstrated to have inevitable impact on living organisms during space flights and should be considered as important factors for estimating the potential health risk for astronauts. Therefore, the question whether radiation effects could be modulated by microgravity is an important aspect in such risk evaluation. Space particles at low dose and fluence rate, directly affect only a fraction of cells in the whole organism, which implement radiation-induced bystander effects (RIBE) in cellular response to space radiation exposure. The fact that all of the RIBE experiments are carried out in a normal gravity condition bring forward the need for evidence regarding the effect of microgravity on RIBE. In the present study, a two-dimensional rotation clinostat was adopted to demonstrate RIBE in microgravity conditions, in which the RIBE was assayed using an experimental system of root-localized irradiation of Arabidopsis thaliana (A. thaliana) plants. The results showed that the modeled microgravity inhibited significantly the RIBE-mediated up-regulation of expression of the AtRAD54 and AtRAD51 genes, generation of reactive oxygen species (ROS) and transcriptional activation of multicopy P35S:GUS, but made no difference to the induction of homologous recombination by RIBE, showing divergent responses of RIBE to the microgravity conditions. The time course of interaction between the modeled microgravity and RIBE was further investigated, and the results showed that the microgravity mainly modulated the processes of the generation or translocation of the bystander signal(s) in roots.

  13. Dragon's blood and its extracts attenuate radiation-induced oxidative stress in mice.

    Science.gov (United States)

    Ran, Yuanyuan; Wang, Ran; Gao, Qian; Jia, Qiutian; Hasan, Murtaza; Awan, Muhammad Umer Farooq; Tang, Bo; Zhou, Rui; Dong, Yiming; Wang, Xiao; Li, Qiang; Ma, Hong; Deng, Yulin; Qing, Hong

    2014-07-01

    Dragon's blood (DB) possesses great medicinal values due to the presence of several phenolic compounds. This study was designed to investigate the effects of DB and its extracts (DBEs) on oxidative stress in mice exposed to whole body (60)Co-γ irradiation (4 Gy). DB and DBEs were intragastrically administered to mice for 5 d prior to radiation. The antioxidant activities, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in liver and spleen were measured using kits. Furthermore, DB and DBE effects were determined by organ indices and histology of liver and spleen. Our results indicated that the DB and DBE-treated groups showed a significant decrease (P < 0.05) in levels of MDA in liver and spleen compared with the irradiation-only group. Moreover, the activity of SOD, CAT and the level of GSH in liver and spleen tissue were enhanced significantly (P < 0.05) in the DB and DBE groups. DB and DBE also had a significant effect on the recovery of thymus indices. The histological observations of groups having treatment with DB and DBE indicated significant reduction in the radiation-induced damage to the liver and spleen, together with improvement in the morphology of the liver and spleen. These results suggest that DB and DBE treatment prevents radiation-induced oxidative stress injury and restores antioxidant status and histopathological changes in the liver and spleen, but there is need for further study to explore the precise molecular mechanism and strategy for optimal practical application of DB and DBE.

  14. p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xu Rui; LIU Yong Ai; SUN Fang; LI He; LEI Su Wen; WANG Ju Fang

    2016-01-01

    Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest. Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation. Depletion of p21 was carried out by employing the siRNA technique. Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28, an M-phase marker. Senescence was assessed by senescence-associated-β-galactosidase (SA-β-gal) staining combined with Ki67 staining, a cell proliferation marker. Results Accompanying increased p21, the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays. Furthermore, these irradiated cells were blocked at the G2 phase followed by cellular senescence. Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases, as well as the high expression of histone H3 phosphorylated at Ser28. Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells. However, cells with serious DNA damage failed to undergo cytokinesis, leading to the accumulation of multinucleated cells. Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation. Downregulation of p21 by siRNA resulted in G2-arrested cells entering into mitosis with serious DNA damage. This is the first report on elucidating the role of p21 in the bypass of mitosis.

  15. REDD1 protects osteoblast cells from gamma radiation-induced premature senescence.

    Directory of Open Access Journals (Sweden)

    Xiang Hong Li

    Full Text Available Radiotherapy is commonly used for cancer treatment. However, it often results in side effects due to radiation damage in normal tissue, such as bone marrow (BM failure. Adult hematopoietic stem and progenitor cells (HSPC reside in BM next to the endosteal bone surface, which is lined primarily by hematopoietic niche osteoblastic cells. Osteoblasts are relatively more radiation-resistant than HSPCs, but the mechanisms are not well understood. In the present study, we demonstrated that the stress response gene REDD1 (regulated in development and DNA damage responses 1 was highly expressed in human osteoblast cell line (hFOB cells after γ irradiation. Knockdown of REDD1 with siRNA resulted in a decrease in hFOB cell numbers, whereas transfection of PCMV6-AC-GFP-REDD1 plasmid DNA into hFOB cells inhibited mammalian target of rapamycin (mTOR and p21 expression and protected these cells from radiation-induced premature senescence (PS. The PS in irradiated hFOB cells were characterized by significant inhibition of clonogenicity, activation of senescence biomarker SA-β-gal, and the senescence-associated cytokine secretory phenotype (SASP after 4 or 8 Gy irradiation. Immunoprecipitation assays demonstrated that the stress response proteins p53 and nuclear factor κ B (NFkB interacted with REDD1 in hFOB cells. Knockdown of NFkB or p53 gene dramatically suppressed REDD1 protein expression in these cells, indicating that REDD1 was regulated by both factors. Our data demonstrated that REDD1 is a protective factor in radiation-induced osteoblast cell premature senescence.

  16. Inhibition of radiation induced dissolution of UO2 by sulfide - A comparison with the hydrogen effect

    Science.gov (United States)

    Yang, Miao; Barreiro Fidalgo, Alexandre; Sundin, Sara; Jonsson, Mats

    2013-03-01

    In this work we have studied the influence of H2S on radiation induced dissolution of spent nuclear fuel using simple model systems. The reaction between H2O2 and H2S/HS- has been studied experimentally as well as the effect of H2S/HS- on γ-radiation induced dissolution of a UO2 pellet. The experiments clearly show that the reaction of H2O2 and H2S/HS- is fairly rapid and that H2O2 and H2S/HS- stoichiometry is favorable for inhibition. Radiolysis experiments show that H2S/HS- can effectively protect UO2 from oxidative dissolution. The effect depends on sulfide concentration in combination with dose rate. Autoclave experiments were also conducted to study the role of H2S/HS- in the reduction of U(VI) in the presence and absence of H2 and Pd particles in anoxic aqueous solution. The aqueous solutions were pressurized with H2 or N2 and two different concentrations of H2S/HS- were used in the presence and absence of Pd. No catalytic effect of Pd on the U(VI) reduction by H2S/HS- could be found in N2 atmosphere. U(VI) reduction was found to be proportional to H2S/HS- concentration in H2 and N2 atmosphere. It is clearly shown the Pd catalyzed H2 effect is more powerful than the effect of H2S/HS-. H2S/HS- poisoning of the Pd catalyst is not observed under the present conditions.

  17. Identifying radiation-induced survivorship syndromes affecting bowel health in a cohort of gynecological cancer survivors

    Science.gov (United States)

    Steineck, Gunnar; Skokic, Viktor; Bull, Cecilia; Alevronta, Eleftheria; Dunberger, Gail; Bergmark, Karin; Wilderäng, Ulrica; Oh, Jung Hun; Deasy, Joseph O.; Jörnsten, Rebecka

    2017-01-01

    Background During radiotherapy unwanted radiation to normal tissue surrounding the tumor triggers survivorship diseases; we lack a nosology for radiation-induced survivorship diseases that decrease bowel health and we do not know which symptoms are related to which diseases. Methods Gynecological-cancer survivors were followed-up two to 15 years after having undergone radiotherapy; they reported in a postal questionnaire the frequency of 28 different symptoms related to bowel health. Population-based controls gave the same information. With a modified factor analysis, we determined the optimal number of factors, factor loadings for each symptom, factor-specific factor-loading cutoffs and factor scores. Results Altogether data from 623 survivors and 344 population-based controls were analyzed. Six factors best explain the correlation structure of the symptoms; for five of these a statistically significant difference (P< 0.001, Mann-Whitney U test) was found between survivors and controls concerning factor score quantiles. Taken together these five factors explain 42 percent of the variance of the symptoms. We interpreted these five factors as radiation-induced syndromes that may reflect distinct survivorship diseases. We obtained the following frequencies, defined as survivors having a factor loading above the 95 percent percentile of the controls, urgency syndrome (190 of 623, 30 percent), leakage syndrome (164 of 623, 26 percent), excessive gas discharge (93 of 623, 15 percent), excessive mucus discharge (102 of 623, 16 percent) and blood discharge (63 of 623, 10 percent). Conclusion Late effects of radiotherapy include five syndromes affecting bowel health; studying them and identifying the underlying survivorship diseases, instead of the approximately 30 long-term symptoms they produce, will simplify the search for prevention, alleviation and elimination. PMID:28158314

  18. Stat5 is critical for the development and maintenance of myeloproliferative neoplasm initiated by Nf1 deficiency.

    Science.gov (United States)

    Sachs, Zohar; Been, Raha A; DeCoursin, Krista J; Nguyen, Hanh T; Mohd Hassan, Nurul A; Noble-Orcutt, Klara E; Eckfeldt, Craig E; Pomeroy, Emily J; Diaz-Flores, Ernesto; Geurts, Jennifer L; Diers, Miechaleen D; Hasz, Diane E; Morgan, Kelly J; MacMillan, Margaret L; Shannon, Kevin M; Largaespada, David A; Wiesner, Stephen M

    2016-10-01

    Juvenile myelomonocytic leukemia is a rare myeloproliferative neoplasm characterized by hyperactive RAS signaling. Neurofibromin1 (encoded by the NF1 gene) is a negative regulator of RAS activation. Patients with neurofibromatosis type 1 harbor loss-of-function mutations in NF1 and have a 200- to 500-fold increased risk of juvenile myelomonocytic leukemia. Leukemia cells from patients with juvenile myelomonocytic leukemia display hypersensitivity to certain cytokines, such as granulocyte-macrophage colony-stimulating factor. The granulocyte-macrophage colony-stimulating factor receptor utilizes pre-associated JAK2 to initiate signals after ligand binding. JAK2 subsequently activates STAT5, among other downstream effectors. Although STAT5 is gaining recognition as an important mediator of growth factor signaling in myeloid leukemias, the contribution of STAT5 to the development of hyperactive RAS-initiated myeloproliferative disease has not been well described. In this study, we investigated the consequence of STAT5 attenuation via genetic and pharmacological approaches in Nf1-deficient murine models of juvenile myelomonocytic leukemia. We found that homozygous Stat5 deficiency extended the lifespan of Nf1-deficient mice and eliminated the development of myeloproliferative neoplasm associated with Nf1 gene loss. Likewise, we found that JAK inhibition with ruxolitinib attenuated myeloproliferative neoplasm in Nf1-deficient mice. Finally, we found that primary cells from a patient with KRAS-mutant juvenile myelomonocytic leukemia displayed reduced colony formation in response to JAK2 inhibition. Our findings establish a central role for STAT5 activation in the pathogenesis of juvenile myelomonocytic leukemia and suggest that targeting this pathway may be of clinical utility in these patients.

  19. A role for TRAIL/TRAIL-R2 in radiation-induced apoptosis and radiation-induced bystander response of human neural stem cells.

    Science.gov (United States)

    Ivanov, Vladimir N; Hei, Tom K

    2014-03-01

    Adult neurons, which are terminally differentiated cells, demonstrate substantial radioresistance. In contrast, human neural stem cells (NSC), which have a significant proliferative capacity, are highly sensitive to ionizing radiation. Cranial irradiation that is widely used for treatment of brain tumors may induce death of NSC and further cause substantial cognitive deficits such as impairing learning and memory. The main goal of our study was to determine a mechanism of NSC radiosensitivity. We observed a constitutive high-level expression of TRAIL-R2 in human NSC. On the other hand, ionizing radiation through generation of reactive oxygen species targeted cell signaling pathways and dramatically changed the pattern of gene expression, including upregulation of TRAIL. A significant increase of endogenous expression and secretion of TRAIL could induce autocrine/paracrine stimulation of the TRAIL-R2-mediated signaling cascade with activation of caspase-3-driven apoptosis. Furthermore, paracrine stimulation could initiate bystander response of non-targeted NSC that is driven by death ligands produced by directly irradiated NSC. Experiments with media transfer from directly irradiated NSC to non-targeted (bystander) NSC confirmed a role of secreted TRAIL for induction of a death signaling cascade in non-targeted NSC. Subsequently, TRAIL production through elimination of bystander TRAIL-R-positive NSC might substantially restrict a final yield of differentiating young neurons. Radiation-induced TRAIL-mediated apoptosis could be partially suppressed by anti-TRAIL antibody added to the cell media. Interestingly, direct gamma-irradiation of SK-N-SH human neuroblastoma cells using clinical doses (2-5 Gy) resulted in low levels of apoptosis in cancer cells that was accompanied however by induction of a strong bystander response in non-targeted NSC. Numerous protective mechanisms were involved in the maintenance of radioresistance of neuroblastoma cells, including

  20. Contribution of endogenous and exogenous damage to the total radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1980-01-01

    Radical scavengers such as polyethylene glycol 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous damage to the total radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous.

  1. Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells.

