Sample records for budr

  1. Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma

    International Nuclear Information System (INIS)

    Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients - of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, the authors believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma

  2. Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas

    International Nuclear Information System (INIS)

    In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe, continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas

  3. Effect of 5-bromouracil and 5-bromo-2-deoxyuridine in combination with 8-azaadenine on UV sensitivity of bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, H.E. (Akademie der Wissenschaften der DDR, Jena. Zentralinstitut fuer Mikrobiologie und Experimentelle Therapie); Golovinsky, E. (Bylgarska Akademiya na Naukite, Sofia)


    The presence of 5-bromouracil (BU) as well as 5-bromo-2-deoxyuridine (BUdR) in the cultivation media of bacteria results in the distinct increase of UV sensitivity. With the nucleic acid base analogue 8-azaadenine (8-AA) a similar effect was confirmed, however, not so pronounced. The combined action of BU or BUdR and 8-AA on Escherichia coli, Proteus mirabilis, Bacillus subtilis and Bacillus cereus was investigated. The sensitization effect of BUdR does not increase if 8-AA is present additionally during cultivation. On the contrary, a decrease of sensibilization occurs. This may be caused by the protective effect of the adenine derivative against UV irradiation, if it is present in the cell, but not incorporated into the DNA.

  4. Alteration of radiosensitivity of quiescent cell populations in solid tumors irradiated with X-rays twice at various intervals

    International Nuclear Information System (INIS)

    5-Bromo-2'-deoxyuridine (BUdR) was injected into SCC VII or EMT6/KU tumor-bearing mice intraperitoneally to label all the proliferating tumor cells. First, the mice were irradiated with X-rays at a dose of 10 Gy, followed by a dose of 0-20 Gy at 0, 12, 24 or 48 h later. During the interval, no BUdR was injected. Immediately after the second irradiation, the tumors were excised and trypsinized. The micronucleus (MN) frequency in cells without BUdR labeling was determined by means of incubation with cytochalasin-B (a cytokinesis-blocker) and immunofluorescence staining for BUdR. When the tumors were not pretreated with BUdR before the first irradiation, the MN frequency in all tumor cells was determined. To determine the labeling indices of SCC VII and EMT6/KU tumors at the time of the second irradiation, each group also included mice that were continuously administered BUdR until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the first irradiation. The MN frequency of all tumor cell populations obtained immediately after the second irradiation decreased in proportion to the increase in interval time. However, in both tumor systems, the MN frequency of unlabeled cell populations, which could be regarded as quiescent cells in the tumors at the time of the first irradiation, was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings support the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation. (author)

  5. uv photobiology: excision repair

    International Nuclear Information System (INIS)

    The following topics are discussed: steps in nucleotide excision; damage to DNA by uv-endonuclease; use of complementation to study DNA repair in Escherichia coli and mammalian cells; role of BUDR photolysis in excision repair, relation between DNA repair defect and human disease; base excision repair; and excision repair by removal of damaged region of a base in DNA without excision

  6. Different radiosensitization effects of the halogenated compounds on the human chromosome in vitro

    International Nuclear Information System (INIS)

    Unscheduled DNA synthesis and chromosome aberrations were compared following X- or UV-irradiation or methyl methanesulfonate treatment in cultures of HeLa S3 or KB cells or human and rabbit lymphocytes. The sensitization by incorporation of the halouridines BUdR and IUdR was also investigated. Unscheduled DNA synthesis occurred in two established cell lines after irradiation with 0 to 10 kR of X-rays. The rate of unscheduled synthesis was dose dependent and differed for the two cell lines. The unscheduled synthesis was not correlated with the modal chromosome number nor with the number of aberrations produced. UV-irradiated rabbit lymphocytes exhibited unscheduled DNA synthesis which saturated after a dose of 250 ergs/mm2. In contrast the incorporation of BUdR or IUdR eliminated this saturation and caused an increasing effect with increasing dose up to 1000 ergs/mm2. The degree of sensitization varied between the two halo-uridines, BUdR being more effective at high doses while IUdR was a more potent sensitizer at low doses. Chromosome aberrations were not directly related to unscheduled DNA synthesis but were sensitized by halo-uridine incorporation. In this case IUdR was more potent than BUdR at all doses studied. Methyl methanesulfonate was an effective producer of chromosome aberration in human lymphocytes of both the chromosome and chromatid type. Prior incorporation of BUdR or IUdR did not increase the total aberration produced but did increase the number of chromosome type aberration at the expense of the chromatid type

  7. Mild phenotypic effects of a de novo deletion Xpter {yields} Xp22.3 and duplication 3pter {yields} 3p23

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    Kulharya, A.S.; Roop, H.; Kukolich, M.K. [Texas Dept. of Health, Denton, TX (United States)] [and others


