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Sample records for radiation resistant tumors

  1. Radiation induction of drug resistance in RIF-1 tumors and tumor cells

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Moulder, J.E.

    1989-01-01

    The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

  2. Autophagy contributes to resistance of tumor cells to ionizing radiation.

    Science.gov (United States)

    Chaachouay, Hassan; Ohneseit, Petra; Toulany, Mahmoud; Kehlbach, Rainer; Multhoff, Gabriele; Rodemann, H Peter

    2011-06-01

    Autophagy signaling is a novel important target to improve anticancer therapy. To study the role of autophagy on resistance of tumor cells to ionizing radiation (IR), breast cancer cell lines differing in their intrinsic radiosensitivity were used. Breast cancer cell lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell survival and induction of autophagy after radiation exposure and pharmacological interference of the autophagic process. As marker for autophagy the appearance of LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting. Formation of autophagic vacuoles was monitored by immunofluorescence staining of LC3. LC3-I and LC3-II formation differs markedly in radioresistant MDA-MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231 cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence analysis of LC3-II positive vacuoles confirmed this differential effect. Pre-treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise, pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells. Our data clearly indicate that radioresistant breast tumor cells show a strong post-irradiation induction of autophagy, which thus serves as a protective and pro-survival mechanism in radioresistance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

    International Nuclear Information System (INIS)

    Moulder, J.E.; Hopwood, L.E.; Volk, D.M.; Davies, B.M.

    1991-01-01

    The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors

  4. Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

    International Nuclear Information System (INIS)

    Vordermark, D.; Brown, J.M.

    2003-01-01

    Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1α responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1α overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a benefit from specific hypoxia

  5. Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

    Energy Technology Data Exchange (ETDEWEB)

    Vordermark, D. [Dept. of Radiation Oncology, Univ. of Wuerzburg (Germany); Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States); Brown, J.M. [Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States)

    2003-12-01

    Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1{alpha} responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1{alpha} overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a

  6. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    International Nuclear Information System (INIS)

    Bree, Chris van; Kreder, Natasja Castro; Loves, Willem J.P.; Franken, Nicolaas A.P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5-fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000 were determined by clonogenic assay. Bivariate flowcytometry was performed to study cell cycle changes. Results: In the SWg, a complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein level. This was accompanied by a 10-fold decrease in dCK activity which resulted in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50-100 μM dFdC) induced radioenhancement in the dFdC-resistant cell lines similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in the parental lines. An early S-phase arrest was found in all cell lines after dFdC treatment where radioenhancement was achieved. Conclusions: In the dFdC-resistant lung tumor cell line SWg, the deficiency in dCK is related to the resistance to dFdC and ara-C. No cross-resistance was observed to other anti-tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing radiation was not altered in two different dFdC-resistant cell lines. Resistance to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation

  7. Dual responsive promoters to target therapeutic gene expression to radiation-resistant hypoxic tumor cells

    International Nuclear Information System (INIS)

    Chadderton, Naomi; Cowen, Rachel L.; Sheppard, Freda C.D.; Robinson, Suzanne; Greco, Olga; Scott, Simon D.; Stratford, Ian J.; Patterson, Adam V.; Williams, Kaye J.

    2005-01-01

    Purpose: Tumor hypoxia is unequivocally linked to poor radiotherapy outcome. This study aimed to identify enhancer sequences that respond maximally to a combination of radiation and hypoxia for use in genetic radiotherapy approaches. Methods and materials: The influence of radiation (5 Gy) and hypoxia (1% O 2 ) on reporter-gene expression driven by hypoxia (HRE) and radiation (Egr-1) responsive elements was evaluated in tumor cells grown as monolayers or multicellular spheroids. Hypoxia-inducible factor-1α (HIF-1α) and HIF-2α protein expression was monitored in parallel. Results: Of the sequences tested, an HRE from the phosphoglycerate kinase-1 gene (PGK-18[5+]) was maximally induced in response to hypoxia plus radiation in all 5 cell lines tested. The additional radiation treatment afforded a significant increase in the induction of PGK-18[5+] compared with hypoxia alone in 3 cell lines. HIF-1α/2α were induced by radiation but combined hypoxia/radiation treatment did not yield a further increase. The dual responsive nature of HREs was maintained when spheroids were irradiated after delivery of HRE constructs in a replication-deficient adenovirus. Conclusions: Hypoxia-responsive enhancer element sequences are dually responsive to combined radiation and hypoxic treatment. Their use in genetic radiotherapy in vivo could maximize expression in the most radio-resistant population at the time of radiation and also exploit microenvironmental changes after radiotherapy to yield additional switch-on

  8. Acquired Tumor Cell Radiation Resistance at the Treatment Site Is Mediated Through Radiation-Orchestrated Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Aravindan, Natarajan, E-mail: naravind@ouhsc.edu [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Aravindan, Sheeja; Pandian, Vijayabaskar; Khan, Faizan H.; Ramraj, Satish Kumar; Natt, Praveen [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Natarajan, Mohan [Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2014-03-01

    Purpose: Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Results: Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cells were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF-α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF-α, IL-1α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Conclusions: Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.

  9. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

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    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  10. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    International Nuclear Information System (INIS)

    Bradshaw, Tyler J.; Bowen, Stephen R.; Deveau, Michael A.; Kubicek, Lyndsay; White, Pamela; Bentzen, Søren M.; Chappell, Richard J.; Forrest, Lisa J.; Jeraj, Robert

    2015-01-01

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV max ; SUV mean ) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R 2 . Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV mean (P=.018), and midtreatment FLT SUV max (P=.006). Large decreases in FLT SUV mean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV max (P=.022) in combination with large FLT response from

  11. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    NARCIS (Netherlands)

    van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

  12. Vasculatures in Tumors Growing From Preirradiated Tissues: Formed by Vasculogenesis and Resistant to Radiation and Antiangiogenic Therapy

    International Nuclear Information System (INIS)

    Chen, Fang-Hsin; Chiang, Chi-Shiun; Wang, Chun-Chieh; Fu, Sheng-Yung; Tsai, Chien-Sheng; Jung, Shih-Ming; Wen, Chih-Jen; Lee, Chung-Chi; Hong, Ji-Hong

    2011-01-01

    Purpose: To investigate vasculatures and microenvironment in tumors growing from preirradiated tissues (pre-IR tumors) and study the vascular responses of pre-IR tumors to radiation and antiangiogenic therapy. Methods and Materials: Transgenic adenocarcinoma of the mouse prostate C1 tumors were implanted into unirradiated or preirradiated tissues and examined for vascularity, hypoxia, and tumor-associated macrophage (TAM) infiltrates by immunohistochemistry. The origin of tumor endothelial cells was studied by green fluorescent protein-tagged bone marrow (GFP-BM) transplantation. The response of tumor endothelial cells to radiation and antiangiogenic agent was evaluated by apoptotic assay. Results: The pre-IR tumors had obvious tumor bed effects (TBE), with slower growth rate, lower microvascular density (MVD), and more necrotic and hypoxic fraction compared with control tumors. The vessels were dilated, tightly adhered with pericytes, and incorporated with transplanted GFP-BM cells. In addition, hypoxic regions became aggregated with TAM. As pre-IR tumors developed, the TBE was overcome at the tumor edge where the MVD increased, TAM did not aggregate, and the GFP-BM cells did not incorporate into the vessels. The vessels at tumor edge were more sensitive to the following ionizing radiation and antiangiogenic agent than those in the central low MVD regions. Conclusions: This study demonstrates that vasculatures in regions with TBE are mainly formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Tumor bed effects could be overcome at the edge of larger tumors, but where vasculatures are formed by angiogenesis and sensitive to both treatments. Vasculatures formed by vasculogenesis should be the crucial target for the treatment of recurrent tumors after radiotherapy.

  13. Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

    2006-01-01

    Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

  14. Diffuse Reflectance Spectroscopy (DRS) of radiation-induced re-oxygenation in sensitive and resistant head and neck tumor xenografts

    Science.gov (United States)

    Dadgar, Sina; Rodríguez Troncoso, Joel; Rajaram, Narasimhan

    2018-02-01

    Currently, anatomical assessment of tumor volume performed several weeks after completion of treatment is the clinical standard to determine whether a cancer patient has responded to a treatment. However, functional changes within the tumor could potentially provide information regarding treatment resistance or response much earlier than anatomical changes. We have used diffuse reflectance spectroscopy to assess the short and long-term re-oxygenation kinetics of a human head and neck squamous cell carcinoma xenografts in response to radiation therapy. First, we injected UM-SCC-22B cell line into the flank of 50 mice to grow xenografts. Once the tumor volume reached 200 mm3 (designated as Day 1), the mice were distributed into radiation and control groups. Members of radiation group underwent a clinical dose of radiation of 2 Gy/day on Days 1, 4, 7, and 10 for a cumulative dose of 8 Gy. DRS spectra of these tumors were collected for 14 days during and after therapy, and the collected spectra of each tumor were converted to its optical properties using a lookup table-base inverse model. We found statistically significant differences in tumor growth rate between two groups which is in indication of the sensitivity of this cell line to radiation. We further acquired significantly different contents of hemoglobin and scattering magnitude and size in two groups. The scattering has previously been associated with necrosis. We furthermore found significantly different time-dependent changes in vascular oxygenation and tumor hemoglobin concentration in post-radiation days.

  15. DNA from radiation resistant human tumor cells transfers resistance to NIH/3T3 cells with varying degrees of penetrance

    International Nuclear Information System (INIS)

    Kasid, U.; Dritschilo, A.; Weichselbaum, R.

    1987-01-01

    Experimental evidence suggests that clinical radiation resistance may correlate with in vitro radiation survival parameters. Specifically, they isolated several cell lines from radioresistant head and neck carcinomas with D/sub 0/ values greater than 2 Gy. The authors co-transfected DNA from cell line SQ2OB (D/sub 0/ = 2.4 Gy) with the rhoSVNeO plasmid into NIH/3T3 cells (D/sub 0/ = 1.7 Gy). Antibiotic G418 resistant, transformed clones were isolated and confirmed by Southern blotting to contain human alu, as well as rhoSVNeO sequences. Screening for radiation resistance with 8Gy (Cs-137) revealed that 3 of 4 tested hybrid clones show a radiation survival intermediate between NIH/3T3 and SQ2OB. This suggests that radiation resistance is a dominant, transfectable phenotype of mammalian cells and can be expressed in more sensitive cells. Karyotyping of resistant hybrid clones shows the presence of double minute chromosomes. Secondary transfection results and experiments to clone the genetic factors responsible for radiation resistance are in progress and results will be reported

  16. Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors.

    Science.gov (United States)

    Narayanasamy, Ganesh; Zhang, Xin; Meigooni, Ali; Paudel, Nava; Morrill, Steven; Maraboyina, Sanjay; Peacock, Loverd; Penagaricano, Jose

    2017-08-01

    Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear-quadratic cell survival model. HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1-5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2 t ) value of 0·5. In addition, the mean ± SD of TR values for SF2 t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2 t value of 0.5. HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

  17. Cytoplasmic superoxide dismutase and catalase activity and resistance to radiation lethality in murine tumor cells

    International Nuclear Information System (INIS)

    Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Rosenberg, S.O.

    1986-01-01

    Reduced species of molecular oxygen are produced by the interaction of ionizing radiation with aqueous solutions containing molecular oxygen. The enzymes catalase and superoxide dismutase (SOD) are thought to function in vivo as scavengers of metabolically produced peroxide and superoxide respectively. SOD has been shown to protect against the lethal effects of ionizing radiation in vitro and in vivo. The authors have investigated the relationship between the cytosolic SOD catalase content and the sensitivity to radiation lethality of a number of murine cell lines (402AX, EL-4, MB-2T3, MB-4, MEL, P-815, SAI, SP-2, and SV-3T3). K/sub i/(CN - ) for murine Cu-Zn-SOD was determined to be 6.8 x 10 -6 M. No cytosolic Mn-SOD activity was found in any of the cell lines studied. No correlation was found between the cytosolic Cu-Zn-SOD or cytosolic catalase activity and the resistance to radiation lethality or the murine cell lines studied

  18. Tumor radiation responses and tumor oxygenation in aging mice

    International Nuclear Information System (INIS)

    Rockwell, S.

    1989-01-01

    EMT6 mouse mammary tumors transplanted into aging mice are less sensitive to radiation than tumors growing in young adult animals. The experiments reported here compare the radiation dose-response curves defining the survivals of tumor cells in aging mice and in young adult mice. Cell survival curves were assessed in normal air-breathing mice and in mice asphyxiated with N 2 to produce uniform hypoxia throughout the tumors. Analyses of survival curves revealed that 41% of viable malignant cells were severely hypoxic in tumors in aging mice, while only 19% of the tumor cells in young adult animals were radiobiologically hypoxic. This did not appear to reflect anaemia in the old animals. Treatment of aging animals with a perfluorochemical emulsion plus carbogen (95% O 2 /5% CO 2 ) increased radiation response of the tumors, apparently by improving tumor oxygenation and decreasing the number of severely hypoxic, radiation resistant cells in the tumors. (author)

  19. A study of radiation sensitivity and drug-resistance by DNA methylation in human tumor cell lines

    International Nuclear Information System (INIS)

    Jung, Il Lae; Kim, In Gyu; Kim, Kug Chan

    2009-12-01

    It has recently been known that functional loss of tumor suppressive genes may com from DNA methylation on the chromosome. This kind of tumorigenesis has became one of the major field related to the epigenetics, whose study would be an important fundamental approach in cancer therapy market. In this study, we firstly selected two radiation-resistant mutant H460 cells, which doesn't show any significant cytotoxic effect compared to their parental wild type H460. We found that the two mutants has decreased level of PTEN, whose expression has known to be related to the cell differentiation and growth. We also found that the level of PTEN was greatly different in two lung adenocarcinoma, H460 and A549, in which more radiation-resistant A549 cells showed the decreased PTEN expression. This difference in PTEN expression between two cells was resulted from their different methylation on 5 CpG islands. We expect to know more profoundly through investigating the PTEN-related downstream genes

  20. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  1. Tumor Heterogeneity and Drug Resistance

    International Nuclear Information System (INIS)

    Kucerova, L.; Skolekova, S.; Kozovska, Z.

    2015-01-01

    New generation of sequencing methodologies revealed unexpected complexity and genomic alterations linked with the tumor subtypes. This diversity exists across the tumor types, histologic tumor subtypes and subsets of the tumor cells within the same tumor. This phenomenon is termed tumor heterogeneity. Regardless of its origin and mechanisms of development it has a major impact in the clinical setting. Genetic, phenotypic and expression pattern diversity of tumors plays critical role in the selection of suitable treatment and also in the prognosis prediction. Intratumoral heterogeneity plays a key role in the intrinsic and acquired chemoresistance to cytotoxic and targeted therapies. In this review we focus on the mechanisms of intratumoral and inter tumoral heterogeneity and their relationship to the drug resistance. Understanding of the mechanisms and spatiotemporal dynamics of tumor heterogeneity development before and during the therapy is important for the ability to design individual treatment protocols suitable in the given molecular context. (author)

  2. Radiation resistant modified polypropylene

    International Nuclear Information System (INIS)

    Bojarski, J.; Zimek, Z.

    1997-01-01

    Radiation technology for production of radiation resistant polypropylene for medical use has been presented. The method consists in radiation induced copolymerization of polypropylene with ethylene and addition of small amount of copolymer of polyethylene and vinyl acetate. The material of proposed composition has a very good mechanical properties and elevated radiation resistivity decided on possibility of radiosterilization of products made of this material and designed for medical use. 3 figs, 3 tabs

  3. Biological improvement of radiation resistance

    Energy Technology Data Exchange (ETDEWEB)

    Chun, K J; Lee, Y K; Kim, J S; Kim, J K; Lee, S J

    2000-08-01

    To investigate the mechanisms of gene action related to the radiation resistance in microorganisms could be essentially helpful for the development of radiation protectants and hormeric effects of low dose radiation. This book described isolation of radiation-resistant microorganisms, induction of radiation-resistant and functionally improved mutants by gamma-ray radiation, cloning and analysis of the radiation resistance related genes and analysis of the expressed proteins of the radiation resistant related genes.

  4. Biological improvement of radiation resistance

    International Nuclear Information System (INIS)

    Chun, K. J.; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.

    2000-08-01

    To investigate the mechanisms of gene action related to the radiation resistance in microorganisms could be essentially helpful for the development of radiation protectants and hormeric effects of low dose radiation. This book described isolation of radiation-resistant microorganisms, induction of radiation-resistant and functionally improved mutants by gamma-ray radiation, cloning and analysis of the radiation resistance related genes and analysis of the expressed proteins of the radiation resistant related genes

  5. The influence of the stem cell marker ALDH and the EGFR-PI3 kinase act signaling pathway on the radiation resistance of human tumor cell lines

    International Nuclear Information System (INIS)

    Mihatsch, Julia

    2014-01-01

    Cancer is the second leading cause of death in industriated nations. Besides surgery and chemotherapy, radiotherapy (RT) is an important approach by which about 60% of patients are treated. The response of these patients to RT is very heterogenous. On the one hand, there are patients with tumors which are radiosensitive and can be cured, but on the other hand patients bear tumors which are quite resistant to radiotherapy. A Radioresistant phenotype of tumor cells causes treatment failure consequently leading to a limited response to radiotherapy. It is proposed, that radiotherapy outcome mainly depends on the potential of radiation on controlling growth, proliferation and survival of a specific population of tumor cells called cancer stem cells (CSCs) or tumor-initiating cells. Based on experimental studies so far reported it is assumed that the population of CSC varies in tumors from different entities and is relatively low compared to the tumor bulk cells in general. According to the CSC hypothesis, it might be concluded that the differential response of tumors to radiotherapy depends on CSC populations, since these supposedly slow replicating cells are able to initiate a tumor, to self renew indefinitely and to generate the differentiated progeny of a tumor. Besides the role of cancer stem cells in radiotherapy response, ionizing radiation (IR) activates the epidermal growth factor receptor (EGFR) and its downstream signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK) and Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathways. Among these pathways, PI3K/Akt is one of the most important pathways involved in post-irradiation survival: Activation of Akt results in activation of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs). DNA-PKcs is a core enzyme involved in repair of IR-induced DNA-double strand breaks (DNA-DSB) through non-homologous end joining (NHEJ). The aim of the

  6. Radiation therapy for digestive tumors

    International Nuclear Information System (INIS)

    Piedbois, P.; Levy, E.; Thirion, P.; Martin, L.; Calitchi, E.; Otmezguine, Y.; Le Bourgeois, J.P.

    1995-01-01

    This brief review of radiation therapy of digestive tumors in 1994 seeks to provide practical answers to the most commonly asked questions: What is the place of radiation therapy versus chemotherapy for the treatment of these patients ? What are the approved indications of radiation therapy and which avenues of research are being explored ? Radiation therapy is used in over two-thirds of patients referred to an oncology department for a gastrointestinal tract tumor. The main indications are reviewed: cancer of the rectum and anal canal and, to a lesser extent, cancer of the esophagus and pancreas. The main focuses of current research include radiation therapy-chemotherapy combinations, intraoperative radiation therapy, and radiation therapy of hepatobiliary tumors. (authors). 23 refs., 1 fig

  7. Effects of combinations of chemotherapy and radiation on the emergence of drug resistant cells in 9L rat brain tumor spheroids

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Arundel, C.; Vines, C.M.

    1987-01-01

    Repeated administration of antineoplastic chemotherapeutic agents is generally considered to induce and/or select for drug resistant cells. The authors recently begun to investigate whether chemotherapy interdigitated with radiation can minimize or eliminate the emergence of drug resiistent cells in 9L rat brain tumor spheroids grown from defined mixtures of cells sensitive (9L) and resistant (R/sub 3/) to BCNU. In this experimental system, the sister chromatid exchange (SCE) assay is used to quantitate the proportions of sensitive and resistant cells within the spheroids. While 9L and R/sub 3/ cell have different sensitivities to BCNU, they are equally sensitive to radiation. Mixed-cell spheroids consisting of 1% R/sub 3/ cells were treated with three doses of BCNU (10 μM) every 72 hr resulting in a shift in the 9L to R/sub 3/ ratio to greater than 50% R/sub 3/ cells. The combined protocols to be investigated will involve γ rays administered either 36 hr before or after each BCNU treatment. By initiating these combined protocols on spheroids of different sizes, the effectiveness of each protocol is evaluated with respect to the number of resistant cells present

  8. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

    2014-01-01

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  9. Radiation therapy of brain tumor

    International Nuclear Information System (INIS)

    Sung, K. J.; Lee, D. H.; Park, C. Y.

    1980-01-01

    One hundred and six cases of brain tumors were treated at the Yonsei Cancer Center from January 1972 to August 1978 by Co-60 teletherapy unit. We analyses their clinical findings, histopathological findings, treatment and results. In those cases which computerized tomography had been used before and after radiation therapy, changes in tumor size and the presence of edema or necrosis following treatment was evaluated. 1. Among 106 cases, 90 cases were primary brain tumors and 16 cases were metastatic brain tumors. Pituitary tumors (38), glioma (34) and pinealoma (10) composed of most of primary brain tumors. 2. Post treatment follow-up was possible in 38 cases more than 1 years. Four among 11 cases of giloma expired and survivors had considerable neurological symptoms except 2 cases. Sixty five percent (12/20) of pituitary tumors showed improvement of visual symptoms and all cases (7) of pinealoma which post treatment follow-up was possible, showed remarkable good response. 3. Findings of CT scan after radiation treatment were compatible with results of clinical findings and post treatment follow-up. It showed complete regression of tumor mass in one case of pinealoma and medulloblastoma. One case of pituitary tumor showed almost complete regression of tumor mass. It also showed large residual lesion in cases of glioblastoma multiforme and cystic astrocytoma.

  10. NEW RADIATION RESISTANT GREASES

    Energy Technology Data Exchange (ETDEWEB)

    DasGupta, Sharda; Slobodian, J. T.

    1962-11-20

    New radiation resistant greases were prepared from commercially available greases by carrying out radioinduced reactions with styrene. The radiation tolerances of the products were 250-1000 fold more than the starting materials and any product of similar properties now available. The various properties of the new products initially and after exposure to large radiation doses were in no case inferior to the original greases and in some respects improvements were observed. Radiation tolerance of commercial greases could be enhanced by the addition of polystyrene to form a physical mixture rather than copolymers. The reaction mechanisms involved at all stages were studied using infrared spectroscopic techniques. (P.C.H.)

  11. Intrinsic radiation resistance in human chondrosarcoma cells

    International Nuclear Information System (INIS)

    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A.

    2006-01-01

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16 ink4a , one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16 ink4a contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16 ink4a expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16 ink4a expression on chondrosarcoma cell resistance to low-dose γ-irradiation (1-5 Gy). p16 ink4a expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16 ink4a transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16 ink4a plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas

  12. Tumor control probability after a radiation of animal tumors

    International Nuclear Information System (INIS)

    Urano, Muneyasu; Ando, Koichi; Koike, Sachiko; Nesumi, Naofumi

    1975-01-01

    Tumor control and regrowth probability of animal tumors irradiated with a single x-ray dose were determined, using a spontaneous C3H mouse mammary carcinoma. Cellular radiation sensitivity of tumor cells and tumor control probability of the tumor were examined by the TD 50 and TCD 50 assays respectively. Tumor growth kinetics were measured by counting the percentage of labelled mitosis and by measuring the growth curve. A mathematical analysis of tumor control probability was made from these results. A formula proposed, accounted for cell population kinetics or division probability model, cell sensitivity to radiation and number of tumor cells. (auth.)

  13. Radiation resistant lining material

    International Nuclear Information System (INIS)

    Ouchi, Koki; Okagawa, Seigo; Tamaki, Hidehiro.

    1990-01-01

    Rigidity, viscoelasticity, flexibility, radiation resistance, leaching resistance, rust-proofness, endurance, etc. are required for the lining materials to wall surfaces and floor surfaces of facilities used under the effect of radiation rays and for the inner surface protection of vessels for radioactive wastes. The present invention provides radiation resistant lining material capable of satisfying such various requirements in a well-balanced manner. That is, the material contains (A) 100 parts by weight of rapidly curing cement, (B) 50 to 300 % by weight of aggregate, and (C) 80 to 120 parts by weight of polymer emulsion. As the specific example, the ingredient (A) is commercially available under the trade name of Jet Cement. The aggregate of the ingredient (B) has preferably from about 0.6 to 0.2 mm of size and is made of material, preferably, silicon or iron grains. As the ingredient (C), acrylic resin emulsion is preferred. As a result of example, these ingredient constitutions can satisfy each of the required performance described above. (I.S.)

  14. Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells

    International Nuclear Information System (INIS)

    Chamoto, Kenji; Wakita, Daiko; Takeshima, Tsuguhide

    2009-01-01

    Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG+OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG+OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG+OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG+OVA-liposome allowed the augmented induction of OVA-tetramer + LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (author)

  15. Communication equipment radiation resistance ensurance

    International Nuclear Information System (INIS)

    Myrova, L.O.; Chelizhenko, A.Z.

    1983-01-01

    A review of works on radiation resistance of electronic equipment (epsilon epsilon) for 15 years is presented. The effect of ionizing radiation appearing as a result of nuclear explosions in nuclear facilities and in outerspace on epsilon epsilon has been considered. Types of radiation effects in epsilon epsilon, radiation effect on semiconductor devices and integrated circUits, types of epsilon epsilon failures, as well as the procass of radiation-resistant epsilon epsilon designing and selection of its main parameters have been described. The methods of epsilon epsilon flowsheet optimization, application of mathematical simulation and peculiarities of ensurance of epsilon epsilon radiation resistance of communication systems are considered. Peculiarities of designing of radiation-resistant quartz generators, secondary power supply sources and amplifiers are discussed

  16. Radiation resistance of elastomers

    International Nuclear Information System (INIS)

    Hourquebie, P.; Bigarre, J.; Forveille, J.L.; Raby, J.; Lazare, L.

    2002-01-01

    The COMOR group is a network of laboratories from both the CEA and the CNRS. This network is particularly involved in fundamental and applied studies on the ageing of polymers under irradiation. COMOR has studied the ageing of EPDM (ethylene-propylene-diene-monomer) because this elastomer is often used in nuclear environment (in cable coating for instance). In this study, we have prepared materials with different formulations and we have characterised their use-condition properties (dielectric and mechanical) before and after γ irradiation. The dielectric measurements are well adapted to study the oxidation and the crosslinking phenomena which appear during the irradiation ageing. We have shown that after a short time, the oxidation is limited by the diffusion of oxygen. A phenolic antioxidant is not able to protect the polymer against the oxidation. However, we used a concentration typical of a purely thermal stabilisation case (0,1%). On the other hand, a diamine type additive with a concentration of 1% showed efficient stabilisation. The mechanical properties of the regular EPDM are strongly affected by the irradiation but there is little difference with regard to radiation resistance between both types of raw materials. Nevertheless, the NORDEL IP 3725 stabilised with the amine has better initial mechanical properties whereas the NORDEL 2722 offers higher strength above 300 kGy. Our results emphasize the stake of a proper stabilisation of polymers with respect to ionising radiation. (authors)

  17. Effects of low dose radiation on tumor-bearing mice

    International Nuclear Information System (INIS)

    Feng Li; Hou Dianjun; Huang Shanying; Deng Daping; Wang Linchao; Cheng Yufeng

    2007-01-01

    Objective: To explore the effects of low-dose radiation on tumor-bearing mice and radiotherapy induced by low-dose radiation. Methods: Male Wistar mice were implanted with Walker-256 sarcoma cells in the right armpit. On day 4, the mice were given 75 mGy whole-body X-ray radiation. From the fifth day, tumor volume was measured, allowing for the creation of a graph depicting tumor growth. Lymphocytes activity in mice after whole-body X-ray radiation with LDR was determinned by FCM. Cytokines level were also determined by ELISA. Results: Compared with the radiotherapy group, tumor growth was significantly slower in the mice pre-exposed to low-dose radiation (P<0.05), after 15 days, the average tumor weight in the mice pre- exposed to low-dose radiation was also significantly lower (P<0.05). Lymphocytes activity and the expression of the CK in mice after whole-body y-ray radiation with LDR increased significantly. Conclusions: Low-dose radiation can markedly improve the immune function of the lymphocyte, inhibit the tumor growth, increase the resistant of the high-dose radiotherapy and enhance the effect of radiotherapy. (authors)

  18. Radiation-resistant asporogenic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Yano, K [Tokyo Univ. (Japan). Faculty of Agriculture

    1975-09-01

    This paper reports the biological and ecological examinations on the radiation-resistant asporogenic bacteria (mainly concerning Micrococcus radiodurans). Radiation-resistant asporogenic bacteria were isolated from the irradiated areas of the natural world as well as from the general areas and from the Rn waters in the Misasa hot spring. The acquiring of the tolerance to radiation in bacteria was also examined. In addition, the future problems of microbiological treatment with irradiation were mentioned.

  19. Radiation-resistant asporogenic bacteria

    International Nuclear Information System (INIS)

    Yano, Keiji

    1975-01-01

    This paper reports the biological and ecological examinations on the radiation-resistant asporogenic bacteria (mainly concerning Micrococcus radiodurans). Radiation-resistant asporogenic bacteria were isolated from the irradiated areas of the natural world as well as from the general areas and from the Rn waters in the Misasa hot spring. The acquiring of the tolerance to radiation in bacteria was also examined. In addition, the future problems of microbiological treatment with irradiation were mentioned. (Tsukamoto, Y.)

  20. Radiation therapy of thoracic and abdominal tumors

    International Nuclear Information System (INIS)

    LaRue, S.M.; Gillette, S.M.; Poulson, J.M.

    1995-01-01

    Until recently, radiotherapy of thoracic and abdominal tumors in animals has been limited. However, the availability of computerized tomography and other imaging techniques to aid in determining the extent of tumor, an increase in knowledge of dose tolerance of regional organs, the availability of isocentrically mounted megavoltage machines, and the willingness of patients to pursue more aggressive treatment is making radiation therapy of tumors in these regions far more common. Tumor remission has been reported after radiation therapy of thymomas. Radiation therapy has been used to treat mediastinal lymphoma refractory to chemotherapy, and may be beneficial as part of the initial treatment regimen for this disease. Chemodectomas are responsive to radiation therapy in human patients, and favorable response has also been reported in dogs. Although primary lung tumors in dogs are rare, in some cases radiation therapy could be a useful primary or adjunctive therapy. Lung is the dose-limiting organ in the thorax. Bladder and urethral tumors in dogs have been treated using intraoperative and external-beam radiation therapy combined with chemotherapy. These tumors are difficult to control locally with surgery alone, although the optimal method of combining treatment modalities has not been established. Local control of malignant perianal tumors is also difficult to achieve with surgery alone, and radiation therapy should be used. Intraoperative radiation therapy combined with external-beam radiation therapy has been used for the management of metastatic carcinoma to the sublumbar lymph nodes. Tolerance of retroperitoneal tissues may be decreased by disease or surgical manipulation

  1. Considering the role of radiation therapy for gastrointestinal stromal tumor

    Directory of Open Access Journals (Sweden)

    Corbin KS

    2014-05-01

    Full Text Available Kimberly S Corbin,1 Hedy L Kindler,2 Stanley L Liauw31Department of Radiation Oncology, Memorial Medical Center, Springfield, IL, USA; 2Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA; 3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USAAbstract: Gastrointestinal stromal tumors (GISTs are rare mesenchymal tumors arising in the gastrointestinal tract. Over the last decade, the management and prognosis of GISTs has changed dramatically with molecular characterization of the c-kit mutation and the adoption of targeted systemic therapy. Currently, the standard of care for resectable tumors is surgery, followed by adjuvant imatinib for tumors at high risk for recurrence. Inoperable or metastatic tumors are treated primarily with imatinib. Despite excellent initial response rates, resistance to targeted therapy has emerged as a common clinical problem, with relatively few therapeutic solutions. While the treatment of GISTs does not commonly include radiotherapy, radiation therapy could be a valuable contributing modality. Several case reports indicate that radiation can control locally progressive, drug-resistant disease. Further study is necessary to define whether radiation could potentially prevent or delay the onset of drug resistance, or improve outcomes when given in combination with imatinib.Keywords: GIST, imatinib, radiotherapy

  2. Maximizing Tumor Immunity With Fractionated Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

    2012-07-15

    Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma} enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

  3. Maximizing Tumor Immunity With Fractionated Radiation

    International Nuclear Information System (INIS)

    Schaue, Dörthe; Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H.

    2012-01-01

    Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-γ enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4 + CD25 hi Foxp3 + T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

  4. Radiation resistance of Rhizopus stolonifer

    International Nuclear Information System (INIS)

    Robbertse, P.J.; Du Toit, T.L.; Van der Merwe, L.J.; Koekemoer, M.L.; Eilers, I.M.I.

    1983-01-01

    A problem encountered with the irradiation of food is that certain micro-organisms are highly resistant to gamma rays. This includes the fungus, Rhizopus stolonifer, associated with most fruits. The Nuclear Development Corporation of South Africa (NUCOR) has found that a combination of radiation and mild heat treatment reduces the radiation dose necessary to kill 90% of R. stolonifer by approximately half. Treatment at 50 degrees Celsius for 10 minutes or at 55 degrees Celsius for five minutes is sufficient. The article discusses the mechanism of radiation resistance in R. stolonifer and the way in which heating affects this resistance

  5. Radiation-resistant camera tube

    International Nuclear Information System (INIS)

    Kuwahata, Takao; Manabe, Sohei; Makishima, Yasuhiro

    1982-01-01

    It was a long time ago that Toshiba launched on manufacturing black-and-white radiation-resistant camera tubes employing nonbrowning face-plate glass for ITV cameras used in nuclear power plants. Now in compliance with the increasing demand in nuclear power field, the Company is at grips with the development of radiation-resistant single color-camera tubes incorporating a color-stripe filter for color ITV cameras used under radiation environment. Herein represented are the results of experiments on characteristics of materials for single color-camera tubes and prospects for commercialization of the tubes. (author)

  6. Radiation Therapy of Suprasellar Germ Cell Tumors

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Choi, Doo Ho; Choi, Eun Kyung; Kim, Il Han; Ha, Sung Whan; Park, Charn Il

    1988-01-01

    A retrospective study was performed on 15 patients with suprasellar germ cell tumors treated by megavoltage external beam irradiation between Feb. 1979 and Dec. 1985. Follow-up period of survivors was 30 to 91 months. Histologic diagnosis was obtained before radiation therapy in 10 patients (9 germinomas and 1 mixed). Five patients were treated without histologic verification. In 9 patients with biopsy-proven germinomas radiation therapy was delivered to the craniospinal axis in 6, to the whole brain in 3. In 5 patients with mixed germ cell tumor or elevated tumor marker, irradiation was delivered to the craniospinal axis in 2, to the whole brain in 2, and to the primary site only in 1. Total doses ranged from 5,000 to 5,500 cGy to the primary site, 3,000 to 4,400 cGy to the whole brain, and 1,300 to 3,000 cGy to the spine. In these 14, local tumor was controlled and primary or spinal failure was not observed. One patient without elevated tumor marker was treated to the whole brain, The tumor was not controlled and he had spinal recurrence. It is proven that radiation therapy is an effective treatment for suprasellar germ cell tumors. The neuroendocrinologic presentation, tumor marker status, early response to radiation measured on CT seem to be useful means for selecting patients for radiation therapy when tissue diagnosis is not available

  7. Mechanisms of Intrinsic Tumor Resistance to Immunotherapy

    Directory of Open Access Journals (Sweden)

    John Rieth

    2018-05-01

    Full Text Available An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO overexpression, loss of phosphatase and tensin homologue (PTEN expression, and overexpression of the Wnt–β-catenin pathway. Current work in immunotherapy continues to identify various tumor resistance mechanisms; future work is needed to develop adjuvant treatments that target those mechanisms, in order to improve the efficacy of immunotherapy and to expand its scope.

  8. Diagnostic radiation and its prognosis of pineal region tumor

    International Nuclear Information System (INIS)

    Momose, Toshimitsu; Aoki, Yukimasa; Akanuma, Atsuo; Machida, Tohru; Iio, Masahiro; Takakura, Kimitomo

    1984-01-01

    20 Gy of local irradiation was performed for the patients with pineal region tumor. We evaluated the tumor volume on X-CT in the pre-radiation and 20 Gy of post-radiation state. If tumor is sensitive enough to radiation therapy, we add 40 Gy of whole brain and 30 to 40 Gy of whole spine irradiation. If not, we transfer patients to neurosurgeons for the purpose of tumor ressection. We call this procedure ''Diagnostic Radiation.'' We proposed the concept of TRR (Tumor Regression Ratio) in order to evaluate our protocol more objctively. TRR is as follows: TRR (%) = [1-Total Tumor Volume (at each dose) / Total Tumor Volume (at o Gy)] x 100 (%) Total Tumor Volume(mm 3 ) = slice thickness(mm) x siguma HDA (mm 2 ) on each slice: where HDA is high density area on enhanced CT. Eleven patients were studied and TRR of each patients was calculated. The relations between TRR, tumor markers, CSF seeding and prognoiss was discussed. From our study, (1) TRR at 20Gy was important and might predict approximate prognosis of each cae case. A) TRR = 100 → very good B) TRR < 20 → poor C) 20 <= TRR < 100 → high possibility (2) Majority of TRR < 100 cases have turned out to be histologically in teratoma category. (3) Good correlation between the level of tumor markers and prognosis was observed. Cases with elevated level of AFP and/or HCG were radio- resistant and had poor prognosis. (4) Distant metastasis must also be kept in mind in the treatment of pineal region tumor. (author)

  9. Radiation-resistant control system

    International Nuclear Information System (INIS)

    Cable, T.C.; Jones, S.

    1995-01-01

    REMOTEC has developed a open-quotes radiation resistanceclose quotes control system under a U.S. Department of Energy Small Business Innovative Research (SBIR) contract with assistance from the University of Florida. The SBIR goal was to develop a radiation resistant mobile robot from the ANDROS family of hazardous duty mobile robots that REMOTEC manufactures. See Refs. 1 and 2 for additional SBIR results. The control system, as well as the entire ANDROS robot, was redesigned, where necessary, to withstand radiation doses in excess of 10 6 rad. Those components of the robot that could not be purchased as open-quotes radiation hardenedclose quotes were tested under standard operating conditions for determination of their open-quotes radiation resistance.close quotes The entire ANDROS robot was then assembled with these new components and tested to > 10 6 rad

  10. Enhanced radiation resistant fiber optics

    International Nuclear Information System (INIS)

    Lyons, P.B.; Looney, L.D.

    1993-01-01

    A process for producing an optical fiber having enhanced radiation resistance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation. 4 figures

  11. Enhanced radiation resistant fiber optics

    Science.gov (United States)

    Lyons, P.B.; Looney, L.D.

    1993-11-30

    A process for producing an optical fiber having enhanced radiation resistance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation. 4 figures.

  12. Resistive Memory Devices for Radiation Resistant Non-Volatile Memory

    Data.gov (United States)

    National Aeronautics and Space Administration — Ionizing radiation in space can damage electronic equipment, corrupting data and even disabling computers. Radiation resistant (rad hard) strategies must be employed...

  13. Radiation Therapy of Pituitary Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Park, Moon Baik; Hong, Seong Eong [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    Radiation treatment results were analyzed in a retrospective analysis of 47 patients with pituitary adenoma treated with radiation alone or combined with surgery from 1974 through 1987 at the Department of Therapeutic Radiology of Kyung Hee University. The 5-year overall survival rates for all patients was 80.4%. Radiation therapy was effective for improving visual symptoms and headache, but could not normalize amenorrhea and galactorrhoea. There was no difference of survival rate between radiation alone and combination with surgery. Prognostic factors such as age, sex, disease type, visual field, headache and surgical treatment were statistically no significant in survival rates of these patients.

  14. Radiation Therapy of Pituitary Tumors

    International Nuclear Information System (INIS)

    Park, Moon Baik; Hong, Seong Eong

    1989-01-01

    Radiation treatment results were analyzed in a retrospective analysis of 47 patients with pituitary adenoma treated with radiation alone or combined with surgery from 1974 through 1987 at the Department of Therapeutic Radiology of Kyung Hee University. The 5-year overall survival rates for all patients was 80.4%. Radiation therapy was effective for improving visual symptoms and headache, but could not normalize amenorrhea and galactorrhoea. There was no difference of survival rate between radiation alone and combination with surgery. Prognostic factors such as age, sex, disease type, visual field, headache and surgical treatment were statistically no significant in survival rates of these patients

  15. Radiation-resistant plastic insulators

    International Nuclear Information System (INIS)

    Sturm, B.J.; Parkinson, W.W.

    1975-01-01

    A high molecular weight organic composition useful as an electric insulator in radiation fields is provided and comprises normally a solid polymer of an organic compound having a specific resistance greater than 10 19 ohm-cm and containing phenyl groups and 1 to 7.5 weight percent of a high molecular weight organic phosphite. In one embodiment the composition comprises normally solid polystyrene having 7.5 weight percent tris-β-chloroethyl phosphite as an additive; the composition exhibited an increase in the post-irradiation resistivity of over an order of magnitude over the post-irradiation resistivity of pure polystyrene. (Patent Office Record)

  16. Pulsed laser radiation therapy of skin tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kozlov, A.P.; Moskalik, K.G.

    1980-11-15

    Radiation from a neodymium laser was used to treat 846 patients with 687 precancerous lesions or benign tumors of the skin, 516 cutaneous carcinomas, 33 recurrences of cancer, 51 melanomas, and 508 metastatic melanomas in the skin. The patients have been followed for three months to 6.5 years. No relapses have been observed during this period. Metastases to regional lymph nodes were found in five patients with skin melanoma. Pulsed laser radiation may be successfully used in the treatment of precancerous lesions and benign tumors as well as for skin carcinoma and its recurrences, and for skin melanoma. Laser radiation is more effective in the treatment of tumors inaccessible to radiation therapy and better in those cases in which surgery may have a bad cosmetic or even mutilating effect. Laser beams can be employed in conjunction with chemo- or immunotherapy.

  17. Adriamycin resistance and radiation response

    International Nuclear Information System (INIS)

    Belli, J.A.; Harris, J.R.

    1979-01-01

    Mammalian cells (V79) in culture developed resistance to Adriamycin during continuous exposure to low levels of drug. This resistance was accompanied by change in x-ray survival properties which, in turn, depended upon the isolation of subpopulations from resistant sub lines. These changes in x-ray survival properties were characterized by reduced D/sub Q/ values and a decrease in the D/sub O/. However, these changes were not observed together in the same cell sub line. Adriamycin-resistant cells did not appear to be radiation damage repair deficient. Other phenotypic changes (cell morphology, DNA content and chromosome number) suggested mutational events coincident with the development of Adriamycin resistance

  18. Radiation resistance of Candida parapsilosis

    International Nuclear Information System (INIS)

    Kristensen, H.

    1982-01-01

    The radiation resistance of 30 strains classified as Candida parapsilosis was examined. The strains originated partly from environments where ionizing radiation was used for research or routine purposes, partly from environments with no known possibility for selection of strains with unusually high radiation resistance. D-6 values between 1.5 and 2.4 Megarads were found when the cells were irradiated in the dried state, a D-6 value being the dose necessary to reduce the initial number of colony-forming units with a factor of 10 6 . The majority of D-6 values were between 1.9 and 2.1 Megarads. D-6 values for the cells irradiated in liquid media were about 2/3 of tose in the dried state. No difference in resistance was revealed depending on the origin of the strains examined. For radiation sterilization of medical products the demonstrated resistance of Candida parapsilosis might be of importance of routine use of minimum doses below 2.5 Megarads were to be accepted. (author)

  19. Radiogenetic therapy: strategies to overcome tumor resistance.

    Science.gov (United States)

    Marples, B; Greco, O; Joiner, M C; Scott, S D

    2003-01-01

    The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

  20. Ionizing radiation in tumor promotion and progression

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.

    1990-08-01

    Chronic exposure to beta radiation has been tested as a tumor promoting or progressing agent. The dorsal skins of groups of 25 female SENCAR mice were chemically initiated with a single exposure to DMBA, and chronic exposure to strontium-90/yttrium-90 beta radiation was tested as a stage 1, stage 2 or complete skin tumor promoter. Exposure of initiated mice to 0.5 gray twice a week for 13 weeks produced no papillomas, indicating no action as a complete promoter. Another similar group of animals was chemically promoted through stage 1 (with TPA) followed by 0.5 gray of beta radiation twice a week for 13 weeks. Again no papillomas developed indicating no action of chronic radiation as a stage 2 tumor promoter. The same radiation exposure protocol in another DMBA initiated group receiving both stage 1 and 2 chemical promotion resulted in a decrease in papilloma frequency, compared to the control group receiving no beta irradiation, indicating a tumor preventing effect of radiation at stage 2 promotion, probably by killing initiated cells. Chronic beta radiation was tested three different ways as a stage 1 tumor promoter. When compared to the appropriate control, beta radiation given after initiation as a stage 1 promoter (0.5 gray twice a week for 13 weeks), after initiation and along with a known stage 1 chemical promoter (1.0 gray twice a week for 2 weeks), or prior to initiation as a stage 1 promoter (0.5 gray twice a week for 4 weeks), each time showed a weak (∼ 15% stimulation) but statistically significant (p<0.01) ability to act as a stage 1 promoter. When tested as a tumor progressing agent delivered to pre-existing papillomas, beta radiation (0.5 gray twice a week for 13 weeks) increased carcinoma frequency from 0.52 to 0.68 carcinoma/animal, but this increase was not statistically significant at the 95% confidence level. We conclude that in the addition to the known initiating, progressing and complete carcinogenic action of acute exposures to ionizing

  1. Radiation therapy for metastatic spinal tumors

    International Nuclear Information System (INIS)

    Kida, Akio; Fukuda, Haruyuki; Taniguchi, Shuji; Sakai, Kazuaki

    2000-01-01

    The results of radiation therapy for metastatic spinal tumors were evaluated in terms of pain relief, improvement of neurological impairment, and survival. Between 1986 and 1995, 52 symptomatic patients with metastatic spinal tumors treated with radiation therapy were evaluated. The patients all received irradiation of megavoltage energy. Therapeutic efficacy was evaluated in terms of pain relief and improvement of neurological impairment. Pain relief was observed in 29 (61.7%) of 47 patients with pain. Therapy was effective for 17 (70.8%) of 24 patients without neurological impairment, and efficacy was detected in 12 (52.2%) of 23 patients with neurological impairment. Improvement of neurological symptoms was obtained in seven (25.0%) of 28 patients with neurological impairment. Radiation therapy was effective for pain relief in patients with metastatic spinal tumors. In patients with neurological impairment, less pain relief was observed than in those without impairment. Improvement of neurological impairment was restricted, but radiation therapy was thought to be effective in some cases in the early stage of neurological deterioration. Radiation therapy for metastatic spinal tumors contraindicated for surgery was considered effective for improvement of patients' activities of daily living. (author)

  2. Radiation resistant ducted superconductive coil

    International Nuclear Information System (INIS)

    Schleich, A.

    1976-01-01

    The radiation-resistant ducted superconductive coil consists of a helically wound electrical conductor constituted by an electrically conductive core of superconductive material provided with a longitudinally extending cooling duct. The core is covered with a layer of inorganic insulating material and the duct is covered by an electrically conductive metallic gas-tight sheath. The metallic sheaths on adjacent turns of the coil are secured together. 2 Claims, 4 Drawing Figures

  3. Imaging after radiation therapy of thoracic tumors

    International Nuclear Information System (INIS)

    Ghaye, B.; Wanet, M.; El Hajjam, M.