    Science.gov (United States)

    Kobashigawa, Shinko; Kashino, Genro; Mori, Hiromu; Watanabe, Masami

    2015-03-01

    Ionizing radiation-induced cellular senescence is thought to be caused by nuclear DNA damage that cannot be repaired. However, here we found that radiation induces delayed increase of intracellular oxidative stress after irradiation. We investigated whether the relief of delayed oxidative stress by ascorbic acid would suppress the radiation-induced cellular senescence in Syrian golden hamster embryo (SHE) cells. We observed that the level of oxidative stress was drastically increased soon after irradiation, then declined to the level in non-irradiated cells, and increased again with a peak on day 3 after irradiation. We found that the inductions of cellular senescence after X-irradiation were reduced along with suppression of the delayed induction of oxidative stress by treatment with ascorbic acid, but not when oxidative stress occurred immediately after irradiation. Moreover, treatment of ascorbic acid inhibited p53 accumulation at 3 days after irradiation. Our data suggested a delayed increase of intracellular oxidative stress levels plays an important role in the process of radiation-induced cellular senescence by p53 accumulation.

  2. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands

    NARCIS (Netherlands)

    Lombaert, IMA; Wierenga, PK; Kok, T; Kampinga, HH; deHaan, G; Coppes, RP

    2006-01-01

    Purpose: One of the major reasons for failure of radiotherapeutic cancer treatment is the limitation in dose that can be applied to the tumor because of coirradiation of the normal healthy tissue. Late radiation-induced damage reduces the quality of life of the patient and may even be life threateni

  3. External validation of a normal tissue complication probability model for radiation-induced hypothyroidism in an independent cohort

    DEFF Research Database (Denmark)

    Rønjom, Marianne F; Brink, Carsten; Bentzen, Søren M

    2015-01-01

    BACKGROUND: A normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism (RIHT) was previously derived in patients with squamous cell carcinoma of the head and neck (HNSCC) discerning thyroid volume (Vthyroid), mean thyroid dose (Dmean), and latency as predictive...

  4. Discriminating Gene Expression Signature of Radiation-Induced Thyroid Tumors after Either External Exposure or Internal Contamination

    Directory of Open Access Journals (Sweden)

    Sylvie Chevillard

    2011-12-01

    Full Text Available Both external radiation exposure and internal radionuclide contamination are well known risk factors in the development of thyroid epithelial tumors. The identification of specific molecular markers deregulated in radiation-induced thyroid tumors is important for the etiological diagnosis since neither histological features nor genetic alterations can discriminate between sporadic and radiation-induced tumors. Identification of highly discriminating markers in radiation-induced tumors is challenging as it relies on the ability to identify marker deregulation which is associated with a cellular stress that occurred many years before in the thyroid cells. The existence of such a signature is still controversial, as it was not found in several studies while a highly discriminating signature was found in both post-radiotherapy and post-Chernobyl series in other studies. Overall, published studies searching for radiation-induced thyroid tumor specificities, using transcriptomic, proteomic and comparative genomic hybridization approaches, and bearing in mind the analytical constraints required to analyze such small series of tumors, suggest that such a molecular signature could be found. In comparison with sporadic tumors, we highlight molecular similarities and specificities in tumors occurring after high-dose external radiation exposure, such as radiotherapy, and in post-Chernobyl tumors that occurred after internal 131I contamination. We discuss the relevance of signature extrapolation from series of tumors developing after high and low doses in the identification of tumors induced at very low doses of radiation.

  5. Discriminating gene expression signature of radiation-induced thyroid tumors after either external exposure or internal contamination.

    Science.gov (United States)

    Ory, Catherine; Ugolin, Nicolas; Schlumberger, Martin; Hofman, Paul; Chevillard, Sylvie

    2011-12-21

    Both external radiation exposure and internal radionuclide contamination are well known risk factors in the development of thyroid epithelial tumors. The identification of specific molecular markers deregulated in radiation-induced thyroid tumors is important for the etiological diagnosis since neither histological features nor genetic alterations can discriminate between sporadic and radiation-induced tumors. Identification of highly discriminating markers in radiation-induced tumors is challenging as it relies on the ability to identify marker deregulation which is associated with a cellular stress that occurred many years before in the thyroid cells. The existence of such a signature is still controversial, as it was not found in several studies while a highly discriminating signature was found in both post-radiotherapy and post-Chernobyl series in other studies. Overall, published studies searching for radiation-induced thyroid tumor specificities, using transcriptomic, proteomic and comparative genomic hybridization approaches, and bearing in mind the analytical constraints required to analyze such small series of tumors, suggest that such a molecular signature could be found. In comparison with sporadic tumors, we highlight molecular similarities and specificities in tumors occurring after high-dose external radiation exposure, such as radiotherapy, and in post-Chernobyl tumors that occurred after internal 131I contamination. We discuss the relevance of signature extrapolation from series of tumors developing after high and low doses in the identification of tumors induced at very low doses of radiation.

  6. [Solcoseryl--dental adherent paste in the treatment of acute radiation-induced inflammation of oral mucosa, gingivae and tongue].

    Science.gov (United States)

    Kryst, L; Kowalik, S; Bartkowski, S; Henning, G

    1990-07-01

    On the basis of a study carried out in three teaching departments of maxillofacial surgery the effect was analysed of Solcoseryl dental adherent paste and Linomag in the treatment of acute radiation-induced stomatitis. Both drugs were effective but Solcoseryl was superior to the other drug since it accelerated healing by about 50% and formed a protecting dressing on the inflamed mucosa.

  7. A Novel Approach for the Treatment of Radiation-Induced Hemorrhagic Cystitis with the GreenLight™ XPS Laser

    Directory of Open Access Journals (Sweden)

    Daniel Roberto Martinez

    2015-06-01

    Full Text Available ABSTRACTIntroduction:The treatment of pelvic malignancies with radiotherapy can develop severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a progressive disease that can lead to the need for blood transfusion, hospitalizations, and surgical interventions. This tends to affect the quality of life of these patients, and management can at times be difficult. We have evaluated the GreenLight Xcelerated Performance System (XPS with TruCoag, although primarily used for management of benign prostatic hypertrophy (BPH, for the treatment of radiation-induced hemorrhagic cystitis.Materials and Methods:After International Review Board (IRB approval, a retrospective chart review was performed in addition to a literature search. A series of four male patients, mean age of 81 years, with radiation-induced hemorrhagic cystitis secondary to radiotherapy for pelvic malignancies (3 prostate cancer, 1 rectal cancer were successfully treated with the GreenLight laser after unsuccessful treatment with current therapies described in the literature.Results:All four patients treated with the GreenLight laser had resolution of their hematuria after one treatment and were discharge from the hospital with clear urine.Conclusion:The GreenLight XPS laser shows promising results for the treatment of patients with radiation-induced hemorrhagic cystitis, and deserves further evaluation and validation, especially since there is limited data available in the literature regarding the use of this technology for the treatment of this devastating condition.

  8. Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

    Science.gov (United States)

    Lee, James C.; Kinniry, Paul A.; Arguiri, Evguenia; Serota, Matthew; Kanterakis, Stathis; Chatterjee, Shampa; Solomides, Charalambos C.; Javvadi, Prashanthi; Koumenis, Constantinos; Cengel, Keith A.; Christofidou-Solomidou, Melpo

    2010-01-01

    The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1%or 5%(w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-α production in lungs, only 5%dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation. PMID:20426658

  9. Regulatory T Cells Promote β-Catenin–Mediated Epithelium-to-Mesenchyme Transition During Radiation-Induced Pulmonary Fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Shanshan; Pan, Xiujie; Xu, Long; Yang, Zhihua [Beijing Institute of Radiation Medicine, Beijing (China); Guo, Renfeng [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Gu, Yongqing; Li, Ruoxi; Wang, Qianjun; Xiao, Fengjun; Du, Li; Zhou, Pingkun [Beijing Institute of Radiation Medicine, Beijing (China); Zhu, Maoxiang, E-mail: zhumx@nic.bmi.ac.cn [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-10-01

    Purpose: Radiation-induced pulmonary fibrosis results from thoracic radiation therapy and severely limits radiation therapy approaches. CD4{sup +}CD25{sup +}FoxP3{sup +} regulatory T cells (Tregs) as well as epithelium-to-mesenchyme transition (EMT) cells are involved in pulmonary fibrosis induced by multiple factors. However, the mechanisms of Tregs and EMT cells in irradiation-induced pulmonary fibrosis remain unclear. In the present study, we investigated the influence of Tregs on EMT in radiation-induced pulmonary fibrosis. Methods and Materials: Mice thoraxes were irradiated (20 Gy), and Tregs were depleted by intraperitoneal injection of a monoclonal anti-CD25 antibody 2 hours after irradiation and every 7 days thereafter. Mice were treated on days 3, 7, and 14 and 1, 3, and 6 months post irradiation. The effectiveness of Treg depletion was assayed via flow cytometry. EMT and β-catenin in lung tissues were detected by immunohistochemistry. Tregs isolated from murine spleens were cultured with mouse lung epithelial (MLE) 12 cells, and short interfering RNA (siRNA) knockdown of β-catenin in MLE 12 cells was used to explore the effects of Tregs on EMT and β-catenin via flow cytometry and Western blotting. Results: Anti-CD25 antibody treatment depleted Tregs efficiently, attenuated the process of radiation-induced pulmonary fibrosis, hindered EMT, and reduced β-catenin accumulation in lung epithelial cells in vivo. The coculture of Tregs with irradiated MLE 12 cells showed that Tregs could promote EMT in MLE 12 cells and that the effect of Tregs on EMT was partially abrogated by β-catenin knockdown in vitro. Conclusions: Tregs can promote EMT in accelerating radiation-induced pulmonary fibrosis. This process is partially mediated through β-catenin. Our study suggests a new mechanism for EMT, promoted by Tregs, that accelerates radiation-induced pulmonary fibrosis.

  10. Critical appraisal of the role of ruxolitinib in myeloproliferative neoplasm-associated myelofibrosis

    Directory of Open Access Journals (Sweden)

    Barosi G

    2015-05-01

    Full Text Available Giovanni Barosi,1 Vittorio Rosti,1 Robert Peter Gale2 1Center for the Study of Myelofibrosis, IRCCS Policlinico S Matteo Foundation, Pavia, Italy; 2Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK Abstract: The recent approval of molecular-targeted therapies for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF has dramatically changed its therapeutic landscape. Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is now widely used for first- and second-line therapy in persons with MPN-MF, especially those with disease-related splenomegaly, intermediate- or high-risk disease, and constitutional symptoms. The goal of this work is to critically analyze data supporting use of ruxolitinib in the clinical settings approved by the US Food and Drug Administration (FDA and European Medicines Agency (EMA. We systematically reviewed the literature and analyzed the risk of biases in the two randomized studies (COMFORT I and COMFORT II on which FDA and EMA approval was based. Our strategy was to apply the Grading of Recommendation, Assessment, Development and Evaluation (GRADE approach by evaluating five dimensions of evidence: (1 overall risk of bias, (2 imprecision, (3 inconsistency, (4 indirectness, and (5 publication bias. Based on these criteria, we downgraded the evidence from the COMFORT I and COMFORT II trials for performance, attrition, and publication bias. In the disease-associated splenomegaly sphere, we upgraded the quality of evidence because of large effect size but downgraded it because of comparator choice and outcome indirectness (quality of evidence, low. In the sphere of treating persons with intermediate- or high-risk disease, we downgraded the evidence because of imprecision in effect size measurement and population indirectness. In the sphere of disease-associated symptoms, we upgraded the evidence because of the large effect size, but downgraded it

  11. Radiation-induced VEGF-C expression and endothelial cell proliferation in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Hsuan [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Pan, Shiow-Lin; Wang, Jing-Chi; Teng, Che-Ming [National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Kuo, Sung-Hsin [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Department of Internal Medicine, Taipei (China); Cheng, Jason Chia-Hsien [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Graduate Institute of Clinical Medicine, Taipei (China)

    2014-12-15

    The present study was undertaken to investigate whether radiation induces the expression of vascular endothelial growth factor C (VEGF-C) through activation of the PI3K/Akt/mTOR pathway,subsequently affecting endothelial cells. Radiotherapy-induced tumor micro-lymphatic vessel density (MLVD) was determined in a lung cancer xenograft model established in SCID mice. The protein expression and phosphorylation of members of the PI3K/Akt/mTOR pathway and VEGF-C secretion and mRNA expression in irradiated lung cancer cells were assessed by Western blot analysis, enzyme-linked immunosorbent assays (ELISAs), and reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, specific chemical inhibitors were used to evaluate the role of the PI3K/Akt/mTOR signaling pathway. Conditioned medium (CM) from irradiated control-siRNA or VEGF-C-siRNA-expressing A549 cells was used to evaluate the proliferation of endothelial cells by the MTT assay. Radiation increased VEGF-C expression in a dose-dependent manner over time at the protein but not at the mRNA level. Radiation also up-regulated the phosphorylation of Akt, mTOR, 4EBP, and eIF4E, but not of p70S6K. Radiation-induced VEGF-C expression was down-regulated by LY294002 and rapamycin (both p < 0.05). Furthermore, CM from irradiated A549 cells enhanced human umbilical vein endothelial cell (HUVEC) and lymphatic endothelial cell (LEC) proliferation, which was not observed with CM from irradiated VEGF-C-siRNA-expressing A549 cells. Radiation-induced activation of the PI3K/Akt/mTOR signaling pathway increases VEGF-C expression in lung cancer cells, thereby promoting endothelial cell proliferation. (orig.) [German] Die vorliegende Studie untersucht, ob die Strahlung die Expression von VEGF-C (vascular endothelial growth factor C) mittels Aktivierung des PI3K/Akt/mTOR-Signalwegs induziert und anschliessend die endothelialen Zellen beeinflusst. Die durch Strahlentherapie induzierte Mikrolymphgefaessdichte (MLVD) im Tumor wurde in