    We report on a girl with a de novo monosomy Xpter {yields} Xp22.3 and trisomy 3pter {yields} 3p23, normal development and stature, mildly affected phenotype, and learning disabilities with a low normal level of intelligence. Late replication studies using BudR demonstrated that the entire der(X) was inactive in 30% of cells. In 62% of cells the inactivation did not spread to the autosomal segment in the der(X). The normal X was inactivated in 8% of cells. Quantitative X-inactivation studies using the human androgen receptor locus assay (HAR) on peripheral leukocytes and buccal epithelial cells showed extreme skewing of methylation (90.4% of the paternal allele). The correlation of cytogenetic and molecular data suggest that the mild phenotype of the proposita is most likely due to preferential inactivation of the entire der(X), which seems to be of paternal origin. 11 refs., 5 figs., 3 tabs.

  8. Use of halogenated thymidine analogs as clinical radiosensitizers: rationale, current status, and future prospects: non-hypoxic cell sensitizers

    International Nuclear Information System (INIS)

    The halogenated pyrimidine analogs, bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) have been recognized as potential clinical radiosensitizers for over two decades. In vivo and in vitro experimental studies document that radiosensitization is directly dependent on the amount of thymidine replacement in DNA by these analogs. Based on recent in vivo and clinical pharmacology studies on continuous intravenous infusions of these drugs, clinical trials are underway evaluating the potential of radiosensitization in high grade gliomass and other poorly radioresponsive tumors using the technically safer intravenous route of administration. In this paper, the authors review the basic strategy for the use of these analogs, the ongoing clinical trials and the potential areas for future experimental and clinical studies

  9. Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice (United States)

    Hayes, N. L.; Nowakowski, R. S.


    The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.

  10. Induction of sister chromatid exchanges in xeroderma pigmentosum cells after exposure to ultraviolet light

    International Nuclear Information System (INIS)

    The role of DNA repair mechanisms in the induction of sister chromatid exchanges (SCE) after exposure to ultraviolet radiation was investigated in xeroderma pigmentosum cells. Cells from different excision-deficient XP strains, representing the 5 complementation groups in XP, A, B, C, D and E, and from excision-proficient XP variant strains were irradiated with low doses of UVR (0-3.5 J/m2). The number of SCE was counted after two cycles in the presence of BUdR. In cells of the complementation groups A, B, C and D the number of SCE was significantly higher than in UV-exposed control cells. The frequencies of SCE in group E cells and in XP variant cells were not different from those in control cells. Treatment with caffeine (0-200 μg/ml) did not result in a different response of variant cells compared with normal cells. A simple correlation between SCE frequency and residual excision-repair activity was not observed. The response of the excision-repair deficient cells suggests that unrepaired damage, produced by UVR is involved in the production of SCE

  11. Effects of 2'-chlorothymidine on Chinese hamster cells irradiated with x-rays and ultraviolet light

    International Nuclear Information System (INIS)

    Effects of 2'-chlorothymidine (2'-Cl-TdR) and its mother compound, thymidine (TdR), on cell killing induced by X- and UV-irradiation have been investigated. Chinse hamster V-79 (TK+) cells as well as thymidine kinase deficient (TK-) variant cells, which were isolated from parental V-79 cells following stepwise treatment with BUdR, were incubated in a medium containing 2'-Cl-TdR and TdR after X- and UV-irradiation. In the TK+ cells, both 2'-Cl-TdR and TdR enhanced the killing efficiency of X-rays and ultraviolet light. On the other hand, in the TK- cells, only 2'-Cl-TdR enhanced the killing efficiency of X- and UV-irradiation, and no effect of TdR was observed. These results suggest that phosphorylation of TdR by the enzyme is essential for its ability to modify radiation response, while the enhancement of cell killing by 2'-Cl-TdR must be explained by a mechanism at least partly independent of phosphorylation. (author)

  12. Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes. (United States)

    Zhou, J; Crawford, L; McLean, L; Sun, X Y; Stanley, M; Almond, N; Smith, G L


    The L1 gene of human papillomavirus type 16 (HPV-16) driven by the vaccinia virus major late 4b gene promoter has been inserted into three different sites of the vaccinia virus genome. Insertion into the thymidine kinase (TK) gene was achieved by selection of TK- mutants in BUdR on TK- cells. Insertion into two vaccinia virus serine protease inhibitor (serpin) genes was achieved by co-insertion of the Escherichia coli xanthine guanine phosphoribosyltransferase gene linked to the vaccinia virus 7.5K promoter and selection of mycophenolic acid-resistant recombinant viruses. Each recombinant virus expressed a 57K L1 protein at similar levels and with similar kinetics. However, immunization of mice with these recombinant viruses induced different levels of antibody to the L1 protein. Viruses lacking serpin genes B13R and B24R induced significantly higher antibody levels than did viruses lacking the TK gene. The presence of functional B13R and B24R gene products is therefore somehow immunosuppressive at least for antibody responses to the L1 protein of HPV-16.