    2016-01-01

    Radiation-induced lung disease (RILD) is frequent after therapeutic irradiation of thoracic malignancies. Many technique-, treatment-, tumor- and patient-related factors influence the degree of injury sustained by the lung after irradiation. Based on the time interval after the completion of the treatment RILD presents as early and late features characterized by inflammatory and fibrotic changes, respectively. They are usually confined to the radiation port. Though the typical pattern of RILD is easily recognized after conventional two-dimensional radiation therapy (RT), RILD may present with atypical patterns after more recent types of three or four-dimensional RT treatment. Three atypical patterns are reported: the modified conventional, the mass-like and the scar-like patterns. Knowledge of the various features and patterns of RILD is important for correct diagnosis and appropriate treatment. RILD should be differentiated from recurrent tumoral disease, infection and radiation-induced tumors. Due to RILD, the follow-up after RT may be difficult as response evaluation criteria in solid tumours (RECIST) criteria may be unreliable to assess tumor control particularly after stereotactic ablation RT (SABR). Long-term follow-up should be based on clinical examination and morphological and/or functional investigations including CT, PET-CT, pulmonary functional tests, MRI and PET-MRI. (authors)

  4. Heterogeneity in induced thermal resistance of rat tumor cell clones

    International Nuclear Information System (INIS)

    Tomasovic, S.P.; Rosenblatt, P.L.; Heitzman, D.

    1983-01-01

    Four 13762NF rat mammary adenocarcinoma clones were examined for their survival response to heating under conditions that induced transient thermal resistance (thermotolerance). Clones MTC and MTF7 were isolated from the subcutaneous locally growing tumor, whereas clones MTLn2 and MTLn3 were derived from spontaneous lung metastases. There was heterogeneity among these clones in thermotolerance induced by either fractionated 45 0 C or continuous 42 0 C heating, but the order of sensitivity was not necessarily the same. The clones developed thermal resistance at different rates and to different degrees within the same time intervals. There was heterogeneity between clones isolated from within either the primary site or metastatic lesions. However, clones derived from metastatic foci did not intrinsically acquire more or less thermotolerance to fractionated 45 0 C or continuous 42 0 C heating than did clones from the primary tumor. Further, there was no apparent relationship between any phenotypic properties that conferred more or less thermotolerance in vitro and any phenotypic properties that conferred enhanced metastatic success of these same clones by spontaneous (subcutaneous) or experimental (intravenous) routes in vivo. These tumor clones also differ in their karyotype, metastatic potential, cell surface features, sensitivity to x-irradiation and drugs, and ability to repair sublethal radiation damage. These results provide further credence to the concept that inherent heterogeneity within tumors may be as important in therapeutic success as other known modifiers of outcome such as site and treatment heterogeneity

  5. Predictive value of histologic tumor necrosis after radiation.

    Science.gov (United States)

    Chen, Y; Taghian, A G; Rosenberg, A E; O'Connell, J; Okunieff, P; Suit, H D

    2001-12-20

    Postsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS-26, SCC-21, and HGL-21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One-half of the tumor was divided into 1-mm(3) fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCD(p) (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. Copyright 2001 Wiley-Liss, Inc.

  6. Electron Paramagnetic Resonance pO2 Image Tumor Oxygen-Guided Radiation Therapy Optimization.

    Science.gov (United States)

    Epel, Boris; Maggio, Matt; Pelizzari, Charles; Halpern, Howard J

    2017-01-01

    Modern standards for radiation treatment do not take into account tumor oxygenation for radiation treatment planning. Strong correlation between tumor oxygenation and radiation treatment success suggests that oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. We have developed an OGRT protocol for rodents. Electron paramagnetic resonance (EPR) imaging is used for recording oxygen maps with high spatial resolution and excellent accuracy better than 1 torr. Radiation is delivered with an animal intensity modulated radiation therapy (IMRT) XRAD225Cx micro-CT/ therapy system. The radiation plan is delivered in two steps. First, a uniform 15% tumor control dose (TCD 15 ) is delivered to the whole tumor. In the second step, an additional booster dose amounting to the difference between TCD 98 and TCD 15 is delivered to radio-resistant, hypoxic tumor regions. Delivery of the booster dose is performed using a multiport conformal beam protocol. For radiation beam shaping we used individual radiation blocks 3D-printed from tungsten infused ABS polymer. Calculation of beam geometry and the production of blocks is performed next to the EPR imager, immediately after oxygen imaging. Preliminary results demonstrate the sub-millimeter precision of the radiation delivery and high dose accuracy. The efficacy of the radiation treatment is currently being tested on syngeneic FSa fibrosarcoma tumors grown in the legs of C3H mice.

  7. Design of radiation dose tumor response assays

    International Nuclear Information System (INIS)

    Suit, H.D.; Hwang, T.; Hsieh, C.; Thames, H.

    1985-01-01

    The efficient utilization of animals in a radiation dose response assay for tumor control requires a definition of the goal, e.g., TCD50 or slope. A series of computer modelled ''experiments'' have been performed for each of a number of allocations of dose levels (DL) and number of animals/DL. The authors stipulated that the assumed TCD50 was .85 of true value; assumed slope was correct. They stipulated a binominal distribution of observed tumor control results at each dose level. A pilot assay used 6 tumors at 7 DL (from TCD1-TCD97). The second assay used 30 tumors assigned to 2,3,5 or 9 DL and to selected tumor control probabilities (TCP derived from the pilot run. Results from 100 test runs were combined with the pilot run for each of the combination of DL and TCP values. Logit regression lines were fitted through these ''data'' and the 95% CL around the TCD50 and the TCD37 values and the variances of the slopes were computed. These experiments were repeated using the method suggested by Porter (1980). Results show that a different strategy is needed depending upon the goal, viz. TCD50 or TCD37 vs slope. The differences between the two approaches are discussed

  8. Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Davies, B.M.; Moulder, J.E.

    1990-01-01

    RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance

  9. Molecular diagnostics detect radio resistant tumor in cancer cervix

    International Nuclear Information System (INIS)

    Nagarajan, B.

    2004-01-01

    After successful external radiation/intracavitary and interstitial radiation therapy some cancer cervix patients presented with recurrent tumors on 6-12 months follow up period. They had high level of IL-6 on first reporting. This augurs well with the premise that up regulation of IL-6 might be involved in tumor progression

  10. Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Ruman Rahman

    2010-01-01

    Full Text Available Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm.

  11. Gravitational radiation resistance, radiation damping and field fluctuations

    International Nuclear Information System (INIS)

    Schaefer, G.

    1981-01-01

    Application is made of two different generalised fluctuation-dissipation theorems and their derivations to the calculation of the gravitational quadrupole radiation resistance using the radiation-reaction force given by Misner, Thorne and Wheeler (Gravitation (San Francisco: Freeman) ch 36,37 (1973)) and the usual tidal force on one hand and the tidal force and the free gravitational radiation field on the other hand. The quantum-mechanical version (including thermal generalisations) of the well known classical quadrupole radiation damping formula is obtained as a function of the radiation resistance. (author)

  12. γ-radiation induces cellular sensitivity and aberrant methylation in human tumor cell lines.

    Science.gov (United States)

    Kumar, Ashok; Rai, Padmalatha S; Upadhya, Raghavendra; Vishwanatha; Prasada, K Shama; Rao, B S Satish; Satyamoorthy, Kapettu

    2011-11-01

    Ionizing radiation induces cellular damage through both direct and indirect mechanisms, which may include effects from epigenetic changes. The purpose of this study was to determine the effect of ionizing radiation on DNA methylation patterns that may be associated with altered gene expression. Sixteen human tumor cell lines originating from various cancers were initially tested for radiation sensitivity by irradiating them with γ-radiation in vitro and subsequently, radiation sensitive and resistant cell lines were treated with different doses of a demethylating agent, 5-Aza-2'-Deoxycytidine (5-aza-dC) and a chromatin modifier, Trichostatin-A (TSA). Survival of these cell lines was measured using 3-(4, 5-Dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium (MTT) and clonogenic assays. The effect of radiation on global DNA methylation was measured using reverse phase high performance liquid chromatography (RP-HPLC). The transcription response of methylated gene promoters, from cyclin-dependent kinase inhibitor 2A (p16(INK4a)) and ataxia telangiectasia mutated (ATM) genes, to radiation was measured using a luciferase reporter assay. γ-radiation resistant (SiHa and MDAMB453) and sensitive (SaOS2 and WM115) tumor cell lines were examined for the relationship between radiation sensitivity and DNA methylation. Treatment of cells with 5-aza-dC and TSA prior to irradiation enhanced DNA strand breaks, G2/M phase arrest, apoptosis and cell death. Exposure to γ-radiation led to global demethylation in a time-dependent manner in tumor cells in relation to resistance and sensitivity to radiation with concomitant activation of p16(INK4a) and ATM gene promoters. These results provide important information on alterations in DNA methylation as one of the determinants of radiation effects, which may be associated with altered gene expression. Our results may help in delineating the mechanisms of radiation resistance in tumor cells, which can influence diagnosis, prognosis and

  13. Radiation therapy for malignant lid tumor

    International Nuclear Information System (INIS)

    Totsuka, Seiichi; Itsuno, Hajime

    1991-01-01

    The case of a 42-year-old man with Meibomian gland carcinoma in his right lower lid is reported. The tumor found in the nasal part of the lower lid, was 12 mm x 13 mm in size. First, surgical resection was performed. The pathological diagnosis of the frozen section was 'undifferentiated basal cell epithelioma'. Second, cryotherapy was performed all over the cut surface. Later, the permanent section was pathologically diagnosed as 'undifferentiated Meibomian gland carcinoma'. Total 50 Gy irradiation therapy was therefore performed using a 9 Mev Linac electron beam, 25 x 20 mm field, with a lead protector for the cornea and lens. A lead contact lens did not afford good results because it was too easily shifted on the cornea, owing to its weight. Therefore, we made a racket-shaped lead protector. Fixed well with tape, this protector afforded good protective effect. Three years after treatment, the patient has good visual function, with no recurrence. This racket-shaped lead protector is thought to be useful in radiation therapy for malignant lid tumors. (author)

  14. CERN selects Fujikura's radiation resistant fiber

    CERN Multimedia

    2007-01-01

    "Fujikura Europe Ltd. (search for Fujikura Europe) today announced that its radiation resistant singlemode optical fiber has been selected by CERN to provide communicaton links within the world's largest particle accelerator..."(2/3 page)

  15. Radiation resistance of polymer materials for space

    International Nuclear Information System (INIS)

    Miyauchi, Masahiko; Iwata, Minoru; Yokota, Rikio

    2011-01-01

    The thin film of thermoplastic polyimide with a new asymmetric structure is used in the solar sail 'IKAROS'. Here, the relation of its chemical structure to its thermodynamic properties and radiation resistance is introduced. (M.H.)

  16. Radiation-induced autologous in situ tumor vaccines

    International Nuclear Information System (INIS)

    Guha, Chandan

    2014-01-01

    Radiation therapy (RT) has been used as a definitive treatment for many solid tumors. While tumoricidal properties of RT are instrumental for standard clinical application, irradiated tumors can potentially serve as a source of tumor antigens in vivo, where dying tumor cells would release tumor antigens and danger signals and serve as autologous in situ tumor vaccines. Using murine tumor models of prostate, metastatic lung cancer and melanoma, we have demonstrated evidence of radiation-enhanced tumor-specific immune response that resulted in improved primary tumor control and reduction in systemic metastasis and cure. We will discuss the immunogenic properties of RT and determine how immunotherapeutic approaches can synergize with RT in boosting immune cells cell function. (author)

  17. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    Energy Technology Data Exchange (ETDEWEB)

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  18. Physiological and genetics studies of highly radiation-resistant bacteria

    International Nuclear Information System (INIS)

    Keller, L.C.

    1981-01-01

    The phenomenon of radiation resistance was studied using micrococci and Moraxella-Acinetobacter capable of surviving very high doses of gamma radiation which were isolated from foods. Physiological age, or growth phase, was found to be an important factor in making comparisons of radiation-resistance among different bacteria and their mutants. Radiation-resistant bacteria were highly resistant to the lethal effect of nitrosoguanidine used for mutagenesis. Studies of relative resistance of radiation-resistant bacteria, radiation-sensitive mutants, and nonradiation-resistant bacteria to killing by different chemical mutagens did not reveal a correlation between the traits of radiation resistance and mutagen resistance among different strains. Comparisons of plasmid profiles of radiation-resistant bacteria and selected radiation-sensitive mutants suggested the possibility that plasmids may carry genes involved in radiation resistance

  19. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy

    International Nuclear Information System (INIS)

    Karakashev, Sergey V; Reginato, Mauricio J

    2015-01-01

    Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance

  20. Oxygenation of spontaneous canine tumors during fractionated radiation therapy

    International Nuclear Information System (INIS)

    Achermann, R.E.; Ohlerth, S.M.; Bley, C.R.; Inteeworn, N.; Schaerz, M.; Wergin, M.C.; Kaser-Hotz, B.; Gassmann, M.; Roos, M.

    2004-01-01

    Background and purpose: tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. Material and methods: tumor oxygen partial pressure (pO 2 ) measurements were performed with the eppendorf-pO 2 -Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO 2 was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). Results: 15/26 tumors had a pretreatment median pO 2 ≤ 10 mmHg. The pO 2 values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO 2 of initially hypoxic tumors (pretreatment median pO 2 ≤ 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO 2 decreased. Conclusion: hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were ≥ 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic. (orig.)

  1. Radiation-induced tumors of the nervous system

    International Nuclear Information System (INIS)

    Bernstein, M.; Laperriere, N.

    1991-01-01

    Therapeutic and nontherapeutic ionizing radiation has long been recognized as a putative carcinogenic agent, but the evidence that radiation causes tumors is circumstantial at worst and statistically significant at best. There are no distinct histological, biochemical, cytogenetic, or clinical criteria that can be used to determine if an individual tumor was caused directly by previous irradiation of the anatomic area. Additional supportive evidence for radiation-induced tumors includes a position correlation between radiation dose and tumor incidence (usually in the low dose range) and experimental induction of the same neoplasm in appropriate animal models. even if these criteria are fulfilled, coincidental development of a second tumor can never be discounted in an individual patient, particularly if there is an underlying diathesis to develop multiple tumors of different histology, such as in Recklinghausen's disease, or if there is an strong family history for the development of neoplastic disease. In this paper, the authors critically evaluate the available evidence to support the hypothesis that radiation induces tumors in the nervous system. The current concepts of radiation carcinogenesis are discussed and are followed by a discussion of animal data and clinical experience in humans. Finally, a brief discussion on treatment of radiation-induced nervous system tumors is presented

  2. Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors

    DEFF Research Database (Denmark)

    Persson, Bertil R R; Koch, Catrin Bauréus; Grafström, Gustav

    2010-01-01

    Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumor...

  3. Oncogenes and radiation resistance - a review

    International Nuclear Information System (INIS)

    Dritschilo, A.

    1992-01-01

    Oncogenes exert their effects on the genetic programs of cells by regulating signal transduction pathways, resulting in multi-factorial genetic responses. By such actions, the genetic elements responsible for the cellular responses to ionizing radiation may be affected. Reports implicating the association of oncogene expression with modulation of the radiation response include the ras, raf, and myc genes. Experiments overexpressing H-ras and c-raf-1 using genetically engineered constructs result in enhanced post-radiation cellular survival. Conversely, inhibition of raf gene expression has resulted in relative radiation sensitization and delay of human squamous cell carcinoma tumor growth in nude mice. There appears to be a potential strategy for therapeutic intervention. The identification of genes that confer survival advantage following radiation exposure, and understanding their mechanisms of action, may permit a genetically based intervention for radiation sensitization. One such approach employs oligo-deoxynucleotides complementary to oncogene-encoded in RNA's (antisense DNA). (author)

  4. Anti-tumor effect of low dose radiation in mice

    International Nuclear Information System (INIS)

    Fan Zhengping; Lu Jiaben; Zhu Bingchai

    1997-01-01

    The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice

  5. Final Report for Radiation Resistant Magnets II

    International Nuclear Information System (INIS)

    A. F. Zeller

    2005-01-01

    Report on techniques for the fabrication of radiation resistant magnets for the RIA Fragment Separator. The development of magnet designs capable of reasonable life times in high-radiation environments and having reasonable performance is of paramount importance for RIA as well as other high-intensity projects under consideration, such as the Neutrino Factory and FAIR project at GSI. Several approaches were evaluated for radiation resistant superconducting magnets. One approach was to simply use a more radiation resistant epoxy for the coil fabrication. Another approach for cryostable magnets, like the S800 Spectrograph dipole, is the use of all-inorganic materials. The final approach was the development of radiation resistant Cable-In-Conduit-Conductor (CICC) like that used in fusion magnets; though these are not radiation resistant because an organic insulator is used. Simulations have shown that the nuclear radiation heating of the first quadrupoles in the RIA Fragment Separator will be so large that cold mass minimization will be necessary with the magnet iron being at room temperature. Three different types of conductor for radiation resistant superconducting magnets have been built and successfully tested. The cyanate ester potted coils will work nicely for magnets where the lifetime dose is a factor of 20 less than the end of life of the superconductor and the rate of energy deposition is below the heat-removal limit of the coil. The all-inorganic cryostable coil and the metal oxide insulated CICC will provide conductor that will work up to the life of the superconductor and have the ability to remove large quantities of nuclear heating. Obviously, more work needs to be done on the CICC to increase the current density and to develop different insulations; and on the cyanate esters to increase the heat transfer

  6. Physiologic mechanisms in radiation resistance

    International Nuclear Information System (INIS)

    Reichard, S.M.

    1976-01-01

    Some topics discussed are as follows: role of the reticuloendothelial system in the regeneration of the hematopoietic system; uptake of colloidal agents by liver and spleen cells following graded doses of x radiation; effects of x radiation on peritoneal macrophages of rats; stimulation of phagocytic activity of the reticuloendothelial system by estrogens, serum albumin, and bacterial endotoxins; and sequestration of particulate material within the reticuloendothelial organs following x irradiation

  7. Development of radiation resistant PEEK insulation cable

    International Nuclear Information System (INIS)

    Mio, Keigo; Ogiwara, Norio; Hikichi, Yusuke; Furukori, Hisayoshi; Arai, Hideyuki; Nishizawa, Daiji; Nishidono, Toshiro

    2009-04-01

    Material characterization and development has been carried out for cable insulation suitable for use in the J-PARC 3-GeV RCS radiation environment. In spite of its high cost, PEEK (polyether-ether-ketone) has emerged as the leading candidate satisfying requirements of being non-halogen based, highly incombustible and with radiation resistant at least 10 MGy, along with the usual mechanical characteristics such as good elongation at break, which are needed in a cable insulation. Gamma-ray irradiation tests have been done in order to study radiation resistance of PEEK cable. Further, mechanical, electrical and fire retardant characteristics of a complete cable such as would be used at the J-PARC RCS were investigated. As a result, PEEK cables were shown to be not degraded by radiation up to at least 10 MGy, and thus could be expected to operate stably under the 3-GeV RCS radiation environment. (author)

  8. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    International Nuclear Information System (INIS)

    Chen, Miao-Fen; Hsieh, Ching-Chuan; Chen, Wen-Cheng; Lai, Chia-Hsuan

    2012-01-01

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6–neutralizing antibody for 24 hours or stably transfected with IL-6–silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6–silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  9. Determination of the dynamics of tumor hypoxia during radiation therapy using biological imaging on mouse xenograft tumors

    OpenAIRE

    Maftei, Constantin Alin

    2013-01-01

    Background: Chronic, acute and hypoxemic hypoxia can lead to resistance to radiation therapy. The purpose of this thesis was to shed light on the role of these three hypoxia subtypes in radiotherapy. Methods: The amount of total hypoxia and hypoxia subtypes were assessed ex-vivo in xenograft tumors via (immuno-)fluorescence and H&E staining. For the non-invasive detection of hypoxia, tumor-bearing mice were injected with 18F-FMISO and underwent a dynamic PET/CT scan. The hypoxic fraction ...

  10. Development of application technology of radiation-resistant microorganism

    International Nuclear Information System (INIS)

    Kim, Dong Ho; Lim, Sang Yong; Joe, Min Ho; Jung, Jin Woo; Jung, Sun Wook; Song, Du Sup; Choi, Young Ji

    2009-02-01

    The scope of the project is divided into of three parts; (i) to define the survival strategy of radiation-resistant microbes, especially Deinococcus (ii) acquisition of gene resources encoding the novel protein and related with the production of functional materials (iii) development of control technology against radiation-resistant microbes. To this aim, first, the whole transcriptional response of the D. radiodurans strain haboring pprI mutation, which plays an important role in radiation resistance, was analyzed by cDNA microarray. The anti-oxidant activity of the major carotenoid of D. radiodurans, deinoxanthin, was analyzed and the strain was constructed, in which the gene necessary for bio- synthesis of deinoxanthin is deleted. The response to cadmium of D. radiodurans was also investigated through cDNA microarray analysis. Radiogenic therapy, one of the cancer treatments, is designed to use radiation-inducible gene for the treatment. To develop the gene-transfer vehicle for radiogenic therapy, we have investigated the virulence mechanism of Salmonella, which is tumor-targeting bacteria and studied the synergistic effect of some anti-cancer agents on radiation treatment for cancer. Finally, we confirmed that irradiation could decompose a fungus toxin, patulin, into various harmless by-products

  11. Development of application technology of radiation-resistant microorganism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Ho; Lim, Sang Yong; Joe, Min Ho; Jung, Jin Woo; Jung, Sun Wook; Song, Du Sup; Choi, Young Ji [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-02-15

    The scope of the project is divided into of three parts; (i) to define the survival strategy of radiation-resistant microbes, especially Deinococcus (ii) acquisition of gene resources encoding the novel protein and related with the production of functional materials (iii) development of control technology against radiation-resistant microbes. To this aim, first, the whole transcriptional response of the D. radiodurans strain haboring pprI mutation, which plays an important role in radiation resistance, was analyzed by cDNA microarray. The anti-oxidant activity of the major carotenoid of D. radiodurans, deinoxanthin, was analyzed and the strain was constructed, in which the gene necessary for bio- synthesis of deinoxanthin is deleted. The response to cadmium of D. radiodurans was also investigated through cDNA microarray analysis. Radiogenic therapy, one of the cancer treatments, is designed to use radiation-inducible gene for the treatment. To develop the gene-transfer vehicle for radiogenic therapy, we have investigated the virulence mechanism of Salmonella, which is tumor-targeting bacteria and studied the synergistic effect of some anti-cancer agents on radiation treatment for cancer. Finally, we confirmed that irradiation could decompose a fungus toxin, patulin, into various harmless by-products.

  12. Radiation effects on tumor-specific DTH response, 2

    International Nuclear Information System (INIS)

    Nobusawa, Hiroshi; Hachisu, Reiko.

    1991-01-01

    Tumor-specific immunity was induced in C3H mice by immunizing with syngeneic MH134 hepatoma cells. Radiation sensitivity of anti-tumor activity of immunized spleen cells were examined and compared with the radiation sensitivity of the delayed-type hypersensitivity (DTH)-response. The spleen cells were irradiated in vitro, then mixed with the tumor cells. DTH-response intensity was determined from the footpad increment twenty-four hours after inoculation of tumor cells with immunized spleen cells. Anti-tumor activity of the spleen cells, based on growth inhibition of tumor cells, was measured by a cytostatic test in vivo with diffusion chambers. Tumor-specific DTH response was suppressed dose-dependently in the range of 12-24 Gy irradiation. No suppression was observed below 12 Gy. Without irradiation, growth of tumor cells was inhibited by immunized spleen cells more effectively than by normal spleen cells. Anti-tumor activity of immunized and normal spleen cells was diminished by irradiation doses of 20 Gy and 10 Gy, respectively. Comparing our report with others that analyzed the type of anti-tumor effector cells induced in this experimental system, we concluded that tumor-specific anti-tumor activity (tumor growth inhibition in vivo) that was radiosensitive at 10-20 Gy depended on a DTH-response. (author)

  13. Research of radiation-resistant microbial organisms

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dongho; Lim, Sangyong; Joe, Minho; Park, Haejoon; Song, Hyunpa; Im, Seunghun; Kim, Haram; Kim, Whajung; Choi, Jinsu; Park, Jongchun

    2012-01-15

    Many extremophiles including radiation-resistant bacteria Deinococcus radiodurans have special characteristics such as novel enzymes and physiological active substances different from known biological materials and are being in the spotlight of biotechnology science. In this research, basic technologies for the production of new genetic resources and microbial strains by a series of studies in radiation-resistant microbial organisms were investigated and developed. Mechanisms required for radiation-resistant in Deinococcus radiodurans were partly defined by analyzing the function of dinB, pprI, recG, DRA{sub 0}279, pprM, and two-component signal transduction systems. To apply genetic resource and functional materials from Deinococcus species, omics analysis in response to cadmium, construction of macroscopic biosensor, and characterization of carotenoids and chaperon protein were performed. Additionally, potential use of D. geothermalis in monosaccharide production from non-biodegradable plant materials was evaluated. Novel radiation resistant yeasts and bacteria were isolated and identified from environmental samples to obtain microbial and genomic resources. An optimal radiation mutant breeding method was set up for efficient and rapid isolation of target microbial mutants. Furthermore, an efficient ethanol producing mutant strain with high production yield and productivity was constructed using the breeding method in collaboration with Korea Research Institute of Bioscience and Biotechnology. Three Deinococcal bioindicators for radiation dosage confirmation after radiation sterilization process were developed. These results provide a comprehensive information for novel functional genetic elements, enzymes, and physiological active substances production or application. Eventually, industrial microbial cell factories based on radiation resistant microbial genomes can be developed and the technologies can be diffused to bioindustry continuously by this project.

  14. Research of radiation-resistant microbial organisms

    International Nuclear Information System (INIS)

    Kim, Dongho; Lim, Sangyong; Joe, Minho; Park, Haejoon; Song, Hyunpa; Im, Seunghun; Kim, Haram; Kim, Whajung; Choi, Jinsu; Park, Jongchun

    2012-01-01

    Many extremophiles including radiation-resistant bacteria Deinococcus radiodurans have special characteristics such as novel enzymes and physiological active substances different from known biological materials and are being in the spotlight of biotechnology science. In this research, basic technologies for the production of new genetic resources and microbial strains by a series of studies in radiation-resistant microbial organisms were investigated and developed. Mechanisms required for radiation-resistant in Deinococcus radiodurans were partly defined by analyzing the function of dinB, pprI, recG, DRA 0 279, pprM, and two-component signal transduction systems. To apply genetic resource and functional materials from Deinococcus species, omics analysis in response to cadmium, construction of macroscopic biosensor, and characterization of carotenoids and chaperon protein were performed. Additionally, potential use of D. geothermalis in monosaccharide production from non-biodegradable plant materials was evaluated. Novel radiation resistant yeasts and bacteria were isolated and identified from environmental samples to obtain microbial and genomic resources. An optimal radiation mutant breeding method was set up for efficient and rapid isolation of target microbial mutants. Furthermore, an efficient ethanol producing mutant strain with high production yield and productivity was constructed using the breeding method in collaboration with Korea Research Institute of Bioscience and Biotechnology. Three Deinococcal bioindicators for radiation dosage confirmation after radiation sterilization process were developed. These results provide a comprehensive information for novel functional genetic elements, enzymes, and physiological active substances production or application. Eventually, industrial microbial cell factories based on radiation resistant microbial genomes can be developed and the technologies can be diffused to bioindustry continuously by this project

  15. Radiation therapy for primary spinal cord tumors in adults

    International Nuclear Information System (INIS)

    Jeremic, B.; Grujicic, D.; Jovanovic, D.; Djuric, L.; Mijatovic, L.

    1990-01-01

    This paper evaluates the role of radiation therapy in management of primary spinal cord tumors in adults. Records of 21 patients with primary spinal cord tumors treated with radiation therapy after surgery were retrospectively reviewed. Histologic examination showed two diffuse and 10 localized ependymomas, six low-grade gliomas, and three malignant gliomas. Surgery consisted of gross tumor resection in six patients, subtotal resection in three patients, and biopsy in 12 patients. Three patients also received chemotherapy. Radiation dose range from 45 to 55 Cy

  16. Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance.

    Science.gov (United States)

    Ruggiero, Raúl A; Bruzzo, Juan; Chiarella, Paula; di Gianni, Pedro; Isturiz, Martín A; Linskens, Susana; Speziale, Norma; Meiss, Roberto P; Bustuoabad, Oscar D; Pasqualini, Christiane D

    2011-11-15

    Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. ©2011 AACR

  17. Radiation resistance of plastic solid

    International Nuclear Information System (INIS)

    Moriyama, Noboru; Dojiri, Shigeru; Wadachi, Yoshiki

    1985-01-01

    The radiation from nucleides contained in solidified wates have some effects on the degradation of the solidification materials. This report deals with effects of such radiation on the mechanical strength of waste-plastics composites and on the generation of gasses. It is shown that the mechanical strength of polyethylene and polyester solids will not decrease at a total absorbed dose of 10 6 rad, a dose which a low-level waste composite is expected to receive during an infinite period of time. Rather, it increases in the case of polyethylene. The amount of gas generated from degraded polyethylene is about three times as large as that from polyester, namely, about 6 l per 200 l drum can at 10 6 rad. Hydrogen accounts for about 80 % of the total gas generated from polyethylene. On the other hand, the gas from polyester solid mainly contains hydrogen, carbon dioxide, carbon monoxide and methane, with a composition greatly dependent on the type of the waste contained. It is concluded from these results that plastic materials can serve satisfactorily as for as the effects of radiation on their mechanical strength and gas generation are concerned. A more important problem still remaining to be solved is the effects of radiation on the leaching of radioactive nuclides. (Nogami, K.)

  18. Radiation resistance of ethylene-styrene copolymers

    International Nuclear Information System (INIS)

    Matsumoto, Kaoru; Ikeda, Masaaki; Ohki, Yoshimichi; Kusama, Yasuo; Harashige, Masahiro; Yazaki, Fumihiko.

    1988-01-01

    In this paper, the radiation resistance of ethylene-styrene copolymer, a polymeric resin developed newly by the authors, is reported. Resin examined were five kinds of ethylene-styrene copolymers: three random and two graft copolymers with different styrene contents. Low-density polyethylene was used as a reference. The samples were irradiated by 60 Co γ-rays to total absorbed doses up to 10 MGy. The mechanical properties of the smaples were examined. Infrared spectroscopy, differential scanning calorimetry and X-ray scattering techniques were used to examine the morphology of the samples. The random copolymers are soft and easy to extend, because benzene rings which exisist highly at random hinder the crystallization. As for the radiation resistance, they are highly resistant to γ-rays in the aspects of carbonyl group formation, gel formation, and elongation. Further, they show even better radiation resistance when proper additives were compounded in. The graft copolymers are hard to extend, because they consist of segregated polystyrene and polyethylene regions which are connected with each other. The tensile strength of irradiated graft copolymers does not decrease below that of unirradiated copolymers, up to a total dose of 10 MGy. As a consequence, it can be said that ethylene-styrene copolymers have good radiation resistance owing to the so-called 'sponge' effect of benzene rings. (author)

  19. Radiation therapy for resistant sternal hydatid disease

    International Nuclear Information System (INIS)

    Ulger, S.; Barut, H.; Tunc, M.; Aydinkarahaliloglu, E.; Aydin, E.; Karaoglanoglu, N.; Gokcek, A.

    2013-01-01

    Hydatid disease is a zoonotic infectious disease for which there are known treatment procedures and effective antibiotics; however, there are resistant cases that do not respond to medication or surgery. We report a case diagnosed as hydatid disease of the chest wall and treated with radiation therapy (RT) after medical and surgical therapy had failed. In conclusion, RT represents an alternative treatment modality in resistant cases. (orig.)

  20. On the honeybee resistance to gamma radiation

    International Nuclear Information System (INIS)

    Courtois, G.; Lecomte, J.

    1960-01-01

    The honeybee, when irradiated by gamma radiations from a cobalt-60 source can stand a 18000 r dose without any apparent harm. Noticeable harm is observed for 90000 r. while immediate death of 100% of the individuals is obtained with a 200000 r dose. The physiological condition of the honeybee plays an important role in its resistance to gamma radiation. Reprint of a paper published in Annales de l'abeille, IV, 1959, p. 285-290 [fr

  1. Intensity-Modulated Radiation Therapy for Primary Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhong-min Wang

    2004-01-01

    Radiation therapy has been used to treat primary brain tumors as standard primary and/or adjunctive therapies for decades. It is difficult for conventional radiotherapy to deliver a lethal dose of radiation to the tumors while sparing surrounding normal brain due to complicated structures and multifunction in human brain. With the understanding of radiation physics and computer technology, a number of novel and more precise radiotherapies have been developed in recent years. Intensity modulated radiotherapy (IMRT) is one of these strategies. The use of IMRT in the treatment of primary brain tumors is being increasing nowadays. It shows great promise for some of primary brain tumors and also presents some problems, This review highlights current IMRT in the treatment of mainly primary brain tumors.

  2. Radiation resistance in a melphalan-resistant subline of a rat mammary carcinoma

    International Nuclear Information System (INIS)

    Lehnert, S.; Vestergaard, J.; Batist, G.; Aloui-Jamali, M.A.

    1994-01-01

    A subline of a rat mammary carcinoma (MATB 13762), selected for resistance to melphalan, is cross-resistant to other alkylating drugs, to unrelated drugs and to ionizing radiation. The difference in radioresponse between the sensitive wild-type cell line and the melphalan- and radiation-resistant line (MLN r ) is related to the size of the α component in the linear-quadratic model. Reduction of dose rate does not affect the response of MLN r cells but does increase survival for wild-type cells. MLN r cells have elevated levels of reduced glutathione (GSH) and overexpress redox enzymes glutathione-S-transferase and glutathione peroxidase. Modest depletion of GSH (to 50% of control) radiosensitizes MLN r cells but not wild-type cells. On the basis of the results of an excitation assay, growth delay and tumor control experiments, MATB MLN r tumors are also more radioresistant than wild-type cells when irradiated in situ. However, wild-type cells irradiated shortly after excision of the tumor are much more radioresistant than the same cells irradiated 24 h after excision or maintained in culture, and their response resembles that of MLN r cells irradiated under the same conditions. These results suggest that, in spite of some similarity between the in vivo and in vitro observations, intrinsic radioresistance is not the most important factor influencing the response of MLN r cells in vivo. 22 refs., 7 figs., 4 tabs

  3. Bacterial and archaeal resistance to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Confalonieri, F; Sommer, S, E-mail: fabrice.confalonieri@u-psud.fr, E-mail: suzanne.sommer@u-psud.fr [University Paris-Sud, CNRS UMR8621, Institut de Genetique et Microbiologie, Batiments 400-409, Universite Paris-Sud, 91405 Orsay (France)

    2011-01-01

    Organisms living in extreme environments must cope with large fluctuations of temperature, high levels of radiation and/or desiccation, conditions that can induce DNA damage ranging from base modifications to DNA double-strand breaks. The bacterium Deinococcus radiodurans is known for its resistance to extremely high doses of ionizing radiation and for its ability to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Recently, extreme ionizing radiation resistance was also generated by directed evolution of an apparently radiation-sensitive bacterial species, Escherichia coli. Radioresistant organisms are not only found among the Eubacteria but also among the Archaea that represent the third kingdom of life. They present a set of particular features that differentiate them from the Eubacteria and eukaryotes. Moreover, Archaea are often isolated from extreme environments where they live under severe conditions of temperature, pressure, pH, salts or toxic compounds that are lethal for the large majority of living organisms. Thus, Archaea offer the opportunity to understand how cells are able to cope with such harsh conditions. Among them, the halophilic archaeon Halobacterium sp and several Pyrococcus or Thermococcus species, such as Thermococcus gammatolerans, were also shown to display high level of radiation resistance. The dispersion, in the phylogenetic tree, of radioresistant prokaryotes suggests that they have independently acquired radioresistance. Different strategies were selected during evolution including several mechanisms of radiation byproduct detoxification and subtle cellular metabolism modifications to help cells recover from radiation-induced injuries, protection of proteins against oxidation, an efficient DNA repair tool box, an original pathway of DNA double-strand break repair, a condensed nucleoid that may prevent the dispersion of the DNA fragments and specific radiation-induced proteins involved in

  4. Naturally occurring and radiation-induced tumors in SPF mice, and genetic influence in radiation leukemogenesis

    International Nuclear Information System (INIS)

    Kasuga, T.

    1979-01-01

    The data obtained so far in this study point to a strong genetic influence not only on the types and incidence of naturally occurring and radiation-induced tumors but also on radiation leukemogenesis. (Auth.)

  5. Design of online testing system of material radiation resistance

    International Nuclear Information System (INIS)

    Wan Junsheng; He Shengping; Gao Xinjun

    2014-01-01

    The capability of radiation resistance is important for some material used in some specifically engineering fields. It is the same principal applied in all existing test system that compares the performance parameter after radiation to evaluate material radiation resistance. A kind of new technique on test system of material radiation resistance is put forward in this paper. Experimentation shows that the online test system for material radiation resistance works well and has an extending application outlook. (authors)

  6. Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

    International Nuclear Information System (INIS)

    Nagane, Masaki; Yasui, Hironobu; Yamamori, Tohru; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Kameya, Hiromi; Nakamura, Hideo; Fujii, Hirotada; Inanami, Osamu

    2013-01-01

    Highlights: •IR-induced NO increased tissue perfusion and pO 2 . •IR increased NO production in tumors without changes in the mRNA and protein levels of NOS isoforms. •NOS activity assay showed that IR upregulated eNOS activity in tumors. •IR-induced NO decreased tumor hypoxia and altered tumor radiosensitivity. -- Abstract: Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO 2 in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy × 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy

  7. Enhanced tumor responses through therapies combining CCNU, MISO and radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, S.A.

    1984-01-01

    Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

  8. CERN selects Fujikura's radiation resistant fiber

    CERN Multimedia

    2007-01-01

    "Fujikura recently announced that its radiation resistant single mode optical fiber has been selected by CERN, the European Laboratory for Particle Physics, to provide communication links within the world's largest particle accelerator - the Large Hadron Collider (LHC) - near Geneva, Switzerland." (1/2 page)

  9. CERN selects Fujikura's radiation resistant fibre

    CERN Multimedia

    2007-01-01

    "Fujikura today announced that its radiation resistant single mode optical fibre has been selected by CERN, the European Laboratory for Particle Physics, to provide communication links within the world's largest particle accelerator - the Large hadron Collider (LHC) - near Genevan, Switzerland. (1/2 page)

  10. Radiation-resistant beamline components at LAMPF

    International Nuclear Information System (INIS)

    Macek, R.J.; Grisham, D.L.; Lambert, J.e.; Werbeck, R.

    1983-01-01

    A variety of highly radiation-resistant beamline components have been successfully developed at LAMPF primarily for use in the target cells and beam stop area of the intense proton beamline. Design features and operating experience are reviewed for magnets, instrumentation, targets, vacuum seals, vacuum windows, collimators, and beam stops

  11. A stunning resistance to radiations

    International Nuclear Information System (INIS)

    Etien, S.

    2010-01-01

    The Deinococus radiodurans bacteria (DRB) can survive extreme radiation doses as high as 100 times the doses that kill other bacteria. The number of DNA breaking due to irradiation is the same as in other bacteria but DRB benefits from a very efficient DNA repairing system. This system relies on the fact that DRB owns 4 to 10 identical copies of its genome and because of this high number of copies the repair process is very likely to find a no-damaged part of the DNA in one copy to reconstitute the DNA. It appears that this process does not involve specific enzymes but enzymes that are present in any other bacteria. The efficiency of the repairing process relies on two things: first, the circular shape of the genome that avoids the spreading in the cell of the DNA breaks, and secondly, the enzymes are protected from irradiation oxidation by a high concentration in manganese and iron. (A.C.)

  12. The influence of the stem cell marker ALDH and the EGFR-PI3 kinase act signaling pathway on the radiation resistance of human tumor cell lines; Der Einfluss des Stammzellmarkers ALDH und des EGFR-PI3 Kinase-Akt Signalwegs auf die Strahlenresistenz humaner Tumorzelllinien

    Energy Technology Data Exchange (ETDEWEB)

    Mihatsch, Julia

    2014-07-14

    Cancer is the second leading cause of death in industriated nations. Besides surgery and chemotherapy, radiotherapy (RT) is an important approach by which about 60% of patients are treated. The response of these patients to RT is very heterogenous. On the one hand, there are patients with tumors which are radiosensitive and can be cured, but on the other hand patients bear tumors which are quite resistant to radiotherapy. A Radioresistant phenotype of tumor cells causes treatment failure consequently leading to a limited response to radiotherapy. It is proposed, that radiotherapy outcome mainly depends on the potential of radiation on controlling growth, proliferation and survival of a specific population of tumor cells called cancer stem cells (CSCs) or tumor-initiating cells. Based on experimental studies so far reported it is assumed that the population of CSC varies in tumors from different entities and is relatively low compared to the tumor bulk cells in general. According to the CSC hypothesis, it might be concluded that the differential response of tumors to radiotherapy depends on CSC populations, since these supposedly slow replicating cells are able to initiate a tumor, to self renew indefinitely and to generate the differentiated progeny of a tumor. Besides the role of cancer stem cells in radiotherapy response, ionizing radiation (IR) activates the epidermal growth factor receptor (EGFR) and its downstream signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK) and Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathways. Among these pathways, PI3K/Akt is one of the most important pathways involved in post-irradiation survival: Activation of Akt results in activation of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs). DNA-PKcs is a core enzyme involved in repair of IR-induced DNA-double strand breaks (DNA-DSB) through non-homologous end joining (NHEJ). The aim of the

  13. Effect of physiological age on radiation resistance of some bacteria that are highly radiation resistant

    International Nuclear Information System (INIS)

    Keller, L.C.; Maxcy, R.B.

    1984-01-01

    Physiological age-dependent variation in radiation resistance was studied for three bacteria that are highly radiation resistant: Micrococcus radiodurans, Micrococcus sp. isolate C-3, and Moraxella sp. isolate 4. Stationary-phase cultures of M. radiodurans and isolate C-3 were much more resistant to gamma radiation than were log-phase cultures. This pattern of relative resistance was reversed for isolate 4. Resistance of isolate 4 to UV light was also greater during log phase, although heat resistance and NaCl tolerance after heat stresses were greater during stationary phase. Radiation-induced injury of isolate 4 compared with injury of Escherichia coli B suggested that the injury process, as well as the lethal process, was affected by growth phase. The hypothesis that growth rate affects radiation resistance was tested, and results were interpreted in light of the probable confounding effect of methods used to alter growth rates of bacteria. These results indicate that dose-response experiments should be designed to measure survival during the most resistant growth phase of the organism under study. The timing is particularly important when extrapolations of survival results might be made to potential irradiation processes for foods. 17 references

  14. Radiation resistant characteristics of optical fibers

    International Nuclear Information System (INIS)

    Nakasuji, Masaaki; Tanaka, Gotaro; Watanabe, Minoru; Kyodo, Tomohisa; Mukunashi, Hiroaki

    1983-01-01

    It is required to develop the optical fibers with good radiation resistivity because the fibers cause the increase of transmission loss due to glass colouring when they are used under the presence of radiation such as γ-ray. Generally, it is known that SI (step index) fibers are more resistive to radiation than GI (graded index) fibers. However, since a wide band can not be obtained with SI fibers, the development of radiation resistive GI optical fibers is desirable. In this report, the production for trial of the GI fibers of fluorine-doped silica core, the examination of radiation effect on their optical transmission loss by exposing them to γ-ray, thermal and fast neutron beams and also of mechanical strength are described. The GI fibers of fluorine-doped silica core show better radiation resistivity than Ge-doped ones. The B- and F-doped GI fibers show small increase of loss due to γ-ray, but large increase of loss due to thermal neutron beam. This is supposed to be caused by the far greater neutron absorption cross-section of boron than that of other elements. Significant increase of loss was not recognized when 14 MeV fast neutrons (8.6 x 10 4 n/cm 2 .s) were applied by 1.8 x 10 9 n/cm 2 . It was found that ETFE-covered fiber cores generated fluorine-containing gas due to γ irradiation, and the strength was remarkably lowered, but the lowering of strength can be prevented by adding titanium-white to the covering material. (Wakatsuki, Y.)

  15. Sustainably Sourced, Thermally Resistant, Radiation Hard Biopolymer

    Science.gov (United States)

    Pugel, Diane

    2011-01-01

    This material represents a breakthrough in the production, manufacturing, and application of thermal protection system (TPS) materials and radiation shielding, as this represents the first effort to develop a non-metallic, non-ceramic, biomaterial-based, sustainable TPS with the capability to also act as radiation shielding. Until now, the standing philosophy for radiation shielding involved carrying the shielding at liftoff or utilizing onboard water sources. This shielding material could be grown onboard and applied as needed prior to different radiation landscapes (commonly seen during missions involving gravitational assists). The material is a bioplastic material. Bioplastics are any combination of a biopolymer and a plasticizer. In this case, the biopolymer is a starch-based material and a commonly accessible plasticizer. Starch molecules are composed of two major polymers: amylase and amylopectin. The biopolymer phenolic compounds are common to the ablative thermal protection system family of materials. With similar constituents come similar chemical ablation processes, with the potential to have comparable, if not better, ablation characteristics. It can also be used as a flame-resistant barrier for commercial applications in buildings, homes, cars, and heater firewall material. The biopolymer is observed to undergo chemical transformations (oxidative and structural degradation) at radiation doses that are 1,000 times the maximum dose of an unmanned mission (10-25 Mrad), indicating that it would be a viable candidate for robust radiation shielding. As a comparison, the total integrated radiation dose for a three-year manned mission to Mars is 0.1 krad, far below the radiation limit at which starch molecules degrade. For electron radiation, the biopolymer starches show minimal deterioration when exposed to energies greater than 180 keV. This flame-resistant, thermal-insulating material is non-hazardous and may be sustainably sourced. It poses no hazardous

  16. Radiation resistance of optical fibers, (10)

    International Nuclear Information System (INIS)

    Tsunoda, Tsunemi; Ara, Katsuyuki; Morimoto, Naoki; Sanada, Kazuo; Inada, Koichi.

    1991-01-01

    Optical fibers have many excellent characteristics such as the light weight of the material, insulation, the noninductivity of electromagnetic interference noise, the wide band of signal transmission, and small loss. Also in the field of atomic energy, the utilization of optical fibers is positively expanded, and the research on the method of application and so on has been advanced. However in optical fibers, there is the problem that color centers are formed at the relatively low level of radiation, and they are colored. Accordingly, for effectively utilizing optical fibers in radiation environment, it is indispensable to improve their radiation resistance. For the purpose of solving this problem, the authors have carried out the basic research on the effect that radiation exerts to optical fibers and the development of the optical fibers having excellent radiation resistance. For the purpose of expanding the range of application of GeO 2 -doped silica core fibers including GI type in radiation regions, the transmission characteristics of the fibers during irradiation were examined by using the Cl content as the parameter. Therefore, the results are reported. The fibers put to the test, the testing method and the results are described. (K.I.)