  12. Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor, E-mail: ikoturbash@uams.edu [Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Miousse, Isabelle R. [Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Sridharan, Vijayalakshmi [Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Nzabarushimana, Etienne; Skinner, Charles M. [Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Melnyk, Stepan B.; Pavliv, Oleksandra [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Hauer-Jensen, Martin [Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205 (United States); Nelson, Gregory A. [Departments of Basic Sciences and Radiation Medicine, Loma Linda University, Loma Linda, CA 92354 (United States); Boerma, Marjan [Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2016-05-15

    Highlights: • Radiation-induced dynamic changes in cardiac DNA methylation were detected. • Early LINE-1 hypomethylation was followed by hypermethylation at a later time-point. • Radiation affected one-carbon metabolism in the heart tissue. • Irradiation resulted in accumulation of satellite DNA mRNA transcripts. - Abstract: DNA methylation is a key epigenetic mechanism, needed for proper control over the expression of genetic information and silencing of repetitive elements. Exposure to ionizing radiation, aside from its strong genotoxic potential, may also affect the methylation of DNA, within the repetitive elements, in particular. In this study, we exposed C57BL/6J male mice to low absorbed mean doses of two types of space radiation—proton (0.1 Gy, 150 MeV, dose rate 0.53 ± 0.08 Gy/min), and heavy iron ions ({sup 56}Fe) (0.5 Gy, 600 MeV/n, dose rate 0.38 ± 0.06 Gy/min). Radiation-induced changes in cardiac DNA methylation associated with repetitive elements were detected. Specifically, modest hypomethylation of retrotransposon LINE-1 was observed at day 7 after irradiation with either protons or {sup 56}Fe. This was followed by LINE-1, and other retrotransposons, ERV2 and SINE B1, as well as major satellite DNA hypermethylation at day 90 after irradiation with {sup 56}Fe. These changes in DNA methylation were accompanied by alterations in the expression of DNA methylation machinery and affected the one-carbon metabolism pathway. Furthermore, loss of transposable elements expression was detected in the cardiac tissue at the 90-day time-point, paralleled by substantial accumulation of mRNA transcripts, associated with major satellites. Given that the one-carbon metabolism pathway can be modulated by dietary modifications, these findings suggest a potential strategy for the mitigation and, possibly, prevention of the negative effects exerted by ionizing radiation on the cardiovascular system. Additionally, we show that the methylation status and

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

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available 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.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.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.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 applicability of these

  14. Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suzy [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Kwon, Eun Kyung; Lee, B. S.; Lee, Seung Hee; Park, B. S.; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2007-12-15

    Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according

  15. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms

    Science.gov (United States)

    Pietra, D; Rumi, E; Ferretti, V V; Buduo, C A Di; Milanesi, C; Cavalloni, C; Sant'Antonio, E; Abbonante, V; Moccia, F; Casetti, I C; Bellini, M; Renna, M C; Roncoroni, E; Fugazza, E; Astori, C; Boveri, E; Rosti, V; Barosi, G; Balduini, A; Cazzola, M

    2016-01-01

    A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation of CALR, the calreticulin gene. A 52-bp deletion (type 1) and a 5-bp insertion (type 2 mutation) are the most frequent variants. These indels might differentially impair the calcium binding activity of mutant calreticulin. We studied the relationship between mutation subtype and biological/clinical features of the disease. Thirty-two different types of CALR variants were identified in 311 patients. Based on their predicted effect on calreticulin C-terminal, mutations were classified as: (i) type 1-like (65%); (ii) type 2-like (32%); and (iii) other types (3%). Corresponding CALR mutants had significantly different estimated isoelectric points. Patients with type 1 mutation, but not those with type 2, showed abnormal cytosolic calcium signals in cultured megakaryocytes. Type 1-like mutations were mainly associated with a myelofibrosis phenotype and a significantly higher risk of myelofibrotic transformation in essential thrombocythemia. Type 2-like CALR mutations were preferentially associated with an essential thrombocythemia phenotype, low risk of thrombosis despite very-high platelet counts and indolent clinical course. Thus, mutation subtype contributes to determining clinical phenotype and outcomes in CALR-mutant myeloproliferative neoplasms. CALR variants that markedly impair the calcium binding activity of mutant calreticulin are mainly associated with a myelofibrosis phenotype. PMID:26449662

  16. Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

    Science.gov (United States)

    Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

    2016-06-01

    At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels 3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients.

  17. Real world epidemiology of myeloproliferative neoplasms: a population based study in Korea 2004-2013.

    Science.gov (United States)

    Byun, Ja Min; Kim, Young Jin; Youk, Taemi; Yang, John Jeongseok; Yoo, Jongha; Park, Tae Sung

    2017-03-01

    Myeloproliferative neoplasms (MPNs), with an expected increment in number, impose substantial economic and social burdens. To this end, we conducted a nationwide population-based descriptive epidemiology study. We also investigated medical cost associated with MPNs. Prevalence was the highest for essential thrombocythemia (ET) (range 4.1-9.0 per 100,000), followed by polycythemia vera (PV) (range 2.8-5.4 per 100,000) and primary myelofibrosis (PMF) (range 0.5-0.9 per 100,000). ET incurred the highest cumulative total cost at US$35 million and the most frequent hospital visits, while PMF incurred the highest average cost per person at US$5000. The mean hemoglobin level was 16.9 ± 2.2 g/dL for PV males and 15.5 ± 2.7 g/dL for PV females. Further analyses on hemoglobin levels showed the true positive rate of PV from the significantly elevated hemoglobin group (defined as >18.5 g/dL for men and >16.5 g/dL for women) was 3.01% and that of MPNs was 3.1%. Here, we provide the biggest population-based report on MPN epidemiology that can readily be used as a representative Asian data.

  18. The Mutation Profile of Calreticulin in Patients with Myeloproliferative Neoplasms and Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Jingyi Wang

    2016-08-01

    Full Text Available Objective: Calreticulin (CALR plays important roles in cell proliferation, apoptosis, and immune responses. CALR mutations were described recently in Janus kinase 2 gene (JAK2-negative or MPLnegative primary myelofibrosis (PMF and essential thrombocythemia (ET patients. CALR trails JAK2 as the second most mutated gene in myeloproliferative neoplasms (MPNs. However, little is known about CALR mutation in Chinese patients with leukemia. In the present study, a cohort of 305 Chinese patients with hematopoietic neoplasms was screened for CALR mutations, with the aim of uncovering the frequency of CALR mutations in leukemia and MPNs. Materials and Methods: Polymerase chain reaction and direct sequencing were performed to analyze mutations of CALR in 305 patients with hematopoietic malignancies, including 135 acute myeloid leukemia patients, 57 acute lymphoblastic leukemia patients, and 113 MPN patients. Results: CALR mutations were found in 10.6% (12 of 113 of samples from patients with MPNs. CALR mutations were determined in 11.3% (6 of 53, 21.7% (5 of 23, and 9.1% (1/11 of patients with ET, PMF, and unclassifiable MPN, respectively. Conclusion: We showed that MPN patients carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels compared to those with mutated JAK2. However, all of the leukemia patients had negative results for CALR mutations.

  19. Atomistic Analysis Of Radiation-Induced Segregation In Ion-Irradiated Stainless Steel 316

    Directory of Open Access Journals (Sweden)

    Lee G.-G.

    2015-06-01

    Full Text Available Stainless steel (SS is a well-known material for the internal parts of nuclear power plants. It is known that these alloys exhibit radiation-induced segregation (RIS at point defect sinks at moderate temperature, while in service. The RIS behavior of SS can be a potential problem by increasing the susceptibility to irradiation-assisted stress corrosion cracking. In this work, the RIS behavior of solute atoms at sinks in SS 316 irradiated with Fe4+ ions were characterized by atom probe tomography (APT. There were torus-shaped defects along with a depletion of Cr and enrichment of Ni and Si. These clusters are believed to be dislocation loops resulting from irradiation. The segregation of solutes was also observed for various defect shapes. These observations are consistent with other APT results from the literature. The composition of the clusters was analyzed quantitatively almost at the atomic scale. Despite the limitations of the experiments, the APT analysis was well suited for discovering the structure of irradiation defects and performing a quantitative analysis of RIS in irradiated specimens.

  20. Simulating and Detecting Radiation-Induced Errors for Onboard Machine Learning

    Science.gov (United States)

    Wagstaff, Kiri L.; Bornstein, Benjamin; Granat, Robert; Tang, Benyang; Turmon, Michael

    2009-01-01

    Spacecraft processors and memory are subjected to high radiation doses and therefore employ radiation-hardened components. However, these components are orders of magnitude more expensive than typical desktop components, and they lag years behind in terms of speed and size. We have integrated algorithm-based fault tolerance (ABFT) methods into onboard data analysis algorithms to detect radiation-induced errors, which ultimately may permit the use of spacecraft memory that need not be fully hardened, reducing cost and increasing capability at the same time. We have also developed a lightweight software radiation simulator, BITFLIPS, that permits evaluation of error detection strategies in a controlled fashion, including the specification of the radiation rate and selective exposure of individual data structures. Using BITFLIPS, we evaluated our error detection methods when using a support vector machine to analyze data collected by the Mars Odyssey spacecraft. We found ABFT error detection for matrix multiplication is very successful, while error detection for Gaussian kernel computation still has room for improvement.

  1. Radiation-induced degradation of sodium alginate and its plant growth promotion effect

    Directory of Open Access Journals (Sweden)

    H.L. Abd El-Mohdy

    2017-02-01

    Full Text Available Alginate was irradiated as a solid with 60Co gamma rays in the dose range of 20–100 kGy to investigate the effect of radiation on alginates. One of the principle factors for reducing the cost is achieving the degradation at low irradiation doses which occurs with addition of chemical initiator to NaAlg during irradiation process that leads to a synergistic effect, which remarkably increases the degradation efficiency of alginate. The factors affecting the degradation process such as irradiation dose and potassium per-sulfate (KPS addition were studied. The average molecular weight of the irradiated alginate was investigated in detail by using several complementary techniques such as chromatography and viscometry. The lowest molecular weight of alginate resulted at 100 kGy and added KPS, whereas the highest one at 20 kGy in absence of KPS. Characterization of the oligoalginates obtained by radiation degradation was performed by FT-IR and UV–vis spectroscopy, XRD and TGA. The effect of water-soluble radiation-induced alginate fractions on the growth promotion of Faba bean plant was studied. The highest plant growth and seed yield compared with control occurred for plants sprayed with low molecular weight NaAlg fractions (treated with 100 kGy and added KPS.

  2. Low-dose X-ray radiation induces structural alterations in proteins.

    Science.gov (United States)

    Borshchevskiy, Valentin; Round, Ekaterina; Erofeev, Ivan; Weik, Martin; Ishchenko, Andrii; Gushchin, Ivan; Mishin, Alexey; Willbold, Dieter; Büldt, Georg; Gordeliy, Valentin

    2014-10-01

    X-ray-radiation-induced alterations to protein structures are still a severe problem in macromolecular crystallography. One way to avoid the influence of radiation damage is to reduce the X-ray dose absorbed by the crystal during data collection. However, here it is demonstrated using the example of the membrane protein bacteriorhodopsin (bR) that even a low dose of less than 0.06 MGy may induce structural alterations in proteins. This dose is about 500 times smaller than the experimental dose limit which should ideally not be exceeded per data set (i.e. 30 MGy) and 20 times smaller than previously detected specific radiation damage at the bR active site. To date, it is the lowest dose at which radiation modification of a protein structure has been described. Complementary use was made of high-resolution X-ray crystallography and online microspectrophotometry to quantitatively study low-dose X-ray-induced changes. It is shown that structural changes of the protein correlate with the spectroscopically observed formation of the so-called bR orange species. Evidence is provided for structural modifications taking place at the protein active site that should be taken into account in crystallographic studies which aim to elucidate the molecular mechanisms of bR function.

  3. Anisotropic Radiation-Induced Segregation in 316L Austenitic Stainless Steel with Grain Boundary Character

    Energy Technology Data Exchange (ETDEWEB)

    Christopher M. Barr; Gregory A. Vetterick; Kinga A. Unocic; Khalid Hattar; Xian-Ming Bai; Mitra L. Taheri

    2014-04-01

    Radiation-induced segregation (RIS) and subsequent depletion of chromium along grain boundaries has been shown to be an important factor in irradiation-assisted stress corrosion cracking in austenitic face-centered cubic (fcc)-based alloys used for nuclear energy systems. A full understanding of RIS requires examination of the effect of the grain boundary character on the segregation process. Understanding how specific grain boundary structures respond under irradiation would assist in developing or designing alloys that are more efficient at removing point defects, or reducing the overall rate of deleterious Cr segregation. This study shows that solute segregation is dependent not only on grain boundary misorientation, but also on the grain boundary plane, as highlighted by markedly different segregation behavior for the __3 incoherent and coherent grain boundaries. The link between RIS and atomistic modeling is also explored through molecular dynamic simulations of the interaction of vacancies at different grain boundary structures through defect energetics in a simple model system. A key insight from the coupled experimental RIS measurements and corresponding defect–grain boundary modeling is that grain boundary–vacancy formation energy may have a critical threshold value related to the major alloying elements’ solute segregation.