  13. Whole brain radiotherapy with radiosensitizer for brain metastases

    Directory of Open Access Journals (Sweden)

    Viani Gustavo


    Full Text Available Abstract Purpose To study the efficacy of whole brain radiotherapy (WBRT with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. Methods A meta-analysis of randomized controlled trials (RCT was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently. Results A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77. Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03 and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3 when the two arms were compared. Conclusion Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide, have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast to have positive action in lung and breast carcinoma brain metastases in association with WBRT.

  14. Silibinin reverses drug resistance in human small-cell lung carcinoma cells (United States)

    Sadava, David; Kane, Susan E.


    Small-cell lung carcinoma (SCLC) has a dismal prognosis in part because of multidrug resistance (MDR). Silibinin is a flavonolignan extracted from milk thistle (Silybum marianum), extracts of which are used in traditional medicine. We tested the effects of silibinin on drug-sensitive (H69) and multi-drug resistant (VPA17) SCLC cells. VPA17 cells did not show resistance to silibinin (IC50 = 60µM for H69 and VPA17). Flow cytometry analysis after incubation in 30 µM silibinin showed no changes in cell cycle phases in VPA17 or H69 cells compared with untreated cells. Silibinin (30 µM) incubation was pro-apoptotic in VPA17 cells after >3 days, as measured by ELISA of BUdR labeled DNA fragments. Apoptosis was also indicated by an increase in caspase-3 specific activity and decrease in survivin in VPA17 MDR cells. VPA17 cells had increased Pgp -mediated efflux of calcein acetoxymethyl ester (calcein AM); however, this was inhibited in cells pre-incubated in silibinin for 5 days. Pre-incubation of VPA17 cells in 30 µM silibinin for 5 days also reversed resistance to etoposide (IC50 = 5.50 uM to 0.65 µM) and doxorubicin (IC50 = 0.620 µM to 0.035 µM). The possible synergistic relationship between silibinin and chemotherapy drugs was determined by exposure of VPA17 cells to 1:1 ratios of their respective IC50 values, with serial dilutions at 0.25–2.0 × IC50 and calculation of the combination index (CI). Silibinin and etoposide showed synergism (CI = 0.46 at ED50), as did silibinin and doxorubicin (CI = 0.24 at ED50). These data indicate that in SCLC, silibinin is pro-apoptotic, reverses MDR and acts synergistically with chemotherapy drugs. Silibinin, a non-toxic natural product may be useful in the treatment of drug-resistant SCLC. PMID:23879966

  15. The method validation step of biological dosimetry accreditation process

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    Roy, L.; Voisin, P.A.; Guillou, A.C.; Busset, A.; Gregoire, E.; Buard, V.; Delbos, M.; Voisin, Ph. [Institut de Radioprotection et de Surete Nucleaire, LDB, 92 - Fontenay aux Roses (France)


    One of the missions of the Laboratory of Biological Dosimetry (L.D.B.) of the Institute for Radiation and Nuclear Safety (I.R.S.N.) is to assess the radiological dose after an accidental overexposure suspicion to ionising radiation, by using radio-induced changes of some biological parameters. The 'gold standard' is the yield of dicentrics observed in patients lymphocytes, and this yield is converted in dose using dose effect relationships. This method is complementary to clinical and physical dosimetry, for medical team in charge of the patients. To obtain a formal recognition of its operational activity, the laboratory decided three years ago, to require an accreditation, by following the recommendations of both 17025 General Requirements for the Competence of Testing and Calibration Laboratories and 19238 Performance criteria for service laboratories performing biological dosimetry by cyto-genetics. Diagnostics, risks analysis were realized to control the whole analysis process leading to documents writing. Purchases, personnel department, vocational training were also included in the quality system. Audits were very helpful to improve the quality system. One specificity of this technique is that it is not normalized therefore apart from quality management aspects, several technical points needed some validations. An inventory of potentially influent factors was carried out. To estimate their real effect on the yield of dicentrics, a Placket-Burman experimental design was conducted. The effect of seven parameters was tested: the BUdr (bromodeoxyuridine), PHA (phytohemagglutinin) and colcemid concentration, the culture duration, the incubator temperature, the blood volume and the medium volume. The chosen values were calculated according to the uncertainties on the way they were measured i.e. pipettes, thermometers, test tubes. None of the factors has a significant impact on the yield of dicentrics. Therefore the uncertainty linked to their use was

  16. Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, phase I-II study

    International Nuclear Information System (INIS)

    .v. BUdR and indicate the need to proceed with randomized Phase III studies utilizing halogenated pyrimidines and radiation. One such study has already been activated, RTOG no. 94-04