  17. Study on radiation necrosis following intraoperative radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Tanaka, Yoshiaki; Takeshita, Nagayuki; Niwa, Kohkichi; Kamata, Noriko; Matsuda, Tadayoshi; Matsutani, Masao

    1989-01-01

    Ninety-five patients with primary or metastatic brain tumors were treated with the intraoperative radiotherapy (IORT). In seven cases, surgery was performed a second time because of suspected of tumor recurrence, later found to be a radiation necrosis. Tumorous lesions were irradiated by IORT in the range of 15 Gy to 20 Gy together with external radiotherapy in the 30 Gy to 72 Gy range. In follow-up postcontrast CT studies, irregularly-shaped lesions appeared at the IORT site and increased in size with the perifocal low density area on subsequent scans. The images resembled those seen in tumor recurrence. Histopathologic changes seen during the follow-up surgery were thought to be mainly the result of radiation necrosis, though viable tumor cells at the marginal tumor site were one possible etiology. A coagulation necrosis with a fibrin exudate was observed in the IORT portal area and the vascular walls exhibited marked degeneration which is symptomatic of delayed radiation necrosis. Thus, post-IORT radiation necrosis is thought to be a direct reaction to this technique, and the delayed absorption of necrotic tissue to be a direct reaction to this technique, and the delayed absorption of necrotic tissue clearly indicates the possibility of adverse effects in its use for treatment of brain tumors. (author)

  18. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    Science.gov (United States)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-08-06

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed.

  19. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    International Nuclear Information System (INIS)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed

  20. Effectiveness of radiation therapy for metastatic spinal tumors producing neurologic impairment

    International Nuclear Information System (INIS)

    Yamamoto, Shuichiro; Nomoto, Satoshi; Imada, Hajime; Nakata, Hajime

    2002-01-01

    The purpose of this study was to evaluate the efficacy of radiation therapy (RT) for treating neurological impairment and improving quality of life (QOL) in patients with metastatic spinal tumors. From 1985 through 2001, 75 patients with metastatic spinal tumors were treated with RT. Neurologic status and Karnofsky performance status were assessed before and after RT. The rate of neurologic improvement was significantly higher in patients with radio-sensitive tumors (75%) than in patients with radio-resistant tumors (37%). Few patients with Karnofsky performance status less than 40% before RT had good QOL after RT. The response to RT did not differ significantly on the basis of duration of paralysis before RT. RT is useful for treating neurologic impairment caused by metastatic spinal tumors, particularly those that are radiosensitive. To have good QOL after RT, treatment should be started in the early stage of neurological impairment. (author)

  1. Clinical implications of heterogeneity of tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Suit, H.; Skates, S.; Taghian, A.; Okunieff, P.; Efird, J.T.

    1992-01-01

    Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinical defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO 2 , (SH), cell proliferation, etc. (author). 39 refs., 7 figs., 3 tabs

  2. MR imaging assisted radiation therapy planning of brain tumors

    International Nuclear Information System (INIS)

    Just, M.; Roesler, H.P.; Higer, H.P.; Kutzner, J.; Thelen, M.

    1990-01-01

    This paper reports on the improvement of the accuracy of treatment portals in radiation therapy of brain tumors with use of MR imaging. After proper processing, the parasagittal MR image showing the largest tumor size and the midline sagittal image were superimposed. With common anatomic landmarks of midline tomogram and lateral simulation radiograph, commensurate reference grids were laid over both images in identical positions. Tumor coordinates were then transferred from the synthesized MR image to the lateral radiograph. Rectangular fields or individual shielding blocks encompassing the tumor could be drawn directly. This new method was used in 17 patients, and results were compared with CT-assisted results

  3. Canine tumor and normal tissue response to heat and radiation

    International Nuclear Information System (INIS)

    Gillette, E.L.; McChesney, S.L.

    1985-01-01

    Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

  4. Some resistance mechanisms to ultraviolet radiation

    International Nuclear Information System (INIS)

    Alcantara D, D.

    2002-12-01

    The cyclical exposure of bacterial cells to the ultraviolet light (UV) it has as consequence an increment in the resistance to the lethal effects of this type of radiation, increment that happens as a result of a selection process of favorable genetic mutations induced by the same UV light. With object to study the reproducibility of the genetic changes and the associate mechanisms to the resistance to UV in the bacteria Escherichia coli, was irradiated cyclically with UV light five different derived cultures of a single clone, being obtained five stumps with different resistance grades. The genetic mapping Hfr revealed that so much the mutation events like of selection that took place during the adaptation to the UV irradiation, happened of random manner, that is to say, each one of the resistant stumps it is the result of the unspecified selection of mutations arisen at random in different genes related with the repair and duplication of the DNA. (Author)

  5. Pharmacological doses of daily ascorbate protect tumors from radiation damage after a single dose of radiation in an intracranial mouse glioma model.

    Science.gov (United States)

    Grasso, Carole; Fabre, Marie-Sophie; Collis, Sarah V; Castro, M Leticia; Field, Cameron S; Schleich, Nanette; McConnell, Melanie J; Herst, Patries M

    2014-01-01

    Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumor environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionizing radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitizing GBM cells will improve survival of GBM patients. Here, we demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a second group received daily intraperitoneal injections of ascorbate (day 8-45) after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumor progression, intraperitoneal ascorbate alone had no effect on tumor progression. Tumor progression was faster in tumor-bearing mice treated with radiation and daily ascorbate than in those treated with radiation alone. Histological analysis showed less necrosis in tumors treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumor microenvironment, which determines whether ascorbate remains outside the cell, acting as a pro-oxidant, or whether it enters the cells and acts as an anti-oxidant.

  6. Radiation treatment of brain tumors: Concepts and strategies

    International Nuclear Information System (INIS)

    Marks, J.E.

    1989-01-01

    Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.72 references

  7. Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

    International Nuclear Information System (INIS)

    Bourke, Vincent A.; Zhao Dawen; Gilio, Joseph; Chang, C.-H.; Jiang Lan; Hahn, Eric W.; Mason, Ralph P.

    2007-01-01

    Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by 19 F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm 3 ) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO 2 ) than their smaller counterparts ( 3 ). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO 2 , and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO 2 > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy

  8. Malignant tumors arising in the maxillary region after radiation therapy

    International Nuclear Information System (INIS)

    Shimizu, Sawamichi; Shirahata, Yuichi; Uchida, Yutaka

    1984-01-01

    Although radiotherapy has proven of great therapeutic value in the treatment of malignant tumors, it should also be borne in mind that radiation has a serious potential risk of giving rise to a secondary malignancy. We recently experienced 2 cases each of carcinoma and sarcoma arising in the irradiated areas long after radiation therapy for malignant tumors. In these 4 cases, 2 males and 2 females, the primary neoplastic diseases were squamous cell carcinoma, epidermoid carcinoma, carcinoma of unknown pathology and malignant lymphoma, and the secondary tumors were epidermoid carcinoma, squamous cell carcinoma, osteosarcoma and chondrosarcoma, respectively. The sites of occurrence of these malignancies were invariably in the maxillary region; the mean latent period was 15 years, aside from an infantile case with a latent period of 5 years. In view of the primary diseases being malignant tumors the following criteria were set up for the diagnosis of radiation-induced malignancies: (1) the site of occurrence is within the confines of a previously irradiated area, (2) the latent period is prolonged and (3) the malignancy occurs as a double tumor. Therapy was primarily by operation. The prognosis was exceedingly ominous, the average survival time being 22 months. This was probably and mainly because of rapidity of tumor growth. Thus, the secondary tumors had already spread back to inward by the time they were first discovered. This should be kept in mind during a long-term follow-up of patients receiving radiotherapy for malignancy. (author)

  9. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

    To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

  10. Radiation-induced malignant tumors of skin and their histogenesis

    International Nuclear Information System (INIS)

    Li Guomin; Chen Yunchi; Yang Yejing

    1987-01-01

    Seven cases of radiation-induced malignant tumors and 60 cases of chronic radiation damage of skin are reported. Severe hyperplasia, false epitheliomatoid hyperpiasia and atypical proliferation of epithelia and atypical proliferation of fibrohistocytes were the main changes found in chronic radiation damage of skin. The development of malignant tumors from chronic radiation damage of skin can be divided into 4 periods: necrotic and degenerative change period, benign proliferative period, atypical proliferative period and malignant change period. The incidence of hyperplastic changes of skin is related to the time elapse after irradiation and the integrated dose of radiation. The longer the duration after irradiation and the larger the integrated dose are, the higher will be the incidence of hyperplastic changes

  11. Movie prediction of lung tumor for precise chasing radiation therapy

    International Nuclear Information System (INIS)

    Chhatkuli, Ritu Bhusal; Demachi, Kazuyuki; Kawai, Masaki; Sakakibara, Hiroshi; Uesaka, Mitsuru

    2012-01-01

    In recent years, precision for radiation therapy is a major challenge in the field of cancer treatment. When it comes to a moving organ like lungs, limiting the radiation to the target and sparing the surrounding healthy tissue is always a concern. It can induce the limit in the accuracy of area irradiated during lung cancer radiation therapy. Many methods have been introduced to compensate the motion in order to reduce the effect of radiation to healthy tissue due to respiratory motion. The motion of lung along with the tumor makes it very difficult to spare the healthy tissue during radiation therapy. The fear of this unintended damage to the neighboring tissue often limits the dose that can be applied to the tumor. The purpose of this research is the prediction of future motion images for the improvement of tumor tracking method. We predict the motion images by using principal component analysis (PCA) and multi-channel singular spectral analysis (MSSA) method. Time series x-ray images are used as training images. The motion images were successfully predicted and verified using the developed algorithm. The real time implementation of this method in future is believed to be significant for higher level of real time tumor tracking during radiation therapy. (author)

  12. Combination effect of cisplatin and radiation in murine solid tumors

    International Nuclear Information System (INIS)

    Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

    1986-01-01

    The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

  13. Tumor induction by small doses ionising radiation

    International Nuclear Information System (INIS)

    Putten, L.M. van

    1981-01-01

    Tumour induction by low radiation doses is in general a non-linear process. However, two exceptions are well known: myeloid leukemia in Rf mice and mamma tumours in Sprague-Dawley rats. The hypothesis that radiation is highly oncogenic in combination with cell growth stimuli, as reaction to massive cell death after damage of nuclear DNA, is applied to man and the consequences are discussed. (Auth.)

  14. arXiv Radiation resistant LGAD design

    CERN Document Server

    Ferrero, M.; Boscardin, M.; Cartiglia, N.; Dalla Betta, G.F.; Galloway, Z.; Mandurrino, M.; Mazza, S.; Paternoster, G.; Ficorella, F.; Pancheri, L.; Sadrozinski, H-F W.; Sola, V.; Staiano, A.; Seiden, A.; Zhao, Y.

    In this paper, we report on the radiation resistance of 50-micron thick LGAD detectors manufactured at the Fondazione Bruno Kessler employing several different doping combinations of the gain layer. LGAD detectors with gain layer doping of Boron, Boron low-diffusion, Gallium, Carbonated Boron and Carbonated Gallium have been designed and successfully produced. These sensors have been exposed to neutron fluences up to $\\phi_n \\sim 3 \\cdot 10^{16}\\; n/cm^2$ and to proton fluences up to $\\phi_p \\sim 9\\cdot10^{15}\\; p/cm^2$ to test their radiation resistance. The experimental results show that Gallium-doped LGADs are more heavily affected by initial acceptor removal than Boron-doped LGAD, while the presence of Carbon reduces initial acceptor removal both for Gallium and Boron doping. Boron low-diffusion shows a higher radiation resistance than that of standard Boron implant, indicating a dependence of the initial acceptor removal mechanism upon the implant width. This study also demonstrates that proton irradiati...

  15. Extreme Ionizing-Radiation-Resistant Bacterium

    Science.gov (United States)

    Vaishampayan, Parag A.; Venkateswaran, Kasthuri J.; Schwendner, Petra

    2013-01-01

    There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing micro-organisms. Eradi cation techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation-based sterilization processes. Due to their resistance to a variety of perturbations, the nonspore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-sporeforming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/m2), and desiccation (years). These resistive phenotypes of Deinococcus enhance the

  16. High Radiation Resistance IMM Solar Cell

    Science.gov (United States)

    Pan, Noren

    2015-01-01

    Due to high launch costs, weight reduction is a key driver for the development of new solar cell technologies suitable for space applications. This project is developing a unique triple-junction inverted metamorphic multijunction (IMM) technology that enables the manufacture of very lightweight, low-cost InGaAsP-based multijunction solar cells. This IMM technology consists of indium (In) and phosphorous (P) solar cell active materials, which are designed to improve the radiation-resistant properties of the triple-junction solar cell while maintaining high efficiency. The intrinsic radiation hardness of InP materials makes them of great interest for building solar cells suitable for deployment in harsh radiation environments, such as medium Earth orbit and missions to the outer planets. NASA Glenn's recently developed epitaxial lift-off (ELO) process also will be applied to this new structure, which will enable the fabrication of the IMM structure without the substrate.

  17. Radiation therapy of 9L rat brain tumors

    International Nuclear Information System (INIS)

    Henderson, S.D.; Kimler, B.F.; Morantz, R.A.

    1981-01-01

    The effects of radiation therapy on normal rats and on rats burdened with 9L brain tumors have been studied. The heads of normal rats were x-irradiated with single exposures ranging from 1000 R to 2700 R. Following acute exposures greater than 2100 R, all animals died in 8 to 12 days. Approximately 30% of the animals survived beyond 12 days over the range of 1850 to 1950 R; following exposures less than 1850 R, all animals survived the acute radiation effects, and median survival times increased with decreasing exposure. Three fractionated radiation schedules were also studied: 2100 R or 3000 R in 10 equal fractions, and 3000 R in 6 equal fractions, each schedule being administered over a 2 week period. The first schedule produced a MST of greater than 1 1/2 years; the other schedules produced MSTs that were lower. It was determined that by applying a factor of 1.9, similar survival responses of normal rats were obtained with single as with fractionated radiation exposures. Animals burdened with 9L gliosarcoma brain tumors normally died of the disease process within 18 to 28 days ater tumor inoculation. Both single and fractionated radiation therapy resulted in a prolongation of survival of tumor-burdened rats. This prolongation was found to be linearly dependent upon the dose; but only minimally dependent upon the time after inoculation at which therapy was initiated, or upon the fractionation schedule that was used. As with normal animals, similar responses were obtained with single as with fractionated exposures when a factor (1.9) was applied. All tumor-bearing animals died prior to the time that death was observed in normal, irradiated rats. Thus, the 9L gliosarcoma rat brain tumor model can be used for the pre-clinical experimental investigation of new therapeutic schedules involving radiation therapy and adjuvant therapies

  18. Bcl-2 inhibitors potentiate the cytotoxic effects of radiation in Bcl-2 overexpressing radioresistant tumor cells

    International Nuclear Information System (INIS)

    Hara, Takamitsu; Omura-Minamisawa, Motoko; Chao Cheng; Nakagami, Yoshihiro; Ito, Megumi; Inoue, Tomio

    2005-01-01

    Purpose: Bcl-2, an inhibitor of apoptosis frequently shows elevated expression in human tumors, thus resulting in resistance to radiation therapy. Therefore, inhibiting Bcl-2 function may enhance the radiosensitivity of tumor cells. Tetrocarcin A (TC-A) and bcl-2 antisense oligonucleotides exhibit antitumor activity by inhibiting Bcl-2 function and transcription, respectively. We investigated whether these antitumor agents would enhance the cytotoxic effects of radiation in tumor cells overexpressing Bcl-2. Methods and materials: We used HeLa/bcl-2 cells, a stable Bcl-2-expressing cell line derived from wild-type HeLa (HeLa/wt) cells. Cells were incubated with TC-A and bcl-2 antisense oligonucleotides for 24 h after irradiation, and cell viability was then determined. Apoptotic cells were quantified by flow cytometric assay. Results: The HeLa/bcl-2 cells were more resistant to radiation than HeLa/wt cells. At concentrations that are not inherently cytotoxic, both TC-A and bcl-2 antisense oligonucleotides increased the cytotoxic effects of radiation in HeLa/bcl-2 cells, but not in HeLa/wt cells. However, in HeLa/bcl-2 cells, additional treatment with TC-A in combination with radiation did not significantly increase apoptosis. Conclusions: The present results suggest that TC-A and bcl-2 antisense oligonucleotides reduce radioresistance of tumor cells overexpressing Bcl-2. Therefore, a combination of radiotherapy and Bcl-2 inhibitors may prove to be a useful therapeutic approach for treating tumors that overexpress Bcl-2

  19. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  20. Radiation resistance of track etched membranes

    International Nuclear Information System (INIS)

    Buczkowski, M.; Sartowska, B.; Wawszczak, D.; Starosta, W.

    2001-01-01

    Track etched membranes (TEMs) obtained by irradiation of polymer films with heavy ions and subsequent etching of latent tracks can be applied in many fields and among others in biomedicine as well. It is important to know radiation resistance of TEMs because of wide use of radiation sterilization in the case of biomedical devices. Tensile properties of TEMs made of PET and PC films with the thickness of 10 μm after electron irradiation at different doses are known from literature. Nowadays TEMs are being manufactured from thicker (20 μm) PET and PC films as well as polyethylene naphthalate (PEN) films are proposed for TEMs. It seems to be important to get data about radiation resistance of new kinds of TEMs. Samples of polymer films made of PET and PEN with the thickness of 19-25 μm and TEMs made of such materials have been irradiated using 10 MeV electron beam with doses up to 990 kGy. Tensile properties and SEM photographs of the samples after irradiation are given in the paper

  1. Radiation resisting features of pure quartz fiber

    International Nuclear Information System (INIS)

    Fujii, Takashi; Nagasawa, Yoshiya; Hoshi, Hiroshi; Tomon, Ryoichi; Ooki, Yoshimichi; Yahagi, Kichinosuke

    1985-01-01

    The control of the generation of color centers is essential for optical fibers used in radiation environment. Even pure quartz which is the best radiation resisting material is not exceptional also elucidarion of the mechanism of the generation of color center is necessary for the development of optical fiber with higher radiation resisting feature. Previously, it was assumed that color centers are distributed uniformly throughout cores. Determination of the distribution of color centers was attempted. Cores were etched with HF after γ-ray irradiation, and the changes of intensity of ESR signals of NBOHC and E'-center were determined. NBOHC were not found in circumferential part, and concentrated in the central part. In other words the tendency of distribution is diametral. Thus, the distribution of precursor is supposed to be affected by certain external cause and the generation of NBOHC was depressed in circumferential area. The distribution of E'-center of high OH sample showed similar tendency and high in the center. Where as the distribution in low OH sample was uniform. The external cause is supposed to be hydrogen derived from silicone clad and silicone buffer. Two kind of precursor is suspected for the explanation of the difference of the E'-center in high OH sample and low OH sample. (Ishimitsu, A.)

  2. Radiobiologic effect of intermittent radiation exposure in murine tumors

    International Nuclear Information System (INIS)

    Sugie, Chikao; Shibamoto, Yuta; Ito, Masato; Ogino, Hiroyuki; Miyamoto, Akihiko; Fukaya, Nobuyuki; Niimi, Hiroshige; Hashizume, Takuya

    2006-01-01

    Purpose: In stereotactic irradiation using a linear accelerator, the effect of radiation may be reduced during intermittent exposures owing to recovery from sublethal damage in tumor cells. After our previous in vitro study suggesting this phenomenon, we investigated the issue in murine tumors. Methods and Materials: We used EMT6 and SCCVII tumors approximately 1 cm in diameter growing in the hind legs of syngeneic mice. Three schedules of intermittent radiation were investigated. First, 2 fractions of 10 Gy were given at an interval of 15-360 min to investigate the pattern of recovery from sublethal damage. Second, 5 fractions of 4 Gy were given with interfraction intervals of 2.5-15 min each. Third, 10 fractions of 2 Gy were given with interfraction intervals of 1-7 min each. Doses of 15-20 Gy were also given without interruption to estimate the dose-modifying factors. Tumors were excised 20 h later, and tumor cell survival was determined by an in vivo-in vitro assay. Results: In the 2-fraction experiment, the increase in cell survival with elongation of the interval was much less than that observed in our previous in vitro study. In the 5- and 10-fraction experiments, no significant increase in cell survival was observed after the intermittent exposures. Moreover, cell survival decreased at most points of the 5-fraction experiments by interruption of radiation in both EMT6 and SCCVII tumors. In the 10-fraction experiment, cell survival also decreased when the interruption was 3 or 7 min in EMT6 tumors. Conclusion: The results of the present in vivo studies were different from those of our in vitro studies in which cell survival increased significantly when a few minutes or longer intervals were posed between fractions. This suggests that recovery from sublethal damage in vivo may be counterbalanced by other phenomena such as reoxygenation that sensitizes tumor cells to subsequent irradiation

  3. Evaluation of texaphyrins as tumor selective radiation sensitizers

    International Nuclear Information System (INIS)

    Qing Fan; Woodburn, Kathryn W.; Young, Stuart W.

    1997-01-01

    Texaphyrins are expanded porphyrin macrocycles that selectively localize and are retained in cancerous lesions. The function of the texaphyrin can be manipulated by the incorporation of different metal ions into the macrocycle's central cavity. Gadolinium texaphyrin (Gd-Tex) and lutetium texaphyrin (Lu-Tex) were evaluated as radiation sensitizers. Radiation sensitization studies were performed using SMT-F and EMT6 mammary tumor-bearing mice. Single and multifraction dose regimens were performed. SMT-F bearing DBA/2N mice and EMT6 bearing Balb/c mice were intravenously administered with Gd-Tex of Lu-Tex (5-40 μmol/kg) 30 minutes to 5 hours prior to radiation (10-50 Gray) for the single fraction studies. The more radioresistant EMT-6 sarcoma model was used for the multifraction studies. The tumor bearing animals were injected with Gd-Tex (5, 20, or 40 μmol/kg) to 2 hours prior radiation (1, 2, or 4 Gray), this regimen was performed for five consecutive days. Gd-Tex is paramagnetic and has a strong fluorescence signal. Tumor selectivity was determined by MRI and fluorescence spectral imaging before and up to 24 hours following the administration of Gd-Tex. Gd-Tex but not Lu-Tex, proved to be an effective radiation sensitizer. Administration of Gd-Tex (40 μmol/kg) prior to a single dose of 30 Gray radiation provided a significant improvement in survival in SMT-F-bearing DBA/2N mice as compared to animals receiving radiation alone (p = 0.0034). A significant radiation sensitization effect was also found in multiple fraction studies (five consecutive days) with Balb/C mice bearing EMT-6 neoplasma-- following 1 Gray of radiation for 5 days there was a significant difference between the 20 and 40 μmol/kg group and controls (p = 0.003, p = 0.005 respectively). MRI and fluorescence spectral imaging studies of tumor bearing animals revealed excellent contrast enhancement of the tumor which persisted up to 24 hours. Texaphyrins localize in neoplasms as visualized using MRI

  4. Microenvironment around tumors and their radiation sensitivity. The possibility of molecular target for radiation sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Akimoto, Tetsuo; Ishikawa, Hitoshi [Gunma Univ., Maebashi (Japan). School of Medicine; Mitsuhashi, Norio [Tokyo Women' s Medical Coll. (Japan)

    2001-12-01

    There have been scarce studies concerning the effect of microenvironment around tumors on their radiation sensitivity and this review describes the influence of environmental factors of cell adhesion, growth factors, cytokines, hypoxia and angiogenesis on the sensitivity and response to radiation and on the signal transduction to consider the possibility of molecular target for radiation sensitization. Cell-cell adhesion and cell-matrix interaction in response to radiation may have a role in inducing apoptotic process like anti-apoptotic or pro-apoptotic one. Growth factors and cytokines can affect the tumor response to radiation in more extent than p53 gene status since apoptosis induction is not always an indication of radiation sensitivity in many tumors clinically encountered. Radiation sensitivity is low in tumor cells under hypoxic conditions and it is important to know the relationship between those hypoxic cell response and angiogenesis by factors like HIF (hypoxia-inducible factor)-1. Molecular targets for radiation sensitization are now under development and both basic and clinical studies are important for future application of those sensitizing agents for the radiotherapy of tumors. (K.H.)

  5. Microenvironment around tumors and their radiation sensitivity. The possibility of molecular target for radiation sensitization

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Ishikawa, Hitoshi

    2001-01-01

    There have been scarce studies concerning the effect of microenvironment around tumors on their radiation sensitivity and this review describes the influence of environmental factors of cell adhesion, growth factors, cytokines, hypoxia and angiogenesis on the sensitivity and response to radiation and on the signal transduction to consider the possibility of molecular target for radiation sensitization. Cell-cell adhesion and cell-matrix interaction in response to radiation may have a role in inducing apoptotic process like anti-apoptotic or pro-apoptotic one. Growth factors and cytokines can affect the tumor response to radiation in more extent than p53 gene status since apoptosis induction is not always an indication of radiation sensitivity in many tumors clinically encountered. Radiation sensitivity is low in tumor cells under hypoxic conditions and it is important to know the relationship between those hypoxic cell response and angiogenesis by factors like HIF (hypoxia-inducible factor)-1. Molecular targets for radiation sensitization are now under development and both basic and clinical studies are important for future application of those sensitizing agents for the radiotherapy of tumors. (K.H.)

  6. Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

    Energy Technology Data Exchange (ETDEWEB)

    Bourke, Vincent A [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Dawen, Zhao [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Gilio, Joseph [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Chang, C -H [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Lan, Jiang [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Hahn, Eric W [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Mason, Ralph P [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States)

    2007-03-15

    Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by {sup 19}F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm{sup 3}) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO{sub 2}) than their smaller counterparts (<1.5 cm{sup 3}). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO{sub 2}, and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO{sub 2} > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy.

  7. A study for radiation-related tumor microenvironment

    International Nuclear Information System (INIS)

    Son, Young Sook; Hong, Seok Il; Kim, Young Soon; Jin Yong Jae; Lee, Tae Hee; Chung, Eun Kyung; Yi, Jae Yeun; Park, Myung Jin; Kim, Yun Young; Kang, Sin Keun

    1999-04-01

    In this study, we attempted to elucidate the mechanism involved in radiation-induced modification and changes of biological factors and physicochemical factors of tumor microenvironment and develop techniques and agents for the modification of tumor microenvironment which is favorable for efficient radio-cancer therapy based on our basic study. We established in vitro tumor invasion and angiogenesis model, elucidated the importance of MMPs activation and the MMPs/TIMPs complex in the invasive transition of tumor. Furthermore we showed the signaling pathway for MMPs induction through EGF receptor and TGF beta 1 stimulated E-M transition. We also established primary culture of human endothelial cells and tubule forming condition which is utilized for the detection of novel angiogenic factors. We also identified hypoxia induced signaling pathway and showed that GBE improved blood perfusion which may increase the effectiveness of radio-cancer therapy

  8. A study for radiation-related tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Son, Young Sook; Hong, Seok Il; Kim, Young Soon; Jin Yong Jae; Lee, Tae Hee; Chung, Eun Kyung; Yi, Jae Yeun; Park, Myung Jin; Kim, Yun Young; Kang, Sin Keun

    1999-04-01

    In this study, we attempted to elucidate the mechanism involved in radiation-induced modification and changes of biological factors and physicochemical factors of tumor microenvironment and develop techniques and agents for the modification of tumor microenvironment which is favorable for efficient radio-cancer therapy based on our basic study. We established in vitro tumor invasion and angiogenesis model, elucidated the importance of MMPs activation and the MMPs/TIMPs complex in the invasive transition of tumor. Furthermore we showed the signaling pathway for MMPs induction through EGF receptor and TGF beta 1 stimulated E-M transition. We also established primary culture of human endothelial cells and tubule forming condition which is utilized for the detection of novel angiogenic factors. We also identified hypoxia induced signaling pathway and showed that GBE improved blood perfusion which may increase the effectiveness of radio-cancer therapy.

  9. WE-E-BRE-12: Tumor Microenvironment Dynamics Following Radiation

    International Nuclear Information System (INIS)

    Campos, D; Niles, D; Adamson, E; Torres, A; Kissick, M; Eliceiri, K; Kimple, R

    2014-01-01

    Purpose: This work aims to understand the radiation-induced interplay between tumor oxygenation and metabolic activity. These dynamics can potentially serve as biomarkers in assessing treatment response allowing for patient-specific adaptive radiotherapy. Methods: Using patient-derived xenografts of head and neck cancer we assessed tumor oxygenation via fiber-optic probe monitored hemoglobin saturation and Blood Oxygen Level Dependent (BOLD) MRI. Measurements were taken before and after a 10 Gy dose of radiation. Changes in metabolic activity were measured via Fluorescence Lifetime IMaging (FLIM) with the appropriate controls following a 10 Gy dose of radiation. FLIM can non-invasively monitor changes in fluorescence in response to the microenvironment including being able to detect free and bound states of the intrinsically fluorescent metabolite NADH (Nicotinamide Adenine Dinucleotide). With this information FLIM can accurately quantify the metabolic state of cells that have been radiated. To model the observed changes, a two-compartment, source-sink simulation relating hemoglobin saturation and metabolic activity was performed using MATLAB. Results: Hemoglobin saturation as measured by interstitial probe and BOLD-MRI decreased by 30% within 15 minutes following radiation. FLIM demonstrated a decrease in the mean fluorescence lifetime of NADH by 100 ps following 10 Gy indicating a shift towards glycolytic pathways. Simulation of radiation-induced alterations in tumor oxygenation demonstrated that these changes can be the result of changes in either vasculature or metabolic activity. Conclusion: Radiation induces significant changes in hemoglobin saturation and metabolic activity. These alterations occur on time scales approximately the duration of common radiation treatments. Further understanding these dynamics has important implications with regard to improvement of therapy and biomarkers of treatment response

  10. Cross-resistance to radiation in human squamous cell carcinoma cells with induced cisplatin resistance

    International Nuclear Information System (INIS)

    Komori, Keiichi

    1998-01-01

    Accumulated evidence indicates that drug resistance is induced in tumor cells treated with a variety of anti-cancer drugs and that there is a possibility of cross-resistance to ionizing radiation associated with induced drug resistance. Most in vitro studies have shown inconsistent results on cross-resistance probably because of different cell lines used and protocols for drug induction. In this study, TE3 human squamous cell carcinoma cell line was treated with a 4-day cycle of cisplatin (cis-diamminedichloroplatinum (II); CDDP) at a concentration yielding 10% cell survival. The treatment was repeated up to 3 cycles. After treatment, cells were tested for CDDP and X-ray sensitivity. One cycle of CDDP treatment induced CDDP resistance with a factor of 1.41 and 2 cycles of the treatment with a factor of 1.86. The resistance factor reached a plateau at 3 cycles of treatment. For analyzing the correlation of CDDP and X-ray resistance, 30 clones from both untreated and 3-cycle treated cells were isolated and analyzed for CDDP and X-ray sensitivity. The sensitivity was expressed as the concentration of drug or dose of X-ray required to reduce the cell survival to x% (Dx). The correlation coefficient of clones with 3-cycle treatment between CDDP and X-ray sensitivity increased gradually by increasing the end point of Dx from D 10 to D 90 , resulting in significant correlation at D 90 . The result suggested that there is a certain common repair-related mechanism affecting both CDDP and X-ray resistance in CDDP-treated cells. (author)

  11. Ultraviolet radiation resistance in Halobacterium salinarium

    International Nuclear Information System (INIS)

    Kristoff, S.R.

    1985-01-01

    An obvious characteristic of wild type H. salinarium is its red pigmentation. A non-pigmented mutant was isolated to test the role of pigmentation in UV radiation resistance. Survival curves of UV-irradiated wild type and mutant cells show that pigmentation does not play a direct role in protecting DNA from UV damage. Pigmentation does play a role, however, in repairing UV damage. UV-irradiated wild type cells show more efficient recovery by photoreactivation with 405 nm light than do UV-irradiated non-pigmented mutants. High internal cation concentrations found in H. salinarium may also be partly responsible for the relative resistance of H. salinarium to UV radiation by causing the DNA to assume a conformation less conducive to the production of pyrimidine dimers. In vitro irradiation of DNA extracted from H. salinarium, dissolved in solutions of different ionic strengths, indicate that pyrimidine dimers may not form as readily in DNA which is in an environment with high salt concentration

  12. SU-C-303-01: Activation-Induced Cytidine Deaminase Confers Cancer Resistance to Radiation Therapy

    International Nuclear Information System (INIS)

    Yi, S; La Count, S; Liu, J; Bai, X; Lu, L

    2015-01-01

    Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types

  13. Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

    International Nuclear Information System (INIS)

    Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

    1991-01-01

    We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

  14. Radiation resistance of quartz core fibers, (6)

    International Nuclear Information System (INIS)

    Suzuki, Toshiya; Morisawa, Masaaki; Gozen, Toshikazu; Tanaka, Yukihiro; Shintani, Takeshi; Okamoto, Shin-ichi.

    1988-01-01

    Quatz optical fibers have been used for the communication channels for long distance and large capacity, in addition, their application to the communication system in radiation environment such as nuclear power plants and artificial statellites has been positively examined. In the case of the application to aircrafts and communication satellites, optical fibers are exposed to the temperature variation of wider range than the system on the ground. Particularly, the radiation resistance of optical fibers depends largely on temperature, and at low temperature, the increase of loss is remarkable, therefore, it is important to know the characteristics in low temperature radiation environment. This time, five kinds of the core materials were prepared, and gamma-ray was irradiated at -80degC to evaluate the characteristics of increasing loss and restoration. In this report, based on the results of these evaluation, the wavelength dependence, the effect of impurities in the cores and so on are described. The absorption loss increased remarkably in short wavelength. The increase of loss in high OH fibers became high particularly in the case of low optical power. The effect of Cl was especially conspicuous in the restoration characteristics. Chlorine-free core fibers have the excellent restoration characteristics independent of wavelength and optical power. (K.I.)

  15. Chronic ionizing radiation exposure as a tumor promoter in mouse skin

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Trivedi, A.

    1992-01-01

    We have tested a chronic exposure to 90 Y beta-radiation as a tumor promoter in mouse skin previously exposed to a chemical tumor initiator. Three different tests of radiation as a stage I tumor promoter, in skin subsequently given chemical stage II promotion, all indicated that the beta-radiation acted as a weak stage I skin tumor promoter. It showed no action as either a stage II or complete tumor promoter. (author)

  16. Isolation and identification of radiation resistant yeasts from sea water

    International Nuclear Information System (INIS)

    Park, Jong Cheon; Jeong, Yong Uk; Kim, Du Hong; Jo, Eun A

    2011-12-01

    This study was conducted to isolate radiation-resistant yeasts from sea water for development of application technology of radiation-resistant microorganism. · Isolation of 656 yeasts from sea water and selection of 2 radiation-resistant yeasts (D 10 value >3) · Identification of isolated yeasts as Filobasidium elegans sharing 99% sequence similarity · Characterization of isolated yeast with ability to repair of the DNA damage and membrane integrity to irradiation

  17. Differential thermo-resistance of multicellular tumor spheroids

    International Nuclear Information System (INIS)

    Khoei, S.; Goliaei, B.; Neshasteh-Rize, A.

    2004-01-01

    Many cell lines, when cultured under proper conditions, can form three dimensional structures called multicellular spheroids. These spheroids resemble in vivo tumor models in several aspects. Therefore, studying growth characteristics and behavior of spheroids is beneficial in understanding the behavior of tumors under various experimental conditions. In this work, we have studied the growth properties, along with the thermal characteristics of spheroids of Du 145 human prostate carcinoma cell lines and compared the results to monolayer cultures of these cells. For this purpose, The Du 145 cells were cultured either as monolayer or spheroids. At various times after initiation of cultures, the growth properties of spheroids as a function of seeding cell number was determined. To evaluate the thermal characteristics of spheroids, they were heated at various stages of growth at 43 d ig c for various periods. The thermal response was judged by the survival fraction of colony forming cells in spheroids or monolayer culture following heat treatment. The results showed spheroids were more resistant to heat than monolayer cultures at all stages of development. However, the extent of this thermal resistant was dependent on the age, and consequently, the size of the spheroid. The result suggests that the differential thermal resistance of the spheroid cultures develop gradually during the growth of spheroid cultures of Du 145 cell line

  18. Radiation resistance of microorganisms on unsterilized infusion sets

    DEFF Research Database (Denmark)

    Christensen, E. Ahrensburg; Kristensen, H.; Hoborn, J.

    1991-01-01

    Three different methods were used for detecting and isolating microorganisms with high radiation resistance from the microbial contamination on infusion sets prior to sterilization. By all three methods, microorganisms with a radiation resistance high enough to be a critical factor in a steriliza......Three different methods were used for detecting and isolating microorganisms with high radiation resistance from the microbial contamination on infusion sets prior to sterilization. By all three methods, microorganisms with a radiation resistance high enough to be a critical factor...

  19. Acoustic Radiation Force Impulse Elastography for Focal Hepatic Tumors: Usefulness for Differentiating Hemangiomas from Malignant Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Eun [Department of Radiology, Gyeongsang National University School of Medicine, Jinju 660-702 (Korea, Republic of); Lee, Jae Young [Department of Radiology and Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Bae, Kyung Soo [Department of Radiology, Gyeongsang National University School of Medicine, Jinju 660-702 (Korea, Republic of); Han, Joon Koo; Choi, Byung Ihn [Department of Radiology and Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

    2013-07-01

    The purpose of this study is to investigate whether acoustic radiation force impulse (ARFI) elastography with ARFI quantification and ARFI 2-dimensional (2D) imaging is useful for differentiating hepatic hemangiomas from malignant hepatic tumors. One-hundred-and-one tumors in 74 patients were included in this study: 28 hemangiomas, 26 hepatocellular carcinomas (HCCs), three cholangiocarcinomas (CCCs), 20 colon cancer metastases and 24 other metastases. B-mode ultrasound, ARFI 2D imaging, and ARFI quantification were performed in all tumors. Shear wave velocities (SWVs) of the tumors and the adjacent liver and their SWV differences were compared among the tumor groups. The ARFI 2D images were compared with B-mode images regarding the stiffness, conspicuity and size of the tumors. The mean SWV of the hemangiomas was significantly lower than the malignant hepatic tumor groups: hemangiomas, 1.80 ± 0.57 m/sec; HCCs, 2.66 ± 0.94 m/sec; CCCs, 3.27 ± 0.64 m/sec; colon cancer metastases, 3.70 ± 0.61 m/sec; and other metastases, 2.82 ± 0.96 m/sec (p < 0.05). The area under the receiver operating characteristics curve of SWV for differentiating hemangiomas from malignant tumors was 0.86, with a sensitivity of 96.4% and a specificity of 65.8% at a cut-off value of 2.73 m/sec (p < 0.05). In the ARFI 2D images, the malignant tumors except HCCs were stiffer and more conspicuous as compared with the hemangiomas (p < 0.05). ARFI elastography with ARFI quantification and ARFI 2D imaging may be useful for differentiating hepatic hemangiomas from malignant hepatic tumors.

  20. Breast cancers radiation-resistance: key role of the cancer stem cells marker CD24

    International Nuclear Information System (INIS)

    Bensimon, Julie

    2013-01-01

    This work focuses on the characterization of radiation-resistant breast cancer cells, responsible for relapse after radiotherapy. The 'Cancer Stem Cells' (CSC) theory describes a radiation-resistant cellular sub-population, with enhanced capacity to induce tumors and proliferate. In this work, we show that only the CSC marker CD24-/low defines a radiation resistant cell population, able to transmit the 'memory' of irradiation, expressed as long term genomic instability in the progeny of irradiated cells. We show that CD24 is not only a marker, but is an actor of radiation-response. So, CD24 expression controls cell proliferation in vitro and in vivo, and ROS level before and after irradiation. As a result, CD24-/low cells display enhanced radiation-resistance and genomic stability. For the first time, our results attribute a role to CD24-/low CSCs in the transmission of genomic instability. Moreover, by providing informations on tumor intrinsic radiation-sensitivity, CD24- marker could help to design new radiotherapy protocols. (author)

  1. Radiation resistant modified polypropylene; Polipropylen modyfikowany odporny radiacyjnie

    Energy Technology Data Exchange (ETDEWEB)

    Bojarski, J; Zimek, Z [Institute of Nuclear Chemistry and Technology, Warsaw (Poland)

    1997-10-01

    Radiation technology for production of radiation resistant polypropylene for medical use has been presented. The method consists in radiation induced copolymerization of polypropylene with ethylene and addition of small amount of copolymer of polyethylene and vinyl acetate. The material of proposed composition has a very good mechanical properties and elevated radiation resistivity decided on possibility of radiosterilization of products made of this material and designed for medical use. 3 figs, 3 tabs.

  2. Radiation resistance of organic azo dyes in aqueous solutions

    International Nuclear Information System (INIS)

    Khabarov, V.N.; Kozlov, L.L.

    1987-01-01

    The resistance to the action of the ionizing radiation of aqueous and aqueous-alcoholic solutions of organic mono- and diazo dyes was studied. The radiation chemical yield of decolorization of the dye, determined from the kinetic decolorization curves served as a quantitative criterion of the radiation resistance. The influence of pH, addition of ethanol, hydroquinone, thiourea, glucose and oxygen on the radiation resistance of the azo dyes was studied. An attempt was made to relate the efficiency of radiation decolorization to the chemical nature of the dye

  3. Radiation as an inducer of in-situ autologous vaccine in the treatment of solid tumors

    International Nuclear Information System (INIS)

    Ahmed, Mansoor M.

    2013-01-01

    Radiation therapy (RT) is conventionally used for local tumor control. Although local control of the primary tumor can prevent the development of subsequent systemic metastases, tumor irradiation is not effective in controlling pre-existing systemic disease. The concept of radiation-enhanced antigen presentation and immunomodulation allows the harnessing of tumor cell death induced by radiation as a potential source of tumor antigens for immunotherapy. Immunomodulation using RT is a novel strategy of in situ tumor vaccination where primary tumor irradiation can contribute to the control of pre-existing systemic metastatic disease. The absence of systemic immunosuppression (often associated with chemotherapy) and the generally lower toxicity makes radiation a desirable adjuvant regimen for immunotherapy and tumor vaccination strategies. Increased understanding of tumor immunology and the biology of radiation-mediated immune modulation should enhance the efficacy of combining these therapeutic modalities. Here we aim to provide an overview of the biology of radiation-induced immune modulation. (author)

  4. Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

    International Nuclear Information System (INIS)

    Ahmed, M.

    2003-01-01

    Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

  5. Antiangiogenic Agent Might Upgrade tumor Cell Sensitivity to Ionizing Radiation

    International Nuclear Information System (INIS)

    Badr, N.M.S.A.

    2013-01-01

    The understanding of the fundamental role of angiogenesis and metastasis in cancer growth has led to tremendous interest in research regarding its regulatory mechanisms and clinical implications in the management of cancer. The present study was conducted to evaluate the influence of the angiogenic regulators modification on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. Accordingly, the antiangiogenic activity of apigenin and selenium was tested in vitro via MTT assay. The action of Apigenin and or Selenium was examined in vivo by using a model of solid tumor carcinoma (EAC). The growth rate of solid tumor in all experimental groups was measured by Caliper. The irradiated mice were exposed to 6.5 Gy of gamma rays. Apigenin 50 mg/kg body weight and selenium 5 μg per mice were daily administrated for 14 consecutive days after tumor volume reached 1mm 3 . The angiogenic activators TNF-α (key cytokine) in spleen, serum MMP 2 and MMP 9, liver and tumor NO, the lipid peroxidation (LPx) and angiogenic inhibitor TIMP-1 in spleen as well as, antioxidant markers (CAT, SOD, GPX) in tumor and liver tissue and DNA fragmentation in splenocytes were estimated to monitor efficacy of Apigenin and selenium in cancer treatment strategy. All parameters were determined as a time course on days 16 and 22 after tumor volume reached 1mm 3 . The using of MTT assay on EAC cells shows inhibition in EAC cell proliferation after the incubation with apigenin and /or selenium. The administration of apigenin and /or selenium to mice bearing tumor and to irradiated mice bearing tumor reduce significantly the TNF-α expression, MMP 2,9 , NO , LPx level and increased the antioxidant enzymes (GPx , SOD and CAT) activities. The DNA fragmentation and the antiangiogenic factors TIMP-1 were significantly increased when compared with their values in mice bearing tumor or in irradiated mice bearing tumor. From the results

  6. Synchrotron radiation XRF microprobe study of human bone tumor slice

    International Nuclear Information System (INIS)

    Huang Yuying; Zhao Limin; Wang Zhouguang; Shao Hanru; Li Guangcheng; Wu Yingrong; He Wei; Lu Jianxin; He Rongguo

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described. Using the bovine liver as the standard reference, the minimum detection limit (MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe. The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated. The experimental result relation to the clinical medicine was also discussed. (author)

  7. Isolation of radiation-resistant bacteria without exposure to irradiation

    International Nuclear Information System (INIS)

    Sanders, S.W.; Maxcy, R.B.

    1979-01-01

    Resistance to desiccation was utilized in the selection of highly radiation-resistant asporogenous bacteria from nonirradiated sources. A bacterial suspension in phosphate buffer was dried in a thin film at 25 0 C and 33% relative humidity. Storage under these conditions for 15 days or more reduced the number of radiation-sensitive bacteria. Further selection for radiation-resistant bacteria was obtained by irradiation of bacteria on velveteen in the replication process, therby avoiding the toxic effect of irradiated media. The similarity of radiation resistance and identifying characteristics in irradiated and non-irradiated isolates should allay some concerns that highly radiation-resistance bacteria have been permanently altered by radiation selection

  8. Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

    1987-01-01

    Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

  9. Modifiers of radiation response in tumor therapy: strategies and expectations

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1982-01-01

    The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissues, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation, and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifies. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement required from a response modifier to effect significant improvements in tumor cure rates

  10. Modifiers of radiation response in tumor therapy: strategies and expectations

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1982-01-01

    The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissues, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation, and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifiers. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement from a response modifier to effect significant improvements in tumor cure rates

  11. Radiation resistivity of quartz core fiber, 3

    International Nuclear Information System (INIS)

    Gozen, Toshikazu; Suzuki, Toshiya; Hayashi, Tokuji; Tanaka, Hiroyuki; Okamoto, Shinichi.

    1985-01-01

    Radiation resistance characteristics were evaluated for a multi-mode quartz core fiber in low temperature region together with photobleaching effect depending on the incident light power and dependency on the wavelength of measuring rays. This report describes the results of the abovementioned items and the next step study of trial manufacturing of a pure-quartz single-mode fiber for the employment of longer wavelength rays and greater capacity in light transmission communication system. Quartz core fiber specimens were irradiated by 60 Co γ-ray source at -55 deg C to 80 deg C in a constant temperature bath and light transmission loss was determined under irradiation conditions. Low temperature characteristics were superior in an MRT (modified rod-in tube) pure quartz fiber prepared by the plasma method as compared to VAD quartz and Ge-GI fibers. The MRT fiber showed better quality than the Ge-GI fiber also in the photobleaching effect examination. As for the wavelength dependency, light transmission loss of the MRT fiber was less than that of the Ge-GI fiber. The MRT fiber also showed a superior quality in the wide range of irradiation temperatures. Based on the above-mentioned understandings, a pure-quartz single-mode fiber of both BF 3 -doped and F-doped cladding types were developed for longer wavelengths uses. The fibers could attain low light transmission loss of less than 1.0 dB/km at 1.30 μm of wavelength. At the standpoint of radiation resistivity, the BF 3 -doped fiber was found superior. (Takagi, S.)