  4. Exposure to ionizing radiation induced persistent gene expression changes in mouse mammary gland

    Directory of Open Access Journals (Sweden)

    Datta Kamal

    2012-12-01

    Full Text Available Abstract Background Breast tissue is among the most sensitive tissues to the carcinogenic actions of ionizing radiation and epidemiological studies have linked radiation exposure to breast cancer. Currently, molecular understanding of radiation carcinogenesis in mammary gland is hindered due to the scarcity of in vivo long-term follow up data. We undertook this study to delineate radiation-induced persistent alterations in gene expression in mouse mammary glands 2-month after radiation exposure. Methods Six to eight week old female C57BL/6J mice were exposed to 2 Gy of whole body γ radiation and mammary glands were surgically removed 2-month after radiation. RNA was isolated and microarray hybridization performed for gene expression analysis. Ingenuity Pathway Analysis (IPA was used for biological interpretation of microarray data. Real time quantitative PCR was performed on selected genes to confirm the microarray data. Results Compared to untreated controls, the mRNA levels of a total of 737 genes were significantly (p Conclusions Exposure to a clinically relevant radiation dose led to long-term activation of mammary gland genes involved in proliferative and metabolic pathways, which are known to have roles in carcinogenesis. When considered along with downregulation of a number of tumor suppressor genes, our study has implications for breast cancer initiation and progression after therapeutic radiation exposure.

  5. The effect of environmental humidity on radiation-induced degradation of carrageenans.

    Science.gov (United States)

    Sen, Murat; Toprak, Deniz; Güven, Olgun

    2014-12-19

    Better understanding of the chemistry of radiation-induced degradation is becoming of increasing importance on account of the utilization of polymeric materials in a variety of radiation environments as well as beneficial uses of degraded polymers. In this report the importance of environmental humidity on the degrading effect of radiation has been considered from the point of view of controlling the molecular weights of kappa- and iota-carrageenans. These two polysaccharides were irradiated in solid form under strictly controlled environmental humidity conditions by incubating and later irradiating the samples over saturated aqueous salt solutions of NaCl, NaNO3 and MgCl2. The degradation was followed in detail by a careful gel permeation chromatographic analysis of their respective molecular weights before and after irradiation. The chain scission yield values G(S) were found to decrease with the water adsorbed from environment at every absorbed dose in the range of 5-100 kGy. On the other hand at very high water uptakes the yield of chain scission again increases especially at low doses. The decrease in degradation yield was attributed to the plastifying effect of water trapped in between the polymer chains facilitating the macroradical recombinations thus reducing the extent of chain scission. This study showed that although carrageenans were irradiated in solid form, the difference in their water uptake from changing environmental humidity has a profound effect in controlling their molecular weights by irradiation with ionizing radiation.

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

    Science.gov (United States)

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

    2016-12-01

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

  7. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy.

    Science.gov (United States)

    Tamarov, Konstantin P; Osminkina, Liubov A; Zinovyev, Sergey V; Maximova, Ksenia A; Kargina, Julia V; Gongalsky, Maxim B; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P; Sentis, Marc; Ivanov, Andrey V; Nikiforov, Vladimir N; Kabashin, Andrei V; Timoshenko, Victor Yu

    2014-11-13

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50 °C under relatively low nanoparticle concentrations (heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

  8. Prognosis of surgically treated radiation-induced damage to the intestine

    Energy Technology Data Exchange (ETDEWEB)

    Jahnson, S.; Westerborn, O. (Orebro Medical Center Hospital, Orebro (Sweden)); Gerdin, B. (Akademiska Sjukhuset, Uppsala (Sweden))

    1992-10-01

    A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the intestinal tract were retrospectively reviewed and clinical and surgical factors were related to the ultimate prognosis by multivariate analysis. The first operation was performed on the small intestine in 47 patients, the large intestine in 32 patients or both in nine patients. Postoperative complications occurred in 35 patients (40%), with fatal outcome in 12 (13%). Thirty-one patients (35%) required further surgery and altogether 19 patients (22%) ultimately died from RID. Negative prognostic factors after the first operation were post-operative intestinal leak (P < 0.05) and operation for fistula or perforation (P < 0.01). The outcome after the last operation was negatively influenced by intestinal leak (P < 0.001) by the choice of bypass as operative procedure (P < 0.01) and by operation for fistula or perforation (P < 0.01). In addition, 43% of the patients in whom the disease had progressed between two explorations died from RID. Thus, the severity of the RID as diagnosed at laparotomy, and progression of the disease between two subsequent explorations were related to the prognosis. Care should be taken to avoid intestinal leak. Resections should be preferred to bypass of injured intestine whenever possible. (author).

  9. Radiatively Induced Type II seesaw and Vector-like 5/3 Charge Quarks

    CERN Document Server

    Franceschini, R

    2013-01-01

    Understanding small neutrino masses in type II seesaw models with TeV scale SM triplet Higgs bosons requires that its coupling with the standard model Higgs doublet H be dialed down to be order eV to KeV, which is a fine-tuning by a factor of $10^{-11}-10^{-8}$ with respect to the weak scale. We present a SUSY extension of the type II seesaw model where this dimensionful small coupling is radiatively induced, thus making its smallness natural. This model has an exotic vector-like quark doublet which contains a quark X with electric charge 5/3 and a top partner t'. We discuss in details the phenomenology of the model paying special attention to the consequences of the interactions of the the exotic heavy quarks and the scalars of the model. Implications for neutrinoless double beta decay and for the LHC experiments are discussed in detail. Remarkably, in this model both the seesaw triplet and the heavy quarks can manifest at colliders in a host of different signatures, including some that significantly differ ...

  10. The role of niobium carbide in radiation induced segregation behaviour of type 347 austenitic stainless steel

    Science.gov (United States)

    Ahmedabadi, Parag; Kain, Vivekanand; Gupta, Manu; Samajdar, I.; Sharma, S. C.; Bhagwat, P.; Chowdhury, R.

    2011-08-01

    The effect of niobium carbide precipitates on radiation induced segregation (RIS) behaviour in type 347 stainless steel was investigated. The material in the as-received condition was irradiated using double-loop 4.8 MeV protons at 300 °C for 0.43 dpa (displacement per atom). The RIS in the proton irradiated specimen was characterized using double-loop electrochemical potentiokinetic reactivation (DL-EPR) test followed by atomic force microscopic examination. The nature of variation of DL-EPR values with the depth matched with the variation of the calculated irradiation damage (dpa) with the depth. The attack on grain boundaries during EPR tests was negligible indicating absence of chromium depletion zones. The interface between niobium carbide and the matrix acts as a sink for point defects generated during irradiation and this had reduced point defect flux toward grain boundaries. The attack was noticed at a few large cluster of niobium carbide after the DL-EPR test at the depth of maximum attack for the irradiated specimen. Pit-like features were not observed within the matrix indicating the absence of chromium depletion regions within the matrix.

  11. Ultraviolet-radiation-induced methane emissions from meteorites and the Martian atmosphere.

    Science.gov (United States)

    Keppler, Frank; Vigano, Ivan; McLeod, Andy; Ott, Ulrich; Früchtl, Marion; Röckmann, Thomas

    2012-05-30

    Almost a decade after methane was first reported in the atmosphere of Mars there is an intensive discussion about both the reliability of the observations--particularly the suggested seasonal and latitudinal variations--and the sources of methane on Mars. Given that the lifetime of methane in the Martian atmosphere is limited, a process on or below the planet's surface would need to be continuously producing methane. A biological source would provide support for the potential existence of life on Mars, whereas a chemical origin would imply that there are unexpected geological processes. Methane release from carbonaceous meteorites associated with ablation during atmospheric entry is considered negligible. Here we show that methane is produced in much larger quantities from the Murchison meteorite (a type CM2 carbonaceous chondrite) when exposed to ultraviolet radiation under conditions similar to those expected at the Martian surface. Meteorites containing several per cent of intact organic matter reach the Martian surface at high rates, and our experiments suggest that a significant fraction of the organic matter accessible to ultraviolet radiation is converted to methane. Ultraviolet-radiation-induced methane formation from meteorites could explain a substantial fraction of the most recently estimated atmospheric methane mixing ratios. Stable hydrogen isotope analysis unambiguously confirms that the methane released from Murchison is of extraterrestrial origin. The stable carbon isotope composition, in contrast, is similar to that of terrestrial microbial origin; hence, measurements of this signature in future Mars missions may not enable an unambiguous identification of biogenic methane.

  12. Model of radiation-induced gain degradation of NPN bipolar junction transistor at different dose rates

    Science.gov (United States)

    Qifeng, Zhao; Yiqi, Zhuang; Junlin, Bao; Wei, Hu

    2015-06-01

    Ionizing-radiation-induced current gain degradation in NPN bipolar junction transistors is due to an increase in base current as a result of recombination at the surface of the device. A model is presented which identifies the physical mechanism responsible for current gain degradation. The increase in surface recombination velocity due to interface states results in an increase in base current. Besides, changing the surface potential along the base surface induced by the oxide-trapped charges can also lead to an increased base current. By combining the production mechanisms of oxide-trapped charges and interface states, this model can explain the fact that the current gain degradation is more severe at a low dose rate than at a high dose rate. The radiations were performed in a Co60 source up to a total dose of 70 krad(Si). The low dose rate was 0.1 rad(Si)/s and the high dose rate was 10 rad(Si)/s. The model accords well with the experimental results. Project supported by the National Natural Science Foundation of China (Nos. 61076101, 61204092).

  13. Aloe vera for prevention of radiation-induced dermatitis: a self-controlled clinical trial.

    Science.gov (United States)

    Haddad, P; Amouzgar-Hashemi, F; Samsami, S; Chinichian, S; Oghabian, M A

    2013-08-01

    To evaluate an Aloe vera lotion for prevention of radiation-induced dermatitis, all patients with a prescription of radiotherapy to a minimum dose of 40 Gy were eligible provided that their treatment area could be divided into two symmetrical halves. Patients were given a lotion of Aloe vera to use on one half of the irradiated area, with no medication to be used on the other half. The grade of dermatitis in each half was recorded weekly until 4 weeks after the end of radiotherapy. The trial enrolled 60 patients (mean age: 52 years; 67% women). Most patients had breast cancer (38%), followed by pelvic (32%), head-and-neck (22%), and other cancers (8%). Field size was 80-320 cm(2) (mean: 177 cm(2)), and the dose of radiotherapy was 40-70 Gy (mean: 54 Gy). Concurrent chemotherapy was administered in 20 patients. From week 4 to week 6 of radiotherapy and then at weeks 2 and 4 after radiotherapy, the mean grade of dermatitis with and without Aloe vera was 0.81 and 1.10 (p Aloe vera reduces the intensity of radiationinduced dermatitis.

  14. Radiation-induced cell proliferation in the parotid and submandibular glands of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peter, B.; Van Waarde, M.A.W.H.; Konings, A.W.T. [Univ. of Groningen (Netherlands); Vissink, A. [Univ. of Groningen (Netherlands)]|[Univ. Hospital, Groningen (Netherlands); `s-Gravenmade, E.J. [Univ. Hospital, Groningen (Netherlands)

    1994-11-01

    Repopulation of tissues with cells at damaged sites is an important feature in the recovery of radiation-induced tissue injury. To obtain insight into the regenerative process in salivary gland tissue, proliferative activity was measured as a function of time in the different epithelial cell compartments of rat parotid and submandibular glands after local X irradiation with a single dose of 15 Gy. Bromodeoxyuridine-labeling indices were determined before and 10 h and 1, 3, 6, 10, 15, 20 and 30 days after irradiation. In both glands, X irradiation caused cell death and cell cycle delay manifested during the first day. Three days after irradiation, cell proliferation started in the intercalated duct. Six days after irradiation, proliferation was also observed in acinar and granular convoluted tubule cells. The striated ducts showed proliferative activity starting at day 6 (parotid) and day 10 (submandibular), respectively. The results of this study suggest that after 15 Gy of X rays repopulation takes place in all cell compartments. From the present study it cannot be deduced if these cells are originating solely from progenitor cells residing in the intercalated duct or if cells of the other compartments are also stimulated. Proliferative activity was found to be higher in the intercalated duct compartment of the parotid gland than of the submandibular gland, which may be related to the suggested greater radiosensitivity and thus a greater demand for cell replenishment in the parotid gland. 41 refs., 4 figs., 1 tab.

  15. [Salivary gland stem cells : Can they restore radiation-induced salivary gland dysfunction?].

    Science.gov (United States)

    Rotter, N; Schwarz, S; Jakob, M; Brandau, S; Wollenberg, B; Lang, S

    2010-06-01

    Adult stem cells are actively investigated in the fields of regenerative medicine and tissue engineering, as they exhibit specific characteristics that make them promising candidates for cellular therapies. Depending on their tissue of origin these characteristics include long-term proliferation and the capacity to differentiate into various cell types. To date adult stem cells have been isolated from a multitude of tissues. Non-embryogenic adult tissues contain only small numbers of such stem cells and the derivation of such tissues can cause comorbidities. Therefore, there is ongoing interest in the identification and characterisation of novel cell sources for stem cell isolation and characterisation.Recently, salivary gland tissue has also been explored as a possible source of stem cells, first in animals and later in humans. Such salivary gland-derived stem cells might be useful in the treatment of radiation-induced salivary gland hypofunction, and possibly also in other diseases with loss of acinar cells, such as sequelae of radio iodine treatment or Sjögren's disease.In this paper we review the current status of salivary gland stem cell biology and application and discuss the possible role of stem cells in the development of novel therapies for salivary gland dysfunctions such as postradiogenic xerostomia.

  16. Drinking beer reduces radiation-induced chromosome aberrations in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Monobe, Manami [Chiba Univ. (Japan). Graduate School of Science and Technology; Ando, Koichi [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-09-01

    We here investigated and reported the effects of beer drinking on radiation-induced chromosome aberrations in blood lymphocytes. Human blood that was collected either before or after drinking a 700 ml beer was in vitro irradiated with 200 kVp X rays or 50 keV/{mu}m carbon ions. The relation between the radiation dose and the aberration frequencies (fragments and dicentrics) was significantly (P<0.05) lower for lymphocytes collected 3 h after beer drinking than those before drinking. Fitting the dose response to a linear quadratic model showed that the alpha term of carbon ions was significantly (P<0.05) decreased by beer drinking. A decrease of dicentric formation was detected as early as 0.5 h after beer drinking, and lasted not shorter than 4.5 h. The mitotic index of lymphocytes was higher after beer drinking than before, indicating that a division delay would not be responsible for the low aberrations induced by beer drinking. An in vitro treatment of normal lymphocytes with 0.1 M ethanol, which corresponded to a concentration of 6-times higher than the maximum ethanol concentration in the blood after beer drinking, reduced the dicentric formation caused by X-ray irradiation, but not by carbon-ion irradiation. The beer-induced reduction of dicentric formation was not affected by serum. It is concluded that beer could contain non-ethanol elements that reduce the chromosome damage of lymphocytes induced by high-LET radiation. (author)

  17. Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons.

    Science.gov (United States)

    Xu, Shangcheng; Zhou, Zhou; Zhang, Lei; Yu, Zhengping; Zhang, Wei; Wang, Yuan; Wang, Xubu; Li, Maoquan; Chen, Yang; Chen, Chunhai; He, Mindi; Zhang, Guangbin; Zhong, Min

    2010-01-22

    Increasing evidence indicates that oxidative stress may be involved in the adverse effects of radiofrequency (RF) radiation on the brain. Because mitochondrial DNA (mtDNA) defects are closely associated with various nervous system diseases and mtDNA is particularly susceptible to oxidative stress, the purpose of this study was to determine whether radiofrequency radiation can cause oxidative damage to mtDNA. In this study, we exposed primary cultured cortical neurons to pulsed RF electromagnetic fields at a frequency of 1800 MHz modulated by 217 Hz at an average special absorption rate (SAR) of 2 W/kg. At 24 h after exposure, we found that RF radiation induced a significant increase in the levels of 8-hydroxyguanine (8-OHdG), a common biomarker of DNA oxidative damage, in the mitochondria of neurons. Concomitant with this finding, the copy number of mtDNA and the levels of mitochondrial RNA (mtRNA) transcripts showed an obvious reduction after RF exposure. Each of these mtDNA disturbances could be reversed by pretreatment with melatonin, which is known to be an efficient antioxidant in the brain. Together, these results suggested that 1800 MHz RF radiation could cause oxidative damage to mtDNA in primary cultured neurons. Oxidative damage to mtDNA may account for the neurotoxicity of RF radiation in the brain.

  18. Radiation-Induced Changes in Serum Lipidome of Head and Neck Cancer Patients

    Directory of Open Access Journals (Sweden)

    Karol Jelonek

    2014-04-01

    Full Text Available Cancer radiotherapy (RT induces response of the whole patient’s body that could be detected at the blood level. We aimed to identify changes induced in serum lipidome during RT and characterize their association with doses and volumes of irradiated tissue. Sixty-six patients treated with conformal RT because of head and neck cancer were enrolled in the study. Blood samples were collected before, during and about one month after the end of RT. Lipid extracts were analyzed using MALDI-oa-ToF mass spectrometry in positive ionization mode. The major changes were observed when pre-treatment and within-treatment samples were compared. Levels of several identified phosphatidylcholines, including (PC34, (PC36 and (PC38 variants, and lysophosphatidylcholines, including (LPC16 and (LPC18 variants, were first significantly decreased and then increased in post-treatment samples. Intensities of changes were correlated with doses of radiation received by patients. Of note, such correlations were more frequent when low-to-medium doses of radiation delivered during conformal RT to large volumes of normal tissues were analyzed. Additionally, some radiation-induced changes in serum lipidome were associated with toxicity of the treatment. Obtained results indicated the involvement of choline-related signaling and potential biological importance of exposure to clinically low/medium doses of radiation in patient’s body response to radiation.

  19. Radiation-induced defects in strontium carbonate rod for EPR dosimetry applications

    Science.gov (United States)

    Rushdi, M. A. H.; Abdel-Fattah, A. A.; Soliman, Y. S.

    2017-02-01

    The radiation-induced defects in strontium carbonate (SrCO3) rod dosimeter in the dose range of 2.5 Gy-25 kGy was investigated using electron paramagnetic resonance (EPR) technique. The EPR spectra of γ-irradiated strontium carbonate (SC) rods exhibit a strong EPR signal with the spectroscopic splitting g-factor 2.008 and a weak signal at g-factor 2.003. This signal increases with increasing irradiation dose. The dose-response function has a good linearity in the low dose range of 2.5-500 Gy and slight sub-linearity in the high dose range of 0.5-25 kGy. The dosimeter is nearly humidity independent in the level of 33-77% relative humidity during irradiation. The temperature coefficient of the dose-response function is 0.22% per °C in the temperature range of 20-40 °C. The rod dosimeter exhibits a maximum deviation from water equivalency by 7% in the energy range of 0.3-5 MeV. The overall uncertainty of dose determination using SC dosimeter is 5.2% and 4.54% (2σ) for low and high dose range, respectively.

  20. Breast cancer risk among Swedish hemangioma patients and possible consequences of radiation-induced genomic instability

    Energy Technology Data Exchange (ETDEWEB)

    Eidemueller, Markus, E-mail: markus.eidemueller@helmholtz-muenchen.de [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, 85764 Neuherberg (Germany); Holmberg, Erik [Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Goeteborg (Sweden); Jacob, Peter [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, 85764 Neuherberg (Germany); Lundell, Marie [Department of Medical Physics, Radiumhemmet, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Karlsson, Per [Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Goeteborg (Sweden)

    2009-10-02

    Breast cancer incidence among 17,158 female Swedish hemangioma patients was analyzed with empirical excess relative risk models and with a biologically-based model of carcinogenesis. The patients were treated in infancy mainly by external application of radium-226. The mean and median absorbed doses to the breast were 0.29 and 0.04 Gy, and a total of 678 breast cancer cases have been observed. Both models agree very well in the risk estimates with an excess relative risk and excess absolute risk at the age of 50 years, about the mean age of breast cancer incidence, of 0.25 Gy{sup -1}(95% CI 0.14; 0.37) and 30.7 (10{sup 5}BYRGy){sup -1} (95% CI 16.9; 42.8), respectively. Models incorporating effects of radiation-induced genomic instability were developed and applied to the hemangioma cohort. The biologically-based description of the radiation risk was significantly improved with a model of genomic instability at an early stage of carcinogenesis.

  1. Surgical therapy of radiation-induced lesions of the colon and rectum

    Energy Technology Data Exchange (ETDEWEB)

    Miholic, J.; Schwarz, C.; Moeschl, P.

    1988-06-01

    Thirty-six operations for late sequelae of radiotherapy were carried out in 31 patients from 1971 to 1986. The most frequent indications for surgery were stricture (58 percent) and fistula (29 percent). In the first 8 year period from 1971 through 1978, 13 of 14 operations were diversions (colostomy or by-pass). From 1979 through 1986, a more aggressive approach prevailed. Only 32 percent of the operations were diversions. This more aggressive strategy was accompanied by a decrease of the postoperative mortality rate from 21 percent through 1978 to 0 in the later period. The overall complication rate was 23 percent. Complications were relatively more frequent after two-layer sutured or stapled anastomoses and after resection or fistula closure without temporary colostomy. We conclude that in radiation-induced colonic and rectal lesions, diversion should be performed in patients with unproved cure of disease or tumor persistence. Resection and fistula closure can be carried out safely, and a temporary colostomy is strongly recommended.

  2. A human esophageal epithelial cell model for study of radiation induced cancer and DNA repair

    Science.gov (United States)

    Huff, Janice; Patel, Zarana; Hada, Megumi; Cucinotta, Francis A.

    For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma. Development of squamous cell carcinoma of the esophagus is associated with radiation exposure, as revealed by the significant enhanced in incidence rates for this type of cancer in the survivors of the atomic bomb detonations in Japan. It is also associated with poor nutritional status and micronutrient deficiencies, which are also important issues for long duration spaceflight. The possible synergies between nutritional issues and radiation exposure are unknown. Here we present the results of preliminary characterization of both normal and hTERT-immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of gamma-H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron.

  3. Radiation-induced blood-brain barrier changes: pathophysiological mechanisms and clinical implications.

    Science.gov (United States)

    d'Avella, D; Cicciarello, R; Angileri, F F; Lucerna, S; La Torre, D; Tomasello, F

    1998-01-01

    The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely understood. The possibility of a primary change in blood-brain barrier (BBB) associated with microvascular damage was investigated. Rats were exposed to conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid (AIB) technique coupled with standard electron microscopy (EM) and morphometric techniques as well as studies of the transcapillary passage of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB increased significantly in cerebral cortex. EM disclosed vesicular transport of HRP across the intact endothelium without opening of the tight junctions. Ninety days after WBR, well-defined alterations of the microvasculature were observed. The main feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Data suggest a possible association between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain cerebral dysfunction. We hypothesize the following sequence of pathophysiological events: WBR causes an early increase in BBB permeability, which produces perivascular edema and microvascular collapse. The interference with microcirculation affects blood flow and energy supply to the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

  4. Modeling of excimer laser radiation induced defect generation in fluoride phosphate glasses

    Science.gov (United States)

    Natura, U.; Ehrt, D.

    2001-03-01

    Fluoride phosphate (FP) glasses with low phosphate content are high-transparent in the deep ultraviolet (UV) range and attractive candidates for UV-optics. Their optical properties are complementary to fluoride crystals. The anomalous partial dispersion makes them desirable for optical lens designs to reduce the secondary spectrum. Their UV transmission is limited by trace impurities introduced by raw materials and decreases when exposed to UV-radiation (lamps, lasers). The experiments of the paper published previously in this journal were used in order to separate radiation induced absorption bands in the fluoride phosphate glass FP10. In this paper the generation mechanism of the phosphorus-oxygen related hole center POHC 2 is investigated in detail in glasses of various compositions (various phosphate and impurity contents) in order to predict the transmission loss in case of long-time irradiation. Experiments were carried out using ArF- and KrF-excimer lasers (ns-pulses). POHC 2 generation strongly depends on the phosphate content and on the content of Pb 2+. A model was developed on these terms. Rate equations are formulated, incorporating the influence of the Pb 2+-content on the defect generation, a two-step creation term including an energy transfer process and a one-photon bleaching term. This results in a set of coupled nonlinear differential equations. Absorption coefficients and lifetimes of the excited states were calculated as well. Experimental results compared well with the numerical analysis of the theoretical rate equations.

  5. Radiation induced grafting of tetrafluoroethylene on Nafion Films for ion exchange membrane application

    Energy Technology Data Exchange (ETDEWEB)

    Geraldes, Adriana Napoleao; Silva, Dionisio Furtunato da; Ferreto, Helio Fernando Rodrigues; Souza, Camila Pinheiro; Parra, Duclerc Fernandes; Lugao, Ademar Benevolo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Grafting of TFE nanocomposites onto Nafion was studied for synthesis of ion exchange membranes. Radiation-induced grafting of TFE gas onto Nafion films was investigated after simultaneous irradiation using a {sup 60}Co source. The thermal degradation of polytetrafluoroethylene (PTFE) waste has been used for production of TFE. Nafion films were irradiated at 15 kGy dose at room temperature and chemical changes were monitored after contact with TFE gas for grafting. The modified films were evaluated by differential scanning calorimetry analysis (DSC), thermogravimetric analysis (TG), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Characterization by XRD suggests crystallinity changes after TFE grafting. The ion exchange capacity (IEC) of membranes was determined by acid-base titration and the values for modified films were achieved similar to Nafion pristine films. DSC measurements revealed a displacement in the endothermic peaks and it was probably associated with the TFE graft. The graft forces the Nafion polymer chains to re-organize themselves and form a more cross-linked structure within the clusters. (author)

  6. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy

    Science.gov (United States)

    Tamarov, Konstantin P.; Osminkina, Liubov A.; Zinovyev, Sergey V.; Maximova, Ksenia A.; Kargina, Julia V.; Gongalsky, Maxim B.; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P.; Sentis, Marc; Ivanov, Andrey V.; Nikiforov, Vladimir N.; Kabashin, Andrei V.; Timoshenko, Victor Yu

    2014-11-01

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

  7. Measurements of Prompt Radiation-Induced Conductivity of Pyralux®

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, E. Frederick [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; Zarick, Thomas Andrew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; McLain, Michael Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; Sheridan, Timothy J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; Preston, Eric F. [ITT Exelis, Colorado Springs, CO (United States); Stringer, Thomas Arthur [ITT Exelis, Colorado Springs, CO (United States)

    2014-01-01

    In this report, measurements of the prompt radiation-induced conductivity (RIC) in 3 mil samples of Pyralux® are presented as a function of dose rate, pulse width, and applied bias. The experiments were conducted with the Medusa linear accelerator (LINAC) located at the Little Mountain Test Facility (LMTF) near Ogden, UT. The nominal electron energy for the LINAC is 20 MeV. Prompt conduction current data were obtained for dose rates ranging from ~2 x 109 rad(Si)/s to ~1.1 x 1011 rad(Si)/s and for nominal pulse widths of 50 ns and 500 ns. At a given dose rate, the applied bias across the samples was stepped between -1500 V and 1500 V. Calculated values of the prompt RIC varied between 1.39x10-8 Ω-1 · m-1 and 2.67x10-7 Ω-1 · m-1 and the prompt RIC coefficient varied between 1.25x10-18 Ω-1 · m-1/rad/s and 1.93x10-17 Ω-1 · m-1/rad/s.