  12. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  13. Imaging modalities in radiation treatment planning of brain tumors

    International Nuclear Information System (INIS)

    Georgiev, D.

    2009-01-01

    The radiation therapy is a standard treatment after surgery for most of malignant and some of benignant brain tumors. The restriction in acquiring local tumor control is an inability in realization of high dose without causing radiation necrosis in irradiated area and sparing normal tissues. The development of imaging modalities during the last years is responsible for better treatment results and lower early and late toxicity. Essential is the role of image methods not only in the diagnosis and also in the precise anatomical (during last years also functional) localisation, spreading of the tumor, treatment planning process and the effects of the treatment. Target delineation is one of the great geometrical uncertainties in the treatment planning process. Early studies on the use of CT in treatment planning documented that tumor coverage without CT was clearly inadequate in 20% of the patients and marginal in another 27 %. The image fusion of CT, MBI and PET and also the use of contrast materia helps to get over those restrictions. The use of contrast material enhances the signal in 10 % of the patients with glioblastoma multiform and in a higher percentage of the patients with low-grade gliomas

  14. Archway for Radiation and Micrometeorite Occurrence Resistance

    Science.gov (United States)

    Giersch, Louis R.

    2012-01-01

    The environmental conditions of the Moon require mitigation if a long-term human presence is to be achieved for extended periods of time. Radiation, micrometeoroid impacts, high-velocity debris, and thermal cycling represent threats to crew, equipment, and facilities. For decades, local regolith has been suggested as a candidate material to use in the construction of protective barriers. A thickness of roughly 3m is sufficient protection from both direct and secondary radiation from cosmic rays and solar protons; this thickness is sufficient to reduce radiation exposure even during solar flares. NASA has previously identified a need for innovations that will support lunar habitats using lightweight structures because the reduction of structural mass translates directly into additional up and down mass capability that would facilitate additional logistics capacity and increased science return for all mission phases. The development of non-pressurized primary structures that have synergy with the development of pressurized structures is also of interest. The use of indigenous or in situ materials is also a well-known and active area of research that could drastically improve the practicality of human exploration beyond low-Earth orbit. The Archway for Radiation and Micrometeorite Occurrence Resistance (ARMOR) concept is a new, multifunctional structure that acts as radiation shielding and micrometeorite impact shielding for long-duration lunar surface protection of humans and equipment. ARMOR uses a combination of native regolith and a deployed membrane jacket to yield a multifunctional structure. ARMOR is a robust and modular system that can be autonomously assembled on-site prior to the first human surface arrival. The system provides protection by holding a sufficiently thick (3 m) archshaped shell of local regolith around a central cavity. The regolith is held in shape by an arch-shaped jacket made of strong but deployable material. No regolith processing is

  15. Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

  16. Skeletal sequelae of radiation therapy for malignant childhood tumors

    International Nuclear Information System (INIS)

    Butler, M.S.; Robertson, W.W. Jr.; Rate, W.; D'Angio, G.J.; Drummond, D.S.

    1990-01-01

    One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) had scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy

  17. The value of radiation therapy for pituitary tumors

    International Nuclear Information System (INIS)

    Watari, Tsutomu

    1995-01-01

    Following points are discussed in this review. 1) Historical review of our previous therapeutic management. 2) Classification of pituitary adenomas. 3) Clinical analysis of my recent 58 cases. 4) Verification of usefulness of postoperative irradiation which achieved to increase in local control rate. 5) Authoritativeness of radiotherapy. In general, 3 to 4 portal technique or arc therapy were employed. The lateral opposing field technique was avoid to use. The recommended doses using linear accelerator x-ray technique is approximately 5000 cGy in 5 weeks. To prevent radiation hazard; (1) examiner should not use technique of two opposed fields, (2) total doses should not exceed 5000 cGy in 5 to 6 weeks and the use of daily fractions should not exceed 200 cGy. 6) Correlation of hormone secreting tumors and radiation therapy. 7) Problem of radiosurgery and heavy particle. 8) Countermeasure for recurrence cases. 9) Problem of side effects of radiotherapy and its precaution. Complication of radiation for pituitary adenoma found that the significant side effects are negligibly small in recent years. 10) Pituitary tumor are originally slow growing and benign tumor, therefore the response to irradiation takes long time to elapse for final evaluation. For instance, over 80 to 90% of acromegaly patients respond HGH successfully, but this may require from one to several years. 11) Conclusion. (author)

  18. The value of radiation therapy for pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Watari, Tsutomu [Dokkyo Univ., Mibu, Tochigi (Japan). School of Medicine

    1995-09-01

    Following points are discussed in this review. (1) Historical review of our previous therapeutic management. (2) Classification of pituitary adenomas. (3) Clinical analysis of my recent 58 cases. (4) Verification of usefulness of postoperative irradiation which achieved to increase in local control rate. (5) Authoritativeness of radiotherapy. In general, 3 to 4 portal technique or arc therapy were employed. The lateral opposing field technique was avoid to use. The recommended doses using linear accelerator x-ray technique is approximately 5000 cGy in 5 weeks. To prevent radiation hazard; (1) examiner should not use technique of two opposed fields, (2) total doses should not exceed 5000 cGy in 5 to 6 weeks and the use of daily fractions should not exceed 200 cGy. (6) Correlation of hormone secreting tumors and radiation therapy. (7) Problem of radiosurgery and heavy particle. (8) Countermeasure for recurrence cases. (9) Problem of side effects of radiotherapy and its precaution. Complication of radiation for pituitary adenoma found that the significant side effects are negligibly small in recent years. (10) Pituitary tumor are originally slow growing and benign tumor, therefore the response to irradiation takes long time to elapse for final evaluation. For instance, over 80 to 90% of acromegaly patients respond HGH successfully, but this may require from one to several years. (11) Conclusion. (author).

  19. Plasmonic Nanobubbles Rapidly Detect and Destroy Drug-Resistant Tumors

    Science.gov (United States)

    Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Townley, Debra; Wu, Xiangwei; Kupferman, Michael E.; Lapotko, Dmitri O.

    2012-01-01

    The resistance of residual cancer cells after oncological resection to adjuvant chemoradiotherapies results in both high recurrence rates and high non-specific tissue toxicity, thus preventing the successful treatment of such cancers as head and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality of life therefore depend upon the efficacy, selectivity and low non-specific toxicity of the adjuvant treatment. We report a novel, theranostic in vivo technology that unites both the acoustic diagnostics and guided intracellular delivery of anti-tumor drug (liposome-encapsulated doxorubicin, Doxil) in one rapid process, namely a pulsed laser-activated plasmonic nanobubble (PNB). HNSCC-bearing mice were treated with gold nanoparticle conjugates, Doxil, and single near-infrared laser pulses of low energy. Tumor-specific clusters of gold nanoparticles (solid gold spheres) converted the optical pulses into localized PNBs. The acoustic signals of the PNB detected the tumor with high specificity and sensitivity. The mechanical impact of the PNB, co-localized with Doxil liposomes, selectively ejected the drug into the cytoplasm of cancer cells. Cancer cell-specific generation of PNBs and their intracellular co-localization with Doxil improved the in vivo therapeutic efficacy from 5-7% for administration of only Doxil or PNBs alone to 90% thus demonstrating the synergistic therapeutic effect of the PNB-based intracellular drug release. This mechanism also reduced the non-specific toxicity of Doxil below a detectable level and the treatment time to less than one minute. Thus PNBs combine highly sensitive diagnosis, overcome drug resistance and minimize non-specific toxicity in a single rapid theranostic procedure for intra-operative treatment. PMID:23139725

  20. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.

    Science.gov (United States)

    Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

    2017-04-01

    A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compensate for the genome-destabilizing effect of environmental DNA damage and may be expected to result in a more conserved gene order in radiation-resistant species. However, here we show that rates of genome rearrangements, measured as loss of gene order conservation with time, are higher in radiation-resistant species in multiple, phylogenetically independent groups of bacteria. Comparison of indicators of selection for genome organization between radiation-resistant and phylogenetically matched, nonresistant species argues against tolerance to disruption of genome structure as a strategy for radiation resistance. Interestingly, an important mechanism affecting genome rearrangements in prokaryotes, the symmetrical inversions around the origin of DNA replication, shapes genome structure of both radiation-resistant and nonresistant species. In conclusion, the opposing effects of environmental DNA damage and DNA repair result in elevated rates of genome rearrangements in radiation-resistant bacteria. Copyright © 2017 Repar et al.

  1. Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts

    International Nuclear Information System (INIS)

    Wallner, K.; Li, G.

    1985-01-01

    Previous investigators have demonstrated synergistic interaction between hyperthermia and radiation or Adriamycin (ADR), using cell lines that are sensitive to heat or ADR alone. The authors investigated the effect of heat, radiation or ADR on Chinese hamster fibroblasts (HA-1), their heat resistant variants and their ADR resistant variants. Heat for ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. While cells selected for ADR resistance were not cross resistant to heat, they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing combined modality trials

  2. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    International Nuclear Information System (INIS)

    Adam, Jean-Francois

    2005-01-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size 2 ) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal energy, for a

  3. Studies on the radiation resistances of bioburden for medical devices

    International Nuclear Information System (INIS)

    Sekiguchi, Masayuki; Tabei, Masae

    1997-01-01

    Radiation resistances of reference bacteria strains and the bioburden obtained from hypodermic needles were estimated with gamma- and electron- irradiators calibrated with NPL (National Physics Laboratory) alanine dosimeter. Radiation resistances of the TSB-bacteria suspension samples dried on glass test tubes showed about two times higher than those of the water-bacteria suspension dried on glass fiber paper or paper filter. Radiation resistances of the dried TSB-bacteria suspension samples irradiated by both gamma rays and electron beams were fluctuated. The overall increase ratio of radiation resistance was estimated by dividing D-values of TSB-bacteria suspension samples by that of water-bacteria suspension samples for individual bacteria. Then, the survival curve of hypodermic needle bioburden revised by the increase ratio was obtained, and which compared with that of standard distribution of radiation resistances of ISO(SDR). (author)

  4. Development of radiation resistant organic composites for cryogenic use

    International Nuclear Information System (INIS)

    Nishijima, S.

    1997-01-01

    The mechanism of the radiation induced degradation of the mechanical properties in composite materials have been studied and based on the mechanism the radiation resistant organic composites for fusion magnet have been developing. It was found that the degradation was brought by the change of the fracture mode from tensile (or flexural) to shear failure. Consequently the intrinsic parameter which control the degradation was concluded to be the interlaminar shear strength. To develop the radiation resistant composites, therefore, means to develop the composites showing the radiation resistant interlaminar shear strength. The mechanism was confirmed using three dimensional fabric reinforced plastics which do not have the interlaminar area. The roles of matrix in the composites were also revealed. The effects of dose quality and irradiated temperature on the radiation induced degradation were also discussed and the selection standards of the components for radiation resistant composites were proposed

  5. Association of preoperative radiation effect with tumor angiogenesis and vascular endothelial growth factor in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shintani, Satoru; Kiyota, Akihisa; Mihara, Mariko; Nakahara, Yuuji; Terakado, Nagaaki; Ueyama, Yoshiya; Matsumura, Tomohiro

    2000-01-01

    This study examined the relationship between tumor angiogenesis and the radiation-induced response, evaluated based on pathological changes, in oral squamous cell carcinoma patients treated with preoperative radiation therapy. Forty-one cases of squamous cell carcinoma treated with preoperative radiation therapy were investigated. Tumor angiogenesis was assessed by scoring the intratumor microvessel density (IMVD). Expression of vascular endothelial growth factor (VEGF) was also evaluated before and after preoperative radiotherapy. There was no correlation between IMVD in the specimens before therapy and the pathological response to radiation therapy. However, radiation therapy decreased IMVD in the specimens after therapy. A significant association was observed between VEGF expression and resistance to radiation therapy: only 4 of the 21 patients whose tumors exhibited a high level (2+ or 3+) of VEGF staining experienced a major (3+ or 4+) pathological response to radiation therapy. Furthermore, an increasing level of VEGF expression after radiation therapy was observed in non-effective (0 to 2+) response cases. These results suggest that VEGF expression and the induction of this protein are related to radiosensitivity and could be used to predict the effects of preoperative radiation therapy on oral squamous cell carcinoma. (author)

  6. Tumor reoxygenation by aqueous oxygen solutions and its role in cancer treatment with chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    Calderwood, S.K.

    2003-01-01

    Many tumors contain significant areas of hypoxia which cause resistance to tumor radiation therapy and chemotherapy. We have used perfusion into afferent arteries with super saturated aqueous oxygen solutions (AO) to re-oxygenate the hypoxic areas of experimental tumors with the aim of restoring sensitivity to treatment and enhancing cancer therapy. We first concentrated on examining the ability of AO infusion to reoxygenate the MAT B III 13762 rat carcinoma growing in the thighs of rats. In experiments on 33 AO infused tumors using Eppendorf microelectrode monitoring, we consistently observed a significant decrease in the fraction of tumor domains with O 2 less than 5mmHg before and after AO infusion. Significant tumor reoxygenation was observed in most tumors with a volume less than 2.5 cm 3 . We next examined 15 New Zealand white rabbits transplanted with the VX2 carcinoma. Tissue oxygen studies indicated that intramuscular rabbit VX-2 tumor has a consistently lower hypoxic fraction (O 2 2 <5mm Hg). Significant reoxygenation did occur in these infused tumors although the degree of reoxygenation was slightly less than in the rat MAT B III 13762 perhaps reflecting the lower hypoxic fraction. Further studies showed that AO could also be infused directly into tumors with a reduction of hypoxic fraction of between 60-90% Overall, the experiments show that AO infusion into either arterial or intratumor sites is a viable approach to tumor reoxygenation and preliminary studies indicate increase effectiveness in treatment with cyclophosphamide / AO combination

  7. Delayed radiation necrosis of the brain simulating a brain tumor

    International Nuclear Information System (INIS)

    Ikeda, Hiroya; Kanai, Nobuhiro; Kamikawa, Kiyoo

    1976-01-01

    Two cases of delayed radiation necrosis of the brain are reported. Case 1 was a 50-year-old man who had right hemiparesis and disorientation 26 months after Linac irradiation (5,000 rad), preceded by an operation for right maxillar carcinoma. A left carotid angiogram demonstrated a left temporal mass lesion, extending to the frontal lobe. Case 2 was a 41-year-old man who had previously had an operation for right intraorbital plasmocytoma, followed by two Co irradiations (6,400 rad, and 5,000 rad). He had the signs and symptoms of intracranial hypertension 36 months after his last irradiation. A left carotid angiogram demonstrated a left temporal mass lesion. Both cases were treated by administration of steroid hormone (which alleviated the signs and symptoms) and by temporal lobectomy. Microscopic examinations showed necrosis of the brain tissues associated with hyaline degeneration of blood vessel walls and perivascular cell infiltration. The signs and symptoms of intracranial hypertension subsided postoperatively. Thirteen other cases the same as ours were collected from literature. They showed the signs and symptoms simulating a brain tumor (like a metastatic brain tumor) after irradiation to extracranial malignant tumors. Diagnosis of radiation necrosis was made by operation or autopsy. A follow-up for a long time is necessary, because the pathological changes in the brain may be progressive and extending in some cases, although decompressive operations for mass lesions give excellent results. (auth.)

  8. Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

    2000-01-01

    The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

  9. Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

    2000-07-01

    The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

  10. Heat resistant/radiation resistant cable and incore structure test device for FBR type reactor

    International Nuclear Information System (INIS)

    Tanimoto, Hajime; Shiono, Takeo; Sato, Yoshimi; Ito, Kazumi; Sudo, Shigeaki; Saito, Shin-ichi; Mitsui, Hisayasu.

    1995-01-01

    A heat resistant/radiation resistant coaxial cable of the present invention comprises an insulation layer, an outer conductor and a protection cover in this order on an inner conductor, in which the insulation layer comprises thermoplastic polyimide. In the same manner, a heat resistant/radiation resistant power cable has an insulation layer comprising thermoplastic polyimide on a conductor, and is provided with a protection cover comprising braid of alamide fibers at the outer circumference of the insulation layer. An incore structure test device for an FBR type reactor comprises the heat resistant/radiation resistant coaxial cable and/or the power cable. The thermoplastic polyimide can be extrusion molded, and has excellent radiation resistant by the extrusion, as well as has high dielectric withstand voltage, good flexibility and electric characteristics at high temperature. The incore structure test device for the FBR type reactor of the present invention comprising such a cable has excellent reliability and durability. (T.M.)

  11. Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

    NARCIS (Netherlands)

    Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

    Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

  12. Synthesis and radiation resistance of fullerenes and fullerene derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Shilin, V. A., E-mail: shilin@pnpi.spb.ru; Lebedev, V. T.; Sedov, V. P.; Szhogina, A. A. [St. Petersburg Nuclear Physics Institute, National Research Centre “Kurchatov Institute” (Russian Federation)

    2016-07-15

    The parameters of an electric-arc facility for the synthesis of fullerenes and endohedral metallofullerenes are optimized. The resistance of C{sub 60} and C{sub 70} fullerenes and C{sub 60}(OH){sub 30} and C{sub 70}(OH){sub 30} fullerenols against neutron irradiation is studied. It is established that the radiation resistance of the fullerenes is higher than that of the fullerenols, but the radiation resistance of the Gd@C{sub 2n} endometallofullerenes is lower than that of the corresponding Gd@C{sub 2n}(OH){sub 38} fullerenols. The radiation resistance of mixtures of Me@C{sub 2n}(OH){sub 38} (Me = Gd, Tb, Sc, Fe, and Pr) endometallofullerenes with C{sub 60}(OH){sub 30} is determined. The factors affecting the radiation resistance of the fullerenes and fullerenols are discussed.

  13. Radiation response of drug-resistant variants of a human breast cancer cell line

    International Nuclear Information System (INIS)

    Lehnert, S.; Greene, D.; Batist, G.

    1989-01-01

    The radiation response of drug-resistant variants of the human tumor breast cancer cell line MCF-7 has been investigated. Two sublines, one resistant to adriamycin (ADRR) and the other to melphalan (MLNR), have been selected by exposure to stepwise increasing concentrations of the respective drugs. ADRR cells are 200-fold resistant to adriamycin and cross-resistant to a number of other drugs and are characterized by the presence of elevated levels of selenium-dependent glutathione peroxidase and glutathione-S-transferase. MLNR cells are fourfold resistant to melphalan and cross-resistant to some other drugs. The only mechanism of drug resistance established for MLNR cells to date is an enhancement of DNA excision repair processes. While the spectrum of drug resistance and the underlying mechanisms differ for the two sublines, their response to radiation is qualitatively similar. Radiation survival curves for ADRR and MLNR cells differ from that for wild-type cells in a complex manner with, for the linear-quadratic model, a decrease in the size of alpha and an increase in the size of beta. There is a concomitant decrease in the size of the alpha/beta ratio which is greater for ADRR cells than for MLNR cells. Analysis of results using the multitarget model gave values of D0 of 1.48, 1.43, and 1.67 Gy for MCF-7 cells are not a consequence of cell kinetic differences between these sublines. Results of split-dose experiments indicated that for both drug-resistant sublines the extent of sublethal damage repair reflected the width of the shoulder on the single-dose survival curve. For MCF-7 cells in the stationary phase of growth, the drug-resistant sublines did not show cross-resistance to radiation; however, delayed subculture following irradiation of stationary-phase cultures increased survival to a greater extent for ADRR and MLNR cells than for wild-type cells

  14. Effect of radiation resistance additives for insulation materials

    International Nuclear Information System (INIS)

    Yamamoto, Yasuaki; Yagyu, Hideki; Seguchi, Tadao.

    1988-01-01

    For the electric wires and cables used in radiation environment such as nuclear power stations and fuel reprocessing facilities, the properties of excellent radiation resistance are required. For these insulators and sheath materials, ethylene propylene rubber, polyethylene and other polymers have been used, but it cannot be said that they always have good radiation resistance. However, it has been well known that radiation resistance can be improved with small amount of additives, and heat resistance and burning retarding property as well as radiation resistance are given to the insulators of wires and cables for nuclear facilities by mixing various additives. In this research, the measuring method for quantitatively determining the effect of Anti-rad (radiation resistant additive) was examined. Through the measurement of gel fraction, radical formation and decomposed gas generation, the effect of Anti-rad protecting polymers from radiation deterioration was examined from the viewpoint of chemical reaction. The experimental method and the results are reported. The radiation energy for cutting C-H coupling is polymers is dispersed by Anti-rad, and the probability of cutting is lowered. Anti-rad catches and extinguishes radicals that start oxidation reaction. (K.I.)

  15. Development of radiation-resisting high molecular-weight materials

    International Nuclear Information System (INIS)

    Nakagawa, Tsutomu

    1976-01-01

    The excellent radiation-resisting polyvinyl chloride developed at the opportunity of the research on the relationships between the protection of living body and the polymer-technological protection from radiation is reviewed. The report is divided into four main parts, namely 1) the change in the molecular arrangement of market-available, high molecular-weight materials by gamma-ray irradiation, 2) the protection of high molecular-weight materials from radiation, 3) the relationships between the biological radiation-protective substances and the change to radiation-resisting property of synthesized high molecular-weight substances, and 4) the development of the radiation-resisting high molecular-weight materials as metal-collecting agents. Attention is paid to the polyvinyl chloride having N-methyl-dithio-carbamate radical (PMD), synthesized by the author et. al., that has excellent radiation-resisting property. PMD has some possibility to form thiol- and amino-radicals necessary to protect living things from radiation. It is believed that the protection effects of N-methyl-dithio-carbamate radical are caused by the relatively stable S radical produced by the energy transfer. PMD film is suitable for the irradiation of foods, because it hardly changes the permeability of oxygen and carbon dioxide. PMD produces mercaptide or chelate. A new metal-collecting agent (PSDC) having reactivity with the metallic ions with radiation-resisting property was developed, which is derived from polyvinyl chloride and sodium N-methyl-N-carboxy-methyl-dithio-carbamate. (Iwakiri, K.)

  16. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha

    2012-01-01

    Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods....... Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...... the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin....

  17. Increased radiation resistance in lithium-counterdoped silicon solar cells

    Science.gov (United States)

    Weinberg, I.; Swartz, C. K.; Mehta, S.

    1984-01-01

    Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.

  18. Effect of radiation decontamination on drug-resistant bacteria

    International Nuclear Information System (INIS)

    Ito, Hitoshi

    2006-01-01

    More than 80% of food poisoning bacteria such as Salmonella are reported as antibiotic-resistant to at least one type antibiotic, and more than 50% as resistant to two or more. For the decontamination of food poisoning bacteria in foods, radiation resistibility on drug-resistant bacteria were investigated compared with drug-sensitive bacteria. Possibility on induction of drug-resistant mutation by radiation treatment was also investigated. For these studies, type strains of Escherichia coli S2, Salmonella enteritidis YK-2 and Staphylococcus aureus H12 were used to induce drug-resistant strains with penicillin G. From the study of radiation sensitivity on the drug-resistant strain induced from E. coli S2, D 10 value was obtained to be 0.20 kGy compared with 0.25 kGy at parent strain. On S. enteritidis YK-2, D 10 value was obtained to be 0.14 kGy at drug-resistant strain compared with 0.16 kGy at parent strain. D 10 value was also obtained to be 0.15 kGy at drug-resistant strain compared with 0.21 kGy at parent strain of St. aureus H12. Many isolates of E. coli 157:H7 or other type of E. coli from meats such as beef were resistant to penicillin G, and looked to be no relationship on radiation resistivities between drug-resistant strains and sensitive strains. On the study of radiation sensitivity on E. coli S2 at plate agars containing antibiotics, higher survival fractions were obtained at higher doses compared with normal plate agar. The reason of higher survival fractions at higher doses on plate agar containing antibiotics should be recovery of high rate of injured cells by the relay of cell division, and drug-resistant strains by mutation are hardly induced by irradiation. (author)

  19. Macrophage biology plays a central role during ionizing radiation-elicited tumor response

    Directory of Open Access Journals (Sweden)

    Qiuji Wu

    2017-08-01

    Full Text Available Radiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied. The mechanisms underlying radiation-induced macrophage activation remain largely elusive. Various molecular players such as NF-κB, MAPKs, p53, reactive oxygen species, inflammasomes have been involved in these processes. The skewing to a pro-inflammatory phenotype thus results in the activation of anti-tumor immune response and enhanced radiotherapy effect. Therefore, a comprehensive understanding of the mechanism of radiation-induced macrophage activation and its role in tumor response to radiation therapy is crucial for the development of new therapeutic strategies to enhance radiation therapy efficacy.

  20. Evaluation of Radiation Response and Gold Nanoparticle Enhancement in Drug-Resistant Pancreatic Cancer Cells

    Science.gov (United States)

    Abourabia, Assya

    Pancreatic cancer is a major cause of cancer-related death worldwide after lung cancer and colorectal cancer Pancreatic treatment modalities consist of surgery, chemotherapy, and radiation therapy or combination of these therapies. These modalities are good to some extents but they do have some limitations. For example, during the chemotherapy, tumor cells can develop some escape mechanisms and become chemoresistant to protect themselves against the chemo drugs and pass on theses escape mechanisms to their offspring, despite the treatment given. Cancer Cells can become chemoresistant by many mechanisms, for example, decreased drug influx mechanisms, decreased of drug transport molecules, decreased drug activation, altered drug metabolism that diminishes the capacity of cytotoxic drugs, and enhanced repair of DNA damage. Given that some of these chemoresistance mechanisms may impact sensitivity to radiation. Therefore, there is a strong need for a new alternative treatment option to amplify the therapeutic efficacy of radiotherapy and eventually increase the overall efficacy of cancer treatment. Nano-radiation therapy is an emerging and promising modality aims to enhance the therapeutic efficacy of radiotherapy through the use of radiosensitizing nanoparticles. The primary goal of using GNP-enhanced radiation is that GNPs are potent radiosensitizer agents that sensitize the tumor cells to radiation, and these agents promote generation of the free radicals produced by Photo- and Auger- electrons emission at the molecular level which can enhance the effectiveness of radiation-induced cancer cell death. The main aim of this research is to analyze and compare the response to radiation of pancreatic cancer cells, PANC-1, and PANC-1 cells that are resistant to oxaliplatin, PANC-1/OR, and investigate the radiation dose enhancement effect attributable to GNP when irradiating the cells with low-energy (220 kVp) beam at various doses. Based on evidence from the existing

  1. Radiation resistance and injury of Yersinia enterocolitica

    Energy Technology Data Exchange (ETDEWEB)

    El-Zawahry, Y.A.; Rowley, D.B.

    1979-01-01

    The D values of Yersinia enterocolitica strains IP134, IP107, and WA, irradiated at 25/sup 0/C in Trypticase soy broth, ranged from 9.7 to 11.8 krad. When irradiated in ground beef at 25 and -30/sup 0/C, the D value of strain IP107 and 19.5 and 38.8 krad, respectively. Cells suspended in Trypticase soy broth were more sensitive to storage at -20/sup 0/C than those mixed in ground beef. The percentages of inactivation and of injury (inability to form colonies in the presence of 3.0% NaCl) of cells stored in ground beef for 10 days at -20/sup 0/C were 70 and 23%, respectively. Prior irradiation did not alter the cell's sensitivity to storage at -20/sup 0/C, nor did storage at -20/sup 0/C alter the cell's resistance to irradiation at 25/sup 0/C. Added NaCl concentrations of up to 4.0% in Trypticase soy agar (TSA) (which contains 0.5% NaCl) had little effect on colony formation at 36/sup 0/C of unirradiated Y. enterocolitica. With added 4.0% NaCl, 79% of the cells formed colonies at 36/sup 0/C; with 5.0% NaCl added, no colonies were formed. Although 2.5% NaCl added to ground beef did not sensitize Y. enterocolitica cells to irradiation, when added to TSA it reduced the number of apparent radiation survivors. Cells uninjured by irradiation formed colonies on TSA when incubated at either 36 or 5/sup 0/C. More survivors of an exposure to 60 krad were capable of recovery and forming colonies on TSA when incubated at 36/sup 0/C for 1 day than at 5/sup 0/C for 14 days. This difference in count was considered a manifestation of injury to certain survivors of irradiation.

  2. Radiation resistance and injury of Yersinia enterocolitica

    International Nuclear Information System (INIS)

    El-Zawahry, Y.A.; Rowley, D.B.

    1979-01-01

    The D values of Yersinia enterocolitica strains IP134, IP107, and WA, irradiated at 25 0 C in Trypticase soy broth, ranged from 9.7 to 11.8 krad. When irradiated in ground beef at 25 and -30 0 C, the D value of strain IP107 and 19.5 and 38.8 krad, respectively. Cells suspended in Trypticase soy broth were more sensitive to storage at -20 0 C than those mixed in ground beef. The percentages of inactivation and of injury (inability to form colonies in the presence of 3.0% NaCl) of cells stored in ground beef for 10 days at -20 0 C were 70 and 23%, respectively. Prior irradiation did not alter the cell's sensitivity to storage at -20 0 C, nor did storage at -20 0 C alter the cell's resistance to irradiation at 25 0 C. Added NaCl concentrations of up to 4.0% in Trypticase soy agar (TSA) (which contains 0.5% NaCl) had little effect on colony formation at 36 0 C of unirradiated Y. enterocolitica. With added 4.0% NaCl, 79% of the cells formed colonies at 36 0 C; with 5.0% NaCl added, no colonies were formed. Although 2.5% NaCl added to ground beef did not sensitize Y. enterocolitica cells to irradiation, when added to TSA it reduced the number of apparent radiation survivors. Cells uninjured by irradiation formed colonies on TSA when incubated at either 36 or 5 0 C. More survivors of an exposure to 60 krad were capable of recovery and forming colonies on TSA when incubated at 36 0 C for 1 day than at 5 0 C for 14 days. This difference in count was considered a manifestation of injury to certain survivors of irradiation

  3. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  4. Approaches to drug resistance in solid tumors : with emphasis on lung cancer

    NARCIS (Netherlands)

    Bakker, Marleen

    2005-01-01

    De novo or acquired resistance of tumor cells to anticancer agents remains a major problem for the therapeutic efficacy of chemotherapeutic drugs. Most solid tumors are intrinsically insensitive or acquire resistance after initial response to chemotherapy. Different mechanisms seem to play a role in

  5. Holmium-166-chico intracavitary radiation therapy for cystic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, C. H.; Lee, S. H.; Jang, J. S.; Kim, E. H.; Choi, C. W.; Hong, S. W.; Lim, S. M. [Korea Cancer Center, Seoul (Korea, Republic of)

    1997-07-01

    Holmium-166-chitosan complex (Ho-166-chico) is injected into the unresectable seven cystic brain tumors (2 cases of metastatic brain tumors from lung cancer, 1 case of recurrent trigeminal neurinoma, 3 cases of recurrent low grade cystic astrocytomas, and 1 case of craniopharyngioma). The Ommaya reservoir was installed stereotactically. The cyst volume and wall thickness were measured by MRI before Ho-166-chico injection. The thickness of the cyst wall is up to 4 mm. Ho-166-chico (555-740 MBq) injected into the cyst to result in 25 Gy of dose to a cyst wall at a depth of 4 mm. Dose to the cyst wall was estimated by Monte Carlo simulation using the EGS4 code. All Ho-166-chico injected was assumed to be uniformly distributed in the spherical cyst. After Ho-166-chico injection, the distribution of isotopes was monitored by gamma camera. Two injections were administrated in two cases, and one injection in all the others. The response was evaluated with MRI. Four of 7 cases were shrunk in size with thinning of the cyst wall, 2 of 7 cases showed growth arrest, and one case showed progression. Estimated surface dose of cyst wall was between 78 and 2566 Gy. No one showed systemic absorption of Ho-166-chico, and specific complication associated with isotope injection. Ho-166-chico intracavitary radiation therapy for cystic brain tumor may be safe, and reliable method and deserves further evaluation.

  6. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

    OpenAIRE

    Diegeler, Sebastian; Hellweg, Christine E.

    2017-01-01

    Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an e...

  7. Response of the tumor and organs of the tumor-bearing animal to the action of an ionizing radiation

    International Nuclear Information System (INIS)

    Burlakova, E.B.; Gaintseva, V.D.; Pal'mina, N.P.; Sezina, N.P.

    1977-01-01

    Changes in the antioxigenic activity (AOA) of the liver of the tumor-bearing animals and the tumor have been studied after a single whole-body exposure of animals to a dose of 600 R. AOA of the liver of animals having hepatoma 22-a and Ehrlich ascites tumor (EAT) was found to decrease immediately after irradiation while that of the tumor itself can both increase (hepatoma 22-a) and decrease (EAT). Proceeding from the assumption that AOA is connected with tissue radiosensitivity it is suggested that the observed variations in the response of tumor cells and normal tissue to the action of ionizing radiation should be taken into account when developing the schemes of radiation effect on the tumor

  8. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria

    OpenAIRE

    Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

    2017-01-01

    A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compen...

  9. Gene Expression Analysis of Four Radiation-resistant Bacteria

    OpenAIRE

    Gao, Na; Ma, Bin-Guang; Zhang, Yu-Sheng; Song, Qin; Chen, Ling-Ling; Zhang, Hong-Yu

    2009-01-01

    To investigate the general radiation-resistant mechanisms of bacteria, bioinformatic method was employed to predict highly expressed genes for four radiation-resistant bacteria, i.e. Deinococcus geothermalis (D. geo), Deinococcus radiodurans (D. rad), Kineococcus radiotolerans (K. rad) and Rubrobacter xylanophilus (R. xyl). It is revealed that most of the three reference gene sets, i.e. ribosomal proteins, transcription factors and major chaperones, are generally highly expressed in the four ...

  10. [Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

    Science.gov (United States)

    Fischer, H-P

    2005-05-01

    High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

  11. Onconase-induced changes in radiation response and physiological parameters in solid tumors

    International Nuclear Information System (INIS)

    Lee, I.; Shui, C.; Shogen, K.; Mikulski, S.M.; Nunno, M.; Wallner, P.E.

    1996-01-01

    Purpose: Onconase (ONC), previously known as P-30 protein, is a novel basic amphibian protein isolated from eggs of the leopard frog. The original study conducted by Darzynkiewicz et al. (Cell Tissue Kinetics, 1988) demonstrated that ONC shows anti-proliferative and cytotoxic activities against several tumor cell lines in vitro. Since then, to our knowledge, no studies regarding the inhibitory effect of ONC in solid tumor models were performed. ONC is also known to inhibit cell-cycle progression from the radiation-sensitive G 1 phase to the radiation-resistant S phase. Thus, we examined the effect of ONC as a potential radiation sensitizer. The radiation response and physiological parameters were evaluated in C3H mice and/or nude mice bearing various (murine and/or human) tumor models. Materials and Method: First, we examined the effect of ONC on the cellular proliferative, as well as the clonogenic, response of various cell lines (i.e., H4IIE rat hepatoma, AsPC-1 human pancreas adenocarcinoma, DU145 human prostate carcinoma, LS174T human colon adenocarcinoma, A549 human lung carcinoma, MCaIV murine adenocarcinoma, FSaII murine fibrosarcoma, and CCL-209 bovine artery pulmonary endothelial cells) by using the MTT and clonogenic cell survival assays. Second, we determined the enhancement of radiation response before, during, and after treatment with ONC in several cell lines. Third, we determined whether ONC can inhibit the growth of solid tumors in vivo (i.e., FSaII and MCaIV in C3H mice, LS174T in nude mice). Fourth, we examined whether minocycline, an antiangiogenic agent, could amplify the tumoricidal efficacy of ONC in solid tumors. To test our hypothesis: if ONC could eradicate the outgrowth of tumor cells in confined spaces, it could lower the elevated pressure in solid tumors, we measured tumor interstitial fluid pressure (TIFP) using the wick-in-needle method, and systemic pressure using the right carotid artery cannulation method after treatment with ONC

  12. Development of flame retardant, radiation resistant insulating materials

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, M.

    1984-01-01

    On the cables used for nuclear power stations, in particular those ranked as IE class, flame retardation test, simulated LOCA environment test, radiation resistance test and so on are imposed. The results of the evaluation of performance by these tests largely depend on the insulating materials mainly made of polymers. Ethylene propylene copolymer rubber has been widely used as cable insulator because of its electrical characteristics, workability, economy and relatively good radiation resistance, but it is combustible, therefore, in the practical use, it is necessary to make it fire resistant. The author et al. have advanced the research on the molecular design of new fire retarding materials, and successfully developed acenaphthylene bromide condensate, which is not only fire resistant but also effective for improving radiation resistance. The condition of flame retardant, radiation resistant auxiliary agents is explained, and there are additive type and reaction type in fire retarding materials. The synthesis of acenaphthylene bromide condensate and its effect of giving flame retardant and radiation resistant properties are reported. The characteristics of the cables insulated with the flame retardant ethylene propylene rubber containing acenaphthylene bromide condensate were tested, and the results are shown. (Kako, I.).

  13. Trial manufacture of flame retardant and radiation resistant cables

    Energy Technology Data Exchange (ETDEWEB)

    Oshima, Yunosuke; Hagiwara, Miyuki (Japan Atomic Energy Research Inst., Takasaki, Gunma. Takasaki Radiation Chemistry Research Establishment); Oda, Eisuke

    1983-04-01

    High radiation resistance as well as incombustibility is required for the wires and cables used for nuclear facilities such as nuclear power stations. In order to give such performance to general purpose insulation materials such as ethylene-propylene copolymerized rubber, acenaphthylene bromide condensation product was developed anew. Moreover, by the use of this agent, the new flame retardant and radiation resistant cables were manufactured for trial, which are not different from ordinary plastic rubber cables in the handling such as flexibility, and withstand the radiation nearly up to 1000 Mrad. The requirement for the agent giving flame retardant and radiation resistant properties is explained. The synthesis of acenaphthylene bromide and its condensation product and the effect of giving flame retardant and radiation resistant properties are described. The test resultd of the prevention of spread of flame, the endurance in LOCA-simulating environment, and radiation resistance for the cables manufactured for trial are reported. It was confirmed that the cables of this type are suitable to the use in which the maintenance of mechanical properties after radiation exposure is required.

  14. Radiation resistant passivation of silicon solar cells

    International Nuclear Information System (INIS)

    Swanson, R.M.; Gan, J.Y.; Gruenbaum, P.E.

    1991-01-01

    This patent describes a silicon solar cell having improved stability when exposed to concentrated solar radiation. It comprises a body of silicon material having a major surface for receiving radiation, a plurality of p and n conductivity regions in the body for collecting electrons and holes created by impinging radiation, and a passivation layer on the major surface including a first layer of silicon oxide in contact with the body and a polycrystalline silicon layer on the first layer of silicon oxide

  15. Resistance to BN myelogenous leukemia in rat radiation chimeras

    International Nuclear Information System (INIS)

    Singer, D.E.; Haynor, D.R.; Williams, R.M

    1980-01-01

    Lewis → LBNFl rat radiation chimeras showed marked resistance to transplanted BN myelogenous leukemia when compared to naive LBNFl, LBNFl → LBNFl, or BN → LBNFl. This occurred in the absence of overt graft versus host disease or of anti-BN response in mixed lymphocyte culture. Bone marrow specific antigens may serve as the target of the resistance mechanism. (author)

  16. Utilization of SRNL-developed radiation-resistant polymer in high radiation environments

    Energy Technology Data Exchange (ETDEWEB)

    Skibo, A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-09-27

    The radiation-resistant polymer developed by the Savannah River National Laboratory is adaptable for multiple applications to enhance polymer endurance and effectiveness in radiation environments. SRNL offers to collaborate with TEPCO in evaluation, testing, and utilization of SRNL’s radiation-resistant polymer in the D&D of the Fukushima Daiichi NPS. Refinement of the scope and associated costs will be conducted in consultation with TECPO.

  17. Radiation resistance of a hemolytic micrococcus isolated from chicken meat

    International Nuclear Information System (INIS)

    Tan, S.T.

    1982-01-01

    The effects of environmental factors on a highly radiation-resistant hemolytic micrococcus isolated from chicken meat were studied. NaCl tolerance and gamma radiation resistance of the cells were growth phase-related. The cells were resistant to injury from drying or freezing/thawing. Under certain conditions, cells in the frozen state required approximately 5 Mrad to inactivate 90% of the population; 0.2 Mrad injured an equivalent proportion. Survival curve of the cells heated at 60 0 C showed a unique pattern which was in three distinct phases. Heat-stressed cells were much more sensitive to radiation inactivation than unheated cells. When suspended in fresh m-Plate Count Broth (PCB), the injured cells repaired without multiplication during incubation at 32 0 C. The repair process in this bacterium, however, was slower compared to thermally injured organisms studied by other workers. An improved replica-plating technique, was devised for isolation of radiation-sensitive mutants of pigmented bacteria. A simple method to demonstrate radiation-inducible radiation resistance in microbial cells was developed. The new method required neither washing/centrifugation nor procedures for cell enumeration. Mutagenesis treatment of radiation-resistant micrococcal bacterium with N-methyl-N'-nitro-N-nitrosoguanidine (NTG) followed by FPR and screening steps resulted in isolation of two radiation-sensitive mutants. The more sensitive mutant strain, designated as 702, was seven times as sensitive to gamma or UC radiation as the wild type. No apparent difference was observed between 702 and the wild type in (1) cell morphology, colonial morphology, and pigment production or (2) tolerance to NaCl, drying/storage, freezing/thawing, and heating. Sodium dodecyl sulfate treatment (for curing) of wild type did not result in isolation of a radiation-sensitive mutant

  18. Radiation-resistant composite for biological shield of personnel

    Science.gov (United States)

    Barabash, D. E.; Barabash, A. D.; Potapov, Yu B.; Panfilov, D. V.; Perekalskiy, O. E.

    2017-10-01

    This article presents the results of theoretical and practical justification for the use of polymer concrete based on nonisocyanate polyurethanes in biological shield structures. We have identified the impact of ratio: polymer - radiation-resistant filling compound on the durability and protection properties of polymer concrete. The article expounds regression dependence of the change of basic properties of the aforementioned polymer concrete on the absorbed radiation dose rate. Synergy effect in attenuation of radioactivity release in case of conjoint use of hydrogenous polymer base and radiation-resistant powder is also addressed herein.

  19. A Novel Radiation-Resistant Yeast, Filobasidium elegans RRY1

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Harinder; Kim, Ha Ram; Song, Hyun Pa; Lim, Sang Yong; Kim, Dong Ho [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2012-05-15

    The tolerance to ionizing radiation stress is present among different classes and species of organisms. As listed by Rainey et al., ionizing radiation resistant organisms were isolated from a variety of different sources like processed/canned food items, paper industry, soil and water samples. Apart from extensively reported bacteria and Archea group, many fungal species like Aspergillus, Curvularia, Alternaria, Cryptococcus, and Ustilago maydis have been found to be resistant to ionizing radiation. However, different environmental sources are constantly been explored for novel radioresistant organisms, which can help in understanding the molecular mechanism behind these extreme stress responses. On the basis of this, present study was initiated to find novel radiation resistant yeast from sea water source

  20. Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell–Mediated Killing

    Energy Technology Data Exchange (ETDEWEB)

    Gameiro, Sofia R.; Malamas, Anthony S. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bernstein, Michael B. [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Vassantachart, April; Sahoo, Narayan; Tailor, Ramesh; Pidikiti, Rajesh [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Guha, Chandan P. [Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York (United States); Hahn, Stephen M.; Krishnan, Sunil [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Hodge, James W., E-mail: jh241d@nih.gov [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2016-05-01

    Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen–specific T cells with proton radiation therapy to exploit the activity of those T cells. Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibility leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells. Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.

  1. Cell kinetics of Ehrlich ascites carcinoma transplanted in mice with different degrees of tumor resistance

    International Nuclear Information System (INIS)

    Brandt, K.L.B.

    1974-01-01

    Cell proliferation kinetics of Ehrlich ascites carcinoma grown in two strains of mice with different degrees of resistance to this tumor were examined. In the first portion of the study, growth of Ehrlich ascites carcinoma in nonresistant Swiss (Iowa) and slightly resistant CF1 mice was examined by measuring animal weight gain and host survival time after intraperitoneal injection of tumor cells. Since it appeared that CF1 mice were inherently more resistant than Swiss mice to the Ehrlich carcinoma, the second part of this investigation involved attempts to immunize CF1 mice against the tumor. Subcutaneous injections of Ehrlich cells previously exposed in vitro to 5000 R of 250 kVp x rays were utilized. One immunizing inoculation of lethally irradiated tumor cells afforded protection against an intraperitoneal challenge of 40 thousand Ehrlich cells. By varying the number and timing of immunizing inoculations it was possible to induce different degrees of tumor resistance in these mice. The most effective immunizing procedure utilized multiple inoculations of lethally irradiated tumor cells (LITC), followed by challenges with viable tumor cells (less than 1 million) which were rejected. These mice could then resist challenge inocula of 4 million viable tumor cells. In a few animals the immunizing procedures were ineffective; these animals, when challenged, developed even larger tumors than control mice. Tumor cell proliferation kinetics in these animals as well as in mice that were rejecting the tumor were examined in the third phase of the project. A shortening of the cell cycle was observed in almost all LITC-treated mice, whether tumor growth was eventually inhibited or stimulated. Decreased duration of the DNA-synthesis phase (S) of the tumor cell cycle was also a consistent finding. The role of the immune response in stimulating mitosis as well as in killing foreign cells was discussed. (U.S.)

  2. Stimulation of cytolytic T lymphocytes by azaguanine-resistant mouse tumor cells in selective hat medium

    International Nuclear Information System (INIS)

    Snick, J. van; Uyttenhove, C.; Pel, A. van; Boon, T.

    1981-01-01

    Primed syngeneic or umprimed allogeneic mouse spleen cells were stimulated with azaguanine-resistant P815 tumor cells that were killed by the addition of aminopterin to the stimulation medium. The recovery of lymphocytes and their cytolytic activity and specificity were similar to those obtained after stimulation with irradiated cells. This method conveniently replaces the inactivation of stimulatory cells by irradiation or mitomycin treatment. Moreover, it has the advantage of inactivating not only the stimulatory cells but also the tumor cells that often contaminate the spleens of tumor-bearing animals, provided these animals have been inoculated with azaguanine-resistant tumor cell mutants. (Auth.)

  3. The role of radiation therapy in the management of desmoid tumors

    International Nuclear Information System (INIS)

    Schulz-Ertner, D.; Zierhut, D.; Mende, U.; Harms, W.; Branitzki, P.; Wannenmacher, M.

    2002-01-01

    Purpose: To investigate the role of radiation therapy (RT) in the management of desmoid tumors. Patients and Methods: Retrospective analysis was performed on 28 patients with desmoid tumors treated with radiation therapy between March 1989 and March 1999. Tumor site was intraabdominal in three, abdominal wall in three and extraabdominal in 22 patients. Median tumor dose was 48 Gy (range 36-60 Gy). Radiation therapy was delivered postoperatively in 26 of 28 patients, two patients received radiation therapy for unresectable recurrent tumors. Results: Median follow-up was 46 months (range 13-108 months). Actuarial 5-year control rate was 73%. We observed six recurrences, located within the radiation field in one patient, out of field in two and at the field margin in three patients. All patients with intraabdominal tumors have been controlled without severe side effects. Conclusions: Radiation therapy is an effective treatment after incomplete resection of desmoid tumors. We did not observe a benefit for tumor doses exceeding 50 Gy. In some patients with circumscribed intraabdominal desmoid tumors, radiation therapy might be a treatment option with low toxicity, if 3-D treatment planning is utilized. (orig.) [de

  4. Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

    International Nuclear Information System (INIS)

    Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

    2004-01-01

    Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

  5. Radiation resistant polymers and coatings for nuclear fuel reprocessing plants

    International Nuclear Information System (INIS)

    Kamachi Mudali, U.; Mallika, C.; Lawrence, Falix

    2014-01-01

    Polymer based materials are extensively used in the nuclear industry for the reprocessing of spent fuels in highly radioactive and corrosive environment. Hence, these polymer materials are susceptible to damage by ionizing radiation, resulting in the degradation in properties. Polymers containing aromatic molecules generally possess higher resistance to radiation degradation than the aliphatic polymers. For improving the radiation resistance of polymers various methods are reported in the literature. Among the aromatic polymers, polyetheretherketone (PEEK) has the radiation tolerance up to 10 Mega Grey (MGy). To explore the possibility of enhancing the radiation resistance of PEEK, a study was initiated to develop PEEK - ceramic composites and evaluate the effect of radiation on the properties of the composites. PEEK and PEEK - alumina (micron size) composites were irradiated in a gamma chamber using 60 Co source and the degradation in mechanical, structural, electrical and thermal properties, gel fraction, coefficient of friction and morphology were investigated. The degradation in the mechanical properties owing to radiation could be reduced by adding alumina filler to PEEK. Nano alumina filler was observed to be more effective in suppressing the damage caused by radiation on the polymer, when compared to micron alumina filler. For the protection of aluminium components in the manipulators and the rotors and stators of the motors of the centrifugal extractors employed in the plant from the attack by nitric acid vapour, PEEK coating based on liquid dispersion was developed, which has resistance to radiation, chemicals and wear. The effect of radiation and chemical vapour on the properties of the PEEK coating was estimated. The performance of the coating in the plant was evaluated and the coating was found to give adequate protection to the motors of centrifugal extractors against corrosion. (author)

  6. High NOTCH activity induces radiation resistance in non small cell lung cancer

    International Nuclear Information System (INIS)

    Theys, Jan; Yahyanejad, Sanaz; Habets, Roger; Span, Paul; Dubois, Ludwig; Paesmans, Kim; Kattenbeld, Bo; Cleutjens, Jack; Groot, Arjan J.; Schuurbiers, Olga C.J.; Lambin, Philippe; Bussink, Jan; Vooijs, Marc

    2013-01-01

    Background and purpose: Patients with advanced NSCLC have survival rates <15%. The NOTCH pathway plays an important role during lung development and physiology but is often deregulated in lung cancer, making it a potential therapeutic target. We investigated NOTCH signaling in NSCLC and hypothesized that high NOTCH activity contributes to radiation resistance. Materials and methods: NOTCH signaling in NSCLC patient samples was investigated using quantitative RT-PCR. H460 NSCLC cells with either high or blocked NOTCH activity were generated and their radiation sensitivity monitored using clonogenic assays. In vivo, xenograft tumors were irradiated and response assessed using growth delay. Microenvironmental parameters were analyzed by immunohistochemistry. Results: Patients with high NOTCH activity in tumors showed significantly worse disease-free survival. In vitro, NOTCH activity did not affect the proliferation or intrinsic radiosensitivity of NSCLC cells. In contrast, xenografts with blocked NOTCH activity grew slower than wild type tumors. Tumors with high NOTCH activity grew significantly faster, were more hypoxic and showed a radioresistant phenotype. Conclusions: We demonstrate an important role for NOTCH in tumor growth and correlate high NOTCH activity with poor prognosis and radioresistance. Blocking NOTCH activity in NSCLC might be a promising intervention to improve outcome after radiotherapy

  7. Molecular alterations in thyroid tumors induced after exposure to ionising radiation in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Bounacer, A.; Wicker, R.; Sarasin, A.; Suarez, H.G. [Institut Gustave Roussy, 94 - Villejuif (France); Schlumberger, M.; Caillou, B. [Institut de Recherches sur le Cancer, 94 - Villejuif (France)

    1997-03-01

    We investigated the presence of molecular lesions in the ras, gsp and ret genes, in epithelial thyroid tumors developed in patients who had received ionising radiation therapy in infancy for benign or malignant conditions. Our data showed: a similar frequency of ras and gsp activating mutations in radiation-associated and `spontaneous` tumors. However, while the mutations are only transversions in the radiation-associated tumors, they are transversions as well as transitions in the `spontaneous` ones and a mutation in codon 691 giving rise to a polymorphism in the ret gene, and frequently associated to a C-cell hyperplasia in radiation-associated tumors. The frequency of this mutation was significantly higher (60%) in these tumors, than in normal controls (21%) or `spontaneous` epithelial thyroid tumors (23%). (author)

  8. Molecular alterations in thyroid tumors induced after exposure to ionising radiation in infancy

    International Nuclear Information System (INIS)

    Bounacer, A.; Wicker, R.; Sarasin, A.; Suarez, H.G.; Schlumberger, M.; Caillou, B.

    1997-01-01

    We investigated the presence of molecular lesions in the ras, gsp and ret genes, in epithelial thyroid tumors developed in patients who had received ionising radiation therapy in infancy for benign or malignant conditions. Our data showed: a similar frequency of ras and gsp activating mutations in radiation-associated and 'spontaneous' tumors. However, while the mutations are only transversions in the radiation-associated tumors, they are transversions as well as transitions in the 'spontaneous' ones and a mutation in codon 691 giving rise to a polymorphism in the ret gene, and frequently associated to a C-cell hyperplasia in radiation-associated tumors. The frequency of this mutation was significantly higher (60%) in these tumors, than in normal controls (21%) or 'spontaneous' epithelial thyroid tumors (23%). (author)

  9. Research progress and application prospect of radiation-resistant prokaryotic microbe

    International Nuclear Information System (INIS)

    Wang Wei; Zhu Jing; Zhang Zhidong; Tang Qiyong; Chen Ming

    2013-01-01

    Radiation-resistant microbe is becoming the research hotspot because of its special life phenomenon and physiological mechanism. Radiation-resistant bacteria are one kind of the most studied radiation-resistant microbe. This article summarized some aspects of the research on radiation-resistant bacteria, including the radiation resistant bacteria resources, and discussed its potential application prospects in the environmental engineering, biotechnology, human health, military and space et al. (authors)

  10. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

    Science.gov (United States)

    Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

    2010-01-25

    Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

  11. Radiation curable resistant coatings and their preparation

    International Nuclear Information System (INIS)

    Brack, K.

    1976-01-01

    A prepolymer containing unsaturated hydrocarbon groups is prepared and mixed on a roller mill with one or more acrylic ester monomers and various additives to make a coating formulation of a desired viscosity. In general, low viscosity formulations are used for overprint varnishes, on paper or foil, or with pigments, for certain types of printing inks. Higher viscosity formulations are used to apply thick films on panels, tiles, or other bodies. Thin films are cured to hardness by brief exposure to ultraviolet light. Thicker films require more energetic radiation such as plasma arc and electron beam radiation. The prepolymers particularly useful for making such radiation curable coatings are the reaction products of polyether polyols and bis- or polyisocyanates and hydroxy alkenes or acrylic (or methacrylic) hydroxy esters, and, likewise, reactive polyamides modified with dicarboxy alkenes, their anhydrides or esters. A small amount of wax incorporated in the coating formulations results in coatings with release characteristics similar to those of PTFE coatings. 10 claims

  12. Computational Modeling of Medical Images of Brain Tumor Patients for Optimized Radiation Therapy Planning

    DEFF Research Database (Denmark)

    Agn, Mikael

    In brain tumor radiation therapy, the aim is to maximize the delivered radiation dose to the targeted tumor and at the same time minimize the dose to sensitive healthy structures – so-called organs-at-risk (OARs). When planning a radiation therapy session, the tumor and the OARs therefore need...... to be delineated on medical images of the patient’s head, to be able to optimize a radiation dose plan. In clinical practice, the delineation is performed manually with limited assistance from automatic procedures, which is both time-consuming and typically suffers from poor reproducibility. There is, therefore...

  13. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  14. Insulating materials resistance in intense radiation beams

    International Nuclear Information System (INIS)

    Oproiu, Constantin; Martin, Diana; Scarlat, Florin; Timus, Dan; Brasoveanu, Mirela; Nemtanu, Monica

    2002-01-01

    The paper emphasizes the main changes of the mechanical and electrical properties of some organic insulating materials exposed to accelerated electron beams. These materials are liable to be used in nuclear plants and particle accelerators. The principal mechanical and electrical properties analyzed were: tensile strength, fracture strength, tearing on fracture, dielectric strength, electrical resistivity, dielectric constant and tangent angle of dielectric losses. (authors)

  15. Radiation-resistant micro-organisms isolated from textiles

    International Nuclear Information System (INIS)

    Kristensen, H.; Christensen, E.A.

    1981-01-01

    Towels from private homes and public offices and underwear contaminated by being used by employees at a public health laboratory were examined for occurrence of radiation-resistant bacteria and fungi. Three different methods were used for isolation of the most resistant organisms, one with multiplication of the microbial population prior to an irradiation used for selection, and two witout this multiplication and with the organisms placed on membrane filters or in situ on the textiles, respectively. A total of 44 different strains were isolated. Differences in the three methods used for selection of the most radiation-resistant microorganisms were not reflected in the results. 16 pigmentproducing Gram-positive cocci, tentatively classified as Micrococcus radiodurans, were the most radiation-resistant and were isolated in about half of the examinations. Other Gram-positive cocci, nonspore forming rods, some Nocardia and Candida parapsilosis strains and two Bacillus strains constituted the rest of the collection. With few exceptions dose-response curves for the strains were upward convex. D-6 values determined to be between 1.5 megarad for the most radiation sensitive, a Candida, and 5.7 megarad for the most resistant, tentatively classified as M. radiodurans. The D-6 values for the Bacillus strains were in both cases 1.8 megarad, consistent with a D-value of 0.3 megarad. The same resistance is reported to be the maximum resistance for B. pumilus, strain E601, commonly used as reference strain in the literature on radiation sterilization of medical devices and supplies. (author)

  16. Radiation-resistant micro-organisms isolated from textiles

    Energy Technology Data Exchange (ETDEWEB)

    Kristensen, H; Christensen, E A [Statens Seruminstitut, Copenhagen (Denmark)

    1981-01-01

    Towels from private homes and public offices and underwear contaminated by being used by employees at a public health laboratory were examined for occurrence of radiation-resistant bacteria and fungi. Three different methods were used for isolation of the most resistant organisms, one with multiplication of the microbial population prior to an irradiation used for selection, and two witout this multiplication and with the organisms placed on membrane filters or in situ on the textiles, respectively. A total of 44 different strains were isolated. Differences in the three methods used for selection of the most radiation-resistant microorganisms were not reflected in the results. 16 pigmentproducing Gram-positive cocci, tentatively classified as Micrococcus radiodurans, were the most radiation-resistant and were isolated in about half of the examinations. Other Gram-positive cocci, nonspore forming rods, some Nocardia and Candida parapsilosis strains and two Bacillus strains constituted the rest of the collection. With few exceptions dose-response curves for the strains were upward convex. D-6 values determined to be between 1.5 megarad for the most radiation sensitive, a Candida, and 5.7 megarad for the most resistant, tentatively classified as M. radiodurans. The D-6 values for the Bacillus strains were in both cases 1.8 megarad, consistent with a D-value of 0.3 megarad. The same resistance is reported to be the maximum resistance for B. pumilus, strain E601, commonly used as reference strain in the literature on radiation sterilization of medical devices and supplies.

  17. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

    Science.gov (United States)

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

  18. Metal-nanotube composites as radiation resistant materials

    Energy Technology Data Exchange (ETDEWEB)

    González, Rafael I.; Valencia, Felipe; Mella, José; Kiwi, Miguel, E-mail: m.kiwi.t@gmail.com [Departamento de Física, Facultad de Ciencias, CEDENNA, Universidad de Chile, Casilla 653, Santiago 7800024 (Chile); Duin, Adri C. T. van [Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States); So, Kang Pyo; Li, Ju [Department of Nuclear Science and Engineering and Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Bringa, Eduardo M. [CONICET and Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza 5500 (Argentina)

    2016-07-18

    The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role of nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.

  19. Metal-nanotube composites as radiation resistant materials

    International Nuclear Information System (INIS)

    González, Rafael I.; Valencia, Felipe; Mella, José; Kiwi, Miguel; Duin, Adri C. T. van; So, Kang Pyo; Li, Ju; Bringa, Eduardo M.

    2016-01-01

    The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role of nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.

  20. Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shintani, Satoru; Mihara, Mariko; Li, Chunnan; Nakahara Yuuji; Hino, Satoshi; Nakashiro, Koh-ichi; Hamakawa, Hiroyuki

    2003-01-01

    DNA-PK is a nuclear protein with serine/threonine kinase activity and forms a complex consisting of the DNA-PKcs and a heterodimer of Ku70 and Ku80 proteins. Recent laboratory experiments have demonstrated that the DNA-PK complex formation is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. In this study, we evaluated the relationship between expression levels of DNA-PKcs, Ku70 and Ku80 proteins and radiation sensitivity in oral squamous cell carcinoma (OSCC) cell lines and in OSCC patients treated with preoperative radiation therapy. The OSCC cell lines greatly differed in their response to irradiation, as assessed by a standard colony formation assay. However, the expression levels of the DNA-PK complex proteins were all similar, and there was no association between the magnitude of their expression and the tumor radiation sensitivity. Expression of DNA-PK complex proteins increased after radiation treatment, and the increased values correlated with the tumor radiation resistance. Expression of DNA-PKcs and Ku70 after irradiation was increased in the surviving cells of OSCC tissues irradiated preoperatively. These results suggest that up-regulation of DNA-PK complex protein, especially DNA-PKcs, after radiation treatment correlates to radiation resistance. DNA-PKcs might be a molecular target for a novel radiation sensitization therapy of OSCC. (author)

  1. Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-13-1-0163 TITLE: Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer ...Prostate Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Feng Yang, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: fyang@bcm.edu...W81XWH-13-1-0163 " Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer " Introduction AR signaling

  2. Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine.

    Science.gov (United States)

    Eke, Iris; Makinde, Adeola Y; Aryankalayil, Molykutty J; Ahmed, Mansoor M; Coleman, C Norman

    2016-11-01

    New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. Published by Elsevier Ireland Ltd.

  3. Data base of radiation-resistant dielectric and insulating materials

    International Nuclear Information System (INIS)

    Hama, Yoshimasa; Sunazuka, Hideo; Nashiyama, Isamu; Kakuta, Tsunemi.

    1987-01-01

    In the data base of radiation-resistant dielectric and insulating materials, the data format contains such items as to give the summary; the data sheet contains the data in concrete form of respective properties from the references; the sheet of references contains the references in the former two. In the above three, there are attached code No., data sheet No., reference No. and key words. In the three areas as radiation-resistant dielectric and insulating materials, i.e., organic materials, inorganic materials and optical fibers, the following are explained: data format, data sheet and objectives. (Mori, K.)

  4. Ways of providing radiation resistance of magnetic field semiconductor sensors

    CERN Document Server

    Bolshakova, I A; Holyaka, R; Matkovskii, A; Moroz, A

    2001-01-01

    Hall magnetic field sensors resistant to hard ionizing irradiation are being developed for operation under the radiation conditions of space and in charged particle accelerators. Radiation resistance of the sensors is first determined by the properties of semiconductor materials of sensitive elements; we have used microcrystals and thin layers of III-V semiconductors. Applying complex doping by rare-earth elements and isovalent impurities in certain proportions, we have obtained magnetic field sensors resistant to irradiation by fast neutrons and gamma-quanta. Tests of their radiation resistance were carried out at IBR-2 at the Joint Institute for Nuclear Research (Dubna). When exposed to neutrons with E=0.1-13 MeV and intensity of 10 sup 1 sup 0 n cm sup - sup 2 s sup - sup 1 , the main parameter of the sensors - their sensitivity to magnetic fields - changes by no more than 0.1% up to fluences of 10 sup 1 sup 4 n cm sup - sup 2. Further improvement of radiation resistance of sensor materials is expected by ...

  5. Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction

    International Nuclear Information System (INIS)

    Noonan, K.E.; Beck, C.; Holzmayer, T.A.; Chin, J.E.; Roninson, I.B.; Wunder, J.S.; Andrulis, I.L.; Gazdar, A.F.; Willman, C.L.; Griffith, B.; Von Hoff, D.D.

    1990-01-01

    The resistance of tumor cells ot chemotheraprutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in bitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refactory tumors untreated with chemotherapeutic drugs. The authors have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clincal samples, based on the polymerase chain reaction. They have used this assay to measure MDR1 gene expression in MDR cell lines and >300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expression were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of samples without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were ost common among tumor types known to be relatively responsive to chemotherapy

  6. Heat- and radiation-resistant scintillator for electron microscopes

    International Nuclear Information System (INIS)

    Kosov, A.V.; Petrov, S.A.; Puzyr', A.P.; Chetvergov, N.A.

    1987-01-01

    The use of a scintillator consisting of a single crystal of bismuth orthogermanate, which has high heat and radiation resistance, in REM-100, REM-200, and REM-100U electron microscopes is described. A study of the heat and radiation stabilities of single crystals of bismuth orthogermanate (Bi 4 Ge 3 O 12 ) has shown that they withstood multiple electron-beam heating redness (T ∼ 800 0 C) without changes in their properties

  7. Radiation resistivity of pure-silica core image guide

    International Nuclear Information System (INIS)

    Hayami, H.; Ishitani, T.; Kishihara, O.; Suzuki, K.

    1988-01-01

    Radiation resistivity of pure-silica core image guides were investigated in terms of incremental spectral loss and quality of pictures transmitted through the image guides. Radiation-induced spectral losses were measured so as to clarify the dependences of radiation resistivity on such parameters as core materials (OH and Cl contents), picture element dimensions, (core packing density and cladding thickness), number of picture elements and drawing conditions. As the results, an image guide with OH-and Cl-free pure-silica core, 30-45% in core packing density, and 1.8 ∼ 2.2 μm in cladding thickness showed the lowest loss. The parameters to design this image guide were almost the same as those to obtain a image guide with good picture quality. Radiation resistivity of the image guide was not dependent on drawing conditions and number of picture elements, indicating that the image guide has large allowable in production conditions and that reliable quality is constantly obtained in production. Radiation resistivity under high total doses was evaluated using the image guide with the lowest radiation-induced loss. Maximum usable lengths of the image guide for practical use under specific high total doses and maximum allowable total doses for the image guide in specific lengths were extrapolated. Picture quality in terms of radiation-induced degradation in color fidelity in the pictures transmitted through image guides was quantitatively evaluated in the chromaticity diagram based on the CIE standard colorimetric system and in the color specification charts according to three attributes of colors. The image guide with the least spectral incremental loss gives the least radiation-induced degradation in color fidelity in the pictures as well. (author)

  8. Genetic variation in resistance to ionizing radiation

    International Nuclear Information System (INIS)

    Ayala, F.J.

    1991-01-01

    We proposed an investigation of genetically-determined individual differences in sensitivity to ionizing radiation. The model organism is Drosophila melanogaster. The gene coding for Cu,Zn superoxide dismutase (SOD) is the target locus, but the effects of variation in other components of the genome that modulate SOD levels are also taken into account. SOD scavenges oxygen radicals generated during exposure to ionizing radiation. It has been shown to protect against ionizing radiation damage to DNA, viruses, bacteria, mammalian cells, whole mice, and Drosophila. Two alleles, S and F, are commonly found in natural populations of D. melanogaster; in addition we have isolated from a natural population ''null'' (CA1) mutant that yields only 3.5% of normal SOD activity. The S, F, and CA1 alleles provide an ideal model system to investigate SOD-dependent radioresistance, because each allele yields different levels of SOD, so that S > F >> CA1. The roles of SOD level in radioresistance are being investigated in a series of experiments that measure the somatic and germ-line effects of increasing doses of ionizing radiation. In addition, we have pursued an unexpected genetic event-namely the nearly simultaneous transformation of several lines homozygous for the SOD ''null'' allele into predominately S lines. Using specifically designed probes and DNA amplification by means of the Tag polymerase chain reaction (PCR) we have shown that (1) the null allele was still present in the transformed lines, but was being gradually replaced by the S allele as a consequence of natural selection; and (2) that the transformation was due to the spontaneous deletion of a 0.68 Kb truncated P-element, the insertion of which is characteristic of the CA1 null allele

  9. Tumor response to ionizing radiation and combined 2-deoxy-D-glucose application in EATC tumor bearing mice: monitoring of tumor size and microscopic observations

    International Nuclear Information System (INIS)

    Latz, D.; Thonke, A.; Jueling-Pohlit, L.; Pohlit, W.

    1993-01-01

    The present study deals with the changes induced by two fractionation schedules (5x9 Gy and 10x4.5 Gy; 30 MeV-electrons) of ionizing radiations and 2-Deoxy-D-Glucose (2-DG) application on EATC tumor bearing swiss albino mice. The monitoring of tumor response was carried out by means of calliper measurement on the macroscopic level and by histopathological examination of tumor preparations stained with hematoxiline and eosine on the microscopic level. The tumor material was assessed at suitable intervals after treatment by killing the animals. The tumor response was analysed in the histological preparations and the thickness of the tumor band was determined quantitatively by an ocularmicrometric technique. Tumor damage was most extensive in the combined treated animals (5x9 Gy + 2-DG). Only in this group local tumor control was achievable. The histological analysis of tumor preparations revealed additional data about treatment-induced changes in the tumor compared to the measurement of the tumor volume with mechanical callipers. We also found that the treatment outcome could be predicted from the histopathological analysis. It is concluded that studies involving histopathological examinations may give some insight into the way cancer is controlled by radiotherapy and may be of value in prognosis and selection of treatment in patients. (orig.) [de

  10. Radiation resistance of clinical Acinetobacter spp.: A need for concern

    International Nuclear Information System (INIS)

    Christensen, E.A.; Gerner-Smidt, P.; Kristensen, H.

    1991-01-01

    As part of an epidemiological investigation of hospital infections caused by Acinetobacter spp. the radiation resistance of 15 clinical isolates and four reference strains was assessed. The radiation resistance (in D-6 values, viz. the dose necessary for reducing the initial number of colony forming units by a factor of 10(6)) was, in general, higher in the isolates of A. radioresistens than in the isolates of the A. calcoaceticus-A. baumannii complex and of A. lwoffi. However, the least resistant isolates of A. radioresistens had a D-6 value equal to or lower than the most resistant isolates of the other groups. The lowest D-6 values found were for two of the reference strains. The highest D-6 value was 35 kGy. Three isolates of A. johnsonii could not survive long enough in a dried preparation to make an assessment of the D-6 values possible. The radiation resistance of the 15 clinical isolates in the present study was higher than the resistance found in a study of similar isolates in 1970

  11. Radiation resistance of clinical Acinetobacter spp. : A need for concern

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, E.A.; Gerner-Smidt, P.; Kristensen, H. (Control Department, Statens Seruminstitut, Copenhagen (Denmark))

    1991-06-01

    As part of an epidemiological investigation of hospital infections caused by Acinetobacter spp. the radiation resistance of 15 clinical isolates and four reference strains was assessed. The radiation resistance (in D-6 values, viz. the dose necessary for reducing the initial number of colony forming units by a factor of 10(6)) was, in general, higher in the isolates of A. radioresistens than in the isolates of the A. calcoaceticus-A. baumannii complex and of A. lwoffi. However, the least resistant isolates of A. radioresistens had a D-6 value equal to or lower than the most resistant isolates of the other groups. The lowest D-6 values found were for two of the reference strains. The highest D-6 value was 35 kGy. Three isolates of A. johnsonii could not survive long enough in a dried preparation to make an assessment of the D-6 values possible. The radiation resistance of the 15 clinical isolates in the present study was higher than the resistance found in a study of similar isolates in 1970.

  12. Homozygous mutations in the Fhit gene results in resistance to ionizing radiation and inhibition of apoptosis

    International Nuclear Information System (INIS)

    Turner, B.C.; Potoczek, M.B.; Ottey, M.; Croce, C.M.; Huebner, K.

    2001-01-01

    radiation compared to parental mammalian cells expressing wild-type Fhit protein. Finally, we demonstrated that breast tumors from breast cancer patients with local breast tumor recurrences following breast conserving therapy more often lacked immunhistochemical detection of Fhit protein compared to tumors from breast cancer patients without local breast cancer recurrence (p=0.02). Interestingly, the adjacent benign regions of these sections contained similar levels of Fhit protein expression suggesting that a somatic alteration is critical in the clinical resistance to ionizing radiation observed in these patients. Apoptotic pathways regulating the aberrant response to DNA damage-induced apoptosis in Fhit knock-out cells are currently being studied. Conclusion: Mouse epithelial cells containing homozygous Fhit mutations are resistant to single fraction low and high dose ionizing radiation with decreased levels of radiation-induced apoptotic cell death. Breast tumors from women with local breast cancer recurrence following breast conserving therapy have low levels of Fhit protein. These findings may have important biologic and treatment implications including those for cancer patients with tumors having mutations in Fhit and suggest that treatment with ionizing radiation in these patients may not result in optimal responses

  13. The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

    Directory of Open Access Journals (Sweden)

    Gayle E. Woloschak

    2012-12-01

    Full Text Available The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.

  14. Factors affecting radiation injury after interstitial brachytherapy for brain tumors

    International Nuclear Information System (INIS)

    Leibel, S.A.; Gutin, P.H.; Davis, R.L.

    1991-01-01

    The effects of brachytherapy on normal brain tissue are not easily delineated in the clinical setting because of the presence of concurrent radiation-induced changes in the coexistent brain tumor. Sequential morphologic studies performed after the implantation of radioactive sources into the brains of experimental animals have provided a better understanding of the character and magnitude of the structural changes produced by interstitial irradiation on normal brain tissue. Furthermore, the clinical experience accumulated thus far provides not only relevant information, but also some guidelines for future treatment policies. In this paper, the authors summarize the experimental findings and review the pathologic and clinical features of brain injury caused by interstitial brachytherapy. A number of studies in the older literature examined the effects of radioisotopes such as radium-226 (38--43), radon-22 (44--46), gold-198 (29,47--50), tantalum-182 (29,51,52) yttrium-9- (50,53,54), and cobalt-60 (29,50,55). This review is restricted to low- and high-activity encapsulated iodine-125 ( 125 I) and iridium-192 ( 192 Ir), the isotopes that are most commonly used in current clinical practice

  15. Physics of radiation therapy of head and neck tumors

    International Nuclear Information System (INIS)

    Almond, P.R.

    1987-01-01

    Radiotherapy treatment of head and neck cancers probably requires more individual planning than for any other cancer site because of the large number of variables that exist. The fact that tumors may be superficial or relatively deep-seated, the complex shape of the head and neck region, the presence of significant inhomogeneities such as bone and air spaces, and the need to spare critical structures such as the eyes or central nervous system all add to the need for careful considerations of the physical parameters involved in radiotherapy. In addition, the high mobility of the head allows it to assume a wide variety of positions so that techniques have had to be developed for careful simulation, repositioning, and immobilization during treatment. In the head and neck region shaping of the beam becomes important, and therefore, blocked fields, compensators, or wedges are often used. Although the specific radiotherapy techniques for each site of head and neck cancer are described in the various chapters of this book, a general description of the various types of radiation beams, radioactive sources, beam modifiers, treatment planning techniques, and treatment implementation is given in this chapter. The discussion is divided into three main categories: (1) external beam, (2) brachytherapy, and (3) simulation and immobilization

  16. Induction of Apoptosis and expression of Apoptosis-related gene products in response to radiation in murine tumors

    International Nuclear Information System (INIS)

    Seong, J. S.

    1997-01-01

    To analyze the involvement of apoptosis regulatory genes p53, p21 waf1/cip1 , bax and bcl-2 in induction of apoptosis by radiation in murine tumors. The radiation-sensitive ovarian carcinoma OCa-I and the radiation-resistant hepatocarcinoma HCa-I were used. Tumors, 8mm in diameter, were irradiated with 25Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. Both tumors were positive for wild-type p53. Radiation induced apoptosis in OCa-I but not in HCa-I. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h. In OCa-I radiation upregulated the expression of p53, p21 waf1/cip1 , and the bcl-2/bax ratio was decreased. In HCa-I radiation increased the expression of both p53 and p21 waf1/cip1 , although the increase of the latter was small. The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis. The development of apoptosis required upregulation of both p53 and p21 waf1/cip1 as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio prevented apoptosis in the presence of upregulated p53 and p21 waf1/cip1 . These findings identified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for predicting the outcome of cancer therapy with cytotoxic agents. (author)

  17. Induction of Apoptosis and expression of Apoptosis-related gene products in response to radiation in murine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Seong, J S [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine; Hunter, N R; Milas, L [Texas Univ., Houston, TX (United States)

    1997-09-01

    To analyze the involvement of apoptosis regulatory genes p53, p21{sup waf1/cip1}, bax and bcl-2 in induction of apoptosis by radiation in murine tumors. The radiation-sensitive ovarian carcinoma OCa-I and the radiation-resistant hepatocarcinoma HCa-I were used. Tumors, 8mm in diameter, were irradiated with 25Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. Both tumors were positive for wild-type p53. Radiation induced apoptosis in OCa-I but not in HCa-I. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h. In OCa-I radiation upregulated the expression of p53, p21{sup waf1/cip1}, and the bcl-2/bax ratio was decreased. In HCa-I radiation increased the expression of both p53 and p21{sup waf1/cip1}, although the increase of the latter was small. The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis. The development of apoptosis required upregulation of both p53 and p21{sup waf1/cip1} as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio prevented apoptosis in the presence of upregulated p53 and p21{sup waf1/cip1}. These findings identified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for predicting the outcome of cancer therapy with cytotoxic agents. (author).

  18. Radiation-associated breast tumors display a distinct gene expression profile

    DEFF Research Database (Denmark)

    Broeks, Annegien; Braaf, Linde M; Wessels, Lodewyk F A

    2010-01-01

    PURPOSE: Women who received irradiation for Hodgkin's lymphoma have a strong increased risk for developing breast cancer. Approximately 90% of the breast cancers in these patients can be attributed to their radiation treatment, rendering such series extremely useful to determine whether a common...... radiation-associated cause underlies the carcinogenic process. METHODS AND MATERIALS: In this study we used gene expression profiling technology to assess gene expression changes in radiation-associated breast tumors compared with a set of control breast tumors of women unexposed to radiation, diagnosed...... at the same age. RNA was obtained from fresh frozen tissue samples from 22 patients who developed breast cancer after Hodgkin's lymphoma (BfHL) and from 20 control breast tumors. RESULTS: Unsupervised hierarchical clustering of the profile data resulted in a clustering of the radiation-associated tumors...

  19. Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Huamani, Jessica; Fu, Allie; Hallahan, Dennis E.

    2006-01-01

    The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer

  20. Tumourigenicity and radiation resistance of mesenchymal stem cells.

    Science.gov (United States)

    D'Andrea, Filippo P; Horsman, Michael R; Kassem, Moustapha; Overgaard, Jens; Safwat, Akmal

    2012-05-01

    Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under nontreated and irradiated conditions, were assessed with microarrays (Affymetrix Human Exon 1.0 ST array). The cellular functions affected by the altered gene expressions were assessed through gene pathway mapping (Ingenuity Pathway Analysis). Based on the clonogenic assay the nontumourigenic cell line was found to be more sensitive to radiation than the tumourigenic cell line. Using the exon chips, 297 genes were found altered between untreated samples of the cell lines whereas only 16 genes responded to radiation treatment. Among the genes with altered expression between the untreated samples were PLAU, PLAUR, TIMP3, MMP1 and LOX. The pathway analysis based on the alteration between the untreated samples indicated cancer and connective tissue disorders. This study has shown possible common genetic events linking tumourigenicity and radiation response. The PLAU and PLAUR genes are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are involved in regulation of the surrounding matrix. The first group may contribute to the difference in radiation resistance observed and the latter could be a major contributor to the tumourigenic capabilities by degrading the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin.

  1. Radiation resistant organic composites for superconducting fusion magnets

    International Nuclear Information System (INIS)

    Nishijima, S.; Okada, T.

    1993-01-01

    Organic composite materials (usually reinforced by glas fibers: GFRP) are to be used in fusion superconducting magnets as insulating and/or structural materials. The fusion superconducting magnets are operated under radiation environments and hence the radiation induced degradation of magnet components is ought to be estimated. Among the components the organic composite materials were evaluated to be the most radiation sensitive. Consequently the development of radiation resistant organic composite materials is thought one of the 'key' technologies for fusion superconducting magnets. The mechanism of radiation-induced degradation was studied and the degradation of interlaminar shear strength (ILSS) was found to be the intrinsic phenomenon which controlled the overall degradation of organic composite materials. The degradation of ILSS was studied changing matrix resin, reinforcement and type of fabrics. The possible combination of the organic composites for the fusion superconducting magnet will be discussed. (orig.)

  2. Increased seroreactivity to glioma-expressed antigen 2 in brain tumor patients under radiation.

    Directory of Open Access Journals (Sweden)

    Sabrina M Heisel

    Full Text Available BACKGROUND: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation. CONCLUSIONS/SIGNIFICANCE: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

  3. Response of rat prostate and lung tumors to ionizing radiation combined with the angiogenesis inhibitor AMCA

    Energy Technology Data Exchange (ETDEWEB)

    Kal, H.B. [Dept. of Radiotherapy, Univ. Medical Centre Utrecht (Netherlands); Struikmans, H. [Dept. of Radiotherapy, Univ. Medical Centre Utrecht (Netherlands); Dept. of Radiotherapy, Medical Centre Haaglanden, Westeinde Hospital, The Hague (Netherlands); Gebbink, M.F.B.G.; Voest, E.E. [Dept. of Medical Oncology, Univ. Medical Centre Utrecht (Netherlands)

    2004-12-01

    Aim: to determine whether radiation combined with Trans-4-AminoMethyl cyclohexane carboxylic acid (AMCA, or tranexamic acid, Cyklokapron registered) results in a better tumor response than radiation alone. Materials and methods: we evaluated the responses of the L44 lung tumor in BN rats and R3327-MATLyLu (MLL) prostate tumor in Copenhagen rats, to single and fractionated X-ray doses with and without AMCA (1.5 g/kg). Tumors were grown subcutaneously in the flank of the animal. AMCA was administered subcutaneously twice daily for at least 2 weeks. Response to treatment was evaluated according to excess growth delay and specific growth delay. Results: L44 and MLL tumors treated with AMCA only experienced a non-significant growth delay. L44 tumors treated with 4 daily dose fractions of 2.5 Gy had a significant excess and specific growth delay when treated with AMCA, the enhancement ratio was 1.6-1.7. The enhancement ratio based on the calculated excess biologically effective dose of the linear-quadratic concept was 1.4-1.5. MLL tumors treated with a single dose of 20 Gy and AMCA had no significant excess growth delay. Conclusion: the enhancement ratio of 1.4-1.7 for the L44 tumor, but not for the MLL tumor, due to AMCA treatment, indicates that AMCA may potentiate the anti-tumor effect of ionizing radiation in distinct tumor types. (orig.)

  4. Response of rat prostate and lung tumors to ionizing radiation combined with the angiogenesis inhibitor AMCA

    International Nuclear Information System (INIS)

    Kal, H.B.; Struikmans, H.; Gebbink, M.F.B.G.; Voest, E.E.

    2004-01-01

    Aim: to determine whether radiation combined with Trans-4-AminoMethyl cyclohexane carboxylic acid (AMCA, or tranexamic acid, Cyklokapron registered) results in a better tumor response than radiation alone. Materials and methods: we evaluated the responses of the L44 lung tumor in BN rats and R3327-MATLyLu (MLL) prostate tumor in Copenhagen rats, to single and fractionated X-ray doses with and without AMCA (1.5 g/kg). Tumors were grown subcutaneously in the flank of the animal. AMCA was administered subcutaneously twice daily for at least 2 weeks. Response to treatment was evaluated according to excess growth delay and specific growth delay. Results: L44 and MLL tumors treated with AMCA only experienced a non-significant growth delay. L44 tumors treated with 4 daily dose fractions of 2.5 Gy had a significant excess and specific growth delay when treated with AMCA, the enhancement ratio was 1.6-1.7. The enhancement ratio based on the calculated excess biologically effective dose of the linear-quadratic concept was 1.4-1.5. MLL tumors treated with a single dose of 20 Gy and AMCA had no significant excess growth delay. Conclusion: the enhancement ratio of 1.4-1.7 for the L44 tumor, but not for the MLL tumor, due to AMCA treatment, indicates that AMCA may potentiate the anti-tumor effect of ionizing radiation in distinct tumor types. (orig.)

  5. pH regulation in sensitive and multidrug resistant Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Litman, Thomas; Pedersen, S F; Kramhøft, B

    1998-01-01

    Maintenance and regulation of intracellular pH (pHi) was studied in wild-type Ehrlich ascites tumor cells (EHR2) and five progressively daunorubicin-resistant, P-glycoprotein (P-gp)-expressing strains, the maximally resistant of which is EHR2/1.3. Steady-state pHi was similar in cells expressing...

  6. Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization

    Energy Technology Data Exchange (ETDEWEB)

    Leung, F.L.; Park, J.F.; Dagle, G.E.

    1993-06-01

    In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 of 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.

  7. Radiation resistance of concrete of nuclear reactor vessel

    International Nuclear Information System (INIS)

    Belyakov, V.V.; Denisov, A.V.; Korenevskij, V.V.; Muzalevskij, L.P.; Dubrovskij, V.B.; Ivanov, D.A.; Nazarov, I.L.; Sashin, N.L.

    1992-01-01

    Results of calculational-experimental determination of radiation resistance for concrete bases on limestone gravel and quartz sand, which are the most perspective materials for manufacturing prestressed concrete of the VG-400 reactor vessel are considered. Material samples under investigation were irradiated in the channels of the IBR-2 research reactor for the purpose of the calcultional result verification

  8. Radiation resistivity of frozen insulin solutions and suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Soboleva, N N; Ivanova, A I; Talrose, V L; Trofimov, V I; Fedotov, V P [AN SSSR, Moscow. Inst. Fizicheskoj Khimii; Research Institute for Biological Testing of Chemicals, Moscow (USSR); Institute of Experimental Endocrinology and Hormon Chemistry, Moscow (USSR))

    1981-10-01

    The effect of great increase in radiation resistance of insulin solutions and suspensions after irradiation at low temperatures in the frozen state was observed by absorption spectrophotometry, paper chromatography and biological analysis. The data obtained suggest irradiation of frozen insulin solutions and suspensions as a method for its sterilization.

  9. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    Energy Technology Data Exchange (ETDEWEB)

    Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavrommatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.; Detter, Chris; Brettin, Thomas; Saunders, Elizabeth; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.; Wolf, Yuri I.; Sorokin, Alexander; Gerasimova, Anna V.; Gelfand, Mikhail S.; Fredrickson, James K.; Koonin, Eugene V.; Daly, Michael J.

    2007-07-24

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at itsoptimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  10. Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors.

    Science.gov (United States)

    Bagrodia, Aditya; Lee, Byron H; Lee, William; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Pietzak, Eugene J; Gao, Sizhi Paul; Zabor, Emily C; Ostrovnaya, Irina; Kaffenberger, Samuel D; Syed, Aijazuddin; Arcila, Maria E; Chaganti, Raju S; Kundra, Ritika; Eng, Jana; Hreiki, Joseph; Vacic, Vladimir; Arora, Kanika; Oschwald, Dayna M; Berger, Michael F; Bajorin, Dean F; Bains, Manjit S; Schultz, Nikolaus; Reuter, Victor E; Sheinfeld, Joel; Bosl, George J; Al-Ahmadie, Hikmat A; Solit, David B; Feldman, Darren R

    2016-11-20

    Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture-based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic

  11. Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Luzhna, Lidia [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada); Kovalchuk, Olga, E-mail: olga.kovalchuk@uleth.ca [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada)

    2010-02-05

    Chemoresistant tumors often fail to respond to other cytotoxic treatments such as radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are not fully understood and are believed to be epigenetic in nature. We hypothesize that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may exhibit different responses to ionizing radiation due to their dissimilar epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore, we found that MCF-7/DOX cells had lower background apoptosis levels and were less responsive to radiation than MCF-7 cells. Decreased radiation responsiveness correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here, for the first time, we show that the radiation resistance of MCF-7/DOX cells can be reversed by an epigenetic treatment - the application of methyl-donor SAM. SAM-mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF-7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher methylated MCF-7 cells resulted in a decrease in their radiation responsiveness. This data suggests that a fine balance of DNA methylation is needed to insure proper radiation and drug responsiveness.

  12. Radiation and concurrent chemotherapy for the treatment of Lewis lung tumor and B16 melanoma tumor in C57/BL mice

    International Nuclear Information System (INIS)

    Pedersen, J.E.; Barron, G.

    1984-01-01

    C57/BL mice bearing either Lewis lung tumor or B16 melanoma tumor were treated with radiation and concurrent chemotherapy. The treatment results were determined in vivo by tumor regrowth delay assay. When continuous infusion of either Cyclophosphamide (CYCLO) or 5-Fluorouracil (5-FU) or Adriamycin (ADRIA) or Mitomycin-C (MITO-C) was used in combination with continuous radiation at 1 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. When multiple drug chemotherapy, FAM (5-FU, ADRIA, MITO-C) was administered in combination with radiation at 80 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. In these two murine tumor models, when clinically relevant concentrations of commonly used chemotherapy agents were combined with radiation, no therapeutic advantage was observed

  13. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

    Directory of Open Access Journals (Sweden)

    Sebastian Diegeler

    2017-06-01

    Full Text Available Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

  14. Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities.

    Science.gov (United States)

    Diegeler, Sebastian; Hellweg, Christine E

    2017-01-01

    Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

  15. Molecular events in the induction of murine tumors by ionizing radiation

    International Nuclear Information System (INIS)

    Andrews, K.L.

    1993-01-01

    A new method is presented to identify and clone novel transforming genes from radiation-induced tumors. It involves the creation of a cDNA expression library from radiation-induced tumors. The library is transfected into non-transformed cells, and the nude mouse tumorigenicity assay functionally defines the acquisition of a transformed phenotype. cDNA clones responsible for transformation are rescued by PCR amplification. This method is applicable to a variety of mammalian systems. The only requirement is a functional assay with which to measure the acquisition of an altered phenotype following transfection of a cDNA library. This method has identified a cDNA for the 16 kD subunit of v-H + -ATPase, which has been associated with cellular transformation. Two protocols were used to generate radiation-induced tumors. One experiment utilizing fractionated doses of ionizing radiation had a much greater tumor yield than the second protocol using a single dose of 11.25 Gy. To determine if the mechanism of gene activation is different in radiation- and chemically-induced tumors, the expression pattern of five tumor-associated genes was analyzed. The expression patterns of mals 1-4 were not significantly different. However, transin, a secreted protease, was overexpressed in radiation-induced papillomas and undetectable in chemically-induced papillomas. Transin degrades basement membrane proteins and may be involved in the progression of benign, encapsulated tumors to malignant, invasive squamous cell carcinomas. Isolation and characterization of genes with dominant transforming activity from radiation-induced tumors will provide information to bridge the gap between the initial ionizing radiation event and the subsequent development of malignant tumors. The function of these genes may also provide information about the development of human malignancies. An understanding the natural biology of cells will help elucidate the pathogenesis cancer and other diseases

  16. The role of radiation therapy in the multidisciplinary treatment of patients with malignant tumors. Radiation pathological stand point

    International Nuclear Information System (INIS)

    Niibe, Hideo

    1998-01-01

    Estimations suggest that about 60% of all cancer patients will require some form of radiation therapy during their lifetime. Although 40 to 50% of cancer patients in Europe and the United States receive radiation therapy, only about 20% of patients with cancer in Japan undergo such treatment. This is largely due to the lack of understanding of the role of radiation therapy by many medical personnel in Japan, as well as to ''''radiation allergy'''' among many of the general population in Japan, a country that has been undergone atomic bombing. From our perspective as specialists in radiation therapy, the chronic shortage of radiation oncologist also poses a serious problem. Although there are approximately 700 hospitals throughout Japan where radiation therapy is available, no more than half this number of medical facilities have a full-time radiation oncologist. Perhaps the reason for this is that radiation therapy is perceived as unnecessary in Japan. However, it is absolutely essential. In our experience, the 5-year relative survival rate of patients with malignant tumors who have undergone radiation therapy in our clinic is 65 percent. Thus, radiation therapy has proven very useful in the treatment of malignant tumors. Moreover, better estimates of prognosis of cancer patients treated with radiation therapy are becoming possible. This article discusses the role of radiation therapy, from a radiation pathological perspective, in a multidisciplinary approach to treatment of cancer patients. I also emphasize the critical importance of training radiation oncologists who can function as part of multidisciplinary teams that care for patients with malignant tumors. (author). 50 refs

  17. Radiation Resistance Test of Wireless Sensor Node and the Radiation Shielding Calculation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Liqan; Sur, Bhaskar [Atomic Energy of Canada Limited, Ontario (Canada); Wang, Quan [University of Western Ontario, Ontario (Canada); Deng, Changjian [The University of Electronic Science and Technology, Chengdu (China); Chen, Dongyi; Jiang, Jin [Applied Physics Branch, Ontario (Korea, Republic of)

    2014-08-15

    A wireless sensor network (WSN) is being developed for nuclear power plants. Amongst others, ionizing radiation resistance is one essential requirement for WSN to be successful. This paper documents the work done in Chalk River Laboratories of Atomic Energy of Canada Limited (AECL) to test the resistance to neutron and gamma radiation of some WSN nodes. The recorded dose limit that the nodes can withstand before being damaged by the radiation is compared with the radiation environment inside a typical CANDU (CANada Deuterium Uranium) power plant reactor building. Shielding effects of polyethylene, cadmium and lead to neutron and gamma radiations are also analyzed using MCNP simulation. The shielding calculation can be a reference for the node case design when high dose rate or accidental condition (like Fukushima) is to be considered.