  8. Measurements of the temperature dependence of radiation induced conductivity in polymeric dielectrics

    Science.gov (United States)

    Gillespie, Jodie

    This study measures Radiation Induced Conductivity (RIC) in five insulating polymeric materials over temperatures ranging from ~110 K to ~350 K: polyimide (PI or Kapton HN(TM) and Kapton E(TM)), polytetraflouroethylene (PTFE or Teflon(TM)), ethylene-tetraflouroethylene (ETFE or Tefzel(TM)), and Low Density Polyethylene (LDPE). RIC occurs when incident ionizing radiation deposits energy and excites electrons into the conduction band of insulators. Conductivity was measured when a voltage was applied across vacuum-baked, thin film polymer samples in a parallel plate geometry. RIC was calculated as the difference in sample conductivity under no incident radiation and under an incident ~4 MeV electron beam at low incident dose rates of 0.01 rad/sec to 10 rad/sec. The steady-state RIC was found to agree well with the standard power law relation, sigmaRIC(D˙) = kRIC(T) D˙Delta(T) between conductivity, sigmaRIC and adsorbed dose rate, D˙. Both the proportionality constant, kRIC, and the power, Delta, were found to be temperature-dependent above ~250 K, with behavior consistent with photoconductivity models developed for localized trap states in disordered semiconductors. Below ~250 K, kRIC and Delta exhibited little change in any of the materials.

  9. Dislocation dynamics simulations of interactions between gliding dislocations and radiation induced prismatic loops in zirconium

    Science.gov (United States)

    Drouet, Julie; Dupuy, Laurent; Onimus, Fabien; Mompiou, Frédéric; Perusin, Simon; Ambard, Antoine

    2014-06-01

    The mechanical behavior of Pressurized Water Reactor fuel cladding tubes made of zirconium alloys is strongly affected by neutron irradiation due to the high density of radiation induced dislocation loops. In order to investigate the interaction mechanisms between gliding dislocations and loops in zirconium, a new nodal dislocation dynamics code, adapted to Hexagonal Close Packed metals, has been used. Various configurations have been systematically computed considering different glide planes, basal or prismatic, and different characters, edge or screw, for gliding dislocations with -type Burgers vectors. Simulations show various interaction mechanisms such as (i) absorption of a loop on an edge dislocation leading to the formation of a double super-jog, (ii) creation of a helical turn, on a screw dislocation, that acts as a strong pinning point or (iii) sweeping of a loop by a gliding dislocation. It is shown that the clearing of loops is more favorable when the dislocation glides in the basal plane than in the prismatic plane explaining the easy dislocation channeling in the basal plane observed after neutron irradiation by transmission electron microscopy.

  10. Bevacizumab as a treatment option for radiation-induced cerebral necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; Nawatny, Jens [Univ. Hospital Duesseldorf (Germany). Dept. of Radiology; Hoffmann, Thomas K. [Duisburg-Essen Univ., Essen (Germany). Dept. of Otorhinolaryngology; Peiper, Matthias; Orth, Klaus [Hospital Essen-Sued, Essen (Germany). Dept. of Surgery; Gerber, Peter Arne [Univ. Hospital Duesseldorf (Germany). Dept. of Dermatology; Rusnak, Ethelyn [State Univ. of New York, Buffalo, NY (United States). Dept. of Anesthesiology; Lammering, Guido [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; MAASTRO Clinic, Maastricht (Netherlands). Radiation Oncology

    2011-02-15

    Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

  11. Radiation induced skin cancer the chest wall 30 years later from breast cancer operation

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Kouji; Togawa, Tamotsu; Hasegawa, Takeshi; Matsunami, Hidetoshi; Ikeda, Tsuneko [Matsunami General Hospital, Kasamatsu, Gifu (Japan); Matsuo, Youichi

    1998-10-01

    This paper describes the skin cancer on the frontal chest wall induced by postoperative irradiation 30 years later from mastectomy. The patients was a 62-year-old woman, who received mastectomy of the right breast cancer (invasive ductal carcinoma, comedo type) at 31 years old, and received the postoperative radiotherapy of total 11,628 rad over 38 times. On the first medical examination in author`s hospital, the patient had an ulcer of about 10 cm diameter and was diagnosed the radiation induced skin cancer (well differentiated squamous cell carcinoma) in the biopsy. Because of the general condition of the patient was extremely bad and the skin cancer had highly developed, the excision was thought to be impossible. The radiotherapy (16 Gy) and combined local chemotherapy by OK 432 and Bleomycin were performed. In spite of the short term treatment, these therapies were effective on the reduction of the tumor size and the hemostasis, and brought the patient the improvement of QOL. The general condition of the patient improved to be stable and she recovered enough to go out from the hospital for 6 months. After 10 months, she showed anorexia and dyspnea and died after about 1 year from the admission. The present case is extremely rare, and it is required the radical therapy like the excision of chest wall at early stage. (K.H.)

  12. Structure and properties of the radiation-induced intermediates produced from HCN in noble gas matrices

    Science.gov (United States)

    Kameneva, Svetlana V.; Tyurin, Daniil A.; Feldman, Vladimir I.

    2016-07-01

    In this work we report the results of systematic studies on the radiation-induced transformations in HCN/Ng systems (Ng=Ne, Ar, Kr or Xe) at 7 K using a combination of FTIR and EPR spectroscopy. It was shown that HCN underwent efficient decomposition producing H atoms, CN radicals and HNC isomer. The thermally induced reactions of H atoms in different matrices result in the formation of two isomeric radicals, H2CN and trans-HCNH, the former being predominated. The temperature dependent dynamics of CN and H2CN radicals in a krypton matrix was observed by EPR spectroscopy in solid krypton. The vibrational frequencies, IR intensities and magnetic resonance parameters of H2CN and trans-HCNH radicals calculated at the CCSD(T) level are in reasonable agreement with the experimental results. It was found that HCNH radical could be effectively bleached with visible light. The comparison of experimental and computational data made it possible to assign a new vibrational band at 918 cm-1 in an Ar matrix (and the corresponding bands in Kr and Xe) to trans-HCNH radical. In addition, HKrCN was found in the case of krypton, whereas HXeCN and HXeNC were produced in solid xenon. The reaction mechanisms and contribution of different channels are discussed.

  13. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide.

    Science.gov (United States)

    Damian, Diona L; Patterson, Clare R S; Stapelberg, Michael; Park, Joohong; Barnetson, Ross St C; Halliday, Gary M

    2008-02-01

    UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub

  14. On the radiation-induced segregation: Contribution of interstitial mechanism in Fe–Cr alloys

    Energy Technology Data Exchange (ETDEWEB)

    Pechenkin, V.A.; Molodtsov, V.L.; Ryabov, V.A. [Institute of Physics and Power Engineering, 249033 Obninsk (Russian Federation); Terentyev, D., E-mail: dterenty@sckcen.be [SCK-CEN, Nuclear Materials Science Institute, Boeretang 200, B-2400 Mol (Belgium)

    2013-02-15

    In this work, we perform molecular dynamics simulations to study the diffusion characteristics of a self-interstitial atom (SIA) in BCC Fe–Cr alloys and corresponding mass transport of Fe and Cr atoms via SIA migration mechanism. The calculations have been performed in the temperature range 600–1000 K in the alloys with Cr content 5–25 at.%, which is relevant for ferritic/martensitic steels. The results of atomistic simulations have been applied to evaluate the contribution of SIA diffusion mechanism to radiation-induced segregation (RIS) phenomenon. An original treatment is proposed in this work to account for the contribution from both vacancy and SIA mechanisms to RIS at sinks for point defects in multi-component system. By combining available experimental data on diffusion of Fe and Cr via vacancy mechanism with the results of MD simulations for SIAs, we demonstrate that enrichment of sinks by Cr atoms is possible in the Fe–Cr alloys containing less than 13% Cr. This result is discussed in the light of available experimental data on the RIS in Fe–Cr alloys and ferritic/martensitic steels. It is predicted that the degree of the Cr enrichment goes up with decreasing Cr content in the alloy and irradiation temperature.

  15. Radiation-induced decomposition of U(VI) phases to nanocrystals of UO"2 [rapid communication

    Science.gov (United States)

    Utsunomiya, Satoshi; Ewing, Rodney C.; Wang, Lu-Min

    2005-12-01

    U 6+-phases are common alteration products, under oxidizing conditions, of uraninite and the UO 2 in spent nuclear fuel. These U 6+-phases are subjected to a radiation field caused by the α-decay of U, or in the case of spent nuclear fuel, incorporated actinides, such as 239Pu and 237Np. In order to evaluate the effects of α-decay events on the stability of the U 6+-phases, we report, for the first time, the results of ion beam irradiations (1.0 MeV Kr 2+) of U 6+-phases. The heavy-particle irradiations are used to simulate the ballistic interactions of the recoil-nucleus of an α-decay event with the surrounding structure. The Kr 2+-irradiation decomposed the U 6+-phases to UO 2 nanocrystals at doses as low as 0.006 displacements per atom (dpa). U 6+-phases accumulate substantial radiation doses (˜1.0 displacement per atom) within 100,000 yr if the concentration of incorporated 239Pu is as high as 1 wt.%. Similar nanocrystals of UO 2 were observed in samples from the natural fission reactors at Oklo, Gabon. Multiple cycles of radiation-induced decomposition to UO 2 followed by alteration to U 6+-phases provide a mechanism for the remobilization of incorporated radionuclides.

  16. Mechanisms of radiation-induced emesis. Technical report, 10 February 1984-1 March 1987

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.

    1988-08-31

    Nausea and vomiting following radiation exposure are factors which may seriously limit the ability of humans to perform in military situations and are side effects of such significance in radiation therapy that they may limit the patient's acceptance of treatment regimes (1). At doses of 1.5 Gy approximately 50% of humans experience nausea and vomiting, while at 3.0 Gy the figure approaches 100%. While irradiation almost anywhere may produce symptoms, the upper abdomen is the most-sensitive site. Dogs, cats, and monkeys also vomit on exposure to ionizing radiation, although cats and monkeys are considerably more resistant than dogs and man. These studies were designed to attempt to determine the roles of the area postrema and the vagus in radiation-induced emesis by ablation and electrophysiological studies, and to test the effects of some drugs on the emetic response. In addition, the authorrecorded from neurons in the dog area postrema, applying substances which may be emetic, in an attempt to determine which transmitters, peptides and hormones might function as chemical mediators of emesis. Finally, he have tested the emetic effects of some of these substances given intravenously in awake dogs, with particular emphasis on study of the mechanism of action of emetic agents on the area postrema neurons.

  17. Original Research: Label-free detection for radiation-induced apoptosis in glioblastoma cells.

    Science.gov (United States)

    Qi, Dandan; Feng, Jingwen; Yang, Chengwen; Jin, Changrong; Sa, Yu; Feng, Yuanming

    2016-10-01

    Current flow cytometry (FCM) requires fluorescent dyes labeling cells which make the procedure costly and time consuming. This manuscript reports a feasibility study of detecting the cell apoptosis with a label-free method in glioblastoma cells. A human glioma cell line M059K was exposed to 8 Gy dose of radiation, which enables the cells to undergo radiation-induced apoptosis. The rates of apoptosis were studied at different time points post-irradiation with two different methods: FCM in combination with Annexin V-FITC/PI staining and a newly developed technique named polarization diffraction imaging flow cytometry. Totally 1000 diffraction images were acquired for each sample and the gray level co-occurrence matrix (GLCM) algorithm was used in morphological characterization of the apoptotic cells. Among the feature parameters extracted from each image pair, we found that the two GLCM parameters of angular second moment (ASM) and sum entropy (SumEnt) exhibit high sensitivities and consistencies as the apoptotic rates (Pa) measured with FCM method. In addition, no significant difference exists between Pa and ASM_S, Pa and SumEnt_S, respectively (P > 0.05). These results demonstrated that the new label-free method can detect cell apoptosis effectively. Cells can be directly used in the subsequent biochemical experiments as the structure and function of cells and biomolecules are well-preserved with this new method.

  18. Heavy-ion radiation induced Photosynthesis changes in Oryza sativa L.

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Li, Xishan; Meng, Qingmei

    The abnormal development of rice was observed frequently after the seed was exposed to heavy-ion radiation. The heavy-ion radiation could change the chloroplast structure in mesophyll cell by decreasing chloroplast grana and loosing the thylakoid lamellas. To study the mechanism of heavy-ion radiation induced photosynthesis changes, rice seed was exposed to 0-20 Gy dose of (12) C radiation. By measuring the changes of chlorophyll fluorescence parameters, the content of chlorophyll as well as the expression of CP24 in the leaves of rice at the three-leaf stage, we analyzed the influence mechanism of heavy-ion radiation on photosynthesis in rice. The results indicated that chlorophyll fluorescence parameter Fv/Fm and content of chlorophyll (including chlorophyll a, chlorophyll b and total chlorophyll) changed significantly in different doses. Both the relative expression of CP24 and its encoding gene lhcb6 altered after exposed to different dose of radiation. By using Pearson correlation analysis, we found that the 1 Gy was the bound of low-dose radiation. The possible molecular mechanisms and biological consequences of the observed changes are discussed. Key Words: Heavy-ion Radiation; Rice; Photosynthesis; Fv/Fm; CP24.

  19. The role of ER stress response on ionizing radiation-induced apoptosis in intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sang; Kim, Kwang Seok; Woo, Sang Keun; Lee, Yong Jin; Jeong, Jae Hoon; Lee, Yoon Jin; Kang, Seong Man; Lim, Young Bin [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-04-15

    Apoptosis in the intestinal epithelium is the primary pathologic factor that initiates radiation-induced intestinal injury. However, mechanism involved in ionizing radiation (IR)-induced apoptosis in the intestinal epithelium is not clearly understood. The endoplasmic reticulum (ER) stress is triggered by perturbation of the ER functions, leading to the activation of the unfolded protein response (UPR), an adaptive signaling cascade aimed at restoring ER homeostasis by facilitating the degradation of misfolded proteins and expanding the protein folding capacity of the cell. Recently, IR has also been shown to induce ER stress, thereby activating the UPR signaling pathway in intestinal epithelial cells. In this study, we report the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhance IR-induced caspase3 activation. Knockdown of xbp1 or atf6 with siRNA leads to inhibition of IR-induced caspase3 activation. Taken together, our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Our findings could contribute to the development of new strategies based on modulating ER stress responses to prevent IR-induced intestinal injury.

  20. Radiation induced dissolution of UO 2 based nuclear fuel - A critical review of predictive modelling approaches

    Science.gov (United States)

    Eriksen, Trygve E.; Shoesmith, David W.; Jonsson, Mats

    2012-01-01

    Radiation induced dissolution of uranium dioxide (UO 2) nuclear fuel and the consequent release of radionuclides to intruding groundwater are key-processes in the safety analysis of future deep geological repositories for spent nuclear fuel. For several decades, these processes have been studied experimentally using both spent fuel and various types of simulated spent fuels. The latter have been employed since it is difficult to draw mechanistic conclusions from real spent nuclear fuel experiments. Several predictive modelling approaches have been developed over the last two decades. These models are largely based on experimental observations. In this work we have performed a critical review of the modelling approaches developed based on the large body of chemical and electrochemical experimental data. The main conclusions are: (1) the use of measured interfacial rate constants give results in generally good agreement with experimental results compared to simulations where homogeneous rate constants are used; (2) the use of spatial dose rate distributions is particularly important when simulating the behaviour over short time periods; and (3) the steady-state approach (the rate of oxidant consumption is equal to the rate of oxidant production) provides a simple but fairly accurate alternative, but errors in the reaction mechanism and in the kinetic parameters used may not be revealed by simple benchmarking. It is essential to use experimentally determined rate constants and verified reaction mechanisms, irrespective of whether the approach is chemical or electrochemical.

  1. Radiation-induced polymerization and grafting of {beta}(-)pinene on silica surface

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Franco [Lupi Chemical Research Institute, Via Casilina 1626/A, 00133 Rome (Italy)], E-mail: cdcata@flashnet.it; Ursini, Ornella; Lilla, Edo; Angelini, Giancarlo [CNR, Institute of Chemical Metodologies, Area della Ricerca di Roma 1, Monterotondo Scalo, Rome (Italy)

    2008-05-15

    Poly-{beta}-pinene (pBp) was obtained on silica surface by {gamma} radiation-induced polymerization of {beta}(-)pinene in presence of silica gel with a specific surface area of 300 m{sup 2}/g. Different radiation doses were employed in the range 50-332 kGy. The pBp-silica hybrid samples obtained have been characterized by FT-IR spectroscopy and the amount of pBp on silica surface has been determined both by gravimetric and TGA measurements. The fraction of pBp chemically grafted on silica surface has been determined by the extraction of the pBp-silica hybrid with boiling toluene and was found to be 10-20% of the total pBp formed on silica surface. The optical activity of pBp extracted from the hybrid was studied by polarimetric measurements and found slightly lower than the typical specific optical rotation of pBp polymerized in bulk with radiation. The thermal stability of the pBp-silica hybrid materials was studied by thermogravimetric and differential thermal analysis. The results show lower thermal stability for the pBp-silica hybrid in comparison to pure pBp. Evidently, silica catalyzes the thermal decomposition of pBp at lower temperatures. Use of the pBp-silica hybrid as stationary phase for liquid chromatography for chiral separations has been proposed.

  2. Extract of Xylopia aethiopica (Annonaceae) protects against gamma-radiation induced testicular damage in Wistar rats.

    Science.gov (United States)

    Adaramoye, Oluwatosin Adekunle; Adedara, Isaac Adegboyega; Popoola, Bosede; Farombi, Ebenezer Olatunde

    2010-01-01

    Ionizing radiation is an important environmental risk factor and, a major therapeutic agent for cancer treatment. This study was designed to evaluate the protective effect of extract of Xylopia aethiopica (XA) on gamma-radiation-induced testicular damage in rats. Vitamin C (VC) served as the reference antioxidant during the study. The study consists of 4 groups of 11 rats each. Group I received corn oil (vehicle), groups II and IV were pretreated with XA (250 mg/kg) and VC (250mg/kg) for 6 weeks before and 8 weeks after exposure to gamma-radiation; group III was exposed to a single dose of gamma-radiation (5 Gy). Biochemical analysis revealed that gamma-irradiation caused a significant increase (p testicular lipid peroxidation (LPO) levels by 217% and 221%, respectively. Irradiated rats had markedly decreased testicular catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and reduced glutathione (GSH) levels. Irradiation resulted in 59% and 40% decreases in spermatozoa motility and live/dead sperm count, respectively, and a 161% increase in total sperm abnormalities. Histologically, testes of the irradiated rats showed extensive degenerative changes in the seminiferous tubules and defoliation of spermatocytes. Supplementation of XA and VC reversed the adverse effects of gamma-radiation on biochemical and histological indices of the rats. These findings demonstrated that Xylopia aethiopica has a protective effect by inhibiting oxidative damage in testes of irradiated rats.

  3. Molecular biology methods in assessing radiation-induced hereditary risks in humans

    Energy Technology Data Exchange (ETDEWEB)

    Kiuru, A. [University of Helsinki, Department of Biosciences, Division of Genetics, Helsinki (Finland)

    2004-12-01

    Effort to predict the genetic consequences for humans of exposure to ionising radiation has been one of the most important issues of human genetics over the past 60 years. To date, there has been little experimental knowledge on the genetic risks of human exposure to ionising radiation. Radiation-induced deleterious hereditary effects have not been detected in human populations - not even among the offspring of atomic bomb survivors in Hiroshima and Nagasaki. This does not mean deleterious hereditary effects do not exist in humans, but rather that they are small and/or difficult to detect because the normal incidence of inherited abnormalities is quite high in the human population. Thus, assessment of radiation-induced hereditary risks in humans has been based on the common knowledge of human heredity and on animal experiments. However, recent data have suggested that hyper-variable tandem repeat minisatellite loci provide a useful and sensitive experimental approach for monitoring radiation-induced germline mutations in humans. In order to investigate the feasibility of the minisatellite mutation screening system in assessing radiation-induced hereditary risks in humans, we examined the amount of hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers. The men studied received a median radiation dose of 109 mSv while working on the cleanup activities after the Chernobyl accident. We compared the minisatellite mutation rates of 155 children born to 147 Estonian Chernobyl cleanup workers after the accident to those of their 148 siblings born prior to it. In addition, 44 Estonian families, where the father had not been exposed to radiation, composed an additional control group. In all of these families, the paternity of the children was ascertained by using 5 minisatellite loci (APOB, HRAS, MCOB19, MCT118, and YNZ-22) in PCR-based analyses. Other 8 minisatellite loci (B6.7, CEB1, CEB15, CEB25, CEB36, MS1, MS31, and MS32) were used

  4. Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.

    Science.gov (United States)

    Guney, Yildiz; Ozel Turkcu, Ummuhani; Hicsonmez, Ayse; Nalca Andrieu, Meltem; Kurtman, Cengiz

    2007-01-01

    Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.

  5. Measurements of Prompt Radiation-Induced Conductivity of Pyralux®

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, E. Frederick [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; Zarick, Thomas Andrew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; McLain, Michael Lee [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; Sheridan, Timothy J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Radiation Effects Experimentation Dept.; Preston, Eric F. [ITT Exelis, Colorado Springs, CO (United States); Stringer, Thomas Arthur [ITT Exelis, Colorado Springs, CO (United States)

    2014-01-01

    In this report, measurements of the prompt radiation-induced conductivity (RIC) in 3 mil samples of Pyralux® are presented as a function of dose rate, pulse width, and applied bias. The experiments were conducted with the Medusa linear accelerator (LINAC) located at the Little Mountain Test Facility (LMTF) near Ogden, UT. The nominal electron energy for the LINAC is 20 MeV. Prompt conduction current data were obtained for dose rates ranging from ~2 x 109 rad(Si)/s to ~1.1 x 1011 rad(Si)/s and for nominal pulse widths of 50 ns and 500 ns. At a given dose rate, the applied bias across the samples was stepped between -1500 V and 1500 V. Calculated values of the prompt RIC varied between 1.39x10-8 Ω-1 · m-1 and 2.67x10-7 Ω-1 · m-1 and the prompt RIC coefficient varied between 1.25x10-18 Ω-1 · m-1/(rad/s) and 1.93x10-17 Ω-1 · m-1/(rad/s).

  6. Effects of different levels of vitamin C on UV radiation-induced DNA damage

    Institute of Scientific and Technical Information of China (English)

    Dianfeng Zhou; Hang Heng; Kang Ji; Weizhong Ke

    2005-01-01

    The Raman spectra of DNA in different levels of vitamin C with 10- and 30-min ultraviolet (UV) radiations were reported. The intensity of UV radiation was 18.68 W/m2. The experimental results proved that vitamin C could alone prevent UV radiation from damaging DNA, but the effects depended on the concentration of vitamin C. When the concentration of vitamin C was about 0.08-0.4 mmol/L, vitamin C decreased UV radiation-induced DNA's damage. When the concentration of vitamin C exceeded 0.4 mmol/L, vitamin C accelerated DNA's damage instead. Maybe the reason is that when DNA in aqueous solution is radiated by UV, free radicals come into being, and vitamin C can scavenge free radicals, so vitamin C in lower concentration can protect DNA. The quantity of free radicals is finite, when vitamin C is superfluous, free radicals have been scavenged absolutely and vitamin C is residual. Vitamin C is a strong reductant. When the mixture of DNA and residual vitamin C is radiated by UV, vitamin C reacts with DNA. The more residual vitamin C and the longer time of UV radiation, the more DNA is damaged.

  7. The role of interstitial binding in radiation induced segregation in W-Re alloys

    Science.gov (United States)

    Gharaee, Leili; Marian, Jaime; Erhart, Paul

    2016-07-01

    Due to their high strength and advantageous high-temperature properties, tungsten-based alloys are being considered as plasma-facing candidate materials in fusion devices. Under neutron irradiation, rhenium, which is produced by nuclear transmutation, has been found to precipitate in elongated precipitates forming thermodynamic intermetallic phases at concentrations well below the solubility limit. Recent measurements have shown that Re precipitation can lead to substantial hardening, which may have a detrimental effect on the fracture toughness of W alloys. This puzzle of sub-solubility precipitation points to the role played by irradiation induced defects, specifically mixed solute-W interstitials. Here, using first-principles calculations based on density functional theory, we study the energetics of mixed interstitial defects in W-Re, W-V, and W-Ti alloys, as well as the heat of mixing for each substitutional solute. We find that mixed interstitials in all systems are strongly attracted to each other with binding energies of -2.4 to -3.2 eV and form interstitial pairs that are aligned along parallel first-neighbor strings. Low barriers for defect translation and rotation enable defect agglomeration and alignment even at moderate temperatures. We propose that these elongated agglomerates of mixed-interstitials may act as precursors for the formation of needle-shaped intermetallic precipitates. This interstitial-based mechanism is not limited to radiation induced segregation and precipitation in W-Re alloys but is also applicable to other body-centered cubic alloys.

  8. Study of radiation-induced leakage current between adjacent devices in a CMOS integrated circuit

    Institute of Scientific and Technical Information of China (English)

    Ding Lili; Guo Hongxia; Chen Wei; Fan Ruyu

    2012-01-01

    Radiation-induced inter-device leakage is studied using an analytical model and TCAD simulation.There were some different opinions in understanding the process of defect build-up in trench oxide and parasitic leakage path turning on from earlier studies.To reanalyze this problem and make it beyond argument,every possible variable is considered using theoretical analysis,not just the change of electric field or oxide thickness independently.Among all possible inter-device leakage paths,parasitic structures with N-well as both drain and source are comparatively more sensitive to the total dose effect when a voltage discrepancy exists between the drain and source region.Since N-well regions are commonly connected to the same power supply,these kinds of structures will not be a problem in a real CMOS integrated circuit.Generally speaking,conduction paths of inter-device leakage existing in a real integrated circuit and under real electrical circumstances are not very sensitive to the total ionizing dose effect.