  18. NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

    Science.gov (United States)

    Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

    2016-01-01

    Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

  19. Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells

    Science.gov (United States)

    2012-01-01

    Introduction The taxanes paclitaxel and docetaxel are widely used in the treatment of breast, ovarian, and other cancers. Although their cytotoxicity has been attributed to cell-cycle arrest through stabilization of microtubules, the mechanisms by which tumor cells die remains unclear. Paclitaxel has been shown to induce soluble tumor necrosis factor alpha (sTNF-α) production in macrophages, but the involvement of TNF production in taxane cytotoxicity or resistance in tumor cells has not been established. Our study aimed to correlate alterations in the TNF pathway with taxane cytotoxicity and the acquisition of taxane resistance. Methods MCF-7 cells or isogenic drug-resistant variants (developed by selection for surviving cells in increasing concentrations of paclitaxel or docetaxel) were assessed for sTNF-α production in the absence or presence of taxanes by enzyme-linked immunosorbent assay (ELISA) and for sensitivity to docetaxel or sTNF-α by using a clonogenic assay (in the absence or presence of TNFR1 or TNFR2 neutralizing antibodies). Nuclear factor (NF)-κB activity was also measured with ELISA, whereas gene-expression changes associated with docetaxel resistance in MCF-7 and A2780 cells were determined with microarray analysis and quantitative reverse transcription polymerase chain reaction (RTqPCR). Results MCF-7 and A2780 cells increased production of sTNF-α in the presence of taxanes, whereas docetaxel-resistant variants of MCF-7 produced high levels of sTNF-α, although only within a particular drug-concentration threshold (between 3 and 45 nM). Increased production of sTNF-α was NF-κB dependent and correlated with decreased sensitivity to sTNF-α, decreased levels of TNFR1, and increased survival through TNFR2 and NF-κB activation. The NF-κB inhibitor SN-50 reestablished sensitivity to docetaxel in docetaxel-resistant MCF-7 cells. Gene-expression analysis of wild-type and docetaxel-resistant MCF-7, MDA-MB-231, and A2780 cells identified changes

  20. Shielding ability of lead loaded radiation resistant gloves

    International Nuclear Information System (INIS)

    Kawano, Takao; Ebihara, Hiroshi

    1990-01-01

    The shielding ability of radiation resistant gloves were examined. The gloves are made of lead loaded (as PbO 2 ) polyvinyl chloride resin and are about 0.4 mm of thickness (70 mg/cm 2 ). Eleven test pieces were sampled from each of three gloves (total were thirty three) and the transmission rates for radiations (X-ray or γ-ray) through the test pieces were measured with radiation sources, 99m Tc, 57 Co, 133 Ba, 133 Xe and 241 Am. The differences of the transmission rate for radiations by the positions of the gloves were smaller than 15%, and the differences by three gloves were smaller than 5% in the case of 60 keV and 141 keV radiations. The average transmission rates for radiations in thirty three test pieces were about 40% for 30 keV radiation, about 90% for 80 keV and 140 keV radiations. The shielding characteristic of the gloves could be equivalent to about 0.026 mm thick lead plate. (author)

  1. Isolation of Radiation-Resistant Bacteria from Mars Analog Antarctic Dry Valleys by Preselection, and the Correlation between Radiation and Desiccation Resistance.

    Science.gov (United States)

    Musilova, Michaela; Wright, Gary; Ward, John M; Dartnell, Lewis R

    2015-12-01

    Extreme radiation-resistant microorganisms can survive doses of ionizing radiation far greater than are present in the natural environment. Radiation resistance is believed to be an incidental adaptation to desiccation resistance, as both hazards cause similar cellular damage. Desert soils are, therefore, promising targets to prospect for new radiation-resistant strains. This is the first study to isolate radiation-resistant microbes by using gamma-ray exposure preselection from the extreme cold desert of the Antarctic Dry Valleys (a martian surface analogue). Halomonads, identified by 16S rRNA gene sequencing, were the most numerous survivors of the highest irradiation exposures. They were studied here for the first time for both their desiccation and irradiation survival characteristics. In addition, the association between desiccation and radiation resistance has not been investigated quantitatively before for a broad diversity of microorganisms. Thus, a meta-analysis of scientific literature was conducted to gather a larger data set. A strong correlation was found between desiccation and radiation resistance, indicating that an increase in the desiccation resistance of 5 days corresponds to an increase in the room-temperature irradiation survival of 1 kGy. Irradiation at -79°C (representative of average martian surface temperatures) increases the microbial radiation resistance 9-fold. Consequently, the survival of the cold-, desiccation-, and radiation-resistant organisms isolated here has implications for the potential habitability of dormant or cryopreserved life on Mars. Extremophiles-Halomonas sp.-Antarctica-Mars-Ionizing radiation-Cosmic rays.

  2. Effects of low dose radiation on antioxidant enzymes after radiotherapy of tumor-bearing mice

    International Nuclear Information System (INIS)

    Li Jin; Gao Gang; Wang Qin; Tang Weisheng; Liu Xiaoqiu; Wang Zhiquan

    2005-01-01

    Objective: To search for effects of low dose radiation on the activities of antioxidant enzymes after radiotherapy of tumor-bearing mice. Methods: Superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) were all determined by chemical colorimetry. Results: Low dose radiation increase the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) in serum of tumor-bearing mice more markedly than those in the unirradiated controls. The activities of antioxidant enzymes SOD, GST, CAT in serum of tumor-bearing mice (d 5 , d 3 ) irradiated with 5cGy 6h before 2.0 Gy radiation are obviously higher than those of the group (c 3 , c 5 ) given with radiotherapy only. Conclusion: The increase in the activities of antioxidant enzymes in serum of tumor-bearing mice triggered by low dose radiation could partly contribute to the protective mechanism. (authors)

  3. Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

    International Nuclear Information System (INIS)

    Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

    2008-01-01

    Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

  4. Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice

    International Nuclear Information System (INIS)

    Itasaka, Satoshi; Komaki, Ritsuko; Herbst, Roy S.; Shibuya, Keiko; Shintani, Tomoaki D.D.S.; Hunter, Nancy R. M.S.; Onn, Amir; Bucana, Corazon D.; Milas, Luka; Ang, K. Kian; O'Reilly, Michael S.

    2007-01-01

    Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice. Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy. Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin. Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse

  5. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  6. Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-06-01

    The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

  7. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

    Science.gov (United States)

    Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

    2014-12-24

    TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

  8. Tumor response parameters for head and neck cancer derived from tumor-volume variation during radiation therapy

    International Nuclear Information System (INIS)

    Chvetsov, Alexei V.

    2013-01-01

    Purpose: The main goal of this paper is to reconstruct a distribution of cell survival fractions from tumor-volume variation for a heterogeneous group of head and neck cancer patients and compare this distribution to the data from predictive assays. Methods: To characterize the tumor-volume variation during radiation therapy treatment, the authors use a two-level tumor-volume model of cell population that separates the entire tumor cell population into two subpopulations of viable cells and lethally damaged cells. This parameterized radiobiological model is integrated with a least squares objective function and a simulated annealing optimization algorithm to describe time-dependent tumor-volume variation rates in individual patients. Several constraints have been used in the optimization problem because tumor-volume variation during radiotherapy is described by a sum of exponentials; therefore, the problem of accurately fitting a model to measured data is ill-posed. The model was applied to measured tumor-volume variation curves from a clinical study on tumor-volume variation during radiotherapy for 14 head and neck cancer patients in which an integrated CT/linear particle accelerator (LINAC) system was used for tumor-volume measurements. Results: The two-level cell population tumor-volume modeling is capable of describing tumor-volume variation throughout the entire treatment for 11 of the 14 patients. For three patients, the tumor-volume variation was described only during the initial part of treatment, a fact that may be related to the neglected hypoxia in the two-level approximation. The predicted probability density distribution for the survival fractions agrees with the data obtained using in vitro studies with predictive assays. The mean value 0.35 of survival fraction obtained in this study is larger than the value 0.32 from in vitro studies, which could be expected because of greater repair in vivo. The mean half-life obtained in this study for the head

  9. Inactivation of the Radiation-Resistant Spoilage Bacterium Micrococcus radiodurans

    Science.gov (United States)

    Duggan, D. E.; Anderson, A. W.; Elliker, P. R.

    1963-01-01

    A simplified technique permitting the pipetting of raw puréed meats for quantitative bacteriological study is described for use in determining survival of these non-sporing bacteria, which are exceptionally resistant to radiation. Survival curves, using gamma radiation as the sterilizing agent, were determined in raw beef with four strains of Micrococcus radiodurans. Survival curves of the R1 strain in other meat substrates showed that survival was significantly greater in raw beef and raw chicken than in raw fish or in cooked beef. Resistance was lowest in the buffer. Cells grown in broth (an artificial growth medium) and resuspended in beef did not differ in resistance from cells that had been grown and irradiated in beef. Survival rate was statistically independent of the initial cell concentration, even though there appeared to be a correlation between lower death rate and lower initial cell concentrations. The initial viable count of this culture of the domesticated R1 strain in beef was reduced by a factor of about 10-5 by 3.0 megarad, and 4.0 megarad reduced the initial count by a factor of more than 10-9. Data suggest that M. radiodurans R1 is more resistant to radiation than spore-forming spoilage bacteria for which inactivation rates have been published. PMID:14063780

  10. Understanding and Targeting Tumor Microenvironment in Prostate Cancer to Inhibit Tumor Progression and Castration Resistance

    Science.gov (United States)

    2016-10-01

    cancer-secreted chemokine to attract Cxcr2-expressing MDSCs and, correspondingly, pharmacological inhibition of Cxcr2 impeded tumor progression...impact of pharmacological inhibition of Cxcl5 and Cxcr2 on MDSCs using the transwell migration assay 26 . First, anti-Cxcl5 neutralizing antibody...and MRI . (B) Generation of the CPPSML chimera model. (C) Fluorescence microscopy and H&E image of snap frozen prostate tumor from chimera showing that

  11. Radiation resistance of wide-bandgap semiconductor power transistors

    Energy Technology Data Exchange (ETDEWEB)

    Hazdra, Pavel; Popelka, Stanislav [Department of Microelectronics, Czech Technical University in Prague (Czech Republic)

    2017-04-15

    Radiation resistance of state-of-the-art commercial wide-bandgap power transistors, 1700 V 4H-SiC power MOSFETs and 200 V GaN HEMTs, to the total ionization dose was investigated. Transistors were irradiated with 4.5 MeV electrons with doses up to 2000 kGy. Electrical characteristics and introduced defects were characterized by current-voltage (I-V), capacitance-voltage (C-V), and deep level transient spectroscopy (DLTS) measurements. Results show that already low doses of 4.5 MeV electrons (>1 kGy) cause a significant decrease in threshold voltage of SiC MOSFETs due to embedding of the positive charge into the gate oxide. On the other hand, other parameters like the ON-state resistance are nearly unchanged up to the dose of 20 kGy. At 200 kGy, the threshold voltage returns back close to its original value, however, the ON-state resistance increases and transconductance is lowered. This effect is caused by radiation defects introduced into the low-doped drift region which decrease electron concentration and mobility. GaN HEMTs exhibit significantly higher radiation resistance. They keep within the datasheet specification up to doses of 2000 kGy. Absence of dielectric layer beneath the gate and high concentration of carriers in the two dimensional electron gas channel are the reasons of higher radiation resistance of GaN HEMTs. Their degradation then occurs at much higher doses due to electron mobility degradation. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Radiation-induced irreparable heritable changes in cells promoting their tumoral transformation

    International Nuclear Information System (INIS)

    Kuzin, A.M.; Vagabova, M.Eh.; Yurov, S.S.

    1988-01-01

    In experiments with model plant tumors (Kalanchoe-ti plasmid Agrobat. tumefaciens C-58D) it was shown that exposure of the recepient plant to low-level γ-radiation of Gy induced changes in cells that were not repaired over two months promoting tumoral transformations in them. Those changes were shown to persist in the offspring of the exposed somatic cells

  13. Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-01-01

    Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

  14. Development of superior radiation resistant materials and cables. 2

    Energy Technology Data Exchange (ETDEWEB)

    Ikehara, Junichiro; Kanemitsuya, Kazuhiko; Ohara, Hideo; Araki, Syogo; Hamachi, Katsuhiko [Mitsubishi Cable Industries Ltd., Tokyo (Japan)

    1996-01-01

    Many nuclear power plants have been constructed in Japan and electric power generation is now highly dependent on this technology. Therefore, the needs for facilities that will enrich and reprocess nuclear fuel from nuclear power stations will be high. As there are areas with high levels of radiation, the cables which can be used in these environments are needed. We have developed a superior radiation-resistant cable which uses halogen flame-retardant materials. This radiation-resistant cable consists of Ethylene-propylene rubber (EPDM) insulation and Chlorosulfonated polyethylene (CSM) sheath can be safely used in areas with high levels of radiation. We developed this product to aid in disaster prevention. Non-halogen, flame-retardant EPDM is used for the insulation, and low-halogen, flame-retardant CSM and new non-halogen, flame-retardant materials are used for the sheath. These cables have superior flame-retardant properties and generate little smoke on corrosive gas. This products can hence reduce the danger of a secondary disaster in a fire. We expect that these cables will find application in areas with high levels of radiation. (author).

  15. Development of superior radiation resistant materials and cables. 2

    International Nuclear Information System (INIS)

    Ikehara, Junichiro; Kanemitsuya, Kazuhiko; Ohara, Hideo; Araki, Syogo; Hamachi, Katsuhiko

    1996-01-01

    Many nuclear power plants have been constructed in Japan and electric power generation is now highly dependent on this technology. Therefore, the needs for facilities that will enrich and reprocess nuclear fuel from nuclear power stations will be high. As there are areas with high levels of radiation, the cables which can be used in these environments are needed. We have developed a superior radiation-resistant cable which uses halogen flame-retardant materials. This radiation-resistant cable consists of Ethylene-propylene rubber (EPDM) insulation and Chlorosulfonated polyethylene (CSM) sheath can be safely used in areas with high levels of radiation. We developed this product to aid in disaster prevention. Non-halogen, flame-retardant EPDM is used for the insulation, and low-halogen, flame-retardant CSM and new non-halogen, flame-retardant materials are used for the sheath. These cables have superior flame-retardant properties and generate little smoke on corrosive gas. This products can hence reduce the danger of a secondary disaster in a fire. We expect that these cables will find application in areas with high levels of radiation. (author)

  16. New three-dimensional moving field radiation therapy for brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuyama, Fuyuki; Kanno, Tetsuo; Nagata, Yutaka; Koga, Sukehiko [Fujita-Gakuen Health Univ., Toyoake, Aichi (Japan); Jain, V K

    1992-06-01

    A new modified rotation radiation method called 'three-dimensional moving field radiation therapy' is described. The new method uses rotation in many planes while maintaining the same isocenter to achieve a good spatial dose distribution. This delivers a high dose to tumors and spares the surrounding normal structures. This easy method can be carried out using the equipment for conventional rotation radiation therapy. The new method was superior to the one plane rotation radiation therapy using a physical phantom with film, a chemical phantom using the iodine-starch reaction, and a new biological model using tumor cells. Treatment of six brain tumors irradiated with total air doses of 50-60 Gy caused no hair loss or radiation necrosis. (author).

  17. Isolation of radiation resistant fungal strains from highly radioactive field

    International Nuclear Information System (INIS)

    Adam, Y.M.; Aziz, N.H.; Attaby, H.S.H.

    1995-01-01

    This study examined the radiation resistance of fungal flora isolated from the hot-lab around the radiation sources, cobalt 137 and radium 226 . The predominant mould species were: Aspergillus flavus, A. Niger, penicillium chrysogenum, cladosporium herbarum, fusarium oxysporum and alternaria citri. The D 10 values of F. Oxysporum; 2.00 KGy, A. Flavus; 1.40 KGy, P. chrysogenum; 1.15 KGy, and A. citri; 0.95 KGy, are about 1.67, 3.10, 1.92 and 1.36 folds as the D 1 0 values of the same isolates recovered from soil

  18. Human Genetic Marker for Resistance to Radiation and Chemicals

    International Nuclear Information System (INIS)

    Lieberman, Howard B.

    2001-01-01

    TO characterize the human HRDAD9 gene and evaluate its potential as a biomarker to predict susceptibility to the deleterious health effects potentially caused by exposure to radiations or chemicals present at DOE hazardous waste cleanup sites. HRAD9 is a human gene that is highly conserved throughout evolution. Related genes have been isolated from yeasts and mice, underscoring its biological significance. Most of our previous work involved characterization of the yeast gene cognate, wherein it was determined that the corresponding protein plays a significant role in promoting resistance of cells to radiations and chemicals, and in particular, controlling cell growth in response to DNA damage

  19. Radiation resistance of InP-related materials

    International Nuclear Information System (INIS)

    Yamaguchi, Masafumi; Takamoto, Tatsuya; Ikeda, Eiji; Kurita, Hiroshi; Ohmori, Masamichi; Ando, Koshi; Vargas-Aburto, C.

    1995-01-01

    Irradiation effects of 1-MeV electrons on InP-related materials such as InP, InGaP and InGaAsP have been examined in comparison with those of GaAs. Superior radiation-resistance of InP-related materials and their devices compared to GaAs has been found in terms of minority-carrier diffusion length and properties of devices such as solar cells and light-emitting devices. Moreover, minority-carrier injection-enhanced annealing of radiation-induced defects in InP-related materials has also been observed. (author)

  20. Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zwicker, F.; Roeder, F.; Debus, J.; Huber, P.E. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology; Kirsner, A.; Weber, K.J. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Peschke, P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology

    2013-08-15

    Background: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. Materials and methods: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. Results: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. Conclusion: DCA induced tumor-specific radiosensitization in vitro but not in vivo

  1. Effect of small dose of radiation on induction of apoptosis in murine tumors

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Pyo, Hong Ryull; Chung, Eun Ji; Kim, Sung Hee; Suh, Chang Ok

    1999-01-01

    To investigate the presence of adaptive response by low dose radiation in murine tumors in relation to radiation induced apoptosis as well as related mechanism. Syngeneic murine tumors, OCa-1 and HCa-l, were given 0.05 Gy pretreatment followed by therapeutic dose of 25 Gy radiation. Induction of apoptosis was analyzed for each treatment group. Regulating molecules of apoptosis. p53, Bcl-2, Sax, Bel-X, were also analyzed by Western blotting. In 0.05 Gy pretreatment group of OCa-l, 25 Gy-induced apoptosis per 1000 cells was 229, which was estimated at 30% lower level than the expected (p<0.05). In contrast, this reduction in radiation induced apoptosis was not seen in HCa-1. In the expression of apoptosis regulating molecules, p53 increased in both tumors in response to radiation. Bcl-2 and Bax did not show significant change in both tumors however, the expression of Bcl-2 surpassed that of Bax in 0.05 Gy pretreatment group of OCa-1. Bcl-X was not expressed in OCa-1. In HCa-l, ScI-X showed increased expression even with 0.05 Gy. Adaptive response by low dose radiation is shown in one murine tumor, OCa-I, in relation to radiation induced apoptosis. Apoptosis regulating molecules including Bcl-2/Bax and Bcl-X, appear to related. This study shows an evidence that adaptive response is present, but not a generalized phenomenon in vivo

  2. CERTIFICATION OF THE RADIATION RESISTANCE OF COIL INSULATION MATERIAL

    CERN Document Server

    Polinski, J; Bogdan, P

    2013-01-01

    The goal of the WP 7.2.1 sub-task of the EuCARD program has been to determine the Nb$_{3}$Sn based accelerator magnet coil electrical insulation resistance against irradiation, which will occur in future accelerators. The scope of the certification covers determination of mechanical, electrical and thermal properties changes due to irradiation. The report presents a selection of the insulation material candidates for future accelerator magnets as well as the definition of the radiation certification methodology with respect of radiation type, energy, doses and irradiation conditions. The test methods and results of the electrical and mechanical insulation materials properties degradation due to irradiation are presented. Thermal conductivity and Kapitza resistance at temperature range from 1.5 K to 2.0 K (superfluid helium conditions) are given.

  3. High resistance of some oligotrophic bacteria to ionizing radiation

    International Nuclear Information System (INIS)

    Nikitin, D.I.; Tashtemirova, M.A.; Pitryuk, I.A.; Sorokin, V.V.; Oranskaya, M.S.; Nikitin, L.E.

    1994-01-01

    The resistance of seven cultures of eutrophic and oligotrophic bacteria to gamma radiation (at doses up to 360 Gy) was investigated. The bacteria under study were divided into three groups according to their survival ability after irradiation. Methylobacterium organophilum and open-quotes Pedodermatophilus halotoleransclose quotes (LD 50 = 270 Gy) were highly tolerant. By their tolerance, these organisms approached Deinococcus radiodurans. Aquatic ring-shaped (toroidal) bacteria Flectobacillus major and open-quotes Arcocella aquaticaclose quotes (LD 5 = 173 and 210 Gy, respectively) were moderately tolerant. Eutrophic Pseudomonas fluorescens and Escherichia coli (LD 50 = 43 and 38 Gy, respectively) were the most sensitive. X-ray microanalysis showed that in tolerant bacteria the intracellular content of potassium increased and the content of calcium decreased after irradiation. No changes in the element composition of the eutrophic bacterium E. coli were detected. Possible mechanisms of the resistance of oligotrophic bacteria to gamma radiation are discussed

  4. Radiation resistance of amorphous silicon alloy solar cells

    International Nuclear Information System (INIS)

    Hanak, J.J.; Chen, E.; Myatt, A.; Woodyard, J.R.

    1987-01-01

    The radiation resistance of a-Si alloy solar cells when bombarded by high energy particles is reviewed. The results of investigations of high energy proton radiation resistance of a-Si alloy thin film photovoltaic cells are reported. Irradiations were carried out with 200 keV and 1.00 MeV protons with fluences ranging betweeen 1E11 and 1E15 cm-2. Defect generation and passivation mechanisms were studied using the AM1 conversion efficiency and isochronal anneals. It is concluded that the primary defect generation mechanism results from the knock-on of Si and Ge in the intrinsic layer of the cells. The defect passivation proceeds by the complex annealing of Si and Ge defects and not by the simple migration of hydrogen

  5. Tumor treatment by sustained intratumoral release of cisplatin: effects of drug alone and combined with radiation

    International Nuclear Information System (INIS)

    Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

    1997-01-01

    Purpose: The effect of intratumoral delivery of cisplatin to a mouse tumor model (RIF-1) by means of a biodegradable polymer implant with and without radiation was studied. Methods and Materials: The polymer bis(p-carboxyphenoxy)propane-sebacic acid (CPP:SA; 80:20) and its degradation products have been characterized. Polymer rods (8 x 0.5 mm) containing 17% cisplatin by weight were prepared by extrusion, and the in vitro degradation rate measured. The implants were placed into mouse tumors and their effect (with and without radiation) on tumor growth delay studied. The levels of Pt in the mouse kidney, tumor, and blood plasma at selected intervals after implant were also determined. These results were compared with those obtained when cisplatin was delivered systematically. Results: When cisplatin was delivered by the polymer implants, higher levels were present in the tumor for longer time periods (cf. systemic delivery of the drug). For both nonirradiated and irradiated tumors, those treated with the polymer implants had significantly longer tumor growth delays compared to nonimplanted controls and to systematically treated tumors. Conclusions: The results show that intratumoral delivery of cisplatin is more efficient than systemic delivery. Using the biodegradable polymer implant, higher doses of cisplatin can be tolerated by the animal as the drug is localized within the tumor, and the high levels of the drug in the tumor can be maintained for an extended period of time. When radiation is given in conjunction with cisplatin, the tumor response is supraadditive for all modes of cisplatin administration but is potentiated to a greater extent when cisplatin is delivered through the polymer implant. The greatest effect is seen for treatment with cisplatin delivered by polymer implant combined with fractionated radiation

  6. Destruction of radiation-resistant cell populations by hyperthermia

    International Nuclear Information System (INIS)

    Roettinger, E.M.; Gerweck, L.E.

    1979-01-01

    Animal experiments with local hyperthermia have shown that the radiauion dose necessary for the local control of 50% of the tumours examined was essentially reduced by heating to 42,5 0 C. In-vitro experients indicated selective destruction of relatively radiation-resistent cell populations by the combination of hyperthermie and reduced hydrogen ion concentration. Experiments with glioblastoma cells confirmed these results qualitatively, but showed quantitatively considerably lower sensitivity towards hyperthermia. (orig.) 891 MG/orig. 892 RDG [de

  7. Study of decontamination and radiation resistance properties of Indian paints

    International Nuclear Information System (INIS)

    Shah, S.M.; Gopinathan, E.; Bhagwath, A.M.

    1976-01-01

    A brief introduction to the study of contamination and radiation resistance properties of Indian paints used as coating for structural materials in the nuclear industry is given. The general composition of paints such as epoxy, vinyl, alkyd, phenolic, chlesimated rubber, etc. is given. Method of sample preparation, processing and actual evaluation of decontaminability are described. The results have been discussed in terms of decontamination factors. Some recommendations based on the performance of the paints studied are also included. (K.B.)

  8. 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors.

    LENUS (Irish Health Repository)

    Yan, Min

    2009-06-09

    Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib\\'s anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.

  9. Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin.

    Science.gov (United States)

    Chekhun, V F; Lozovska, Y V; Burlaka, A P; Lukyanova, N Y; Todor, I N; Naleskina, L A

    2014-09-01

    To study in vivo the peculiarities of changes of iron metabolism and antioxidant system in dynamics of growth of Guerin carcinoma with different sensitivity to cisplatin. In order to evaluate the content of metallothionein-1 (MT-1) in tumor homogenates and blood serum of rats with cisplatin-sensitive and cisplatin-resistant Guerin carcinoma the immunoenzyme method was used. The evaluation of ceruloplasmin activity, content of "free iron" complexes, superoxide and NO-generating acti-vity of NADPH-oxidase and iNOS activity in neutrophils, blood serum and tumor homogenates was measured by EPR-spectro-scopy. Maximal accumulation of MT-1 in blood serum and tumor, more pronounced in resistant strain, at the border of latent and exponential phase of growth has been shown that is the evidence of protective role of this protein in the respect to the generation of free radical compounds. It has been determined that in animals with cisplatin-resistant strain of Guerin carcinoma, increase of "free iron" complexes is more apparent both on the level of tumor and organism on the background on increase of CP/TR ratio that is the consequence of organism antioxidant protection system disorder. Mentioned changes in metabolism of iron with its accumulation in tumor and further reprogramming of mitochondria metabolism and activity of NADPH-oxidase for non-transformed cells are favorable conditions for the formation of oxidative phenotype of tumor.

  10. Visual outcome after fractionated stereotactic radiation therapy of benign anterior skull base tumors

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Wiencke, Anne Katrine; Munck af Rosenschold, Per

    2014-01-01

    To determine visual outcome including the occurrence of radiation induced optic neuropathy (RION) as well as tumor control after fractionated stereotactic radiation therapy (FSRT) of benign anterior skull base meningiomas or pituitary adenomas. Thirty-nine patients treated with FSRT for anterior...

  11. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors.

    Science.gov (United States)

    Espinoza, I; Peschke, P; Karger, C P

    2015-01-01

    In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the model, tumor shrinkage was

  12. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

    International Nuclear Information System (INIS)

    Espinoza, I.; Peschke, P.; Karger, C. P.

    2015-01-01

    Purpose: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. Methods: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. Results: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the

  13. Will parental exposure to radiation induce tumor in sibling ?

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Takahashi, Tadateru; Toyota, Kazuhiro; Ito, Akihiro

    1991-01-01

    There are reports of possible risk of transmission of genetic trait(s) through the germ cell in acquired cancer from parent to sibling. We have confirmed that paternal exposure to 252 Cf neutron irradiation in mice induced sperm abnormality leading to dominant lethals and liver tumors at F 1 offspring. On the other hand, C3H male mice have been known to have high incidence of spontaneous hepatic tumors and increased hepatic tumor risk in F 1 offsprings maybe caused by the genetic transmission of the hepatoma-inducible-trait amplified by 252 Cf neutron irradiation. The present paper describes that paternal exposure to X-ray or chemicals induces heritable characteristics including anomalies and tumors in some special strains of mice and rats. Some possible mechanisms of transmission of genetic trait(s) are also discussed. (author) 52 refs

  14. Radiation resistant polypropylene blended with mobilizer,. antioxidants and nucleating agent

    Science.gov (United States)

    Shamshad, A.; Basfar, A. A.

    2000-03-01

    Post-irradiation storage of medical disposables prepared from isotactic polypropylene renders them brittle due to degradation. To avoid this, isotactic polypropylene [(is)PP] was blended with a mobilizer, dioctyl pthallate (DOP), three antioxidants (hindered amines and a secondary antioxidant) and benzoic acid to obtain radiation-resistant, thermally-stable and transparent material. Different formulations prepared were subjected to gamma radiation to doses of 25 and 50 kGy. Tests of breakage on bending after ageing in an oven at 70°C up to 12 months have shown that the addition of DOP and the antioxidants imparts improved radiation and thermal stability as compared to (is)PP alone or its blend with DOP. All the formulations irradiated or otherwise demonstrated excellent colour stability even after accelerated ageing at 70°C for prolonged periods.

  15. Resistance of Salmonella enteritidis variety typhimurium to gamma radiation

    International Nuclear Information System (INIS)

    Norberg, A.N.; Maliska, C.

    1988-01-01

    The use of ionizing radiations to kill microrganisms responsible for food deterioration, and toxinfections is an example of peaceful use of nuclear energy. Food toxinfections are, amongus, produced mostly by Salmonella enteritidis var. typhimurium. Due to the pauncity of information on the resistance to gamma radiation of Salmonella enteritidis var. typhimurium this paper has the aim to define the 60-Cobalt gamma radiation lethal dose to these bacteria, in experimentally contaminated milk by samples recovered from our geographycal area. One hundred nineteen samples of milk containing about 150.000 bacteria per ml were irradiated with doses ranging from 100 to 1.100 Gy. Two samples of surving bacteria were again irradiated by doses up to 2.500 Gy. The bacteria not previously irradiated were killed by doses of 1.100 Gy. It was concluded that the 60-Cobalt gamma radiation minimal lethal dose to Salmonella enteritidis var. typhimurium is 1.200 Gy. The surviving strains to smaller doses than 1.200 Gy when re-irradiated prompt the forthcoming of more radio-resistant germs. (author) [pt

  16. Radiation resistant quench protection diodes for the LHC

    International Nuclear Information System (INIS)

    Hagedorn, D.; Coull, L.

    1994-01-01

    The quench protection diodes for the proposed Large Hadron Collider at CERN will be located inside the He-II vessel of the short straight section of one half cell, where they could be exposed to a radiation dose of about 50 kGy and a total neutron fluence of about 10 15 n/cm 2 over 10 years at temperatures of about 2 K. To investigate the influence of irradiation on the electrical characteristics of the diodes, newly developed diodes of thin base region of the diffusion type and of the epitaxial type have been submitted to irradiation tests at liquid nitrogen temperature in a target area of the SPS accelerator at CERN. The degradation of the electrical characteristics of the diodes for a radiation dose up to about 20 kGy and neutron fluence of up to about 5 10 14 n/cm 2 and the effect of carrier injection and thermal annealing after irradiation have been measured. The test results show that only the thin base diodes of the epitaxial type are really radiation resistant. A compromise must be found between required blocking characteristics and radiation resistance. Annealing by carrier injection and occasional warm up to room temperature can extend the service life of irradiated diodes quite substantially

  17. Search for the lowest irradiation dose from literatures on radiation-induced bone tumor

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizawa, Y; Kusama, T; Morimoto, K [Tokyo Univ. (Japan). Faculty of Medicine

    1977-04-01

    A survey of past case reports of bone tumor induced by external radiation was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1922 revealed 262 cases of radiation-induced bone tumor. These patients, except a patient with occupational exposure, had received radiation for treatment. The primary conditions as object of radiation therapy were nonmalignan bone diseases such as tuberclosis, giant cell tumor, fibrous dysplasia and bone cyst, and extra-skeletal diseases such as retinoblastoma, breast cancer and uterus cancer. The ratio of male to female patients with radiation-induced bone tumor was 1:1.3. The age of the patient ranged between 5 and 98 years, with an average of 37.6 years. Skeletal distribution of radiation-induced bone tumor was as follows: 20% the frontal and face bones, 17% the femur, 10% the humerus, 9% the vertebral column, and 44% other. The lowest absorbed dose reported was 800 rads in patients irradiated for the treatment of bone disease, but 1800 rads in patients with extra-skeletal disease. The latent period ranged between 2 and 42 years, with an average of 11.7 years. The histopathological findings were as follows: 60% osteosarcoma, 25% fibrosarcoma, 7% chondrosarcoma, and 8% other.

  18. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

    Science.gov (United States)

    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

    2016-12-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

  19. The theoretical basis and clinical methodology for stereotactic interstitial brain tumor irradiation using iododeoxyuridine as a radiation sensitizer and samarium-145 as a brachytherapy source

    International Nuclear Information System (INIS)

    Goodman, J.H.; Gahbauer, R.A.; Kanellitsas, C.; Clendenon, N.R.; Laster, B.H.; Fairchild, R.G.

    1989-01-01

    High grade astrocytomas have proven resistant to all conventional therapy. A technique to produce radiation enhancement during interstitial brain tumor irradiation by using a radiation sensitizer (IdUrd) and by stimulation of Auger electron cascades through absorption of low energy photons in iodine (Photon activation) is described. Clinical studies using IdUrd, 192 Ir as a brachytherapy source, and external radiation have produced promising results. Substituting samarium-145 for 192 Ir in this protocol is expected to produce enhanced results. 15 refs

  20. Concomitant tumor resistance: the role of tyrosine isomers in the mechanisms of metastases control.

    Science.gov (United States)

    Ruggiero, Raúl A; Bruzzo, Juan; Chiarella, Paula; Bustuoabad, Oscar D; Meiss, Roberto P; Pasqualini, Christiane D

    2012-03-01

    Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In a recently published study, we identified this factor as meta-tyrosine and ortho-tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and ortho-tyrosine inhibited tumor growth. Additionally, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G(0)-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients.

  1. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Danika Lindsay

    2016-08-01

    Full Text Available Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  3. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marres, Henri A.M.; Hoogen, Franciscus J.A. van den [Department of Otorhinolaryngology/Head-Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Rijken, Paul F.J.W.; Lok, Jasper; Bussink, Johan; Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-11-01

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  4. Simulating Space Radiation-Induced Breast Tumor Incidence Using Automata.

    Science.gov (United States)

    Heuskin, A C; Osseiran, A I; Tang, J; Costes, S V

    2016-07-01

    Estimating cancer risk from space radiation has been an ongoing challenge for decades primarily because most of the reported epidemiological data on radiation-induced risks are derived from studies of atomic bomb survivors who were exposed to an acute dose of gamma rays instead of chronic high-LET cosmic radiation. In this study, we introduce a formalism using cellular automata to model the long-term effects of ionizing radiation in human breast for different radiation qualities. We first validated and tuned parameters for an automata-based two-stage clonal expansion model simulating the age dependence of spontaneous breast cancer incidence in an unexposed U.S. We then tested the impact of radiation perturbation in the model by modifying parameters to reflect both targeted and nontargeted radiation effects. Targeted effects (TE) reflect the immediate impact of radiation on a cell's DNA with classic end points being gene mutations and cell death. They are well known and are directly derived from experimental data. In contrast, nontargeted effects (NTE) are persistent and affect both damaged and undamaged cells, are nonlinear with dose and are not well characterized in the literature. In this study, we introduced TE in our model and compared predictions against epidemiologic data of the atomic bomb survivor cohort. TE alone are not sufficient for inducing enough cancer. NTE independent of dose and lasting ∼100 days postirradiation need to be added to accurately predict dose dependence of breast cancer induced by gamma rays. Finally, by integrating experimental relative biological effectiveness (RBE) for TE and keeping NTE (i.e., radiation-induced genomic instability) constant with dose and LET, the model predicts that RBE for breast cancer induced by cosmic radiation would be maximum at 220 keV/μm. This approach lays the groundwork for further investigation into the impact of chronic low-dose exposure, inter-individual variation and more complex space radiation

  5. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

  6. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    International Nuclear Information System (INIS)

    Koritzinsky, Marianne

    2015-01-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers

  7. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    Science.gov (United States)

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  8. Radiation resistivity of pure silica core image guides for industrial fiberscopes

    International Nuclear Information System (INIS)

    Okamoto, Shinichi; Ohnishi, Tokuhiro; Kanazawa, Tamotsu; Tsuji, Yukio; Hayami, Hiroyuki; Ishitani, Tadayoshi; Akutsu, Takeji; Suzuki, Koichi.

    1991-01-01

    Industrial fiberscopes incorporating pure silica core image guides have been extensively used for remote visual inspection in radiation fields including nuclear power plants, owing to their superior radiation resistivity. The authors have been intensively conducting R and D on improving radiation resistivity of pure silica core image guides. This paper reports the results of experiments to compare the effects of core materials on radiation resistivity and to investigate the dependence of radiation resistivity on total dose, does rate, and support pipe material. The results confirmed the superior radiation resistivity of the core material containing fluorine at any irradiation condition and indicated the existence of a critical dose rate at which radiation-induced deterioration was stabilized. No difference in radiation resistivity attributable to support layer material was observed. (author)

  9. Radiation damage resistance in mercuric iodide X-ray detectors

    Energy Technology Data Exchange (ETDEWEB)

    Patt, B E; Dolin, R C; Devore, T M; Markakis, J M [EG and G Energy Measurements, Inc., Goleta, CA (USA); Iwanczyk, J S; Dorri, N [Xsirius, Inc., Marina del Rey, CA (USA); Trombka, J [National Aeronautics and Space Administration, Greenbelt, MD (USA). Goddard Space Flight Center

    1990-12-20

    Mercuric iodide (HgI{sub 2}) radiation detectors show great potential as ambient-temperature solid-state detectors for X-rays, gamma rays and visible light, with parameters that are competitive with existing technologies. In a previous experiment, HgI{sub 2} detectors irradiated with 10 MeV protons/cm{sup 2} exhibited no damage. The 10 MeV protons represent only the low range of the spectrum of energies that are important. An experiment has been conducted at the Saturne accelerator facility at Saclay, France, to determine the susceptibility of these detectors to radiation damage by high-energy (1.5 GeV) protons. The detectors were irradiated to a fluence of 10{sup 8} protons/cm{sup 2}. This fluence is equivalent to the cosmic radiation expected in a one-year period in space. The resolution of the detectors was measured as a function of the integral dose. No degradation in the response of any of the detectors or spectrometers was seen. It is clear from this data that HgI{sub 2} has extremely high radiation-damage resistance, exceeding that of most other semiconductor materials used for radiation detectors. Based on the results shown to date, HgI{sub 2} detectors are suitable for applications in which they may be exposed to high integral dose levels. (orig.).

  10. Radiation therapy of tumors of the oral cavity

    International Nuclear Information System (INIS)

    Parsons, J.T.; Million, R.R.

    1987-01-01

    Both operation and irradiation can cure a high percentage of patients with oral cavity carcinomas. The decision as to which modality is best (or whether to combine both modalities or offer only palliative treatment) in a particular patient is frequently complex and involves consideration of a number of factors before rational therapy can be planned. 1. Tumor location and distribution. 2. Tumor volume. 3. Tumor differentiation. 4. Known patterns of spread. 5. Functional, rehabilitative, and cosmetic aspects and their impact on the patient's life style and occupation. 6. The wishes of the patient and family. 7. Availability of a given treatment in the patient's geographic area. 8. Experience of the patient's physicians. 9. Anticipated cure rates with the various modes of therapy. 10. Expense. 11. The patient's age. 12. Tobacco and alcohol consumption. 13. Presence of other serious medical problems

  11. Clinical results of radiation therapy for thymic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

    1991-12-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

  12. Clinical results of radiation therapy for thymic tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki; Takahashi, Masaji; Fushiki, Masato.

    1991-01-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author)

  13. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors

    International Nuclear Information System (INIS)

    Welzel, Grit; Mai, Sabine K.; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Wenz, Frederik; Fleckenstein, Katharina; Duke University Medical Center Durham, NC

    2008-01-01

    The objective of the current study was to evaluate the acute effects of cranial radiation therapy (CNS-RT) using different radiation doses (0, 1.8, 2, 3, ≤ 20 Gy) on cognitive function with special emphasis on memory. We assessed patients with and without intracranial tumors to distinguish between direct and indirect radiation effects on brain tissue. Eighty-two patients were evaluated with neuropsychological testing before and acutely after radiotherapy (RT). Sixty-four patients received RT to the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with RT to the breast served as controls. Patients with intracranial tumor demonstrated attention (19-38th percentile) and verbal memory scores (34-46th percentile) below the population average at baseline. The average Verbal Memory score was significantly different between patients with intracranial tumor and controls both at baseline (38th vs. 58th percentile) and after irradiation (27th vs. 52th percentile). Patients with preexisting peritumoral edema performed worse than patients without edema and controls. Radiation dose-related deficits were seen for working memory performance in patients with intracranial tumor. Our data indicate no measurable impairment of cognitive functioning acutely after prophylactic cranial irradiation. Patients with intracranial tumor show a deterioration of almost all memory functions with a dose-dependent impairment in working memory. Patients with preexisting peritumoral brain edema show the strongest deterioration. (orig.)

  14. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Welzel, Grit; Mai, Sabine K.; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Wenz, Frederik [University Medical Center Mannheim, Heidelberg Univ. (Germany). Dept. of Radiation Oncology; Fleckenstein, Katharina [University Medical Center Mannheim, Heidelberg Univ. (Germany). Dept. of Radiation Oncology]|[Duke University Medical Center Durham, NC (United States). Dept. of Radiation Oncology

    2008-12-15

    The objective of the current study was to evaluate the acute effects of cranial radiation therapy (CNS-RT) using different radiation doses (0, 1.8, 2, 3, {<=} 20 Gy) on cognitive function with special emphasis on memory. We assessed patients with and without intracranial tumors to distinguish between direct and indirect radiation effects on brain tissue. Eighty-two patients were evaluated with neuropsychological testing before and acutely after radiotherapy (RT). Sixty-four patients received RT to the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with RT to the breast served as controls. Patients with intracranial tumor demonstrated attention (19-38th percentile) and verbal memory scores (34-46th percentile) below the population average at baseline. The average Verbal Memory score was significantly different between patients with intracranial tumor and controls both at baseline (38th vs. 58th percentile) and after irradiation (27th vs. 52th percentile). Patients with preexisting peritumoral edema performed worse than patients without edema and controls. Radiation dose-related deficits were seen for working memory performance in patients with intracranial tumor. Our data indicate no measurable impairment of cognitive functioning acutely after prophylactic cranial irradiation. Patients with intracranial tumor show a deterioration of almost all memory functions with a dose-dependent impairment in working memory. Patients with preexisting peritumoral brain edema show the strongest deterioration. (orig.)

  15. Principles of radiation therapy in the treatment of vaginal tumors

    International Nuclear Information System (INIS)

    Nori, D.

    1987-01-01

    Vaginal tumors constitute about 1-1.5% of all gynecological cancers. However, there is a great variety of histological types of vaginal cancers that affect females of all ages. Characteristically embryonal rhabdomyosarcoma (sarcoma botryoides) occurs in infants; diethylstilbestrol-induced clear cell adenocarcinomas in teenage girls; and squamous cell carcinoma, melanoma, sarcoma, and adenocarcinoma in adult women. Because of the rarity of these tumors, few clinicians gain wide experience in their treatment. Treatment of these three clinical entities in three different age groups is presented in this chapter

  16. Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

    International Nuclear Information System (INIS)

    Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

    1985-01-01

    The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

  17. [Vitamin-resistant rickets cured by removal of a bone tumor. Review of the literature].

    Science.gov (United States)

    François, S; Lefort, G; Poli-Merol, M L; Gaillard, D; Roussel, B; Sulmont, V; Daoud, S

    1997-01-01

    with normal vitamin D metabolism. The pathogenesis is not clearly defined. Regardless to the mechanism of osteomalacia, complete removal of the tumor will cure the patient. A diligent search for tumors should be done in patients with vitamin D resistant rickets.

  18. Phenotype switching : tumor cell plasticity as a resistance mechanism and target for therapy

    NARCIS (Netherlands)

    Kemper, K.; de Goeje, P.L.; Peeper, D.S.; van Amerongen, R.

    2014-01-01

    Mutations in BRAF are present in the majority of patients with melanoma, rendering these tumors sensitive to targeted therapy with BRAF and MEK inhibitors. Unfortunately, resistance almost invariably develops. Recently, a phenomenon called "phenotype switching" has been identified as an escape

  19. Celecoxib decreases growth and angiogenesis and promotes apoptosis in a tumor cell line resistant to chemotherapy

    Directory of Open Access Journals (Sweden)

    Carlos Rosas

    2014-01-01

    Full Text Available BACKGROUND: During the last few years it has been shown in several laboratories that Celecoxib (Cx, a non-steroidal anti-inflammatory agent (NSAID normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described. Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR. RESULTS: Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM, inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF production and cell proliferation in the tumor. CONCLUSION: The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.

  20. Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

    Directory of Open Access Journals (Sweden)

    Rogerio M. Castilho

    2017-07-01

    Full Text Available Head and neck squamous carcinoma (HNSCC is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy. Epigenetic alterations occur in an unsystematic manner or as part of the aberrant transcriptional machinery, which promotes selective advantage to the tumor cells. Epigenetic modifications also contribute to cellular plasticity during tumor progression and to the formation of cancer stem cells (CSCs, a small subset of tumor cells with self-renewal ability. CSCs are involved in the development of intrinsic or acquired therapy resistance, and tumor recurrences or relapse. Therefore, the understanding and characterization of epigenetic modifications associated with head and neck carcinogenesis, and the prospective identification of epigenetic markers associated with CSCs, hold the promise for novel therapeutic strategies to fight tumors. In this review, we focus on the current knowledge on epigenetic modifications observed in HNSCC and emerging Epi-drugs capable of sensitizing HNSCC to therapy.

  1. Subacute brain atrophy induced by radiation therapy to the malignant brain tumors

    International Nuclear Information System (INIS)

    Asai, Akio; Matsutani, Masao; Takakura, Kintomo.

    1987-01-01

    In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56 %) and dementia in 23 out of 47 patients (49 %). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2 - 3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy. (author)

  2. Characterization of radiation-resistant vegetative bacteria in beef

    International Nuclear Information System (INIS)

    Welch, A.B.; Maxcy, R.B.

    1975-01-01

    Ground beef contains numerous microorganisms of various types. The commonly recognized bacteria are associated with current problems of spoilage. Irradiation, however, contributes a new factor through selective destruction of the microflora. The residual microorganisms surviving a nonsterilizing dose are predominantly gram-negative coccobacilli. Various classifications have been given, e.g., Moraxella, Acinetobacter, Achromobacter, etc. For a more detailed study of these radiation-resistant bacteria occurring in ground beef, an enrichment procedure was used for isolation. By means of morphological and biochemical tests, most of the isolates were found to be Moraxella, based on current classifications. The range of growth temperatures was from 2 to 50 C. These bacteria were relatively heat sensitive, e.g., D 10 of 5.4 min at 70 0 C or less. The radiation resistance ranged from D 10 values of 273 to 2,039 krad. Thus, some were more resistant than any presently recognized spores. A reference culture of Moraxella osloensis was irradiated under conditions comparable to the enrichment procedure used with the ground beef. The only apparent changes were in morphology and penicillin sensitivity. However, after a few subcultures these bacteria reverted to the characteristics of the parent strain. Thus, it is apparent that these isolates are a part of the normal flora of ground beef and not aberrant forms arising from the irradiation procedure. The significance, if any, of these bacteria is not presently recognized. (auth)

  3. Optical emission behavior and radiation resistance of epoxy resins

    International Nuclear Information System (INIS)

    Kawanishi, Shunichi; Udagawa, Akira; Hagiwara, Miyuki

    1987-11-01

    To make clear a mechanism of radiation resistance of epoxy resin systems, a role of energy trapping site induced in bisphenol A type epoxy resins cured with 4 kinds of aromatic amines (Φ N ) was studied in comparison with the case of aliphatic amine curing system through a measurement of optical emission. In the system of the epoxy resin cured with DETA, the optical emission from an excited state of bisphenol A unit of epoxy resin and a charge transfer complex was observed. On the other hand, the optical emission from Φ N was observed in the aromatic amine curing system. Their excitation spectrum consists of peaks of absorption spectrum of BA and those of Φ N , showing that the excited state of Φ N is formed through the excitation of both BA and Φ N . Therefore, the excited energy of BA transfers to the excited state of Φ N . Emission intensity of Φ N band was 20 ∼ 100 times as large as that of BA. These results indicate that the radiation energy is effectively released as an optical emission from excited state of Φ N in the epoxy resin when cured with aromatic amine. It can be concluded from the above results that aromatic amine hardeners contribute to enhancement of the radiation resistance of epoxy resin by acting as an energy transfer agent. (author)

  4. Radiation resistance characteristics of optical communication system for single mode

    International Nuclear Information System (INIS)

    Ohe, Masamoto; Chigusa, Yoshiki; Kyodo, Tomohisa; Tanaka, Gohtaro; Watanabe, Hajime; Okamoto, Shin-ichi; Yamamoto, Takao.