  9. Organotypic culture in three dimensions prevents radiation-induced transformation in human lung epithelial cells

    Science.gov (United States)

    El-Ashmawy, Mariam; Coquelin, Melissa; Luitel, Krishna; Batten, Kimberly; Shay, Jerry W.

    2016-08-01

    The effects of radiation in two-dimensional (2D) cell culture conditions may not recapitulate tissue responses as modeled in three-dimensional (3D) organotypic culture. In this study, we determined if the frequency of radiation-induced transformation and cancer progression differed in 3D compared to 2D culture. Telomerase immortalized human bronchial epithelial cells (HBECs) with shTP53 and mutant KRas expression were exposed to various types of radiation (gamma, +H, 56Fe) in either 2D or 3D culture. After irradiation, 3D structures were dissociated and passaged as a monolayer followed by measurement of transformation, cell growth and expression analysis. Cells irradiated in 3D produced significantly fewer and smaller colonies in soft agar than their 2D-irradiated counterparts (gamma P = 0.0004 +H P = 0.049 56Fe P < 0.0001). The cell culture conditions did not affect cell killing, the ability of cells to survive in a colony formation assay, and proliferation rates after radiation—implying there was no selection against cells in or dissociated from 3D conditions. However, DNA damage repair and apoptosis markers were increased in 2D cells compared to 3D cells after radiation. Ideally, expanding the utility of 3D culture will allow for a better understanding of the biological consequences of radiation exposure.

  10. Post treatment effect of Grewia asiatica against radiation-induced biochemical alterations in Swiss albino mice.

    Science.gov (United States)

    Sisodia, Rashmi; Singh, Smita; Sharma, K V; Ahaskar, Muktika

    2008-01-01

    The increasing use of nuclear radiation for human welfare necessitates the search for new, safe, and cost-effective radioprotectors not only for the personnel charged with the responsibility of testing or working with radiation in laboratories, but also for the general public. With this view, the present study has been undertaken to find out the possible radioprotective potential of the Grewia asiatica fruit pulp extract (GAE). It is reported to have a high content of antioxidants such as vitamin C, anthocyanin, folate carotenoids, etc. that may play a possible role in radioprotection. In the present investigation, healthy Swiss albino mice were selected from an inbred colony and divided into four groups: (i) control (vehicle treated), (ii) only GAE treated (700 mg/Kg. body wt./day for 15 consecutive days), (iii) irradiated (5 Gy), and (iv) irradiated + GAE treated. Mice were sacrificed at different autopsy intervals posttreatment, viz., 1-30 days. Blood was collected and liver was removed for various biochemical estimations, viz., glutathione (GSH) and lipid peroxidation. The results indicated that GAE posttreatment protects liver and blood against radiation-induced damage by inhibiting glutathione depletion and ameliorating lipid peroxidation levels that attended normal levels by day 30 posttreatment. Moreover, the magnitude of recovery from oxidative damage in terms of TBARS and GSH content was significantly higher (p<0.001) in the irradiated + GAE-treated group.

  11. Heparin fragments modulate the collagen phenotype of fibroblasts from radiation-induced subcutaneous fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    el Nabout, R.; Martin, M.; Remy, J.; Robert, L.; Lafuma, C. (Laboratoire de Biochimie de Tissu Conjonctif, Creteil (France))

    1989-10-01

    Acute local gamma irradiation of porcine skin induces, as in human skin, an extensive and mutilating sclerosis characterized by continuous expansion of the fibrosis invading the adjacent muscle and by accumulation of the macromolecular components of the extracellular matrix. Collagen synthesis, content, and types were studied in the presence of heparin fragments (100 micrograms/10(6) cells) in the culture medium, by measuring the incorporation of the radiolabeled precursor (3H)proline into confluent primary cultures of porcine fibroblasts obtained from normal and irradiated fibrotic dermis. Enhancement in collagen biosynthesis and deposition and preferential increase in collagen type III synthesis were observed in fibrotic fibroblast cultures when compared to those in normal dermis fibroblasts. The total collagen synthesis and the rate of collagen hydroxylation appear unmodified by heparin fragments both in normal and in fibrotic fibroblast cultures. But heparin fragments induce a 10- and 2-fold decrease, respectively, in collagen type III and type V syntheses by fibrosis fibroblasts. As only minor effects upon collagen type III and V are observed in cultures of normal dermis fibroblasts, these results highly suggest that heparin fragments are capable of specifically modulating the collagen phenotype of fibroblasts derived from radiation-induced dermis fibrosis and thus are able to regulate the fibrotic process.

  12. Investigation of gamma radiation induced changes in local structure of borosilicate glass by TDPAC and EXAFS

    Science.gov (United States)

    Kumar, Ashwani; Nayak, C.; Rajput, P.; Mishra, R. K.; Bhattacharyya, D.; Kaushik, C. P.; Tomar, B. S.

    2016-12-01

    Gamma radiation induced changes in local structure around the probe atom (Hafnium) were investigated in sodium barium borosilicate (NBS) glass, used for immobilization of high level liquid waste generated from the reprocessing plant at Trombay, Mumbai. The (NBS) glass was doped with 181Hf as a probe for time differential perturbed angular correlation (TDPAC) spectroscopy studies, while for studies using extended X-ray absorption fine structure (EXAFS) spectroscopy, the same was doped with 0.5 and 2 % (mole %) hafnium oxide. The irradiated as well as un-irradiated glass samples were studied by TDPAC and EXAFS techniques to obtain information about the changes (if any) around the probe atom due to gamma irradiation. TDPAC spectra of unirradiated and irradiated glasses were similar and reminescent of amorphous materials, indicating negligible effect of gamma radiation on the microstructure around Hafnium probe atom, though the quaqdrupole interaction frequency ( ω Q) and asymmetry parameter ( η) did show a marginal decrease in the irradiated glass compared to that in the unirradiated glass. EXAFS measurements showed a slight decrease in the Hf-O bond distance upon gamma irradiation of Hf doped NBS glass indicating densification of the glass matrix, while the cordination number around hafnium remains unchanged.

  13. Radiation-induced luminescence in magnesium aluminate spinel crystals and ceramics

    Science.gov (United States)

    Gritsyna, V. T.; Kazarinov, Yu. G.; Kobyakov, V. A.; Reimanis, I. E.

    2006-09-01

    Radioluminescence (RL) and thermoluminescence (TL) in spinel crystals and ceramics were investigated to elucidate the radiation-induced electronic processes in single crystals grown by Verneuil and Czochralski methods as well as transparent and translucent ceramics. Both RL and TL spectra demonstrate a UV-band related to electron-hole recombination luminescence at intrinsic defects; green and red luminescence are identified with emission of Mn 2+- and Cr 3+-ions, respectively. The kinetics of growth of different RL luminescence bands depending on dose at the prolonged X-irradiation shows the competitive character of charge and energy transfer between defects and impurity ions. The dependence of RL intensity on the temperature of the sample was measured in the range of 300-750 K and compared with TL for different emission bands. The variety of maxima in the temperature dependence of RL and in the glow curves of TL measured for different luminescence bands in spinels of different origins and crystalline forms is used to show that charge carrier traps and luminescence centers are not isolated defects but are complexes of defects and impurities. The formation, structure and properties of these complexes depend on the processing conditions.

  14. Comparison of dependent measures used to quantify radiation-induced taste aversion

    Energy Technology Data Exchange (ETDEWEB)

    Spector, A.C.; Smith, J.C.; Hollander, G.R. (Florida State Univ., Tallahassee (USA). Dept. of Psychology)

    1981-11-01

    Several commonly used measures of conditioned taste aversion were compared under a variety of experimental conditions. In the first experiment an aversion to a saccharin solution (0.1%) was conditioned by pairing this taste substance with a single 100 R exposure to Cobalt-60. Comparisons were performed between the following measures: a short-term single-bottle test, a 22-hour two-bottle preference test, a measure quantifying recovery from the aversion along with other measures derived from these tests. Appropriate control groups received saccharin and sham exposure, water and sham exposure, and water and radiation exposure in order to measure both neophobia and enhanced neophobia. In Experiment 2 the total whole body radiation exposure used to condition the taste aversion was varied in different groups from 50 to 300 R exposures and the effect on conditioning was measured using the dependent variables described in Experiment 1. In Experiment 3 radiation-induced taste aversion was studied in rats which had prior exposures to the saccharin solution. In all three studies it was shown that different interpretations result from measuring the conditioned aversion with the different dependent variables commonly used, and several measures are needed to give a fair and accurate description of learned taste aversion.

  15. Black tea extract: a supplementary antioxidant in radiation-induced damage to DNA and normal lymphocytes.

    Science.gov (United States)

    Ghosh, Debjani; Pal, Sandip; Saha, Chabita; Chakrabarti, Amit Kumar; Datta, Salil C; Dey, Subrata Kumar

    2012-01-01

    Myriad research has contributed significantly toward the understanding and identification of health benefits stemming from tea polyphenols and many other naturally occurring flavonoids present in fruits and vegetables. These flavonoids are known to mitigate reactive oxygen species-induced damage by scavenging them. In this study, hot-water black tea extract rich in flavonoids is evaluated as a supplementary antioxidant. The antioxidant efficacy of black tea extract was investigated by evaluating radioprotection conferred to pBR322 DNA, calf thymus DNA, and normal lymphocytes during gamma irradiation. The protection was measured by gel electrophoresis, fluorimetric study, cell viability assay, cytokinesis-blocked micronuclei assay, and comet assay. The 2,2-diphenyl-1-picrylhydrazyl scavenging ability of the tea extract used increased in a dose-dependent manner (IC50: 182.45 µg/mL). Positive correlation of radioprotection with antioxidant activity of black tea extract was observed in all systems. Maximum protection against radiation-induced damage was observed in pBR322 DNA and calf thymus DNA at ≥200 µg/mL of black tea extract. At a dose of black tea extract as low as 5 µg/mL, efficient radioprotection was observed in normal lymphocytes, which is encouraging and can be tested in the future as a natural antioxidant supplement during radiotherapy.

  16. Radiation-induced defects, energy storage and release in nitrogen solids

    Science.gov (United States)

    Savchenko, E.; Khyzhniy, I.; Uyutnov, S.; Bludov, M.; Barabashov, A.; Gumenchuk, G.; Bondybey, V.

    2017-02-01

    New trends in the study of radiation effects in nitrogen solids with a focus on the defect-induced processes are presented. An electron beam of subthreshold energy was used to generate radiation defects via electronic subsystem. Experimental techniques developed enabled us to detect neutral and charged defects of both signs. Defect production and desorption were monitored using optical and current emission spectroscopy: cathodoluminescence CL, thermally stimulated luminescence TSL and exoelectron emission TSEE along with the detection of postdesorption. Our results show stabilization and accumulation of radiation defects – ionic centres of both signs (N4 +, N3 +, N3 -), trapped electrons and radicals (N, N3). The neutralization reactions: N4 ++e-→N4 *→N2 *(a‘1Σu -)+N2 *(a‘1Σu -) +ΔE 1 →N2 +N2 +2hν+ΔE 2 and N3 ++e-→N*(2D)+N2(1Σg +)+ΔE 3→N(4S)+N2(1Σg +)+h γ+ΔE 3 are shown to be the basis of defect production and anomalous low-temperature post-desorption ALTpD. The part played by pre-existing and radiation-induced defects in energy storage is discussed.

  17. A dose-dependent perturbation in cardiac energy metabolism is linked to radiation-induced ischemic heart disease in Mayak nuclear workers.

    Science.gov (United States)

    Azimzadeh, Omid; Azizova, Tamara; Merl-Pham, Juliane; Subramanian, Vikram; Bakshi, Mayur V; Moseeva, Maria; Zubkova, Olga; Hauck, Stefanie M; Anastasov, Nataša; Atkinson, Michael J; Tapio, Soile

    2017-02-07

    Epidemiological studies show a significant increase in ischemic heart disease (IHD) incidence associated with total external gamma-ray dose among Mayak plutonium enrichment plant workers. Our previous studies using mouse models suggest that persistent alteration of heart metabolism due to the inhibition of peroxisome proliferator-activated receptor (PPAR) alpha accompanies cardiac damage after high doses of ionising radiation. The aim of the present study was to elucidate the mechanism of radiation-induced IHD in humans. The cardiac proteome response to irradiation was analysed in Mayak workers who were exposed only to external doses of gamma rays. All participants were diagnosed during their lifetime with IHD that also was the cause of death. Label-free quantitative proteomics analysis was performed on tissue samples from the cardiac left ventricles of individuals stratified into four radiation dose groups (0 Gy, 500 mGy). The groups could be separated using principal component analysis based on all proteomics features. Proteome profiling showed a dose-dependent increase in the number of downregulated mitochondrial and structural proteins. Both proteomics and immunoblotting showed decreased expression of several oxidative stress responsive proteins in the irradiated hearts. The phosphorylation of transcription factor PPAR alpha was increased in a dose-dependent manner, which is indicative of a reduction in transcriptional activity with increased radiation dose. These data suggest that chronic external radiation enhances the risk for IHD by inhibiting PPAR alpha and altering the expression of mitochondrial, structural, and antioxidant components of the heart.