    1988-01-01

    Optical communication has been utilized also for nuclear power stations and fuel reporocessing plants. As the sufficient safety countermeasures are required there, the amount of information becomes enormous, therefore, optical communication, by which the required space is expected to be reduced, becomes more important. Also in the application to submarine cables, attention must be paid to the radiation resistance as there are the effects of potassium contained in large amount in seawater and uranium deposits in sea bottom. Therefore, the reliability of the components of optical communication systems against radiation becomes a problem. In this study, single mode optical fibers and transmission and receipt modules were selected, and high dose rate irradiation supposing the case of using in a cell and low dose rate, long time irradiation supposing the case of submarine cables were carried out to evaluate the radiation resistance characteristics. The fibers tested were SiO 2 core/F-SiO 2 clad type and GeO 2 -SiO 2 core/SiO 2 clad type. The characteristics of increasing loss in irradiation and restoration after irradiation of the former type were superior to those of the latter type. The output of a receipt module was normal during irradiation, and the output power of a transmission module decreases, but other problems did not arise. (K.I.)

  5. Radiation resistance of insulating materials for electric wires

    International Nuclear Information System (INIS)

    Kanemitsuya, Kazuhiko; Okuda, Tomoaki; Tachibana, Tadao; Yagi, Toshiaki; Seguchi, Tadao.

    1990-01-01

    In no halogen incombustible materials, smoke and poisonous gas generation at the time of burning is small, and corrosive gas rarely arises. Since no halogen electric wires and cables which use these material maintain safety for people and equipment in the case of fires, those are used for ships, tunnels, subways and so on. Also in nuclear power stations, the demand for no halogen cables becomes high although the condition of adoption is difficult. In this study, for the purpose of developing the no halogen cables for nuclear power stations, the basic data on the radiation resistance of no halogen incombustible materials were collected, and by using chemical analysis method, the radiation deterioration behavior was examined. The samples were those with base polymers of VLDPE, ULDPE, EEA, EMA and EVA. Gamma ray irradiation, tensile test, chemi-luminescence measurement, and the determination of gel fraction and swelling rate were carried out. The results are reported, In no halogen materials, when ethylene system copolymer is used as the base polymer instead of PE, the composition with good radiation resistance can be obtained, and by combining amine oxidation inhibitor, it is further improved. (K.I.)

  6. The long-term side effects of radiation therapy for benign brain tumors in adults

    International Nuclear Information System (INIS)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R.

    1990-01-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs

  7. The long-term side effects of radiation therapy for benign brain tumors in adults

    Energy Technology Data Exchange (ETDEWEB)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. (Univ. of Mississippi Medical Center, Jackson (USA))

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  8. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Directory of Open Access Journals (Sweden)

    Patricia Fernandez

    2014-10-01

    Full Text Available Summary: Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis. : The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique tool for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Using a genome-wide RNAi screen, Fernandez et al. now identify the bromodomain protein BRD4 as a mediator of the oncogenic resistance of HGPS cells. This tumor-protective function of BRD4 involves inhibition of oncogenic dedifferentiation and is also active in non-HGPS cells in a tissue-specific manner.

  9. Increase of tumor oxygen tension and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride

    International Nuclear Information System (INIS)

    Amano, Morikazu; Monzen, Hajime; Suzuki, Takatoshi; Hasegawa, Takeo

    2004-01-01

    The effects of pentoxifylline (PTX), vinpocetine (VPT) and ticlopidine hydrochloride (TCD), each drug commonly used for vascular disorders in humans, on the pO 2 in SCC-7 (squamous cell carcinoma) tumors of C3H/HeJ mice on the radioresponse of SCC-7 tumors were investigated. When the SCC-7 implanted in the leg of C3H/HeJ mice grew about 100 mm 3 , the effects of PTX, VPT and TCD on the increase oxygen tension in the tumor was determined with polarography. The mice were injected intraperitoneally (ip) with 5 ml/kg PTX, 5 ml/kg VPT, or 10 ml/kg TCD, the tumor pO 2 increased slowly, peaked about 20-50 min postinjection, and returned to its original level in 60-80 min. When the C3H/HeJ mice bearing SCC-7 tumors in the legs were injected ip with 5 ml/kg PTX, 5 ml/kg VPT or 10 ml/kg TCD and tumors were X-irradiated 30 min later, the radiation induced growth delay of the tumor was greater than that caused by X-irradiation alone. The results in the present study, PTX, VPT and TCD increase the tumor pO 2 in rodent tumors strongly suggest that each drug may be useful for increasing the radiosensitivity of human tumor. (author)

  10. Effect of host age on the transplantation, growth, and radiation response of EMT6 tumors

    International Nuclear Information System (INIS)

    Rockwell, S.

    1981-01-01

    The characteristics of EMT6 tumors in young adult and aged BALB/c KaRw mice were compared. The number of tumor cells implanted s.c. necessary to cause tumors in 50% of the injection sites was lower in aging than in young adult mice. The latent period of intradermally implanted tumors was shorter in aging mice than in young animals; however, the growth curves of established tumors were similar. The number and appearance of lung colonies after injection of cells i.v. and the pattern of spontaneous metastases were similar in young and aged animals. Radiation dose-response curves for the cells of tumors in young and aging mice were different and suggested that the proportion of hypoxic cells was higher in tumors on aging animals. These findings suggest that both immunological and nonimmunological tumor-host interactions differ in young and aged animals and that such factors may influence the natural history of the tumor and the response of the tumor to treatment

  11. Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

    International Nuclear Information System (INIS)

    Welch, D.R.

    1984-01-01

    The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

  12. Place of radiation therapy for the treatment of gynecologic and urologic tumors in 1994

    International Nuclear Information System (INIS)

    Maulard-Durdux, C.; Housset, M.

    1995-01-01

    External-beam radiation therapy and brachytherapy are currently used both as curative and as palliative therapy in patients with gynecologic and urologic tumors. Ionizing radiation plays a key role in the locoregional control of uterine and prostatic tumors, in particular in combination with surgery. External-beam radiation therapy in combination with concomitant radiosensitizing chemotherapy may allow conservation of the bladder in patients with infiltrating vesical tumors classically treated by cystectomy. It has beneficial effects on some of the most incapacitating complications of these cancers: its hemostatic effect is valuable in patients with vaginal bleeding or hematuria and it relieves the pain due to bone metastases, which are particularly common in prostatic cancer. Furthermore, use of high energy accelerators, development of better imaging techniques, and advances in dosimetry have substantially reduced the rate of delayed radiation-induced complications. Thus, external-beam radiation therapy and brachytherapy are important tools for the treatment of gynecologic and urologic tumors. A discussion is provided of the role of radiation therapy in the four most common types of gynecologic and urologic cancer: cancers of the prostate, bladder, uterine cervix, and uterine corpus. (authors). 52 refs., 2 tabs

  13. Radiation-induced ocular motor cranial nerve palsies in patients with pituitary tumor.

    Science.gov (United States)

    Vaphiades, Michael S; Spencer, Sharon A; Riley, Kristen; Francis, Courtney; Deitz, Luke; Kline, Lanning B

    2011-09-01

    Radiation therapy is often used in the treatment of pituitary tumor. Diplopia due to radiation damage to the ocular motor cranial nerves has been infrequently reported as a complication in this clinical setting. Retrospective case series of 6 patients (3 men and 3 women) with pituitary adenoma, all of whom developed diplopia following transsphenoidal resection of pituitary adenoma with subsequent radiation therapy. None had evidence of tumor involvement of the cavernous sinus. Five patients developed sixth nerve palsies, 3 unilateral and 2 bilateral, and in 1 patient, a sixth nerve palsy was preceded by a fourth cranial nerve palsy. One patient developed third nerve palsy. Five of the 6 patients had a growth hormone-secreting pituitary tumor with acromegaly. Following transsphenoidal surgery in all 6 patients (2 had 2 surgeries), 4 had 2 radiation treatments consisting of either radiosurgery (2 patients) or external beam radiation followed by radiosurgery (2 patients). Patients with pituitary tumors treated multiple times with various forms of radiation therapy are at risk to sustain ocular motor cranial nerve injury. The prevalence of acromegalic patients in this study reflects an aggressive attempt to salvage patients with recalcitrant growth hormone elevation and may place the patient at a greater risk for ocular motor cranial nerve damage.

  14. Radiation therapy for glomus tumors of the temporal bone

    International Nuclear Information System (INIS)

    Dall'Igna, Celso; Antunes, Marcelo B.

    2005-01-01

    The treatment of glomic tumors has been controversial since its first description. It can be done with surgery, radiotherapy or just expectation. Aim: the objective of this paper was to evaluate the effectiveness and complications of radiotherapy.Study Design: clinical with transversal cohort. Material and method: it was made a retrospective review in the charts of the patients with glomus jugular tumors treated with radiotherapy. Disease control was determined by (1) no progression of symptoms or cranial nerve dysfunction or (2) no progression of the lesion in radiological follow-up. It was also evaluated the follow-up period and the sequelae of the treatment. Results: twelve patients were included, 8 of then women. The follow-up period was from 3 to 35 years, with a media of 11,6 years. The main symptoms were: hearing loss, pulsate tinnitus, dizziness and vertigo. The signs were pulsate retrotympanic mass, facial palsy and cofosis. The tumors were staged using Fischs classification. The radiotherapy was performed with linear accelerator with dose ranging from 4500-5500 in 4-6 weeks. In the follow-up period were possible to identify sequelaes like dermatitis, meatal stenosis, cofosis and facial palsy. Discussion: the signs and symptoms were the same found in the medical literature. The type and dosages of the radiotherapy were also the same of others reports. All patients had improvement of the symptoms and only one was not considered as having disease controlled. Complications were, in general, minor complications, with exception of the cofosis and facial palsy. Conclusion: radiotherapy is a viable alternative to treatment of these tumors because their good response and low level of complications. It should be considered specially in advanced tumors where a surgical procedure could bring a high level of morbidity. (author)

  15. Downregulation of taurine uptake in multidrug resistant Ehrlich ascites tumor cells

    DEFF Research Database (Denmark)

    Poulsen, K A; Litman, Thomas; Eriksen, J

    2002-01-01

    In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal...... rate constant for the initial taurine uptake was reduced by 45% (high-affinity system) and 49% (low affinity system) in the resistant subline whereas the affinity of the transporters to taurine was unchanged. By immunoblotting we identified 3 TauT protein bands in the 50-70 kDa region. A visible...... reduction in the intensity of the band with the lowest molecular weight was observed in resistant cells. Quantitative RT-PCR indicated a significant reduction in the amount of taurine transporter mRNA in the resistant cells. Drug resistance in DNR Ehrlich cells is associated with overexpression of the mdr1...

  16. Clinical and histological study of radiation-resistant cancer of the larynx

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, K [Osaka Univ. (Japan). Faculty of Medicine

    1979-02-01

    In its early stage, cancer of the larynx is treated mainly by irradiation. A clinical and histological study of the radiation-resistant cancer of the larynx is reported. From 1958 to 1976, 1190 patients with squamous cell carcinoma of the larynx were treated at the Department of Otolaryngology, Osaka University Hospital. Among them, 597 patients (50.2%) were treated by radiation therapy. In 180 patients who had developed local recurrence after initial irradiation, partial or total laryngectomies were performed and 5-year crude survival rates were 71.3%. Gross examination of the specimens and histological studies were performed on these cases, as well as microangiography. The majority of recurrent glottic cancers were located at the anterior commissure and had some subglottic extention. In the supraglottic cancers, marked invasion to the pre-epiglottic space, perichondritis, and edema of the arytenoids were observed. These findings suggested that the unsuccessful radiation therapy was due to the diagnostic failure of the tumor extention. Fixation of the affected vocal cords and ulcer formation were also observed. Histologically, cancer cells invaded deeply the surrounding tissues as scattered cancer nests with marked hypoxic stromal reaction. This study suggests that radiation therapy should be the initial but non-repetitive treatment of choice for earlystage laryngeal cancers.

  17. Development of new radiation resistant, fire-retardant cables

    International Nuclear Information System (INIS)

    Hagiwara, Ko; Morita, Yosuke; Udagawa, Takashi; Fujimura, Shun-ichi; Oda, Eisuke.

    1982-01-01

    For the cables for nuclear facilities, radiation resistance and fire-retardation are severely required. The authors took note of the fact that even in the existing cables for nuclear power plants, their mechanical properties are greatly degraded by the exposure to large dose (for example, 200 Mrad in PWR testing conditions), and attempted the improvement. They employed a new additive, bromated acenaphthylene condensate (con-BACN), which effectively gives radiation resistance and also is a good flame retarder, to be compounded to an insulation material, and examined the characteristics. In this paper, the features of con-BACN and the investigation of fire-retardant EPDM composition are described. As an initial composition, a small amount of zinc white, sulphur, stearic acid, noclac 224 (Ouchi-Shinko Chemicals, Co.), and antimony trioxide, 100 parts of tale and 45 parts of con-BACN were added to 100 parts of EPDM (propylene content 34 %, Japan Synthetic Rubber Co.). As the antiaging agent, it was decided to use phenol series No. 3 as a result of test. The fire-retardant EP rubber-composed cable was produced for trial, its insulation being fabricated, using a Furukawa's pressurized salt bath continuous vulcanizer. The tests of γ-irradiation, simulated LOCA and combustion were carried out, and the test results are reported. It was indicated that the cable resisted against high dose several times as much as 200 Mrad, and was suitable for the applications, in which the mechanical properties such as bending are required to be maintained after radiation exposure. It was also found that con-BACN was safe, and its properties of decomposition, concentration and acute toxicity were all very low. (Wakatsuki, Y.)

  18. Analysis of QTL for resistance to radiation in rice

    International Nuclear Information System (INIS)

    Zhao Fei; Zhou Yifeng; Ren Sanjuan; Fu Junjie; Zhuang Jieyun; Shen Shengquan

    2010-01-01

    The recombinant inbred line (RIL) population derived from rice variates Zhenshan 97B/Miyang 46 and their genetic linkage maps were used to map QTLs controlling resistant to radiation. The trait was measured by the relative germination rate (RGR) and the relative surviving plant rate (RSPR) after the seeds of each line treated with γ-rays irradiation at two 350 and 550 Gy. The results indicated that the lines treated with γ-irradiation showed different performance in resistance to radiation. Under the treatment of 350 Gy, two QTLs with additive effects were detected, of which qRR (g) 81 was only significant for relative germination rate, and it had the positive additive effects from the male parent, explaining 6.53% of the total phenotypic variations. The qRR(s)2-2 was another significant one for relative surviving plant rate, whose positive effects came from the female parent,explaining 12.81% of the total phenotypic variations. Similarly, 4 QTLs were detected under irradiation dose of 550 Gy, and qRR(g)1-2 and qRR(g)8-2 were detected for relative germination rate, with positive effects coming from female and male parent,respectively,explaining 14.38% of the total variations. qRR(s)5-2 and qRR(s)10 were detected for relative surviving plant rate, with positive effects coming from the male parent, explaining 19.65% of total variations. Under different irradiation dose, 9 pairs of double QTL epistasis effects could be identified in this population. The results suggested that the expression of QTL with resistance to radiation might have relation with the irradiation dose. (authors)

  19. Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization

    Directory of Open Access Journals (Sweden)

    Patrick Maier

    2016-01-01

    Full Text Available During the last few decades, improvements in the planning and application of radiotherapy in combination with surgery and chemotherapy resulted in increased survival rates of tumor patients. However, the success of radiotherapy is impaired by two reasons: firstly, the radioresistance of tumor cells and, secondly, the radiation-induced damage of normal tissue cells located in the field of ionizing radiation. These limitations demand the development of drugs for either radiosensitization of tumor cells or radioprotection of normal tissue cells. In order to identify potential targets, a detailed understanding of the cellular pathways involved in radiation response is an absolute requirement. This review describes the most important pathways of radioresponse and several key target proteins for radiosensitization.

  20. Visual outcome, endocrine function and tumor control after fractionated stereotactic radiation therapy of craniopharyngiomas in adults

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Munck Af Rosenschöld, Per; Feldt-Rasmussen, Ulla

    2017-01-01

    BACKGROUND: The purpose of this study was to examine visual outcome, endocrine function and tumor control in a prospective cohort of craniopharyngioma patients, treated with fractionated stereotactic radiation therapy (FSRT). MATERIAL AND METHODS: Sixteen adult patients with craniopharyngiomas were...... eligible for analysis. They were treated with linear accelerator-based FSRT during 1999-2015. In all cases, diagnosis was confirmed by histological analysis. The prescription dose to the tumor was 54 Gy (median, range 48-54) in 1.8 or 2.0 Gy per fraction, and the maximum radiation dose to the optic nerves.......7-13.1) for visual outcome, endocrine function, and tumor control, respectively. RESULTS: Visual acuity impairment was present in 10 patients (62.5%) and visual field defects were present in 12 patients (75%) before FSRT. One patient developed radiation-induced optic neuropathy at seven years after FSRT. Thirteen...

  1. Radiation Resistance and Gain of Homogeneous Ring Quasi-Array

    DEFF Research Database (Denmark)

    Knudsen, H. L.

    1954-01-01

    In a previous paper homogeneous ring quasi-arrays of tangential or radial dipoles were introduced, i.e. systems of dipoles arranged equidistantly along a circle, the dipoles being oriented in tangential or radial directions and carrying currents with the same amplitude, but with a phase that incr......In a previous paper homogeneous ring quasi-arrays of tangential or radial dipoles were introduced, i.e. systems of dipoles arranged equidistantly along a circle, the dipoles being oriented in tangential or radial directions and carrying currents with the same amplitude, but with a phase...... that increases uniformly along the circle. Such quasi-arrays are azimuthally omnidirectional, and the radiated field will be mainly horizontally polarized and concentrated around the plane of the circle. In this paper expressions are obtained for the radiation resistance and the gain of homogeneous ring quasi...

  2. Radiation resistance of electro-optic polymer-based modulators

    International Nuclear Information System (INIS)

    Taylor, Edward W.; Nichter, James E.; Nash, Fazio D.; Haas, Franz; Szep, Attila A.; Michalak, Richard J.; Flusche, Brian M.; Cook, Paul R.; McEwen, Tom A.; McKeon, Brian F.; Payson, Paul M.; Brost, George A.; Pirich, Andrew R.; Castaneda, Carlos; Tsap, Boris; Fetterman, Harold R.

    2005-01-01

    Mach-Zehnder interferometric electro-optic polymer modulators composed of highly nonlinear phenyltetraene bridge-type chromophores within an amorphous polycarbonate host matrix were investigated for their resistance to gamma rays and 25.6 MeV protons. No device failures were observed and the majority of irradiated modulators exhibited decreases in half-wave voltage and optical insertion losses compared to nonirradiated control samples undergoing aging processes. Irradiated device responses were attributed to scission, cross-linking, and free volume processes. The data suggests that strongly poled devices are less likely to de-pole under the influence of ionizing radiation

  3. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

    Science.gov (United States)

    Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

    2009-05-01

    Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

  4. Post-mastectomy radiation in large node-negative breast tumors: Does size really matter?

    International Nuclear Information System (INIS)

    Floyd, Scott R.; Taghian, Alphonse G.

    2009-01-01

    Treatment decisions regarding local control can be particularly challenging for T3N0 breast tumors because of difficulty in estimating rates of local failure after mastectomy. Reports in the literature detailing the rates of local failure vary widely, likely owing to the uncommon incidence of this clinical situation. The literature regarding this clinical scenario is reviewed, including recent reports that specifically address the issue of local failure rates after mastectomy in the absence of radiation for large node-negative breast tumors.

  5. Radiation resistance of solar cells for space application, 1

    International Nuclear Information System (INIS)

    Mitsui, Hiroshi; Tanaka, Ryuichi; Sunaga, Hiromi

    1989-07-01

    A 50-μm thick ultrathin silicon solar cell and a 280-μm thick high performance AlGaAs/GaAs solar cell with high radiation resistance have been recently developed by National Space Development Agency of Japan (NASDA). In order to study the radiation resistance of these cells, a joint research was carried out between Japan Atomic Energy Research Institute (JAERI) and NASDA from 1984 through 1987. In this research, the irradiation method of electron beams, the effects of the irradiation conditions on the deterioration of solar cells by electron beams, and the annealing effects of the radiation damage in solar cells were investigated. This paper is the first one of a series of reports of the joint research. In this paper, the space radiation environment which artificial satellites will encounter, the solar cells used, and the experimental methods are described. In addition to these, the results of the study on the irradiation procedure of electron beams are reported. In the study of the irradiation method of electron beams, three methods, that is, the fixed irradiation method, the moving irradiation method, and the spot irradiation method were examined. In the fixed irradiation method and moving one, stationary solar cells and solar cells moving by conveyer were irradiated by scanning electron beams, respectively. On the other hand, in the spot irradiation method, stationary solar cells were irradiated by non-scanning steady electron beams. It was concluded that the fixed irradiation method was the most proper method. In addition to this, in this study, some pieces of information were obtained with respect to the changes in the electrical characteristics of solar cells caused by the irradiation of electron beams. (author) 52 refs

  6. 3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

    Science.gov (United States)

    Sethi, Pallavi; Jyoti, Amar; Swindell, Elden P; Chan, Ryan; Langner, Ulrich W; Feddock, Jonathan M; Nagarajan, Radhakrishnan; O'Halloran, Thomas V; Upreti, Meenakshi

    2015-11-01

    An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    International Nuclear Information System (INIS)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho

    2005-01-01

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II ∼ IV or WHO tumor type B2 ∼ C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; ρ = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; ρ = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; ρ = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; ρ = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated

  8. Effect of hyperthermia, radiation and adriamycin combinations on tumor vascular function

    International Nuclear Information System (INIS)

    Eddy, H.A.; Chmielewski, G.

    1982-01-01

    Pathophysiologic studies of tumor vascular responses to hyperthermia, radiation or adriamycin given alone or in specific combinations have been made in the cervical carcinoma grown in the transparent cheek pouch chamber of the Syrian hamster. A specially designed chamber containing a compartment for flowing water enabled controlled heating of the tumor and pouch to within 0.2 0 C; the desired temperatures were achieved within one minute. Heating at 42 0 C for 30 minutes was followed, at 1, 5 or 24 hours, by a second heating for 30 minutes at 42 0 C. In addition, the same period of heating was preceded or followed, at 1, 5 or 24 hour intervals, by a single exposure to 2000R or a single intravenous injectionof adriamycin given at a rate of 0.45 mg/100 gm body weight. Of the three modalities, heat appeared to have the greatest acute effect on the tumor vascular system. A single dose of heat produced a rapid but transient constriction followed by a prominent dilation of vessels. Two heating periods given at a 1 hour interval caused persistent stasis in the tumor which progressed to coagulation necrosis. Although heating prior to irradiation or adriamycin, in general, increased the vascular responses to these agents, this sequence gave no tumor control. Radiation or adriamycin given prior to heating had relatively little effect on the vascular response to heating and produced no tumor control except when heat was applied shortly after irradiation. These studies indicate that changes in the microvasculature and perfusion in tumors, in response to hyperthermia alone or combined in specific sequences with radiation, can alter the internal environment of the tumor to produce a greater degree of tumor control than can be attributed to direct cell killing by these agents

  9. Efficacy of continuous treatment with radiation in a rat brain-tumor model

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Kaufman, K.

    1981-01-01

    Rats bearing intracerebral 9L/Ro tumors were treated with 10 daily fractions of cesium-137 gamma-rays, BCNU, or combinations of these to agents beginning on either Day 10 or Day 12 after implantation. The treatments were administered either 5 days/week for 2 weeks, with the weekend off, or 10 consecutive days. The median day of death for untreated tumor-bearing rats was Day 15, so Day 12 tumors can be considered late tumors and Day 10 tumors can be considered moderately early. Although all single- and multiple-agent treatments significantly (p less than 0.05) increased the lifespan of tumor-bearing rats over that of the untreated controls, and all multiple-agent schedules significantly (p less than 0.05) increased the lifespan over that of the single-agent therapies, none of the 10 consecutive day schedules increased the lifespan of tumor-bearing rats significantly (p less than 0.2) over that obtained with the 5-day/week schedules. Thus, the evidence from this tumor model suggests that no significant improvement in lifespan would be expected if malignant brain tumors were treated with radiation 7 days a week, either alone or in combination with chemotherapeutic agents such as BCNU

  10. Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells.

    Science.gov (United States)

    Abdelfatah, Sara A A; Efferth, Thomas

    2015-02-15

    The antihypertensive reserpine is an indole alkaloid from Rauwolfia serpentina and exerts also profound activity against cancer cells in vitro and in vivo. The present investigation was undertaken to investigate possible modes of action to explain its activity toward drug-resistant tumor cells. Sensitive and drug-resistant tumor cell lines overexpressing P-glycoprotein (ABCB1/MDR1), breast cancer resistance protein (ABCG2/BCRP), mutation-activated epidermal growth factor receptor (EGFR), wild-type and p53-knockout cells as well as the NCI panel of cell lines from different tumor origin were analyzed. Reserpine's cytotoxicity was investigated by resazurin and sulforhodamine assays, flow cytometry, and COMPARE and hierarchical cluster analyses of transcriptome-wide microarray-based RNA expressions. P-glycoprotein- or BCRP overexpressing tumor cells did not reveal cross-resistance to reserpine. EGFR-overexpressing cells were collateral sensitive and p53- Knockout cells cross-resistant to this drug compared to their wild-type parental cell lines. Reserpine increased the uptake of doxorubicin in P-glycoprotein-overexpressing cells, indicating that reserpine inhibited the efflux function of P-glycoprotein. Using molecular docking, we found that reserpine bound with even higher binding energy to P-glycoprotein and EGFR than the control drugs verapamil (P-glycoprotein inhibitor) and erlotinib (EGFR inhibitor). COMPARE and cluster analyses of microarray data showed that the mRNA expression of a panel of genes predicted the sensitivity or resistance of the NCI tumor cell line panel with statistical significance. The genes belonged to diverse pathways and biological functions, e.g. cell survival and apoptosis, EGFR activation, regulation of angiogenesis, cell mobility, cell adhesion, immunological functions, mTOR signaling, and Wnt signaling. The lack of cross-resistance to most resistance mechanisms and the collateral sensitivity in EGFR-transfectants compared to wild

  11. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

    Science.gov (United States)

    Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2009-02-01

    Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

  12. Macrophage and tumor cell responses to repetitive pulsed X-ray radiation

    Science.gov (United States)

    Buldakov, M. A.; Tretyakova, M. S.; Ryabov, V. B.; Klimov, I. A.; Kutenkov, O. P.; Kzhyshkowska, J.; Bol'shakov, M. A.; Rostov, V. V.; Cherdyntseva, N. V.

    2017-05-01

    To study a response of tumor cells and macrophages to the repetitive pulsed low-dose X-ray radiation. Methods. Tumor growth and lung metastasis of mice with an injected Lewis lung carcinoma were analysed, using C57Bl6. Monocytes were isolated from a human blood, using CD14+ magnetic beads. IL6, IL1-betta, and TNF-alpha were determined by ELISA. For macrophage phenotyping, a confocal microscopy was applied. “Sinus-150” was used for the generation of pulsed X-ray radiation (the absorbed dose was below 0.1 Gy, the pulse repetition frequency was 10 pulse/sec). The irradiation of mice by 0.1 Gy pulsed X-rays significantly inhibited the growth of primary tumor and reduced the number of metastatic colonies in the lung. Furthermore, the changes in macrophage phenotype and cytokine secretion were observed after repetitive pulsed X-ray radiation. Conclusion. Macrophages and tumor cells had a different response to a low-dose pulsed X-ray radiation. An activation of the immune system through changes of a macrophage phenotype can result in a significant antitumor effect of the low-dose repetitive pulsed X-ray radiation.

  13. Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4.

    Science.gov (United States)

    Todaro, M; Lombardo, Y; Francipane, M G; Alea, M Perez; Cammareri, P; Iovino, F; Di Stefano, A B; Di Bernardo, C; Agrusa, A; Condorelli, G; Walczak, H; Stassi, G

    2008-04-01

    We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2. Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptotic proteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 acts as an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a novel treatment for epithelial cancers.

  14. Smoking: the influence of carboxyhemoglobin (HbCO) on tumor oxygenation and response to radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, R.P.; Bush, R.S.

    1978-01-01

    The effectiveness of localized x radiation on the transplantable KHT sarcoma was studied in nonanesthetized C3H mice possessing blood carboxyhemoglobin (HbCO) levels similar to those observed in heavy smokers. HbCO values of 10 percent were induced in tumor-bearing animals, either acutely just prior to irradiation or chronically during tumor growth and irradiation, by allowing the mice to breathe gas mixtures containing carbon monoxide (CO) in air. Tumors were irradiated either with single doses of 1500, 2000, or 2500 rad or with seven 500 rad fractions given at 24 hr intervals. Tumor cell survival was determined using an in vivo lung colony or an in vitro agar colony assay. The results with single doses of radiation indicate that under conditions of both acute and chronic exposure, the presence of 10 percent HbCO in the blood of the mice at the time of irradiation increases the survival of tumor cells in the hypoxic region of the survival curve by a factor of 2. During the fractionated irradiation, tumor cell survival in the presence of a 10 percent blood HbCO level (induced either acutely or chronically) was found to be significantly higher than that observed in air breathing mice. The results indicate that HbCO levels, such as are observed in heavy smokers, result in a larger fraction of hypoxic tumor cells. These findings suggest that heavy smoking prior to treatment may worsen the prognosis of patients undergoing radiotherapy

  15. Ionizing radiation induces tumor cell lysyl oxidase secretion

    DEFF Research Database (Denmark)

    Shen, Colette J; Sharma, Ashish; Vuong, Dinh-Van

    2014-01-01

    BACKGROUND: Ionizing radiation (IR) is a mainstay of cancer therapy, but irradiation can at times also lead to stress responses, which counteract IR-induced cytotoxicity. IR also triggers cellular secretion of vascular endothelial growth factor, transforming growth factor beta and matrix...

  16. Second primary tumor and radiation induced neoplasma in the uterine cancer

    International Nuclear Information System (INIS)

    Sakurai, Tomoyasu; Nishio, Masamichi; Kagami, Yoshikazu; Murakami, Yoshitaka; Narimatsu, Naoto; Kanemoto, Toshitaka

    1984-01-01

    This report is concerned with multiple primary cancers developing in invasive uterine cancer. Second primary tumors were recorded 27 women with a total of 30 non-uterine cancer (exception of radiation-induced cancer). 17 patients of radiation-induced neoplasm were observed (Rectal cancer 4, soft part sarcoma 4, cancer of urinary bladder 3, bone tumor 3, uterin cancer 2 and cancer of Vulva 1). One case is 4 legions (corpus, sigma, thymoma and stomach), 2 cases are 3 lesions (uterine cervix, stomach and maxillay siuis: uterine cervix, thyroidal gland and radiation-induced soft part sarcoma). Only 5 of these 17 patients were known irradiated dose (50 Gy--55 Gy), however others unknown. The mean latent periods of 17 cases of radiation induced neoplasms are 19.4 years. 16 patients of late second cancers of the cervix appearing from 11 to 36 years (average 19.5 years) after initial radiotherapy were recorded. (author)

  17. Improvement of radiation resistance for polytetrafluoroethylene(PTFE) by radiation cross-linking

    International Nuclear Information System (INIS)

    Oshima, Akihiro; Tabata, Yoneho; Ikeda, Shigetoshi; Seguchi, Tadao.

    1996-01-01

    The crosslinked polytetrafluoroethylene(PTFE) was prepared by electron beams irradiation technique in the molten state at 340degC ± 3degC in inert gas atmosphere. The crosslinking density was changed by the irradiation dose. The radiation resistance of crosslinked PTFE was investigated on the mechanical properties after irradiation by γ-rays at room temperature under vacuum and in air. The dose at half value of elongation at break was about 1MGy for 500kGy-crosslinked PTFE, while the dose for non-crosslinked PTFE was only 3.5kGy. It was found that the radiation resistance of PTFE was extremely improved by crosslinking. (author)

  18. Factors determining sensitivity or resistance of tumor cell lines towards artesunate.

    Science.gov (United States)

    Sertel, Serkan; Eichhorn, Tolga; Sieber, Sebastian; Sauer, Alexandra; Weiss, Johanna; Plinkert, Peter K; Efferth, Thomas

    2010-04-15

    Clinical oncology is still challenged by the development of drug resistance of tumors that result in poor prognosis for patients. There is an urgent necessity to understand the molecular mechanisms of resistance and to develop novel therapy strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We first applied a gene-hunting approach using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA expression profiles. Among the genes identified by this approach were genes from diverse functional groups such as structural constituents of ribosomes (RPL6, RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), transcriptional and translational regulators (SFRS2, TUFM, ZBTB4), signal transducers (FLNA), control of cell growth and proliferation (RPS6), angiogenesis promoting factors (ITGB1), and others (SLC25A19, NCKAP1, BST1, DBH, FZD7, NACA, MTHFD2). Furthermore, we applied a candidate gene approach and tested the role of resistance mechanisms towards established anti-cancer drugs for ART resistance. By using transfected or knockout cell models we found that the tumor suppressor p16(INK4A) and the anti-oxidant protein, catalase, conferred resistance towards ART, while the oncogene HPV-E6 conferred sensitivity towards ART. The tumor suppressor p53 and its downstream protein, p21, as well as the anti-oxidant manganese-dependent superoxide dismutase did not affect cellular response to ART. In conclusion, our pharmacogenomic approach revealed that response of tumor cells towards ART is multi-factorial and is determined by gene expression associated with either ART sensitivity or resistance. At least some of the functional groups of genes (e.g. angiogenesis promoting factors, cell growth and proliferation-associated genes signal transducers and kinases) are also implicated in clinical responsiveness of tumors towards chemotherapy. It merits further investigation, whether ART is responsive in

  19. Spin Lattice Relaxation EPR pO2 Images May Direct the Location of Radiation Tumor Boosts to Enhance Tumor Cure.

    Science.gov (United States)

    Epel, Boris; Krzykawska-Serda, Martyna; Tormyshev, Victor; Maggio, Matthew C; Barth, Eugene D; Pelizzari, Charles A; Halpern, Howard J

    2017-12-01

    Radiation treatment success and high tumor oxygenation and success have been known to be highly correlated. This suggests that radiation therapy guided by images of tumor regions with low oxygenation, oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. Before applying the technique to human subjects, OGRT needs to be tested in animals, most easily in rodents. Electron paramagnetic resonance imaging provides quantitative maps of tissue and tumor oxygen in rodents with 1 mm spatial resolution and 1 torr pO 2 resolution at low oxygen levels. The difficulty of using mouse models is their small size and that of their tumors. To overcome this we used XRAD225Cx micro-CT/ therapy system and 3D printed conformal blocks. Radiation is delivered first to a uniform 15% tumor control dose for the whole tumor and then a boost dose to either hypoxic tumor regions or equal volumes of well oxygenated tumor. Delivery of the booster dose used a multiple beam angles to deliver radiation beams whose shape conforms to that of all hypoxic regions or fully avoids those regions. To treat/avoid all hypoxic regions we used individual radiation blocks 3D-printed from acrylonitrile butadiene styrene polymer infused with tungsten particles fabricated immediately after imaging to determine regions with pO 2 less than 10 torr. Preliminary results demonstrate the efficacy of the radiation treatment with hypoxic boosts with syngeneic FSa fibrosarcoma tumors in the legs of C3H mice.

  20. Gamma knife radiosurgery of radiation-induced intracranial tumors: Local control, outcomes, and complications

    International Nuclear Information System (INIS)

    Jensen, Ashley W.; Brown, Paul D.; Pollock, Bruce E.; Stafford, Scott L.; Link, Michael J.; Garces, Yolanda I.; Foote, Robert L.; Gorman, Deborah A.; Schomberg, Paula J.

    2005-01-01

    Purpose: To determine local control (LC) and complication rates for patients who underwent radiosurgery for radiation-induced intracranial tumors. Methods and Materials: Review of a prospectively maintained database (2,714 patients) identified 16 patients (20 tumors) with radiation-induced tumors treated with radiosurgery between 1990 and 2004. Tumor types included typical meningioma (n = 17), atypical meningioma (n = 2), and schwannoma (n 1). Median patient age at radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2 months). Time-to-event outcomes were calculated with Kaplan-Meier estimates. Results: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3 and 5 years were 100%. Three patients died: 1 had in-field progression 65.1 months after radiosurgery and later died of the tumor, 1 died of progression of a preexisting brain malignancy, and 1 died of an unrelated cause. One patient had increased seizure activity that correlated with development of edema seen on neuroimaging. Conclusions: LC, survival, and complication rates in our series are comparable to those in previous reports of radiosurgery for intracranial meningiomas. Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas. Radiosurgery is a safe and effective treatment option for radiation-induced intracranial tumors, most of which are typical meningiomas

  1. Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation delivery

    Science.gov (United States)

    Dong, Lixin; Kudrimoti, Mahesh; Cheng, Ran; Shang, Yu; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2012-01-01

    This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements. PMID:22312579

  2. A novel radiation-induced p53 mutation is not implicated in radiation resistance via a dominant-negative effect.

    Directory of Open Access Journals (Sweden)

    Yunguang Sun

    Full Text Available Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase 3 and cleaved caspase 3 in radiation resistant cells and the radiation susceptible (parent line were compared, all of which were found to be similar. These patterns held true after analysis of p53 overexpression in H460 cells; however, H1299 cells transfected with mutant p53 did not express p21, whereas those given WT p53 produced a significant amount, as expected. A luciferase assay demonstrated the inability of mutant p53 to bind its consensus elements. An MTS assay using H460 and H1299 cells transfected with WT or mutant p53 showed that the novel mutation did not improve cell survival. In summary, functional characterization of a radiation-induced p53 mutation in the H460 lung cancer cell line does not implicate it in the development of radiation resistance.

  3. Spatial Positioning of RET and H4 Following Radiation Exposure Leads to Tumor Development

    Directory of Open Access Journals (Sweden)

    Yuri E. Nikiforov

    2001-01-01

    Full Text Available Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many others. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a large increase in incidence of thyroid cancer was observed in children exposed to radiation after the Chernobyl nuclear accident [1]. A high prevalence of chromosomal rearrangements involving the RET gene was found among these radiation-induced thyroid tumors [2,3]. As a result of such rearrangement, a portion of the RET gene is fused with another gene, typically with the H4 or ELE1. However, since the DNA targets of ionizing radiation are randomly distributed throughout the cell nucleus, the reason for predilection for the RET rearrangements in thyroid cells was unclear.

  4. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    International Nuclear Information System (INIS)

    Ahmed, Kamran A.; Fulp, William J.; Berglund, Anders E.; Hoffe, Sarah E.; Dilling, Thomas J.; Eschrich, Steven A.; Shridhar, Ravi; Torres-Roca, Javier F.

    2015-01-01

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  5. Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Fulp, William J.; Berglund, Anders E. [Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Hoffe, Sarah E.; Dilling, Thomas J. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Eschrich, Steven A. [Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Shridhar, Ravi [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2015-07-15

    Purpose: We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases. Methods and Materials: Patients were identified from our institutional review board–approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026). Conclusions: Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger

  6. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4.

    Science.gov (United States)

    Todaro, Matilde; Alea, Mileidys Perez; Di Stefano, Anna B; Cammareri, Patrizia; Vermeulen, Louis; Iovino, Flora; Tripodo, Claudio; Russo, Antonio; Gulotta, Gaspare; Medema, Jan Paul; Stassi, Giorgio

    2007-10-11

    A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133(+) cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133(+) cells. Further analysis revealed that the CD133(+) cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, treatment with IL-4Ralpha antagonist or anti-IL-4 neutralizing antibody strongly enhances the antitumor efficacy of standard chemotherapeutic drugs through selective sensitization of CD133(+) cells. Our data suggest that colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4.

  7. Radiation resistance of paralytic shellfish poison (PSP) toxins

    Energy Technology Data Exchange (ETDEWEB)

    San Juan, Edith M

    2000-04-01

    Radiation resistance of paralytic shellfish poison (PSP) toxins, obtained from Pyrodinium bahamense var. compressum in shellstocks of green mussels, was determined by subjecting the semi-purified toxin extract as well as the shellstocks of green mussels to high doses of ionizing radiation of 5, 10, 15 and 20 kGy. The concentration of the PSP toxins was determined by the Standard Mouse Bioassay (SMB) method. The radiation assistance of the toxins was determined by plotting the PSP toxin concentration versus applied dose in a semilog paper. The D{sub 10} value or decimal reduction dose was obtained from the straight line which is the dose required to reduce the toxicity level by 90%. The effects of irradiation on the quality of green mussels in terms of its physico-chemical, microbiological and sensory attributes were also conducted. The effect of irradiation on the fatty acid components of green mussels was determined by gas chromatography. Radiation resistance of the PSP toxins was determined to be lower in samples with initially high toxicity level as compared with samples with initially low toxicity level. The D{sub 10} values of samples with initially high PSP level were 28.5 kGy in shellstocks of green musssels and 17.5 kGy in the semi-purified toxin extract. When the PSP level was low initially, the D{sub 10} values were as high as 57.5 and 43.5 kGy in shellstocks of green mussels for the two trials, and 43.0 kGy in semi-purified toxin extract. The microbial load of the irradiated mussels was remarkably reduced. No differnce in color and odor characteristics were observed in the mussel samples subjected to varying doses of ionizing radiation. There was darkening in the color of mussel meat and its juice. The concentration of the fatty acid components in the fresh green mussels were considerably higher as compared with those present in the irradiated mussels, though some volatile fatty acids were detected as a result of irradiation. (Author)

  8. Radiation resistance of paralytic shellfish poison (PSP) toxins

    International Nuclear Information System (INIS)

    San Juan, Edith M.

    2000-04-01

    Radiation resistance of paralytic shellfish poison (PSP) toxins, obtained from Pyrodinium bahamense var. compressum in shellstocks of green mussels, was determined by subjecting the semi-purified toxin extract as well as the shellstocks of green mussels to high doses of ionizing radiation of 5, 10, 15 and 20 kGy. The concentration of the PSP toxins was determined by the Standard Mouse Bioassay (SMB) method. The radiation assistance of the toxins was determined by plotting the PSP toxin concentration versus applied dose in a semilog paper. The D 10 value or decimal reduction dose was obtained from the straight line which is the dose required to reduce the toxicity level by 90%. The effects of irradiation on the quality of green mussels in terms of its physico-chemical, microbiological and sensory attributes were also conducted. The effect of irradiation on the fatty acid components of green mussels was determined by gas chromatography. Radiation resistance of the PSP toxins was determined to be lower in samples with initially high toxicity level as compared with samples with initially low toxicity level. The D 10 values of samples with initially high PSP level were 28.5 kGy in shellstocks of green musssels and 17.5 kGy in the semi-purified toxin extract. When the PSP level was low initially, the D 10 values were as high as 57.5 and 43.5 kGy in shellstocks of green mussels for the two trials, and 43.0 kGy in semi-purified toxin extract. The microbial load of the irradiated mussels was remarkably reduced. No differnce in color and odor characteristics were observed in the mussel samples subjected to varying doses of ionizing radiation. There was darkening in the color of mussel meat and its juice. The concentration of the fatty acid components in the fresh green mussels were considerably higher as compared with those present in the irradiated mussels, though some volatile fatty acids were detected as a result of irradiation. (Author)

  9. Role of Immunomodulators in Tumor Regression in Mice Exposed to Fractionated Low Dose of Gamma Radiation

    International Nuclear Information System (INIS)

    Rokaya Elsayed Maaroaf Elsayed

    2015-01-01

    Immunotherapy is one of the most promising approaches of cancer treatment. The present study was designed to examine the role of irradiated tumor cell lysate vaccine, IFNα-2b and low dose of gamma irradiation as immunomodulators either alone or combined in tumor regression. Ehrlich ascite carcinoma (EAC) cells and 9 groups of female mice were used. Mice were immunized intramuscularly by tumor cell lysate vaccine one time/week for 3 weeks in the right thigh of mice. After two weeks from last immunization, all mice were challenged with normal viable EAC cells at count of 2.5 ×10 6 /mouse in the opposite left thigh for Ehrlich carcinoma (EC) production. Mice were subcutaneously injected with 10.000 units of IFNα-2b 3 times/week for 4 weeks and others were exposed to fractionated dose of γ- radiation (0.5 Gy/day x 4, day after day). Tumor size, serum tumor markers (TNF-α and CEA), tumor DNA fragmentation and Caspase-3 were evaluated. Oxidative stress (MDA and NO) markers and antioxidants (GSH, GPX and SOD) were determined in spleen and tumor tissues. Histopathological examinations, apoptosis and necrosis in spleen and tumor tissues were also examined. The results revealed significant inhibition in tumor size throughout the observation period either for treatments with vaccine or IFNα-2b either alone or combined with γ-irradiation. DNA fragmentation and Caspase-3 enzyme activities were significantly elevated in immunized mice as compared with EC group along with diminished tumor size while, tumor markers were significantly decreased. MDA and NO were significantly increased in tumor tissue.while, tumor GSH content, GPX and SOD activities were significantly decreased. Combined treatments of female mice bearing EC with IFN-α-2b, tumor cell lysate vaccine and low dose of γ-radiation cause a highly significant decrease in serum TNF-α and CEA levels, increase in Cas-3 activity, no DNA fragmentation, significant increase in MDA, decrease in SOD activity and decreased

  10. Brain tumors in children: long-term survival after radiation treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jenkin, Derek; Greenberg, Mark; Hoffman, Harold; Hendrick, Bruce; Humphreys, Robin; Vatter, Annette

    1995-02-01

    Purpose: To determine the cause of death in children who survive more than 5 years after radiation treatment of a brain tumor. Methods and Material: Nine hundred and twelve consecutive children with a primary brain tumor irradiated at the Princess Margaret Hospital or Toronto-Bayview Regional Cancer Center from 1958 to 1991, were evaluated for long-term outcome. Results: Overall 10- and 20-year survival rates were 44% and 37%. Subsequent survival of 377 5-year survivors was, at an additional 10 and 20 years, 78% and 67%. Most (83%) deaths that occurred more than 5 years from diagnosis were a result of relapse of the original tumor. The 10-year survival rate subsequent to relapse was 9% when the first relapse occurred less than one year from diagnosis, 17% for 1-2 years, and 31% when the time to relapse was 3 years or greater. The cumulative actuarial incidence of, and death from, second malignant tumors at 30 years from diagnosis was 18% and 13%, respectively. Conclusions: Death later than 5 years from diagnosis of a brain tumor in children is common and is usually due to progressive disease in slowly evolving low grade tumors. Death from a second malignant tumor becomes more frequent than death from the original tumor after 15 years from diagnosis.

  11. Influence of low-energy laser radiation on normal skin and certain tumor tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pletnev, S.D.; Karpenko, O.M.

    For some years, the authors' Institute has studied the influence of various types of low-energy laser radiation on normal tissue and the growth of tumors. Radiation at 3 and 30 J/cm/sup 2/ causes an increase in biological activity of various cell elements, manifested as an increase in mitotic activity of the cells in the basal layer of the epidermis, conglomeration of chromatin in the cell nuclei and an increase in degranulation of fat cells in the process of their migration to the reticular layer. Also noted was an increase in content of fibroblastic and lymphohistocytic elements in the dermis, as well as an increase in collagenization of connective tissue. It was found that irradiation of the skin by helium-neon, cadmium-helium and nitrogen lasers before and after grafting of the cells of various tumors modifies the course of the tumor process. This effect is apparently related to the fact that systematic irradiation results in changes creating a favorable background for survival and proliferation of tumor cells in the skin tissue medium. The changes facilitate an increase in survival and growth of both pigmented and nonpigmented tumors. Low power radiation stimulates the activity of the cells or cell structures; medium power stimulates their activity; high power suppresses activity.

  12. Splenomegaly and tumor marker response following selective internal radiation therapy for non-resectable liver metastases from neuroendocrine tumor

    International Nuclear Information System (INIS)

    Shehata, M.; Yan, K.; Itoh, Seiji; King, J.; Glenn, D.; Quinn, R.; Morris, D.L.

    2009-01-01

    The aim of this study was to investigate changes in spleen size, the level of chromogranin A as a tumor marker, and the relationship between these two parameters before and 3 months after selective internal radiation therapy (SIRT) for non-resectable liver metastases from neuroendocrine tumor (NET). Our first serious adverse event with this relatively new treatment is also discussed. A retrospective review of a prospective database identified patients with non-resectable liver metastases from NET who underwent SIRT between 2003 and 2007. Patients who underwent CT scans before and 3 months after treatment were included. The patients were divided into two groups: those with and without a 20% or more increase in splenic volume on the CT scans. The percentages of patients showing a tumor marker response in the two groups were then compared. Fourteen patients were included in the present analysis. A tumor marker response was seen in 6 of 7 patients (85.7%) who showed an increase in splenic volume of >20%, and in 3 of 7 patients (42.9%) without an increase in splenic volume (p=0.266). There was one death as a result of oesophageal variceal bleeding due to portal hypertension at 9 months after treatment. Splenic enlargement after SIRT may be associated with tumor marker response, although this could not be confirmed statistically in this study due to the small number of patients. Long-term splenomegaly and portal hypertension may be important complications of SIRT. This issue needs to be investigated further using a larger number of patients and longer follow-up. (author)

  13. Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas

    Directory of Open Access Journals (Sweden)

    Ming-Fu eChiang

    2013-03-01

    Full Text Available Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs and appears to contribute, in part, to resistance to temozolomide and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1 is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate a potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death.

  14. Radiation Resistant Hybrid Lotus Effect Photoelectrocatalytic Self-Cleaning Anti-Contamination Coatings, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop radiation resistant hybrid Lotus Effect photoelectrocatalytic self-cleaning anti-contamination coatings for application to Lunar...

  15. Secondary solid tumors following radiation in Hodgkin's disease: experience of the Institut Gustave-Roussy

    International Nuclear Information System (INIS)

    Cosset, J.M.; Henry-Amar, M.; Dietrich, P.Y.; Socie, G.; Girinsky, T.; Hayat, M.; Tubiana, M.

    1992-01-01

    From 1961 to 1984, in the Institut Gustave-Roussy, 893 patients have been treated in Hodgkin's disease. The authors study the solid tumors that they have observed after exclusive radiotherapy and chemo-radiotherapy in order to know the radiation effect in the birth of this type of cancer

  16. Radiation enhancement effect of RNA interference for HIF-1α on the transplant tumor

    International Nuclear Information System (INIS)

    Ren Ruimei; Sun Xindong; Zhao Hanxi; Yan Qingxia; Huang Guangwu

    2008-01-01

    Objective: To determine and explore the radiation enhancement of RNA interference for HIF-1α on the transplant tumor using polycationic polyethylenimine (PEI), as a new kind of gene vector. Methods: SPCA-1 nude mouse model was used. 160 nude mice bearing SPCA-1 were randomly divided into 4 treated groups and 1 control groups, each group had 32 mice. The expression of HIF-1α was studied by immunohistochemical method after RNA interference for HIF-1α. The differences of the volume, weight, survival time of the transplant tumor were studied among the simple radiation group, the simple RNA interference for HIF- 1α group and the combination of radiation and RNA interference for HIF-1α. Results: The expression of HIF-1α was decreased after RNA interference for HIF-1α. RNA interference for HIF-1α combined with radiation decreased the volume, weight of the transplant tumor, and prolonged its survival time period significantly than other methods. Conclusions: RNA interference targeting HIF-1α might enhance the radiosensitivity of the transplant tumor using PEI as a new kind of gene vector in vitro. (authors)

  17. Hypoxia and tumor metabolism in radiation oncology: Targets visualized by positron emission tomography

    NARCIS (Netherlands)

    Wijsman, R.; Kaanders, J.H.A.M.; Oyen, W.J.G.; Bussink, J.

    2013-01-01

    Due to the amazing leap of technology in radiation oncology in the past few years, cancer treatment will become more individualized. Molecular imaging with PET contributed to this with its many tracers available, each of them visualizing a specific feature of a tumor and its microenvironment

  18. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Olga A. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Anderson, Robin L. [The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Russell, Prudence A. [Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC (Australia); Ashley Cox, R. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ivashkevich, Alesia [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Laboratory of DNA Repair and Genomics, Centre for Innate Immunity and Infectious Disease, Monash Institute for Medical Research, Monash University, Clayton, VIC (Australia); Swierczak, Agnieszka; Doherty, Judy P. [Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Jacobs, Daphne H.M. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Smith, Jai [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Siva, Shankar; Daly, Patricia E. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ball, David L. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); and others

    2014-02-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.

  19. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    International Nuclear Information System (INIS)

    Martin, Olga A.; Anderson, Robin L.; Russell, Prudence A.; Ashley Cox, R.; Ivashkevich, Alesia; Swierczak, Agnieszka; Doherty, Judy P.; Jacobs, Daphne H.M.; Smith, Jai; Siva, Shankar; Daly, Patricia E.; Ball, David L.

    2014-01-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies

  20. Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

    Science.gov (United States)

    Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

    2016-02-01

    Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

  1. Case of false positive scanning observed after radiation therapy for orbital tumor

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, H [Gifu Prefectural Tajimi Hospital (Japan); Nakamura, K; Maeda, S; Watanabe, R; Miyajima, T

    1978-12-01

    A report was made of 56-year-old female patient of abducensparesis. In the early stage the cause remained undetermined with nothing abnormal noted in scintigraphy. Diplopia disappeared once, but right, exophalmus relapsed. In gammaencepharography, a hot spot was noted in the orbita, sinus ethmoidalis and sirus sphenoidalis. In an operation, squamous cell carcinoma was removed and radiation therapy was performed (total dose of 3520 r) and, three months later a scintigraphy disclosed a high spot of /sup 203/Hg uptake ratio in the right orbita and its lower portions. The biopsy of these portions disclosed a necrotic tissue instead of a tumor. In scintigraphy after radiation therapy against the tumor, it was reported that a positive scintigraphy was present because of the vascular trouble of said portions, although the tumor had disappeared. Attention should be given as well as an opinion of high density together with the examination by CT, especially as to enhancement.

  2. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

    2002-06-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  3. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    International Nuclear Information System (INIS)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

    2002-01-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  4. Genetic predisposition for radiation-induced bone tumors

    International Nuclear Information System (INIS)

    Rosemann, M.; Luz, A.; Kuosaite, V.; Favor, J.; Atkinson, M.J.; Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg

    1999-01-01

    The interaction between environmental factors and genetic determinants is crucial for the development of malignant tumours. However, the hereditary factors involved in the development of cancer that have been recognised so far are only responsible for at the most ten percent of tumours. It is still a matter of dispute whether the remaining 90 percent - so-called sporadic tumours - really have a cause that is free of genetic influence. There are good reasons for believing that there are a large number of genes in the human genome that confer resistance or susceptibility for tumorigenesis, and thus lead to natural genetic variability. (orig.) [de

  5. Solid tumor models for the assessment of different treatment modalities. XIV. The evaluation of host and tumor response to cyclophosphamide and radiation

    International Nuclear Information System (INIS)

    Looney, W.B.; Hopkins, H.A.; MacLeod, M.S.; Ritenour, E.R.

    1979-01-01

    The effect of increasing doses of cyclophosphamide (50 to 250 mg/kg) on the time of occurrence of maximal and minimal tumor growth rates, tumor volume reduction, and linear doubling times (LDT) on the solid tumor model H-4-II-E has been determined. Tumor response to cyclophosphamide was classified as class I, tumor regression; class II, pseudo-regression; and class III, slow-down. The overall treatment efficiency (OTE) has been used to assess the magnitude of tumor volume changes after treatment. The maximum OTE occurred after 150 mg/kg of cyclophosphamide. Increasing the dose to 200 and 250 mg/kg of cyclophosphamide resulted in a decrease in OTE. Similar parameters were utilized to measure the effectiveness of increasing doses of local tumor radiation (750, 1500, 2000, 2500, 3000 and 3500R). The major increase in OTE occurs when the radiation dose is increased from 750R to 2000R. Increasing the dose further to 3500R results in smaller incremental increases in the OTE. Results of the study indicate that increasing the cyclophosphamide dose beyond a certain level (i.e., 150 mg/kg) increases mortality and morbidity without concomitant therapeutic benefit. The effects of increasing the dose of local tumor radiation on life span have given results which suggest that increasing the total radiation dose beyond a certain limit is less effective in increasing life span

  6. The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

    International Nuclear Information System (INIS)

    Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

    2007-01-01

    Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

  7. The necrotic signal induced by mycophenolic acid overcomes apoptosis-resistance in tumor cells.

    Directory of Open Access Journals (Sweden)

    Gwendaline Guidicelli

    Full Text Available BACKGROUND: The amount of inosine monophosphate dehydrogenase (IMPDH, a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP, is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA-mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL-overexpressing cells. All tested cells remained sensitive to MPA-mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers. CONCLUSIONS/SIGNIFICANCE: These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells.

  8. Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis

    Directory of Open Access Journals (Sweden)

    Derek White

    2014-03-01

    Full Text Available Purpose: To investigate the usefulness of Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI changes in signal intensity related to oxygen challenge for predicting tumor response to radiation therapy.Methods: Dynamic MR signal changes were acquired using Varian 4.7T small animal MR scanner prior to image-guided radiation therapy (IGRT of small (n = 6 and large subcutaneous (n = 5 prostate tumors in adult male rats. An interleaved blood-oxygen level dependent (BOLD and tissue-oxygen level dependent (TOLD data acquisition or (IBT was performed using a baseline of medical air as positive control and using medical oxygen as a breathing challenge. BOLD used a 2-D multi-slice spoiled gradient-echo with multi-echo sequence. TOLD used a 2-D multi-slice spoiled gradient-echo sequence. Voxel changes in signal intensity were determined by a correlation coefficient mapping technique. Irradiation technique planned consisted of 1F × 15 Gy AP/PA or 2F × 7.5 Gy AP/PA to the gross tumor volume (GTV. Tumor growth measurements were recorded over time to assess the response to IGRT.Results: BOLD and TOLD signals variously illustrated positive or negative impulse responses in the tumor ROI due to inhaling medical oxygen. Correlation coefficient mapping demonstrated heterogeneity in tumors after inhaling medical oxygen. BOLD and TOLD signals exhibited increased changes in signal intensities after the first fraction of dose. Multi-fractionation had minimum effect until the second fraction of dose was applied. Tumor growth delays were observed when inhaling medical oxygen during IGRT.Conclusion: OE-MRI is a non-invasive imaging modality that can provide insight to the oxygen status of tumors. Observed increase percent changes in BOLD and TOLD signal intensities after the first fraction of dose suggest tumors experienced reoxygenation. OE-MRI could be used for predicting tumor response to IGRT when using medical oxygen for increasing GTV radiosensitivity, suggesting

  9. Image-based modeling of tumor shrinkage in head and neck radiation therapy1

    Science.gov (United States)

    Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569

  10. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    International Nuclear Information System (INIS)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  11. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 and Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States); Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

    2010-05-15

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  12. Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

    International Nuclear Information System (INIS)

    Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

    1997-01-01

    Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

  13. WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Grassberger, C; Paganetti, H

    2016-01-01

    Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumed to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation

  14. WE-H-BRA-03: Development of a Model to Include the Evolution of Resistant Tumor Subpopulations Into the Treatment Optimization Process for Schedules Involving Targeted Agents in Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Grassberger, C; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States)

    2016-06-15

    Purpose: To develop a model that includes the process of resistance development into the treatment optimization process for schedules that include targeted therapies. Further, to validate the approach using clinical data and to apply the model to assess the optimal induction period with targeted agents before curative treatment with chemo-radiation in stage III lung cancer. Methods: Growth of the tumor and its subpopulations is modeled by Gompertzian growth dynamics, resistance induction as a stochastic process. Chemotherapy induced cell kill is modeled by log-cell kill dynamics, targeted agents similarly but restricted to the sensitive population. Radiation induced cell kill is assumed to follow the linear-quadratic model. The validation patient data consist of a cohort of lung cancer patients treated with tyrosine kinase inhibitors that had longitudinal imaging data available. Results: The resistance induction model was successfully validated using clinical trial data from 49 patients treated with targeted agents. The observed recurrence kinetics, with tumors progressing from 1.4–63 months, result in tumor growth equaling a median volume doubling time of 92 days [34–248] and a median fraction of pre-existing resistance of 0.035 [0–0.22], in agreement with previous clinical studies. The model revealed widely varying optimal time points for the use of curative therapy, reaching from ∼1m to >6m depending on the patient’s growth rate and amount of pre-existing resistance. This demonstrates the importance of patient-specific treatment schedules when targeted agents are incorporated into the treatment. Conclusion: We developed a model including evolutionary dynamics of resistant sub-populations with traditional chemotherapy and radiation cell kill models. Fitting to clinical data yielded patient specific growth rates and resistant fraction in agreement with previous studies. Further application of the model demonstrated how proper timing of chemo-radiation

  15. Protective Role of Hsp27 Protein Against Gamma Radiation-Induced Apoptosis and Radiosensitization Effects of Hsp27 Gene Silencing in Different Human Tumor Cells

    International Nuclear Information System (INIS)

    Aloy, Marie-Therese; Hadchity, Elie; Bionda, Clara; Diaz-Latoud, Chantal; Claude, Line; Rousson, Robert; Arrigo, Andre-Patrick; Rodriguez-Lafrasse, Claire

    2008-01-01

    Purpose: The ability of heat shock protein 27 (Hsp27) to protect cells from stressful stimuli and its increased levels in tumors resistant to anticancer therapeutics suggest that it may represent a target for sensitization to radiotherapy. In this study, we investigate the protective role of Hsp27 against radiation-induced apoptosis and the effect of its attenuation in highly expressing radioresistant cancer cell lines. Methods and Materials: We examined clonogenic death and the kinetics of apoptotic events in different tumor cell lines overexpressing or underexpressing Hsp27 protein irradiated with photons. The radiosensitive Jurkat cell line, which does not express Hsp27 constitutively or in response to γ-rays, was stably transfected with Hsp27 complementary DNA. Attenuation of Hsp27 expression was accomplished by antisense or RNAi (interfering RNA) strategies in SQ20B head-and-neck squamous carcinoma, PC3 prostate cancer, and U87 glioblastoma radioresistant cells. Results: We measured concentration-dependent protection against the cytotoxic effects of radiation in Jurkat-Hsp27 cells, which led to a 50% decrease in apoptotic cells at 48 hours in the highest expressing cells. Underlying mechanisms leading to radiation resistance involved a significant increase in glutathione levels associated with detoxification of reactive oxygen species, a delay in mitochondrial collapse, and caspase activation. Conversely, attenuation of Hsp27 in SQ20B cells, characterized by their resistance to apoptosis, sensitizes cells to irradiation. This was emphasized by increased apoptosis, decreased glutathione basal level, and clonogenic cell death. Sensitization to irradiation was confirmed in PC3 and U87 radioresistant cells. Conclusion: Hsp27 gene therapy offers a potential adjuvant to radiation-based therapy of resistant tumors

  16. Effects of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Lu Yanda

    2001-01-01

    Objective: To study the effect of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in the tumor-bearing mice. Methods: Kunming strain male mice were implanted with S 180 sarcoma cells in the right inguen subcutaneously as an experimental in situ animal model. Six hours before implantation the mice were given 75 mG whole-body X-ray irradiation and tumor-formation rate was counted 5 days late. From then, every two days the tumor volume was measured to draw a tumor growth curve. Fifteen days later, all mice were killed to measure the tumor weight, observe the necrosis area and the tumor-infiltration lymphoreticular cells (TIL) in the tumor pathologically. At the same time, erythrocyte immune function and activity of SOD were tested. Results: (1) The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without a pre-exposed (P < 0.05). (2) The tumor growth slowed down significantly in mice receiving a low does irradiation; The average tumor weight in mice receiving a low dose irradiation was lighter too (P < 0.05). (3) The tumor necrosis areas were larger and TILs were more in the irradiation group than those of the control group. (4) The erythrocyte immune function and activity of SOD in the irradiation group were all higher significantly than those of the control group ( P < 0.05). Conclusion: Low dose radiation could markedly increase anti-tumor ability of the organism and improve the erythrocyte immune function and activity of SOD in red cells, suggesting it could be useful in clinical cancer treatment

  17. Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

    International Nuclear Information System (INIS)

    Wentworth, Stacy; Pinn, Melva; Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth; Ellis, Thomas L.; Glazier, Steven S.; McMullen, Kevin P.; Munley, Michael; Stieber, Volker W.; Tatter, Stephen B.; Shaw, Edward G.

    2009-01-01

    Purpose: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. Methods and Materials: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. Results: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. Conclusions: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors

  18. Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

    International Nuclear Information System (INIS)

    Pulsifer, Margaret B.; Sethi, Roshan V.; Kuhlthau, Karen A.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

    2015-01-01

    Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy

  19. Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pulsifer, Margaret B., E-mail: mpulsifer@mgh.harvard.edu [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kuhlthau, Karen A. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-10-01

    Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy.

  20. 2-deoxy-d-glucose (2-DG) inhibits radiation induced carcinogenesis (skin tumors) in mice

    International Nuclear Information System (INIS)

    Singh, Saurabh; Bhuria, Vikas; Pandey, Sanjay; Saluja, Daman; Dwarakanath, B.S.

    2014-01-01

    One of the late effects of radiation exposure i.e. carcinogenesis is exemplified by atomic bomb survivors, radiotherapy patients and occupational workers. Enhanced glucose metabolism (Warburg's effect) is a fundamental metabolic change in transformed cells which drives tumorigenesis. It is suggested that Dietary Energy Restriction (DER) that targets glucose metabolism may afford protection against radiation-induced carcinogenesis. However, DER is practically difficult to sustain in humans. Therefore, we have hypothesized that the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), a potential energy restriction mimetic agent (ERMA) may impair the process of tumorigenesis as an alternative to DER. In the present studies we investigated the effects of dietary 2-DG on radiation induced papillomas in mice. Swiss albino mice (male) were irradiated with a fractionated dose schedule (1.5 Gy ionizing radiation/week for four weeks) focally on the shaved back followed by the application of tumor promoting agent (TPA) once weekly till the termination of the study. Mice were administered 2-DG (0.2% and 0.4% w/v) containing water starting a week after last irradiation. A significant reduction in the tumor incidence, tumor burden, besides increase in the latency period was observed in the 2-DG fed mice. The average tumor incidence (papillomas formation) was reduced to 25% and 37% in 0.2% and 0.4% 2-DG group respectively from 47% in the control group with a significant delay in the onset. Under these conditions, 2-DG considerably enhanced the level of reduced glutathione (GSH) with a concomitant decrease in the lipid peroxidation. 2-DG fed tumor bearing mice showed decrease in splenic CD4 + to CD8 + T-cell ratio and prevented the tumor induced augmentation of T-regulatory cells (CD4 + CD25 + ) which correlated with an increase in CD8 + (CTLs) cells. Dietary 2-DG also reduced the tumor associated and radiation induced angiogenesis. These observations suggest that dietary 2-DG

  1. Evaluation of tumor registry validity in Samsung medical center radiation oncology department

    International Nuclear Information System (INIS)

    Park, Won; Huh, Seung Jae; Kim, Dae Yong; Shin, Seong Soo; Ahn, Yong Chan; Lim, Do Hoon; Kim, Seon Woo

    2004-01-01

    A tumor registry system for the patients treated by radiotherapy at Samsung Medical Center since the opening of a hospital at 1994 was employed. In this study, the tumor registry system was introduced and the validity of the tumor registration was analyzed. The tumor registry system was composed of three parts: patient demographic, diagnostic, and treatment information. All data were input in a screen using a mouse only. Among the 10,000 registered cases in the tumor registry system until Aug, 2002, 199 were randomly selected and their registration data were compared with the patients' medical records. Total input errors were detected in 15 cases (7.5%). There were 8 error items in the part relating to diagnostic information: tumor site 3, pathology 2, AJCC staging 2 and performance status 1. In the part relating to treatment information there were 9 mistaken items: combination treatment 4, the date of initial treatment 3 and radiation completeness 2. According to the assignment doctor, the error ratio was consequently variable. The doctors who did no double-checks showed higher errors than those that did (15.6%: 3.7%). Our tumor registry had errors within 2% for each item. Although the overall data quality was high, further improvement might be achieved through promoting sincerity, continuing training periodic validity tests and keeping double-checks. Also, some items associated with the hospital information system will be input automatically in the next step

  2. Prevention of spontaneous and radiation-induced tumors in rats by reduction of food intake

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.

    1990-01-01

    In our previous studies carried out on inbred Sprague-Dawley rats, we reported a striking increase in the incidence of tumors following total-body gamma-irradiation [150 rads (1.5 Gy) five times at weekly intervals]. Subsequently, we observed that two or three irradiations, and to a lesser extent even a single irradiation, were sufficient to induce an impressive increase in the incidence of tumors, particularly in females. A significant reduction of the incidence of radiation-induced tumors resulted when the rats were placed on calorically restricted diet. In experiments reported here, we increased slightly the amount of food given to animals on restricted diet. In the new study, among 102 irradiated females on full diet, 91 (89%) developed tumors, as compared with 29 out of 128 female rats (23%) also irradiated but maintained on restricted diet and 43 out of 89 (48%) untreated control females. None of 77 nonirradiated females on restricted diet developed tumors. Among 65 irradiated male rats, 29 (45%) developed tumors, as compared with 5 out of 74 (7%) rats also irradiated but maintained on restricted diet. Of the 49 males in the nonirradiated groups, 2 (4%) developed tumors. There was a significant weight reduction in both females and males maintained on restricted diet; animals on restricted diet lived longer than those on full diet

  3. Effect of carbon monoxide breathing on hypoxia and radiation response in the SCCVII tumor in vivo

    International Nuclear Information System (INIS)

    Grau, C.; Marianne, M.D.; Nordsmark, M.; Khalil, A.A.; Horsman, M.R.; Overgaard, J.

    1994-01-01

    The purpose of this study was the influence of a clinically relevant concentration of carbon monoxide (CO) on tumor oxygenation and responses to irradiation. The murine tumor model was the SCCVII squamous cell carcinoma transplanted to the feet of C3H/Km mice. Sixty minutes of breathing CO at 200 ppm resulted in a carboxyhemoglobin level of 15%. This resulted in a reduction in p50 (the oxygen partial pressure at which hemoglobin is 50% saturated) to 78% of the control value, and a decrease in tumor blood perfusion to 73% of the control value. The combined effect of a decrease in effective hemoglobin and blood perfusion resulted in a reduction in tumor oxygen supply to 62% of the control value. In agreement with this, intratumoral pO 2 measurements showed a significant increase in tumor hypoxia, such that the percentage of measurements with low pO 2 (≤ 5 mmHg) increased from 33% to 62%. The fraction of clonogenic hypoxic cells, measured radiobiologically by paired cell survival curves, similarly increased from 0.2% to 3.8%. Radiation sensitivity, evaluated from in vivo-in vitro excision assay, was significantly decreased by CO in 1, 4, 8, and 12 fractions were 0.71, 0.77, 0.83, and 0.71, respectively. The present SCCVII tumor data confirm the general experimental observation that CO breathing significantly increases tumor hypoxia and reduces the effectiveness of ionizing irradiation. 22 refs., 3 figs., 2 tabs

  4. Role of membrane Hsp70 in radiation sensitivity of tumor cells

    International Nuclear Information System (INIS)

    Murakami, Naoya; Kühnel, Annett; Schmid, Thomas E.; Ilicic, Katarina; Stangl, Stefan; Braun, Isabella S.; Gehrmann, Mathias; Molls, Michael; Itami, Jun; Multhoff, Gabriele

    2015-01-01

    The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in the cytosol and integrated in the plasma membrane of tumor cells via lipid anchorage. Following stress such as non-lethal irradiation Hsp70 synthesis is up-regulated. Intracellular located Hsp70 is known to exert cytoprotective properties, however, less is known about membrane (m)Hsp70. Herein, we investigate the role of mHsp70 in the sensitivity towards irradiation in tumor sublines that differ in their cytosolic and/or mHsp70 levels. The isogenic human colon carcinoma sublines CX + with stable high and CX − with stable low expression of mHsp70 were generated by fluorescence activated cell sorting, the mouse mammary carcinoma sublines 4 T1 (4 T1 ctrl) and Hsp70 knock-down (4 T1 Hsp70 KD) were produced using the CRISPR/Cas9 system, and the Hsp70 down-regulation in human lung carcinoma sublines H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD was achieved by small interfering (si)RNA against Heat shock factor 1 (HSF-1). Cytosolic and mHsp70 was quantified by Western blot analysis/ELISA and flow cytometry; double strand breaks (DSBs) and apoptosis were measured by flow cytometry using antibodies against γH2AX and real-time PCR (RT-PCR) using primers and antibodies directed against apoptosis related genes; and radiation sensitivity was determined using clonogenic cell surviving assays. CX + /CX − tumor cells exhibited similar cytosolic but differed significantly in their mHsp70 levels, 4 T1 ctrl/4 T1 Hsp70 KD cells showed significant differences in their cytosolic and mHsp70 levels and H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD lung carcinoma cell sublines had similar mHsp70 but significantly different cytosolic Hsp70 levels. γH2AX was significantly up-regulated in irradiated CX − and 4 T1 Hsp70 KD with low basal mHsp70 levels, but not in their mHsp70 high expressing counterparts, irrespectively of their cytosolic Hsp70 content. After

  5. Gamma radiation shielding materials improved with burning resistance

    International Nuclear Information System (INIS)

    Nakamura, Michio; Nakamura, Ken-ichi; Yukawa, Katsunori.

    1985-01-01

    Purpose: To obtain gamma irradiation shielding materials excellent in workability and resistant to burning by using a two component type room temperature vulcanizing silicon rubber composition as the base material. Method: Silicon rubber comprising a diorganopolysiloxane polymer, an alkyl silicate as a crosslinker and a suitable sulfurdizing catalyst, for example, a carboxylate is mixed with iron powder and silicon oxide powder as reinforcing and flame retardant material and applied with molding. The iron powder and the silica rocks powder have grain size of 50 - 150 μm and 1 - 70 μm and charged by the amount of from 55 to 60 % by weight and from 20 to 25 % by weight respectively. The fluidizing property is impaired if the particle size of the silica rocks powder is less than 1 μm and, while on the other hand, no desired specific gravity of a predetermined value can be obtained for the molding product if the filled amount of the iron powder is less than 55 %. The oxygen index of the molding product is 45 to improve the burning resistance. The materials are excellent in the air-tightness, gamma radiation shielding performance, elasticity and workability required for the cable penetrations in a nuclear power plant and they generate noxious gases neither. (Kawakami, Y.)

  6. Tamper and radiation resistant instrumentation for safeguarding special nuclear materials

    International Nuclear Information System (INIS)

    Parsons, B.B.; Wells, J.L.

    1977-01-01

    A tamper-resistant liquid level/accountability instrumentation system for safeguards use has been developed and tested. The tests demonstrate the accuracy of liquid level measurement using TDR (Time Domain Reflectometry) techniques and the accuracy of differential pressure and temperature measurements utilizing a custom designed liquid level sensor probe. The calibrated liquid level, differential pressure, and temperature data provide sufficient information to accurately determine volume, density, and specific gravity. Test solutions used include ordinary tap water, diluted nitric acid in varying concentrations, and diluted uranium trioxide also in varying concentrations. System operations and preliminary test results conducted at the General Electric Midwest Fuel Recovery Plant and the National Bureau of Standards, respectively, suggest that the system will provide the safeguards inspector with an additional tool for real-time independent verification of normal operations and special nuclear materials accountancy data for chemical reprocessing plants. This paper discusses the system design concepts, including a brief description of the tamper and radiation resistant features, the preliminary test results, and the significance of the work

  7. Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

    Science.gov (United States)

    Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

    2017-11-15

    Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional

  8. The radiation resistance of thermoset plastics: Pt. 1

    International Nuclear Information System (INIS)

    Gilfrich, H.-P.; Roesinger, S.; Wilski, H.

    1991-01-01

    Not much is known about the influence of ionising radiation on thermoset plastics. In particular the influence of the dose rate on the radiation resistance has not yet been investigated. To get more information about this subject we have irradiated a number of thermoset plastics of different chemical compositions in two ways: irradiation with electrons at a high dose rate and under exclusion of oxygen and irradiation at an extremely low dose rate in air with the γ-rays of a cobalt-60 source. The latter experiment lasting over a period of 10 years (and in some cases even 16 years). In this first part of our report we describe the experimental conditions as well as the results obtained using two phenolic plastics with different inorganic fillers. In no case did we find any improvement in the properties tested. The mechanical properties deteriorated at high doses, the effects being particularly noticeable in long term experiments. Both materials became more sensitive to the influence of heat and humidity. A relatively reliable extrapolation of the results to a working period of 50 years seems to be possible. (author)

  9. Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

    Science.gov (United States)

    Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

    2014-05-05

    Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

  10. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Wang Weimin; Li Jinliang; Huang Yongqiang

    2010-01-01

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  11. Assessment of the radiation resistance of some aromatic polyesters

    International Nuclear Information System (INIS)

    Choi, E.J.; Hill, D.J.T.; Kim, K.Y.

    1998-01-01

    Full text: For many applications, polyesters have more useful properties than vinyl polymers, and they can be degraded to their monomer components and recycled. In addition, aromatic polyesters are known to display a resistance to high temperatures and high-energy ionizing radiation. Recently, we have reported the γ-radiolysis for some aromatic polyesters at low radiation dose; The G-values of radical formation at 77 K were determined to be in the range 0.38∼0.46 for the polyesters of bisphenol A with fluorine substitution at isopropylidene units and in the range 0.71∼1.18 for the polyesters of halogenated bisphenol A with decamethylene segments. While the radiation sensitivities of the latter polymers were dependent on the position and content of halogen substitution, those of the former polymers were slightly dependent on these factors as assessed by the G-values at 77 K. We also have studied the radiolysis of the commercial aromatic polyesters (UP) and polycarbonate (PC). UP has been found to be more radiation stable than PC with respect to the total yield of radicals formed. The G-values for radical formation at 77K was determined to be 0.31 and 0.5 for UP and PC, respectively. In this work, we have prepared poly(ethylene-, butylene- or decalene-terephthalate)s (PET, PBT or PDT) and poly(ethylene-, buthylene- or decalene-2,6-naphthalenedicarboxylate)s (PEN, PBN or PDN) by standard melt polymerization methods, and have examined their γ-radiolysis at 77 K or room temperature, and in vacuum or air, through the applications of ESR spectroscopy and thermal analysis. Inherent viscosities of the polyesters used for the radiation studies were in the range of 0.16∼0.69 dL/g. The values of G(R) indicates that PEN-related polymers have more radiation stable than PET-related polymers and the E, B and D order is one of decreasing stability as one might expect. The significant decrease in the G(R)-values of the polyester being in the range of 0.1∼0.41 at 77 K by

  12. The role of granulocyte macrophage colony stimulating factor (GM-CSF) in radiation-induced tumor cell migration.

    Science.gov (United States)

    Vilalta, Marta; Brune, Jourdan; Rafat, Marjan; Soto, Luis; Graves, Edward E

    2018-03-13

    Recently it has been observed in preclinical models that that radiation enhances the recruitment of circulating tumor cells to primary tumors, and results in tumor regrowth after treatment. This process may have implications for clinical radiotherapy, which improves control of a number of tumor types but which, despite continued dose escalation and aggressive fractionation, is unable to fully prevent local recurrences. By irradiating a single tumor within an animal bearing multiple lesions, we observed an increase in tumor cell migration to irradiated and unirradiated sites, suggesting a systemic component to this process. Previous work has identified the cytokine GM-CSF, produced by tumor cells following irradiation, as a key effector of this process. We evaluated the ability of systemic injections of a PEGylated form of GM-CSF to stimulate tumor cell migration. While increases in invasion and migration were observed for tumor cells in a transwell assay, we found that daily injections of PEG-GM-CSF to tumor-bearing animals did not increase migration of cells to tumors, despite the anticipated changes in circulating levels of granulocytes and monocytes produced by this treatment. Combination of PEG-GM-CSF treatment with radiation also did not increase tumor cell migration. These findings suggest that clinical use of GM-CSF to treat neutropenia in cancer patients will not have negative effects on the aggressiveness of residual cancer cells. However, further work is needed to characterize the mechanism by which GM-CSF facilitates systemic recruitment of trafficking tumor cells to tumors.

  13. Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

    Science.gov (United States)

    ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

    2016-01-01

    Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

  14. Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow

    International Nuclear Information System (INIS)

    Ono, K.; Wandl, E.; Sasai, K.; Tsutsui, K.; Shibamoto, Y.; Takahashi, M.; Abe, M.; Vienna Univ.

    1990-01-01

    The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 μg/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, D q decreased from 3.3 Gy to 1.4 Gy without changing D 0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1>p>0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination. (orig.)

  15. Survival of tumor bearing mice by sequencing of low dose rate (LDR) neutron and photon radiation

    International Nuclear Information System (INIS)

    Onomura, C.I.; Feola, J.M.; Maruyama, Y.

    1984-01-01

    Cf-252 neutron radiation (NT) has been shown to be effective therapy for bulky, hypoxic human tumor and to produce consistent rapid clearance and 5 year cures. NT has been found to be more or less effective depending upon the schedule in which it is used and upon mixing with photon radiation. In an effort to study this scheduling and photon effect, LSA tumor was irradiated in vivo in a hypoxic, advanced state, in different schedules in combination of NT with Co-60 photons. The LSA lymphoma of C57BL/ym mice represents an accurate system to assess dose-response of tumor cells in vivo. Mean survival time was used as endpoint. A high RBE for LDR Cf-252 NT was observed with a RBE(n) of -- 5.0. The effect was not greatly sensitive to sequence in which photons were used. Comparison studies were also tested relative to LDR Cs-137 photon radiation. The results support the high efficacy of LDR NT for destruction of hypoxic tumor in vivo

  16. Treatment of a solid tumor using engineered drug-resistant immunocompetent cells and cytotoxic chemotherapy.

    Science.gov (United States)

    Dasgupta, Anindya; Shields, Jordan E; Spencer, H Trent

    2012-07-01

    Multimodal therapy approaches, such as combining chemotherapy agents with cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector cells. Overcoming such toxic effects of anticancer cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of immunocompetent cells, thereby allowing for the coadministration of cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into immunocompetent cells. In the present study, we evaluated a DRI-based strategy that incorporates the immunocompetent cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector cells efficiently lysed neuroblastoma cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant cellular therapy when combined with cytotoxic chemotherapy approaches.

  17. Molecular mechanisms of drug resistance and tumor promotion involving mammalian ribonucleotide reductase

    Energy Technology Data Exchange (ETDEWEB)

    Choy, B.B.K.

    1991-01-01

    Mammalian ribonucleotide reductase is a highly regulated, rate-limiting activity responsible for converting ribonucleoside diphosphates to the deoxyribonucleotide precursors of DNA. The enzyme consists of two nonidentical proteins called M1 and M2, both of which are required for activity. Hydroxyurea is an antitumor agent which inhibits ribonucleotide reductase by interacting with the M2 component specifically at a unique tyrosyl free radical. Studies were conducted on a series of drug resistant mouse cell lines, selected by a step-wise procedure for increasing levels of resistance to the cytotoxic effects of hydroxyurea. Each successive drug selection step leading to the isolation of highly resistant cells was accompanied by stable elevations in cellular resistance and ribonucleotide reductase activity. The drug resistant cell lines exhibited gene amplification of the M2 gene, elevated M2 mRNA, and M2 protein. In addition to M2 gene amplification, posttranscriptional modulation also occurred during the drug selection. Studies of the biosynthesis rates with exogenously added iron suggest a role for iron in regulating the level of M2 protein when cells are cultured in the presence of hydroxyurea. The hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron centre, which readily releases iron. Altered expression of ferritin appears to be required for the development of hydroxyurea resistance in nammalian cells. The results show an interesting relationship between the expressions of ribonucleotide reductase and ferritin. The phorbol ester tumor promoter, TPA, is also able to alter the expression of M2. TPA was able to induce M2 mRNA levels transiently up to 18-fold within 1/2 hour. This rapid and large elevation of ribonucleotide reductase suggests that the enzyme may play a role in tumor promotion. Studies of the M2 promoter region were undertaken to better understand the mechanism of TPA induction of M2.

  18. Stimulatory effect of low dose radiation on the immune function in tumor-bearing mice

    International Nuclear Information System (INIS)

    Zhang Ying; Li Xiujuan; Li Xiuyi; Liu Shuzheng

    1999-01-01

    Objective: The author aims at investigating the effect of whole body irradiation (WBI) with low dose radiation on immune function in tumor-bearing mice. Methods: C57BL/6J mine implanted with Lewis lung carcinoma cells in the right thighs were used as an experimental animal model. WBI with 75 mGy X-rays was given at the 10 th day after implantation and immunological parameters were detected 18 hours after irradiation. The immunological parameters included the spontaneous incorporation of 3 H-TdR into thymocytes, the number of splenocytes, the reaction of splenocytes to ConA and LPS, the splenic production of IL-2, the cytotoxic activities of natural killer (NK) and lymphokine activated killer cells (LAK) as well as specific cytotoxic T lymphocytes (CTL). Results: The immunological parameters of irradiated tumor-bearing mice were significantly increased compared with those of sham-irradiated tumor-bearing mice (P<0.05∼0.01). Conclusion: Low dose radiation could significantly increase the immune function of tumor-bearing mice, and this stimulatory effect may be of some potential significance in tumor therapy

  19. Development of new radiation resistant, fire-retardant cables. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, Ko; Morita, Yosuke; Udagawa, Takashi (Japan Atomic Energy Research Inst., Takasaki, Gunma. Takasaki Radiation Chemistry Research Establishment); Fujimura, Shun-ichi; Oda, Eisuke

    1982-12-01

    For the cables for nuclear facilities, radiation resistance and fire-retardation are severely required. The authors took note of the fact that even in the existing cables for nuclear power plants, their mechanical properties are greatly degraded by the exposure to large dose (for example, 200 Mrad in PWR testing conditions), and attempted the improvement. They employed a new additive, bromated acenaphthylene condensate (con-BACN), which effectively gives radiation resistance and also is a good flame retarder, to be compounded to an insulation material, and examined the characteristics. In this paper, the features of con-BACN and the investigation of fire-retardant EPDM composition are described. As an initial composition, a small amount of zinc white, sulphur, stearic acid, noclac 224 (Ouchi-Shinko Chemicals, Co.), and antimony trioxide, 100 parts of tale and 45 parts of con-BACN were added to 100 parts of EPDM (propylene content 34 %, Japan Synthetic Rubber Co.). As the antiaging agent, it was decided to use phenol series No. 3 as a result of test. The fire-retardant EP rubber-composed cable was produced for trial, its insulation being fabricated, using a Furukawa's pressurized salt bath continuous vulcanizer. The tests of ..gamma..-irradiation, simulated LOCA and combustion were carried out, and the test results are reported. It was indicated that the cable resisted against high dose several times as much as 200 Mrad, and was suitable for the applications, in which the mechanical properties such as bending are required to be maintained after radiation exposure. It was also found that con-BACN was safe, and its properties of decomposition, concentration and acute toxicity were all very low.

  20. Interest of synchrotron radiation for the therapy of brain tumors: methodology and preclinical applications

    International Nuclear Information System (INIS)

    Regnard, P.

    2007-12-01

    Microbeam radiation (M.R.T.) and stereotactic synchrotron radiation therapy (S.S.R.T.) are innovative techniques currently developed at the european Synchrotron radiation facility. these techniques led to promising, but rarely reproduced, results. the use of different tumoral models for each techniques limit comparisons. M.R.T. experiments on rats bearing 9L tumors 14 days after implantation displayed a double median survival time ( from 20 to 40 days) with a 200 μm spacing irradiation, while a 100 μm spacing irradiation tripled this median (67 days) but damaged normal tissue. the impact of the device dividing synchrotron beam into micro-beams, named multi sit collimator, was also demonstrated. combination of drugs with M.R.T. irradiation was tested. promising results (median survival time: 40 days and 30% of long term survivors) were obtained with an intratumoral injection of gadolinium coupled with a crossing M.R.T. irradiation at 460 Gy. Moreover, earlier M.R.T. irradiation (tumor at D10) quadrupled the median survival time (79 days) with 30% of long term survivors. A new imaging device to target the tumor before irradiation and an adapted collimator will increase the M.R.T. results. As the differences existing between tumoral models used in M.R.T. (9L models) and in S.S.R.T. (F98 models) are major, M.R.T./S.S.R.T. comparative experiments were realised on these two models. Results showed that the two techniques have the same efficacy on F98 model and that the M.R.T. is more effective on 9L model. This can help to define adapted tumor type for these techniques. (author)

  1. On the influence of ultraviolet radiation on spontaneous tumors in NMRI mice

    International Nuclear Information System (INIS)

    Koenigsmann, G.; Kinkel, H.J.; Bocionek, P.; Wolff, F.

    1981-01-01

    During a period of 12 and 15 months respectively, female NMRI mice were irradiated twelve hours per day with specific parts of the ultraviolet spectrum (three groups, each comprising 100 animals: non-irradiated control group, animals irradiated with B units, animals irradiated with A/B units). No considerable influence of the chronic exposure to ultraviolet radiation could be demonstrated with regard to the development of the body weight and the hematologic condition. Group B had the same rate of spontaneous tumors of the respiratory tract as the control group; this rate was higher in group A/B. As to the development of spontaneous tumors in the lymphatic tissues, there seems to be a dependence on radiation: the animals of group B presented a slightly higher, those of group A/B a higher development than the animals of the nonirradiated control group. It cannot be definitely clarified yet to what extent this increased tumor rate was additionally induced by the higher environmental temperature or other influences involved by experiment. Harding-Passey melanomas were inoculated in NMRI mice and, 48 hours later, they were exposed to defined emission spectra within the natural ultraviolet spectrum. The exposed animals showed a slower growth of the transplanted tumors than the non-exposed animals, and especially the animals exposed to UVB radiation had a longer survival time. This chronic irradiation test was carried out in order to examine the influence of defined emission spectra on autochthonous tumors in NMRI mice and on their spontaneous tumor rate and blood count. (orig.) [de

  2. In vivo studies of radiation potentiaton by iodoacetamide and observations on tumor transplantation immunity

    Energy Technology Data Exchange (ETDEWEB)

    Richards, W. Robert [Univ. of California, Berkeley, CA (United States); Kelly, Lola S. [Univ. of California, Berkeley, CA (United States)

    1970-10-01

    Iodoacetamide has been shown by others to be a radiation sensitizer for bacteria and for certain mammalian cells tested in vitro. This work describes an examination of the effectiveness of iodoacetamide used in vivo. Survival of ascites tumor cells maintained in the peritoneal cavity of mice was used as an indicator of sensitization. Survival was assessed using TD50 and total tumor cell population determination methods. A comparison of results obtained by these methods is made. The effects of oxygen tension and radiation dose rate upon results was examined. Iodoacetamide was found to be effective as a radiation sensitizer under all conditions although to a lesser degree than that reported by others for in vitro experiments with bacteria. Radioactive tracer studies indicate that iodoacetamide has rapid and total access to most if not all tissues of the body. This fact coupled with the observation of a sensitization in an in vivo system where the anoxia so prevalent in well developed tumors was present, suggests the possibility of clinical usefulness of iodoacetamide in cancer radiation therapy. Certain observations are reported on the effect of various cell and host treatment procedures upon cell population growth kinetics seen subsequent to inoculation of hosts with the cells. A hypothesis is presented which can account for the observations made by the author and also for those made by some others who report that large inocula, i.e., greater than 10 cells, are required to give rise to a lethal tumor in isologous hosts of the strain of tumor origin. The hypothesis may also account for what is known in the literature as the 'Hybrid Effect.'

  3. VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation

    International Nuclear Information System (INIS)

    Fujisawa, Hiroshi; Nakajima, Nakako Izumi; Sunada, Shigeaki; Lee, Younghyun; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi

    2015-01-01

    High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. The online version of this article (doi:10.1186/s13014-015-0464-y) contains supplementary material, which is available to authorized users

  4. Effects of low dose radiation combined with cyclophosphamide on tumor cell apoptosis, cell cycle and proliferation of bone marrow in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

    2004-01-01

    Objective: To study the effect of low dose radiation (LDR) combined with cyclophosphamide on tumor cell apoptosis, cell cycle, and proliferation of bone marrow in mice tumor-bearing mice. Methods: Kunming strain male mice were implanted with S180 sarcoma cells in the left hind leg subcutaneously as an experimental animal model. Five and 8 days after implantation, the mice were given 75 mGy whole-body γ-ray radiation and CTX(300 mg/kg) by intraperitoneal injection 36 hour after LDR. All mice were sacrificed to measure the tumor volume, tumor cell apoptosis, and cell cycle; the proliferation of bone marrow was analyzed by flow cytometry. Results: Tumor growth was significantly slowed down in the treated groups. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G 1 phase in CTX and CTX+LDR groups, more significantly in the latter group than in the former group. Concentration of bone marrow cells and proliferation index in CTX + LDR group were higher than those in CTX group, although concentration of bone marrow cells in CTX and CTX+LDR groups were much lower than that in normal mice. Conclusion: Low dose radiation combined with cyclophosphamide causes more significant G 1 -phase arrest than cyclophosphamide alone and enhances anti-tumor effect markedly. At the same time LDR significantly protects hematopoietic function of bone marrow, which is of practical significance as an adjuvant chemotherapy

  5. Estimation of interface resistivity in bonded Si for the development of high performance radiation detectors

    International Nuclear Information System (INIS)

    Kanno, Ikuo; Yamashita, Makoto; Nomiya, Seiichiro; Onabe, Hideaki

    2007-01-01

    For the development of high performance radiation detectors, direct bonding of Si wafers would be an useful method. Previously, p-n bonded Si were fabricated and they showed diode characteristics. The interface resistivity was, however, not investigated in detail. For the study of interface resistivity<